[Autoantibodies in nephrology].
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Autoantibodies↗
Biomedical subjects
M Marx
Publications and source records attributed to M Marx.
[Molecular regulatory processes in glomerular cells of the kidney].
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Animals↗
Addition of oral clonidine to postoperative patient-controlled analgesia with i.v. morphine.
Using a randomized, double-blind, placebo-controlled design, we have investigated, in 40 patients undergoing major abdominal surgery, the effect of oral clonidine 300 micrograms, 1 h before and 12 h after surgery on postoperative morphine requirements (evaluated by PCA). During the 24 h of the study, pain scores measured every 6 h did not differ significantly. Morphine requirements tended to be reduced in the clonidine group but the difference was not significant. There were no significant differences also in mean arterial pressure, ventilatory frequency and the incidence of pruritus and nausea. Heart rate was significantly lower until 18 h after surgery and sedation was significantly more pronounced in patients receiving clonidine. We cannot recommend routine oral administration of clonidine before surgery to improve postoperative analgesia.
Administration, Oral↗
Differences in intravenous and subcutaneous application of recombinant human erythropoietin: a multicenter trial.
The aims of this clinical study were to compare the maintenance doses for intravenous (i.v.) and subcutaneous (SC) administration of recombinant human erythropoietin (rhEPO) and to investigate whether there is any difference in the increase of the packed cellular volume (PCV) per week under i.v. and SC administration of rhEPO from two production sites (Genetics Institute, Cambridge, USA; and Boehringer Mannheim, Penzberg, Germany). A total of 90 patients suffering from end-stage renal disease were included in the study. All patients had already been treated for at least 6 months with chronic hemodialysis. The study was carried out as a randomized, multicenter parallel group comparison study with a 1-week pretreatment phase, a subsequent 8-week double-blind phase, and a final open phase. The final open phase consisted of a correction phase and a maintenance phase. The production site had no influence on the PCV increase per week, and there were no differences with respect to tolerability. The median rhEPO dose required to maintain the target PCV of 30 to 35 vol.% was 33 U/kg body weight three times a week in the i.v. group compared with 22 U/kg in the SC group (i.e., an average of 30% less with SC administration). Development or aggravation of hypertension under rhEPO therapy was observed, especially during the correction phase and more frequently in the SC group than in the i.v. group. During the maintenance phase, there was no essential difference between the two groups.
Adult↗
Functional and biological properties of an avian variant long terminal repeat containing multiple A to G conversions in the U3 sequence.
We previously reported that infection of chicken embryonic neuroretina cells with Rous-associated virus type 1 leads to the frequent occurrence of spliced readthrough transcripts containing viral and cellular sequences. Generation of such chimeric transcripts constitutes a very early step in oncogene transduction. We report, here, the isolation of a c-mil transducing retrovirus, designated IC4, which contains a highly mutated U3 sequence in which 48% of A is converted to G. Functional analysis of this variant U3 indicated that these mutations do not impair viral transcription and replication; however, they abolish functioning of its polyadenylation signal, thus allowing readthrough transcription of downstream cellular sequences. On the basis of these results, we designed a nonreplicative retroviral vector, pIC4Neo, expressing the neomycin resistance (Neo(r)) gene under the control of the IC4 long terminal repeat. Infection of nondividing neuroretina cells with virus produced by a packaging cell line transfected with pIC4Neo occasionally resulted in sustained cell proliferation. Two independent G418-resistant proliferating cultures were found to express hybrid RNAs containing viral and cellular sequences. These sequences were characterized by reverse transcription-PCR and were identified in both cultures, suggesting that proliferation was correlated with a common integration locus. These results indicate that IC4Neo virus functions as a useful insertional mutagen and may allow identification of genes potentially involved in regulation of cell division.
Adenine↗
L-arginine reduces heart collagen accumulation in the diabetic db/db mouse.
