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Biomedical subjects

G Willems

Publications and source records attributed to G Willems.

At least 73 records · Page 4Linked to original sources
PubMed1995

Effect of the histamine-2 agonist impromidine on stem cell proliferation of rat oxyntic mucosa.

BACKGROUND: The trophic effect of gastrin on the histamine-containing enterochromaffin-like cell is pronounced but on the stem cell of the oxyntic mucosa it is only modest. In the rat, gastrin stimulates acid secretion mainly by releasing histamine from enterochromaffin-like cells. This study was designed to test the hypothesis that the trophic effect of gastrin on stem cells is also mediated by histamine released from the enterochromaffin-like cell. METHODS: We stimulated rats with the histamine-2 agonist impromidine. Impromidine, 0.2 mg/h, was given for 2 days by subcutaneously implanted osmotic minipumps, and the trophic effect on stem cells was assessed by incorporation of tritiated thymidine. RESULTS: The plasma gastrin concentrations were 33.9 (9.4) pM and 27.3 (6.0) pM, and the stem cell labelling index values were 5.92 (1.94) and 8.09 (3.78) in the controls and impromidine-stimulated animals, respectively (mean value (SD)). These differences were not statistically significant. CONCLUSION: The present study provides no evidence that histamine-2 receptors mediate a trophic effect on the stem cell of the rat oxyntic mucosa.

Animals↗
PubMed1995

Inhibition of prothrombinase by antithrombin-heparin at a macroscopic surface.

The antithrombin-dependent inhibition of prothrombinase, assembled at a macroscopic surface, was studied under flow conditions utilizing a tubular flow reactor that consists of a phospholipid-coated glass capillary. Prothrombinase activity was determined from steady-state rates of thrombin production upon perfusion with prothrombin and from factor Va-associated factor Xa activity present in the flow reactor. The prothrombinase density was maintained at a low level (0.03 fmol/cm2) to assure that the rate of thrombin production reflected the amount of prothrombinase present in the capillary. Perfusion of the flow reactor with antithrombin resulted in an exponential decrease of prothrombinase activity in time. The second order rate constant (8.5 x 10(4) M-1min-1) is comparable with the rate of inactivation of free factor Xa. Inhibition was much faster when antithrombin was complexed with heparin. The second order rate constants of inhibition decreased with decreasing heparin chain length: 9.6 x 10(7), 4.5 x 10(7) and 0.39 x 10(7) M-1min-1 for unfractionated heparin, low molecular weight heparin and synthetic pentasaccharide heparin, respectively. In the presence of prothrombin (0.2 microM), however, the heparin-dependent rate of inhibition of prothrombinase was about 50-fold lower. The heparin-independent inhibition of prothrombinase by antithrombin (4 microM) in the presence of prothrombin (0.2 microM) was virtually negligible. At a 70-fold higher surface density of prothrombinase (2 fmol/cm2) prothrombinase activity was much faster inactivated. The rate of thrombin production, however, was not affected. In conclusion, at low prothrombinase densities, prothrombin efficiently protects prothrombinase from inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Antithrombin III↗
PubMed1995

Kinetics of the inhibition of tissue factor-factor VIIa by tissue factor pathway inhibitor.

Tissue factor-factor VIIa catalysed activation of factor IX is inhibited by the complex of tissue factor pathway inhibitor (TFPI) and factor Xa. At present, no information is available as to what extent the kinetics of complex formation between TFPI and factor Xa during factor X activation contribute to the overall rate of inactivation of the factor X converting complex. We have determined the kinetic parameters of the individual reactions, i.e. factor X activation, formation of the TFPI-factor Xa complex, and inactivation of tissue factor-factor VIIa by the TFPI-factor Xa complex. We modelled the overall reaction by assuming a two-step reaction: factor Xa generated by tissue factor-factor VIIa forms a reversible complex with TFPI and in the second step this complex forms a reversible quaternary complex with tissue factor-factor VIIa. The validity of the model was demonstrated by analysis of factor Xa generation curves in the presence of TFPI. Independently determined constants for factor X activation (kcat = 12 s-1, Km = 70 nM) and inhibition of tissue factor-factor VIIa by TFPI-factor Xa complex (rate constant of inhibition of 1.1 x 10(8) M-1S-1) were used. The association rate constant of the formation of the TFPI-factor Xa complex was estimated by fitting the model to the data.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗
PubMed1994

Kinetics of the inhibition of human factor Xa by full-length and truncated recombinant tissue factor pathway inhibitor.

