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Jin Huk Choi Joe Dekker Stephen C. Schafer Jobby John Craig E. Whitfill Christopher S. Petty Eid E. Haddad Maria A. Croyle 《Clinical and Vaccine Immunology : CVI》2012,19(1):84-95
The immune response to recombinant adenoviruses is the most significant impediment to their clinical use for immunization. We test the hypothesis that specific virus-antibody combinations dictate the type of immune response generated against the adenovirus and its transgene cassette under certain physiological conditions while minimizing vector-induced toxicity. In vitro and in vivo assays were used to characterize the transduction efficiency, the T and B cell responses to the encoded transgene, and the toxicity of 1 × 1011 adenovirus particles mixed with different concentrations of neutralizing antibodies. Complexes formed at concentrations of 500 to 0.05 times the 50% neutralizing dose (ND50) elicited strong virus- and transgene-specific T cell responses. The 0.05-ND50 formulation elicited measurable anti-transgene antibodies that were similar to those of virus alone (P = 0.07). This preparation also elicited very strong transgene-specific memory T cell responses (28.6 ± 5.2% proliferation versus 7.7 ± 1.4% for virus alone). Preexisting immunity significantly reduced all responses elicited by these formulations. Although lower concentrations (0.005 and 0.0005 ND50) of antibody did not improve cellular and humoral responses in naïve animals, they did promote strong cellular (0.005 ND50) and humoral (0.0005 ND50) responses in mice with preexisting immunity. Some virus-antibody complexes may improve the potency of adenovirus-based vaccines in naïve individuals, while others can sway the immune response in those with preexisting immunity. Additional studies with these and other virus-antibody ratios may be useful to predict and model the type of immune responses generated against a transgene in those with different levels of exposure to adenovirus. 相似文献
995.
Stephen Boorjian 《Urologic oncology》2013,31(1):129-130
996.
Maarten Milders Stephen Bell Angus Lorimer Tom MacEwan Alison McBain 《Geriatric nursing (New York, N.Y.)》2013
Cognitive stimulation (CS) is a psychological intervention for people with dementia aimed at maintaining cognitive functioning. CS provided by caregivers would allow long-term maintenance without greatly increasing demands on health services, but raises questions concerning treatment fidelity and acceptability, which were investigated in this study. Caregivers of home-living people with dementia were trained to provide CS activities to their relative with dementia. Recordings of intervention sessions and analysis of training manuals suggested adequate delivery of the intervention. Dyads continued with the activities after caregiver training had stopped. In addition, presentation of the activities without supervision from a health care professional had no detrimental effect on well-being in the caregiver or the person with dementia. The majority of caregivers indicated that, even though they experienced some burden from doing the activities with their relative, they themselves had also benefited from the intervention and intended to continue with some of the activities. 相似文献
997.
The safe and effective management of aggression has become an increasingly critical skill for mental health nurses, particularly those working in acute inpatient settings. There is considerable evidence to suggest that the psychological constructs of self-efficacy and locus of control are closely related to work performance in a variety of occupations. By drawing upon literature published in the past 15 years, this paper highlights this evidence and draws attention to the relationship between self-efficacy and locus of control. The central argument of the paper is that there may be direct relationships among mental health nurses” self-efficacy, their degree of internality or externality in relation to locus of control, and their ability to safely and effectively manage aggressive incidents. We argue the need to further investigate these relationships and discover whether these variables can be modified through professional development activities. 相似文献
998.
Lucas Restrepo Phillip Stafford Stephen Albert Johnston 《Journal of neuroimmunology》2013,254(1-2):154-160
A practical diagnostic test is needed for early Alzheimer's disease (AD) detection. Immunosignaturing, a technology that employs antibody binding to a random-sequence peptide microarray, generates profiles that distinguish transgenic mice engineered with familial AD mutations (APPswe/PSEN1-dE9) from non-transgenic littermates. It can also detect an AD-like signature in humans. Here, we assess the changes in the immunosignature at different time points of the disease in mice and humans. We also evaluate the accuracy of the late-stage signature as a test to discriminate between young mice with familial AD mutations from non-transgenic littermates. Plasma samples from AD patients were assayed 3–12 months apart, while APPswe/PSEN1-dE9 and non-transgenic controls supplied plasma at monthly intervals until they reached 15 months of age. Microarrays with 10,000 random-sequence peptides were used to compare antibody binding patterns. These patterns gradually changed over the life-span of mice. Strong, characteristic signatures were observed in transgenic mice at early, mid and late stages, but these profiles had minimal overlap. The signature of young transgenic mice had an error rate of 18% at classifying plasma samples from late-stage transgenic mice. Conversely, the late-stage transgenic mice signature discriminated between young transgenic mice and littermates with an error rate of 21%. Less distinctive profiles were recognizable throughout the transgenic mice lifespan, being detectable as early as 2 months. The human signature had minimal change on short-term follow-up. Our results call for a reappraisal of the way incipient AD is studied, as biomarkers seen in late-stages of the disease may not be relevant in earlier stages. 相似文献
999.
Alexandre B. Laudet Stephen Magura Charles M. Cleland Howard S. Vogel Edward L. Knight Andrew Rosenblum 《Journal of psychoactive drugs》2013,45(2):207-216
Abstract A large percentage of individuals are dually-diagnosed with a psychiatric disorder and a substance use disorder. Such persons typically face more difficulties and have poorer outcomes than do single disorder substance users. Among noncomorbid substance users, treatment and participation in 12-Step groups have been shown to enhance the likelihood of abstinence from substance misuse. Specialized 12-Step based fellowships have recently emerged to address the recovery needs of dually-diagnosed persons. The present study is a longitudinal investigation of the effect of such 12-Step based groups on abstinence among dually-diagnosed persons. Participants were members of Double Trouble in Recovery (DTR) who were recruited at community-based meetings in New York City and reinterviewed twice at yearly intervals. Generalized estimating equation analysis indicated that, over the two-year study period, ongoing DTR attendance was significantly associated with a greater likelihood of abstinence after controlling for other pertinent variables, such as mental health symptoms. For clinicians, these findings underline the importance of fostering stable affiliation with specialized 12-Step based groups among their clients. 相似文献
1000.
William H. Gaze Stephen M. Krone D.G. Joakim Larsson Xian-Zhi Li Joseph A. Robinson Pascal Simonet Kornelia Smalla Mohammed Timinouni Ed Topp Elizabeth M. Wellington Gerard D. Wright Yong-Guan Zhu 《Emerging infectious diseases》2013,19(7)
The clinical failure of antimicrobial drugs that were previously effective in controlling infectious disease is a tragedy of increasing magnitude that gravely affects human health. This resistance by pathogens is often the endpoint of an evolutionary process that began billions of years ago in non–disease-causing microorganisms. This environmental resistome, its mobilization, and the conditions that facilitate its entry into human pathogens are at the heart of the current public health crisis in antibiotic resistance. Understanding the origins, evolution, and mechanisms of transfer of resistance elements is vital to our ability to adequately address this public health issue. 相似文献