BACKGROUND: Diabetic cardiomyopathy presents with significant collagen accumulation; decreased solubility, increased glucose-mediated abnormal cross-linking, free radical cross-linking, or glucose-induced increased transcription of collagen is incriminated. In a previous study, we reduced collagen accumulation in the kidneys of diabetic mice by treatment with oral arginine. This observation led us to examine the effect of arginine on cardial fibrosis. METHODS AND RESULTS: Twenty-nine db/db spontaneously diabetic mice were used in the experiments. Sixteen were given L-arginine (free base, in tap water, 50 mg/kg body wt per day) for 4 months. At the end of the experiment, we determined total collagen content of total ventricular tissue, acid solubility, carboxymethyllysine, O-tyrosine, glutathione, blood glucose, and fructosamine as parameters for glycemic control. Heart collagen level was significantly (P = .0001) reduced in the experimental group (mean, 0.24 +/- 0.05) compared with the control group (mean, 0.49 +/- 0.10 mumol hydroxyproline per 100 mg heart tissue). Significantly more collagen could be eluted from heart samples of the experimental group (P = .02). Carboxymethyllysine and O-tyrosine did not differ when related to heart weight. Glutathione level was significantly higher in the untreated group (P = .003). Parameters of glycemic control did not differ between the groups. CONCLUSIONS: Our findings clearly indicate that L-arginine reduced total heart collagen and increased acid solubility of heart collagen. Both findings are compatible with the cross-linking hypothesis. The data for carboxymethyllysine, O-tyrosine, and glutathione would rule out the glycoxidation hypothesis and, therefore, free radical cross-linking. The postulated mechanism of action is most likely the blocking of reactive carbonyl functions by L-arginine in analogy to aminoguanidine activity. Correlations of collagen with glycemic control, however, point to an association of glucose with collagen metabolism, a phenomenon documented in cell cultures at the transcriptional level.
Animals↗
Modulation of platelet-derived growth factor receptor expression in microvascular endothelial cells during in vitro angiogenesis.
Microvascular endothelial cells in vivo exhibit a plastic phenotype, forming a nonproliferative, differentiated capillary network, while retaining their ability to respond to injury by proliferation, migration and neovascularization. The presence of PDGF receptors and PDGF responsiveness in microvascular endothelial cells and the significance of PDGF isoforms in the control of endothelial cell growth and differentiation remain controversial. Since culture of microvascular endothelial cells in a three-dimensional (3D) system induced cell differentiation and angiogenesis and inhibited proliferation, the present study investigates the role of different extracellular matrix environments in inducing different microvascular endothelial cell phenotypes on microvascular endothelial cell PDGF receptor expression and PDGF responsiveness. In conventional two-dimensional (2D) culture, microvascular endothelial cells expressed both PDGF receptor alpha and beta chains. Suramin treatment demonstrated continuous downregulation of the alpha receptor surface expression. PDGF BB and, to a lesser extent, PDGF AB were mitogenic in 2D-culture, PDGF AA failed to induce any proliferative response despite inducing receptor autophosphorylation. During in vitro angiogenesis induced by 3D-culture, both PDGF receptors were rapidly downregulated. Assessment of cell proliferation showed quiescent cells and PDGF unresponsiveness. We conclude that the induction of a differentiated phenotype during in vitro angiogenesis (tube formation) driven in part by the spatial organization of the surrounding matrix is associated with a downregulation of PDGF receptors. Identification of the molecular cell-matrix interactions involved in this receptor regulation may allow for targeted manipulation of cell growth in vivo and lead to novel therapeutic applications for PDGF.
Adipose Tissue↗
Steps and mechanisms of oncogene transduction by retroviruses.
Oncogene transduction, the process by which a cellular gene is captured by a retrovirus was mainly described in vivo. We have developed a biological system allowing stepwise analysis of transduction mechanisms in tissue culture. Avian neuroretina (NR) cells dissected at the 8th day of embryonic development rapidly cease to divide and differentiate in culture. Serial passaging of a retrovirus that does not carry an oncogene on such cultures leads with a high frequency to the emergence of new viruses that have transduced oncogenes from the mil/raf family of serine/threonine kinases. These viruses have been selected by their ability to induce NR cell division. This experimental system allowed the isolation of the following molecular intermediates generated during the successive steps of oncogene transduction: a chimeric transcript containing viral and cellular sequences joined together by an alternative splicing mechanism; then a complete retrovirus with a 5' end identical to that of chimeric RNA; finally, a retrovirus that has acquired additional gag sequences and consequently, an increased replicative capacity. Structural analysis of these molecules led us to propose a general model for oncogene transduction in which the key step is the synthesis of chimeric RNAs. This model also explains generation of the vast majority of acutely transforming retroviruses isolated in vivo.
