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121.
Lack of Viral Escape and Defective In Vivo Activation of Human Immunodeficiency Virus Type 1-Specific Cytotoxic T Lymphocytes in Rapidly Progressive Infection 下载免费PDF全文
Christine M. Hay Debbie J. Ruhl Nesli O. Basgoz Cara C. Wilson James M. Billingsley Maria Pia DePasquale Richard T. DAquila Steven M. Wolinsky John M. Crawford David C. Montefiori Bruce D. Walker 《Journal of virology》1999,73(7):5509-5519
Human immunodeficiency virus type 1 (HIV-1)-specific immune responses over the course of rapidly progressive infection are not well defined. Detailed longitudinal analyses of neutralizing antibodies, lymphocyte proliferation, in vivo-activated and memory cytotoxic T-lymphocyte (CTL) responses, and viral sequence variation were performed on a patient who presented with acute HIV-1 infection, developed an AIDS-defining illness 13 months later, and died 45 months after presentation. Neutralizing-antibody responses remained weak throughout, and no HIV-1-specific lymphocyte proliferative responses were seen even early in the disease course. Strong in vivo-activated CTL directed against Env and Pol epitopes were present at the time of the initial drop in viremia but were quickly lost. Memory CTL against Env and Pol epitopes were detected throughout the course of infection; however, these CTL were not activated in vivo. Despite an initially narrow CTL response, new epitopes were not targeted as the disease progressed. Viral sequencing showed the emergence of variants within the two targeted CTL epitopes; however, viral variants within the immunodominant Env epitope were well recognized by CTL, and there was no evidence of viral escape from immune system detection within this epitope. These data demonstrate a narrowly directed, static CTL response in a patient with rapidly progressive disease. We also show that disease progression can occur in the presence of persistent memory CTL recognition of autologous epitopes and in the absence of detectable escape from CTL responses, consistent with an in vivo defect in activation of CTL. 相似文献
122.
The maternal determinant VegT is required for both endoderm and mesoderm formation by the Xenopus embryo. An important downstream mediator of VegT action is Xsox17, which has been proposed to be induced in cell-autonomous, then signal-dependent phases. We show that Xsox17 is a direct VegT target, but that direct induction of Xsox17 by VegT is rapidly inhibited. This inhibition is relieved by TGF- beta signalling, to which the future endoderm cell is sensitised by VegT, resulting in the observed dependence on cell contact for maintained Xsox17 expression. We propose that this change in regulation is a consequence of a VegT-induced repressor, inhibiting direct induction of early endoderm markers by VegT, and contributing to the formation of the boundary of the endodermal domain. 相似文献
123.
Edward Brown Judith Mantell Debbie Carter Gini Tilly Paul Verkade 《Seminars in cell & developmental biology》2009,20(8):910-919
Correlative Light Electron Microscopy (CLEM) aims at combining the best of light and electron microscopy in one experiment. Light microscopy (LM) is especially suited for providing a general overview with data from lots of different cells and by using live cell imaging it can show the history or sequence of events between or inside cells. Electron microscopy (EM) on the other hand can provide a much higher resolution image of a particular event and provide additional spatial information, the so-called reference space. CLEM thus has certain strengths over the application of both LM and EM techniques separately. But combining both modalities however generally also means making compromises in one or both of the techniques. Most often the preservation of ultrastructure for the electron microscopy part is sacrificed. Ideally samples should be visualized in its most native state both in the light microscope as well as the electron microscope. For electron microscopy this currently means that the sample will have to be cryo-fixed instead of the standard chemical fixation. In this paper we will discuss the rationale for using cryofixation for CLEM experiments. In particular we will highlight a CLEM technique using high-pressure freezing in combination with live cell imaging. In addition we examine some of the EM analysis tools that may be useful in combination with CLEM techniques. 相似文献
124.
