Myosin light chains and muscle pathology

We evaluated the isoform composition of heavy and light chains of myosin in single muscle fibers from patients with Duchenne dystrophy, myotonic dystrophy, or polymyositis. In all myopathic muscles, there was an increase in the proportion of intermediate fibers which, by analysis of myosin isoforms, fell into two subpopulations, one that contained both fast and slow myosin and another that contained myosin molecular hybrids. The increased proportion of intermediate (or transitional) fibers suggests changes in the equilibrium between fast and slow motor units. These changes could result from regeneration and subsequent maturation of fibers or from direct transformation of mature fibers of one type into the opposite.     

Older adults’ preferences for exercising alone versus in groups: Considering contextual congruence

Background: A growing body of research suggests that older exercisers prefer to exercise alone rather than in group-based settings. One limitation of these studies, however, has been that researchers have failed to take into account the age-related characteristics of groups when asking adults about their preferences for exercise settings.Purpose: The overall purpose of this study was to examine the exercise preferences of 947 adults for involvement in standard exercise classes populated by participants from various categories across the age spectrum.Results: The results revealed that when faced with the prospect of exercising with considerably older or younger exercisers, participants found such an exercise context to be largely unappealing. However, in accordance with the basic tenets of self-categorization theory, the results revealed that older and younger adults alike express a positive preference for exercising in standard exercise classes comprised of similarly aged participants.Conclusions: The findings of this study challenge a growing call for exercise interventions for older adults to be primarily directed at the individual-level, and suggest that group-related intervention strategies may indeed be attractive to older exercisers.     

The sequential hypothesis of sleep function. IV. A correlative analysis of sleep variables in learning and nonlearning rats.

Female adult rats were trained for a two-way active avoidance task (4 h), and allowed free sleep (3 h). Control rats (C) were left in their home cages during the acquisition period. Dural electrodes and an intraventricular cannula, implanted one week in advance, were used for EEG recording during the period of sleep and for the injection of [3H]thymidine at the beginning of the training session, respectively. Rats were killed at the end of the sleep period, and the DNA-specific activity was determined in the main brain regions and in liver. Correlations among sleep, behavioral and biochemical variables were assessed using Spearman's nonparametric method. In learning rats (L), the number of avoidances was negatively correlated with SS-W variables, and positively correlated with SS-PS variables (episodes of synchronized sleep followed by wakefulness or paradoxical sleep, respectively) and with PS variables. An inverse pattern of correlations was shown by the number of escapes or freezings. No correlations occurred in rats unable to achieve the learning criterion (NL). In L rats, the specific activity of brain DNA was negatively correlated with SS-W variables and positively correlated with SS-PS variables, while essentially no correlation concerned PS variables. On the other hand, in NL rats, comparable correlations were positive with SS-W variables and negative with SS-PS and PS variables. Few and weak correlations occurred in C rats. The data support a role of SS in brain information processing, as postulated by the sequential hypothesis on the function of sleep. In addition, they suggest that the elimination of nonadaptive memory traces may require several SS-W episodes and a terminal SS-PS episode. During PS episodes, adaptive memory traces cleared of nonadaptive components may be copied in more suitable brain sites.     

Early increase of oxidative stress and soluble CD40L in children with hypercholesterolemia.

OBJECTIVES: The aim of the study was to analyze the behavior of oxidative stress and its interplay with CD40L, a protein that is implicated in atherosclerosis, in hypercholesterolemic children. BACKGROUND: Oxidative stress has been suggested to play a major role in premature atherosclerosis. METHODS: Forty-one children with hypercholesterolemia (mean age 9.28 +/- 0.5 years) and 40 children with normocholesterolemia (mean age 9.02 +/- 0.69 years) were matched for gender and age. Within each group, children were classified as having or not having a family history of cardiovascular disease. Serum levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative stress, and plasma levels of soluble CD40L (sCD40L) were measured in each child. In a subgroup of children with high (n = 8) or normal (n = 8) levels of serum cholesterol, platelet p38 mitogen-activated protein (MAP) kinase phosphorylation, a protein involved in the activation of nicotinamide adenine dinucleotide phosphate oxidase, was determined. RESULTS: Children with hypercholesterolemia had higher values of 8-OHdG and sCD40L compared with control subjects (0.55 +/- 0.06 ng/ml vs. 0.21 +/- 0.02 ng/ml, p < 0.001 and 0.55 +/- 0.04 ng/ml vs. 0.19 +/- 0.03 ng/ml, p < 0.001, respectively). A significant correlation between 8-OHdG and sCD40L was observed in children with high (r = 0.676, p < 0.001) or normal (r = 0.878, p < 0.001) levels of cholesterol. Children with a family history of cardiovascular disease tended to have higher values of 8-OHdG and sCD40L, but the difference was not significant. Analysis of platelet p38 MAP kinase showed that it was phosphorylated more in children with hypercholesterolemia compared with control subjects (36.8 +/- 5.8 AU vs. 8.0 +/- 4.5 AU, p < 0.001 respectively). CONCLUSIONS: Children with hypercholesterolemia have an early increase of oxidative stress that may be responsible for up-regulation of CD40L and potentially predispose to premature atherosclerosis.     

Effect of interferon-alpha therapy on epitope-specific cytotoxic T lymphocyte responses in hepatitis C virus-infected individuals.

The majority of hepatitis C virus (HCV)-infected individuals fail to resolve the infection and become chronically infected despite the presence of HCV-specific CTL responses directed to different HCV-derived peptide antigens. Only a minority of individuals is able to clear the virus by mounting efficient CTL responses early after acute infection, but at present it is not clear whether viral clearance is associated with CTL responses of defined specificity. To elucidate those responses associated with improvement of the disease, we analyzed CTL responses to 16 different HLA-A2-presented, HCV-derived epitopes in 12 chronically infected patients, 14 chronically infected patients treated with interferon-alpha, and in one patient with acute symptomatic disease. We show here that the majority of chronically infected individuals present CTL responses directed to an NS4-derived peptide antigen (amino acids 1789-1797). Treated patients presented stronger HCV-specific CTL responses and therapy-induced changes in CTL target choice. In particular, 13 out of 14 individuals responded to an NS3-derived epitope (amino acids 1073-1081). By longitudinal analysis we show that five individuals responding to IFN-alpha therapy with decreases in alanine aminotransferase levels presented a strong CTL activity directed to the NS3-derived epitope. One patient that spontaneously resolved the infection presented a generally strong CTL activity specific for HCV-derived epitopes with a dominant response to the NS3-derived peptide antigen. This suggests that CTL responses directed to this NS3-derived antigen may be beneficial for the control of HCV infection. Improvement of these responses may represent a therapeutic intervention in chronic HCV infection.