Animals↗
[Comparison of surgical techniques and various suture materials for correction of aortic isthmus stenosis].
UNLABELLED: Clinical examination and Doppler ultrasound were performed in 31 children after repair of coarctation of the aorta. Median postoperative follow-up period was 4.5 years. The aim of our study was a comparison of different operation techniques and suture materials. In 16 infants subclavian flap repair had been performed using polydioxanone absorbable sutures (PDS) in 8 cases and polypropylene (Prolene) sutures in the other 8 cases. Resection and end-to-end repair had been carried out in 8 infants using PDS and in 7 using Prolene sutures. Doppler-echocardiographically derived gradients across the reconstructed aorta were significantly lower in infants operated with the subclavian flap technique (p < 0.05). The length of the arm on the side of the subclavian flap operation was shorter (median 1.2 cm), but there were no signs of ischaemic complications. Using PDS sutures the aortic arch and the aortic isthmus were each morphologically significantly wider in both operation techniques. Noninvasive two-dimensional echocardiography demonstrated good anatomical repair and no anastomotic aneurysm formation after aortic repair using polydioxanone. CONCLUSION: Regarding the doppler-echocardiographically derived gradients in the anastomotic region this intermediate follow-up study reveals better results using the subclavian flap technique; absorbable polydioxanone sutures favour normal growth of the anastomotic site without vascular complications.
Anastomosis, Surgical↗
Course and prognosis of anti-basement membrane antibody (anti-BM-Ab)-mediated disease: report of 35 cases.
Anti-basement membrane antibody (anti-BM Ab) mediated disease is reported to be a rare disorder frequently leading to severe deterioration of renal function. It was our purpose to work out parameters necessary to predict the outcome reliably and to examine, who will benefit most from therapy. Data from 35 patients were evaluated retrospectively. Diagnosis was based on the detection of linear IgG staining (n = 28) along the glomerular basement membrane (GBM) in renal biopsies and/or on the demonstration of anti-BM Ab both by ELISA and immunoblotting (n = 35). Patients were followed up for at least 6 months. Several variables were analysed as to whether they are appropriate prognostic factors. Twenty patients (57%) presented with Goodpasture's syndrome, 13 (37%) had anti-GBM glomerulonephritis alone, whereas two patients suffered solely from pulmonary haemosiderosis. Frequent initial symptoms were haemoptysis (n = 18), haematuria (n = 26), proteinuria (n = 26) and elevated serum creatinine (n = 27). Among all, 10 patients improved, having stable renal function. Twenty-one patients developed end-stage renal failure and four died. Parameters indicating a poor prognosis were a serum(s)-creatinine greater than 600 mumol/l and crescent formation in more than 50% of the glomeruli on renal biopsy. By combining these two parameters the outcome could be reliably predicted. The initial antibody titre and cigarette smoking were without predictive value. In conclusion, the earlier therapy starts, the better will be the result. Patients presenting early with a serum creatinine < 200 mumol/l and without severe glomerular alterations gained the most benefit from therapy, indicating that outcome may be improved by early diagnosis.
Adult↗
Synthesis of phosphocholine and quaternary amine ether lipids and evaluation of in vitro antineoplastic activity.
