Recent studies have shown that human papillomavirus (HPV) DNA can be found in circulating blood, including peripheral blood mononuclear cells (PBMCs), sera, plasma, and arterial cord blood. In light of these findings, DNA extracted from PBMCs from healthy blood donors were examined in order to determine how common HPV DNA is in blood of healthy individuals. Blood samples were collected from 180 healthy male blood donors (18-76 years old) through the Australian Red Cross Blood Services. Genomic DNA was extracted and specimens were tested for HPV DNA by PCR using a broad range primer pair. Positive samples were HPV-type determined by cloning and sequencing. HPV DNA was found in 8.3% (15/180) of the blood donors. A wide variety of different HPV types were isolated from the PBMCs; belonging to the cutaneous beta and gamma papillomavirus genera and mucosal alpha papillomaviruses. High-risk HPV types that are linked to cancer development were detected in 1.7% (3/180) of the PBMCs. Blood was also collected from a healthy HPV-positive 44-year-old male on four different occasions in order to determine which blood cell fractions harbor HPV. PBMCs treated with trypsin were negative for HPV, while non-trypsinized PBMCs were HPV-positive. This suggests that the HPV in blood is attached to the outside of blood cells via a protein-containing moiety. HPV was also isolated in the B cells, dendritic cells, NK cells, and neutrophils. To conclude, HPV present in PBMCs could represent a reservoir of virus and a potential new route of transmission.

Cutaneous human papillomavirus (HPV) has been widely detected in healthy skin. Previous studies have found that UV radiation can activate several HPV types, and a possible role for cutaneous HPV in the development of non-melanoma skin cancer has been suggested. This study investigated the prevalence and type-spectrum of cutaneous HPV in relation to UV radiation by studying forehead skin swab samples from 50 healthy males frequently exposed to the sun and 50 healthy males who were not frequently exposed to the sun. A questionnaire including ethnic background of the participants, history of cancers and a self-assessment of sun-exposure was also conducted and analysed. PCR with the FAP primer pair was carried out to detect HPV DNA in samples. HPV prevalence was higher in individuals who spent more time outdoors and in individuals with a history of skin cancers (P50.044 and P50.04, respectively). Furthermore, individuals wearing sunglasses as a means of sun protection had a lower prevalence of HPV (P50.018). Interestingly, HPV-76 was only detected in the group without frequent sun-exposure (P50.001). These results suggest that increased UV radiation exposure may be a factor leading to a difference in prevalence of cutaneous HPV types. INTRODUCTIONHuman papillomaviruses (HPVs) infect cutaneous and mucosal epithelia and are recognized as the causative agents of warts. It has recently become apparent that clinically normal skin harbours many different HPV types, and many of these HPV types have not been described previously (Antonsson et al., 2000(Antonsson et al., , 2003a Astori et al., 1998). Furthermore, it has been shown that asymptomatic HPV infections are acquired very early in infancy with a broad spectrum of HPV types (Antonsson et al., 2003b), and that the prevalence of HPV DNA in healthy skin increases with age (Antonsson et al., 2000). Moreover, cutaneous HPV infections on healthy skin have often been found to persist over time (Hazard et al., 2006). Many studies have also suggested a role for HPV in the carcinogenesis of non-melanoma skin cancer (NMSC). Squamous cell carcinoma (SCC) can metastasize, and is known as the unfavourable form of NMSC compared with basal cell carcinoma (BCC). Interestingly, BCCs are found approximately three times more frequently in immunocompetent individuals; however, in immunosuppressed organ-transplant recipients, SCCs are more prevalent (Pfister, 2003). It has been reported that more HPV types have been found in actinic keratosis and SCC skin lesions than in normal skin (Alotaibi et al., 2006), and a greater variety of HPV types have also been found in immunosuppressed individuals than in immunocompetent individuals (Harwood et al., 2004). Both SCC and BCC develop mostly on sun-exposed sites (Frost & Green, 1994), and some specific types of HPV, including HPV-5, HPV-8, HPV-20 and HPV-77, have been shown to be activated by UV radiation (Akgül et al., 2005;Massimi et al., 2008;Michel et al., 2006;Purdie et al., 1999;Storey et al., 1998). Evidence of UV-induced E6/E7 oncogenici...

Chronic bronchiectasis is the irreversible dilation of the airways that can result from a variety of insults to the airway walls. This airway dilation is accompanied by chronic inflammation, mucus hypersecretion and recurrent bacterial infection. Whilst an association exists with severe childhood respiratory infection, the origin of bronchiectasis is considered idiopathic in a substantial proportion of cases. Bronchiectasis is characterised by a chronic, neutrophil dominated, inflammatory response. The cellular and molecular nature of the inflammation are poorly understood.Identification of the mechanisms that drive this inflammation is important for the improvement of therapy. Macrolide antibiotics can influence mucus production and inflammatory response. In particular, azithromycin and erythromycin have been shown to be beneficial in patients with chronic respiratory diseases. However, the mechanisms by which these positive treatment outcomes are achieved are not known.This project aimed to characterise the nature of inflammation in bronchiectasis, the expression of mucin glycoproteins, the expression of tissue remodelling markers, and the response of these parameters to macrolide therapy (erythromycin). To address this, bronchial biopsies, bronchoalveolar lavage fluid (BALF) and induced sputum samples were collected as part of the BLESS randomised trial of placebo vs long term low dose oral erythromycin.Concentrations of pro-inflammatory chemokines and cytokines associated with both innate and adaptive immunity including IL-8, IL-1β, TNF-α, IFN-, IL-13, IL-17A and IL-23 (P<0.001), were elevated in bronchoalveolar lavage fluid from bronchiectatic patients, demonstrating a complex mixed inflammatory response. Significant correlations were observed between sputum levels of IL-8 and IL-1 and the presence of bacterial pathogens in sputum, elevated serum CRP and poor lung function. Airway biopsies from bronchiectasis subjects showed increased expression of genes encoding chemokines (IL-8), antimicrobial molecules (DEFB1, LYZ, SAA1, SERPINA3) and goblet cell/mucin associated proteins (AGR2, TFF1, TFF3). The relative abundance of a specific isoform of the key airway gel-forming mucin, MUC5B, was also significantly higher in induced-sputum from bronchiectatic vs healthy individuals. Concentrations of tissue remodelling markers were also elevated in BALF from bronchiectatic subjects (EGF, bFGF, neutrophil elastase and total MMP activity). However, concentration of VEGF-A in BALF from bronchiectatic subjects was lower than in healthy individuals, and was negatively correlated to the number of total exacerbations in the preceding 12 months. Neither VEGF-A concentrations nor mucin protein levels correlated with levels of any individual inflammatory cytokine. Patterns of inflammation in BALF remained largely v