Search PubMed⌕ Search

Biomedical subjects

M Leski

Publications and source records attributed to M Leski.

At least 37 records · Page 2Linked to original sources
PubMed1990

Interaction of single-chain urokinase-type plasminogen activator with human endothelial cells.

The interaction of urokinase-type plasminogen activators with receptors on the surface of endothelial cells may play an important role in the regulation of fibrinolysis and cell migration. Therefore, we investigated whether human umbilical vein endothelial cells (HUVEC) express receptors for single-chain urokinase (scu-PA) on the cell surface and examined the effect of such binding on plasminogen activator activity. Binding of 125I-labeled scu-PA to HUVEC, performed at 4 degrees C, was saturable, reversible, and specific (k+1 4 +/- 1 X 10(6) min-1 M-1, k-1 6.2 +/- 1.4 X 10(-3) min-1, Kd 2.8 +/- 0.1 nM; Bmax 2.2 +/- 0.1 X 10(5) sites/cell; mean +/- S.E.). Binding of radiolabeled scu-PA was inhibited by both natural and recombinant wild-type scu-PA, high molecular weight two-chain u-PA (tcu-PA), catalytic site-inactivated tcu-PA, an amino-terminal fragment of u-PA (amino acids 1-143), and a smaller peptide (amino acids 4-42) corresponding primarily to the epidermal growth factor-like domain. Binding was not inhibited by low molecular weight urokinase or by a recombinant scu-PA missing amino acids 9-45. Cell-bound scu-PA migrated at its native molecular mass on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. In the presence of plasminogen, scu-PA bound to endothelial cells generated greater plasmin activity than did scu-PA in the absence of cells. In contrast, when tcu-PA was added directly to HUVEC, sodium dodecyl sulfate-stable complexes formed with cell or matrix-associated plasminogen activator inhibitors with a loss of plasminogen activator activity. These studies suggest that endothelial cells in culture express high affinity binding sites for the epidermal growth factor domain of scu-PA. Interaction of scu-PA with these receptors may permit plasminogen activator activity to be expressed at discrete sites on the endothelial cell membrane.

Binding, Competitive↗
PubMed1990

Multiple site estimates of erythropoietin and renin in polycythemic kidney transplant patients.

The development of polycythemia after renal transplantation is a well known phenomenon and its etiology remains controversial. In particular, it is unknown whether inappropriate erythropoietin (EPO) production could be a reason. Utilizing a sensitive radioimmunoassay for EPO we have measured EPO concentrations in venous blood from native and grafted kidneys in three normocythemic and seven polycythemic patients. We found that (1) in our posttransplantation polycythemic patients there are inappropriately high systemic EPO levels, hence that posttransplantation polycythemia is related to EPO overproduction. (2) This high EPO production comes from the native kidneys. (3) There is a correlation between EPO and renin levels in the peripheral as well as in native and transplanted kidneys' venous samples.

Adult↗
PubMed1990

Comparison of two hemodialysis membranes, polyacrylonitrile and cellulose acetate, on complement and coagulation systems.

Two hemodialysis membranes, polyacrilonitrile (AN 69) and cellulose acetate (CA), were compared for their effects on complement and hemostasis. Two groups of 5 patients, in dialysis for more than 5 years, were successively dialysed for 4 weeks periods with each type of membrane. We measured C3a (complement activation), platelets and beta-thromboglobulin (platelet activation), thrombin-antithrombin III complexes and fibrinopeptide A (coagulation activation), using C-Reactive Protein as a control for dilution effects. As previously shown, activation of complement was more important with CA than with AN 69 (p less than 0.01). In contrast, activation of coagulation (increase in fibrinopeptide A and thrombin-antithrombin III complexes) was more pronounced with AN 69 than with CA. This study emphasizes the need to consider different biological systems when the bioincompatibility of a hemodialysis membrane is evaluated.

Acrylic Resins↗
PubMed1989

[Kidney transplantation].