The in vitro antineoplastic activity of many phosphorus-containing (e.g., phosphocholines) and non-phosphorus-containing (e.g., quaternary ammonium salts) ether lipids has been evaluated in the HL-60 promyelocytic cell line. These compounds are analogues of ET-18-OMe (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine). Structural modification of 1-(alkylamido)-, -(alkylthio)-, and -(alkyloxy)propyl backbones has provided further insight into the structure-activity relationships of these lipids. In this study, a long saturated C-1 chain and a three-carbon backbone with a single short C-2 substituent were preferred. At the positively charged nitrogen of phosphocholines, fewer than three substituents caused a significant loss of activity, and substituents larger than methyl decreased activity slightly. In the nonphosphorus compounds, many nitrogen heterocycles and also a sulfonium moiety were incorporated without changing the degree of activity; however, a thiazolium group decreased activity. The most active compound, 29 [N-[3-(hexadecyloxy)-2-methoxypropyl]-3-(hydroxymethyl)pyridinium bromide], was approximately twice as active as the reference standard, ET-18-OMe, in a trypan blue dye exclusion assay.
Antineoplastic Agents↗
Genomic organization and nucleotide sequence of the coding region of the chicken c-Rmil(B-raf-1) proto-oncogene.
c-Rmil is the cellular allele of the v-Rmil oncogene, transduced during in vitro passaging of Rous associated virus type 1 in chicken embryonic neuroretina (NR) cells. The c-Rmil proto-oncogene is the avian homolog of the mammalian B-raf gene and belongs to the mil/raf oncogene family of serine/threonine protein kinases. We recently reported that the avian c-Rmil gene encodes two proteins of 94 and 95 kDa, resulting from an alternative splicing mechanism. We describe here the exon-intron organization of the coding region of the chicken c-Rmil locus. We show that c-Rmil proteins are encoded by 19 exons lying within about 100 kbp of genomic DNA. Comparison of the organization of this gene with those of the other mil/raf genes shows strong similarities within three conserved domains previously identified in mil/raf protein kinases. However, c-Rmil contains two additional 5' coding exons that are not present in the other mil/raf genes.
Amino Acid Sequence↗
Quantitative EEG before and after open heart surgery in children. A significant decrease in the beta and alpha 2 bands postoperatively.
Quantitative EEGs of 30 patients undergoing open heart surgery were investigated before, 6 days, 11 days and 44 days after operation. The study was conducted in order to investigate whether quantitative EEGs can show postoperative changes in children after open heart surgery. In 28 children, no new neurological signs of cerebral involvement were seen postoperatively. The most striking feature in these children was a significant decrease in the beta and the alpha 2 bands 6 and 11 days postoperatively. The pattern in the delta band was dominated by an increase 6 days postoperatively. Except for a slight decrease in alpha 2 waves, all variables were restored to preoperative values at 44 days after the operation. We found a significant decrease in plasma sodium and chloride after surgery but children with no or slight declines (1-3 mmol/l) also showed increased slow activity postoperatively. Therefore we conclude that an organic brain syndrome, although usually mild and transient, is a general phenomenon after open heart surgery.
Adolescent↗
Pulmonary autograft valve replacement in the dilated and asymmetric aortic root.
Pulmonary autograft aortic valve replacement is the only technique for implantation of a biologic, vital and thus nondegenerating valve. The technique of root replacement overcomes problems of asymmetric aortic roots and reduces the risk of malalignment, but bears the risk of dilatation. We have performed pulmonary autograft aortic root replacement in 20 patients (mean age 22 years, range 5-38). Twelve presented with aortic incompetence, 3 with stenosis and 5 with combined defects. Initially roots were implanted just supraannularly with two running suture lines. As the neo-aortic roots gradually dilated, we started to implant autografts intraannulary, but still one valve dilated and aortic incompetence (AI) increased from grade I to II. Consequently the remaining aortic wall was wrapped around the new root and the composite subsequently was reinforced by a circular absorbable mesh. In addition, the aorta and pulmonary valve were exactly sized and the aortic root was reduced by commissuroplasty stitches up to 6 mm in diameter in seven cases. The ventricular size decreased in all patients 10 days after surgery, the left ventricular end-diastolic diameters (LVEDD) from 58 +/- 12 to 52 +/- 10 mm (P = 0.0002; paired t-test) and left ventricular end-systolic diameter (LVESD) from 41 +/- 12 to 36 +/- 10 mm (P = 0.008), but the contractility did not change significantly (fractional shortening from 31 +/- 9% to 30 +/- 9%). The diameter of the new aortic ring increased for the supraannular position but size matching and the intraannular valve position reduced the new ring size significantly (P = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Spatial organization of the extracellular matrix modulates the expression of PDGF-receptor subunits in mesangial cells.
