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Due to its low level of nephrotoxicity and capacity to harness tolerogenic pathways, sirolimus (SRL) has been proposed as an alternative to calcineurin inhibitors in transplantation. The exact mechanisms underlying its unique immunosuppressive profile in humans, however, are still not well understood. In the current study, we aimed to depict the in vivo effects of SRL in comparison with cyclosporin A (CSA) by employing gene expression profiling and multiparameter flow cytometry on blood cells collected from stable kidney recipients under immunosuppressant monotherapy. SRL recipients displayed an increased frequency of CD4 + CD25highFoxp3 + T cells. However, this was accompanied by an increased number of effector memory T cells and by enrichment in NFkB-related pro-inflammatory expression pathways and monocyte and NK cell lineage-specific transcripts. Furthermore, measurement of a transcriptional signature characteristic of operationally tolerant kidney recipients failed to detect differences between SRL and CSA-treated recipients. In conclusion, we show here that the blood transcriptional profile induced by SRL monotherapy in vivo does not resemble that of operationally tolerant recipients and is dominated by innate immune cells and NFkB-related pro-inflammatory events. These data provide novel insights on the complex effects of SLR on the immune system in clinical transplantation.

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Body dysmorphic disorder (B.D.D.) consists of a preoccupation with an imagined or slight physical defect. This study is the first European report on prevalence and several clinical and functional characteristics of patients with B.D.D. in a cosmetic surgery setting. Comparisons with defect- and severity-matched subjects without B.D.D. were also performed.

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Capillary zone electrophoresis was used to show the coupling between NH2-terminated poly(ethylene oxide) and oligomers of lactic acid activated by transforming carboxyl chain ends to acyl chloride ones. The demonstration was based on the use of fused-silica capillary physically modified by pre-adsorption of polycations in the reversed polarity mode. As poly(ethylene oxide) macromolecules are UV transparent, indirect UV detection was used. A creatinine solution at pH 4.8 was selected as background electrolyte. Commercially available polycations with different structures were tested. It was shown that the reversed electroosmosis could be modulated according to the structure of the polycation. The method was then applied to analyse a commercial alpha,omega-diamino poly(ethylene oxide), namely Jeffamine ED 600 characterised by a broad mass dispersion. Data showed that the method can detect and separate amino poly(ethylene oxide) of different structures. When applied to analyse post coupling products, no free NH2-terminated poly(ethylene oxide) segments were detected. Moreover, the method allowed detection of water-soluble oligomers generated by partial degradation of lactic segments during the reaction.

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Capillary zone electrophoresis (CZE) with neutral phosphate buffer as the background electrolyte was used to analyse water-soluble oligomers obtained by polycondensation of racemic lactic acid. Two CZE separation modes were tested. The first mode was based on normal separation (injection at the anodic side) using a fused-silica capillary. Eight peaks were observed within a 60-min migration time range. They were ascribed to dimer and higher water-soluble oligomers. Peaks from dimer to tetramer were split due to sensitivity for the fine structures at the level of the distribution of chiral lactic acid moieties in oligomer chains. The second mode was based on reverse separation (injection at the cathodic side) using a fused-silica capillary modified by adsorption of a polycation on its inner wall. Under these conditions, oligomers were rapidly separated without peak splitting. Considering the forces which are involved in CZE, data were plotted as a function of 1/t scale, according to the equation [signal]=f((-1)(k)/t) where k=0 and k=1 for normal and reverse separation modes, respectively. Such a plot allowed direct comparison between the various runs after a simple translation along the 1/t axis, regardless of the separation mode and the variation of electroosmotic flow. The second separation mode allowed separation of 3-hydroxybutyric acid and 6-hydroxyhexanoic acid oligomers. For the former series of oligomers, a side reaction generating crotyl bonds was observed due to the high sensitivity of CZE. It was shown that separation was governed by the ratio charge/mass of the oligoesters whatever their structure.

