Abstract：
:Significant advances have been made over the past few years concerning the cellular and molecular events underlying neuron death. Recently, it is becoming increasingly clear that some of genes induced during cerebral ischemia may actually serve to rescue the cell from death. However, the injured cell may not be capable of expressing protein at high enough levels to be protective. One of the most exciting arenas of such interventions is the use of viral vectors to deliver potentially neuroprotective genes at high levels. Neurotropic herpes simplex viral (HSV) strains are an obvious choice for gene therapy to the brain, and we have used bipromoter vectors that are capable of transferring various genes to neurons. Using this system in experimental models of stroke, cardiac arrest, and excitotoxicity, we have found that it is possible to enhance neuron survival against such cerebral insults by overexpressing genes that target various facets of injury. These include energy restoration by the glucose transporter (GLUT-1), buffering calcium excess by calbindin, preventing protein malfolding or aggregation by stress proteins and inhibiting apoptotic death by BCL-2. We show that in some cases, gene therapy is also effective after the onset of injury, and also address whether successful gene therapy necessarily spares function. Although gene therapy is limited to the few hundred cells the vector is capable of transfecting, we consider the possibility of such gene therapy becoming relevant to clinical neurology in the future.
journal_name
Ann N Y Acad Scijournal_title
Annals of the New York Academy of Sciencesauthors
Yenari MA,Dumas TC,Sapolsky RM,Steinberg GKdoi
10.1111/j.1749-6632.2001.tb03643.xsubject
Has Abstractpub_date
2001-06-01 00:00:00pages
340-57eissn
0077-8923issn
1749-6632journal_volume
939pub_type
杂志文章,评审abstract：:Paget's disease is a common skeletal disorder with a strong genetic component, which is characterized by focal increases in disorganized bone remodeling, predominantly affecting the axial skeleton. Current evidence suggests that classical Paget's disease of bone (PDB) is caused by a combination of rare alleles of larg...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：10.1111/j.1749-6632.2011.06228.x
更新日期：2011-12-01 00:00:00
abstract：:Clinicians use the combination of Tanner stage 5 (T5) of puberty, final height, and epiphyseal fusion to define maturity. We tested the hypothesis that changes in body composition related to age are identifiable during T5. Asian, Black, Hispanic, and White T5 adolescents (n = 148, 72 females) had measurements taken of...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.2000.tb06491.x
更新日期：2000-05-01 00:00:00
abstract：:Population trends indicate that in the near future the size of the elderly population will increase. This will result in a large increment in the numbers of persons suffering mild to severe levels of cognitive impairment. While considerable efforts continue to be made to explain brain changes associated with Alzheimer...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.1996.tb34395.x
更新日期：1996-01-17 00:00:00
abstract：:Evidence from experimental animal studies show that sex hormones influence the glucocorticoid response to a variety of inflammatory and noninflammatory stimuli. In this study we assessed gender differences in the response of ACTH and cortisol in normal young male and female humans following intravenous infusion of hum...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.2002.tb04203.x
更新日期：2002-06-01 00:00:00
abstract：:Lewisite and many other similar arsenicals are warfare vesicants developed and weaponized for use in World Wars I and II. These chemicals, when exposed to the skin and other epithelial tissues, cause rapid severe inflammation and systemic damage. Here, we show that topically applied arsenicals in a murine model produc...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/nyas.14475
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abstract：:Despite neuropathological and electrophysiological evidence for the involvement of parahippocampal structures in temporal lobe epilepsy (TLE), little attention has been paid to morphometric changes in these structures, and the relation of these changes to TLE. We performed high-resolution MRI volumetric analysis to ex...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.2000.tb06752.x
更新日期：2000-06-01 00:00:00
abstract：:We have successfully expressed the active tyrosinase of Streptomyces antibioticus in Escherichia coli under the control of the trp promoter by fusing the sequence to the ORF438 gene. Because our attempt to connect the polycistronic gene of ORF438 and tyrosinase directly to the trp promoter of E. coli resulted in the e...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.1994.tb47374.x
更新日期：1994-05-02 00:00:00
