abstract：:The neural tube defects (NTDs) spina bifida and anencephaly are widely prevalent severe birth defects. The mouse mutant curly tail (ct/ct) has served as a model of NTDs for 50 years, even though the responsible genetic defect remained unrecognized. Here we show by gene targeting, mapping and genetic complementation st...

journal_title：Nature medicine

authors： Ting SB,Wilanowski T,Auden A,Hall M,Voss AK,Thomas T,Parekh V,Cunningham JM,Jane SM

更新日期：2003-12-01 00:00:00

abstract：:The human protein apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like-3G (APOBEC3G), also known as CEM-15, mediates a newly described form of innate resistance to retroviral infection by catalyzing the deamination of deoxycytidine to deoxyuridine in viral cDNA replication intermediates. Because DNA deamina...

journal_title：Nature medicine

authors： Sheehy AM,Gaddis NC,Malim MH

更新日期：2003-11-01 00:00:00

abstract：:To understand the integrin requirements of T-helper (T(H)) effector subsets, we investigated the contribution of CD18 (beta(2) integrin) to T(H)1 and T(H)2 function in vitro and in relevant disease models. CD18-deficient (Itgb2(-/-)) T cells showed largely normal in vitro function. Compared with wild-type mice, Itgb2(...

journal_title：Nature medicine

authors： Lee SH,Prince JE,Rais M,Kheradmand F,Shardonofsky F,Lu H,Beaudet AL,Smith CW,Soong L,Corry DB

更新日期：2003-10-01 00:00:00

abstract：:Whereas uncoupling protein 1 (UCP-1) is clearly involved in thermogenesis, the role of UCP-2 is less clear. Using hybridization, cloning techniques and cDNA array analysis to identify inducible neuroprotective genes, we found that neuronal survival correlates with increased expression of Ucp2. In mice overexpressing h...

journal_title：Nature medicine

authors： Mattiasson G,Shamloo M,Gido G,Mathi K,Tomasevic G,Yi S,Warden CH,Castilho RF,Melcher T,Gonzalez-Zulueta M,Nikolich K,Wieloch T

更新日期：2003-08-01 00:00:00

abstract：:Members of the suppressor of cytokine signaling (SOCS) family are involved in the pathogenesis of many inflammatory diseases. SOCS-3 is predominantly expressed in T-helper type 2 (T(H)2) cells, but its role in T(H)2-related allergic diseases remains to be investigated. In this study we provide a strong correlation bet...

journal_title：Nature medicine

authors： Seki Y,Inoue H,Nagata N,Hayashi K,Fukuyama S,Matsumoto K,Komine O,Hamano S,Himeno K,Inagaki-Ohara K,Cacalano N,O'Garra A,Oshida T,Saito H,Johnston JA,Yoshimura A,Kubo M

更新日期：2003-08-01 00:00:00

abstract：:The ubiquitin-proteasome pathway is the central mediator of regulated proteolysis in cells, and defects in this pathway are associated with cancer and neurodegenerative diseases. To assess 26S proteasome function in living animals, we developed a ubiquitin-luciferase reporter for bioluminescence imaging. The reporter ...

journal_title：Nature medicine

authors： Luker GD,Pica CM,Song J,Luker KE,Piwnica-Worms D

更新日期：2003-07-01 00:00:00

abstract：:Amyloid-beta peptide (Abeta) interacts with the vasculature to influence Abeta levels in the brain and cerebral blood flow, providing a means of amplifying the Abeta-induced cellular stress underlying neuronal dysfunction and dementia. Systemic Abeta infusion and studies in genetically manipulated mice show that Abeta...

journal_title：Nature medicine

authors： Deane R,Du Yan S,Submamaryan RK,LaRue B,Jovanovic S,Hogg E,Welch D,Manness L,Lin C,Yu J,Zhu H,Ghiso J,Frangione B,Stern A,Schmidt AM,Armstrong DL,Arnold B,Liliensiek B,Nawroth P,Hofman F,Kindy M,Stern D,Zlokov

更新日期：2003-07-01 00:00:00

abstract：:Angiogenic tumor vessels are promising targets for the activity and the selective delivery of cancer therapeutics. The bone marrow contributes different cell types to the tumor stroma, including hematopoietic cells and, as recently suggested, vascular endothelial cells (ECs). Thus, transplantation of genetically modif...

