Eyebrow hairs from actinic keratosis patients harbor the highest number of cutaneous human papillomaviruses

BACKGROUND: Cutaneous human papillomavirus (HPV) infections seem to be associated with the onset of actinic keratosis (AK). This study compares the presence of cutaneous HPV types in eyebrow hairs to those in tissues of normal skin and skin lesions of 75 immunocompetent AK patients. METHODS: Biopsies from AK lesions, normal skin and plucked eyebrow hairs were collected from each patient. DNA from these specimens was tested for the presence of 28 cutaneous HPV (betaPV and gammaPV) by a PCR based method. RESULTS: The highest number of HPV prevalence was detected in 84% of the eyebrow hairs (63/75, median 6 types) compared to 47% of AK lesions (35/75, median 3 types) (p< 0.001) and 37% of normal skin (28/75, median 4 types) (p< 0.001), respectively. A total of 228 HPV infections were found in eyebrow hairs compared to only 92 HPV infections in AK and 69 in normal skin. In all three specimens HPV20, HPV23 and/or HPV37 were the most prevalent types. The highest number of multiple types of HPV positive specimens was found in 76% of the eyebrow hairs compared to 60% in AK and 57% in normal skin. The concordance of at least one HPV type in virus positive specimens was 81% (three specimens) and 88-93% of all three combinations with two specimens. CONCLUSIONS: Thus, eyebrow hairs revealed the highest number of cutaneous HPV infections, are easy to collect and are an appropriate screening tool in order to identify a possible association of HPV and AK

Lung Epithelial Injury by B. Anthracis Lethal Toxin Is Caused by MKK-Dependent Loss of Cytoskeletal Integrity

Bacillus anthracis lethal toxin (LT) is a key virulence factor of anthrax and contributes significantly to the in vivo pathology. The enzymatically active component is a Zn2+-dependent metalloprotease that cleaves most isoforms of mitogen-activated protein kinase kinases (MKKs). Using ex vivo differentiated human lung epithelium we report that LT destroys lung epithelial barrier function and wound healing responses by immobilizing the actin and microtubule network. Long-term exposure to the toxin generated a unique cellular phenotype characterized by increased actin filament assembly, microtubule stabilization, and changes in junction complexes and focal adhesions. LT-exposed cells displayed randomly oriented, highly dynamic protrusions, polarization defects and impaired cell migration. Reconstitution of MAPK pathways revealed that this LT-induced phenotype was primarily dependent on the coordinated loss of MKK1 and MKK2 signaling. Thus, MKKs control fundamental aspects of cytoskeletal dynamics and cell motility. Even though LT disabled repair mechanisms, agents such as keratinocyte growth factor or dexamethasone improved epithelial barrier integrity by reducing cell death. These results suggest that co-administration of anti-cytotoxic drugs may be of benefit when treating inhalational anthrax

Detection and typing of cutaneous human papillomavirus types - a comparison of three different methods

Cutaneous human papillomavirus (HPV) may play a role in the development of cutaneous squamous cell carcinoma. HPV copy numbers in cutaneous squamous cell carcinoma are very low and hence sensitive and reliable detection methods are important, particularly to examine the natural history of cutaneous HPV. In the present study, the presence of cutaneous HPV types was examined in 194 skin swabs and in a subgroup of 91 skin swabs, and compared using three different PCR based methods: (i) beta/gamma cutaneous HPV PCR reverse-line-blotting (BGC-PCR RIB), (ii) multiplex cutaneous papillomavirus genotyping (McPG) and (iii) FAP PCR. The HPV prevalence was 75% (68/91) with BGC-PCR RLB, 64% (124/194) with McPG and 72% (139/194) with FAP PCR. The agreement for the detection of HPV between the three methods in the subset of 91 samples was 73% (66/91; kappa = 0.34) for BGC-PCR RLB and McPG, 75% (68/91; kappa = 0.32) for BGC-PCR RLB and FAP PCR, and 69% (63/91; kappa = 0.25) for McPG and FAP PCR. For McPG and PAP PCR, 194 specimens were tested in total, with an overall agreement of 66% (129/194; kappa = 0.24) for the detection of HPV. The concordance between the three methods was moderate, which could be explained by different HPV types detectable with each method; the high number of multiple infections and the low viral copy number in human skin. Overall, many cutaneous HPV types were identified and multiple HPV types were found frequently in the human skin swabs