Immunohistochemical investigations and introduction of new therapeutic strategies in scleromyxoedema: Case report

BACKGROUND: Scleromyxoedema is a rare chronic skin disease of obscure origin, which may often be associated with severe internal co-morbidity. Even though different casuistic treatment modalities have been described, to date, curing still seems to be impossible. CASE PRESENTATION: We report a 44-year-old Caucasian female presenting with remarkable circumscribed, erythematous to skin-coloured, indurated skin eruptions at the forehead, arms, shoulders, legs and the gluteal region. Routine histology and Alcian blue labelling confirmed a massive deposition of acid mucopolysaccharides. Immunohistochemical investigations revealed proliferating fibroblasts and a discrete lymphocytic infiltration as well as increased dermal expression of MIB-1(+ )and anti-mastcell-tryptase(+ )cells. Bone marrow biopsies confirmed a monoclonal gammopathy of undetermined significance without morphological characteristics of plasmocytoma; immunofixation unveiled the presence of IgG-kappa paraproteins. CONCLUSIONS: Taking all data into account, our patient exhibited a complex form of lichen mxyoedematosus, which could most likely be linked a variant of scleromyxoedema. Experimental treatment with methotrexate resulted in a stabilisation of clinical symptoms but no improvement after five months of therapy. A subsequent therapeutic attempt by the use of medium-dose ultraviolet A1 cold-light photomonotherapy led to a further stabilisation of clinical symptoms, but could not induce a sustained amelioration of skin condition

Modulation of cathepsin G expression in severe atopic dermatitis following medium-dose UVA1 phototherapy

BACKGROUND: During the last decade, medium-dose UVA1 phototherapy (50 J/cm(2)) has achieved great value within the treatment of severe atopic dermatitis (AD). The purpose of our study was to investigate to what extent UVA1 irradiation is able to modulate the status of protease activity by the use of a monoclonal antibody labeling cathepsin G. METHODS: In order to further elucidate the mechanisms by which medium-dose UVA1 irradiation leads to an improvement of skin status in patients with AD, biopsy specimens from 15 patients before and after treatment were analyzed immunohistochemically for proteolytic activation. RESULTS: Compared to lesional skin of patients with AD before UVA1 irradiation, the number of cells positive for cathepsin G within the dermal infiltrate decreased significantly after treatment. The decrease of cathepsin G(+) cells was closely linked to a substantial clinical improvement in skin condition. CONCLUSIONS: In summary, our findings demonstrated that medium-dose UVA1 irradiation leads to a modulation of the expression of cathepsin G in the dermal inflammatory infiltrate in patients with severe AD. Cathepsin G may attack laminin, proteoglycans, collagen I and insoluble fibronectin, to provoke proinflammatory events, to degrade the basement membrane, to destroy the tissue inhibitor of metalloproteinases and to increase the endothelial permeability. Therefore, its down-regulation by UVA1 phototherapy may induce the reduction of skin inflammation as well as improvement of the skin condition

Impact of UVA exposure on psychological parameters and circulating serotonin and melatonin

BACKGROUND: People tend to feel better after exposure to ultraviolet (UV) radiation. This study was performed to investigate the impact of UVA exposure on psychological and neuroendocrine parameters. METHODS: Fifty-three volunteers were separated into 42 individuals who had UVA exposure and 11 individuals who had no UVA exposure. The UVA-exposed volunteers had irradiation sessions six times in a three-week period. All volunteers completed two questionnaires at baseline (T1) and at the end of the study (T3). For the determination of serotonin and melatonin serum levels of all volunteers blood samples were collected at baseline (T1), after the first UVA exposure (T2), and at the end of the study after the sixth exposure (T3). RESULTS: UVA-exposed volunteers felt significantly more balanced, less nervous, more strengthened, and more satisfied with their appearance at T3. By contrast, the controls did not show significant changes of psychological parameters. In comparison to T1 and T3, serum serotonin was significantly higher and the serum melatonin was significantly lower for the volunteers exposed to UVA at T2. Both, for exposed and non-exposed volunteers serotonin and melatonin levels did not significantly differ at T1 and T3. CONCLUSIONS: It remains obscure, whether the exposure to UVA or other components of the treatment were responsible for the psychological benefits observed. The changes of circulating neuroendocrine mediators found after UVA exposure at T2 may be due to an UVA-induced effect via a cutaneous pathway. Nevertheless, the positive psychological effects observed in our study cannot be attributed to circulating serotonin or melatonin

Analysis of the PARP1, ADP-Ribosylation, and TRIP12 Triad With Markers of Patient Outcome in Human Breast Cancer