Michael A. McClurkin Leah Rae Yingling Colby Ayers Rebecca Cooper-McCann Visakha Suresh Ann Nothwehr Debbie S. Barrington Tiffany M. Powell-Wiley 《PloS one》2015,10(11)
Background
Little is known about the association between cardiovascular (CV) health and health insurance status. We hypothesized that U.S. adults without health insurance coverage would have a lower likelihood of ideal cardiovascular health.Methods and Results
Using National Health and Nutrition Examination Survey (NHANES) data from 2007–2010, we examined the relationship between health insurance status and ideal CV health in U.S. adults aged ≥19 years and <65 (N = 3304). Ideal CV health was defined by the American Heart Association (AHA) as the absence of clinically manifested CV disease and the simultaneous presence of 6–7 “ideal” CV health factors and behaviors. Logistic regression modeling was used to determine the relationship between health insurance status and the odds of ideal CV health. Of the U.S. adult population, 5.4% attained ideal CV health, and 23.5% were without health insurance coverage. Those without health insurance coverage were more likely to be young (p<0.0001), male (p<0.0001), non-white (p<0.0001), with less than a high school degree (p<0.0001), have a poverty-to-income ratio less than 1 (p<0.0001) and unemployed (p<0.0001) compared to those with coverage. Lack of health insurance coverage was associated with a lower likelihood of ideal CV health; however, this relationship was attenuated by socioeconomic status.Conclusions
U.S. adults without health insurance coverage are less likely to have ideal CV health. Population-based strategies and interventions directed at the community-level may be one way to improve overall CV health and reach this at-risk group. 相似文献125.
126.
Slobodan V Jovanovic Debbie Clements Kent MacLeod 《Free radical biology & medicine》1998,25(9):1044-1048
There is convincing epidemiological and in vitro evidence of chronic oxidative stress in individuals with Down syndrome (DS). These individuals develop Alzheimer like changes in the brain in their 30s and 40s. The incidence of autoimmune diseases and cataracts is significantly increased, and the overall ageing process is accelerated. In vitro studies show that impaired viability of DS neurons may be amended by simple chemical antioxidants, such as vitamin E, BHT and propyl gallate, clearly indicative of oxyl radical involvement. However, because of the lack of in vivo experiments, the role of oxidative stress in DS remains controversial. We report here on the results of the chemical analyses of urine samples of 166 individuals, where DS subjects were matched by their siblings. The levels of 8-hydroxy-2′-deoxyguanosine (2.35 ± 1.69 in DS vs. 1.35 ± 1.04 in controls, P = 0.00011), a biomarker of oxidative damage to DNA, and malondialdehyde (0.255 ± 0.158 in DS vs. 0.204 ± 0.128 in controls, P = 0.033), a biomarker of lipid peroxidation, are significantly elevated in individuals with DS. Dietary influences failed to show any significant correlation with the oxidative stress biomarkers. These results provide direct evidence for increased oxidative stress in individuals with DS. 相似文献
127.
Natalie A. Sawaya Nava Baran Shelby Mahank Arvind Varsani Debbie Lindell Mya Breitbart 《Environmental microbiology》2021,23(11):6622-6636
Advances in metagenomics have revealed the ubiquity of single-stranded DNA (ssDNA) phage belonging to the subfamily Gokushovirinae in the oceans; however, the abundance and ecological roles of this group are unknown. Here, we quantify gokushoviruses through adaptation of the polony method, in which viral template DNA is immobilized in a gel, amplified by PCR, and subsequently detected by hybridization. Primers and probes for this assay were designed based on PCR amplicon diversity of gokushovirus major capsid protein gene sequences from a depth profile in the Gulf of Aqaba, Red Sea sampled in September 2015. At ≥95% identity, these 87 gokushovirus sequences formed 14 discrete clusters with the largest clades showing distinct depth distributions. The application of the polony method enabled the first quantification of gokushoviruses in any environment. The gokushoviruses were most abundant in the upper 40 m of the stratified water column, with a subsurface peak in abundance of 1.26 × 105 viruses ml−1. These findings suggest that discrete gokushovirus genotypes infect bacterial hosts that differentially partition in the water column. Since the designed primers and probe are conserved across marine ecosystems, this polony method can be applied broadly for the quantification of gokushoviruses throughout the global oceans. 相似文献
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S100B protein is found in brain, has been used as a marker for brain injury and is neurotrophic. Using a well-characterized in vitro model of brain cell trauma, we have previously shown that strain injury causes S100B release from neonatal rat neuronal plus glial cultures and that exogenous S100B reduces delayed post-traumatic neuronal damage even when given at 6 or 24 h post-trauma. The purpose of the current studies was to measure post-traumatic S100B release by specific brain cell types and to examine the effect of an antibody to S100 on post-traumatic delayed (48 h) neuronal injury and the protective effect of exogenous S100B. Neonatal rat cortical cells grown on a deformable elastic membrane were subjected to a strain (stretch) injury produced by a 50 ms displacement of the membrane. S100B was measured with an ELISA kit. Trauma released S100B from pure cultures of astrocytes, microglia, and neurons. Anti-S100 reduced released S100B to below detectable levels, increased delayed neuronal injury in traumatized cells and negated the protective effect of exogenous S100B on injured cells. Heat denatured anti-S100 did not exacerbate injury. These studies provide further evidence for a protective role for S100B following neuronal trauma. 相似文献