Changing patterns of abnormal vascular wall F-18 fluorodeoxyglucose uptake on follow-up PET/CT studies.

BACKGROUND: Fluorine 18 fluorodeoxyglucose (FDG) uptake may be increased in atherosclerotic plaques in asymptomatic patients. Repeat positron emission tomography (PET)/computed tomography (CT) studies were assessed for changes in patterns of FDG uptake and CT calcifications. METHODS AND RESULTS: Fifty consecutive cancer patients (mean age, 68 +/- 8 years) had repeat PET/CT studies 8 to 26 months apart. PET, CT, and PET/CT images were retrospectively evaluated for vascular wall abnormalities and for interval changes in the thoracic and abdominal aortas, as well as in carotid and iliac arteries, classified as PET+/CT+, PET+/CT-, and PET-/CT+. There were 485 abnormal sites in the first study and 495 in the second. CT calcifications were found in 46 patients (92%) in the first study and in 47 (94%) in the second. Vascular wall FDG uptake was found in both studies in 37 patients (74%). The pattern changed in 57 of 119 PET+ sites (48%) in the second study compared with 15 of 366 PET- sites (4%) (P < .0001). In the second study new PET+ sites were observed in 36 of 111 sites (32%) versus new PET-/CT+ sites in 19 of 384 sites (5%) (P < .0001). CONCLUSIONS: Changes in vascular FDG activity and CT calcifications can be assessed by repeat PET/CT. FDG-avid foci may represent a dynamic process, transient inflammation, whereas CT calcifications may indicate stable atherosclerosis. These preliminary results support the need for further research.     

Expression of the protein related to Dan and Cerberus gene--prdc--During eye, pharyngeal arch, somite, and swim bladder development in zebrafish.

The protein related to Dan and Cerberus, or PRDC, is a secreted glycoprotein, which belongs to the DAN subfamily of bone morphogenetic protein (BMP) antagonists. In zebrafish, prdc is expressed initially around 17 hours postfertilization in the developing eyes and the first two pharyngeal arches. Expression in the eye starts in the outer layers of the optic cup. Later, prdc expression domains are juxtaposed at the edges of the optic cup surrounding the choroid fissure, then gradually becoming restricted to a small site in the ventral marginal zone. Prdc expression in the arch mesenchyme expands stepwise to the remaining posterior arches. Prdc is also detectable in the ventral part of the somites and the mesenchyme of the swim bladder. The relatively late appearance during development is a unique feature of Prdc among BMP antagonists. Moreover, the complexity of the prdc expression pattern suggests possible roles in eye development, pharyngeal arch remodeling, somitogenesis, and swim bladder organogenesis.     

The combination of plasmid interleukin-12 with a single DNA vaccine is more effective than Mycobacterium bovis (bacille Calmette-Guèrin) in protecting against systemic Mycobacterim avium infection

Sub‐unit vaccines utilizing purified mycobacterial proteins or DNA vaccines induce partial protection against mycobacterial infections. For example, immunization with DNA vaccines expressing the gene for the immunodominant 35 000 MW protein, common to Mycobacterium avium and Mycobacterium leprae but absent from the Mycobacterium tuberculosis complex, conferred significant protection against infection with either virulent M. avium or M. leprae in mice. However, the level of protection was equivalent to that obtained with the viable, attenuated vaccine, Mycobacterium bovis, bacille Calmette–Guèrin (BCG). The cytokine, interleukin (IL)‐12, is essential for priming naïve CD4⁺ T lymphocytes to differentiate into interferon‐γ (IFN‐γ)‐secreting T cells. We have used a novel self‐splicing vector expressing both chains of murine IL‐12 to determine if plasmid IL‐12 would increase the efficacy of a vaccine expressing the M. avium 35 000 MW protein (DNA‐Av35). Co‐immunization with p2AIL‐12 and DNA‐Av35 led to a significant increase in the number of antigen‐specific IFN‐γ secreting cells and total amount of IFN‐γ released, but a concomitant fall in the antibody response to the 35 000 MW protein. This pattern of response was associated with enhanced clearance of M. avium from the liver and spleen of coimmunized mice, and was significantly more effective than BCG or DNA‐Av35. alone. Following M. avium challenge there was significant increase in the expansion of the 35 000 MW antigen‐reactive T cells in the coimmunized mice. Therefore, plasmid‐delivered IL‐12 acts as an effective adjuvant to increase the protective efficacy of a single DNA vaccine against M. avium infection above that achieved by BCG, and this strategy may improve the efficacy of subunit vaccines against M. leprae and M. tuberculosis.     

