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Murine gammaherpesvirus-68 (MHV68) is genetically related to human Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus and provides a tractable model to study gammaherpesvirus-host interactions in vivo and in vitro. The MHV68-encoded v-RCA product inhibits murine complement activation and shares sequence homology with other virus and host regulators of complement activation. Here we show that v-RCA is required for efficient MHV68 replication in primary murine macrophages, but not in murine embryonic fibroblasts. v-RCA-deficient MHV68 mutant viruses display defects in viral DNA synthesis in infected macrophages. Importantly, attenuated growth of v-RCA mutant viruses is not rescued in macrophages lacking critical components of the complement system including C3, indicating that the macrophage-specific role of v-RCA in MHV68 replication is complement-independent. This contrasts with the situation in vivo in which attenuated neurovirulence of v-RCA mutant viruses is rescued in C3-deficient mice. This study shows a novel, complement independent cell-type-specific function of a gammaherpesvirus RCA protein. 相似文献
84.
John H. Boman IV Ph.D. John Stogner Ph.D Bryan Lee Miller Ph.D 《Journal of psychoactive drugs》2013,45(3):218-226
Abstract While it is commonly understood that the substance use of peers influences an individual's substance use, much less is understood about the interplay between substance use and friendship quality. Using a sample of 2,148 emerging adults nested within 1,074 dyadic friendships, this study separately investigates how concordance and discordance in binge drinking and marijuana use between friends is related to each friend's perceptions of friendship quality. Because “friendship quality” is a complex construct, we employ a measure containing five sub-elements – companionship, a lack of conflict, willingness to help a friend, relationship security, and closeness. Results for both binge drinking and marijuana use reveal that individuals in friendship pairs who are concordant in their substance use perceive significantly higher perceptions of friendship quality than individuals in dyads who are dissimilar in substance use. Specifically, concordant binge drinkers estimate significantly higher levels of companionship, relationship security, and willingness to help their friend than concordant non-users, discordant users, and discordant non-users. However, the highest amount of conflict in friendships is found when both friends engage in binge drinking and marijuana use. Several interpretations of these findings are discussed. Overall, concordance between friends’ binge drinking and marijuana use appears to help some elements of friendship quality and harm others. 相似文献
85.
Ralph L. Cooper James C. Lamb IV Sue M. Barlow Karin Bentley Angela M. Brady Nancy G. Doerrer 《Critical reviews in toxicology》2013,43(1):69-98
Aproposal has been developed by the Agricultural Chemical Safety Assessment (ACSA) Technical Committee of the ILSI Health and Environmental Sciences Institute (HESI) for an improved approach to assessing the safety of crop protection chemicals. The goal is to ensure that studies are scientifically appropriate and necessary without being redundant, and that tests emphasize toxicological endpoints and exposure durations that are relevant for risk assessment. The ACSA Life Stages Task Force proposes a tiered approach to toxicity testing that assesses a compound's potential to cause adverse effects on reproduction, and that assesses the nature and severity of effects during development and adolescence, with consideration of the sensitivity of the elderly. While incorporating many features from current guideline studies, the proposed approach includes a novel rat reproduction and developmental study with enhanced endpoints and a rabbit development study. All available data, including toxicokinetics, ADMEdata, and systemic toxicity information, are considered in the design and interpretation of studies. Compared to existing testing strategies, the proposed approach uses fewer animals, provides information on the young animal, and includes an estimation of human exposure potential for making decisions about the extent of testing required. 相似文献
86.
