1,721,033 research outputs found

    Involvement of protein kinase Cε in the stimulation of anionic amino acid transport in cultured human fibroblasts

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    Protein kinase C (PKC) activation stimulates transport system X-(AG) for anionic amino acids in cultured human fibroblasts (Franchi-Gazzola, R., Visigalli, R., Bussolati, O., and Gazzola, G. C. (1994) FEBS Lett. 352, 109- 112). To identify which PKC isoform is responsible for this effect, aspartate transport through system X-(AG), PKC activity, and the subcellular distribution of PKC isoforms have been studied before and after treatment with phorbol 12,13-dibutyrate (PDBu) in fibroblasts maintained at low serum for 1 (control cells) or 7 days (quiescent cells). In control cells aspartate transport and PKC activity in the particulate fraction were stimulated by short term PDBu treatment; both stimulatory effects were down-regulated by a prolonged exposure to the phorbol. In contrast, in quiescent cells aspartate transport and particulate PKC activity were higher than control under basal conditions, unaffected by a short term PDBu treatment, and lowered by a prolonged incubation with the phorbol. In both control and quiescent cells a short term PDBu treatment modified PKCα distribution, increasing its membrane-associated fraction. PKCδ was mostly in the soluble fraction and scarcely sensitive to PDBu. A brief exposure to PDBu increased membrane- associated PKCε in control but not in quiescent cells. In these cells ε isoform was found exclusively in the particulate fraction even in PDBu- untreated cells. A prolonged PDBu treatment caused a partial down-regulation of membrane-associated PKCε in control cells and its marked decrease in quiescent cells. It is concluded that PKC-dependent changes in system X(AG)- activity parallel the behavior of PKCε, thus suggesting a specific role for this isoform in system X(AG)- regulation

    How do students approach the study of the history of med-icine? Some considerations after the final exams at the first year and fourth year

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    Background and aim: Reports about the teaching of the History of Medicine in universities world-wide can be found easily in medical literature. They are often comparative studies in which the opinions provided by the professors are collected and the teaching programs are compared. Our study focuses instead on the relationship between the students and the discipline, what they look for from it, and how their interest changes with the progress of the course of study. Methods: The final tests of the students of two Italian universities, Parma and Bologna, were analyzed, in which the candidate had the ability to choose the topic of discussion and to outline his personal analysis. The course year in which the final examination was faced is different: in the first year in Bologna, in the fourth year in Parma. Results: This survey show that in both universities most students have carried out autonomous research regardless of the educational material made available to them. This attitude can be interpreted as a real interest in the history of medicine, widening their search throughout all the fields of the discipline. Conclusions: These results seem to suggest to teachers of History of Medicine to convey to their students the methodology of historical and epistemological research, giving the student to the pupils the opportunity to become passionate about history in the way he/she prefers. (www.actabiomedica.it)

    The last battle of Alessandro Farnese (1545-1592): Some medical considerations regarding the health of the renaissance leader who changed Europe

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    Background and aim: Alessandro Farnese (1545-1592), 3rd Duke of Parma and Piacenza, one of the most important generals and politicians of his age. He died after a rapid deterioration of his health. The available documents testify that the Duke suffered for a long time from various health problems, such as jaundice, intestinal disorders, gout, dropsy but very little is known about the cause(s) of his death. The aim of this article is to offer for the first time a complete clinical interpretation of Alessandro Farnese’s last months of life Methods: A collection of descriptions of symptoms and signs described by his court physician and by the leading biographers of Farnese has been compiled. This collected medical evidence has been interpreted in the light of current medical knowledge, to obtain a final interpretation. Results: The results led us to consider liver diseases, neoplastic diseases (especially pancres) and infectious diseases (including typhus and malaria) as causes or contributing causes of death. Conclusions: The accurate autopsy description, in association with the anamnestic information provided by the historical documents studied, suggests that Alessandro Farnese was a hepatopathic patient suffering from spontaneous bacterial peritonitis. In the pre-antibiotic era, the pathologi-cal organ alterations described certainly have at least contributed to making the infectious episode (that the autopsy describes of pulmonary origin) fatal. (www.actabiomedica.it)