A novel system to diagnose cutaneous adverse drug reactions employing the cellscan--comparison with histamine releasing test and Inf-gamma Releasing Test

Background: There are several mechanisms to describe allergic drug reactions yet the methods to diagnose them are limited. Objective: To compare several conventional clinical and laboratory methods to diagnose skin reactions to drugs to a new method of diagnosing drug reactions by the CellScan system. Methods: The study entailed 21 patients who were diagnosed as suffering from drug eruptions, and 105 healthy controls with no history of drug allergy. The drugs were classified into two groups according to suspicion of causing drug allergy: high and low. Most of the patients were on more than one drug, leading to 41 patient-drug interactions (assays). Histamine releasing test (HRT), interferon (INF)-γ releasing test and CellScan examination were performed on lymphocytes of the patients and controls. Results: The HRT was interpreted as positive in 9 out of 18 (50%) patients and in 13 out of 35 (37%) assays. Based on the INF-γ releasing test, positive results were observed in 16 out of 21 (76%) patients and in 24 out of 41 (59%) assays. In the CellScan test (CST), positive results were observed in 17 out of 21 (81%) patients and in 29 out of 41 (71%) assays. The rate of identifying the drug for eruption in the high suspicion level drugs was 9 out of 22 (41%) assays in the HRT, 20 out of 24 (83%) assays in the INF-γ releasing test, and 21 out of 24 (87%) studies with the CellScan method. The rate of determining of the drug that caused the eruption in the low suspicion level drugs was 4 out of 13 (31%) in the HRT, 4 out of 17 (24%) assays in the INF-γ releasing test, and 8 out of 17 (47%) analyses in the CST. When examined in the CellScan, 99 out of 105 (94%) controls were interpreted as negative. Conclusion: This preliminary study indicates that the CellScan seems to be an easy and promising method for the detection of drugs responsible for adverse skin reactions. In contrast to the HRT and to the Interferon-γ secretion test, the CellScan method is characterized by its ability to track and monitor the reaction of individual cells. By measuring the kinetic parameters of selected cells before and after adding the suspected drug, we were able to identify the culprit drug. The CellScan method had the highest sensitivity, and the interferon-γ secretion test had the highest specificity for detection of the culprit drug. In contrast, the analysis of 105 normal control sera disclosed a high specificity of 94% for the CellScan method.     

Antigen-specific suppression of a primed immune response by dendritic cells mediated by regulatory T cells secreting interleukin-10

Antigen-specific suppression of a previously primed immune response is a major challenge for immunotherapy of autoimmune disease. RelB activation is required for myeloid DC differentiation. Here, we show that antigen-exposed DCs in which RelB function is inhibited lack cell surface CD40, prevent priming of immunity, and suppress previously primed immune responses. DCs generated from CD40-deficient mice similarly confer suppression. Regulatory CD4+ T cells induced by the DCs transfer antigen-specific "infectious" tolerance to primed recipients in an interleukin-10-dependent fashion. Thus CD40, regulated by RelB activity, determines the consequences of antigen presentation by myeloid DCs. These observations have significance for autoimmune immunotherapy and suggest a mechanism by which peripheral tolerance might be constitutively maintained by RelB(-) CD40(-) DCs.     

Cross-cultural adaptation,validity and reliability of Turkish version of Oxford Ankle Foot Questionnaire for children with congenital talipes equinovarus

BackgroundThe purpose of the study was to evaluate the reliability and validity of the Turkish version of the Oxford Ankle Foot Questionnaire (OxAFQ) to provide cultural adaptation.MethodsThis study involved translation, back translation, and cross-cultural adaptation. Forty-nine patients with congenital talipes equinovarus were evaluated using the Turkish version of OxAFQ. Turkish version of the Childhood Health Assessment Questionnaire (CHAQ) was used as a gold standard to validate the Turkish version of the OxAFQ. The validation was assessed with Spearman correlation analysis by using CHAQ. The reliability of the questionnaire was assessed with Cronbach alpha (internal consistency) and exploratory factor analysis.ResultsHigh validity was found between OxAFQ and CHAQ (r = -0.422?0.292) (p < 0.01). Reliability analysis showed that OxAFQ had a high level of Cronbach alpha (α = 0.88?0.96) and internal consistency (ICC = 0.90?0.96).ConclusionThe Turkish version of OxAFQ is a valid, reliable and useful quality of life questionnaire in patients with congenital talipes equinovarus and it is proper for use by health professionals and researchers.