An anti-MUC1-antibody-interleukin-2 fusion protein that activates resting NK cells to lysis of MUC1-positive tumour cells

MUC1 mucin is aberrantly glycosylated and overexpressed in a number of epithelial malignancies and is therefore a promising tumour-associated antigen for target-directed immunotherapy of a panel of malignant diseases. In MUC1-positive tumours, MHC class I expression is frequently downregulated and MUC1-specific cytotoxic T cells (CTLs) are either not available or in a state of anergy allowing tumour growth without limitation by CTL control. To activate lymphocytes and natural killer (NK) cells, we here generated an anti-MUC1-scFv-IL2 fusion protein (C595scFv-Fc-IL2) that contains the C595 single-chain antibody for MUC1 binding, the human IgG1 CH2CH3 domain for protein dimerisation, and interleukin-2 (IL2) for activation of immunological effector cells. The fusion protein binds to MUC1-derived peptides and to MUC1-positive tumour cells with the same specificity as does the C595 monoclonal antibody. Bound to MUC1, the C595scFv-Fc-IL2 fusion protein stimulates proliferation of human activated lymphocytes in vitro. Upon binding to MUC1-positive MCF7 breast carcinoma cells, moreover, the fusion protein activates resting NK cells to tumour cell lysis. These properties make the C595scFv-Fc-IL2 fusion protein a suitable candidate for the immunotherapy of MUC1-positive tumours.     

Volumetry of ventilated airspaces by 3He MRI: preliminary results

RATIONALE AND OBJECTIVES: To develop a validated post-processing routine for volumetry of the ventilated airspaces by 3He MRI. METHODS: 3Helium MRI and pulmonary function tests were performed in seven healthy volunteers. After segmentation of ventilated airspaces, their volumes were calculated. Functional residual capacity (FRC) was used as a reference. For comparison of absolute volumes, correction factors were evaluated. RESULTS: Mean lung volume (+/- standard deviation) calculated from 3He MRI was 4,082 +/- 908 mL and mean FRC was 3,696 +/- 1166 mL, with a mean difference of 386 mL (r = 0.88). After correction for the relative pulmonary air content (factor 0.82), posture (0.72), and the individual tidal volume, 3He MRI volume was 3,348 +/- 744 mL and mean FRC was 3,422 +/- 817 mL, with the mean difference down to -74 mL (r = 0.9). Comparison on an individual basis confirmed an improvement in the estimation of absolute lung volume. CONCLUSIONS: Volumetry of ventilated lung from 3He MRI shows high correlation and good agreement with the results of pulmonary function tests.     

Identification and treatment of acute myocardial infarction by electrocardiographic site classification.

The nature and severity of an acute myocardial infarction may be related to the region of myocardial involvement. Four possible sites of infarction are inferior, anterior, posterior, and lateral. Knowledge of ECG tracings common to each of these areas, the coronary artery source of each, clinical complications, and signs and symptoms is vital to subsequent nursing management.     

Glycosphingolipid expression on murine L1-fibrosarcoma cells: analysis of clonal in vivo and in vitro selected sublines with different lung colonisation potential

The patterns of acidic and neutral glycosphingolipids (GSLs) were examined in a syngeneic tumour system in Balb/c mice consisting of closely related cell lines with different colonisation potentials directed to the murine lungs (in vivo selected highly metastatic sublines of L1-fibrosarcoma cells and their WGA-resistant mutants with low metastatic potential). GSLs were analysed by high-performance thin-layer chromatography and structurally identified by fast atom bombardment mass spectrometry combined with compositional analyses and exo-glycosidase digestion. The results suggest that highly metastatic sublines L1-LM and L1-LM12 derived by in vivo selection from mouse fibrosarcoma cells (cell line L1) exhibit a drastic increase of polar ganglioside expression and a restriction to globo-series GSLs. Contrasting with this the low metastatic mutant cells (L1-LM13WGA) express a reduced portion of acidic GSLs and exhibit a shift to less polar ganglioside components. Total cellular and plasma membrane-integrated GSLs were demonstrated to exhibit largely identical patterns. Concomitant with a significant decrease in LacCer expression a substantial reduction of GM2 and a complete lack of GM3 expression can be assigned to the highly metastatic sublines of L1-cells. On the other hand, the more polar gangliosides GM1a and, to an even greater extent, GD1a (exceeding 70% of total gangliosides) accumulate on L1-LM and their clonal sublines. The shift to acidic GSLs of higher polarity is less pronounced on the low metastatic WGA-resistant mutant cells (L1-LM13WGA) showing a preponderance of GM1a. The portion of GD1a within the fractions of acidic GSLs does not correspond to the cellular activities of CMP-NeuAc/GM1 (alpha 2-3) sialyltransferase measured for high and low metastatic cell variants. Total sialic acid content of the various cell lines differs, but is not associated with the metastatic potential. Gangliosides on L1-cells exhibit a significant substitution of N-glycolyl for N-acetylneuraminic acid (13%) compared to their metastatic sublines and to mutant cells (less than 1%). A conversion of surface exposed GD1a to GM1a on membranes of metastatic cells by in situ treatment with Vibrio cholerae sialidase is associated with a significant reduction of tumour cell colonisation directed to the murine lungs.     

