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Biomedical subjects

G Mourad

Publications and source records attributed to G Mourad.

At least 73 records · Page 4Linked to original sources
PubMed1996

[Lipoprotein glomerulopathy: a new French case with recurrence on the transplant].

Lipoprotein glomerulopathy is defined by the presence of lipidic deposits in the capillary lumen giving them a dialted and microaneurysmal aspect and the presence of quantitative and/or qualitative alterations of plasma apolipoprotein E. We describe here the long-term follow-up of a young female patient who presented with corticoresistant nephrotic syndrome in 1979 and progressed to chronic renal failure requiring dialysis in 1990. The three renal biopsies performed during the follow-up showed markedly enlarged capillary loops due to intra-luminal fibrinolipidic material deposition forming true intracapillary thrombi. She received a cadaver renal transplant in 1993. One year after transplantation, nephrotic syndrome reappeared and graft biopsy showed recurrence of the initial glomerular disease on the transplant. The plasma lipid profile showed hypercholesterolemia, hypertriglyceridemia, and elevated plasma ApoE levels with an abnormal Apo E phenotype. Our case report is a new typical case of lipoprotein glomerulopathy with recurrence of the initial disease on the renal allograft.

Adult↗
PubMed1996

Oral vitamin D or calcium carbonate in the prevention of renal bone disease?

It is well known that hyperparathyroidism begins early in renal failure and progresses, probably not linearly, throughout the natural course of renal diseases and dialysis therapy. Recent progress in basic medical science has improved our understanding of the mechanisms by which the classically known stimuli for parathyroid hormone synthesis and secretion may act, including hypocalcaemia, hyperphosphataemia and vitamin D3 metabolism disturbances. In the treatment of hyperparathyroidism, although some authors stress the benefit of treating one of these stimuli, it is probably more effective to combine the treatment of them all. There is conclusive recent work showing the efficacy of using both CaCO3 and vitamin D3, either in chronic renal failure or in dialysis patients at every stage of hyperparathyroidism. Therefore, the treatment of hyperparathyroidism should start early, long before dialysis, and it should aim to correct any of the causal factors. Both CaCO3 and vitamin D3 derivatives may be used in the prevention and treatment of renal bone disease. The limits of this association are the increasingly often reported adynamic bone disease, which in our experience has not yet given major clinical problems, and hyperphosphataemia. Uncontrolled serum phosphate levels would counterbalance the beneficial effect of vitamin D3 derivatives on hyperparathyroidism.

Administration, Oral↗
PubMed1996

Renal transplantation relieves the symptoms but does not reverse beta 2-microglobulin amyloidosis.

Renal transplantation is considered to be the treatment of choice of dialysis-related beta 2-microglobulin amyloidosis (DRA), as it provides near-normal serum levels of beta 2-microglobulin and obviates the need for dialysis. However, the long-term outcome of DRA after transplantation has not been fully assessed, and its evolution after transplant failure has not been reported. This study examined 17 patients with histologically confirmed DRA who underwent kidney transplantation and had a dialysis-free follow-up period in excess of 1 yr. Immunosuppressive treatment included low-dose prednisolone, cyclosporine, and/or azathioprine. Symptoms related to DRA were sought at every outpatient visit, and bone x-rays were performed at time of transplantation and annually thereafter. The number and size of the bone cysts were determined. Most of the DRA symptoms, and particularly shoulder stiffness, disappeared within the first wk after transplantation and this persisted throughout the transplant follow-up period (58.5 +/- 9 months). However, the number of bone cysts remained remarkably constant even in those patients with still-functioning grafts (12 +/- 7.5 and 12.1 +/- 7.7, before and at last transplantation follow-up examination, respectively). Beta 2-microglobulin amyloid was found to be present in one patient operated on for hip fracture 2 yr after receiving a well-functioning transplant. Seven patients experienced graft failure and returned to dialysis after 47 +/- 39 months of transplantation. Severe DRA symptoms reappeared strikingly early after resuming hemodialysis, and five out of the seven patients required surgery for carpal tunnel syndrome, three of them within the first yr (mean, 17 +/- 12 months). The number of cysts significantly increased from 17 +/- 11 to 21 +/- 11 during the second dialysis period. These findings provide further evidence suggesting that although the clinical expression of DRA is arrested during transplantation, the anatomical lesions and the pathological processes underlying it are unlikely to be reversed.

Adult↗
PubMed1995

An acetohydroxy acid synthase mutant reveals a single site involved in multiple herbicide resistance.

Acetohydroxy acid synthase (AHAS) is an essential enzyme for many organisms as it catalyzes the first step in the biosynthesis of the branched-chain amino acids valine, isoleucine, and leucine. The enzyme is under allosteric control by these amino acids. It is also inhibited by several classes of herbicides, such as the sulfonylureas, imidazolinones and triazolopyrimidines, that are believed to bind to a relic quinone-binding site. In this study, a mutant allele of AHAS3 responsible for sulfonylurea resistance in a Brassica napus cell line was isolated. Sequence analyses predicted a single amino acid change (557 Trp-->Leu) within a conserved region of AHAS. Expression in transgenic plants conferred strong resistance to the three classes of herbicides, revealing a single site essential for the binding of all the herbicide classes. The mutation did not appear to affect feedback inhibition by the branched-chain amino acids in plants.

