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51.
52.
Epsilon toxin from Clostridium perfringens acts on oligodendrocytes without forming pores,and causes demyelination
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Laetitia Wioland Jean‐Luc Dupont Frédéric Doussau Stéphane Gaillard Flavia Heid Philippe Isope Serge Pauillac Michel R. Popoff Jean‐Louis Bossu Bernard Poulain 《Cellular microbiology》2015,17(3):369-388
Epsilon toxin (ET) is produced by Clostridium perfringens types B and D and causes severe neurological disorders in animals. ET has been observed binding to white matter, suggesting that it may target oligodendrocytes. In primary cultures containing oligodendrocytes and astrocytes, we found that ET (10?9 M and 10?7 M) binds to oligodendrocytes, but not to astrocytes. ET induces an increase in extracellular glutamate, and produces oscillations of intracellular Ca2+ concentration in oligodendrocytes. These effects occurred without any change in the transmembrane resistance of oligodendrocytes, underlining that ET acts through a pore‐independent mechanism. Pharmacological investigations revealed that the Ca2+ oscillations are caused by the ET‐induced rise in extracellular glutamate concentration. Indeed, the blockade of metabotropic glutamate receptors type 1 (mGluR1) prevented ET‐induced Ca2+ signals. Activation of the N‐methyl‐D‐aspartate receptor (NMDA‐R) is also involved, but to a lesser extent. Oligodendrocytes are responsible for myelinating neuronal axons. Using organotypic cultures of cerebellar slices, we found that ET induced the demyelination of Purkinje cell axons within 24 h. As this effect was suppressed by antagonizing mGluR1 and NMDA‐R, demyelination is therefore caused by the initial ET‐induced rise in extracellular glutamate concentration. This study reveals the novel possibility that ET can act on oligodendrocytes, thereby causing demyelination. Moreover, it suggests that for certain cell types such as oligodendrocytes, ET can act without forming pores, namely through the activation of an undefined receptor‐mediated pathway. 相似文献
53.
Margrete Solheim Mari C Brekke Lars G Snipen Rob JL Willems Ingolf F Nes Dag A Brede 《BMC microbiology》2011,11(1):3
Background
Enterococci rank among the leading causes of nosocomial infections. The failure to identify pathogen-specific genes in Enterococcus faecalis has led to a hypothesis where the virulence of different strains may be linked to strain-specific genes, and where the combined endeavor of the different gene-sets result in the ability to cause infection. Population structure studies by multilocus sequence typing have defined distinct clonal complexes (CC) of E. faecalis enriched in hospitalized patients (CC2, CC9, CC28 and CC40). 相似文献54.
Duijnisveld BJ Bigot A Beenakker KG Portilho DM Raz V van der Heide HJ Visser CP Chaouch S Mamchaoui K Westendorp RG Mouly V Butler-Browne GS Nelissen RG Maier AB 《Arthritis research & therapy》2011,13(6):R207-10
Introduction
Chronic inflammation is a profound systemic modification of the cellular microenvironment which could affect survival, repair and maintenance of muscle stem cells. The aim of this study was to define the role of chronic inflammation on the regenerative potential of satellite cells in human muscle.Methods
As a model for chronic inflammation, 11 patients suffering from rheumatoid arthritis (RA) were included together with 16 patients with osteoarthritis (OA) as controls. The mean age of both groups was 64 years, with more females in the RA group compared to the OA group. During elective knee replacement surgery, a muscle biopsy was taken from the distal musculus vastus medialis. Cell populations from four RA and eight OA patients were used for extensive phenotyping because these cell populations showed no spontaneous differentiation and myogenic purity greater than 75% after explantation.Results
After mononuclear cell explantation, myogenic purity, viability, proliferation index, number of colonies, myogenic colonies, growth speed, maximum number of population doublings and fusion index were not different between RA and OA patients. Furthermore, the expression of proteins involved in replicative and stress-induced premature senescence and apoptosis, including p16, p21, p53, hTERT and cleaved caspase-3, was not different between RA and OA patients. Mean telomere length was shorter in the RA group compared to the OA group.Conclusions
In the present study we found evidence that chronic inflammation in RA does not affect the in vitro regenerative potential of human satellite cells. Identification of mechanisms influencing muscle regeneration by modulation of its microenvironment may, therefore, be more appropriate. 相似文献55.
