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21.
Surojit Paul Peter Olausson Deepa V Venkitaramani Irina Ruchkina Timothy D Moran Natalie Tronson Evan Mills Shawn Hakim Michael W Salter Jane R Taylor Paul J Lombroso 《Neuropsychopharmacology》2007,61(9):1049-1061
BACKGROUND: Formation of long-term memories is critically dependent on extracellular-regulated kinase (ERK) signaling. Activation of the ERK pathway by the sequential recruitment of mitogen-activated protein kinases is well understood. In contrast, the proteins that inactivate this pathway are not as well characterized. METHODS: Here we tested the hypothesis that the brain-specific striatal-enriched protein tyrosine phosphatase (STEP) plays a key role in neuroplasticity and fear memory formation by its ability to regulate ERK1/2 activation. RESULTS: STEP co-localizes with the ERKs within neurons of the lateral amygdala. A substrate-trapping STEP protein binds to the ERKs and prevents their nuclear translocation after glutamate stimulation in primary cell cultures. Administration of TAT-STEP into the lateral amygdala (LA) disrupts long-term potentiation (LTP) and selectively disrupts fear memory consolidation. Fear conditioning induces a biphasic activation of ERK1/2 in the LA with an initial activation within 5 minutes of training, a return to baseline levels by 15 minutes, and an increase again at 1 hour. In addition, fear conditioning results in the de novo translation of STEP. Inhibitors of ERK1/2 activation or of protein translation block the synthesis of STEP within the LA after fear conditioning. CONCLUSIONS: Together, these data imply a role for STEP in experience-dependent plasticity and suggest that STEP modulates the activation of ERK1/2 during amygdala-dependent memory formation. The regulation of emotional memory by modulating STEP activity may represent a target for the treatment of psychiatric disorders such as posttraumatic stress disorder (PTSD), panic, and anxiety disorders. 相似文献
22.
Implementation of a successful endovascular surgical program in a non-teaching tertiary-care centre in Ontario. 总被引:1,自引:0,他引:1
Rod P N Willoughby John A Fenton Santosh R Pudupakkam Robert A Greco Evan W D Roberts Guy DeRose Stewart Kribs 《Canadian journal of surgery》2004,47(3):182-188
Endovascular surgical techniques have become an accepted standard of care for high-risk patients with abdominal aortic aneurysms and for certain patients with thoracic aortic pathology and peripheral arterial aneurysms. In Canada, endovascular surgery has been concentrated in tertiary-care academic teaching institutions. As the technology evolves and as expertise advances, the applicability of endovascular techniques will expand. With time, and as the demand for endovascular techniques rises, this expertise will increasingly need to be delivered by dedicated vascular surgical services in nonteaching institutions. The dissemination of endovascular surgical capabilities represent a unique challenge. We report the successful implementation of an endovascular surgical program in a tertiary-care nonteaching institution using a carefully planned preceptorship model. We review our initial 49 cases and discuss 6 factors important to the successful establishment of an endovascular surgical service: education, teamwork, strict selection of patients, use of a single stent-graft manufacturer, industry support and endovascular preceptorship. Our experience may be used as a model by other institutions in Canada. 相似文献
23.
24.
Large-scale variation among human and great ape genomes determined by array comparative genomic hybridization 总被引:6,自引:1,他引:6 下载免费PDF全文
Locke DP Segraves R Carbone L Archidiacono N Albertson DG Pinkel D Eichler EE 《Genome research》2003,13(3):347-357
Large-scale genomic rearrangements are a major force of evolutionary change and the ascertainment of such events between the human and great ape genomes is fundamental to a complete understanding of the genetic history and evolution of our species. Here, we present the results of an evolutionary analysis utilizing array comparative genomic hybridization (array CGH), measuring copy-number gains and losses among these species. Using an array of 2460 human bacterial artificial chromosomes (BACs) (12% of the genome), we identified a total of 63 sites of putative DNA copy-number variation between humans and the great apes (chimpanzee, bonobo, gorilla, and orangutan). Detailed molecular characterization of a subset of these sites confirmed rearrangements ranging from 40 to at least 175 kb in size. Surprisingly, the majority of variant sites differentiating great ape and human genomes were found within interstitial euchromatin. These data suggest that such large-scale events are not restricted solely to subtelomeric or pericentromeric regions, but also occur within genic regions. In addition, 5/9 of the verified variant sites localized to areas of intrachromosomal segmental duplication within the human genome. On the basis of the frequency of duplication in humans, this represents a 14-fold positional bias. In contrast to previous cytogenetic and comparative mapping studies, these results indicate extensive local repatterning of hominoid chromosomes in euchromatic regions through a duplication-driven mechanism of genome evolution. 相似文献
25.
