Adiponectin and chronic kidney disease.

Enhanced chronic inflammation and reduced insulin sensitivity are often present in chronic kidney disease (CKD). Cardiovascular disease remains a major cause of morbidity and mortality in end-stage renal patients. Adiponectin (ADP) is a hormone exclusively produced by adipocytes and possesses anti-inflammatory and cardioprotective properties. Despite the high prevalence of insulin resistance and cardiovascular disease, levels of ADP are increased among end-stage renal disease patients on hemo or peritoneal dialysis but also among patients with moderate renal failure or with the nephrotic syndrome. Furthermore, lower ADP levels are associated with poor cardiovascular outcome. In this review, we examine ADP modifications in CKD and discuss the different factors that may have an impact on this adipokine metabolism in renal failure.     

Expression of myosin heavy chain isoforms in Duchenne muscular dystrophy patients and carriers

The expression of MHC isoforms in the skeletal muscles of nine patients with Duchenne muscular dystrophy (DMD) (from 2.5 to 15 yr of age) and three DMD carriers was studied using different specific anti-MHC MAbs. We also analyzed muscle fiber size and fiber reactivity with acridine orange and/or with a surface antigen marker. One-quarter of all fibers of DMD patients, or less with age, were of normal size and contained only adult slow MHC. Half of the muscle fibers contained adult and developmental MHCs. Only half of these fibers were representative of an active regenerative process. MHC co-expression also altered the proportion of normal fast or slow fibers. Adult fast MHCs were expressed as unique MHC only in small and very small fibers in the oldest DMD patients. In DMD carrier muscles, the greatest alterations in MHC expression were observed in patients with the most reduced dystrophin expression. However, MHC changes in dystrophin-positive fibers were similar to those observed in dystrophin-free fibers. In conclusion, disruptions or delays in the switching of all genes coding for adult fast and slow MHC and developmental MHC coincided with dystrophin deletion and with perturbations in its expression.     

CASPER, a Computer ASsisted PERicardial puncture system: first clinical results.

Pericardial puncture is the percutaneous insertion of a needle into the pericardial space to drain a pathological pericardial effusion. The challenge for the operating surgeon is to reach percutaneously a target zone in the vicinity of the mobile heart, in a soft-tissue environment. The surgeon's ability to accomplish this depends on his own mental picture of the effusion. CASPER is a navigation software using an optical localizer which assists the surgeon by enhancing the representation of the effusion and guiding the needle's progress. Using a localized and calibrated echographic probe, the surgeon acquires a set of images in the region of interest. This zone is then manually segmented on each image, a common zone is computed, and the surgeon defines a trajectory for the needle. During the puncture procedure, the surgeon follows the position of the localized needle on a computer monitor. After initial validation on an experimental phantom, a feasibility study was performed using canine and porcine models. The optical localization device was changed from an Optotrak to a Polaris device for easier use in the clinical setting. Prior to clinical application, various tests were performed concerning the mobility of the thoracic cage, the reproducibility of the thoracic position over several apneas, and the stability of anatomic structures relative to the thoracic cage. Finally, a first clinical application was successfully performed using this system. The present paper reports on these last two stages.     

5-Lipoxygenase-activating protein is the target of a novel hybrid of two classes of leukotriene biosynthesis inhibitors.

An 18-kDa leukocyte membrane protein, termed 5-lipoxygenase-activating protein (FLAP), has recently been shown to be the target of two structurally distinct classes of leukotriene biosynthesis inhibitors. These classes of inhibitors are based on indole and quinoline structures and are represented by MK-886 and L-674,573, respectively. A novel class of hybrid structure based on the indole and quinoline classes of inhibitors, termed quindoles, has recently been developed. These compounds, exemplified by L-689,037, are potent inhibitors of leukotriene biosynthesis, both in vitro and in vivo. In the present study, we have developed and characterized a potent radioiodinated photoaffinity analogue of L-689,037, termed [125I]L-691,678. This compound was used in immunoprecipitation studies with FLAP antisera to show that the quindole series of leukotriene biosynthesis inhibitors interact directly with FLAP. In addition, we show that MK-886, L-674,573, and L-689,037 specifically compete, in a concentration-dependent manner, with both [125I]L-691,678 and [125I]L-669,083, a photoaffinity analogue of MK-886, for binding to FLAP. These results suggest that these three classes of leukotriene biosynthesis inhibitors share a common binding site on FLAP, providing further evidence that FLAP represents a suitable target for structurally diverse classes of leukotriene biosynthesis inhibitors.     

