Abstract:
:Temporal lobe epilepsy is the most prevalent seizure disorder in adults. Compromised inhibitory neurotransmitter function in the hippocampus contributes to the hyperexcitability generating this condition, but the underlying molecular mechanisms are unknown. Combining patch-clamp recording and single-cell mRNA amplification (aRNA) techniques in single dentate granule cells, we demonstrate that expression of GABA(A) receptor subunit mRNAs is substantially altered in neurons from epileptic rats. These changes in gene expression precede epilepsy onset by weeks and correlate with profound alterations in receptor function, indicating that aberrant GABA(A) receptor expression and function has an essential role in the process of epileptogenesis.
journal_name
Nat Medjournal_title
Nature medicineauthors
Brooks-Kayal AR,Shumate MD,Jin H,Rikhter TY,Coulter DAdoi
10.1038/2661subject
Has Abstractpub_date
1998-10-01 00:00:00pages
1166-72issue
10eissn
1078-8956issn
1546-170Xjournal_volume
4pub_type
杂志文章相关文献
NATURE MEDICINE文献大全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
pub_type: 杂志文章
doi:10.1038/nm1185
更新日期:2005-02-01 00:00:00
abstract::Misfolding of Cu/Zn-superoxide dismutase (SOD1) is emerging as a mechanism underlying motor neuron degeneration in individuals with amyotrophic lateral sclerosis (ALS) who carry a mutant SOD1 gene (SOD1 ALS). Here we describe a structure-guided approach to developing an antibody that specifically recognizes monomer-mi...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1559
更新日期:2007-06-01 00:00:00
abstract::The principles that govern the evolution of tumors exposed to targeted therapy are poorly understood. Here we modeled the selection and propagation of an amplification in the BRAF oncogene (BRAFamp) in patient-derived tumor xenografts (PDXs) that were treated with a direct inhibitor of the kinase ERK, either alone or ...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.4369
更新日期:2017-08-01 00:00:00
abstract::Targeting the mammalian target of rapamycin (mTOR) protein is a promising strategy for cancer therapy. The mTOR kinase functions in two complexes, TORC1 (target of rapamycin complex-1) and TORC2 (target of rapamycin complex-2); however, neither of these complexes is fully inhibited by the allosteric inhibitor rapamyci...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.2091
更新日期:2010-02-01 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature medicine
pub_type: 杂志文章,已发布勘误
doi:10.1038/s41591-020-1057-3
更新日期:2020-09-01 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
pub_type: 杂志文章
doi:10.1038/nm1192
更新日期:2005-03-01 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
pub_type: 杂志文章
doi:10.1038/nm903
更新日期:2003-08-01 00:00:00
abstract::Activating mutations in genes encoding G protein α (Gα) subunits occur in 4-5% of all human cancers, but oncogenic alterations in Gβ subunits have not been defined. Here we demonstrate that recurrent mutations in the Gβ proteins GNB1 and GNB2 confer cytokine-independent growth and activate canonical G protein signalin...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3751
更新日期:2015-01-01 00:00:00
abstract::The rate of expansion of primary prostatic carcinoma is comparatively slow, with tumours frequently taking years or decades to reach clinically relevant size. We now report the presence of an endogenous inhibitor, derived from aqueous extracts of human prostate tissue, which blocks prostatic carcinoma cell proliferati...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm1095-1040
更新日期:1995-10-01 00:00:00
abstract::Technologies are needed to map and image biological barriers in vivo that limit solid tumor delivery and, ultimately, the effectiveness of imaging and therapeutic agents. Here we integrate proteomic and imaging analyses of caveolae at the blood-tumor interface to discover an active transendothelial portal to infiltrat...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3623
更新日期:2014-09-01 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
pub_type: 杂志文章
doi:10.1038/nm1457
更新日期:2006-11-01 00:00:00
abstract::Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR) that compromise its chloride channel activity. The most common mutation, p.Phe508del, results in the production of a misfolded CFTR protein, which has residual channel activity but is prematu...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.4305
更新日期:2017-05-01 00:00:00
abstract::Conventional leg prostheses do not convey sensory information about motion or interaction with the ground to above-knee amputees, thereby reducing confidence and walking speed in the users that is associated with high mental and physical fatigue1-4. The lack of physiological feedback from the remaining extremity to th...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/s41591-019-0567-3
更新日期:2019-09-01 00:00:00
abstract::A chimeric RNA/DNA oligonucleotide was constructed to induce a sequence mutation in the rat factor IX gene, resulting in prolonged coagulation. Oligonucleotides were targeted to hepatocytes in cell culture or in vivo by intravenous injection. Nucleotide conversion was both site-specific and dose-dependent. The mutated...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0398-285
更新日期:1998-03-01 00:00:00
