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The skeletal muscles are the major living component of the human body. They are constituted by stable cells, the myofibres, and by adult multipotent stem cells, the satellite cells, which can multiply to regenerate and repair the damaged tissues. Injections of DNA in muscle cells have been used to produce recombinant proteins with opposite goals: somatic reparation of genetic defects, which needs to elicit no inflammatory or immune response, and DNA vaccination, which needs a robust immune response. Because of possible therapeutical interventions, a growing body of information is being produced dealing with every aspect of the myofibres during inflammatory and autoimmune responses: skeletal muscle-antigen presenting cell (APC) interaction and intrinsic APC capabilities of myoblasts and myocytes, the response to released cytokines and their endogenous production, the regulation of Toll-like receptors and major histocompatibility complex expression. According to these data, the muscle tissue is now emerging no longer as a passive bystander, but more as an active player that, when correctly manipulated, can drive tolerance or immunization to these de novo produced proteins. In the present review, we summarize the recent developments on the control of muscle immune function. [ABSTRACT FROM AUTHOR]

We studied a well-selected population of patients with active rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) without immunosuppressive therapy. Control and patient peripheral blood mononuclear cells (PBMC) were incubated with IL-1β, IL-10, TGF-β or LPS for 20 h and the in vitro basal and stimulated secretions of IL-6, TNF-α, IL-1β and IL-1ra were measured by ELISA. We found that in the SLE patients the basal secretion of IL-6 was significantly lower and that of IL-1ra significantly higher than in control subjects, while in the RA group the basal IL-1ra secretion was higher than in healthy subjects. SLE and RA PBMC responded to LPS and IL-1β reaching higher cytokine secretion values than controls. The in vitro response of SLE and RA PBMC to TGFβ was normal, while that to IL-10 was defective: IL-10 was able to stimulate the production of IL-6 and IL-1ra in PBMC from normal subjects, but it was unable to enhance IL-6 secretion in RA cells and it was also completely ineffective in inducing IL-1ra secretion in both SLE and RA PBMC. Our work add new data useful for the evaluation of IL-10 and IL-1ra as therapeutic agents in rheumatic diseases. [ABSTRACT FROM AUTHOR]

Examines the rearrangement patterns of T cell receptor delta genes in pediatrics with acute lymphoblastic leukemia. Persistence of leukemic clones during therapy; Comparison between the effectiveness of polymerase chain reaction and southern blot assay; Extraction of genomic DNA from mononuclear cells.

We investigated the relationship between the MHC-I, MHC-II and intercellular adhesion molecule-1 (ICAM-1) expression on myofibres and the presence of inflammatory cells in muscle specimens of 18 patients with inflammatory myopathies (nine polymyositis, seven dermatomyositis, two inclusion body myositis). We observed MHC-I expression in muscle fibres, infiltrating mononuclear cells and endothelial cells in every specimen. In seven patients, some muscle fibres were MHC-I-positive for the DR antigen, while the DP and DQ antigens were absent. ICAM-I expression, detected in seven patients, was found in clusters of myofibres, associated with a marked MHC-1 positivity and a widespread mononuclear infiltration. Most of the ICAM-1-positive fibres were regenerating fibres. Furthermore, some fibres expressed both ICAM-I and DR antigens near infiltrating cells. This finding could support the hypothesis that myofibres may themselves be the site of autosensitization. [ABSTRACT FROM AUTHOR]

A detailed study of the operation of a novel ionisation gauge, recently proposed as a reference standard by the consortium of the European project 16NRM05, is performed with focus on the influence of electron trajectories and the interaction of electrons with electrode surfaces. The strategy behind the gauge design was to provide well defined primary electron trajectories that form an electron beam. This investigation seeks to correlate experimental investigations of improper primary beam focusing, electron beam profiling, electron stimulated desorption and outgassing, with charged particle optics simulations that include space charge effects, and a detailed study of secondary electron emission. The main outcome of the research is that control of the primary electron trajectories, quantified by electron transmission efficiency, is essential for its proper operation mainly as a pressure measurement device but also as a vacuum gauge sensitivity reference standard. Once all primary electrons end their trajectories in a Faraday cup, being one of the gauge electrodes, two additional problems are identified: escape of a very small fraction of electrons from the Faraday cup and electron stimulated desorption of neutrals. Their contribution is of low significance when using this device as a sensitivity reference standard in the high vacuum range, which meets the major goal of the 16NRM05 project. However, these effects might represent an obstacle for the gauge application, mainly as a measurement device, at lower pressures. Approaches to mitigate the mentioned potential problems are discussed. • Electron trajectories may strongly influence operation of the novel ionisation gauge. • Primary beam is sufficiently narrow to avoid collisions with the ionisation cage. • Electron stimulated desorption is the major source of the pressure limit. • Transmission efficiency below unity is due to electron escape from the Faraday Cup. [ABSTRACT FROM AUTHOR]

