Stage-associated overexpression of the ubiquitin-like protein, ISG15, in bladder cancer

Bladder cancer is among the most prevalent malignancies, and is characterised by frequent tumour recurrences and localised inflammation, which may promote tissue invasion and metastasis. Microarray analysis was used to compare gene expression in normal bladder urothelium with that in tumours at different stages of progression. The innate immune response gene, interferon-stimulated gene 15 kDa (ISG15, GIP2), was highly expressed at all stages of bladder cancer as compared to normal urothelium. Western blotting revealed a tumour-associated expression of ISG15 protein. ISG15 exhibited a stage-associated expression, with significantly (P<0.05) higher levels of ISG15 protein in muscle-invasive T2–T4 tumours, compared with normal urothelium. Although ISG15 is involved in the primary immune response, ISG15 expression did not correlate with bladder inflammation. However, immunohistochemical staining revealed expression of ISG15 protein in both cancer cells and stromal immune cells. Interestingly, a significant fraction of ISG15 protein was localised to the nuclei of tumour cells, whereas no nuclear ISG15 staining was observed in ISG15-positive stromal cells. Taken together, our findings identify ISG15 as a novel component of bladder cancer-associated gene expression

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

Functional impairment of systemic scleroderma patients with digital ulcerations: results from the DUO Registry

OBJECTIVES: Digital ulcers (DUs) are frequent manifestations of systemic scleroderma (SSc). This study assessed functional limitations due to DUs among patients enrolled in the Digital Ulcer Outcome (DUO) Registry, an international, multicentre, observational registry of SSc patients with DU disease. METHODS: Patients completed at enrolment a DU-specific functional assessment questionnaire with a 1-month recall period, measuring impairment in work and daily activities, and hours of help needed from others. Physician-reported clinical parameters were used to describe the population. For patients who completed at least part of the questionnaire, descriptive analyses were performed for overall results, and stratified by number of DUs at enrolment. RESULTS: This study included 2327 patients who completed at least part of the questionnaire. For patients with 0, 1–2, and ≥3 DUs at enrolment, mean overall work impairment during the prior month among employed/self-employed patients was 28%, 42%, and 48%, respectively. Across all included patients, ability to perform daily activities was impaired on average by 35%, 54%, and 63%, respectively. Patients required a mean of 2.0, 8.7, and 8.8 hours of paid help and 17.0, 35.9, and 63.7 hours of unpaid help, respectively, due to DUs in the prior month. Patients with DUs had more complications and medication use than patients with no DUs. CONCLUSIONS: With increasing number of DUs, SSc patients reported more impairment in work and daily activities and required more support from others

Spatial distribution of parasitism on Phyllocnistis citrella Stainton, 1856 (Lepidoptera: Gracillariidae) in citrus orchards

Many species of microhymenopterous parasitoids have been registered on Phyllocnistis citrella, the citrus leafminer. The present study aimed to identify the spatial distribution pattern of the native and introduced parasitoids of P. citrella in two citrus orchards in Montenegro, RS. The new shoots from 24 randomly selected trees in each orchard were inspected at the bottom (0-1.5 m) and top (1.5-2.5 m) stratum and had their position relative to the quadrants (North, South, East and West) registered at every 15 days from July/2002 to June/2003. The leaves with pupae were collected and kept isolated until the emergence of parasitoids or of the leaf miner; so, the sampling was biased towards parasitoids that emerge in the host pupal phase. The horizontal spatial distribution was evaluated testing the fitness of data to the Poisson and negative binomial distributions. In Montenegrina, there was no significant difference in the number of parasitoids and in the mean number of pupae found in the top and bottom strata (χ2 = 0.66; df = 1; P > 0.05) (χ2 = 0.27; df =1; P > 0.05), respectively. In relation to the quadrants, the highest average numbers of the leafminer pupae and of parasitoids were registered at the East quadrant (χ2 = 11.81; df = 3; P < 0.05), (χ2 = 10.36; df = 3; P < 0.05). In the Murcott orchard, a higher number of parasitoids was found at the top stratum (63.5%) (χ2 = 7.24; df =1 P < 0.05), the same occurring with the average number of P. citrella pupae (62.9%) (χ2 = 6.66; df = 1; P < 0.05). The highest number of parasitoids and of miners was registered at the North quadrant (χ2 = 19. 29; df = 3; P < 0.05), (χ2 = 4.39; df = 3; P < 0.05). In both orchards, there was no difference between the numbers of shoots either relative to the strata as well as to the quadrants. As the number of shoots did not varied much relative to the quadrants, it is possible that the higher number of miners and parasitoids in the East and West quadrants would be influenced by the higher solar exposure of these quadrants. The data of the horizontal spatial distribution of the parasitism fit to the negative binomial distribution in all sampling occasions, indicating an aggregated pattern