Serpinb9 is a marker of antigen cross-presenting dendritic cells.

Serpinb9 (Sb9, also called Spi6) is an intracellular inhibitor of granzyme B (grB) that protects cytotoxic lymphocytes from grB-mediated death. In addition, Sb9 is also expressed in accessory immune cells, including dendritic cells (DCs), although its role is debated. Recently, we have demonstrated that Sb9 plays a grB-independent role in cross-presentation of antigens by CD8+ DCs. Here, using a mouse line expressing green fluorescent protein knocked in under the control of the Sb9 promoter, we demonstrate that Sb9 expression is highest in those tissue-resident and migratory DC subsets capable of cross-presentation. Further, we show that CD8+ DCs can be divided into two subsets based on Sb9 expression, and that only the subset expressing higher levels of Sb9 is capable of cross-presentation. These findings add support for role for Sb9 cross-presentation, and indicate that high Sb9 expression is a novel marker of cross-presentation capable DCs.

A quantitative approach to histopathological dissection of elastin-related disorders using multiphoton microscopy.

BACKGROUND: Multiphoton microscopy (MPM) is a novel imaging technology that has recently become applicable for diagnostic purposes. The use of (near) infrared light in MPM allows for deep tissue imaging. In addition, this modality exploits the autofluorescent nature of extracellular matrix fibres within the skin. OBJECTIVES: To quantitate the structure and abundance of elastic fibres in human dermis in three dimensions utilizing autofluorescent signals generated by MPM for the objective examination of elastin-related skin disorders. METHODS: Cross-sections of skin samples from elastin-related disorders were analysed by MPM and correlated to histopathology. In situ visualization of elastic fibres by MPM was conducted by en face imaging of ex vivo skin samples through the intact epidermis. Image analysis software was used to quantify elastic fibres in three dimensions. RESULTS: Based on the MPM-detected elastin-specific autofluorescence, we developed the Dermal Elastin Morphology Index (DEMI), calculated as the ratio of elastic fibre surface area and volume. This enabled objective three-dimensional quantification of elastic fibres. Quantitative scoring of sun-damaged skin using DEMI correlated with qualitative histopathological grading of the severity of solar elastosis. Furthermore, this approach was applied to changes in elastic fibre architecture in other disorders, such as pseudoxanthoma elasticum (PXE), PXE-like syndrome, elastofibroma, focal dermal elastosis, anetoderma, mid-dermal elastolysis and striae distensae. We imaged elastic fibres in intact ex vivo skin imaged en face through the epidermis, indicating that this approach could be used in vivo. CONCLUSIONS: MPM has the potential for noninvasive in vivo visualization of elastic fibres in the dermis with near histological resolution. DEMI allows objective assessment of elastic fibres to support diagnosis and monitoring of disease progress or therapy of elastin-related skin disorders.

Treatment and survival from colorectal cancer: the experience of patients at South Australian teaching hospitals between 1980 and 2002.

AIMS: To evaluate trends in colorectal cancer survival and treatment at South Australian teaching hospitals and degree of adherence to treatment guidelines which recommend adjuvant chemotherapy for Dukes' C colon cancers and combined chemotherapy and radiotherapy for high-risk rectal cancers. MATERIALS AND METHODS: Trends in disease specific survival and primary treatment were analysed, and comparisons drawn between diagnostic epochs, using cancer registry data from South Australian teaching hospitals. Statistical methods included univariate and multivariable disease specific survival analyses. RESULTS: Five-year survival increased from 48% in 1980-1986 to 56% in 1995-2002. Largest gains were for stage C, where survivals were higher when chemotherapy was part of the primary treatment. By comparison, gains in 1-year survival were largest for stage D. Chemotherapy was provided for 4% of patients with colorectal cancers in 1980-1986, increasing to 32% in 1995-2002. Among stage C cases below 70 years at diagnosis, the proportion having chemotherapy increased to 83% in 1995-2002. The most common chemotherapy was fluorouracil (5FU) as a single agent in 1980-1986 and 5FU with leucovorin in 1995-2002. As expected, radiotherapy was used more frequently for rectal than colon cancers, and particularly for stage C. Among stage C rectal cases below 70 years, the proportion having radiotherapy increased from 10% in 1980-1986 to 57% in 1995-2002. Approximately 93% of colorectal cancers were treated surgically. Patients not treated surgically tended to be aged 80 years or more and to present with distant metastases. CONCLUSIONS: Trends in chemotherapy and radiotherapy accord with evidence-based recommendations. There have been reassuring gains in survivals after adjusting for stage, grade and other prognostic indicators. The data show survival gains and treatment patterns that individual hospitals can use as benchmarks when evaluating their own experience.