The aim of this study was to test the hypothesis that changes in the extracellular matrix environment regulate rat mesangial cell growth by modulation of the expression of both PDGF-receptor alpha- and beta-subunits. We investigated the mitogenic effects of the PDGF isoforms AA, AB and BB in conventional two-dimensional (2D) culture on laminin, fibronectin, type I, IV and V collagen and in the different spatial organization of matrix in type I collagen gels in three-dimensional culture (3D). In 2D culture PDGF BB was a potent mitogen, AB elicited an intermediate response while AA had no effect on cell proliferation. Extracellular matrix did not modify the PDGF responsiveness in 2D-culture. The different effects of the three PDGF isoforms were due to differential expression and isoform specific association of the PDGF-receptor subunits. Specifically, the beta-receptor was strongly expressed, whereas the alpha-receptor was only barely detectable on the cell surface. Metabolic labeling revealed synthesis and intracellular accumulation of the complete alpha-receptor protein, and treatment with suramin increased its surface expression, suggesting continuous receptor down-regulation by endogenous PDGF. Morphological and ultrastructural analysis in 3D culture revealed a change in mesangial cell phenotype, forming a branching network of multicellular structures. Assessment of proliferation in 3D culture showed quiescent cells and PDGF unresponsiveness. Investigation of the PDGF beta-receptors revealed a rapid down-regulation in 3D culture; both receptor subunits were not detectable on the cell surface. We conclude that 3D culture promotes the induction of a different mesangial cell phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Renal matrix and adhesion in injury and inflammation.
Over the past year, there have been major advances in the descriptive analysis of the extracellular matrix in the kidney. Several aspects of the interaction of matrix molecules with renal and, in particular with glomerular cells via specific integrin receptors, have also been studied. Most results on cell-matrix interactions have been obtained by in vitro investigations of glomerular mesangial cells in two-dimensional culture. The regulation of matrix formation and degradation has been shown to involve the concerted action of several soluble factors, notably transforming growth factor-beta, as well as the effects of nonsoluble matrix components themselves, such as collagens and proteoglycans. The mediation of such complex interactions between cells, matrix, and cytokines is facilitated by the tightly regulated expression of cell surface receptors, eg, cytokine receptors and integrins of the beta 1 series, which bind specific matrix molecules. New results have yielded more insight into the regulation not only of matrix formation but also of the specific interactions between cells and matrix and of the modulation of cytokine activity by matrix molecules. Using experimental rat models and transgenic mouse models of kidney disease, the first in vivo findings using immunohistochemistry and mRNA analysis have confirmed that major changes occur in the expression of matrix molecules, integrins, and cytokines in the process of glomerular inflammation. With the advent of specific modulators of the bioactivity of ligands and receptors, it is hoped that more information will be forthcoming on the functional relevance of various components of the cell-matrix-cytokine crosstalk in the normal and injured kidney.
Animals↗
Occurrence of alternatively spliced leader-delta onc-poly(A) transcripts in chicken neuroretina cells infected with Rous-associated virus type 1: implication in transduction of the c-mil/c-raf and c-Rmil/B-raf oncogenes.
We previously reported that serial passaging of Rous-associated virus type 1 in nondividing chicken embryo neuroretina cells leads to reproducible generation of acutely mitogenic retroviruses that transduced the catalytic domain of c-mil/c-raf or c-Rmil/B-raf. On the basis of structural analysis of several retroviruses, we proposed that the early step of oncogene transduction is the constitution of alternatively spliced leader-delta onc-poly(A) transcripts. Here, we show that neuroretina cells do synthesize hybrid leader-delta mil and leader-delta Rmil RNAs and that these RNAs exhibit mitogenic properties and serve as templates for the generation of transducing retorviruses.
Alternative Splicing↗
Xylocaine plus methylene blue vs methylene blue alone for marking breast tissue preoperatively.
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Anesthesia, Local↗