Moore DM Hogg RS Yip B Wood E Tyndall M Braitstein P Montaner JS 《Journal of acquired immune deficiency syndromes (1999)》2005,40(3):288-293
OBJECTIVE: To examine the independent association of discordant virologic and immunologic responses to highly active antiretroviral therapy (HAART) with mortality. METHODS: A population-based study of 1527 treatment-naive individuals initiating HAART used Cox proportional hazards modeling to determine the independent association of treatment response at 3 to 9 months with nonaccidental mortality. Logistic regression was used to examine associations with discordant responses. RESULTS: Viral load (VL)/CD4 discordant responses were seen in 235 (15.4%) of subjects, and VL/CD4 responses were seen in 179 (11.7%) of subjects. In adjusted Cox regression models, discordant responses were found to be independently associated with an increased risk of mortality (VL/CD4: relative hazard [RH] = 1.87, 95% confidence interval [CI]: 1.15 to 3.04; VL/CD4: RH = 2.47, 95% CI: 1.54 to 3.95). VL/CD4 discordance was found to be associated with increasing age, baseline HIV RNA load <100,000 copies/mL, baseline CD4 counts <50 cells/muL, the use of lamivudine (3TC)/zidovudine (ZDV), and poor adherence to therapy. VL/CD4 discordance was associated with younger age; injection drug use; baseline HIV RNA load >100,000 copies/mL; the use of 3TC/ZDV, didanosine (ddI)/3TC, or ddI/stavudine; and poor adherence to therapy. CONCLUSION: Discordant responses are independently associated with an increased risk of mortality and are, in turn, associated with poor adherence to therapy. 相似文献
26.
Evan M. McIntosh 《Current genetics》1993,24(3):185-192
27.
Craig C. Reed Edward G.A. Iglesia Scott P. Commins Evan S. Dellon 《Annals of allergy, asthma & immunology》2019,122(3):296-301
Background
Disease activity may correlate with environmental aeroallergen exposure in eosinophilic esophagitis. The association between seasons and flares of eosinophilic esophagitis (EoE) histologic activity has not been extensively studied.Objective
We aimed to assess the frequency of seasonal exacerbations of eosinophilic esophagitis, as well as changes in symptom reporting, endoscopic findings, and histologic findings attributed to aeroallergens in an EoE cohort.Methods
In this retrospective cohort study, we analyzed EoE patients in histologic remission (<15 eosinophil/high-power field) but who doubled the esophageal eosinophil count between seasons without change in eosinophilic esophagitis–specific therapy. Outcomes were: symptomatic global worsening (yes/no); change in endoscopic severity (EREFS scoring system); and histologic change (peak eosinophil count).Results
Of 782 patients, 13 (4%) met inclusion criteria (mean age: 36.2; 85% male; 86% white; 85% atopic disease diagnosis), and 14 exacerbations were recorded. Of these, 71% occurred in fall and summer months. Peak eosinophil counts increased from 6.8 to 86.8 eosinophil per high-power field (P < .001). Four patients (31%) reported worsening of seasonal allergies and 5 (38%) a global worsening of symptoms. Endoscopic severity was also significantly worse during seasonal exacerbations (total EREFS 3.7 vs 1.7; P = .01). Baseline features differed by atopic diagnoses and endoscopic findings between patients with and without seasonal exacerbations.Conclusion
Seasonal exacerbations of eosinophilic esophagitis were uncommon in this cohort and most commonly recorded over the summer and fall months. These data support a role of aeroallergens in the pathogenesis of eosinophilic esophagitis in some patients, and clinicians should consider aeroallergens as a potential cause of disease exacerbation. 相似文献28.