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In order to analyze the alginate components of alginate dressings and the fractions which are released when the dressing is in contact with model biological fluids, the use of various analytical methods was considered. The first step was the conversion of a calcium alginate batch to pure sodium alginate. The recovery of the latter from either insoluble or soluble mixed sodium/calcium alginates was performed by complexation of calcium ions with sodium citrate followed by ultrafiltration. Comparisons were made between sugar analysis, 1H NMR and circular dichroism (CD) data to determinate the contents in guluronic and mannuronic acids of sodium alginate chains. It was shown that CD measurements afford a rapid and nondestructive method for determination of %G when one takes the ratio theta200/theta220 into account. Fractionation of crude alginate (generally ranging from 30 to 70% G) was achieved by the triangle dissolution/precipitation method in order to increase the range of alginate in sugar composition. The various validated procedures were applied to investigate the effects of irradiation sterilization on alginate dressings. It was shown that sugar composition is retained whereas molecular weight decreased dramatically due to chain scission.

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Poly(L-malate) is an unusual polyanion found in nuclei of plasmodia of Physarum polycephalum. We have investigated, by enzymatic and fluorimetric methods, whether poly(L-malate) and structurally related polyanions can interact with DNA-polymerase-alpha-primase complex and with histones of P. polycephalum. Poly(L-malate) is found to inhibit the activities of the DNA-polymerase-alpha-primase complex and to bind to histones. The mode of inhibition is competitive with regard to DNA in elongation and noncompetitive in the priming of DNA synthesis. Spermidine, spermine, and histones from P. polycephalum and from calf thymus bind to poly(L-malate) and antagonize the inhibition. The polyanions poly(vinyl sulfate), poly(acrylate), poly(L-malate), poly(D,L-malate), poly(L-aspartate), poly(L-glutamate) have been examined for their potency to inhibit the DNA polymerase. The degree of inhibition is found to depend on the distance between neighboring charges, given by the number of atoms (N) interspaced between them. Poly(L-malate) (N = 5) and poly(D,L-malate) (N = 5) are the most efficient inhibitors, followed by poly(L-aspartate) (N = 6), poly(acrylate) (N = 3), poly(L-glutamate) (N = 8), poly(vinyl sulfate) (N = 3). It is proposed that poly(L-malate) interacts with DNA-polymerase-alpha-primase of P. polycephalum. According to its physical and biochemical properties, poly(L-malate) may alternatively function as a molecular chaperone in nucleosome assembly in the S phase and as both an inhibitor and a stock-piling agent of DNA-polymerase-alpha-primase in the G2 phase and M phase of the plasmodial cell cycle.

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Primary skin fibroblast cultures were grown from forearm pinch skin biopsies obtained from 24 patients with Duchenne muscular dystrophy (DMD) and ten normal controls matched for sex and age. The first subcultures were grown for 7 days and incubated with L-(3H)-proline for 24 hours. Intracellular collagen incorporation was significantly decreased (2.2 X) and extracellular collagen incorporation significantly increased (1.8 X) in fibroblast cultures from patients with DMD by both collagenase assay and polyacrylamide gel electrophoresis. The synthesis of noncollagen proteins showed low values from the DMD fibroblast cultures. The alterations in synthesis and secretion of collagen and noncollagen proteins were characteristic only for the log phase of DMD fibroblasts.

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Acquired maxillo-facial deformities and in particular those related to problems of facial expression are nevertheless influenced by certain hereditary factors, amongst which the constitutional type or the temperament of the individual play a major role. Morpho-psychology (L. Corman), or the art of relating physical details (especially the shape and characteristics of the face) with psychological state demonstrates correlations between the type of deformity and that of the temperament and explains them. After a brief review of the essential principles of morpho-psychology, the authors study a number of special morpho-psychological types presenting with a significant frequency maxillo-facial deformities, themselves special, and which for this reason they call "morpho-psychological types with a high orthodontic risk". They conclude that it would appear that insufficient importance is attributed at present to psychological factors in the aetiopathogenesis of dysmorphoses and feel that an overall approach to the deformed child is indispensable to progress in the specialty.

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Muscle samples for cultures were obtained from the quadriceps by open biopsy under local anesthesia in five patients with early stage of Duchenne muscular dystrophy (DMD) and 10 controls. Primary cultures were grown in Eagle's Minimum Essential Medium (MEM) with 20 per cent fetal calf serum. After 4 weeks, cells were trypsinized, counted, subcultured for 5 days in MEM with 5 per cent horse serum and finally incubated for 4 h with (3H) leucine. Ttal protein synthesis showed a significant decrease (half of control values) only in muscle cultures from patients with DMD. Addition of calclium chloride alone or with A23187 ionophore normalized this defect in protein synthesis. By contrast, myosin heavy chain synthesis was measured and found normal in all paitents.

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