Biomedical subjects

E J Menzel

Publications and source records attributed to E J Menzel.

At least 37 records · Page 2Linked to original sources

PubMed1997

Effects of aminoguanidine on adhesion molecule expression of human endothelial cells.

The effect of aminoguanidine (AG) on the expression of adhesion molecules on nonactivated human umbilical vein endothelial cells (HUVEC) was investigated in vitro. Nonactivated HUVEC cultivated on long-term glycated fibronectin (FN) as compared to native FN showed a significant upregulation of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and CD31 which could be further promoted by long-term glycated bovine serum albumin. AG, at a concentration of 0.01 mol/l, caused an upregulation of ICAM-1 of 48 +/- 17.4% in HUVEC cultivated on gelatin. In contrast, VCAM-1 and E-selectin remained unaffected. At this concentration, formation of advanced glycation end products (AGE) was inhibited by 57%, as determined immunologically, and by 50%, as verified by AGE-specific fluorescence. A hypothesis concerning the upregulation of ICAM-1 by AG as compared to VCAM-1 is proposed relating to its relative redox insensitivity. Our results demonstrate that the beneficial effect of AG in reducing the risk of accelerated development of atherosclerosis in diabetic patients by inhibiting formation of AGE on matrix proteins such as FN might be hampered by its tendency to upregulate ICAM-1 on endothelial cells.

Animals↗

PubMed1996

Ibuprofen inhibits pyrogen-dependent expression of VCAM-1 and ICAM-1 on human endothelial cells.

Leukocyte adhesion and transmigration through the endothelial cell (EC) layer plays a crucial role in inflammation. IL-1 alpha and TNF alpha increase EC-adhesiveness for leukocytes by stimulating surface expression of ICAM-1 (intercellular adhesion molecule 1, CD54), VCAM-1 (vascular cell adhesion molecule 1, CD106) and E-selectin (CD62E). In this study, the effects of ibuprofen on IL-1 alpha and TNF alpha-induced expression of ICAM-1, VCAM-1 and E-selectin on cultured human umbilical vein EC (HUVEC) were analyzed. Exposure to IL-1 alpha or TNF alpha resulted in an increased expression of VCAM-1, ICAM-1, and E-selectin. Ibuprofen was identified as a potent inhibitor of IL-1 alpha and TNF alpha-induced surface expression of VCAM-1 and a less potent inhibitor of pyrogen-induced expression of ICAM-1, whereas no effect on E-selectin was found. The effects of ibuprofen on VCAM-1 expression were dose-dependent (IC50 [IL-1 alpha]: 0.5 mM; IC50 [TNF alpha]: 0.5 mM) and time-dependent with maximum responses observed after 18 h. Moreover, ibuprofen abrogated pyrogen-dependent adhesion of leukocytes to HUVEC. Ibuprofen also inhibited VCAM-1 mRNA expression in pyrogen activated EC. VCAM-1-downregulation on EC by ibuprofen may contribute to the anti-inflammatory actions of the drug.

Base Sequence↗

PubMed1996

Comparison of the effect of different inhibitors of the non-enzymatic glycation of rat tail tendons and bovine serum albumin.

The biomechanical and biochemical properties of collagen are changed by non-enzymatic glycation culminating in increased cross-linking. We have previously shown that dibasic amino acids such as L-arginine inhibit in vitro the non-enzymatic glycation of soluble proteins and insoluble connective tissue macromolecules. In the present in vitro study we obtained evidence that the nucleophilic hydrazine derivative aminoguanidine and the non-steroidal anti-rheumatic drug ibuprofen inhibit the formation of fluorescent advanced glycation end products (AGEs) to a comparable extent, while arginine is ineffective as a consequence of its tendency to form AGEs itself. Periodic replacement of glycated arginine in the rat tail tendon system, however, engendered an inhibition of fluorescence similar to that obtained by the other inhibitors. Long-term glycation of rat tail tendons caused a significant increase in Young's modulus, which could also be inhibited by periodically renewed arginine. In contrast to ibuprofen, aminoguanidine and arginine-lysine inhibited the marked increase in maximum contraction force of long-term glycated rat tail tendons. As opposed to other inhibitors, aminoguanidine also reduced the thermal contraction force of native tendons, shifted the maximum contraction temperature to markedly lower values and solubilized a significant part of the rat tail tendon collagen. These findings indicate that the in vitro alterations of rat tail tendon collagen induced by non-enzymatic glycation can be prevented by arginine, arginine-lysine and aminoguanidine. However, collagen structure is seriously affected by aminoguanidine.

