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Biomedical subjects

M P Jacob

Publications and source records attributed to M P Jacob.

At least 37 records · Page 2Linked to original sources
PubMed1997

Relationship of serum elastin peptide level to single breath transfer factor for carbon monoxide in French coal miners.

BACKGROUND: Clinical and epidemiological studies have given discordant results on the usefulness of the level of circulating elastin peptide (EP), a potential marker of both elastin destruction (a key phenomenon in pulmonary emphysema) and neosynthesis, for assessing structural changes in the lung extracellular matrix. The aim of the present study was to explore the relationship between levels of EP and forced expiratory volume in one second (FEV1) and single breath transfer factor for carbon monoxide (TLCO and KCO) in coal miners. METHODS: The study population comprised 227 working coal miners aged 34-50 years consisting of 75 miners heavily exposed to underground coal dust with pulmonary radiographs classified as 0/1 or 1/0 by the International Labour Office classification, 75 exposed miners with radiographs classified as normal (0/0), and 77 miners slightly exposed to coal dust with normal radiographs. The subjects answered a standardised questionnaire and performed spirometric tests and a carbon monoxide (CO) transfer test. RESULTS: No association was observed between EP levels and % predicted FEV1 (or FEV1/FVC). The level of EP increased significantly with decreased % predicted TLCO (r = -0.20). Miners in the lowest % predicted KCO quintile had higher EP levels than the rest (3.28 (1.37) vs 2.47 (1.16)). A significantly lower EP level was observed in miners with radiographs classified as 1/0 or 0/1, especially in those with round opacities, compared with miners with a normal radiograph, and in current smokers compared with the rest. CONCLUSIONS: The results of this study suggest that the level of EP may reflect some remodelling activity in emphysema and lung fibrosis.

Adult↗
PubMed1996

Lack of a relationship of elastin peptide level to emphysema assessed by CT scans.

Clinical reports suggest that peptide (EP) concentration may be used as a subclinical marker of pulmonary emphysema. This hypothesis was tested in a clinical study by comparing EP concentration in male emphysematous patients with the level in two control groups, and by exploring the relation of elastin peptide level to high-resolution computed tomography (HRCT) scan emphysema score among emphysematous patients. Serum EP level was determined among male emphysematous patients with at least 20% of emphysema (n = 27) and in two populations of male workers, drawn from epidemiologic studies (227 coal miners and 310 policemen). No difference in elastin peptide concentration was observed between emphysematous patients and control subjects (mean +/- SD = 2.39 +/- 1.18 micrograms/ml in patients versus 2.55 +/- 1.34 micrograms/ml in policemen and 2.59 +/- 1.20 micrograms/ml in coal miners). The correlation of elastin peptide concentration with percentage of pulmonary emphysema was negative and of borderline significance (r = -0.36; p = 0.06). These results cast doubts on the usefulness of elastin peptide level as a predictive marker of pulmonary emphysema.

Adult↗
PubMed1995

Bovine elastin and kappa-elastin secondary structure determination by optical spectroscopies.

Elastin is the macromolecular polymer of tropoelastin molecules responsible for the elastic properties of tissues. The understanding of its specific elasticity is uncertain because its structure is still unknown. Here, we report the first experimental quantitative determination of bovine elastin secondary structures as well as those of its corresponding soluble kappa-elastin. Using circular dichroism and Fourier transform infrared and near infrared Fourier transform Raman spectroscopic data, we estimated the secondary structure contents of elastin to be approximately 10% alpha-helices, approximately 45% beta-sheets, and approximately 45% undefined conformations. These values were very close to those we had previously determined for the free monomeric tropoelastin molecule, suggesting thus that elastin would be constituted of a closely packed assembly of globular beta structural class tropoelastin molecules cross-linked to form the elastic network (liquid drop model of elastin architecture). The presence of a strong hydration shell is demonstrated for elastin, and its possible contribution to elasticity is discussed.

Amino Acids↗
PubMed1995

Elastin in blood vessels.

