Search PubMed⌕ Search

Biomedical subjects

F W Janssen

Publications and source records attributed to F W Janssen.

At least 19 recordsLinked to original sources
PubMed2001

Signal characteristics of multichannel epicardial electrograms in chronic ischaemic and scarred myocardium: electromechanical mismatch indicates viability in regions of myocardial dysfunction.

BACKGROUND: To predict the outcome after myocardial revascularisation, a clear separation between hibernation and/or repetitive stunning on the one hand and myocardial scarring on the other hand is of importance. METHODS AND RESULTS: A total of 44 patients was included in this study. In 35 patients with chronic myocardial ischaemia and an indication for coronary bypass-surgery, epicardial mapping of local activation was performed. Nine patients with LV aneurysm and an indication for antitachycardia surgery were also included. For simultaneous recording of the local electrograms during sinus rhythm, a sock electrode with 102 bipolar leads was used. The regional myocardial contraction pattern was assessed from preoperative angiograms and regional myocardial metabolism (viability) from 18F-FDG PET, respectively. The results were projected on the grid of the intraoperative position of the sock electrode. This enabled regional comparison of electrogram characteristics to local contraction patterns and viability. For the characterisation of local electrograms, peak-to-peak amplitude and duration of activation were calculated using custom-made automated computer-algorithms. Dysfunctional but viable areas showed normal or almost normal electrographic signal characteristics. In contrast, dysfunctional and non-viable myocardium showed a distinct reduction of local amplitudes and prolongation of signal duration. These changes were even more intense in areas of LV aneurysms. CONCLUSIONS: In patients with chronic ischaemic myocardium, a mismatch between mechanical function and local electrogram characteristics was observed in areas with preserved metabolism. Thus, normal epicardial electrograms in regions of myocardial dysfunction may be an indicator for myocardial viability.

Adult↗
PubMed2001

[MRI study of left ventricular function in patients with coronary disease and myocardial dysfunction before and after coronary revascularization].

PURPOSE: To evaluate left ventricular (LV) myocardial function in ten patients with coronary artery disease (CAD) preoperatively and 6 months after coronary bypass grafting (CABG) by cardiac MRI. MATERIAL AND METHODS: Ten patients (mean 65.2 +/- 5.9 years) with angiographically proven CAD and an indication for elective CABG underwent prospective evaluation of global LV function and regional wall motion by Cine-MRI at rest using a multiphase FLASH-2D sequence following regions of interest (ROI)-defined diagnostics of regional myocardial wall motion by means of levocardiography. Within the ROIs a total of 613 LV myocardial segments were analyzed preceding and following surgical revascularization. Results were compared with the data of 10 healthy volunteers. RESULTS: Preoperatively, patients showed reduced stroke volume and ejection fraction compared with volunteers (p < 0.01). Enddiastolic wall thickness (EDWT) and systolic wall thickening (SWT) were significantly lower in the patients (p < 0.01). Based on preoperative levocardiography ROI-defined myocardial segments showed a significantly lower preoperative EDWT in areas with wall motion abnormalities (7.4 +/- 2.5 mm; p < 0.01) than in normal myocardium (9.2 +/- 2.1 mm). Ejection fraction (p < 0.05), endsystolic wall thickness, and SWT (p < 0.01) improved significantly after bypass surgery. On ROI-defined analysis myocardial segments with impaired preoperative wall motion (n = 243) showed a significant increase of EDWT, ESWT and SWT (p < 0.01). CONCLUSION: In patients with CAD, cardiac MRI enables the non-invasive determination of postinfarctional LV remodeling with an increased EDWT of myocardial segments with normal regional wall motion and of the improvement in global and regional myocardial function following coronary bypass surgery.

Aged↗
PubMed2001

Analysis and clinical effects of gluten in coeliac disease.

The prolamin working group coordinates research on laboratory gluten analysis in food and on clinical evaluation of patient sensitivity to prolamins. As an observer organization to the Codex Alimentarius Commission, the group summarizes current data on analysis and effects of gluten in coeliac disease. All types of gliadin, the ethanol-soluble fraction of gluten, contain the coeliac-active factor. However, coeliac toxicity and immunogenicity (humoral and cellular) of various prolamins are not identical in coeliac patients. There are no conclusive data on the threshold of gluten sensitivity of coeliac patients. Information as to the long-term risk to coeliac patients exposed to small doses of gliadin is lacking. Therefore, every effort should be made to keep the diet of coeliac patients as gluten-free as possible. The prolamin group is currently evaluating a new enzyme-linked immunosorbent assay (ELISA) protocol for gluten analysis that could serve as a basis for further Codex regulations. The group recommends adherence to a single Codex limit for gluten-free foods. The current limit of 200 ppm gluten is questionable and requires reconsideration based on new information that will be available soon.

Celiac Disease↗
PubMed1987

Interactions between oxaprozin glucuronide and human serum albumin.

1. The first step in the interaction between oxaprozin glucuronide and human serum albumin (HSA) is formation of a reversible complex which then leads to the following reactions; (a) acyl migration of the aglycone from position 1 to positions 2, 3 and 4 of the glucuronic acid moiety; (b) hydrolysis of the glycosidic bond; and (c) covalent binding of oxaprozin to the HSA molecule. The isomers of oxaprozin glucuronide formed in (a) and the covalently bonded drug in (c) are also hydrolyzed to oxaprozin. 2. Oxaprozin and ligands known to bind at Site II as classified by Sudlow et al. (1976), also called the benzodiazepine binding site (Müller and Wollert 1975), inhibit these reactions with oxaprozin glucuronide, while ligands which are known to bind at other sites on HSA do not. 3. Modification of a single tyrosine residue, located within Site II, with tetranitromethane, diisopropylfluorophosphate, and p-nitrophenylacetate causes significant reduction of the covalent binding of oxaprozin to HSA. 4. Tetranitromethane modification of HSA decreases all three reactions, while not inhibiting the formation of the reversible complex, indicating that the tyrosine located in Site II (tyr-411)acts as the nucleophile in these reactions. 5. Chemical modification of lysine residues has only a small effect on the reactions while modification of the lone free sulphhydryl (cys) in HSA has no effect.