Animals↗

PubMed1996

On the orthogonal anisotropy of human skin as a function of anatomical region.

Skin samples were obtained from 8 anatomical sites of 6 human deceased at ages ranging from 30 to 80 years 24 hours post mortem. As shown by biochemical analysis the collagen content varied between 71% and 78% depending on the anatomical location of the skin samples. The content of collagen type III was in the range of 19.2% to 22.2% of the total collagen concentration. As to the biomechanical analysis the axes of minimum and maximum shrinkage after excision were determined and correlated with Langer cleavage line drawn on the specimen with a marker after incision. Two-dimensional biomechanical tests were conducted with a multiaxial tensile testing device consisting of 12 loading axes. The in vivo configuration was a circle with 30 mm diameter. The in vivo stresses were determined by restoring the original shape of the specimen. According to the nonlinear stress-strain relationship incremental strains were applied to the sample with the in vivo configuration and states of uniform extension as reference. The corresponding stresses were recorded after stress relaxation was completed and the equilibrium stresses were regarded as the elastic contribution to the viscoelastic biomechanical behavior. The elastic parameters as a function of the initial strain level were calculated using a set of different incremental strains and stresses. The highest in vivo stresses were found in patella, and upper and lower back. The maximum deviation of the direction of maximum in vivo stress from the Langer cleavage line was found in upper back, the volar part of thigh, and sternum. In vivo orthogonal anisotropy was most pronounced in patella and hollow of the knee.

Adult↗

PubMed1996

Intracellular distribution of ibuprofen within monocytes.

The interaction of ibuprofen (CAS 15687-27-1) with muscle proteins was investigated in vitro and binding to actin was found to be more marked than to other muscle proteins. Actin polymerization, however, was not influenced by this interaction. The kinetics of ibuprofen internalization by human monocytes/macrophages from peripheral blood at 37 degrees C and its partitioning to different cellular compartments was studied and compared to the actin content of these subcellular fractions. The bulk of cell-bound ibuprofen (89.7%) was found in the cell debris fraction (1,000 g sediment), 7.3% were recovered in the 10,000 g sediment, only 0.5% in the 100,000 g sediment and 2.5% in the cytosolic fraction. The distribution of F-actin to the different subcellular fractions was verified by fluorescence analysis using NBD-phallacidin. Four times more F-actin was found in the 1,000 g sediment than in the 10,000 g fraction, while the microsomal fraction contained only 8% of total F-actin. In the cytosol, significant amounts of soluble actin were detected. These data indicate that ibuprofen could theoretically interact with actin in all the cellular subfractions to which it is distributed after internalization.

Actins↗

PubMed1995

Proteins lose their nitric oxide stabilizing function after advanced glycosylation.

In vivo generated nitric oxide, NO, circulates in plasma mainly as an S-nitroso adduct of serum albumin. Compared to free NO, this NO-adduct is relatively long-lived. It exerts EDRF-like effects of vasodilation and platelet inhibition. Free NO is directly inactivated ('quenched') by advanced glycosylation end products (AGEs), glucose-derived protein moieties that form nonenzymatically and accumulate primarily on long-lived tissue proteins. They have been implicated in many of the long-term complications of diabetes mellitus. We found that the antiproliferative effects of thiol-stabilized NO (SNO-BSA) on Con A-stimulated lymphocytes from peripheral blood were even stronger than those of the NO-generating drug SNAP. The antimitogenic activity of SNO-BSA, however, was not significantly enhanced by the low molecular weight NO-carrier glutathione. NO liberated from SNO-BSA in molar excess was almost completely quenched by AGE-BSA. NO-dependent activating effects such as enhanced rate of glucose uptake or generation of cGMP in resting peripheral mononuclear cells (PBMC) and the antiproliferative activity of the NO-carrier BSA on Con A-stimulated cells were thereby abolished. In contrast, advanced glycosylation impaired the ability of BSA to function as NO-carrier, as evidenced by the lack of antiproliferative activity of NO-AGE-BSA and its inability to activate glucose transport or cGMP generation.

