Three-dimensional modeling of the anatomy of the heart and great vessels

Summary The anatomic constraints imposed on a total artificial heart (TAH) require specific anatomic studies. A thoracic anatomic study was performed with a scanning device equipped with three-dimensional (3-D) reconstruction software on 15 male patients, between the ages of 41 to 63 years (52 ± 6 years). All were candidates for heart transplantation. The 3-D reconstructions of the cardiovascular structures obtained from surgical anatomy data specific to TAH implantation allowed a volumetric measurement of these structures. A modeling diagram of these structures permitted reproducible quantitative measurements of the 35 geometrical parameters which characterized shape, orientation, and position of these structures within the thorax. Most of the measured parameters were characterized by low variability (coefficient of variation from 10 to 25%).

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Modélisation tridimensionnelle de l'anatomie du cur et des gros vaisseaux

Résumé Les contraintes anatomiques imposées au cur artificiel total (CAT) nécessitent des études anatomiques spécifiques. Une étude anatomique thoracique a été réalisée avec un scanner doté d'un logiciel de reconstruction tridimensionnelle (3-D) chez 15 patients, tous de sexe masculin, agés de 41 à 63 ans (52 ± 6 ans), et candidats à une transplantation cardiaque. Les reconstructions 3-D des structures cardio-vasculaires réalisées selon les données de l'anatomie chirurgicale propre à l'implantation du CAT ont permis la mesure volumétrique de ces structures. Un schéma de modélisation de ces structures a permis des mesures quantitatives reproductibles de 35 paramètres géométriques caractéristiques de la forme, de l'orientation, de la position de ces structures dans le thorax. Les résultats de ces mesures ont pu être exprimés en termes statistiques. La plupart des paramètres mesurés étaient caractérisés par une faible variabilité (coefficients de variations de 10 à 25%).

     

HLA antigens in ulcerative colitis: a study in the Sicilian population

HLA antigens were investigated in 41 Sicilian patients with ulcerative colitis and in 151 healthy controls. Frequencies of HLA-B5 and DR2 were increased in the group of patients with ulcerative colitis whereas the DR3 antigen frequency was decreased. However the corrected p values were not significant. Thus, present results indicate that in ulcerative colitis HLA linked genetic factors play a marginal role, if any.     

Expression of gamma interferon on circulating lymphocytes in viral infections.

Peripheral blood lymphocytes from a total of 111 patients and 40 healthy individuals were studied for gamma interferon (IFN-gamma) expression on their surfaces by indirect immunofluorescence assay and flow cytometry, with a new anti-IFN-gamma monoclonal antibody (IGMB-14) as a specific reagent. Of 64 patients with proven acute viral infections, 59 had a significantly higher percentage of lymphocytes expressing IFN-gamma on their membranes than healthy individuals did. On the other hand, only 3 (8.9%) of 34 patients with proven bacterial infections had an increased percentage of IFN-gamma-expressing lymphocytes. None of the eight patients with other infections and none of the five with systemic lupus erythematosus showed an increased percentage of IFN-gamma-positive lymphocytes. The percentage of IFN-gamma-expressing lymphocytes during a viral infection was found to be related to different stages of the disease. Finally, some applications of this rapid IFN-gamma assay method in viral diseases are discussed.     

Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes

Friedreich ataxia is a progressive neurodegenerative disorder caused by loss of function mutations in the frataxin gene. In order to unravel frataxin function we developed monoclonal antibodies raised against different regions of the protein. These antibodies detect a processed 18 kDa protein in various human and mouse tissues and cell lines that is severely reduced in Friedreich ataxia patients. By immunocytofluorescence and immunocytoelectron microscopy we show that frataxin is located in mitochondria, associated with the mitochondrial membranes and crests. Analysis of cellular localization of various truncated forms of frataxin expressed in cultured cells and evidence of removal of an N-terminal epitope during protein maturation demonstrated that the mitochondrial targetting sequence is encoded by the first 20 amino acids. Given the shared clinical features between Friedreich ataxia, vitamin E deficiency and some mitochondriopathies, our data suggest that a reduction in frataxin results in oxidative damage.      

CD40 expression by gingival fibroblasts: correlation of phenotype with function

CD40, a member of the tumor necrosis factor-alpha receptor family, is constitutively expressed by cells of hematopoietic and non- hematopoietic origin, including fibroblasts. Signaling through this receptor molecule regulates inflammatory cytokine secretion by many cell types. Based on the recently described cytokine secretory heterogeneity of fibroblast cell subsets, we hypothesized that secretion of inflammatory cytokines by gingival fibroblast cultures may be dictated by the existence of differential proportions of cytokine- secreting subpopulations which express high levels of CD40. After examining a large number of gingival fibroblast (GF) cultures we find that the frequency of IL-6- and IL-8-secreting cells mirrors the frequency of cells expressing high levels of CD40 in these cultures. In addition, we demonstrate a direct functional relationship between CD40 expression and IL-6 or IL-8 secretion by showing that ligation of this molecule on GF, and CD40+ fibroblast subsets in particular, up- regulates secretion of these cytokines in vitro.      

Cytokine production pathway in the elderly

It is well known that aging is associated with various alterations in lymphoid cell functions, particularly with a progressive decline in immune responsiveness to exogenous antigens and increasing incidence of autoimmune phenomena. Many studies have been focused on the mechanisms of the immunologic features of aging. This review describes our results of studies performed to determine the influence of age on the capacity to produce interleukin-2 (IL-2), interferon-γ (IFN-γ), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-6 (IL-6) and tumor necrosis factor (TNF). Mitogen-stimulated cultures of mononuclear cells (MNC) from human beings were assessed for cytokine-producing capacity. A significant decrease in IFN-γ and IL-2 production by MNC cultures from elderly individuals was observed. No significant difference was instead observed between cultures from elderly individuals and those from young ones as regards TNF-α, IL-4 and IL-6 production. Mitogen or antigen-stimulated cultures of MNC from aged mice also displayed a significant decrease in IFN-γ and IL-2 production as well as TNF-β. Instead IL-4 and IL-5 production significantly increased in these cultures. We suggest that this imbalanced cytokine production may well account for the pattern of immune response which may be observed in the elderly, i.e. a normal or increased humoral response (including autoimmune responses) in face of a low T cell immune responsiveness.     

Prognostic significance of standardized AgNOR analysis in early and advanced gastric carcinomas

 To assess the prognostic significance of silver-stained nucleolar organizer region (AgNOR) proteins, a standardized AgNOR analysis was performed on 78 patients affected by early (EGC, n=24) or advanced (AGC, n=54) gastric carcinomas. The histopathological diagnosis, grading and staging were done according to WHO and UICC recommendations; the mean follow-up time was 56.9 months. Visualization and quantification of AgNORs were made in formalin-fixed, paraffin-embedded sections as specified in the guidelines of the Committee on AgNOR Quantification (1995). Statistical analysis was performed on the mean AgNOR area values (NORA). Highly significant differences (P<0.001) were found in NORA values between EGC and AGC, between low- and high-grade gastric carcinomas and between patients dead from gastric cancer and living patients. In addition, significant P values were found on comparison of NORA values relating to pT status, pN status and stage. Comparison of Kaplan-Meier survival curves revealed that patients affected by gastric carcinomas with higher NORA values (>5.213 μm²) had a worse prognosis. Finally, using Cox multiple regression analysis, the AgNOR quantity emerged as a useful independent prognostic variable to predict the final outcome of patients affected by EGC or AGC. Received: 26 September 1997 / Accepted: 26 January 1998