The inhibition equilibrium and kinetics of association and dissociation of the binding of three types of recombinant tissue factor pathway inhibitor (TFPI), namely full-length TFPI, C-terminal-truncated TFPI, and TFPI without the third Kunitz domain (TFPI1-161), to factor Xa have been measured. Formation and dissociation of the complexes were monitored by continuous measurement of the changes in the rate of hydrolysis of a peptidyl-p-nitroanilide substrate. Progress curves of product formation were fitted to a set of equations describing a one-step bimolecular inhibitory reaction in the presence of a competing substrate. For full-length TFPI the rate constants of association (kon) and dissociation (koff) were (5.1 +/- 0.7) x 10(6) M-1.s-1 and (2.6 +/- 0.9) x 10(-4)s-1 respectively. Thus, although the inhibition constant (50 pM) is far below the plasma concentration (2.5 nM) of TFPI, the half-time for transition to equilibrium in plasma is rather long (66s). The truncated forms of TFPI differ in that they have a 4-fold lower kon value but a similar dissociation rate constant. Therefore the inhibition constant, Ki, is 4-fold higher (0.2 nM) and the half-time to achieve equilibrium is prolonged to 250 s. The kon values of full-length and C-terminal-truncated TFPI, but not that of TFPI1-161, were found to decrease with increasing ionic strength.

Binding Sites↗
PubMed1994

Analysis of thrombin generation in plasma.

Thrombin is the central enzyme of haemostasis. Information on the production and inhibition of thrombin in plasma is important for evaluating the state of the coagulation system. Measurement of thrombin generation in plasma using small oligopeptide chromogenic substrates gives rise to a signal that not only reflects the enzymatic activity of free thrombin, but also contains a contribution of the complex of thrombin with one of its inhibitors, alpha 2-macroglobulin. This paper describes a mathematical procedure to extract from the measured curves the signal due to free thrombin only. The time integral of this free thrombin curve, which we call the thrombin potential, is a parameter which condenses much of the information present in such a curve. Thrombin production from prothrombin can be calculated from the concentration of free thrombin, when the rate constants governing the decay of thrombin are known. It is described how this calculation can be performed, accounting for the consumption of some of the inhibitors of thrombin during coagulation. Measurement of the time integral of the thrombin concentration promises clinical applicability of thrombin generation tests. It is based on the continuous registration of conversion of chromogenic substrate by thrombin during coagulation in plasma. It is shown how the curves obtained by this test can be analysed by a procedure which is analogous to the analysis of curves measured by subsampling from clotting plasma.

Blood Coagulation↗
PubMed1994

Brain glucose utilisation in acquired childhood aphasia associated with a sylvian arachnoid cyst: recovery after shunting as demonstrated by PET.

Regional brain glucose utilisation was investigated with PET and fluorodeoxyglucose (FDG) in a case of epileptic aphasia (Landau-Kleffner syndrome) associated with a left sylvian arachnoid cyst. CT and MRI had failed to disclose any mass effect of the cyst on surrounding brain structures. Sequential metabolic measurements showed a comparable pronounced hypometabolism in cortical regions around the cyst, involving speech areas, and suggested mild but chronic compression of the developing brain. After placement of a cyst-peritoneal shunt system, significant metabolic improvement occurred in all cortical regions, especially the inferior frontal gyrus and the perisylvian area, with predominant residual deficit in the left superior temporal gyrus. These findings were correlated with a pronounced increase in word fluency and slower progress in verbal auditory comprehension. This report suggests that PET is able to evaluate the functional disturbances associated with expanding arachnoid cysts, and to follow the neurological improvement after drainage.

Aphasia↗
PubMed1994

Hyperplastic manifestations of enterochromaffin-like cells in the stomach of rats with congenital moderate hypergastrinemia.