Due to advances in immunosuppressive therapy, renal transplantation now offers ESRD patients a better quality of life with short and long-term survival at least equal to the other replacement therapies. Absolute contraindications are rare and are not related to age itself but to associated severe extrarenal diseases. Even absolute psychiatric contraindications are out of the ordinary. Hyperimmunization is still often an insuperable problem. In fact the shortage of transplantable organs, which has become steadily more acute in the last three years, is the main reason why the vast majority of ESRD patients cannot benefit from a functioning graft.

Cadaver↗
PubMed1989

[Rheumatologic complications in patients treated with intermittent hemodialysis].

Long-term hemodialysis is complicated by rheumatological problems. They can vary from pain syndromes without clinical signs to severe destructive arthritis. The latter is often associated with severe disability. Its origin can be related to deposition of amyloid or synovial overloading with aluminium or iron. Different factors influence its occurrence, such as the type of dialysis membrane used or the quantity of aluminium consumed by these hemodialysed patients. The authors evaluated the frequency and the type of rheumatic disorders in the hemodialysis center of the HCU in Geneva. A comparison of these findings with previous reports is presented and the etiopathogenesis is discussed.

Adult↗
PubMed1988

Bolus dose response characteristics of single chain urokinase plasminogen activator and tissue plasminogen activator in a dog model of arterial thrombosis.

Tissue plasminogen activator (t-PA) and single chain urokinase-plasminogen activator (scu-PA) are relatively "fibrin-specific" thrombolytic drugs with short plasma half lives of 6-8 minutes. Most treatment regimens with these agents utilize a bolus injection followed by continuous drug infusion, usually combined with anticoagulant therapy. The purpose of this study was to establish the dose-response characteristics for scu-PA and t-PA, when given as a single intravenous bolus injection, in a dog model of arterial thrombosis. Eight groups of 6 dogs each were given one of the following doses of scu-PA (mg/kg): 0.20, 0.50, 1.00, 2.00; or t-PA: 0.05, 0.10, 0.20; or an equivalent amount of saline (control group). All doses were given as a single bolus injection 60 minutes after formation of a totally occlusive femoral artery thrombus. Thrombolysis was measured by monitoring the continuous decrement of 125I activity from a radiolabelled thrombus. Ninety minutes after drug injection, all scu-PA treated dogs showed greater thrombolysis (30%, 45%, 56%, and 67%, respectively) than the control group (15%, p less than 0.01). The 0.10 and 0.20 mg/kg t-PA treated dogs showed greater thrombolysis (35% and 49%, respectively) than the control group (15%, p less than 0.01). Both scu-PA and t-PA caused a partial and dose-dependent decrease in alpha 2-antiplasmin activity but scu-PA caused a greater depletion (72% vs. 18%, respectively, p less than 0.05) at 60 minutes after the highest dose of drug administration. Both drugs showed a longer than expected thrombolytic effect based upon the known half lives. Neither drug caused significant changes in the prothrombin time, activated partial thromboplastin time, thrombin time, hematocrit, platelet count, or fibrin degradation product concentration. Single bolus injections of scu-PA and t-PA produce safe and effective thrombolysis in this dog model of arterial thrombosis.

Animals↗
PubMed1988

Effect of factors inhibiting HLA-DR antibodies before transplantation on kidney graft survival.

Blood transfusions administered before renal allografts are known to enhance graft survival. Among alternative hypotheses proposed to explain this effect, one of the most attractive is the possible induction of antiidiotypic antibodies directed against the specific antigen-binding site of donor-specific antibodies. In order to determine if such blocking antibodies are generated after blood transfusions, serial serum samples obtained before transplantation from 44 kidney recipients were analyzed for the development of HLA-DR alloantisera inhibitory activity by a microcytotoxicity inhibition assay. A significant correlation was found between the presence of inhibitory factors before transplantation and prolonged graft survival. However a clear relation between the development of inhibitory factors and the administration of transfusions could not be established. In addition the sera of 36 patients were studied for the presence of circulating immune complexes (CIC) before grafting. The presence of CIC was clearly associated with that of inhibitory factors, and with a prolonged graft survival. Thus these studies provide support for the development of blocking (possibly antiidiotypic) antibodies to anti-MHC in human renal graft recipients.

