Search PubMed⌕ Search

Biomedical subjects

B Faller

Publications and source records attributed to B Faller.

At least 19 recordsLinked to original sources
PubMed1992

Heparin-induced conformational change and activation of mucus proteinase inhibitor.

Low molecular mass heparin (5.1 kDa) forms a tight complex with mucus proteinase inhibitor, the physiologic neutrophil elastase inhibitor of the upper respiratory tract. This binding strongly enhances the intrinsic fluorescence of the inhibitor and the rate of neutrophil elastase inhibitor association. One mole of this heparin fragment binds 1 mol of inhibitor with a Kd of 50 nM. From the variation of Kd with ionic strength, it is inferred that (i) 85% of the heparin--inhibitor binding energy i due to electrostatic interactions, (ii) about seven ionic interactions are involved in heparin--inhibitor binding. strength, it is inferred that (i) 85% of the heparin--inhibitor binding energy is due to electrostatic interactions, (ii) about seven ionic interactions are involved in heparin--inhibitor binding. and (iii), about one-third of low quantum yield of Trp30, the single tryptophan residue of the inhibitor, blue-shifts its maximum emission wavelength by 6 nm, decreases the acrylamide quenching rate constant by a factor of 4, and increases the mean intensity weighted lifetime by a factor of 2.5. These important spectroscopic changes evidence a heparin--induced conformational change of the inhibitor which buries Trp30 in a very hydrophobic environment. Heparin accelerates the inhibition of elastase in a concentration-dependent manner. When both enzyme and inhibitor are saturated by the polymer, the second-order association rate constant is 7.7 x 10(7) M-1 s-1, a value that is 27-fold higher than that measured with the free partners. This finding may have important physiologic and therapeutic bearing.

Amino Acid Sequence↗
PubMed1992

Heparin interferes with the inhibition of neutrophil elastase by its physiological inhibitors.

Heparin depresses the second-order rate constant kass for the inhibition of neutrophil elastase by alpha 1-proteinase inhibitor. For high and low molecular weight heparin the decrease in kass is 290-fold and 40-fold, respectively. This is due to a tight binding of the polymer to elastase: Kd = 3.3 nM or 89 nM for high or low molecular weight heparin respectively. In contrast heparin increases the rate of inhibition of elastase by mucus proteinase inhibitor. For low molecular weight heparin, there is a 27-fold increase in kass. This is due to a strong binding of the polymer to the inhibitor (Kd = 50 nM) which undergoes a conformational change.

Chromatography, Affinity↗
PubMed1991

Kinetics of the interaction of chymotrypsin with eglin c.

The kinetics of binding of recombinant eglin c to bovine pancreatic chymotrypsin was studied by conventional and stopped-flow techniques. With nanomolar enzyme and inhibitor concentrations, the inhibition was fast and pseudo-irreversible (k(assoc.) = 4 x 10(6) m-1.s-1 at 7.4 and 25 degrees C). Reaction of the enzyme-inhibitor complex with alpha 1-proteinase inhibitor, an irreversible chymotrypsin ligand, resulted in a slow release of free eglin c, which was monitored by electrophoresis (k(dissoc.) approximately 1.6 x 10(-6) s-1, t1/2 approximately 5 days). The proflavin displacement method and a stopped-flow apparatus were used to monitor the association of chymotrypsin with eglin c under a wide range of inhibitor concentration and under pseudo-first-order conditions. At pH 7.4 and 25 degrees C or 5 degrees C, or at pH 5.0 and 25 degrees C, the pseudo-first-order rate constant of proflavin displacement increased linearly with eglin c up to the highest concentration tested, suggesting a one-step bimolecular association reaction: E + I in equilibrium with EI. However, kassoc. is much lower than the rate constant for a bimolecular reaction and its activation energy (66 kJ.mol-1 at pH 7.4 and 78 kJ.mol-1 at pH 5.0) is far too high for a diffusion-controlled step. The enzyme-inhibitor association may therefore occur via a loose pre-equilibrium complex EI* (Ki* much greater than 5 x 10(-4) M) that rapidly isomerizes (k2 much greater than 2 x 10(3) s-1) into an extremely stable final complex (Ki approximately 4 x 10(-13) M). Unlike other proteinase-inhibitor systems, the chymotrypsin-eglin association is virtually pH-independent.

