High-risk human papillomavirus in non-melanoma skin lesions from renal allograft recipients and immunocompetent patients.

BACKGROUND: High-risk human papillomaviruses (HR-HPVs) can be detected in a proportion of non-melanoma skin cancers. Data on prevalence are inconclusive, but are essential to estimate the relevance of HR-HPV, particularly with regard to prophylactic HPV vaccines for skin cancer prevention. METHODS: High-risk human papillomavirus DNA was investigated in 140 non-melanoma skin lesions from 54 immunocompetent patients and 33 immunosuppressed renal allograft recipients. Expression of p16(INK4a), a marker for HR-HPV oncogene expression in the uterine cervix, and of p53 and pRB was evaluated immunohistochemically. RESULTS: The highest prevalence of HR-HPV was found in squamous cell cancer (SCC) (46.2% (6 out of 13) in immunosuppressed and 23.5% (4 out of 17) in immunocompetent patients). High-risk human papillomavirus positivity was accompanied by diffuse p16(INK4a) expression in most SCC (P<0.001) and basal cell cancers (P=0.02), while almost all SCC in situ were p16(INK4a) positive irrespective of HR-HPV presence (P=0.66). Diffuse p16(INK4a) expression was associated with lack of pRB expression (P=0.001). p53 was strongly expressed in 40.0% (56 out of 140) of the lesions irrespective of HR-HPV presence. CONCLUSION: High-risk human papillomavirus can be detected in lesions of keratinised squamous epithelia. The association of HR-HPV with diffuse p16(INK4a) expression might indicate HR-HPV oncogene expression in a proportion of lesions. Overexpression of p53 suggests p53 pathway alterations in HR-HPV-positive and -negative lesions.

Effects of mycophenolic acid on human fibroblast proliferation, migration and adhesion in vitro and in vivo.

Mycophenolic acid (MPA) is a potent inhibitor of the inosine monophosphate dehydrogenase and used as an immunosuppressive drug in transplantation. MPA inhibits proliferation of T- and B-lymphocytes by guanosine depletion. Since fibroblasts rely on the de novo synthesis of guanosine nucleotides, it is assumed that MPA interacts with fibroblasts causing an increased frequency of wound healing problems. We show a downregulation of the cytoskeletal proteins vinculin, actin and tubulin in fibroblasts exposed to pharmacological doses of MPA using microarray technology, real-time polymerase chain reaction (PCR) and Western blot. This reduction in RNA and protein content is accompanied by a substantial rearrangement of the cytoskeleton in MPA-treated fibroblasts as documented by immunofluorescence. The dysfunctional fibroblast growth was validated by scratch test documenting impaired migrational capacity. In contrast, cell adhesion was increased in MPA-treated fibroblasts. The results of the cultured human fibroblasts were applied to skin biopsies of renal transplant recipients. Skin biopsies of patients treated with MPA expressed less vinculin, actin and tubulin as compared to control biopsies that could explain potential wound healing problems posttransplantation. The perspective of MPA-induced cytoskeletal dysfunction may go beyond wound healing disturbances and may have beneficial effects on (renal) allografts with respect to scarring.

[Increase in the number of cases of epidemic nephropathy in Germany. Virological and ecological aspects]. / Zunehmende Verbreitung der Nephropathia epidemica in Deutschland. Virologische und ökologische Aspekte.

Epidemic nephropathy (EN) is transmitted to humans via rodents. The causative agent of this virus-borne renal disease is the Hantavirus Puumala. Other members of the genus Hantavirus cause hemorrhagic fever with renal syndrome (HFRS) or hantaviral pulmonary syndrome (HPS). As with all zoonoses the prevalence of the virus depends on the distribution of the reservoir species. Climate changes have direct impact on the number of host animals and influence the incidence of hantaviral infections. A number of studies demonstrate the epidemiological relationship between climate, food supply, rodent population and outbreaks of HFRS and HPS. In Germany the number of cases of EN has increased in the past few years and huge rise in the incidence of the infection, more than 1600 cases, occurred in 2007.

[Emerging zoonoses: Hantavirus infections]. / Emerging Zoonoses: Hantavirus-Infektionen.

Among the emerging viruses, hantaviruses are being focused on more and more due to their increasing number and worldwide distribution. Transmission occurs via inhalation of aerosolized infected rodent excreta. The symptoms and course of disease vary with the infecting hantavirus species. The distribution of the different hantavirus species correlates with the geographical distribution of the virus-type-specific rodent host. Hantaviruses in Europe and Asia cause hemorrhagic fever with renal syndrome (HFRS). Infection with Puumala, the prevalent virus type in Germany, results in a more moderate form of HFRS, nephropathia epidemica. Infections with virus species on the American continents lead to a clinical picture with predominantly pulmonary pathology (hantaviral pulmonary syndrome). No specific antiviral therapy or approved vaccines are available for any hantavirus species. Controlling the rodent populations and avoiding contact with rodent excrement are the only measures that can be undertaken to contain and prevent infection.