Blood Proteins↗

PubMed1995

Biomechanical properties of normal tendons, normal palmar aponeuroses, and tissues from patients with Dupuytren's disease subjected to elastase and chondroitinase treatment.

Normal tendons, normal palmar aponeuroses and palmar aponeuroses from patients with Dupuytren's disease were subjected to elastase or chondroitinase treatment. Young's modulus was derived from the linear portion of stress-strain graph. It showed the lowest value for the apparently normal palmar aponeuroses and the highest value for tendon samples. Elastase treatment caused an increase of extensibility and a reduction of Young's modulus of normal palmar aponeuroses and tendons, but not of contracture bands. In normal tendons, normal palmar aponeuroses and apparently normal palmar aponeuroses residual strain and hysteresis loop increased significantly as a linear function of the amount of digested elastin. In contrast these biomechanical parameters were not affected significantly in contracture bands. In normal and apparently normal areas incubation with chondroitinase ABC resulted in a significant increase of residual strain and, as opposed to elastase, a decrease of normalized hysteresis loop. In contracture bands, however, these biomechanical parameters remained unchanged. RELEVANCE: The increasing evidence of a correlation between morphological changes of palmar elastin and ground substance with the progress of Dupuytren's disease emphasizes the need to determine the relative importance of these connective tissue components for the pathogenesis of Dupuytren's disease.

Journal Article↗

PubMed1995

Two-dimensional elastic properties of human skin in terms of an incremental model at the in vivo configuration.

The two-dimensional biomechanical behaviour and the collagen content of human skin samples from different anatomical sites was examined. The axes of minimum and maximum shrinkage after excision were determined and correlated with the 'Langer' cleavage lines. Test equipment was developed to restore the original geometry and to measure the loads acting perpendicular to the circumference of the skin specimens. These loads were normalized with respect to the thickness and collagen content and considered as the in vivo tension generated by the surrounding skin area. Using the in vivo geometry of the specimen as reference a set of incremental strains was applied. After stress relaxation was completed the final values of stresses were recorded and related to the incremental strains. The two-dimensional stress-strain relationship was the basis for the evaluation of the incremental elastic moduli. Orthotropic mechanical behaviour was found mainly in regions of reduced in vivo tension. The relationship between the degree of anisotropy at the in vivo configuration and the morphological structure is discussed.

Adult↗

PubMed1995

Biomechanical properties of normal tendons, normal palmar aponeuroses and palmar aponeuroses from patients with Dupuytren's disease subjected to elastase and chondroitinase treatment.

Normal tendons, normal palmar aponeuroses and specimens from patients with Dupuytren's disease, namely apparently normal palmar aponeuroses and contracture bands were subjected to elastase and chondroitinase ABC digestion. Maximum Young's modulus, normalized hysteresis loop and residual elongation were determined before and after enzyme treatment. In normal tendons, normal and apparently normal palmar aponeuroses both normalized hysteresis loop and residual elongation increased significantly after elastase treatment, whereas the stiffness decreased. Normalized hysteresis loop and residual elongation display changes corresponding to the amount of digested elastin. The increased viscosity of untreated contracture bands containing less elastin, as compared to normal palmar aponeurosis, was not affected by elastase. Obviously, the elastic fibers in normal shape and distribution are responsible for maintaining an elastic status with a low viscous stress component. With the exception of contracture bands chondroitinase ABC caused a minor increase of residual elongation and as opposed to elastase a decrease of normalized hysteresis loop indicating an increased mobility of the tissue fibers.

Animals↗

PubMed1994

The influence of L-arginine on biomechanical parameters of native and nonenzymatically glycated rat tail tendons.