Adult↗
PubMed1983

[Periarteritis nodosa: clinical presentation limited to severe kidney failure accompanied by arterial hypertension].

Two cases of severe renal failure and hypertension of a few weeks duration are reported. There were no symptoms nor signs suggestive of extra-renal involvement and the laboratory tests, more specifically those for the detection of inflammatory parameters, were normal. Renal angiograms revealed intraparenchymal arterial microaneuvrysms which led to the diagnosis of vasculitis of the periarteritis nodosa type. Combined immunosuppressive and steroid treatment was successful in both cases regarding blood pressure control and improvement of renal function. The importance of renal angiography as a diagnostic tool in this type of clinical setting is underlined, as well as the necessity for prompt and prolonged immunosuppressive therapy.

Adult↗
PubMed1982

[Isolated renal involvement in periarteritis nodosa].

Periarteritis nodosa (PAN) is a disease involving the kidneys in 70% of cases but always affecting other organs. Initial presentation with acute renal failure (ARF) and high blood pressure (HBP) is unusual. In two patients presenting those two features without any clinical or biochemical signs of other organ involvements, diagnosis of PAN was based on the presence of microaneurysms on renal angiograms. Combined immunosuppressive and steroid treatment resulted in control of blood pressure of both patients and improvement of renal function in one. ARF associated with HBP without evidence of other organ involvements is consistent with the diagnosis of PAN. In this clinical setting, renal angiography should be performed to confirm the diagnosis and establish the appropriate therapy.

Acute Kidney Injury↗
PubMed1982

Association of a better kidney graft survival with the presence of circulating immune complexes before transplantation.

The presence of circulating immune complexes was investigated using the C1q-binding assay before and after kidney transplantation in 48 patients with renal failure. Circulating immune complexes were found in 54% of the patients. The presence of circulating immune complexes prior to grafting was associated with a better renal graft survival. Median survival time of grafts in patients with circulating immune complexes was more than 18 months as compared with 21/2 months in patients without such complexes. The incidence of circulating immune complexes in patients before transplant could not be related to the renal disease, viral infections, blood transfusions, or serum levels of lymphocytotoxic antibodies, IgG, or IgM.

Antigen-Antibody Complex↗
PubMed1981

[Chronic ambulatory peritoneal dialysis].

Continuous ambulatory peritoneal dialysis for end-stage renal failure was first described in 1976. The purpose of the present study was to establish the value of this method in a group of eight patients with various renal diseases who were controlled monthly for one year. Main benefit was correction of anemia, better control of calcium and phosphate, and excellent blood pressure control. Hyperlipoproteinemia was observed in all patients, as was an increase in plasma renin activity and aldosterone. Thyroid values were in the low normal range. A low incidence of peritonitis was observed and cases of peritonitis were treated on an ambulatory basis. The results suggest that more patients could be included in this new treatment for end-stage renal disease.

Adult↗
PubMed1981

[Renal osteodystrophy in patients on maintenance hemodialysis: statistical study of clinical, radiological and biochemical features].

Sixty radiological, clinical and biochemical features were simultaneously recorded in a population of 46 patients on maintenance hemodialysis. Radiological signs of bone reabsorption (hands, acromio-clavicular and sacro-iliac joints) were demonstrated in 65% and were quantified as a radiological index of hyperparathyroidism. The index was correlated with the levels of parathormone and of alkaline phosphatase (p less than 0.01) and with the duration of renal failure (p less than 0.01), and inversely related to bone densitometry (p less than 0.05). Discriminant analysis confirmed the redundant value of parathormone and alkaline phosphatases in predicting bone lesions. Factorial analysis showed the existence of 12 classes of patients statistically close to one another. These results demonstrate the heterogeneity of renal osteodystrophy.

Bone and Bones↗