Elastin fibres give blood vessels important rheological properties, such as the postsystolic elastic recoil. The age-dependent increase of Ca2+ and lipid content, and elastolytic degradation of the fibres progressively impairs their function and produces circulating elastin peptides. Their interaction with the elastin receptor on smooth muscle cells induces not only increased cell-elastin fibre adhesion and endothelium-dependent vasorelaxation but also the release of lytic enzymes and oxygen free radicals from monocytes penetrating the vascular wall during atherogenesis. The age-dependent 'uncoupling' of the receptor has been shown to be involved in the loss of Ca2+ homeostatic mechanisms and the progressive calcification of the vessel wall.

Aging↗
PubMed1994

Interaction between cells and elastin fibers: an ultrastructural and immunocytochemical study.

Mesenchymal cells (fibroblasts, smooth muscle cells) and endothelial cells were shown to interact with elastin fibers. The strong adhesion of elastin fibers to these cells is mediated by a cell membrane complex with a major glycoprotein component of 120 kDa designated as elastonectin. This interaction was studied by transmission electron microscopy (TEM) and immunocytochemical techniques using antibodies raised against the elastin adhesive proteins. When fibroblasts and smooth muscle cells were cultured in presence of elastin fibers, TEM showed an adhesion mechanism that takes place over several sites along the plasma membrane of these cells. Endothelial cells showed a very close association with elastin, emitting "pseudopodia" that embody the fibers. TEM, indirect immunofluorescence, immunoperoxidase, and confocal microscopy showed the presence and localization of cell membrane components synthesized in large quantities when cells were incubated in presence of elastin. Cells without elastin fibers barely revealed the adhesive membrane complex. These results confirm and extend previous findings concerning the presence of an inducible cell membrane complex that mediates the adhesion of elastin fibers to these cell types.

Adult↗
PubMed1994

[Role of the elastin-laminin receptor in the vasoregulation].

The elastin-laminin receptor was shown to be present on several benign and malignant cell types and to mediate several important cell reactions such as chemotactic movements of fibroblasts and monocytes, release of lytic enzymes and oxygen free radicals from leucocytes, increased adhesion of mesenchymal cells to elastin fibers as well as modifications of ion fluxes-increase of calcium and sodium influxes and decrease of ouabain-dependent potassium influx. We now demonstrated that the addition of elastin peptides to rat aorta rings precontracted with noradrenaline produced an endothelium-dependent vasorelaxation. The inhibition of this effect by laminin and lactose is in favor of the mediation of this action of elastin peptides by the 67 kDa subunit of the elastin-laminin receptor which possesses a lectin site. As elastin peptides are present in the circulating blood and their concentration was shown to increase in some pathological conditions, this phenomenon may well have physiopathological significance.

Animals↗
PubMed1993

Elastin peptide concentration in human serum: variation with antibodies and elastin peptides used for the enzyme-linked immunosorbent assay.

Discrepancies exist between the reported values for the mean elastin peptide (EP) concentration in human sera. In order to understand these discrepancies, several EP preparations were obtained in vitro and monoclonal and polyclonal antibodies were produced against them. These different EP preparations and antibodies were used in an enzyme-linked immunosorbent assay (ELISA) to study cross-reactivity between EP preparations and to quantitate EP concentration in human sera. The method of purification of elastin, the method of hydrolysis of elastin and the molecular weight of EP influence their reactivity with antibodies and the results of EP measurements in human sera. However, there is a good correlation between EP measurements carried out in several human sera with the different EP preparations and different antibodies. Although absolute values of the EP concentrations varied with the EP preparation and antibodies used for the ELISA, the variations of this EP concentration measured from one human serum to another are significant.

Antibodies, Monoclonal↗
PubMed1993

Biological markers as indicators of exposure and pneumoconiotic risk: prospective study.

This research is designed to evaluate a number of biological markers to estimate harmful exposure on coal miners from different mining regions in France and to relate the outcome to differences in prevalence of coal worker pneumoconiosis (CWP) between these regions. Eight epidemiological groups of active and ex-miners (smokers and non-smokers) have been selected in the French collieries (North, Lorraine and Provence) according to their occupational and pneumoconiotic status. The following biomarkers have been evaluated: cellularity of sputum, elementary analysis of particles in TEM/EDAX, plasma neutral metalloendo-peptidase elastase type (NMEP), leucocyte elastase (HLE), fibronectin (FN) and elastin peptides. Pulmonary alveolitis, expressed by sputum cellularity, is different between active workers groups but not related to the general background of pneumoconiosis prevalence in the French collieries. In the plasma parameters, fibronectin, HLE and NMEP significantly increased in all groups of coal mine workers as compared to the control group, except for fibronectin parameter in Lorraine collierie. The degree of increase of these parameters allow us to discriminate the different groups and suggest that plasma FN, HLE and NMEP may be considered as biological markers of chronic inhalation of coal mine dust particles. The decrease of elastin peptides level in the Lorraine group alone suggests a specific alteration of elastin metabolism. These parameters were not related to the development of pneumoconiosis and its degree of severity.