Rat tail tendons from animals of an age range from 35 days to 900 days were glycated using different glucose concentrations. After nonenzymatic glycation the biomechanical properties of tendons from young rats approached that of old tendons. In tendons from old animals the glucose incorporation was significantly lower than in young rat tail tendons. Addition of L-arginine to the glucose solution reduced the incorporation of glucose especially in young rats. The concentration of early glycation products and of advanced glycation end products were measured via affinity chromatography on boronic acid agarose and relative fluorescence per collagen content respectively. Both parameters were significantly reduced by an addition of 10 mmol/l arginine. Biomechanical changes due to glycation were partially reversed. Incubation of rat tail tendons in L-arginine in the absence of glucose caused a dose dependent binding of the amino acid mainly to the proteoglycan matrix. High concentrations of L-arginine induced pronounced biomechanical alterations contrary to the action of glucose. The biomechanical effect of L-arginine is compared to the action of Na+ and Ca2+ and discussed on the basis of a structural model of the proteoglycan matrix. Incubation of already glycated rat tail tendons with L-arginine caused a reduction of the elastic stress component This effect was diminished by increasing the preincubation interval with glucose. The equilibrium values of the elastic fraction were achieved after approximately five days incubation with the amino acid.

Aging↗

PubMed1994

[Binding capacity of ibuprofen to muscle proteins].

From former studies it is well known, that ibuprofen (CAS 15687-27-1) binds to muscular tissue in a higher degree than to tendons or ligaments. It is not known, however, what constituents of muscle tissue are responsible for this binding. Therefore the binding capacity of ibuprofen to different muscular proteins was studied. Actin, actomyosin, myosin, myoglobin, tropomyosin, lecithin, and native human collagen type I were incubated with 14C-ibuprofen and the specific binding was measured in relation to the total radioactivity. It could be shown that ibuprofen binds most markedly to actin. This binding could be inhibited by pre-incubation of ibuprofen with soluble actin. In comparison to the other proteins studied the specific binding of ibuprofen to actin was 4 to 5 times higher. As actin is a constituent of the cytoskeleton which plays an important role in generating oxygen radicals, its possible inhibition by ibuprofen could additionally explain the antiphlogistic effect of this compound.

Actins↗

PubMed1991

Antibody formation against human collagen and C1q in response to a bovine collagen implant.

The humoral immune response to commercially available bovine collagen implants (Zyderm, Zyplast) is characterized in a 45-year-old female patient. Circulating anti-collagen antibodies were detected after eight injections of Zyderm and after two injections of Zyplast given during a period of 3 years. The specificity of these antibodies for bovine and human collagens as well as for the collagen-like region of C1q (a subcomponent of the first component of complement), was investigated by affinity chromatography. Serum levels of anti-collagen and anti-C1q antibodies were measured using ELISA. High levels of antibodies to bovine collagens, showing a strong cross-reactivity with human collagen type III were detected in the patient's serum. Only weak cross-reactivity with human collagen type I and IV and no reactivity with type II were observed. In addition, these antibodies specifically cross-reacted with the collagen-like region of C1q. The antibody levels decreased continuously and disappeared 1 year after cessation of treatment. These results demonstrate for the first time the formation of autoantibodies upon treatment with a bovine collagen implant. Although antibodies to collagens and C1q have been found in various autoimmune diseases, neither adverse reactions to the bovine collagen implant nor any other clinical symptoms were observed in association with the described antibody response.

Animals↗

PubMed1991

Alterations of biochemical and biomechanical properties of rat tail tendons caused by non-enzymatic glycation and their inhibition by dibasic amino acids arginine and lysine.

The influence of dibasic amino acids arginine and lysine on non-enzymatic glycation of tail tendon fibers from old (900-day-old) and young (61-day-old) rats was investigated in vitro. The biomechanical changes in tendon fibers of young rats after an incubation interval of 7 or 14 days in a glucose solution were abolished by the addition of arginine or lysine (molar ratio amino acid:glucose 1:10). Glucose incorporation into rat tail tendon fibers as well as Amadori product formation was decreased significantly in the presence of the amino acids. The inhibitory effect of arginine was further confirmed by measurement of the amount of ketoamine formed during the glycation reaction using soluble albumin as a protein target. The effective inhibition of non-enzymatic glycation by arginine or lysine suggests their potential use in vivo as a means of controlling protein over-glycation.

Aging↗

PubMed1991

Biomechanical properties of elastase treated palmar aponeuroses.

