Suppression of the CD8 T cell response by human papillomavirus type 16 E7 occurs in Langerhans cell-depleted mice.

Human papillomavirus (HPV) is an epitheliotropic virus that is the primary causal agent for cervical cancer. Langerhans cells (LC) are skin antigen presenting cells that are reduced in number in HPV-infected skin. The aim of this study was to understand the immune-modulatory effects of HPV16 E7 on LC and on the CD8 T cell response to a skin-expressed antigen. To test this, HPV16 E7 was expressed in mouse skin keratinocytes with the model antigen ovalbumin (Ova). Similar to what is observed in HPV-infected human skin, LC numbers were significantly reduced in E7-expressing mouse skin. This shows that expression of the E7 protein alone is sufficient to mediate LC depletion. Expression of E7 with Ova in keratinocytes strongly suppressed the Ova-specific CD8+ T cell response in the skin draining lymph node. When tested in LC-ablated mice, the CD8 T cell response to skin-expressed Ova in control mice was not affected, nor was the T cell response to Ova restored in E7-expressing skin. These data indicate a role for E7 in regulation of LC homeostasis in the skin and in suppression of antigen specific CD8 T cell expansion, but suggest that these two effects occur independent of each other.

Perineal impalement injury by steel bar - A near miss.

Adult perianal impalement injuries are uncommon but can carry high morbidity and mortality. We report a case of a penetrating perineal trauma in a construction worker highlighting an innovative use of a Sengstaken tube to control his pelvic bleeding, as well as the operative management of his sphincteric injury. This article illustrates principles of effective acute care and discusses a diagnostic approach to evaluating a potentially complex injury, as well as the decision-making process with regard to fecal diversion and choice of sphincteric repair.

Deregulation of E-cadherin by human papillomavirus is not confined to high-risk, cancer-causing types.

BACKGROUND: E-cadherin is a tumour suppressor protein, which is normally expressed on keratinocytes and antigen-presenting Langerhans cells (LCs) in the epidermis. We have previously shown that E-cadherin is lost from tissues infected with the high-risk cancer-causing human papillomavirus (HPV) type 16. OBJECTIVES: To test if E-cadherin dysregulation is associated with the cancer risk of the infecting HPV and to establish if it is conserved among HPVs in the α, ß, γ and µ genera. METHODS: Forty-seven lesions infected with low- or high-risk HPV types spanning four HPV genera were stained for E-cadherin, P-cadherin and CD1a to detect LCs. RESULTS: Surface E-cadherin was reduced in tissues infected with members of the α4, α7 and α9 species and the γ and µ genera but was equivalent to normal epidermis in the ß only-infected lesions tested and patchy in α10-infected tissues. There was a direct relationship between atypical E-cadherin expression and a significant reduction in LCs. Expression of P-cadherin, a protein that is increased in the E-cadherin constitutive knockout mouse, was increased in lesions with reduced E-cadherin. CONCLUSIONS: These data show that E-cadherin dysregulation by HPV is widely conserved across the majority of HPV genera. E-cadherin expression was reduced or lost in epidermis irrespective of the cancer risk of the infecting HPV type or the ability of the virus to degrade retinoblastoma protein or p53. A correlation between dysregulated E-cadherin and reduced numbers of LCs supports viral regulation of surface E-cadherin contributing to viral evasion of the host immune system.

Intravenous clonazepam in eclampsia.

A case of postpartum eclampsia is reported, controlled by intravenous clonazepam, a benzodiazepine anticonvulsant. Clonazepam was effective in controlling the myoclonic jerks, which were a feature in this patient, without producing excessive sedation. The literature reveals several reports on the use of clonazepam in severe preeclampsia, but its use in Australia has not been widely employed.