Structural changes of human RNase L upon homodimerization investigated by Raman spectroscopy.

RNase L, a key enzyme in the host defense system, is activated by the binding of 2'-5'-linked oligoadenylates (2-5A) to the N-terminal ankyrin repeat domain, which causes the inactive monomer to form a catalytically active homodimer. We focused on the structural changes of human RNase L as a result of interactions with four different activators: natural 2-5 pA(4) and three tetramers with 3'-end AMP units replaced with ribo-, arabino- and xylo-configured phosphonate analogs of AMP (pA(3)X). The extent of the RNase L dimerization and its cleavage activity upon binding of all these activators were similar. A drop-coating deposition Raman (DCDR) spectroscopy possessed uniform spectral changes upon binding of all of the tetramers, which verified the same binding mechanism. The estimated secondary structural composition of monomeric RNase L is 44% α-helix, 28% ß-sheet, 17% ß-turns and 11% of unordered structures, whereas dimerization causes a slight decrease in α-helix and increase in ß-sheet (ca. 2%) content. The dimerization affects at least three Tyr, five Phe and two Trp residues. The α-ß structural switch may fix domain positions in the hinge region (residues ca. 336-363) during homodimer formation.

Risk factors for early-onset basal cell carcinoma in a German institution.

BACKGROUND: Genetic predisposition and ultraviolet (UV) exposure are the most important risk factors for basal cell carcinoma (BCC). Recent reports have demonstrated an increasing incidence of BCC among younger patients. We investigated potential risk factors for sporadic BCC in a subset of young German patients. METHODS: Twenty-five patients with BCC at the age of 19 to 40 years (mean 34.4 years) were included in the study. They were selected from a total of 2,058 patients who received surgical treatment for BCC between December 2004 and November 2008. Patients were contacted by telephone interview and asked about sun habits, associated medical conditions, and lifestyle-related variables. Data were compared with interview results from sex-, age- and skin type-matched controls. RESULTS: We found 1.4% (29) of 2,058 BCC patients to be ≤40 years of age. Four patients had Gorlin-Goltz syndrome and were excluded from further analysis. Multivariate analysis showed tanning bed use (OR= 25.0; IC95%: 2.26-277.36) and smoking (OR=13.34; IC95%: 1.56-113.8) to be the most significant independent risk factors for BCC, while sunscreen use had a protective effect. CONCLUSION: BCCs in young patients were only rarely related to hereditary syndromes, but were associated with environmental carcinogens, i.e. UV radiation and smoking.

A controlled trial of photodynamic therapy of actinic keratosis comparing different red light sources.

BACKGROUND: Photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA) with red light is well established for actinic keratosis (AK). Differences have been observed concerning pain and efficacy rates with different red light sources. OBJECTIVES: To compare pain scores, short- and long-term efficacy rates of PDT of multiple AKs when employing different red light sources. MATERIAL AND METHODS: In a controlled trial, 88 patients (310 AK lesions) received ALA-PDT in combination with either visible light (VIS) + water-filtered infrared A (wIRA) light (PhotoDyn(®) 750 (PD750), 580-1400 nm) for 30 min or incoherent light (Waldmann(®) 1200L (Wa1200L), 600-720 nm) for 10-11 min. Follow-up visits were performed after 1, 3, 6, and 12 months. If there was no complete cure after 1, 3 or 6 months, a second cycle of PDT was performed. RESULTS: Pain scores were significantly lower in patients illuminated with PD750 rather than Wa1200L. Patient complete clearance rates were 85% and 91% after 1 month, 79% and 92% after 3 months, 97% and 92% after 6 months, and 69% and 85% after 12 months in the PD750 and Wa1200L groups, respectively. Lesion complete clearance rates were 94% and 92% after 1 month, 88% and 97% after 3 months, 96% and 95% after 6 months, and 81% and 89% after 12 months in the PD750 and Wa1200L group, respectively. The efficacy rates were not significantly different. CONCLUSION: A VIS + wIRA light source produced considerably less pain, while efficacy was not much affected in contrast to previously published studies, probably because the illumination time was longer in this study.

Fluorescence diagnostics as a guide for demarcation and biopsy of suspected anal cancer.

BACKGROUND: Malignant epithelial tumors of the perianal skin are relatively rare however show high recurrence rates. A preoperative precise diagnosis and demarcation of the involved cancerous skin remains challenging but is worthwhile to minimize tissue defects and possible limitations of quality of life. OBJECTIVES: To show the use of fluorescence diagnostics (FD) in the management of chronic perianal disease. METHODS: FD was performed using methylaminolevulinate (MAL) for three hours topically followed by visualization with blue light (405 nm). RESULTS: We report on two patients in whom FD helped to demarcate the involved tissue or to direct biopsy to ascertain the final diagnosis. In one patient with a history of Bowen's disease and recurrent anal carcinoma, biopsy showed extramammary Paget's disease and thus was treated by surgical anoplasty. The other patient had a history of chronic anal eczema, and FD-directed biopsy could exclude suspected malignancy so that the anal eczema was treated by local therapy. CONCLUSIONS: FD is a non-invasive technique which can be used in the perianal region in order to delineate pathologic processes which may reduce the number of surgical interventions.

Ultrasound guided ablative-laser assisted photodynamic therapy of basal cell carcinoma (US-aL-PDT).

OBJECTIVE: With proper noninvasive ultrasound measurement of tumor depth, case selection for laser pre-ablation followed by PDT is possible. This combination of methods provides a less invasive approach to the treatment of BCC. BACKGROUND DATA: Basal cell carcinoma (BCC) primarily affects the face, and, therefore, radical excision is problematic because of the possibility of poor aesthetic outcomes. Photodynamic therapy (PDT) offers an advantage in aesthetic outcomes, but topical PDT is only effective for tumors with a depth up to 2 mm. MATERIALS AND METHODS: Seventy-five histologically verified BCCs from 67 patients were selected and divided into three therapeutic groups based on the tumor depth, which was determined by 20 MHz skin ultrasound. The three groups were: A/<2 mm (PDT), B/ 2-3 mm (Er:YAG laser ablation+PDT), and C/>3 mm (diode laser ablation+PDT). The treatment consisted of laser ablation (or no ablation) followed by the application of methyl-aminolevulinate (MAL) and a 3-h treatment period using an occlusive bandage. Subsequently, illumination with 630 nm (MAL-PDT) was performed. MAL-PDT was repeated 1-3 weeks after the first treatment. A clinical evaluation was performed after 6 months. RESULTS: A 100% clearance rate (CR) in the group with the deepest tumors was observed. In addition, a 94.7% CR occurred in the group with tumors 2-3 mm in depth, and an 81.2% CR was observed in the group with superficial tumors. CONCLUSIONS: With proper ultrasound case selection and laser ablation before MAL-PDT, the depth of a BCC lesion is not a limiting factor for PDT, and aesthetic outcomes are very good. Therefore, ultrasound-guided ablative laser-assisted PDT of BCC can be the method of choice, particularly in aesthetically challenging cases.

Equipment for neutron measurements at VR-1 Sparrow training reactor.

The VR-1 sparrow reactor is an experimental nuclear facility for training, student education and teaching purposes. The sparrow reactor is an educational platform for the basic experiments at the reactor physic and dosimetry. The aim of this article is to describe the new experimental equipment EMK310 features and possibilities for neutron detection by different gas filled detectors at VR-1 reactor. Among the EMK310 equipment typical attributes belong precise set-up, simple control, resistance to electromagnetic interference, high throughput (counting rate), versatility and remote controllability. The methods for non-linearity correction of pulse neutron detection system and reactimeter application are presented.