A novel and safe technique for injections into the oral cavity.
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Humans↗
Biomedical subjects
Patrick McGowan
Publications and source records attributed to Patrick McGowan.
Diversity of the CD8+ T-cell response to herpes simplex virus type 2 proteins among persons with genital herpes.
Cytolytic T cells play a major role in controlling herpes simplex virus type 2 (HSV-2) infections in humans. In an effort to more thoroughly evaluate the response to HSV-2 directly, ex vivo, we developed an enzyme-linked immunospot (ELISPOT) assay that utilized pools of overlapping synthetic peptides presented by autologous dendritic cells to purified CD8(+) T cells. Donor response rates to individual open reading frames (ORFs) ranged from fewer than 5% responding to as many as 70% responding, with the greatest frequency of responses (by ORF) being directed against UL39, UL25, UL27, ICP0, UL46, and UL47 in descending order of frequency. HSV-2-seropositive subjects responded to as few as 3 or as many as 46 of the 48 ORFs tested, with a median of 11 ORFs recognized. HLA-B*07 expression correlated with stronger responses overall that were directed primarily against UL49 and UL46. Cumulative precursor frequencies in the blood ranged from 500 to almost 6,000 HSV-2 spot-forming units/10(6) CD8(+) T cells. The magnitude and breadth of the response in the infected population were greater than previously appreciated. Whether this variability in the CD8(+) T-cell response within individuals is associated with the frequency of viral reactivation warrants further study.
CD8-Positive T-Lymphocytes↗
TLR4 agonists as immunomodulatory agents.
Monophosphoryl lipid A (MPL) is a potent vaccine adjuvant derived from Salmonella minnesota that was recently licensed in Europe as a component of an improved vaccine for hepatitis B (Fendrix). MPL, like lipopolysaccharide from which it is derived, signals via the TLR4/MD-2 complex. We have produced a series of synthetic Toll-like receptor 4 (TLR4) agonists that are based upon the structure of the major hexa-acylated congener contained within MPL. These TLR4 agonists, termed the aminoalkyl glucosaminide phosphates (AGPs), stimulate the production of various cytokines by human peripheral blood mononuclear cells in vitro and up-regulate cell surface markers on monocytes, NK cells and B cells. In addition, AGPs provide non-specific resistance to challenge with viral and bacterial pathogens when administered to the upper airways of mice. Structure-activity relationship studies have shown that the activation of innate immune effectors by AGPs depends primarily on the length of the secondary acyl chains and the nature of the functional group attached to the aglycon component. Moreover, AGPs can act as potent adjuvants for mucosal administration of vaccine antigens, enhancing both antigen-specific antibody and cell-mediated immune responses. Thus, by combining the adjuvant and non-specific resistance induction properties of AGPs it may be possible to generate mucosal vaccines that provide innate protection immediately following administration together with long-term acquired immunity.
Adjuvants, Immunologic↗
Qualitative evaluation of Chronic Disease Self Management Program (CDSMP) in Shanghai.
OBJECTIVES: To explore the impact of Chronic Disease Self-Management Program (CDSMP) on participants' perception of their behavior, health status and quality of life and how the program achieve its benefits, and to collect suggestions for future improvement and dissemination. METHODS: Qualitative data were obtained from 57 participants attending all sessions of the CDSMP course using semi-structured interviews and analyzed using content analysis. RESULTS: The interviewees perceived that CDSMP improved their knowledge, self-management skills, positive health behavior, increased self-confidence, health status and quality of life. Behavior change and self-efficacy were the two main transmitters of the effectiveness of CDSMP in Shanghai. The identified deficiencies focused on language, size and style of helpbook and the lack of Chinese relaxing exercises. CONCLUSION: CDSMP was perceived to be effective to participants mainly through behavior change and self-efficacy development, though it had a few deficiencies to be modified. PRACTICE IMPLICATIONS: CDSMP in Shanghai needs further work and research on the content and delivery modification for future improvement and dissemination.
Aged↗
Taking a Toll on human disease: Toll-like receptor 4 agonists as vaccine adjuvants and monotherapeutic agents.
Toll-like receptor (TLR) agonists are being developed for use as vaccine adjuvants and as stand-alone immunomodulators because of their ability to stimulate innate and adaptive immune responses. Among the most thoroughly studied TLR agonists are the lipid A molecules that target the TLR4 complex. One promising candidate, monophosphoryl lipid A, which is a derivative of lipid A from Salmonella minnesota, has proven to be safe and effective as a vaccine adjuvant in > 120,000 human doses. A new class of synthetic lipid A mimetics, the aminoalkyl glucosaminide 4-phosphates (AGPs), have been engineered specifically to target human TLR4 and are showing promise as vaccine adjuvants and as monotherapeutic agents capable of eliciting nonspecific protection against a wide range of infectious pathogens. In this review, the authors provide an update of the preclinical and clinical experiences with the TLR4 agonists, MPL (Corixa Corporation) adjuvant and the AGPs.
Adjuvants, Immunologic↗
Implementation and quantitative evaluation of chronic disease self-management programme in Shanghai, China: randomized controlled trial.
OBJECTIVE: To evaluate the effectiveness of the Shanghai Chronic Disease Self-Management Program (CDSMP). METHODS: A randomized controlled trial with six-month follow-up compared patients who received treatment with those who did not receive treatment (waiting-list controls) in five urban communities in Shanghai, China. Participants in the treatment group received education from a lay-led CDSMP course and one copy of a help book immediately; those in the control group received the same education and book six months later. FINDINGS: In total, 954 volunteer patients with a medical record that confirmed a diagnosis of hypertension, heart disease, chronic lung disease, arthritis, stroke, or diabetes who lived in communities were assigned randomly to treatment (n = 526) and control (n = 428) groups. Overall, 430 (81.7%) and 349 (81.5%) patients in the treatment and control groups completed the six-month study. Patients who received treatment had significant improvements in weekly minutes of aerobic exercise, practice of cognitive symptom management, self-efficacy to manage own symptoms, and self-efficacy to manage own disease in general compared with controls. They also had significant improvements in eight indices of health status and, on average, fewer hospitalizations. CONCLUSION: When implemented in Shanghai, the CDSMP was acceptable culturally to Chinese patients. The programme improved participants' health behaviour, self-efficacy, and health status and reduced the number of hospitalizations six months after the course. The locally based delivery model was integrated into the routine of community government organizations and community health services. Chinese lay leaders taught the CDSMP courses as successfully as professionals.
Aged↗
What do Canadian seniors say supports their quality of life? Findings from a national participatory research study.
BACKGROUND: A national project investigated seniors' perceptions of the influences upon their quality of life. The seven participating cities were Montreal, Quebec City, Ottawa, Toronto, Regina, Vancouver and Whitehorse. The project focussed on policy decisions affecting the quality of life of seniors. It was a participatory study in which seniors controlled the direction and shape of the project in each city. METHODS: Focus groups and individual interviews with seniors and stakeholders. Data analysis used qualitative methods to see the world through the eyes of participants. Each project was committed to hearing the voices of seniors and their views on which issues were affecting the quality of their lives. RESULTS: Across the seven cities, seniors highlighted access to information, health care, housing, income security, safety and security, social contacts and networks, and transportation as key issues that affect the quality of life of seniors in Canada. CONCLUSIONS: The findings affirm the value of participatory activities that involve seniors working with other sectors as a productive policy-informing approach. The Seniors' Quality of Life projects demonstrate the conceptual power of the determinants of health perspective to understand seniors' quality of life issues. While seniors considered health care to be a continuing concern, they also recognized socio-economic issues as significantly affecting the quality of their lives.
Access to Information↗