Technical toxaphene (TT) was last used in commerce in about 1982. Any environmental exposure to toxaphene in this century is to environmentally degraded forms of toxaphene, termed weathered toxaphene. Several hundred chlorinated bornane congeners have been identified in technical toxaphene. The degradation of technical toxaphene to weathered toxaphene can result in various congener mixtures, but the primary mode of degradation is dechlorination. The U.S. Environmental Protection Agency (EPA) presently estimates the risk of exposure to toxaphene by relying upon rat and mouse toxicology studies performed on technical toxaphene. No adjustment is made for the dechlorination of toxaphene in the environment. The European Union (EU), however, has modeled toxaphene risks from eating fish with chlorinated bornane residues through a series of studies on toxaphene degraded by either ultraviolet light, or biodegradation in fish. The EU risk assessment relies upon rat liver studies in vivo and mouse in vitro studies on the inhibition of gap junction intercellular communication (GJIC). This article reviews the current state of knowledge of technical and weathered toxaphene toxicology. We discuss the various current methods and opportunities to advance the risk assessment of weathered toxaphene beyond the existing U.S. EPA assessment of technical toxaphene. 相似文献
87.
Many neurologists and headache specialists are befuddled by inside the Beltway wheelings and dealings as they follow health care politics. A few of us join lobbying efforts, and even fewer become strangers in a strange land. 相似文献
88.
A direct comparison of rejection by CD8 and CD4 T cells in a transgenic model of allotransplantation
Porrett PM Lee MK Lian MM Wang J Caton AJ Deng S Markmann JF Moore DJ 《Archivum immunologiae et therapiae experimentalis》2008,56(3):193-200
INTRODUCTION: The relative contributions of CD4+ and CD8+ T cells to transplant rejection remain unknown. The authors integrated a previous model of CD4-mediated graft rejection with a complementary model of CD8-mediated rejection to directly compare the function of graft-reactive CD4+ and CD8+ lymphocytes in vivo in a model where rejection requires transgenic T cells. These studies allow direct comparison of CD4 and CD8 T cell responses to the same antigen without the confounding effects of T cell depletion or homeostatic proliferation. MATERIALS AND METHODS: Clone 4 and TS1 mice possess MHC class I- and II-restricted CD8+ and CD4+ T cells, respectively, which express transgenic T cell receptors that recognize the influenza hemagglutinin antigen (HA). We compared the in vivo response of CFSE-labeled, HA-specific transgenic CD8+ and CD4+ T cells after adoptive transfer into syngeneic BALB/c mice grafted with HA-expressing skin. RESULTS: As in the authors' CD4+ model, HA104 skin was consistently rejected by both Clone 4 mice (n=9, MST: 14.2) and by 5 x 10(5) Clone 4 lymphocytes transferred to naive BALB/c hosts that do not otherwise reject HA+ grafts. Rejection correlated with extensive proliferation of either graft-reactive T cell subset in the draining lymph nodes, and antigen-specific CD4+ and CD8+ cells acquired effector function and proliferated with similar kinetics. CONCLUSIONS: These data extend the authors' unique transgenic transplantation model to the investigation of CD8 T cell function. The initial results confirm fundamental functional similarity between the CD4 and CD8 T cell subsets and provide insight into the considerable redundancy underlying T cell mechanisms mediating allograft rejection. 相似文献
89.
Evidence for participation of neutrophil gelatinase‐associated lipocalin/matrix metalloproteinase‐9 (NGAL•MMP‐9) complex in the inflammatory response to infection in pregnancies complicated by preterm birth 下载免费PDF全文
90.
David A. Amato Howard Bruckner DuPont Guerry IV Arlene Ash Geoffrey Falkson Ernest C. Borden Richard H. Creech Edwin D. Savlov Thomas J. Cunningham 《Investigational new drugs》1987,5(3):293-297
In this Eastern Cooperative Oncology Group (ECOG) phase II study, dibromodulcitol (DBD) and a combination of actinomycin D, hydroxyurea, and cyclophosphamide (AHC) were compared with methyl-CCNU, the current ECOG standard, in patients who had received no prior chemotherapy for disseminated malignant melanoma. The response rates were 6% (3/50) for AHC, 9% (3/34) for DBD, and 14% (7/49) for methyl-CCNU. Median survival times were 4, 5, and 6 months, respectively. Neither regimen appears to offer any advantage over methyl-CCNU as front-line therapy for patients with disseminated melanoma. 相似文献