abstract：:Intense stress can be detrimental for tissue homeostasis and accelerates aging. On the other hand, repeated mild stresses can have beneficial and even life-prolonging effects. Hypersecretion of glucocorticoids (GCs) represents the major hormonal response to stress. However, besides its life-sustaining role, GC excess ...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：10.1196/annals.1395.050
更新日期：2007-04-01 00:00:00
abstract：:Calcium ions are essential to proper neurotransmission. Impairment in cytosolic Ca(2+) concentration and Ca(2+) signaling disturbs neuronal activity, leading to pathological consequences. In cells, a high-affinity plasma membrane calcium pump (PMCA) keeps free Ca(2+) in the nanomolar range. Among four genes encoding t...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1196/annals.1410.077
更新日期：2008-12-01 00:00:00
abstract：:Calcitonin gene-related peptide has been identified by immunocytochemistry within the thymus of fetal through aged adult mice. Calcitonin gene-related peptide positive nerves are observed from embryonic day 17 throughout the lifespan of the mouse. A sparse cell population positive for CGRP is first observed during the...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：10.1111/j.1749-6632.1994.tb23094.x
更新日期：1994-11-25 00:00:00
abstract：:Social motor coordination (SMC) pertains to the timing of contingent movements during social interactions and is of high relevance for successful social and musical interactions. Semi-automated, objective methods are increasingly being used to analyze SMC, though it is unclear if these methods are feasible in naturali...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/nyas.13651
更新日期：2018-05-04 00:00:00
abstract：:Ibogaine, an alkaloid extracted from Tabemanthe iboga, is being studied as a potential long-acting treatment for oploid and stimulant abuse as well as for alcoholism and smoking. Studies in this laboratory have used animal models to characterize ibogaine's interactions with drugs of abuse, and to investigate the mecha...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：
更新日期：1998-05-30 00:00:00
abstract：:Elevated circulating levels of glucocorticoids are associated with psychiatric symptoms across several different conditions. It remains unknown if this hormonal abnormality is a cause or an effect of the psychiatric conditions. For example, the hypercortisolemia observed in a subset of patients with depression may hav...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：10.1111/j.1749-6632.2009.04980.x
更新日期：2009-10-01 00:00:00
abstract：:The involvement of the c-Myc transcription factor in neoplastic transformation is well documented. However, which of its numerous target genes are crucial for tumorigenesis remains a frequently contested issue. We have recently established a non-transgenic murine model for B-cell lymphoma based on neoplastic conversio...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1196/annals.1339.047
更新日期：2005-11-01 00:00:00
abstract：:Human diploid fibroblasts (WI38) were inoculated into Rose multipurpose culture chambers, using a high population density to develop confluency. After 24 hours, cells from a 1 mm swath were scraped from the center of the chamber. This cleared path was positioned to permit an unobstructed transmission of a 0.9 X 20 mm ...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.1976.tb41605.x
更新日期：1976-01-30 00:00:00
abstract：:The first evidence for the role of the protein elongation factor eEF1A2 in tumorigenesis was reported by Anand and colleagues who demonstrated that eEF1A2 is overexpressed in about 30% of ovarian tumors and some established ovarian cancer cells. This abnormal expression correlates with a poor prognosis. Since this dis...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：10.1111/j.1749-6632.2009.04909.x
更新日期：2009-08-01 00:00:00
abstract：:Mutations in the INSL3 and RXFP2 genes have been associated with human cryptorchidism but with contrasting data. We analyzed the frequency of mutations in these genes in 600 newborns with cryptorchidism (396 unilateral and 204 bilateral) and 300 noncryptorchid subjects. We found five RXFP2 mutations in five bilateral ...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.2008.03784.x
更新日期：2009-04-01 00:00:00
abstract：:Early dissemination, blood circulation, or homing of single tumor cells in bone marrow and other organs is usually undetectable at primary diagnosis, even by high resolution imaging technologies. However, ultrasensitive approaches now enable the detection of "occult" tumor cells. Many researchers are currently focusin...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1111/j.1749-6632.2010.05779.x
更新日期：2010-10-01 00:00:00
abstract：:The APC protein is a crucial regulator of intestinal cell growth, and mutations in the APC gene are a common initial event in the process of human colorectal carcinogenesis. Animals bearing germline mutations in Apc are therefore important models for human colorectal cancer. These animals have been used both to unders...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：10.1111/j.1749-6632.1999.tb08721.x