Amino Acid Sequence↗
PubMed1991

Heparin strongly decreases the rate of inhibition of neutrophil elastase by alpha 1-proteinase inhibitor.

Heparin depresses the second-order rate constant ka for the inhibition of neutrophil elastase by alpha 1-proteinase inhibitor. High molecular mass heparin decreases ka from 1.3 x 10(7) M-1 s-1 to a limit of 4.6 x 10(4) M-1 s-1. Low molecular mass heparin is about 7-fold less effective. Dermatan sulfate and chondroitin sulfate are less efficient. Heparin preparations used in clinical care also strongly depress ka when tested at concentrations corresponding to their clinical efficacy. Heparin also decreases the ka for the elastase/eglin c and the cathepsin G/alpha 1-proteinase inhibitor systems but not that for the alpha 1-proteinase inhibitor/pancreatic elastase or trypsin pairs. These results, together with Sepharose-heparin binding studies, indicate that the ka-depressing effect of the polymer is related to its ability to form a tight complex with elastase but not with alpha 1-proteinase inhibitor. One mol of high molecular mass heparin binds 3 mol of neutrophil elastase with a Kd of 3.3 nM. Low molecular mass heparin binds elastase with a 1:1 stoichiometry and a Kd of 89 nM. For both heparins ka is lowest when elastase is fully saturated with heparin. From this we conclude that heparin decreases ka, because the heparin-elastase complex is able to slowly react with alpha 1-proteinase inhibitor and not because the inhibitor slowly dissociates the heparin-elastase complex. These findings may have important pathophysiological bearing.

Cathepsin G↗
PubMed1991

[Continuous ambulatory peritoneal dialysis].

In contrast with hemodialysis (HD) Continuous Ambulatory Peritoneal Dialysis (CAPD) is a permanent dialysis procedure proposed to the chronic renal patients. Through a permanent peritenoal catheter the patients exchange 2 litres of dialysate 4 times a day, 7 days a week, as soon as the dialysat/plasma concentration for urea reaches 1. Inflow and outflow of the fluid is obtained by gravity, without machine. The short term survival rate is comparable between HD and CAPD. After 5 years, some patients, loosing the residual renal function, need to increase the possibilities of CAPD. The recent disconnect systems reduce the rate of peritonitis down to 1 episode every 36 months. With the actual technology the severe complications such as sclerosing peritonitis decrease or even disappear. Maintenance of an adequate nutritional status in the patients remains an often difficult problem. CAPD may be proposed to nearly all the patients who prefer to be treated at home: children, working adults, diabetics and elderly. Long term studies are still needed to follow the peritoneal performances over time.

Acute Kidney Injury↗
PubMed1991

[Treatment of chronic renal insufficiency: hemodialysis at a center or continuous ambulatory peritoneal dialysis? Comparative retrospective study of the success of both methods].

In a retrospective study, the authors analyse the dialysis-technique success rate in 276 chronic renal patients. 137 patients have been treated with in-center Hemodialysis (CHD) since 1972, 139 patients with Continuous Ambulatory Peritoneal Dialysis (CAPD) since 1978. The 6-year technic success rate reaches 28% in CAPD and 31% in CHD (not statistically significant). The risk factors influence the technic-success rate of both methods in the same way. The results suggest that in the analysed patients CAPD is at least as effective as CHD at maintenance in the technic.

Adolescent↗
PubMed1990

Kinetics of the inhibition of human pancreatic elastase by recombinant eglin c. Influence of elastin.