journal_title：Nature medicine

authors： De Palma M,Venneri MA,Roca C,Naldini L

更新日期：2003-06-01 00:00:00

abstract：:Advances in imaging are transforming our understanding of angiogenesis and the evaluation of drugs that stimulate or inhibit angiogenesis in preclinical models and human disease. Vascular imaging makes it possible to quantify the number and spacing of blood vessels, measure blood flow and vascular permeability, and an...

journal_title：Nature medicine

authors： McDonald DM,Choyke PL

更新日期：2003-06-01 00:00:00

abstract：:Retinal ischemia can cause vision-threatening pathological neovascularization. The mechanisms of retinal ischemia are not fully understood, however. Here we have shown that leukocytes prune the retinal vasculature during normal development and obliterate it in disease. Beginning at postnatal day 5 (P5) in the normal r...

journal_title：Nature medicine

authors： Ishida S,Yamashiro K,Usui T,Kaji Y,Ogura Y,Hida T,Honda Y,Oguchi Y,Adamis AP

更新日期：2003-06-01 00:00:00

abstract：:The live tuberculosis vaccines Mycobacterium bovis BCG (bacille Calmette-Guérin) and Mycobacterium microti both lack the potent, secreted T-cell antigens ESAT-6 (6-kDa early secretory antigenic target) and CFP-10 (10-kDa culture filtrate protein). This is a result of independent deletions in the region of deletion-1 (...

journal_title：Nature medicine

authors： Pym AS,Brodin P,Majlessi L,Brosch R,Demangel C,Williams A,Griffiths KE,Marchal G,Leclerc C,Cole ST

更新日期：2003-05-01 00:00:00

abstract：:The Kaposi's sarcoma-associated herpesvirus (KSHV) latency-associated nuclear antigen (LANA) is expressed in all KSHV-associated tumors, including Kaposi's sarcoma (KS) and primary effusion lymphoma (PEL). We found that beta-catenin is overexpressed in both PEL cells and KS tissue. Introduction of anti-LANA small inte...

journal_title：Nature medicine

authors： Fujimuro M,Wu FY,ApRhys C,Kajumbula H,Young DB,Hayward GS,Hayward SD

更新日期：2003-03-01 00:00:00

abstract：:Hemizygous deletion of chromosome 22q11 (del22q11) causes thymic, parathyroid, craniofacial and life-threatening cardiovascular birth defects in 1 in 4,000 infants. The del22q11 syndrome is likely caused by haploinsufficiency of TBX1, but its variable expressivity indicates the involvement of additional modifiers. Her...

journal_title：Nature medicine

authors： Stalmans I,Lambrechts D,De Smet F,Jansen S,Wang J,Maity S,Kneer P,von der Ohe M,Swillen A,Maes C,Gewillig M,Molin DG,Hellings P,Boetel T,Haardt M,Compernolle V,Dewerchin M,Plaisance S,Vlietinck R,Emanuel B,Gittenb

更新日期：2003-02-01 00:00:00

abstract：:Kidney transplantation has been one of the major medical advances of the past 30 years. However, tissue availability remains a major obstacle. This can potentially be overcome by the use of undifferentiated or partially developed kidney precursor cells derived from early embryos and fetal tissue. Here, transplantation...

journal_title：Nature medicine

authors： Dekel B,Burakova T,Arditti FD,Reich-Zeliger S,Milstein O,Aviel-Ronen S,Rechavi G,Friedman N,Kaminski N,Passwell JH,Reisner Y

更新日期：2003-01-01 00:00:00

abstract：:Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily that exhibits specific tumoricidal activity against a variety of tumors. It is expressed on different cells of the immune system and plays a role in natural killer cell-mediated tumor surveillance. In allogeneic he...

journal_title：Nature medicine

authors： Schmaltz C,Alpdogan O,Kappel BJ,Muriglan SJ,Rotolo JA,Ongchin J,Willis LM,Greenberg AS,Eng JM,Crawford JM,Murphy GF,Yagita H,Walczak H,Peschon JJ,van den Brink MR

更新日期：2002-12-01 00:00:00

abstract：:Levels of insulin-like growth factor I (IGF-I), a neuroprotective hormone, decrease in serum during aging, whereas amyloid-beta (Abeta), which is involved in the pathogenesis of Alzheimer disease, accumulates in the brain. High brain Abeta levels are found at an early age in mutant mice with low circulating IGF-I, and...