The effect of moderate congenital hypergastrinemia on the enterochromaffin-like (ECL) cells was investigated in Zucker rats 4 and 18 months of age by combining autoradiography after tritiated thymidine injection and selective immunocytochemistry. In both age groups the serum gastrin concentration was 200% higher in obese (fa/fa) than in lean (Fa/Fa; Fa/fa) littermates. In 4-month-old obese rats there was a 120% increase (p < 0.05) in the ECL cell labeling index and also a moderate increase in the ECL cell density (p < 0.05) compared with lean controls. In 18-month-old obese rats the hyperplasia was quantitatively more prominent, with both linear and micronodular ECL cell hyperplasia. At this stage, the ECL cell labeling indices in obese and in lean animals were similar. These data support the hypothesis that moderate hypergastrinemia initially accelerates the ECL cell proliferation rate, leading to diffuse ECL cell hyperplasia. In similar conditions, at the latter stage, linear and micronodular ECL cell hyperplasia also develop in most of the hypergastrinemic animals.

Animals↗
PubMed1993

Mathematical analysis of a proteolytic positive-feedback loop: dependence of lag time and enzyme yields on the initial conditions and kinetic parameters.

A model of a proteolytic positive-feedback loop, similar in general terms to feedback loops that occur in blood coagulation and other systems, has been examined by both explicit and numerical analysis. In this loop, modeled as a closed system, each enzyme (E1, E2) catalyzes the formation of the other from its respective zymogen (Z1, Z2), and both enzymes are subject to irreversible inhibition. The system shows three major characteristics. (1) No significant Z1 or Z2 activation occurs unless the combination of initial conditions and kinetic parameters is above a threshold level. This threshold occurs when the product of the enzyme generation rates equals the product of their inhibition rates. When the formation-rate product is less than the inhibition-rate product, there is no response: E1 and E2 generation is minimal and the lag time is effectively infinite. Conversely, when the generation-rate product exceeds the inhibition-rate product, explosive formation of both E1 and E2 is seen. For responses exceeding the threshold, the following obtain. (2) The lag time in E1 and E2 generation is a highly nonlinear function of the zymogen concentrations and the enzyme generation and inhibition rates. In contrast, there is a simple logarithmic relationship between the lag time and the initial trace concentration of the enzyme that is responsible for initiating the system; in this model, E1. (3) The extent of Z1 and Z2 activation is similarly a nonlinear function of the conditions and parameters but is independent of the initiating trace level of E1.(ABSTRACT TRUNCATED AT 250 WORDS)

Enzymes↗
PubMed1993

Hardness and Young's modulus determined by nanoindentation technique of filler particles of dental restorative materials compared with human enamel.

The recently developed nanoindentation technique was used to measure hardness and Young's modulus of small filler particles in resin composites and other dental restoratives. This technique eliminates the need to visualize indentations. Load and displacement are continuously monitored during a loading-unloading sequence, and hardness as well as Young's modulus are then calculated from the load-displacement curves taking into account the geometry of the indenter. Thirteen posterior composites, 3 dental ceramics for CAD/CAM restorations, 1 sintered porcelain, and 1 amalgam were investigated in this study. The results were compared to the hardness and Young's modulus determined by nanoindentation of human enamel. Of the dental materials tested, only five materials contain inorganic filler particles with a nanohardness not statistically different from that of enamel. The predominant fillers in all other materials, except amalgam and the prepolymerized resin fillers in Bell Firm PX, were found to be significantly harder. The dental restorative materials, except the alloy phase in amalgam, were composed of particles with a Young's modulus significantly lower than that of human enamel. The alloy phase in amalgam had a Young's modulus value comparable to that of enamel.

Dental Amalgam↗
PubMed1993

Three-year follow-up of five posterior composites: in vivo wear.

The wear of five posterior composites at occlusal contact areas (OCA) and contact free occlusal areas (CFOA) was evaluated in Class II cavities over a 3-year period with an accurate 3D-measuring technique. A clinical evaluation was also performed. The ultrafine compact-filled composites (Willems et al., 1992) showed acceptable OCA-wear rates ranging from 110 to 149 microns after 3 years. This is very similar to the OCA-wear rate of human enamel on molars, which is about 122 microns after 3 years. The fine compact-filled composite had an unacceptable OCA-wear value of 242 microns after 3 years. The ultrafine midway-filled composite showed an exceptionally high CFOA-wear value of 151 microns after 3 years, which gave the impression of it being gradually washed out of the cavity. Clinically, 70% of the restorations made with the ultrafine midway-filled composite showed excellent colour match after 3 years. For most of the compact-filled composites slightly opaque fillings were noted and 63% of the restorations made with one of these materials were clearly opaque. It can be concluded that the investigated ultrafine compact-filled composites can be considered as amalgam alternatives as far as their wear resistance is concerned.