Recombinant eglin c is a potent reversible inhibitor of human pancreatic elastase. At pH 7.4 and 25 degrees C, kass. = 7.3 x 10(5) M-1.s-1, kdiss. = 2.7 x 10(-4) s-1 and Ki = 3.7 x 10(-10) M. Stopped-flow kinetic indicate that the formation of the stable enzyme-inhibitor complex is not preceded by a fast pre-equilibrium complex or that the latter has a dissociation constant greater than 0.3 microM. The elastase-eglin c complex is much less stable at pH 5.0 and 25 degrees C, where kdiss. = 1.1 x 10(-2) s-1 and Ki = 7.3 x 10(-8) M. At pH 7.4 the activation energy for kass. is 43.9 kJ.mol-1 (10.5 kcal.mol-1). The kass. increases between pH 5.0 and 8.0 and remains essentially constant up to pH 9.0. This pH-dependence could not be described by a simple ionization curve. Both alpha 2-macroglobulin and alpha 1-proteinase inhibitor are able to dissociate the elastase-eglin c complex, as evidenced by measurement of the enzymic activity of alpha 2-macroglobulin-bound elastase or by polyacrylamide-gel electrophoresis of mixtures of alpha 1-proteinase inhibitor and elastase-eglin c complex. The rough estimate of kdiss. obtained with the alpha 2-macroglobulin dissociation experiment (1.6 x 10(-4) s-1) was of the same order of magnitude as the constant measured with the progress curve method. Eglin c strongly inhibits the solubilization of human aorta elastin by human pancreatic elastase. The extent of inhibition is the same whether elastase is added to a suspension of elastin and eglin c or whether elastase is preincubated with elastin for 3 min before addition of eglin c. However, the efficiency of the inhibitor sharply decreases if elastase is reacted with elastin for more prolonged periods.

Elastin↗
PubMed1990

Staphylococcus aureus nasal carriage and infection in patients on continuous ambulatory peritoneal dialysis.

We studied 140 consecutive patients beginning continuous ambulatory peritoneal dialysis (CAPD) at one of seven hospitals to assess the relation of the nasal carriage of Staphylococcus aureus to subsequent catheter-exit-site infection or peritonitis. Shortly before the implantation of the catheters, the patients' anterior nares were cultured for the presence of S. aureus. Antibiotics were not prescribed for the S. aureus carriers, but all the patients were monitored for signs of catheter infection (median follow-up, 10.4 months). At the initiation of CAPD, 63 patients (45 percent) carried S. aureus in the nares. Nasal carriage was more frequent among the 30 patients with diabetes (77 percent) than among the 110 without the disease (36 percent). The carriers of S. aureus had a significantly higher rate of exit-site infection than the noncarriers (0.40 vs. 0.10 episode per year; P = 0.012). Of these episodes, 24 of 34 were caused by S. aureus. The rates of peritonitis of all bacterial types did not differ significantly between the groups, but all 11 episodes of peritonitis caused by S. aureus occurred among the carriers. In 85 percent of the patients with clinical S. aureus infections, the strain from the nares and the strain causing the infection were similar in phage type and antibiotic profile. We conclude that in patients beginning ambulatory peritoneal dialysis, the nasal carriage of S. aureus is associated with an increased risk of catheter-exit-site infection and that the performance of nasal cultures before the implantation of the catheter can identify patients at high risk of subsequent morbidity.

Adult↗
PubMed1990

[Continuous ambulatory peritoneal dialysis in patients over 75 years].

In a clinical retrospective study, the authors report their chronic ambulatory peritoneal dialysis (CAPD) experience in 31 patients, aged more than 75 years. All present 3.7 diseases associated with continuous renal failure. CAPD lasted 24 months/patient and was adapted to the patient's clinical situation and residual kidney function. Twenty patients require help to perform CAPD. The clinical and biological results are good. The nutritional status is acceptable, so is the peritonitis rate: 1 ep/17 patients months. Because the patients stay in hospital 19 days/year, there is a need of backup facilities.

Aged↗
PubMed1990

Continuous ambulatory peritoneal dialysis (CAPD) or center hemodialysis? Retrospective evaluation of the success of both methods.

In a retrospective study, the authors analysed the dialysis-technique success rate in 276 chronic renal patients. Of these, 137 patients have been treated with in center hemodialysis (CHD) from 1972 to 1989 and 139 with continuous ambulatory peritoneal dialysis (CAPD) from 1978 to 1989. The six-year technique success rate was 28% in CAPD and 31% in CHD (statistically not significantly different). Various risk factors influence the technique-success rate of both methods in the same way. The results suggest that in our center CAPD is as effective as CHD in the treatment of patients with end-stage renal failure.

Adolescent↗