Autoantibodies directed against the amino-terminal domain I of human calpastatin (ACAST-DI Ab) in connective tissue diseases. High levels of ACAST-DI Ab are associated with vasculitis in lupus

To identify new autoantibody populations in patients with rheumatic diseases, a cDNA expression library was immunoscreened with a rheumatoid arthritis (RA) patient's serum which contains autoantibodies binding to uncharacterized polypeptides by Western-blotting. One clone encoding the amino-terminal region (Nt) [domain L and half of domain I] of human calpastatin was selected. Different fragments of the selected cDNA were prepared and the corresponding recombinant polypeptides were produced by in vitro translation and analysed by Western blotting. Most RA sera bound to recombinant amino-terminal region and domain I but not to domain L. This prompted us to use a recombinant polypeptide corresponding to the domain I of calpastatin as the antigen in a solid-phase ELISA to test sera from patients with various systemic rheumatic diseases and healthy controls.Anti-calpastatin domain I antibodies (ACAST-DI Ab), were detected by ELISA in RA, systemic lupus erythematosus (SLE), Sj?gren's syndrome and control sera at respective frequencies of 10, 9, 0 and 1%. These Ab did not have prognostic value in early RA; high levels were significantly associated with vasculitis in SLE. Antibodies reacting with the calpastatin amino-terminal region are produced during systemic rheumatic diseases and are predominantly directed against domain I. High levels of these Ab may constitute a marker of vasculitis in SLE.     

Adaptive user interface customization through browsing knowledge capitalization

Hypermedia data browsing is a mean for improving information access. However, the overload and the heterogeneity of medical information, as well as the multitude of possible navigational paths, turn the consultation of data into a difficult task. We present in this paper a solution for the development of adaptive user interfaces in a hypermedia data browsing environment. It is based on the capitalization of the users knowledge in the decision-making process, expressed in terms of navigational paths and of data presentation modes that are customized to the user's preferences and practice. This capitalization offers the user a way to automatically store and reuse the experience accumulated in browsing through patient records. We illustrate our approach with the implementation of HEMA, a clinical workstation prototype that we have specialized for the cardiology domain.     

Human malignant mesothelial cells: Variability of ultrastructural features in established and nude mice transplanted cell lines

The aim of this study was to determine, by transmission electron microscopy, the differentiation features of 21 human malignant mesothelioma cell lines (HMCLs) established from 13 specimens of 12 confirmed human malignant mesotheliomas, and of tumours induced in nude mice injected with 16 HMCLs. Fifty per cent of HMCLs showed typical mesothelial differentiation (long and slender microvilli, desmosomes, perinuclear intermediate filaments); 29 per cent did not show differentiation; and the remainder were poorly differentiated. Three human tumour specimens gave several different HMCLs; the cell lines obtained from a given tumour exhibited variable mesothelial differentiation. Eleven HMCLs were compared with the native tumour. Four were similar to the tumour and seven were less well differentiated, in most cases in relation to their microvilli. With six HMCLs, tumours induced in nude mice were less well differentiated than the corresponding cell lines, whereas with four HMCLs, tumours were equally or better differentiated. However, in most nude mice tumours, typical mesothelial microvilli were present. These results show that cell lines established from malignant mesothelioma may exhibit dedifferentiated features. However, while the variability in ultrastructural differentiation may result from the culture microenvironment, it could also be related to the state of differentiation, of the native tumour sample and to tumour cell heterogeneity.