Identification of classical swine fever virus protein E2 as a target for cytotoxic T cells by using mRNA-transfected antigen-presenting cells.

Vaccination of pigs against Classical swine fever virus (CSFV) by using live-virus vaccines induces early protection before detectable humoral immune responses. Immunological analyses indicate that this is associated with T-cell activation, underlining the importance of targeting cytotoxic T-lymphocyte (CTL) responses for vaccine improvement. Antigen-presenting cells (APCs) transfected with mRNA encoding structural protein E2 or non-structural viral proteins NS3-NS4A were used to identify viral genes encoding CTL epitopes. Monocyte-derived dendritic cells (DCs) and fibrocytes served as the APCs. In vitro translation of the mRNA and microscopic analysis of transfected cells demonstrated that E2 and NS3-NS4A could be identified. APCs transfected with either of the mRNA molecules restimulated CSFV-specific T cells to produce gamma interferon and specific cytotoxic activity against CSFV-infected target cells. The presence of CTL epitopes on E2 was confirmed by using d/d-haplotype MAX cells expressing E2 constitutively as target cells in d/d-haplotype CTL assays. A potent CTL activity against E2 was detected early (1-3 weeks) after CSFV challenge. This work corroborates the existence of CTL epitopes within the non-structural protein domain NS3-NS4A of CSFV. Furthermore, epitopes on the E2 protein can also now be classified as targets for CTLs, having important implications for vaccine design, especially subunit vaccines. As for the use of mRNA-transfected APCs, this represents a simple and efficient method to identify viral genes encoding CTL epitopes in outbred populations.

Prevalence and natural history of female incontinence.

OBJECTIVE: Urinary incontinence is a common and highly embarrassing condition among females of all age groups and has been the subject of several epidemiological studies in the past. METHODS: From an extensive literature search covering the time period from 1954 to 1995, 48 epidemiological studies and several other publications dealing with prevalence and natural history of female incontinence were reviewed. Meta-analysis of reported data was performed in respect of incontinence definitions, investigation methods, home country of survey and age groups. RESULTS: Available data are nonhomogenous and difficult to compare because of differences in definitions of incontinence, target populations and study design in different investigations. By grouping the studies by similarities in the above criteria and analysing the results for each group of studies, an attempt was made to understand the great variation of reported results. Differences in prevalence of incontinence were identified for all examined aspects and for distinct ethnic populations. The little information that exists on the incidence, spontaneous remission rates and risk factors were used to elucidate the natural history of female incontinence. CONCLUSION: A generally accepted definition of incontinence is highly desirable and should comprise aspects of severity and demonstrability of the condition, bother factor and impact on quality of life. Furthermore, basic requirements for epidemiological surveys of incontinence such as validation of questionnaire results need to be defined and standardised to establish a sensible basis for useful epidemiological studies in the future.

Definition of overactive bladder and epidemiology of urinary incontinence.

OBJECTIVES: To review the definition of the overactive bladder and to summarize the results of epidemiologic studies on this specific disorder as well as urinary incontinence (UI) in general. METHODS: From a literature search covering the time period from 1954 through 1995, 48 epidemiologic studies and several other publications dealing with the prevalence and natural history of UI were reviewed. A meta-analysis of reported data was performed with respect to incontinence definitions, investigation methods, home country of survey, sex, and age groups. RESULTS: Differences in definitions of incontinence, target populations, and study design in different investigations resulted in inhomogeneity and difficulties of comparing the available data. By grouping the studies with respect to similarities in the above-mentioned criteria and analyzing the results for each group of studies, an attempt was made to understand the great variation of reported results. Differences in prevalence of incontinence were identified for all examined groups of studies and for distinct ethnic populations. Scarce information about incidence, spontaneous remission rates, and risk factors was used to elucidate the natural history of UI in women and men. CONCLUSIONS: Although generally accepted definitions of the overactive bladder specifically and UI in general are highly desirable, they have not yet been established. Such definitions should comprise aspects of severity and demonstrability of the condition, bother factor, and impact on quality of life. Moreover, basic requirements for epidemiologic surveys of incontinence, such as validation of questionnaire results, need to be defined and standardized to create a sensible basis for useful epidemiologic studies in the future.