Transactivation-deficient p73alpha (p73Deltaexon2) inhibits apoptosis and competes with p53.

p73 has recently been identified as a structural and functional homolog of the tumor suppressor protein p53. Overexpression of p53 activates transcription of p53 effector genes, causes growth inhibition and induced apoptosis. We describe here the effects of a tumor-derived truncated transcript of p73alpha (p73Deltaexon2) on p53 function and on cell death. This transcript, which lacks the acidic N-terminus corresponding to the transactivation domain of p53, was initially detected in a neuroblastoma cell line. Overexpression of p73Deltaexon2 partially protects lymphoblastoid cells against apoptosis induced by anti-Fas antibody or cisplatin. By cotransfecting p73Deltaexon2 with wild-type p53 in the p53 null line Saos 2, we found that this truncated transcript reduces the ability of wild-type p53 to promote apoptosis. This anti-apoptotic effect was also observed when p73Deltaexon2 was co-transfected with full-length p73 (p73alpha). This was further substantiated by suppression of p53 transactivation of the effector gene p21/Waf1 in p73Deltaexon2 transfected cells and by inhibition of expression of a reporter gene under the control of the p53 promoter. Thus, this truncated form of p73 can act as a dominant-negative agent towards transactivation by p53 and p73alpha, highlighting the potential implications of these findings for p53 signaling pathway. Furthermore, we demonstrate the existence of a p73Deltaexon2 transcript in a very significant proportion (46%) of breast cancer cell lines. However, a large spectrum of normal and malignant tissues need to be surveyed to determine whether this transdominant p73 variant occurs in a tumor-specific manner.

Frequent loss of heterozygosity at 1p36 in ovarian adenocarcinomas but the gene encoding p73 is unlikely to be the target.

Loss of heterozygosity (LOH) involving the distal part of the short arm of chromosome 1 occurs frequently in ovarian adenocarcinomas but the tumour suppressor gene(s) targeted by this event is unknown. We have used five microsatellite markers in a panel of 56 ovarian adenocarcinomas to determine which part of 1p34 - 36 is the focus of this LOH. LOH was considerably more common at 1p36 (43%) than at 1p34 - 35 (18%), and 11 tumours showed LOH at 1p36 but not at 1p34 - 35. These data strongly suggest the presence of a tumour suppressor gene inactivated in ovarian adenocarcinoma at 1p36. The p53 homologue, p73, has recently been isolated and mapped to 1p36 and therefore is a candidate for this tumour suppressor gene. However, RT - PCR and Western analyses revealed strong expression of p73 in ovarian adenocarcinoma cell lines but very low or undetectable levels in normal ovarian surface epithelial cells. Immunohistochemical analysis of primary ovarian tumours showed that only 3/22 (14%) contained p73 expressing cells. There was no association between 1p36 LOH and p73 expression in ovarian tumours, nor between p73 and p53 expression. These findings strongly suggest that p73 is not the target of 1p36 LOH in ovarian adenocarcinomas but indicate the presence of an, as yet unidentified, tumour suppressor gene in this region that plays an important role in ovarian tumorigenesis.

"Pack year" smoking histories: what about patients who use loose tobacco?

Life time smoking of ready made cigarettes can be readily quantified as "pack years" smoked, but methods for measuring loose tobacco use are less well established. In this study the frequency of loose tobacco use by 247 hospital in-patients was determined; 64% were current or ex-smokers, 41.3% of whom (25.9% of participants) had smoked loose tobacco. A formula was developed for converting loose tobacco use to pack years smoked, based on the weight of tobacco in ready made cigarettes; 12.5 g or half an ounce of loose tobacco was approximately equivalent to one packet of 20 cigarettes. Using a questionnaire it was found that hospital physicians of all grades were able to convert smoking histories of ready made cigarettes, but not loose tobacco, into number of "pack years" smoked.

Patient satisfaction with store-and-forward teledermatology.

We assessed patient satisfaction with a nurse-led store-and-forward teledermatology service in Manchester. A teledermatology nurse obtained the patient's history, took digital photographs of the patient's skin lesion and then sent the information to a hospital dermatologist, who responded with management advice the following week. Of 141 patients who attended their teledermatology appointment, 123 (50 male, 73 female) completed the study questionnaire (87%). The average age of respondents was 42 years (SD 17, range 18-90 years). Ninety-three per cent reported that they were happy with the teleconsultation while 86% reported that it was more convenient than going to the outpatient clinic. Forty per cent agreed that they would feel more comfortable seeing the dermatologist in person while only 58% were comfortable with not speaking to the dermatologist about their skin condition. The absence of interaction with the dermatologist and the delay in receiving management advice may have contributed to the somewhat low satisfaction rates.

Patient satisfaction with teledermatology is related to perceived quality of life.

BACKGROUND: There is a lack of good data about patient satisfaction with teledermatology and about its potential interaction with quality-of-life factors. OBJECTIVES: To assess the association between perceived skin-related quality of life and patient satisfaction with a nurse-led teledermatology service. METHODS: In a mobile nurse-led teledermatology clinic located in four inner city general practices in Manchester, the teledermatology service used digital cameras to capture and store images of skin conditions for remote diagnosis by dermatologists. One hundred and twenty-three adult patients, non-urgent dermatology referrals from primary care, completed the Dermatology Life Quality Index (DLQI) and a 15-item patient satisfaction questionnaire. RESULTS: In common with other studies of patient satisfaction, subjects reported highly favourable views of 'hotel' aspects of the service (93%) and found it 'convenient' (86%). However, 40% of patients would have preferred to have had a conventional face-to-face consultation with a dermatologist, and 17% felt unable to speak freely about their condition. Patient satisfaction with the service was related to quality of life. Patients reporting lower quality of life as measured by the DLQI were more likely to prefer a face-to-face encounter with a dermatologist (r = 0.216, P < 0.05), and to evince anxiety about being photographed (r = 0.223, P < 0.05). CONCLUSIONS: Patient acceptance and satisfaction with telemedicine services is complicated by patients' subjective health status. Telehealthcare providers need to recognize that patients with poor quality of life may want and benefit from face-to-face interaction with expert clinicians.