Acetolactate Synthase↗
PubMed1995

A double mutant allele, csr1-4, of Arabidopsis thaliana encodes an acetolactate synthase with altered kinetics.

A comparison is made of the kinetic characteristics of acetolactate synthase (EC 4.1.3.18) in extracts from Columbia wild type and four near-isogenic, herbicide-resistant mutants of Arabidopsis thaliana (L.) Heynh. The mutants used were the chlorsulfuron-resistant GH50 (csr1-1), the imazapyr-resistant GH90 (csr1-2), the triazolopyrimidine-resistant Tzp5 (csr1-3) and the multiherbicide-resistant, double mutant GM4.8 (csr1-4), derived from csr1-1 and csr1-2 by intragenic recombination (G. Mourad et al. 1994, Mol. Gen. Genet. 243, 178-184). Kmapp and Vmax values for the substrate pyruvate were unaffected by any of the mutations giving rise to herbicide resistance. Feedback inhibition by L-valine (L-Val), L-leucine (L-Leu) and L-isoleucine (L-Ile) of acetolactate synthase extracted from wild type and mutants fitted a mixed competitive pattern most closely. Ki values for L-Val, L-Leu and L-Ile inhibition were not significantly different from wild type in extracts from csr1-1, csr1-2, and csr1-3. Ki values were significantly higher than wild type by two- and five-fold, respectively, for csr1-4 with L-Val and L-Leu but not L-Ile. GM4.8 (csr1-4) plants were also highly resistant in their growth to added L-Val and L-Leu.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetolactate Synthase↗
PubMed1995

Beta 2 microglobulin isoforms in healthy individuals and in amyloid deposits.

beta 2 microglobulin (beta 2m) is classically known to have isoforms with isoelectric points (pI) 5.7 and 5.3. New isoforms of beta 2m with lower pI, probably due to modifications with advanced glycation end products, were found in the amyloid deposits of dialysis related amyloidosis (DRA), and they were proposed as the amyloidogenic forms of beta 2m. The other modifications in beta 2m from amyloid deposits are partial proteolysis and single amino acid replacement (Asn by ASp at position 17). However, there are no data on the sequence of the different isoforms of beta 2 m from amyloid deposits. Amyloid deposits surgically obtained from the carpal tunnel from 13 dialysis treated patients and urine from 10 healthy volunteers and 5 living-related kidney donors were analyzed for beta 2m content. Two-dimensional gel electrophoresis (2D-PAGE) of beta 2m from amyloid deposits showed the presence of four or more isoforms with pIs < 5.7. All the spots migrating at 12 kDa Mr region and between 4 and 6 pH reacted with rabbit anti-human beta 2m antibody by Western blotting, confirming that they were beta 2m isoforms. beta 2m isoforms from the amyloid deposits were then separately purified with an IEF column (PB94, Pharmacia) for analysis. Enough quantities of three pure beta 2m isoforms could be obtained in two cases. The sequence analysis showed an intact N-terminus in all the isoforms. There was Asn in the 17th residue in all the isoforms sequenced. 2D-PAGE of urine from 8 out of the 10 healthy volunteers showed the presence of beta 2m. In two of them beta 2m also displayed four different isoforms. At least four isoforms were observed in urine of all the kidney donors. The present study shows that the elution peaks of three different beta 2m isoforms in gel isoelectrofocusing contain beta 2m with intact N-terminus. None of them have deamidated their 17th residue. More importantly, the beta 2m isoforms with lower pI are not specific for amyloidosis as they were found in urine from kidney donors and in normal volunteers. These results bring into question the hypothesis that dialysis related amyloidosis is due to the known modifications on beta 2m. They suggest that the precipitation of beta 2m into amyloid fibrils should result from the interaction of beta 2m with other factors with amyloid enhancing activity.

Adult↗
PubMed1995

Serial renal transplant surgery: technical reflections concerning third transplants.

From 1972 to 1993, we carried out 803 consecutive renal transplants including 8 third transplants. Exclusively cadaveric, these third renal transplants were implanted by intraperitoneal approach in right iliac position, without previous homolateral transplantectomy in 5 cases. The arterial anastomoses were common (7) or external iliac and hypogastric (1), and the venous anastomoses external (1) and common iliac (3), or inferior vena cava (4). Restoration of urinary continuity was by ureteronecystostomy (Politano-Leadbetter = 4, Grégoir-Lich = 3) or ureteroureteric anastomosis (1). The level of HLA compatibility varied from 2 to 5 identities (mean 3.1) and 4 of the 7 patients explored were hyperimmunized with lymphocytotoxic antibody levels > or = 80%. With the exception of the first of these third transplants, the immunosuppressive protocol associated azathioprine, prednisolone, antilymphocytic serum and cyclosporin. Postoperative sequels were marked by 3 vascular rejections and 1 death from hyperkalemia. Moreover, 1 urinary fistula on ureteroureteric anastomosis settled after percutaneous nephrostomy and placing of an uteric stent endoprosthesis. With a postoperative follow-up of 8-32 months (mean 24), 5 of the transplanted patients (62.5%) have a functional renal transplant with a serum creatinine from 120 to 180 microM/l (mean 140). This brief series, whose failures are exclusively immunological, reveals the remarkable technical reliability for these third renal transplants in right iliac implantation, by median transabdominal approach and above a former transplant site.

Adult↗