journal_title：Nature medicine

authors： Carro E,Trejo JL,Gomez-Isla T,LeRoith D,Torres-Aleman I

更新日期：2002-12-01 00:00:00

abstract：:The recent development of tissue microarrays-composed of hundreds of tissue sections from different tumors arrayed on a single glass slide-facilitates rapid evaluation of large-scale outcome studies. Realization of this potential depends on the ability to rapidly and precisely quantify the protein expression within ea...

journal_title：Nature medicine

authors： Camp RL,Chung GG,Rimm DL

更新日期：2002-11-01 00:00:00

abstract：:Immunization of transgenic mouse models of Alzheimer disease using amyloid-beta peptide (Abeta) reduces both the Alzheimer disease-like neuropathology and the spatial memory impairments of these mice. However, a therapeutic trial of immunization with Abeta42 in humans was discontinued because a few patients developed ...

journal_title：Nature medicine

authors： McLaurin J,Cecal R,Kierstead ME,Tian X,Phinney AL,Manea M,French JE,Lambermon MH,Darabie AA,Brown ME,Janus C,Chishti MA,Horne P,Westaway D,Fraser PE,Mount HT,Przybylski M,St George-Hyslop P

更新日期：2002-11-01 00:00:00

abstract：:The mechanism by which angiogenic factors recruit bone marrow (BM)-derived quiescent endothelial and hematopoietic stem cells (HSCs) is not known. Here, we report that functional vascular endothelial growth factor receptor-1 (VEGFR1) is expressed on human CD34(+) and mouse Lin(-)Sca-1(+)c-Kit(+) BM-repopulating stem c...

journal_title：Nature medicine

authors： Hattori K,Heissig B,Wu Y,Dias S,Tejada R,Ferris B,Hicklin DJ,Zhu Z,Bohlen P,Witte L,Hendrikx J,Hackett NR,Crystal RG,Moore MA,Werb Z,Lyden D,Rafii S

更新日期：2002-08-01 00:00:00

abstract：:Secretion of gastric inhibitory polypeptide (GIP), a duodenal hormone, is primarily induced by absorption of ingested fat. Here we describe a novel pathway of obesity promotion via GIP. Wild-type mice fed a high-fat diet exhibited both hypersecretion of GIP and extreme visceral and subcutaneous fat deposition with ins...

journal_title：Nature medicine

authors： Miyawaki K,Yamada Y,Ban N,Ihara Y,Tsukiyama K,Zhou H,Fujimoto S,Oku A,Tsuda K,Toyokuni S,Hiai H,Mizunoya W,Fushiki T,Holst JJ,Makino M,Tashita A,Kobara Y,Tsubamoto Y,Jinnouchi T,Jomori T,Seino Y

更新日期：2002-07-01 00:00:00

abstract：:Epstein-Barr virus is ubiquitous and is causally implicated in lymphoid and epithelial malignancies. Virus invades oropharyngeal mucosa and establishes latency in B lymphocytes. Reactivating lymphocytes shed virus into saliva for spread to new hosts. A complex of three virus glycoproteins, gH, gL and gp42, is essentia...

journal_title：Nature medicine

authors： Borza CM,Hutt-Fletcher LM

更新日期：2002-06-01 00:00:00

abstract：:The inwardly rectifying K(+) channel Kir6.1 forms K(+) channels by coupling with a sulfonylurea receptor in reconstituted systems, but the physiological roles of Kir6.1-containing K(+) channels have not been determined. We report here that mice lacking the gene encoding Kir6.1 (known as Kcnj8) have a high rate of sudd...

journal_title：Nature medicine

authors： Miki T,Suzuki M,Shibasaki T,Uemura H,Sato T,Yamaguchi K,Koseki H,Iwanaga T,Nakaya H,Seino S

更新日期：2002-05-01 00:00:00

abstract：:Noninvasive methods are needed to study the kinetic properties of viruses in living organisms. Oncolytic viruses are used increasingly for cancer therapy but there is currently no satisfactory way to measure efficiency of tumor transduction, changing levels of viral gene expression or the timing of virus elimination. ...

journal_title：Nature medicine

authors： Peng KW,Facteau S,Wegman T,O'Kane D,Russell SJ

更新日期：2002-05-01 00:00:00

abstract：:Natural inhibitors of angiogenesis are able to block pathological neovascularization without harming the preexisting vasculature. Here we show that two such inhibitors, thrombospondin-1 and pigment epithelium-derived factor, derive specificity for remodeling vessels from their dependence on Fas/Fas ligand (FasL)-media...

