Light controlled cell-to-cell adhesion and chemical communication in minimal synthetic cells.

Decorating GUVs, used as minimal synthetic cell models, with photoswitchable proteins allows controlling the adhesion between them and their assembly into multicellular structures with light. Thereby, the chemical communication between a sender and a receiver GUV, which strongly depends on their spatial proximity, can also be photoregulated.

Dynamic blue light-switchable protein patterns on giant unilamellar vesicles.

The blue light-dependent interaction between the proteins iLID and Nano allows recruiting and patterning proteins on GUV membranes, which thereby capture key features of patterns observed in nature. This photoswitchable protein interaction provides non-invasive, reversible and dynamic control over protein patterns of different sizes with high specificity and spatiotemporal resolution.

Detection of peripheral embolic consolidations using contrast-enhanced ultrasonography in patients with no evidence of pulmonary embolism on computed tomography: A pilot study.

AIM: To investigate the value of B-mode imaging and contrast-enhanced ultrasonography (CEUS) in patients with clinically suspected pulmonary embolism (PE) but no evidence of central PE on CT. METHODS: Between May 2004 and February 2015, we included in this retrospective study 19 patients with a risk profile for PE according to their Wells' score, sonographic patterns of peripheral embolic consolidations (EC) on B-mode-imaging and CEUS (ie, missing or inhomogeneous enhancement of the pleural lesions), and exclusion of central PE by CT within 1 week of CEUS. RESULTS: On B-mode imaging, 19 pleural defects presented as hypoechoic. The shape of EC was round in 2, wedge-shaped in 12, polygonal in 3, and presented as atelectasis in 2 cases. On CEUS, 5 of the defects demonstrated, at the arterial and parenchymal phase, a lack of enhancement, and 14 showed an inhomogeneous (mixed) enhancement with wedge-shaped peripheral areas of no contrast enhancement. A second radiologic evaluation of the CT scans revealed PE in two patients and lesions suspicious for malignancy in two other patients. CONCLUSIONS: Despite the lack of definite confirmation of peripheral and central PE on CT, peripheral pleural consolidations with no or inhomogeneous enhancement on CEUS, in combination with the risk profile for a PE, are highly suggestive of EC. If there is still some doubt, histologic confirmation is important to confirm EC and exclude malignancy. Thus, CEUS may close a potential diagnostic gap of small peripheral PE on CT. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 45:575-579, 2017.

Node-positive left-sided breast cancer: does VMAT improve treatment plan quality with respect to IMRT?

PURPOSE: The aim of the present work was to explore plan quality and dosimetric accuracy of intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) for lymph node-positive left-sided breast cancer. METHODS: VMAT and IMRT plans were generated with the Pinnacle(3) V9.0 treatment planning system for 10 lymph node-positive left-sided breast cancer patients. VMAT plans were created using a single arc and IMRT was performed with 4 beams using 6, 10, and 15 MV photon energy, respectively. Plans were evaluated both manually and automatically using ArtiView™. Dosimetric plan verification was performed with a 2D ionization chamber array placed in a full scatter phantom. RESULTS: Photon energy had no significant influence on plan quality for both VMAT and IMRT. Large variability in low doses to the heart was found due to patient anatomy (range V(5 Gy) 26.5-95 %). Slightly more normal tissue dose was found for VMAT (e.g., V(Tissue30%) = 22 %) than in IMRT (V(Tissue30%) = 18 %). The manual and ArtiView™ plan evaluation coincided very accurately for most dose metrics (difference < 1 %). In VMAT, 96.7 % of detector points passed the 3 %/3 mm gamma criterion; marginally better accuracy was found in IMRT (98.3 %). CONCLUSION: VMAT for node-positive left-sided breast cancer retains target homogeneity and coverage when compared to IMRT and allows maximum doses to organs at risk to be reduced. ArtiView™ enables fast and accurate plan evaluation.

Breast cancer: patient information needs reflected in English and German web sites.

Individual belief and knowledge about cancer were shown to influence coping and compliance of patients. Supposing that the Internet information both has impact on patients and reflects patients' information needs, breast cancer web sites in English and German language were evaluated to assess the information quality and were compared with each other to identify intercultural differences. Search engines returned 10 616 hits related to breast cancer. Of these, 4590 relevant hits were analysed. In all, 1888 web pages belonged to 132 English-language web sites and 2702 to 65 German-language web sites. Results showed that palliative therapy (4.5 vs 16.7%; P=0.004), alternative medicine (18.2 vs 46.2%; P<0.001), and disease-related information (prognosis, cancer aftercare, self-help groups, and epidemiology) were significantly more often found on German-language web sites. Therapy-related information (including the side effects of therapy and new studies) was significantly more often given by English-language web sites: for example, details about surgery, chemotherapy, radiotherapy, hormone therapy, immune therapy, and stem cell transplantation. In conclusion, our results have implications for patient education by physicians and may help to improve patient support by tailoring information, considering the weak points in information provision by web sites and intercultural differences in patient needs.

