Pharmacological restoration and therapeutic targeting of the B-cell phenotype in classical Hodgkin's lymphoma

Classical Hodgkin's lymphoma (cHL), although originating from B-cells, is characterized by the virtual lack of gene products whose expression constitutes the B-cell phenotype. Epigenetic repression of B-cell-specific genes via promoter hypermethylation and histone deacetylation as well as compromised expression of B-cell-committed transcription factors were previously reported to contribute to the lost B-cell phenotype in cHL. Restoring the B-cell phenotype may not only correct a central malignant property, but render cHL susceptible to clinically established antibody therapies targeting B-cell surface receptors or small compounds interfering with B-cell receptor signaling. We conducted now a high-throughput pharmacological screening based on more than 28,000 compounds in cHL cell lines carrying a CD19 reporter to identify drugs that promote re-expression of the B-cell phenotype. Three chemicals were retrieved that robustly enhanced CD19 transcription. Subsequent chromatin immunoprecipitation-based analyses indicated that action of two of these compounds was associated with lowered levels of the transcriptionally repressive lysine 9-trimethylated histone H3 mark at the CD19 promoter. Moreover, the anti-leukemia agents all-trans retinoic acid and arsenic trioxide (ATO) were found to reconstitute the silenced B-cell transcriptional program and reduce viability of cHL cell lines. When applied in combination with a screening-identified chemical, ATO evoked re-expression of the CD20 antigen, which could be further therapeutically exploited by enabling CD20 antibody-mediated apoptosis of cHL cells. Furthermore, restoration of the B-cell phenotype also rendered cHL cells susceptible to the B-cell Non-Hodgkin's lymphoma-tailored small compound inhibitors Ibrutinib and Idelalisib. In essence, we report here a conceptually novel, re-differentiation-based treatment strategy for cHL

The South African Traditional Belief Scale as an instrument to aid culture-congruent health care

Medical and psychological health care professionals are becoming increasingly aware that effective treatment in culturally diverse societies requires sensitivity to the patient's cultural beliefs and customs (Davidhizar & Giger, 2001:2; Foley & Wurmser, 2004:2; Hickson & Christie, 1989:162; Mkize, 2003:4; Narayanasamy, 2003:1). To this end this article introduces the South African Traditional Belief Scale (SATBS) as an instrument to enable culturecongruent care, not only in the medical field, but also in psychotherapy and counselling. This scale measures the extent to which black South Africans adhere to traditional beliefs and customs. To obtain reliability and validity data, 64 second-year students were randomly selected at the East Rand campus of Vista University. The reliability of the SATBS was established by calculating inter-item correlations. A reliability coefficient, or index of internal consistency of 0.91 (Cronbach alpha) was obtained after the first iteration. In order to establish criterion validity, the South African Traditional Belief Scale was validated against the Degree of Enculturation Survey (DES) by using the same random sample. A validity coefficient of 0.7899 was obtained which indicates a high index of criterion validity. The questionnaire therefore measures what it purports to assess. Keywords: South African Traditional Belief Scale; cultural beliefs and values; culture-congruent care; culture sensitivity; treatment compliance Health SA Gesondheid Vol. 10 (4) 2005: pp. 29-4

Attaining low uncertainties in measurements with RF signal generators and analyzers

In this paper, practical investigations of level accuracy and uncertainties using a Rohde & Schwarz signal generator (R&S SMB-B140) and spectrum analyzer (R&S FSV40) are performed up to 30GHz. We show that it is possible to measure frequency responses of DUTs with uncertainties below ±0.05dB up to 30 GHz instead of ±0.5...1.5dB using auto settings, standard setup, or relying on datasheets. The level linearity of instruments with integrated step attenuators is shown to be improved to ±0.03dB instead of ±0.3...1dB by using a special “hybrid” procedure. Furthermore, it is shown how computer aided measurements procedures should be programmed with these instruments to attain low deviations between measurements

A versatile, automated, cost-effective testing platform for hands-on UHF RFID measurements

In this paper, we present cost-effective techniques to assess UHF RFID performance for real world applications. This includes a positioner, made from roof battens and stepper motors, which can position a tag in 3-D space. It can be used for a variety of measurements, e.g., tag RSSI or phase patterns or influence of distance to materials and other tags. We also present a 1-D positioner from similar materials to lift a reader antenna to show reflections from ground and perform limited motion measurements. For the measurements themselves, we use a commercial off-the-shelf R420 Impinj reader, which we control via LLRP commands, implemented in Python. To verify the communication link between reader and tag, we use a low-cost SDR based on an RTL2832U chip. We also built clamps and adapters from hardware store materials to connect a tag to RF equipment to read the communication and test external antennas. For bulk detection performance testing, we built a frame with RF neutral layers with attached tags