PARP inhibitors (PARPi) are increasingly used in breast cancer therapy, including high-grade triple-negative breast cancer (TNBC) treatment. Varying treatment responses and PARPi resistance with relapse currently limit the efficacy of PARPi therapy. The pathobiological reasons why individual patients respond differently to PARPi are poorly understood. In this study, we analyzed the expression of PARP1, the main target of PARPi, in normal breast tissue, breast cancer, and its precursor lesions using human breast cancer tissue microarrays covering a total of 824 patients, including more than 100 TNBC cases. In parallel, we analyzed nuclear adenosine diphosphate (ADP)-ribosylation as a marker of PARP1 activity and TRIP12, an antagonist of PARPi-induced PARP1 trapping. Although we found PARP1 expression generally increased in invasive breast cancer, PARP1 protein levels and nuclear ADP-ribosylation were lower in higher tumor grade and TNBC samples than non-TNBCs. Cancers with low levels of PARP1 and low levels of nuclear ADP-ribosylation were associated with significantly reduced overall survival. This effect was even more pronounced in cases with high levels of TRIP12. These results indicate that PARP1-dependent DNA repair capacity may be compromised in aggressive breast cancers, potentially fueling enhanced accumulation of mutations. Moreover, the results revealed a subset of breast cancers with low PARP1, low nuclear ADP-ribosylation, and high TRIP12 levels, which may compromise their response to PARPi, suggesting a combination of markers for PARP1 abundance, enzymatic activity, and trapping capabilities might aid patient stratification for PARPi therapy

Improved Resolution of Magnetic Resonance Microscopy in Examination of Skin Tumors

Magnetic resonance imaging has become increasingly important for visualization and tissue differentiation of internal organs. Because of limited resolution, investigation of skin has been of little diagnostic value so far. We combined a homogeneous magnetic field of 9.4 T, as used in magnetic resonance spectroscopy, with gradient fields of 11.7 G/cm and an imaging unit to obtain a voxel resolution of 40 × 40 × 300 μm3. With this magnetic resonance microscopy unit, we studied normal skin, 12 nevocellular nevi, 20 basal cell carcinomas, 8 melanomas, and 8 seborrheic keratoses after excision in vitro. The specimens were visualized in spin-echo images. The proton relaxation times T1 and T2 were determined for the different skin layers and tumor tissues. Interpretation of the spin-echo images was based on comparison with the correlating histology. Epidermis, dermis, subcutaneous tissue, and hair follicle complexes could be distinguished. Stratum corneum and hairs emitted no signal. All tumors presented as distinct, signal-rich, homogeneous structures within the dark, signal-poor dermis. Their shape corresponded to their outline in the histologic sections. Buds of superficial basal cell carcinomas could be resolved. The proton relaxation times T1 and T2 were significantly different among all skin layers and tumors. Our results demonstrate that with sufficient resolution, differentiation of skin tumors is possible using magnetic resonance imaging

Task-Set Generator for Schedulability Analysis using the TACLeBench benchmark suite

ABSTRACT Current real-time embedded systems evolve towards complex systems using new state of the art technologies such as multi-core processors and virtualization techniques. Both technologies requires new real-time scheduling algorithms. For uniprocessor scheduling, utilization-based evaluation methodologies are common and well-established. For multicore systems and virtualization, evaluating and comparing scheduling techniques using the tasks' parameters is more realistic. Evaluating these different scheduling techniques requires relevant and standardised task sets. Scheduling algorithms can be evaluated on three evaluation levels: 1) by using the mathematical model of the scheduling algorithm, 2) by simulating the scheduling algorithm and 3) by implementing the algorithm on the target platform. Generating task sets is straightforward in case of the first two levels; only the parameters of the tasks are required. Evaluating and comparing scheduling algorithms on the target platform itself, however, requires real executable tasks matching the predefined standardised task sets. Generating those executable tasks is not standardized yet. Therefore, we developed a task-set generator that generates reproducible, standardised task sets that are suitable at all levels. Beside generating the tasks' parameters, it includes an executable generator methodology that generates executables by combining publicly available benchmarks with know execution times. This paper presents and evaluates this task-set generator. The executables approximate the wanted execution time on the hardware platform

Protection against ultraviolet radiation by commercial summer clothing: need for standardised testing and labelling

BACKGROUND: The use of clothing as a means of sun protection has been recommended in recent education campaigns. Contrary to popular opinion, however, some fabrics provide insufficient ultraviolet (UV) protection. MATERIAL AND METHODS: We investigated 236 apparel textiles of the spring/summer collections 2000 and 2001. In accordance with the forthcoming European standard the UV protection factor (UPF) of the fabrics was determined spectrophotometrically. RESULTS: Seventy-eight (33%) fabrics had UPF < 15, 45 (19%) had UPF = or > 15 and < 30, and 113 (48%) had UPF = or > 30 (30+). More than 70% of the wool, polyester, and fabric blends, and only less than 30% of the cotton, linen, and viscose fabrics had UPF values of 30+. Fabrics with black, navy-blue, white, green, or beige colours provided most frequently UPF values of 30+. CONCLUSIONS: It is difficult for the sun-aware consumer to choose the 'right' garment, with a third of summer clothing providing insufficient UV protection and only half of the fabrics having UPF 30+, the UPF recommended by the European standard. Therefore, apparel summer fabrics should be measured and labelled in accordance with a standard document