Binding Sites↗
PubMed1986

Reactions of oxaprozin-1-O-acyl glucuronide in solutions of human plasma and albumin.

Hydrolysis and rearrangement (isomerization by acyl migration) of oxaprozin glucuronide are greatly accelerated by plasma and human serum albumin. Albumin accounts for all the hydrolytic activity in plasma and no esterase is involved. The isomeric esters formed by rearrangement are also good substrates for the hydrolysis reaction. Another reaction between oxaprozin glucuronide and albumin leads to covalent binding of the aglycone. Similar reactions leading to covalent binding have been described for other acyl glucuronides by several investigators. In the case of oxaprozin, there is little or no potential for biological significance of covalent binding because the reaction is almost entirely inhibited by low concentrations of the drug. All three reactions are pH dependent but not to the same extent. They can be considered to be transacylations to the hydroxyl ion (hydrolysis), to a different OH-group of the glucuronic acid moiety (rearrangement) or to a nucleophilic group on the albumin molecule (covalent binding). All three reactions are greatly inhibited by the same compounds suggesting a common reaction site. This site has certain features in common with the indole or benzodiazepine binding site of human serum albumin. A scheme is proposed in which the first step is reversible binding of the acyl glucuronide to this site in analogy to the known reversible binding of reactive esters (such as p-nitrophenyl acetate) to the same site. All three reactions are inhibited by compounds such as naproxen and decanoic acid which are known to also inhibit the acylation of albumin by reactive esters and the reversible binding of benzodiazepines.

Carbon Radioisotopes↗
PubMed1986

Detection of soya proteins in heated meat products by "blotting" and "dot blot".

Soy proteins (isolates, concentrates and texturates) as well as meat products containing soya isolate were analysed by SDS-electrophoresis. The separated proteins were blotted on nitrocellulose and stained with a selective immunoperoxidase system with the following sequence: primary (anti-soya) serum, goat anti-rabbit IgG serum and peroxidase-antiperoxidase complex (rabbit allotype). By developing the blot with a peroxidase substrate the antigenic soya fractions were visualised while the meat proteins did not stain. All major (reduced) soya fractions alpha, alpha', beta conglycinin, the acid and basic subunits of glycinin as well as some minor fractions became visible with a commercially available anti-soya serum as primary antiserum. The pattern thus obtained provides a high evidence for the presence of soya protein in meat products. Detection level is about 0.02% of soya protein. During a 24-h incubation at room temp. (before heat processing) of a meat product containing soya product and raw liver a remarkable loss of antigenic material was observed.

Cross-Linking Reagents↗
PubMed1982

Protein binding and clearance of oxaprozin, a highly bound anti-inflammatory agent.

Conventional dialysis cells were used in initial attempts to determine the binding characteristics of oxaprozin (4,5-diphenyl-2-oxazolepropionic acid, Wy-21,743). Equilibration required dialysis times up to 22 hours at 37 degrees C resulting in deterioration of plasma proteins, which in turn leads to highly variable binding values. In contrast, dialysis with Dianorm cells requires less than 4 hours to reach equilibrium. The configuration of the cell optimizes the contact between the solutes and the membrane and allows for a more efficient mixing and exchanging of the solute. The percentage of unbound drug was linearly related to total drug in human plasma samples to which oxaprozin in clinically relevant concentrations (55-405 micrograms/ml) had been added. Likewise, a linear relationship between total drug concentration and the percentage unbound was observed in specimens from a pharmacokinetic study in healthy volunteers. Clearance of total oxaprozin from plasma correlated with the percentage unbound drug. Thus the higher clearance observed under steady-state conditions (where concentrations are higher than following single dose administration) was caused by a larger unbound fraction available to the elimination sites.

Anti-Inflammatory Agents↗
PubMed1980

Metabolism and kinetics of oxaprozin in normal subjects.

Absorption, biotransformation, excretion, and kinetics of oxaprozin (4,5-diphenyl-2-oxazolepropionic acid) were examined in subjects after an oral dose of 14C-oxaprozin alone as well as before, during, and after long-term administration of unlabeled drug. A single dose of 14C-oxaprozin was rapidly absorbed and the unchanged drug was essentially the only labeled substance in plasma. Recovery of radioactivity in excreta, mostly in urine, exceeded 90%. Major biotransformation routes were glucuronidation of the carboxyl group and hydroxylation of the phenyl rings followed by glucuronidation. Administration of unlabeled oxaprozin did not affect the absorption, qualitative, or quantitative metabolite profile, or recovery of 14C-oxaprozin. Following a single dose, the kinetic parameters for 14C and unchanged drug in plasma were nearly the same. A2-compartment model with first-order elimination adequately describes kinetic disposition. The slow clearance (Clp), 0.08 to 0.12 1/hr, was almost entirely due to biotransformation and the plasma half-lifes, which ranged from 49 to 69 hr, reflected the small Clp. The small volume of distribution (VD beta = 8 to 9 1) indicates limited extravascular distribution. Multiple doses of unlabeled drug, especially when given concurrently, increased the Clp of 14C-oxaprozin. This effect is apparently related to decreased binding of high concentrations of oxaprozin to plasma protein. As a result of increased Clp, steady-state levels are only 40% of levels predicted from the single-dose study.

Adult↗