TSG101 is not mutated in lung cancer but a shortened transcript is frequently expressed in small cell lung cancer

Adrenocortical autoantibodies (ACA), present in 60-80% of patients with idiopathic Addison's disease, are conventionally detected by indirect immunofluorescence (IIF) on frozen sections of adrenal glands. The large-scale use of IIF is limited in part by the need for a fluorescence microscope and the fact that histological sections cannot be stored for long periods of time. To circumvent these restrictions we developed a novel peroxidase-labelled protein A (PLPA) technique for the detection of ACA in patients with Addison's disease and compared the results with those obtained with the classical IIF assay. We studied serum samples from 90 healthy control subjects and 22 patients with Addison's disease, who had been clinically classified into two groups: idiopathic (N = 13) and granulomatous (N = 9). ACA-PLPA were detected in 10/22 (45%) patients: 9/13 (69%) with the idiopathic form and 1/9 (11%) with the granulomatous form, whereas ACA-IIF were detected in 11/22 patients (50%): 10/13 (77%) with the idiopathic form and 1/9 (11%) with the granulomatous form. Twelve of the 13 idiopathic addisonians (92%) were positive for either ACA-PLPA or ACA-IIF, but only 7 were positive by both methods. In contrast, none of 90 healthy subjects was found to be positive for ACA. Thus, our study shows that the PLPA-based technique is useful, has technical advantages over the IIF method (by not requiring the use of a fluorescence microscope and by permitting section storage for long periods of time). However, since it is only 60% concordant with the ACA-IIF method, it should be considered complementary instead of an alternative method to IIF for the detection of ACA in human sera.     

The effect of the nasopharyngeal air cavity on x-ray interface doses

We investigated the impact of air cavities in head and neck cancer patients treated by photon beams based on clinical set-ups. The phantom for investigation was constructed with a cubic air cavity of 4 x 4 x 4 cm3 located at the centre of a 30 x 30 x 16 cm3 solid water slab. The cavity cube was used to resemble an extreme case for the nasal cavity. Apart from measuring the dose profiles and central axis percentage depth dose distribution, the dose values in 0.25 x 0.25 x 0.25 cm3 voxels at regions around the air cavity were obtained by Monte Carlo simulations. A mean dose value was taken over the voxels of interest at each depth for evaluation. Single-field results were added to study parallel opposed field effects. For 10 x 10 cm2 parallel opposed fields at 4, 6 and 8 MV, the mean dose at regions near the lateral interfaces of the cavity cube were decreased by 1 to 2% due to the lack of lateral scatter, while the mean dose near the proximal and distal interfaces was increased by 2 to 4% due to the greater transmission through air. Secondary build-up effects at points immediately beyond the air cavity cube are negligible using field sizes greater than 4 x 4 cm2. For most head and neck treatment, the field sizes are usually 6 x 6 cm2 or greater, and most cavity volumes are smaller than our chosen dimensions. Therefore, the influence of closed air cavities on photon interface doses is not significant in clinical treatment set-ups.     

Structure-function of cytochromes P450 and flavin-containing monooxygenases: implications for drug metabolism

This article is a report on a symposium held at Experimental Biology '98 in San Francisco, California. Recent developments in site-directed mutagenesis, computer-modeling, and mechanistic analysis of cytochromes P450 and flavin-containing monooxygenases are described. A unifying theme is the elaboration of general approaches for understanding and predicting the function of individual forms of these enzymes. A related goal is the production of soluble forms of mammalian cytochromes P450 for X-ray crystallography.