Biomarkers↗
PubMed1993

Loss of calcium-homeostatic mechanisms in polymorphonuclear leukocytes of demented and nondemented elderly subjects.

The calcium homeostatic mechanisms were explored in 31 aged individuals some of whom suffered from dementia (11 Alzheimer's disease, 5 other dementias, 15 cognitively normal individuals). Their mean age was 81.2 +/- 9.2 years, varying from 60 to 96 years. Polymorphonuclear leukocytes (PMNs) were isolated from freshly drawn citrated blood and loaded with Fura-2. Resting intracellular free calcium values, [Ca2+]o, were recorded as well as the calcium transients produced by formyl-methionyl-leucyl-phenylalanine 10(-8) M:delta [Ca2+]i. The return to prestimulation values was also recorded. Average [Ca2+]o was 64.6 +/- 16.0 nM and the average delta [Ca2+]i 77.6 +/- 52.7 nM. No correlation was found with age within the range explored nor was there any difference in calcium transients between demented and nondemented patients. The most surprising finding was the inability of about 30% of all examined patients' PMNs to return the elevated [Ca2+]i values to prestimulation values. For some patients, elevated [Ca2+]i remained at the higher value, for others [Ca2+]i continued to rise. Those who could down-regulate poststimulation values did it only very slowly. Previous results obtained with leukocytes from younger individuals (under 45 years) showed a rapid return to prestimulation values. It appears that this loss of calcium-homeostatic mechanisms in old individuals is a progressive process which involves a relatively high proportion of the investigated subjects. The rate of decrease of intracellular calcium (measured by the slope P) did not correlate with diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

[Elastin: preparation, characterization, structure, biosynthesis and catabolism].

Elastin is a component of elastic fibers. It is localized in aorta, lung and skin. Its major property is elasticity. This hydrophobic protein contains two specific cross-links: desmosine and isodesmosine. Elastogenesis begins about mid-gestation in most mammalian tissues, continues at a high rate through late foetal and early neonatal stages and is most completely repressed by maturity. More recent studies were carried out on the gene and the regulation of elastin gene expression. A receptor for elastin peptides was also evidenced.

Amino Acid Sequence↗
PubMed1992

Cell-matrix interactions in the genesis of arteriosclerosis and atheroma. Effect of aging.

The progression of atheroarteriosclerosis was shown to be age dependent. This designation covers two separate entities: arteriosclerosis, the progressive and diffuse hardening of the walls of arteries with loss of elasticity, and atheromatous plaque formation, which can start early in life according to nutrition and genetic factors (LDL-receptor expression). Lipoprotein-receptor interactions play a crucial role in lipidic plaque formation. There is, however, no indication that the diffuse hardening of the vascular wall would also be influenced by these mechanisms. We described recently a high-affinity receptor for elastin peptides, present on smooth muscle cells, fibroblasts, and also on monocytes and PMNs. When activated, this receptor will increase intracellular calcium. Circulating elastin peptides were determined by a sensitive Elisa method and found to be between 0.1 and 20 micrograms/ml, in the range of activation of the elastin receptor. They increase in obliterative arteriopathies and type IIb hyperlipidemia. Elastolysis accompanies aging and vascular pathology; the sensitivity of this receptor changes with age, intracellular Ca++ increases, but the receptor appears to be uncoupled from its normal transmission mechanism. These results may well explain the increasing diffuse calcification of the vessel wall. The previously demonstrated potentiation of cholesterol deposition in elastic fibers by calcium is in agreement with simultaneous deposition of calcium and lipids. The recent demonstration of the efficient competition of fibronectin for LDL in proteoglycan-LDL complexes suggests that this reaction may be involved in foam cell formation by the opsonization of LDL for phagocytosis. Fibronectin was shown to accumulate in atherosclerotic plaques. Altogether these recent results confirm the importance of cell-matrix interactions in atherogenesis and lead to a better understanding of the age dependence of these disease processes.

