TRPS1 is a promising marker for all subtypes of breast cancer.

AIMS: Trichorhinophalangeal syndrome-1 (TRPS1) has been proposed as a novel breast marker with equally high expression in breast cancer (BC) subtypes, making it a useful diagnostic tool. Here, its expression was evaluated alongside other commonly used markers [GATA3, GCDFP15, mammaglobin (MGB) and SOX10] in a large cohort of BCs (n = 1852) and their corresponding nodal metastases. Its usefulness as a diagnostic tool and its correlation with clinicopathological features were assessed. METHODS AND RESULTS: TRPS1 was expressed at 75.8% overall in the BC cohort, with at least 58% expression among BC subtypes. It was less sensitive than GATA3 for luminal and HER2-overexpressing (HER2-OE) cancers (luminal A: 82 versus 97%; luminal B: 80 versus 95%; HER2-OE: 62 versus 76%), but it was the most sensitive for TNBC (60 versus ≤ 41%). It showed a stable expression in nodal metastases (primary tumour 76 versus nodal metastasis 78%), unlike a reduced nodal expression for GATA3 (86 versus 77%). TRPS1 outperformed GATA3 in detecting non-luminal cancers when paired with other breast markers. TRPS1 and GCDFP15 was the most sensitive combination in TNBC detection, with a 76% detection rate. For TRPS1-negative and GCDFP15-negative TNBCs, SOX10 was more sensitive than GATA3 (29 versus 24%). CONCLUSIONS: TRPS1 is a highly sensitive marker for all breast cancer subtypes, outperforming GATA3 in non-luminal cancers and displaying the highest sensitivity for TNBC detection when combined with GCDFP15. It is a valuable addition to the breast marker panel for accurate identification of BC.

Immunization with adenovirus at the large intestinal mucosa as an effective vaccination strategy against sexually transmitted viral infection.

The large intestinal mucosa contains immunological structures that may potentially serve as a site for induction of mucosal immunity against infections. Adenovirus (Ad), which is effective in gene transfer to epithelia, may be an ideal antigen delivery system for vaccination at the large intestinal mucosa. To investigate this potential, we immunized mice with recombinant replication-deficient Ad through a single intracolorectal (ICR) administration. Effective transfer of encoded genes was found in both the epithelial layer and lamina propria of the colorectal mucosa. Dendritic cells were able to transfer antigen to the draining lymph nodes, where antigen-specific CD8(+) T cells were primed. Functional antigen-specific CD8(+) T cells and IgA-specific antibodies were detected during the effector phase in the large intestine. Compared to other immunization routes (intranasal, subcutaneous), ICR immunization induced stronger colorectal immune responses and more potent protection against rectal challenge with pathogenic viruses. Further, this immunization strategy provided vaginal protection, more potent than that induced by vaccination in the nose or skin. Therefore, large intestine mucosal immunization using Ad represents an effective vaccination strategy against virus infection at both rectal and vaginal mucosal tissue sites.

In vitro and intra-oral investigations into the cariogenic potential of human milk.

The acidogenic and cariogenic potential of plain and supplemented human and bovine milk was determined by pH tests and with intra-oral experiments. Human milk produced a lower pH than bovine milk and bovine milk with a 2% lactose supplement. Human milk caused greater softening of enamel than bovine milk in the intra-oral tests. This could be modified by supplementing with calcium and phosphorus to the levels present in bovine milk.

The effect of fluoridated milk on bovine dental enamel.

The concept of intra-oral cariogenicity tests, using naturally accumulated plaque, was pioneered by Koulourides (Koulourides et al., 1974). Tests rely on changes in microhardness of dental enamel after exposure to substrates. We used this model, with significant modifications, to determine the possible caries-protective effect of fluoridated milk. Custom-made cast chrome intra-oral appliances were made to fit the lower arches of volunteers. Four removable, highly polished 3 x 4 mm gauze-covered bovine enamel blocks were slotted into the appliances. These were worn for 48 h so that plaque would build up. The enamel was color-coded with composite (Kerr Kolors, Kerr, Romulus, MI) to ensure error-free removal and immersion extra-orally in the coded test substrates.

Assessment of the cariogenic potential of fruit fingers, muesli bars and jelly beans.

Intra-oral tests of a fruit bar, a muesli bar and jelly beans were performed to establish their cariogenic potential by means of enamel hardness changes. Little difference was found when the fruit finger and muesli bar were compared. Surprisingly, the jelly beans did not produce a greatly increased degree of softening when compared with the fruit fingers. Statistical significance was not reached in either of the experiments carried out.

The biochemical and haemodynamic effects of adrenaline in lignocaine local anaesthetic solutions in patients having third molar surgery under general anaesthesia.

The effects of adrenaline-containing and adrenaline-free lignocaine local anaesthetic solutions injected in doses consistent with clinical practice on plasma potassium concentration, blood glucose levels and haemodynamic responses were investigated in 20 patients having third molar surgery under general anaesthesia. All patients received a standard general anaesthetic regime. Ten patients were given 4.0 ml of 2% lignocaine as an inferior dental and long buccal block during their general anaesthetic and the other 10 received 4.0 ml of 2% lignocaine containing 1:80000 adrenaline in the same manner. There were no significant differences between treatments in blood pressure or heart rate. However, there were significant differences between treatments in plasma potassium concentration and blood glucose levels.

A model for investigating the systemic effects of adrenaline in dental local anaesthetic solutions in patients under surgical stress.

A model has been developed which permits the investigation of the systemic effects of adrenaline injected during dental local anesthesia. The model employs patients undergoing the removal of third molars under general anaesthesia. This design allows the study of the effects of exogenous adrenaline administration in clinical doses in patients experiencing surgical stress. In the present investigation the influence of the intra-oral injection of 50 micrograms adrenaline contained in lignocaine local anaesthetic solution on haemodynamic and biochemical responses was established by comparing the effects of inferior alveolar block injections of 4 ml 2% lignocaine and 4 ml 2% lignocaine with 1:80,000 adrenaline in 20 patients having third molars removed with a standardised general anaesthetic regime. No significant changes in haemodynamic responses between treatments were apparent, however significant changes occurred between treatments in blood glucose and plasma potassium levels.

Intra-oral softening of bovine enamel exposed to Lycasin and sucrose.

In previous experiments, the sucrose substitute Lycasin has been shown to possess low acidogenic potential. Intra-oral cariogenicity tests were carried out in humans to explore the enamel softening effects of Lycasin, using sucrose and saline as controls. The results confirmed that Lycasin would be preferred to sucrose as a sweetener for confections and medicines, although some softening of enamel by Lycasin was evident when compared to the saline controls. The magnitude of this enamel change was small and of doubtful clinical significance.

Fluidised-bead bed in the intensive-therapy unit.

The fluidised-bead bed is a novel way of managing patients in the intensive-therapy unit (ITU) with various nursing problems. It is particularly suitable for the management of pressure areas and for patients at the extremes of weight range. Theoretically, the bed is a way of reducing catabolism, but this has so far not been properly investigated.