Human palmar aponeurosis was treated with elastase in the presence or absence of soybean trypsin inhibitor. The removal of elastic fibers was complete as proved by electron microscopy. Cyclic loading was performed at a constant strain rate. Residual strain was measured and the stiffness and the fraction of dissipated energy of strain energy was calculated and compared to that of untreated samples of palmar aponeurosis. Residual strain and dissipated energy showed a dramatic increase after enzyme treatment, both in presence and absence of soybean trypsin inhibitor. Stiffness, on the other hand was reduced. The remaining collagen fibers show a more viscous behavior. Our results support the hypothesis that the elastin fibers are responsible for the elastic recovery, observed on specimens of untreated palmar aponeurosis.

Adult↗

PubMed1990

[Binding affinity of ibuprofen to collagen and other connective tissue components].

In vitro binding of ibuprofen to various tissue components was studied to explain differences in tissue concentration after local application of ibuprofen cream (Dolgit Creme). Radioactive ibuprofen was incubated with human Collagen Type I to V, Elastine, bovine, Mouse-Laminin, and Matrigel of the mouse, respectively. In low concentrations--similar to plasmaconcentrations after percutaneous application of ibuprofen--a specific binding especially to Laminin and Collagen Type IV could be found. This finding possibly explains previous autoradiographic results, which showed higher concentrations of ibuprofen in connective tissue compared with fat and other surrounding tissues.

Animals↗

PubMed1989

Induction of anti-pepsin antibodies after immunization with pepsin-extracted collagen.

Immunization with pepsin-extracted human type II collagen purified by different precipitation steps, although not showing any contamination with the enzyme on SDS-polyacrylamide gel electrophoresis, resulted in the generation of antibodies to the enzyme in addition to an immune response to collagen. These antibodies could be removed by immune absorption on a pepsin affinity column, leaving reactivity to type II collagen unaltered. High performance liquid chromatography on hydroxylapatite columns indicated that pepsin remained associated with the collagen molecules even after repeated precipitation and coeluted with a fraction of the collagen preparation. These results demonstrate that pepsin-extracted collagens may contain minimal amounts of the enzyme. On immunization, these impurities may induce the formation of unwanted antibodies, which might simulate a false specificity of the antibody preparation.

Antibodies↗

PubMed1988

Autoimmunity and T-cell subpopulations in old age.

To investigate the interrelationship between T-cell-dependent immune functions and autoimmune phenomena in old age we determined T-cell subpopulations in 20 aged healthy individuals (80-96 years old) using monoclonal antibodies. These persons were also investigated as to humoral parameters such as antinuclear antibodies, rheumatoid factors (IgG-, IgA-, IgM-RF), antibodies to collagen types I-IV as well as autoantibodies to organ-specific antigens. In addition, immune complexes were determined. We found that aged individuals have an increased frequency of autoantibodies as compared to a young control population, each aged subject presenting with at least one autoantibody species. Immune complexes, however, were only rarely detected. Three individuals showed a slightly increased T-helper/T-suppressor cell ratio, four had a decreased ratio. An increased number of T-suppressor cells was significantly correlated with a lowered incidence of anticollagen antibodies. Other parameters tested by us: fibronectin, laminin, procollagen type III, C3 and C4 complement components, immunoglobulins and acid alpha 1-glycoprotein. Aged individuals have significantly higher serum levels of fibronectin, while laminin and procollagen concentrations are in the normal range. A large percentage of old individuals had increased serum levels of C3 and/or C4. The acute phase protein orosomucoid, however, was in the normal range.

Adult↗

PubMed1984

Immune complexes in juvenile chronic arthritis.

Twenty children with juvenile chronic arthritis (JCA) and two children with SLE were investigated as to the existence of immune complexes in a long-term survey over 24 months. Two different methods were applied, a solid phase C1q RIA and a polyethylene glycol precipitation test. Detection of immune complexes was compared to the course of the disease and other laboratory data. C1q RIA showed a distinctly higher number of positive tests than the PEG precipitation test. The presence of immune complexes appears to be transitory in the course of JCA, as was demonstrated by C1q RIA. A connection with a more advanced stage of the disease is postulated. The positive test can be regarded as a prognostic parameter which, however, cannot be used for the diagnosis of JCA.

Adolescent↗