Aging↗
PubMed1992

Predictions of the secondary structure and antigenicity of human and bovine tropoelastins.

Secondary structure and antigenicity predictive methods have been applied to the sequences of human and bovine tropoelastins in order to have some insight into the molecular structure of its insoluble counterpart, i.e., elastin. For both tropoelastins, all the predictions yielded 11 major regions, in which the pleated conformation was predominant, separated by 10 strong helical segments of various lengths located within alanyl rich regions of the chains. The overall conformations of human and bovine tropoelastins were estimated to contain 18 +/- 5% alpha-helices, 63 +/- 17% beta-sheets, 13 +/- 13% beta-turns and 6 +/- 6% random coil. For both tropoelastins, antigenicity predictions indicated the presence of seven synthetic decapeptides corresponding to continuous linear epitopes of the molecule. Some of the predicted epitopes are located in the same regions in both species while others are not. These predictions have allowed us to propose an alpha/beta conformation for tropoelastin. Therefore this extracellular matrix macromolecule might be more structured (10 helical segments for about 18% of the overall structure) than previously suggested.

Algorithms↗
PubMed1992

Relation of serum elastin peptide concentration to age, FEV1, smoking habits, alcohol consumption, and protease inhibitor phenotype: an epidemiological study in working men.

BACKGROUND: In clinical investigations elastin peptide concentration has been proposed as one potential marker of lung elastin degradation. No epidemiological study has yet confirmed this hypothesis. METHODS: The relation of elastin peptide concentration to some factors closely related to pulmonary emphysema (age, smoking habits, FEV1 alpha protease inhibitor (PI) phenotype) and to alcohol consumption was examined in an epidemiological study of 310 working men. The elastin peptides used for obtaining antibodies and as reference in an ELISA assay were prepared from chemically hydrolysed elastin. RESULTS: The elastin peptide concentration significantly decreased with age from 2.92 (1.54) micrograms/ml among subjects younger than 30 years to 2.18 (1.14) micrograms/ml among subjects older than 50. Elastin peptide concentration did not differ with smoking habits and was clearly unrelated to FEV1. A lower elastin peptide concentration was observed in all groups of subjects with a protease inhibitor phenotype other than PI MM (PI FM, IM, MP, MS, MZ, and S phenotypes). CONCLUSIONS: The results cast doubts on the usefulness of the elastin peptide concentration as a marker of lung destruction in middle aged, predominantly healthy men. Blood elastin peptide concentration may reflect both elastin degradation and resynthesis. The results of this analysis suggest that several factors (age, alcohol consumption, non-PI MM phenotype) may be associated with decreased resynthesis of lung elastin. Further studies, conducted in various age groups and including estimates of the degree of lung destruction, are needed to unravel the mechanisms underlying lysis and resynthesis of lung elastin.

Adult↗
PubMed1992

[Effect of elastin peptides on cell proliferation].

Elastin peptides were shown to act on a cell membrane receptor coupled to a G-protein, phospholipase C, and its activation increases IP3 and DAG and opens receptor-dependent Ca(++)-channels. As some growth factors also produce similar modifications in intracellular Ca++, we wanted to explore the effect of elastin peptides on cell proliferation using 3H-thymidine incorporation and cell counting. The concentration of peptides needed for the stimulation of cell proliferation varied between large limits (1 microgram/ml to 10 mg/ml) according to the origin of the cells and the nature of the peptides. The proliferation of CCL 39 chinese hamster lung fibroblasts was enhanced in a dose-dependent fashion in the concentration range of 3 to 10 mg/ml. The proliferation of human skin fibroblasts was enhanced in the concentration range of 0.5 to 3.3 mg/ml and inhibited at higher concentrations. This effect depended little on the average molecular weight (MW) of the peptide preparation, high MW peptides (average 75 kDa) and lower MW peptides (average MW 10 kDa) were both efficient approximately to the same extent. It appears probable that only a small fraction of these peptides possesses this growth promoting property; other sequences might have the opposite effect. The conformation of the peptides may also play an important role. Human sera contain circulating elastin peptides in the concentration range of 1.0 to 10 micrograms/ml, increasing in obstructive arteriopathies and in some hyperlipidemias. It appears therefore that the above findings may have physiopathological significance in the regulation of cell proliferation in normal and pathological conditions.

