BackgroundWnt5a is a member of the wingless-type patterning regulators important in pre-natal development. The expression and distribution of Wnt5a and its receptors frizzled (fzd) 3 and fzd 5 in adult human skin have not been comprehensively studied to date.Methodology/Principal FindingsWe here show that Wnt5a, fzd3, fzd5, as well as fzd6 are restricted to specific layers in normal epidermis, analogous to their zonal distribution in hair follicles, suggesting a role in adult skin differentiation. In line, Wnt5a and fzd5 are both overexpressed and re-distributed in the epidermis of psoriasis which involves disturbed keratinocyte differentiation. Functionally, Wnt5a lowers the concentration of IFN required to induce target genes, and increases the magnitude of IFN target gene induction, suggesting a molecular mechanism underlying IFN hypersensitivity in psoriasis. Finally, we identify nedd8 and the amyloid precursor APP, previously shown to be upregulated in psoriasis, as targets of synergistic IFNα/Wnt5a induction.Conclusions/SignificanceThe present data (i) suggest that Wnt5a regulates epidermal differentiation even in adult skin and (ii) identify synergistic induction of type 1 IFN target genes as a novel mode of Wnt5a action. Targeting Wnt5a in the skin may reduce IFN hypersensitivity and be of therapeutical value.
Newer therapies for the treatment of HIV infection and the effectiveness of zidovudine in reducing vertical transmission mean that it is becoming increasingly important to diagnose HIV infection earlier. General practitioners (GPs) attending a local study day on sexually transmitted diseases (STDs) were asked about their likelihood of raising the subject of HIV antibody testing, and their anxiety when doing so, for different patient groups. A high level of anxiety was found when raising this topic in certain patient groups, and a proportion of GPs would never discuss HIV testing, even in very high-risk groups. No respondents were aware that vertical transmission could be reduced by antiretroviral drug therapy. These data advocate that the barriers to raising the issue of HIV testing and the methods of reducing GPs' anxiety associated with it, need to be addressed.
Objectives:To determine the level of awareness of genital chlamydial infection, and level of knowledge related to this infection, in genitourinary medicine (GUM) clinic attenders. Methods: 500 consecutive patients attending a GUM clinic for the first time during a 3 month study period were invited to complete an anonymous self administered questionnaire on aspects of chlamydial infection. Results: 482 (96.4%) questionnaires were available for analysis (57% female). 289 (60%) respondents had heard of Chlamydia trachomatis compared with 472 (98%) for thrush, 467 (97%) for HIV/AIDS, and 434 (90%) for gonorrhoea. Subjective knowledge of chlamydia, relative to the other infections, was poor. Overall, the mean chlamydial knowledge score was 0.38 (range 0.0-1.0). Females scored significantly higher than males (0.45 v 0.26; p<0.00001) and younger females scored significantly higher than older females (p=0.001). More females had experienced genital chlamydial infection than males (22.4% v 12.1%, p=0.004). Those with prior exposure to C trachomatis had higher mean knowledge scores than those without (males 0.55 v 0.25, p<0.00001; females 0.68 v 0.37, p<0.00001). Conclusion:Even for a population considered as "high risk" by their attendance at a GUM clinic, there was poor awareness of genital chlamydial infection, and mean knowledge scores were low. Whether increased knowledge was due to successful health education at the time of diagnosis in those with previous infection remains to be determined. In the future, one would hope for increased knowledge scores in those at risk before the acquisition of infection, which may be achieved by national health education programmes for C trachomatis. (Sex Transm Inf 1999;75:36-40)
The conventional method for antimicrobial susceptibility testing ofChlamydia trachomatis is subjective and potentially misleading. We have developed a reverse transcriptase PCR (RT-PCR)-based method which is more sensitive and less subjective than the conventional method. Using 16 strains of C. trachomatisin triplicate assays, we found the RT-PCR method consistently more sensitive than the conventional technique for all eight antimicrobials tested, with resultant MICs determined by RT-PCR ranging from 1.6-fold higher (erythromycin) to ≥195-fold higher (amoxicillin).
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