journal_title：Nature medicine

authors： Volpert OV,Zaichuk T,Zhou W,Reiher F,Ferguson TA,Stuart PM,Amin M,Bouck NP

更新日期：2002-04-01 00:00:00

abstract：:Skin is an attractive target for delivery of genetic therapies and vaccines. However, new approaches are needed to access this tissue more effectively. Here, we describe a new delivery technology based on arrays of structurally precise, micron-scale silicon projections, which we term microenhancer arrays (MEAs). In a ...

journal_title：Nature medicine

authors： Mikszta JA,Alarcon JB,Brittingham JM,Sutter DE,Pettis RJ,Harvey NG

更新日期：2002-04-01 00:00:00

abstract：:The tumor suppressor p53 inhibits tumor growth primarily through its ability to induce apoptosis. Mutations in p53 occur in at least 50% of human tumors. We hypothesized that reactivation of mutant p53 in such tumors should trigger massive apoptosis and eliminate the tumor cells. To test this, we screened a library of...

journal_title：Nature medicine

authors： Bykov VJ,Issaeva N,Shilov A,Hultcrantz M,Pugacheva E,Chumakov P,Bergman J,Wiman KG,Selivanova G

更新日期：2002-03-01 00:00:00

abstract：:The skin-associated chemokine CCL27 (also called CTACK, ALP and ESkine) and its receptor CCR10 (GPR-2) mediate chemotactic responses of skin-homing T cells in vitro. Here we report that most skin-infiltrating lymphocytes in patients suffering from psoriasis, atopic or allergic-contact dermatitis express CCR10. Epiderm...

journal_title：Nature medicine

authors： Homey B,Alenius H,Müller A,Soto H,Bowman EP,Yuan W,McEvoy L,Lauerma AI,Assmann T,Bünemann E,Lehto M,Wolff H,Yen D,Marxhausen H,To W,Sedgwick J,Ruzicka T,Lehmann P,Zlotnik A

更新日期：2002-02-01 00:00:00

abstract：:The immune-modulating cytokine interleukin-6 (IL-6) is expressed both in adipose tissue and centrally in hypothalamic nuclei that regulate body composition. We investigated the impact of loss of IL-6 on body composition in mice lacking the gene encoding IL-6 (Il6-/- mice) and found that they developed mature-onset obe...

journal_title：Nature medicine

authors： Wallenius V,Wallenius K,Ahrén B,Rudling M,Carlsten H,Dickson SL,Ohlsson C,Jansson JO

更新日期：2002-01-01 00:00:00

abstract：:While searching for alternative reading-frame peptides encoded by influenza A virus that are recognized by CD8+ T cells, we found an abundant immunogenic peptide encoded by the +1 reading frame of PB1. This peptide derives from a novel conserved 87-residue protein, PB1-F2, which has several unusual features compared w...

journal_title：Nature medicine

authors： Chen W,Calvo PA,Malide D,Gibbs J,Schubert U,Bacik I,Basta S,O'Neill R,Schickli J,Palese P,Henklein P,Bennink JR,Yewdell JW

更新日期：2001-12-01 00:00:00

abstract：:The C2 domain of synaptotagmin I, which binds to anionic phospholipids in cell membranes, was shown to bind to the plasma membrane of apoptotic cells by both flow cytometry and confocal microscopy. Conjugation of the protein to superparamagnetic iron oxide nanoparticles allowed detection of this binding using magnetic...

journal_title：Nature medicine

authors： Zhao M,Beauregard DA,Loizou L,Davletov B,Brindle KM

更新日期：2001-11-01 00:00:00

abstract：:Treatment of cocaine addiction is hampered by high rates of relapse even after prolonged drug abstinence. This relapse to compulsive cocaine use can be triggered by re-exposure to cocaine, by re-exposure to stimuli previously associated with cocaine or by exposure to stress. In laboratory rats, similar events reinstat...

journal_title：Nature medicine

authors： De Vries TJ,Shaham Y,Homberg JR,Crombag H,Schuurman K,Dieben J,Vanderschuren LJ,Schoffelmeer AN

更新日期：2001-10-01 00:00:00

abstract：:Diabetes in non-obese diabetic (NOD) mice is mediated by pathogenic T-helper type 1 (Th1) cells that arise because of a deficiency in regulatory or suppressor T cells. V alpha 14-J alpha 15 natural killer T (NKT) cells recognize lipid antigens presented by the major histocompatibility complex class I-like protein CD1d...