Adult↗
PubMed1993

Three-year follow-up of five posterior composites: SEM study of differential wear.

Assessing the wear of both enamel and composite at a shared occlusal contact area offers the opportunity to determine the differential wear between enamel and composite on the same tooth. Differential wear measurements were carried out on five posterior composite materials with an accurate 3D-measuring technique. The distinct wear step between enamel and composite was visualized by means of scanning electron photomicrographs. Both investigated ultrafine midway-filled and fine compact-filled composites (Willems et al., 1992a) have a considerably higher differential wear value and are, therefore, less suitable for rehabilitation of posterior teeth than are the ultrafine compact-filled composites, which have, in this study, a very satisfactory differential wear rate and appear to be highly wear resistant materials suitable for use in stress-bearing areas.

Adult↗
PubMed1993

Dual-cure luting composites: Part I: Filler particle distribution.

Fourteen dual-cure luting composites were analyzed for their filler particle shape, predominant and maximum filler size, and filler weight in function of their clinical use. Polished surfaces were etched with an argon ion beam and studied by means of scanning electron microscopy. The type of filler particles, either inorganic or prepolymerized, could clearly be recognized. Their shapes were angular, rounded or spherical, depending on the product. The maximum filler size varied extremely from less than 1 micron to 250 microns. A particle-size distribution analyser disclosed a bell-shaped filler-size distribution. The predominant filler size for all the products was much smaller than the maximum filler size. The filler weight varied from 36 to 77%. After ion etching, some products showed small areas with a low degree of filler loading. A classification of the luting composites based on the maximum filler size is proposed. Since the particle size varies widely within the group of products analyzed, a standard specification for luting composites is urgently needed.

Adhesives↗
PubMed1993

Assessment by nano-indentation of the hardness and elasticity of the resin-dentin bonding area.

The hardness and Young's modulus of the successive layers across a resin-dentin bonding area were determined by nano-indentation for four commercially-available dentin adhesive systems, of which two were also applied with a different conditioning agent. With a computer-controlled nano-indentation technique, minute triangular indentations were made within a small area of a few micrometers' diameter at a load of a few milli-Newtons. The load and displacement of the indenter were continuously monitored during the loading-unloading sequence, so hardness and Young's modulus could be computed as a function of the indenter geometry and the applied load. The hardness of the resin-dentin interdiffusion zone was significantly lower than that of unaltered dentin. A gradient of moduli of elasticity was observed from the rather stiff dentin over a more elastic resin-dentin interdiffusion zone and adhesive resin layer to the restorative composite. That gradient was more substantial in those systems that produced relatively thick adhesive resin layers or supplementally provided a filled low-viscosity resin as an intermediate layer between the adhesive resin and the bulk restorative composite. Such an elastic bonding area might have a strain capacity sufficient to relieve stresses between the shrinking composite restoration and the rigid dentin substrate, thereby improving the conservation of the dentin bond and, as a consequence, the marginal integrity and retention of the restoration.

Composite Resins↗
PubMed1993

Transvaginal removal of gallbladders with large stones after laparoscopic cholecystectomy.

Very large gallstones sometimes render laparoscopic cholecystectomy time consuming and difficult. In addition, several advantages of laparoscopy, namely decreased postoperative pain and minimal abdominal scarring, could be compromised by the need to enlarge the umbilical incision. Besides the solution of the mechanical or electrohydraulic fragmentation of such large gallstones, as described by several authors, we propose a posterior colpotomy as a simple technique for removing very large gallbladders in women.

Cholecystectomy, Laparoscopic↗
PubMed1993

Composite resins in the 21st century.

Human enamel and dentin should be used as the physiologic standards with which to compare composite resins, especially in the posterior region. The intrinsic surface roughness of composite resins must be equal to or lower than the surface roughness of human enamel on enamel-to-enamel occlusal contact areas (Ra = 0.64 microns). Roughness determines the biologic strength of composite resins. The nanoindentation hardness value of the filler particles (2.91 to 8.84 GPa) must not be higher than that of the hydroxyapatite crystals of human enamel (3.39 GPa). Composite resins intended for posterior use should have a Young's modulus at least equal to, and preferably higher than, that of dentin (18.500 MPa). The compressive strength of enamel (384 MPa) and dentin (297 MPa) and the fracture strength of a natural tooth (molar = 305 MPa; premolar = 248 MPa) offer excellent mechanical standards to select the optimal strength for posterior composite resins. The in vivo occlusal contact area wear rate of composite resins must be comparable to the attritional enamel wear rate (about 39 microns/y) in molars. Differential wear between enamel and composite resin on the same tooth is a new criterion for visualizing and quantifying the wear resistance of composite resins in a biologic way. Posterior resins must have a radiographic opacity that is slightly in excess of that of human enamel (198% Al). Based on these standard criteria, it can be concluded that in the 21st century the ultrafine compact-filled composite resins may be the materials of choice for restoring posterior cavities.