Bossu C Galusca B Normand S Germain N Collet P Frere D Lang F Laville M Estour B 《American journal of physiology. Endocrinology and metabolism》2007,292(1):E132-E137
Constitutional thinness (CT) is characterized by a low and stable body mass index (BMI) without any hormonal abnormality. To understand the weight steadiness, energetic metabolism was evaluated. Seven CT, seven controls, and six anorexia nervosa (AN) young women were compared. CT and AN had a BMI <16.5 kg/m(2). Four criteria were evaluated: 1) energy balance including diet record, resting metabolic rate (RMR) (indirect calorimetry), total energy expenditure (TEE) (doubly labeled water), physical activity; 2) body composition (dual-energy X-ray absorptiometry); 3) biological markers (leptin, IGF-I, free T3); 4) psychological profile of eating behavior. The normality of free T3 (3.7 +/- 0.5 pmol/l), IGF-I (225 +/- 93 ng/ml), and leptin (8.3 +/- 3.4 ng/ml) confirmed the absence of undernutrition in CT. Their psychological profiles revealed a weight gain desire. TEE (kJ/day) in CT (8,382 +/- 988) was not found significantly different from that of controls (8,793 +/- 845) and AN (8,001 +/- 2,152). CT food intake (7,565 +/- 908 kJ/day) was found similar to that of controls (7,961 +/- 1,452 kJ/day) and higher than in AN (4,894 +/- 703 kJ/day), thus explaining the energy metabolism balance. Fat-free mass (FFM) (kg) was similar in CT and AN (32.5 +/- 2.9 vs. 34.1 +/- 1.9) and higher in controls (37.8 +/- 1.6). While RMR absolute values (kJ/day) were lower in CT (4,839 +/- 473) than in controls (5,576 +/- 209), RMR values adjusted for FFM were the highest in CT. TEE-to-FFM ratio was also higher in CT than in controls. Energetic metabolism balance maintains a stable low weight in CT. An increased energy expenditure-to-FFM ratio differentiates CT from controls and could account for the resistance to weight gain observed in CT. 相似文献
56.
Jorit JL Meesters Ann Bremander Stefan Bergman Ingemar F Petersson Aleksandra Turkiewicz Martin Englund 《Arthritis research & therapy》2014,16(5)
Introduction
Depression is frequent in ankylosing spondylitis (AS) patients. However, epidemiological data about the potential increase in risk are lacking. This study compares the rate of doctor-diagnosed depression in a well defined cohort of AS patients to the general population seeking care.Methods
The Skåne Healthcare Register comprises healthcare data of each resident in Region Skåne, Sweden (population 1.2 million), including ICD-10 diagnoses. Using physician coded consultation data from years 1999 to 2011, we calculated depression consultation rates for all AS patients. We obtained standardized depression-rate ratios by dividing the observed depression rate in AS patients by the expected rate based on the corresponding age- and sex-specific rates of depression in the general population seeking care. A ratio >1 equals a higher rate of depression among AS patients.Results
The AS cohort consisted of 1738 subjects (65% men) with a mean age of 54 years. The reference population consisted of 967,012 subjects. During the 13-year observation period 10% (n = 172) of the AS cohort had a doctor-diagnosed depression compared to 6% (n = 105) to be expected. The standardized estimate of depression-rate ratio was 1.81 (95% confidence interval 1.44 to 2.24) in women men and 1.49 (1.20 to 1.89) in men.Conclusions
The rate of doctor-diagnosed depression is increased about 80% in female and 50% in male AS patients. Future challenges are to timely identify and treat the AS patients who suffer from depression. 相似文献57.
Background
The leukocyte common antigen related receptor (LAR) protein has been shown to modulate the signal transduction of a number of different growth factors, including insulin and insulin-like growth factor 1. Splice variants exhibit differing roles and are expressed according to tissue type and developmental stage. 相似文献58.
Esther Heikens Masja Leendertse Lucas M Wijnands Miranda van Luit-Asbroek Marc JM Bonten Tom van der Poll Rob JL Willems 《BMC microbiology》2009,9(1):19-7
Background
Enterococcus faecium has globally emerged as a cause of hospital-acquired infections with high colonization rates in hospitalized patients. The enterococcal surface protein Esp, identified as a potential virulence factor, is specifically linked to nosocomial clonal lineages that are genetically distinct from indigenous E. faecium strains. To investigate whether Esp facilitates bacterial adherence and intestinal colonization of E. faecium, we used human colorectal adenocarcinoma cells (Caco-2 cells) and an experimental colonization model in mice. 相似文献59.
60.