journal_title：Nature medicine

authors： Hong S,Wilson MT,Serizawa I,Wu L,Singh N,Naidenko OV,Miura T,Haba T,Scherer DC,Wei J,Kronenberg M,Koezuka Y,Van Kaer L

更新日期：2001-09-01 00:00:00

abstract：:While investigating the novel anticancer drug ecteinascidin 743 (Et743), a natural marine product isolated from the Caribbean sea squirt, we discovered a new cell-killing mechanism mediated by DNA nucleotide excision repair (NER). A cancer cell line selected for resistance to Et743 had chromosome alterations in a regi...

journal_title：Nature medicine

authors： Takebayashi Y,Pourquier P,Zimonjic DB,Nakayama K,Emmert S,Ueda T,Urasaki Y,Kanzaki A,Akiyama SI,Popescu N,Kraemer KH,Pommier Y

更新日期：2001-08-01 00:00:00

abstract：:Both the risk and the rate of development of atherosclerosis are increased in diabetics, but the mechanisms involved are unknown. Here we report a glucose-mediated increase in CD36 mRNA translation efficiency that results in increased expression of the macrophage scavenger receptor CD36. Expression of CD36 was increas...

journal_title：Nature medicine

authors： Griffin E,Re A,Hamel N,Fu C,Bush H,McCaffrey T,Asch AS

更新日期：2001-07-01 00:00:00

abstract：:From 28 young children in the Netherlands, we isolated a paramyxovirus that was identified as a tentative new member of the Metapneumovirus genus based on virological data, sequence homology and gene constellation. Previously, avian pneumovirus was the sole member of this recently assigned genus, hence the provisional...

journal_title：Nature medicine

authors： van den Hoogen BG,de Jong JC,Groen J,Kuiken T,de Groot R,Fouchier RA,Osterhaus AD

更新日期：2001-06-01 00:00:00

abstract：:Cytochrome P450 3A4 is an important mediator of drug catabolism that can be regulated by the steroid and xenobiotic receptor (SXR). We show here that SXR also regulates drug efflux by activating expression of the gene MDR1, which encodes the protein P-glycoprotein (ABCB1). Paclitaxel (Taxol), a commonly used chemother...

journal_title：Nature medicine

authors： Synold TW,Dussault I,Forman BM

更新日期：2001-05-01 00:00:00

abstract：:Low oxygen tension influences tumor progression by enhancing angiogenesis; and histone deacetylases (HDAC) are implicated in alteration of chromatin assembly and tumorigenesis. Here we show induction of HDAC under hypoxia and elucidate a role for HDAC in the regulation of hypoxia-induced angiogenesis. Overexpressed wi...

journal_title：Nature medicine

authors： Kim MS,Kwon HJ,Lee YM,Baek JH,Jang JE,Lee SW,Moon EJ,Kim HS,Lee SK,Chung HY,Kim CW,Kim KW

更新日期：2001-04-01 00:00:00

abstract：:Oxygen-regulated protein 150 kD (ORP150) is a novel endoplasmic-reticulum-associated chaperone induced by hypoxia/ischemia. Although ORP150 was sparingly upregulated in neurons from human brain undergoing ischemic stress, there was robust induction in astrocytes. Cultured neurons overexpressing ORP150 were resistant t...

journal_title：Nature medicine

authors： Tamatani M,Matsuyama T,Yamaguchi A,Mitsuda N,Tsukamoto Y,Taniguchi M,Che YH,Ozawa K,Hori O,Nishimura H,Yamashita A,Okabe M,Yanagi H,Stern DM,Ogawa S,Tohyama M

更新日期：2001-03-01 00:00:00

abstract：:Metastasis of breast cancer occurs primarily through the lymphatic system, and the extent of lymph node involvement is a key prognostic factor for the disease. Whereas the significance of angiogenesis for tumor progression has been well documented, the ability of tumor cells to induce the growth of lymphatic vessels (...

journal_title：Nature medicine

authors： Skobe M,Hawighorst T,Jackson DG,Prevo R,Janes L,Velasco P,Riccardi L,Alitalo K,Claffey K,Detmar M

更新日期：2001-02-01 00:00:00

abstract：:The World Health Organization estimates that tobacco will become the largest single health problem by 2020, causing an estimated 8.4 million deaths annually. But the smoking burden will not be distributed evenly across the globe; deaths in developed nations are set to rise 50% to 2.4 million while those in Asia will s...

journal_title：Nature medicine

authors： Raw M

更新日期：2001-01-01 00:00:00