Varying rates of phagocytosis of human blood monocytes and breast milk macrophages: effect of intralipid and milk fat globules

Phagocytosis of antibody/complement or anti-D coated and neuraminidase treated erythrocytes by human blood monocytes and milk macrophages has been investigated. About 90% of the blood monocytes phagocytized erythrocytes whereas only 40% of the milk macrophages engulfed pretreated red blood cells. After preincubation of blood monocytes with Intralipid, no erythrocytes were phagocytized, while after preincubation with milk-fat-globules half the monocytes ingested erythrocytes.     

Pancreas cancer and smoking, beverage consumption, and past medical history

Four hundred and ninety pancreas cancer patients representative of confirmed cases in Los Angeles County residents of working age were compared to healthy controls individually matched by age, sex, race, and neighborhood. Home interviews were conducted on occupation, smoking, food and beverage consumption, and medical history. Cigarette smoking was a strong and consistent predictor of pancreas cancer occurrence; the effect disappeared after a decade of nonsmoking, and there was no increase in risk among current smokers as daily dose increased. There was no link between pancreas cancer and past consumption of tea, carbonated beverages, beer, or spirits; and an association with coffee consumption was inconsistent. A strong association between pancreas cancer and history of subtotal gastrectomy at any past time could not be explained by chance or any other factor. Pancreas cancer patients had experienced fewer allergies of any kind.     

Umsatzsteuerpflicht bei ästhetischen Operationen

Abstrakt  1. ?sthetische Operationen unterliegen der Umsatzsteuerpflicht. 2. Ums?tze aus der T?tigkeit als Arzt sind nur dann umsatzsteuerfrei, wenn sie der Diagnose, Behandlung und Heilung von Krankheiten oder Gesundheitsst?rungen dienen.     

Myositis ossificans traumatica of the masticatory muscles: etiology,diagnosis and treatment

Background

Myositis ossificans describes a heterotopic bone formation within a muscle. Thereby myositis ossificans is classified in two different groups: myositis ossificans progressiva (MOP) which describes a genetic autosomal dominant rare disease and myositis ossificans traumatica (MOT). The exact pathogenesis of MOT is unclear. The aim of this article was to analyse and interpret the existing literature reporting MOT of masticatory muscles and compare the results with our own clinical experience with MOT. Risk-factors, etiology, clinical features, diagnostic imaging, as well as different treatment options were evaluated and recommendations for the prevention, diagnosis, and therapy of MOT of the masticatory muscles were given.

Methods

Following the PRISMA-Guidelines, a systematic search within the PubMed/Medline database with a view to record literature of MOT of the masticatory muscles was performed. Furthermore, the database of our own clinic was screened for cases of MOT.

Results

In total, 63 cases of MOT of the masticatory muscles which were reported in English-based literature were included in this study. Overall, 25 female and 37 male patients could be analysed whereas one patient’s gender was unknown. Complication of wisdom-tooth infection (n =?3) as well as the results of dental procedures like dental extraction (n =?7), mandibular nerve block (n =?4), periodontitis therapy (n =?1) were reported as MOT cases. From the 15 reported cases that appeared after dental treatment like extraction or local anesthesia the medial pterygoid (n =?10) was the most affected muscle. Hereof, females were more affected (n =?9) than males (n =?6). The most reported clinical symptom of MOT was trismus (n =?54), followed by swelling (n =?17) and pain (n =?13). One clinical case provided by the authors was detected.

Conclusions

Dental procedures, such as local anesthesia or extractions, may cause MOT of the masticatory musculature. Demographical analyses demonstrate that females have a higher risk of developing MOT with respect to dental treatment. The most important treatment option is surgical excision. Subsequent physical therapy can have beneficial effects. Nevertheless, a benefit of interpositional materials and drugs as therapy of MOT of the masticatory muscles has not yet been proven. Myositis ossificans progressiva has to be excluded.