Animals↗
PubMed1992

[Elastin and arteriosclerosis: determination and characterization of elastin peptides in blood].

During pathologies such as arteriosclerosis and emphysema, degradation of elastin by elastases occurs and elastin peptides are produced. In order to evaluate elastin degradation, measurements of elastin peptide concentration in human blood were carried out. According to elastin peptides used for obtention of antibodies and for ELISA, the measured values are different. Elastin peptides have several biological effects: they are chemotactic, modify ion fluxes and several intracellular mechanisms.

Arteriosclerosis↗
PubMed1991

Mechanisms of interaction between human skin fibroblasts and elastin: differences between elastin fibres and derived peptides.

3H-Labelled kappa-elastin peptides (kE:75 kDa molecular weight) were shown to bind to confluent human skin fibroblast (HSF) cultures in a time-dependent and saturable manner. Scatchard analysis indicated the presence of high affinity binding sites with kD = 2.7 x 10(-10) M and 19,000 sites per cell. Binding of kE to its receptor on HSF accelerates and intensifies the adhesion of insoluble elastin fibres (iE) to confluent HSF. Optimal effect was attained for a kE concentration of 0.3 x 10(-9) M close to kD. This stimulatory effect of kE on the binding of iE to HSF could be inhibited by neomycin, retinal and pertussis toxin, substances which act at different levels of the transduction mechanism following the activation of the receptor and the subsequent triggering of cell biological events (chemotaxis, modification of calcium fluxes). The stimulation of iE adhesion to HSF induced by kE as well as kE binding to the cells could be inhibited by lactose and laminin but not by Arg-Gly-Asp-Ser(RGDS) peptides. This indicates that the elastin peptide receptor on HSF possesses lectin-like properties and shares homology with the laminin receptor as also shown for other cell types. None of the substances tested, that is inhibitors of the transduction mechanism, lactose, laminin and Arg-Gly-Asp-Ser(RGDS) peptides were shown to interfere significantly with the binding of iE (in the absence of added kE) to confluent HSF. The proteins adhering strongly to elastin fibres were isolated by a sequential extraction procedure and the final hydrochloride guanidinium-DTT extract was analysed by SDS-PAGE under reducing conditions, Western blots using specific antibodies against several connective tissue proteins and affinity for [3H]-kE following nitrocellulose electro-transfer of proteins. Fibronectin, vitronectin, tropoelastin(s), and a 120 kDa cysteine rich glycoprotein previously designated as elastonectin were identified. Among these proteins, [3H]-kE was found to bind exclusively to a 65 kDa protein that could be eluted selectively from elastin fibres with a neutral buffer containing 100 mM lactose. Therefore the elastin peptide receptor on human skin fibroblasts shares properties with the elastin receptor characterized from other cell types. Conformational differences between elastin peptides and elastin fibres could explain the differences in the mechanisms of interactions between elastin fibres and elastin peptides with HSF in culture. The stimulatory effect of elastin-derived peptides on the adhesion of elastin fibres to HSF could have implications in the oriented biosynthesis of elastin fibres.

Adult↗
PubMed1990

Altered phosphatidylinositol breakdown after K-elastin stimulation in PMNLs of elderly.

The degradation of elastic fibres during atherosclerotic plaque formation in arterial wall is a well known process. The liberated elastin peptides such as K-elastin possess various biological activities: They are chemotactic for monocytes and fibroblasts, stimulate the oxidative burst and the intracellular free Ca2+ mobilisation through the phosphatidylinositol (PIP2) breakdown in PMNLs. It was found that the PIP2 breakdown induced by K-elastin is a pertussis toxin sensitive process in PMNLs of young subjects. In the case of the elderly, the K-elastin-induced oxidative burst, intracellular free Ca2+ elevation was less than in young, and could not be inhibited by pertussis toxin. Studying the K-elastin-induced inositol phosphate (IP) formation in PMNLs of elderly a disturbed PIP2 breakdown was found. K-elastin stimulated the IP formation at a very low level in PMNLs of elderly. This alteration of the second messenger formation (e.g. IP3 and Ca2+) after KE stimulation, might be the consequence of their originally elevated levels in resting PMNLs of elderly.

Age Factors↗