[Peculiarities of heparin elimination in extracorporeal dialyses].
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Biomedical subjects
Publications and source records attributed to M Kessel.
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Image processing has revealed the attachment site of antibody 54G8 on chaperonin 60 (cpn60) from Bordetella pertussis. This antibody, previously shown to affect the ability of chaperonin 10 (cpn10) to inhibit the ATPase activity of cpn60, is attached at the ends of the cpn60 and links the molecules into long chains. When only Fab fragments, which also affect ATPase activity, are used for labeling, these attach to both ends of the cpn60 molecule, but the long chains are not seen. Some perturbation of cpn60 was seen when Fab fragments were bound (Fab:cpn60 = 28:1).
Cytochrome oxidase vesicle crystals with long-range order have been obtained from cholate-solubilized, highly purified reconstitutively active preparations. These crystals, which are suitable for electron-microscopic structure investigation, show pgg symmetry in the 0 degree projection. Using Fourier reconstruction and modified back-projection methods, a three-dimensional reconstruction has been obtained at a resolution of 25 A. Our structural results are in agreement with the model of Henderson et al. [J. Mol. Biol. 112, 631 (1977)] obtained for their Triton-derived crystals.
Teratocarcinoma cells provide us with a model system for the study of differentiation and development. One of the best characterized cell lines, the embryonal carcinoma stem cell line F9, differentiates after treatment with retinoic acid (RA) and dibutyryl cyclic AMP into parietal endoderm. This differentiation process is accompanied by the induction of several genes, for example, those encoding collagen IV, plasminogen activator and intermediate filaments like laminin. In contrast, a marked reduction of stable messenger RNA has been observed for the gene encoding p53 and for c-myc. Both cellular oncogenes seem to be involved in the regulation of cellular proliferation and neoplastic transformation. For growth-arrested 3T3 fibroblasts, growth-factor-induced changes of myc RNA are controlled at the level of transcription. In contrast, F9 cells provide a differentiation system in which cells are able to change from a tumorigenic state into non-dividing, non-tumorigenic endodermal cells. The latter process enabled us to study the regulation of myc and p53 genes in the same cells at different stages of growth, tumorigenicity and differentiation. Here we report that down-regulation of stable myc and p53 RNA during irreversible differentiation of F9 cells occurs at the post-transcriptional level. Using an in vitro nuclear transcription assay, we found that the polymerase II density on both genes remains constant during differentiation. In agreement with this interpretation, we detected myc RNA as stable transcripts in differentiated F9 cells after treatment of the cells with cycloheximide. The post-transcriptional regulatory mechanisms controlling p53 and myc stability follow different kinetics. Whereas the down-regulation of myc seems to be an early event of F9 differentiation occurring within the first 24 h, the post-transcriptional regulation of p53 occurs at a later stage (two to three days), possibly as a consequence of cell cycle changes.
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Interleukin-1 (Il-1), prostaglandins, and leukotrienes have been identified as inflammatory parameters in the setting of peritoneal dialysis. Recently, it was postulated that chronic overstimulation of peritoneal macrophages (PM) may result in fibrosis and loss of ultrafiltration. The aim of the present study was to investigate whether alternative osmotic agents (polyglucose, amino acids, glycerol, bicarbonate/glucose, gelatine, hydroxyethyl starch) provoke greater eicosanoid release by PMs than glucose. Fifty milliliters of sterile dialysate containing different osmotic agents were injected intraperitoneally into nonuremic guinea pigs. After 4 hours of dwell time, prostaglandin E2 (PGE2), thromboxane B2 (TXB2), and leukotriene B4 (LTB4) production was analyzed in peritoneal effluents using specific radioimmunoassays (RIA) after liquid extraction. Cyclooxygenase products were generated with all osmotic agents: PGE2 concentrations ranged from 0.9 to 2.8 ng/4h, and TXB2 levels ranged from 39 to 49 ng/4h. In addition, the lipoxygenase product LTB4 was found in concentrations between 1.8 and 3.5 ng/4h. There were no significant differences in eicosanoid release among the osmotic agents. Thus, in this experimental setting, the capacity of PM to release inflammatory mediators did not correlate with the chemical composition of the dialysis solutions.
We have previously demonstrated that chemical modification of cellulosic membranes with dimethyl-amino-ethyl (DEAE) groups significantly improves membrane properties in terms of biocompatibility. Here, we show that DEAE substitution also alters the membrane's thrombogenic properties, and cellulosic membranes with various amounts of DEAE substitution were produced. Clinical dialyzers were constructed using two experimental membrane materials: modified cellulose-low (MC-low) and MC-high; standard unsubstituted cellulose was used as a control. Six patients were treated for a period of 3 weeks with each type of dialyzer and a heparin dose of less than 6000 IU/treatment. MC-low exhibited less extracorporeal beta-thromboglobulin and thromboxane B2 release than MC-high or Cuprophan. In addition, residual blood volume after clinical use was lower in the MC-low type. MC-low and MC-high induced less complement activation than Cuprophan, as characterized by extracorporeal C5a and C3a plasma concentrations (75% less C5a generation and 50 to 70% less C3a generation than unsubstituted cellulose).
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