EBV-associated post transplant lymphoproliferative disease (EBV-PTLD) is a life-threatening complication that may occur after hemopoietic SCT. We prospectively screened 80 children on a weekly basis using nested quantitative PCR to evaluate EBV genome copies. EBV viral load <1000 copies per 105 PBMC was observed in 63% of transplants, whereas it was between 1000 and 9999 copies per 105 PBMC in 13%, and between 10 000 and 19 999 in 10%, with no significant increase in percentage of CD20+ lymphocytes. Viral load reached 20 000 copies per 105 PBMC in 14% of patients, and rituximab was administered to 75% of them. None of the patients except one developed a lymphoproliferative disease. Our study found that only 13% of unrelated donor HSCT recipients had a very high risk of EBV-PTLD defined as 20 000 geq per 105 PBMC associated with an increase in CD20+ lymphocyte. We suggest that rituximab could be administered in the presence of very high levels of EBV-DNA viral load or in the presence of mid levels of EBV-DNA viral load associated with an increase in the percentage of CD20+ lymphocytes. Through this approach, we significantly reduced the number of patients treated with rituximab, and consequently the acute and chronic adverse events related to this treatment. [ABSTRACT FROM AUTHOR]

The impact of bone marrow (BM) GD2-positive cells on survival has been evaluated in 145 Italian children with localised neuroblastoma (NB) evaluated at diagnosis by anti-GD2 immunocytochemistry. Nineteen of these (13.1%) were found to be BM GD2-positive, with the number of positive cells ranging between 1 and 155 out of 1 x 10(6) total cells analysed. Seven/19 (38.8%) GD2-positive vs 12/126 (9.5%) GD2-negative patients relapsed. The 5-year event-free survival (EFS) and overall survival of the GD2-positive patients was significantly worse than that of the GD2-negative ones (62.2 vs 89.9%, P<0.001; and 74.9 vs 95.9%, P=0.005, respectively). GD2 positivity was not associated to other known risk factors, and in particular to Myc-N amplification and 1p deletion. Among Myc-N-negative patients, the EFS of those negative for both GD2 and 1p deletion was significantly better than in children positive for either one of these two markers (EFS=96.9 vs 66.0%, P<0.001). In conclusion, GD2 positivity may represent a prognostic marker for patients with non-metastatic NB without Myc-N amplification, and its combination with genetic alterations might help identifying patients that require a more careful follow-up. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To compare the electrophysiological and histopathological features of immunological myasthenia gravis (MG) subtypes. Methods: Fifty MG patients underwent clinical examination, MuSK-Ab and AChR-Ab analysis. The majority underwent quantitative and single-fiber electromyography (QEMG, SFEMG), repetitive nerve stimulation and deltoid muscle biopsy. From muscle specimens with histological mitochondrial dysfunction, we amplified mitochondrial DNA (mtDNA). In specimens with mtDNA deletions, the nuclear gene POLG1 was sequenced. Results: Five AChR-Ab seropositive [AChR(+)] and 5 seronegative [AChR(−)] patients were MuSK-Ab seropositive [MuSK(+)]. Five of 7 neurophysiologically examined MuSK(+) patients (71%) had proximal myopathic pattern, compared to 7 of 31 MuSK(−)/AChR(+) patients (23%) (P=0.012). SFEMG was abnormal in all examined MuSK(+) patients. All 7 biopsied MuSK(+) and 32 MuSK(−) patients (89%) had cytochrome c oxidase (COX) negative fibers. Three of five MuSK(+) and 13 of 20 MuSK(−) patients analyzed had multiple mtDNA deletions but no POLG1 mutations. Conclusions: Similar degree of SFEMG abnormalities was present in proximal muscles among MuSK(+) and AChR(+) patients. Proximal myopathy was over-represented in MuSK(+) patients; however, both MuSK(+) and MuSK(−) patients had mild myopathy with frequent mitochondrial abnormalities. Significance: The weakness in MuSK(+) patients is most likely due to disturbed neuromuscular transmission. The frequently encountered mitochondrial dysfunction in MG warrants further study. [Copyright &y& Elsevier]

a. nostro, m.a. cannatelli, i. morelli, a.d. musolino, f. scuderi, f. pizzimentiand v. alonzo. 2004. To verify the efficiency of Calamintha officinalis essential oil as natural preservative in two current formulations. The 1·0 and 2·0% (v/v) C. officinalis essential oil was assayed for its preservative activity in two product types (cream and shampoo). The microbial challenge test was performed following the standards proposed by the European Pharmacopoeia Commission (E.P.) concerning topical preparations using standard micro-organisms and in addition wild strains, either in single or mixed cultures were used. The results clearly demonstrated that the C. officinalis essential oil at 2·0% concentration reduced the microbial inoculum satisfying the criterion A of the E.P. in the cream formulation and the criterion B in the shampoo formulation. Standard and wild strains showed a behaviour similar, both in cream and in shampoo formulation, with no significant difference (gerarchic variance, P > 0·05). C. officinalis essential oil confirmed its preservative properties but at higher concentration than that shown in previous studies on cetomacrogol cream. The nature of the formulation in which an essential oil is incorporated as preservative could have considerable effect on its efficacy. [ABSTRACT FROM AUTHOR]