Analysis of Variance↗
PubMed1992

Treatment of liver metastases of human colon cancers in nude mice with somatostatin analogue RC-160.

Hepatic metastases of colon 320 DM and WidR human colon cancers in nude mice were treated by s.c. injections of somatostatin analogue RC-160 for 4 weeks. Chronic administration of RC-160 significantly inhibited the incidence and growth of liver metastases of these 2 colon-cancer cell lines. After RC-160 treatment, the incidence of liver metastases decreased by 25% for colon 320 DM cells and by 37.5% for WidR cells. The mean number of metastatic tumors in each liver decreased by 47.9% for colon 320 DM and 42.6% for WidR. Survival times of mice with liver tumors of colon 320 DM and WidR cells were prolonged by 20 days and 7 days, respectively. The inhibitory effect of RC-160 on the growth of these 2 colon cancers implanted s.c. was also observed. After administration of RC-160 for 4 weeks, the mean tumor volume in the treated groups was only 39.8% of that of controls for the colon 320 DM line and 58% for the WidR line. Tumor-growth rate and final tumor weight were also significantly decreased, while tumor-volume doubling time and tumor-growth delay time were prolonged. The effect of RC-160 on cellular proliferation in the tumors was studied by in vivo labelling with bromodeoxyuridine and immunoperoxidase staining. The mean labelling index in the treatment group was reduced by 14.9% and 19.5%, respectively, for colon 320 DM and WidR tumors. The cytostatic effect of RC-160 was also evident from the apparent reduction in DNA and protein content in the tumor tissues of these cancer lines. Our findings suggest that somatostatin analogue RC-160 may be useful for the treatment of patients with hepatic metastases of colon cancer.

Animals↗
PubMed1992

Inhibitory effect of somatostatin analogue RC-160 on the growth of hepatic metastases of colon cancer in rats: a study with magnetic resonance imaging.

The effect of somatostatin analogue RC-160 on the growth of hepatic metastases of colon cancer was investigated in rats using magnetic resonance imaging. Experimental liver metastatic tumors were established in syngeneic BDIX rats after intrasplenic injection of DHD/K12 colon adenocarcinoma cells. Each rat with implanted liver tumors received s.c. injections of somatostatin analogue RC-160 (50 micrograms/kg) or the vehicle (control) twice a day for 4 weeks, starting 3 weeks after tumor inoculation. During the treatment with RC-160, the growth of liver tumors was studied quantitatively by measuring liver tumor volumes in vivo with magnetic resonance imaging at intervals of 7 days. Chronic administration of RC-160 inhibited the growth of hepatic metastases of colon cancer in rats. Significant inhibition of liver tumor growth in RC-160-treated rats was observed throughout the treatment. The final liver tumor volume in the treated rats was decreased by 56.1% as compared to the controls. The treatment with RC-160 reduced the percentage increase in liver tumor volume from 1575 +/- 674% (mean +/- SEM) for the control to 1034 +/- 727% in the treated group. The tumor volume doubling time in treated rats was 3.7 days longer than the controls. The liver tumor growth delay time was 15.1 days. At the end of the treatment, the incidence of ascites and the weights of tumorous livers were also decreased by RC-160 treatment. Administration of RC-160 prolonged the median survival time by 13 days in treated rats. In cell cultures, significant inhibitory effects of somatostatin-14 and RC-160 on the growth of DHD/K12 colon cancer cells were determined by MTT assay and [3H]-thymidine incorporation assay, indicating direct effects of these peptides on the growth of colon cancer cells in vitro. These data suggest that administration of RC-160 could inhibit the growth of colon cancer and their hepatic metastases in rats. Somatostatin analogue RC-160 might be considered as a potential new agent for the treatment of patients with hepatic metastases of colorectal cancers.

Amino Acid Sequence↗