Andrew P. Evan Don A. Hay William G. Dail 《Anatomical record (Hoboken, N.J. : 2007)》1978,191(4):397-413
The present study utilizes the scanning electron microscope (SEM) to reveal the surface morphology of proximal tubular cells and the parietal cells of Bowman's capsule of the adult rabbit nephron. To facilitate the examination of the basal surface of these cells, proximal tubules were dissected free and treated with collagenase to remove the basememt membrane. Other blocks of tissue were cryofractured to expose the lateral cell surfaces of the proximal tubules. Our investigation has shown that the lateral and basal surfaces of both the convoluted and straight segments of the proximal tubule have numerous processes. However, the arrangement and degree of branching is distinctly different in the two segments. The convoluted segment has large lateral ridges which form at the base of the microvilli and fan out to divide into lateral-basal processes. Many of the lateral-basal processes reach the basement membrane intact, interdigitating with complementary processes from adjacent cells. However, some of the lateral-basal processes branch into short, knobby projections (basal villi) which may also reach the basement membrane. Patches of basal villi are interspersed between broad regions of interdigitating lateralbasal processes. Therefore, in the convoluted segment, the lateral-basal processes form the major part of the basal cell surface. In tubular cells of the pars recta, unlike convoluted tubular cells, the majority of the ridges remain unbranched and pass directly to the basal surface where they divide into elaborate basal villi. Thus the basal surface of the pars recta cells is highly complex, appearing leaf-like, being a composite of numerous basal villi with a few lateral ridges. The basal surface of some parietal cells of Bowman's capsule have parallel ridges, which results in patches of striations. 相似文献
29.
Gabriel Lopez-Berestein Luka Milas Nancy Hunter Kapil Mehta Evan M. Hersh Carol G. Kurahara Marjorie Vanderpas Deborah A. Eppstein 《Clinical & experimental metastasis》1984,2(2):127-137
A new lipophilic muramyl dipeptide analog, 6-O-stearoyl-N-acetylmuramyl-L--aminobutyryl-D-isoglutamine, when incorporated in liposomes, was effective in both the prevention and eradication of experimental pulmonary metastases in mice. Multilamellar vesicles composed of synthetic phospholipids (phosphatidylglycerol and phosphatidylcholine) containing saturated myristoyl or unsaturated dioleoyl acyl chains were found to potentiate the antimetastatic activity of this glycopeptide. Prophylactic and therapeutic efficacy was observed against the three murine tumors tested: FSa, an immunogenic fibrosarcoma; NFSa, a nonimmunogenic fibrosarcoma; and B16 melanoma. Neither the administration of empty liposomes or free glycopeptide, nor their coadministration, had a significant antimetastatic effect. This approach is promising for the therapy of cancer metastases in humans, particularly in the prevention of metastatic seeding and in the treatment of micrometastases.This is contribution No. 180 from the Institute of Bio-Organic Chemistry, Syntex Research. 相似文献
30.
Jaffe DB Butler J Gnerre S Mauceli E Lindblad-Toh K Mesirov JP Zody MC Lander ES 《Genome research》2003,13(1):91-96
We previously described the whole-genome assembly program Arachne, presenting assemblies of simulated data for small to mid-sized genomes. Here we describe algorithmic adaptations to the program, allowing for assembly of mammalian-size genomes, and also improving the assembly of smaller genomes. Three principal changes were simultaneously made and applied to the assembly of the mouse genome, during a six-month period of development: (1) Supercontigs (scaffolds) were iteratively broken and rejoined using several criteria, yielding a 64-fold increase in length (N50), and apparent elimination of all global misjoins; (2) gaps between contigs in supercontigs were filled (partially or completely) by insertion of reads, as suggested by pairing within the supercontig, increasing the N50 contig length by 50%; (3) memory usage was reduced fourfold. The outcome of this mouse assembly and its analysis are described in (Mouse Genome Sequencing Consortium 2002). 相似文献