    Changes in neutral amino acid efflux and membrane potential associated with the expression of CFTR protein

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    The expression of wild type CFTR facilitates the efflux of neutral amino acids; as a result, after an extensive depletion of intracellular amino acid pool obtained through an incubation in saline solution, the intracellular leucine levels were lower in murine C127 cells transfected with the wild type CF gene (C127 CFTRw/t) than in cells transfected with either mutant CF (C127 CFTRΔF508 cells) or mock vector only. No change in amino acid efflux was detected when C127 CFTRw/t and C127 CFTRΔF508 cells were studied under conditions known to activate protein kinase A. Upon an incubation in Cl- free medium, a permeant analogue of cAMP caused a marked cell depolarization of C127 CFTRw/t cells but not of C127 CFTRΔF508 cells, thus showing a functional expression of CFTR protein in the former cell line. However, we found that, upon a Cl- free incubation and in the absence of exogenous cAMP, C127 CFTRw/t cells developed a marked hyperpolarization that was not detected in C127 CFTRΔF508 cells. It is concluded that the expression of normal CFTR accelerates amino acid efflux and enhances cell hyperpolarization in Cl- free media; both these effects appear to be independent from PKA stimulation of CFTR

    Changes in cell volume in pancreatic duct cells. Effect of secretagogues and CFTR expression

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    Previous results from our group have demonstrated that, in CFTR-transfected murine C127 cells incubated under Cl--free conditions, "isotonic" shrinkage is more rapid in CFTRw/t than in CFTRΔF508 cells, a difference overcome in the latter model by the addition of exogenous ATP. Moreover, compared with ΔF508 cells, isotonic cell shrinkage of CFTRw/t -expressing cells is associated with a significantly higher ATP extrusion (Rotoli et al., Biochem. Biophys. Res. Commun. 227, 755-761 1996). In the present report changes in cell volume and ion content occurring during secretory processes are evaluated in pancreatic duct cells. The models employed were pancreatic carcinoma cells which express normal (CAPAN-1 line) or ΔF508 (CFPAC-1 line) CFTR. Under isotonic conditions, in CFTR-expressing CAPAN-1 cells secretin or 8-Br-cAMP/ teophilline mixture cause a 30% cell shrinkage associated to significant losses of sodium, chloride, and bicarbonate, as demonstrated by significant changes in cytoplasmic pH. These changes are not observed in ΔF508CFTR CFPAC-1 cells but are mimicked by ATP treatment. As in C127 cells, also in pancreatic duct cells Cl--free incubation triggers isotonic shrinkage and ATP extrusion which is greater in CAPAN-1 than in CFPAC-1 cells. These results suggest that ATP may be involved in the modifications of ion channel activities which occur during secretion in pancreatic duct cells

    The Role of Amino Acids in the Crosstalk Between Mesenchymal Stromal Cells and Neoplastic Cells in the Hematopoietic Niche

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    Within the bone marrow hematopoietic cells are in close connection with mesenchymal stromal cells (MSCs), which influence the behavior and differentiation of normal or malignant lymphoid and myeloid cells. Altered cell metabolism is a hallmark of cancer, and changes in nutrient pools and fluxes are important components of the bidirectional communication between MSCs and hematological cancer cells. Among nutrients, amino acids play a significant role in cancer progression and chemo-resistance. Moreover, selected types of cancer cells are extremely greedy for glutamine, and significantly deplete the extracellular pool of the amino acid. As a consequence, this influences the behavior of MSCs in terms of either cytokine/chemokine secretion or differentiation potential. Additionally, a direct nutritional interaction exists between MSCs and immune cells. In particular, selected subpopulations of lymphocytes are dependent upon selected amino acids, such as arginine and tryptophan, for full differentiation and competence. This review describes and discusses the nutritional interactions existing in the neoplastic bone marrow niche between MSCs and other cell types, with a particular emphasis on cancer cells and immune cells. These relationships are discussed in the perspective of potential novel therapeutic strategies based on the interference on amino acid metabolism or intercellular fluxes
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