abstract::Oral administration of protein can induce antigen-specific immune hyporesponsiveness. However, the utility of oral tolerance to autoantigens in the treatment of autoimmune diseases may be limited when candidate autoantigens cannot be produced by conventional systems in quantities sufficient for clinical studies. Plant...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0797-793
更新日期:1997-07-01 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
pub_type: 杂志文章
doi:10.1038/nm1001-1151
更新日期:2001-10-01 00:00:00
abstract::Understanding the mechanisms of osteoclastogenesis is crucial for developing new drugs to treat diseases associated with bone loss, such as osteoporosis. Here we report that the C-C chemokine receptor-2 (CCR2) is crucially involved in balancing bone mass. CCR2-knockout mice have high bone mass owing to a decrease in n...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.1945
更新日期:2009-04-01 00:00:00
abstract::Proteins in the B cell CLL/lymphoma 2 (BCL-2) family are key regulators of the apoptotic process. This family comprises proapoptotic and prosurvival proteins, and shifting the balance toward the latter is an established mechanism whereby cancer cells evade apoptosis. The therapeutic potential of directly inhibiting pr...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3048
更新日期:2013-02-01 00:00:00
abstract::Parasites of the Leishmania genus are the causative agents of leishmaniasis in humans, a disease that affects more than 12 million people worldwide. These parasites replicate intracellularly in macrophages, and the primary mechanisms underlying host resistance involve the production of nitric oxide (NO). In this study...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3221
更新日期:2013-07-01 00:00:00
abstract::Spinal bulbar muscular atrophy (SBMA) is a motor neuron disease caused by toxic gain of function of the androgen receptor (AR). Previously, we found that co-regulator binding through the activation function-2 (AF2) domain of AR is essential for pathogenesis, suggesting that AF2 may be a potential drug target for selec...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.4500
更新日期:2018-05-01 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
pub_type: 杂志文章
doi:10.1038/nm1439
更新日期:2006-07-01 00:00:00
abstract::Networks of interstitial cells of Cajal embedded in the musculature of the gastrointestinal tract are involved in the generation of electrical pacemaker activity for gastrointestinal motility. This pacemaker activity manifests itself as rhythmic slow waves in membrane potential, and controls the frequency and propagat...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0798-848
更新日期:1998-07-01 00:00:00
abstract::Treating KRAS-mutant lung adenocarcinoma (LUAD) remains a major challenge in cancer treatment given the difficulties associated with directly inhibiting the KRAS oncoprotein. One approach to addressing this challenge is to define mutations that frequently co-occur with those in KRAS, which themselves may lead to thera...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.4407
更新日期:2017-11-01 00:00:00
abstract::Multiple sclerosis is an autoimmune disease of the central nervous system (CNS) that is initiated when self-reactive T cells enter the brain and become locally activated after encountering their specific nervous antigens. When and where the disease-relevant antigen encounters occur is unclear. Here we combined fluores...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3182
更新日期:2013-06-01 00:00:00
abstract::Given the variation in the HIV-1 viral load (VL) set point across subjects, as opposed to a fairly stable VL over time within an infected individual, it is important to identify the characteristics of the host and virus that affect VL set point. Although recently infected individuals with multiple phylogenetically lin...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm.3932
更新日期:2015-10-01 00:00:00
abstract::In the Supplementary Information originally published with this article, a lane was missing in the β-actin blot in Supplementary Fig. 2. The lane has been added. The error has been corrected in the Supplementary Information associated with this article. ...
journal_title:Nature medicine
pub_type: 已发布勘误
doi:10.1038/s41591-018-0168-6
更新日期:2018-10-01 00:00:00
abstract::Although maternal human immunodeficiency virus type 1 (HIV-1) transmission occurs during gestation, intrapartum and postpartum (by breast-feeding), 50-70% of all infected children seem to acquire HIV-1 shortly before or during delivery. Epidemiological evidence indicates that mucosal exposure is an important aspect of...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/72309
更新日期:2000-02-01 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
pub_type: 杂志文章
doi:10.1038/nm0502-466
更新日期:2002-05-01 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
pub_type: 杂志文章
doi:10.1038/nm0102-75
更新日期:2002-01-01 00:00:00
abstract::Breast cancers are either primarily resistant to chemotherapy (intrinsic resistance), or respond to chemotherapy but later recur with a multidrug-resistant phenotype because of overexpression of the multidrug transporter P-glycoprotein. The MDR1 gene encoding P-glycoprotein may be transcriptionally regulated by a Y-bo...
journal_title:Nature medicine
pub_type: 杂志文章
doi:10.1038/nm0497-447
更新日期:1997-04-01 00:00:00