Freshly isolated mouse 4F7+ splenic dendritic cells process and present exogenous antigens to T cells

The antibody 4F7 was reported to recognize an epitope expressed on dendritic cells (DC) from various tissues. To study the ability of splenic 4F7⁺ dendritic cells to process antigen for presentation to CD4⁺ T cells, DC were enriched using a separation procedure avoiding overnight culture which could lead to an altered phenotype. These DC were used as antigen-presenting cells (APC) in stimulation cultures of major histocompatibility complex class II-restricted T cells. It was found that they induce antigen-dependent lymphokine production by T cells and therefore could present exogenous antigens. These processing takes place intracellularly, because fixation abrogates presentation to T cells. Moreover, antigen presentation needs intracellular processing within endo- or lysosomes as chloroquine-treatment prevents T cell activation. Titration of APC numbers revealed that contaminating APC most likely did not account for antigen-specific T cell activation by DC. No evidence was found for release of antigenic peptides or for partial antigen processing possibly done by cell surface located enzymes on DC. In conclusion, these results indicate that freshly enriched DC are able to process antigens similarly to other APC.     

Eating habits in older people in Greece: The role of age, dental status and chewing difficulties

The aim of this study was to investigate the role of age-related parameters on the dietary preferences in a Greek community-dwelling sample. 130 participants aged between 18 and 92 years were interviewed and clinically examined. Data were collected on their socio-demographic characteristics, their dental status, the oral complaints, their chewing difficulties and the frequency of eating a variety of food types. The results revealed that increasing age was associated with increased frequency of consumption of fish, grains and vegetables. Impaired dental status and chewing difficulties did not affect the frequency of eating meat and other “difficult to chew” food, but it was related to more frequent consumption of softer food (chicken, fish, grains, and dairy products). The older Greeks did not exclude any food type from their diet, because of dental impairment. To overcome chewing problems they used various preparing methods to consume their favorite food. The dietary patterns of the older participants adhere to the traditional Mediterranean diet greater than those of the younger ones, revealing the various cultural and social parameters which influence food selection.     

Inhibition of Mitochondrial Permeability Transition Pores by Cyclosporine A Improves Cytochrome c Oxidase Function and Increases Rate of ATP Synthesis in Failing Cardiomyocytes

Background: We previously showed that mitochondrial respiratory function is abnormal in dogs with chronic heart failure (HF). Mitochondrial permeability transition pores (MPTP) can affect mitochondrial inner membrane potential (Δ < eqid1 > _m) and mitochondrial function in normal cardiomyocytes. The potential impact of MPTP on Δ < eqid2 > _m and mitochondrial respiratory function in HF has not yet been determined. We tested the hypothesis that cyclosporine A, a potent blocker of the MPTP, can improve mitochondrial function in HF. Methods: Cardiomyocytes were isolated from the left ventricular myocardium of 7 dogs with HF produced by intracoronary microembolizations and from 7 normal dogs. Cardiomyocytes were treated for 24 hours with cyclosporine A. Δ < eqid3 > _m, cytochrome c oxidase protein expression, mitochondrial cytochrome c oxidase-dependent respiration (CDOR) and ATP synthesis were measured. Results: Δ < eqid4 > _m, protein expression of cytochrome c oxidase, CDOR and the rate of ATP synthesis were decreased in HF compared to normal controls. Inhibition of MPTP in failing cardiomyocytes with low dose of cyclosporine A (0.2 μM) increased Δ < eqid5 > _m, preserved expression of cytochrome c oxidase, improved CDOR and the rate of ATP synthesis. Conclusion: MPTP opening contributes to the loss of mitochondrial function observed in the failing heart. Inhibition of MPTP opening represents a potential therapeutic target for the treatment of HF. This study was supported by a grant from the National Heart, Lung, and Blood Institute PO1 HL074237-01.     

Using amyloid PET imaging to diagnose Alzheimer’s disease in patients with multiple sclerosis

Journal of Neurology - Cognitive dysfunction affects 40–60% of individuals with multiple sclerosis (MS). The neuropsychological profile commonly consists of a subcortical pattern of deficits,...     

Hypoxia,angiotensin-II,and norepinephrine mediated apoptosis is stimulus specific in canine failed cardiomyocytes: a role for p38 MAPK,Fas-L and cyclin D1

BACKGROUND: Apoptosis may contribute to the myocardial dysfunction associated with heart failure (HF). Activation of the p38 MAPK cascade can induce apoptosis in non-cardiac cells through increased expression of Fas-L, or through decreased expression of cyclin D(1). AIMS: We tested the hypothesis that hypoxia (HX), angiotensin-II (A-II) and norepinephrine (NEPI) can mediate apoptosis by activating p38 MAPK, and thus initiating stimulus specific changes in Fas-L and cyclin D(1) expression in failing cardiomyocytes. METHODS AND RESULTS: Cardiomyocytes isolated from ten dogs with HF induced by coronary microembolizations were subjected to HX or A-II or NEPI with and without a p38 MAPK inhibitor (SB 203580). TUNEL staining for DNA fragmentation and Western blots for p38 MAPK, Fas-L and cyclin D(1) detection were performed. HX-induced apoptosis was associated with increased Fas-L expression, A-II-induced apoptosis was associated with increased Fas-L and decreased cyclin D(1) expression, and NEPI-induced apoptosis was associated with decreased cyclin D(1) expression. Inhibition of p38 MAPK activity attenuated stress-induced apoptosis in all experiments and reversed changes in Fas-L and cyclin D(1) expression. CONCLUSIONS: HX, A-II and NEPI mediate apoptosis in failing cardiomyocytes via different effects on Fas-L and cyclin D(1) expression. Inhibition of p38 MAPK reversed these effects, suggesting that apoptosis induced by HX, A-II and NEPI involves activation of p38 MAPK upstream from Fas-L and cyclin D(1).     

Greek centenarians: assessment of functional health status and life-style characteristics

Centenarians represent an intriguing model for ageing studies, since they demonstrate extreme longevity by definition, and at the same time a proportion of them have aged successfully. Here, we present data from the first nationwide study on Greek centenarians concerning their functional health status and life-style characteristics. We have identified 489 individuals (77% women) born in 1900 or before who were still alive between the years 2000 and 2002. Socio-demographic characteristics, activities of daily living (ADLs), living conditions, dependence on other people, former and current diseases and health disorders, current medication, nutrition and personal habits were recorded for every subject. Interestingly, only 2% of Greek centenarians lived in nursing homes, while the majority lived with their family or relatives. Furthermore, 6% were free from severe health disorders, autonomous (based on simple criteria for ADLs) and also leading an active social life, and hence may be considered as being in optimal condition. This group of centenarians may serve as a valuable source of information on genetic, environmental, and psychosocial determinants of successful ageing.