Wilms' tumor gene (WT1) expression in lung cancer, colon cancer and glioblastoma cell lines compared to freshly isolated tumor specimens.

The Wilms' tumor gene (WT1) encodes a transcriptional regulator involved in growth and differentiation of various tissue types. A continuous over-expression of WT1 was found in leukemic blasts, thus suggesting an oncogenic function. Solid cancer entities have also been described as expressing WT1. We systematically analyzed WT1 expression in small-cell and non-small-cell lung cancer, colon cancer and glioblastoma patients and in the respective tumor cell lines. Using reverse transcription/polymerase chain reaction, we found WT1 expression in glioblastoma (5 of 8), lung (5 of 11), and colon cancer (5 of 15) cell lines. While WT1 was expressed in only 1 of 12 lung cancer and 1 of 5 glioblastoma specimens, it was not detected in colon cancer or macroscopically tumor-free colon and lung tissue. In addition, HT29 colon cancer cells showed a loss of WT1 expression when grown to confluence or induced to differentiate by sodium butyrate. From this evidence, testing for WT1 expression is not clinically relevant for colon cancer, lung cancer, or glioblastoma patients. WT1 expression in cancer cell lines can probably be attributed to optimized in vitro growth conditions.

Analysis of Wilms tumor gene (WT1) expression in acute leukemia patients with special reference to the differential diagnosis between eosinophilic leukemia and idiopathic hypereosinophilic syndromes.

Continuous Wilms' tumor gene (WT1) expression is a typical feature of leukemic blasts in AML, ALL, and blast crisis CML patients. It is easily detectable by a variety of RT-PCR protocols, which differ mainly in their sensitivity. The nuclear WT1 protein can be found in blasts of approximately 50-60% of acute leukemia patients at diagnosis. Conversely, WT1 is only transiently expressed in normal hemopoiesis. Early CD34+ hemopoietic progenitors express WT1, whereas no WT1 mRNA transcripts can be found in mature blood cells and differentiation-induced committed CD34- progenitors. As a powerful complementary diagnostic tool, testing for WT1 expression can be helpful to discriminate between eosinophilic leukemia (EoL) patients and patients with idiopathic hypereosinophilic syndromes. Conflicting data about the usefulness of testing for WT1 expression to monitor minimal residual disease (MRD) in treated leukemia patients will be discussed. Finally, research strategies to circumvent shortcomings in detecting leukemia-associated WT1 expression will be outlined.

Predisposing conditions and pathogens in bacteremia in hospitalized children.

Between 1985 and 1995, 1037 bacteremic episodes were recorded in a pediatric tertiary care center and analyzed retrospectively. Gram-positive bacteria accounted for 719 episodes (68%), gram-negative bacteria for 303 (29%), fungi for 16 (2%), and anaerobes for 12 (1%). In 526 (51%) patients, primarily neonates and oncology patients, a predisposing condition was present. In 390 (38%) episodes a clinical source of infection was documented. Mortality was highest in Pseudomonas bacteremia (45%). Since the bacterial spectrum differed widely between patient groups, the choice of empirical antimicrobial therapy should be based on any underlying condition present in the patient and the clinical source of infection. As anaerobes were rarely isolated. the routine use of anaerobic blood cultures in patients without predisposing conditions does not seem warranted.

Distinction of eosinophilic leukaemia from idiopathic hypereosinophilic syndrome by analysis of Wilms' tumour gene expression.

In patients presenting with immature eosinophilic precursors it is notoriously difficult to distinguish acute eosinophilic leukaemia (EoL) from the benign idiopathic hypereosinophilic syndrome (HES), based on morphological, cytochemical and immunophenotyping criteria, alone. Cytogenetic analysis or fluorescence in situ hybridization (FISH) can help in discriminating between these rare haematological disorders, but often treatment decisions cannot wait for the results of these time-consuming techniques. Recently, we and others found Wilms' tumour (WT1) gene expression to be increased in virtually all patients with acute leukaemias, whereas normal haemopoietic progenitors express the WT1 gene at much lower levels or not at all. To determine whether detection of WT1 gene expression is useful to distinguish EoL from HES patients, we analysed, by RT-PCR, bone marrow or blood mononuclear cells from EoL (n=3), HES (n=3) and reactive eosinophilia patients (n = 4) for WT1 gene expression. Using our WT1-RT-PCR protocol, we found WT1 gene expression to be restricted to EoL patients. By detecting WT1 mRNA transcripts in the cerebrospinal fluid using RT-PCR, we were also able to diagnose isolated CNS-relapsed leukaemia, initially confused with bacterial meningitis, in an EoL patient. In conclusion, we show that WT1-RT-PCR is a powerful complementary diagnostic tool to distinguish acute eosinophilic leukaemia from the hypereosinophilic syndromes. This observation needs confirmation in a larger series of EoL and HES patients.