更新日期：1999-01-01 00:00:00
abstract：:Gene regulation mechanisms have evolved allowing cells to finetune the level of "endogenous" oxidative stress and to cope with increased free radicals from external sources. Levels of H2O2 are tightly controlled in E. coli by OxyR, which is activated by H2O2 to increase scavenging activities and limit H2O2 generation ...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：10.1111/j.1749-6632.2000.tb06177.x
更新日期：2000-01-01 00:00:00
abstract：:Neurotrophic factors are secreted peptides that when interacting with specific classes of membrane receptors activate intracellular signaling cascades that prevents neuronal death during embryonic development. The establishment of gene-targeted null mutant mice for the neurotrophic factors, brain-derived neurotrophic ...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：
更新日期：1999-11-28 00:00:00
abstract：:In keeping with the inflammatory paradigm of abdominal aortic aneurysm (AAA) pathophysiology, in vitro studies suggest that aneurysms secrete the proinflammatory cytokine interleukin-6 (IL-6). Circulating IL-6 levels are higher in patients with AAA with elevated circulating IL-6 an independent risk factor for cardiova...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1196/annals.1383.009
更新日期：2006-11-01 00:00:00
abstract：:Amperometry is a powerful tool for studying the exocytotic process. Catecholamines released from a single secretory vesicle are oxidized by a carbon fiber microelectrode placed on a chromaffin cell membrane. This phenomenon can be recorded online as an amperometric signal. Each event of exocytosis is called a secretor...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：10.1111/j.1749-6632.2002.tb04544.x
更新日期：2002-10-01 00:00:00
abstract：:Experiments with enzymes in situ that are dependent on ascorbic acid for maximum activity will provide critical information about ascorbic acid requirements. Our work with chromaffin tissue as a model system eventually will result in the determination of two dose-response curves for norepinephrine biosynthesis, repres...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：10.1111/j.1749-6632.1987.tb23779.x
更新日期：1987-01-01 00:00:00
abstract：:Currently, several rickettsioses are officially being reported in the Russian Federation. These are epidemic typhus and Brill-Zinsser disease, both caused by Rickettsia prowazekii which has a historic prevalence in Russia. Nowadays only single sporadic cases of R. prowazekii infection are reported. The last significan...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：10.1196/annals.1374.006
更新日期：2006-10-01 00:00:00
abstract：:The remarkable hemodynamic changes of normal pregnancy are briefly reviewed. In addition, new findings and current concepts related to the underlying hormonal and molecular mechanisms are presented. Finally, work that is in progress as well as future directions is briefly discussed. ...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：10.1196/annals.1282.022
更新日期：2005-05-01 00:00:00
abstract：:Biologics are playing an increasingly significant role in the practice of modern medicine and surgery in general and orthopedics in particular. Cell-based approaches are among the most important and widely used modalities in orthopedic biologics, with mesenchymal stem cells and other multi/pluripotent cells undergoing...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：10.1111/nyas.13575
更新日期：2017-12-01 00:00:00
abstract：:Although stress is tightly connected with elevated levels of catecholamines, stress effects on target structures of catecholamine action--adrenoceptors (ARs)--has not been deeply studied yet. Similarly, very little is known about changes of muscarinic receptors (MRs) during stress. We determined changes in these recep...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1196/annals.1410.028
更新日期：2008-12-01 00:00:00
abstract：:Cardiomyocytes in the adult mammal retain little or none of their developmental capacity for hyperplastic growth. As a consequence of this differentiated, nonproliferative phenotype, cardiomyocyte loss due to injury or disease is irreversible. Therapeutic intervention in end-stage diseased hearts is currently limited ...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章,评审
doi：10.1111/j.1749-6632.1995.tb17454.x
更新日期：1995-03-27 00:00:00
abstract：:The DNase activity and circulating DNA (cirDNA) concentration in blood plasma of healthy donors, patients with chronic prostatitis, and patients with prostate tumors were analyzed. The concentration of the cirDNA from plasma was determined by PicoGreen fluorescent assay. DNase activity in blood was measured using the ...
journal_title：Annals of the New York Academy of Sciences
pub_type： 杂志文章
doi：10.1196/annals.1448.016
更新日期：2008-08-01 00:00:00
