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M Bodo

Publications and source records attributed to M Bodo.

At least 37 records · Page 2Linked to original sources
PubMed1998

A locus in 2p13-p14 (OFC2), in addition to that mapped in 6p23, is involved in nonsyndromic familial orofacial cleft malformation.

An allelic association between the transforming growth factor alpha gene (TGFA) situated in the chromosome 2p13 region and nonsyndromic cleft lip with or without cleft palate, also named orofacial cleft (OFC), was found in several population studies. However, no linkage between gene and malformation has shown up until now, probably due to the presence of genetic heterogeneity and the small sample size analyzed. Previously, we employed a collection of 38 OFC families to demonstrate linkage to the 6p23 chromosome region with the presence of genetic heterogeneity. In the present study we tested whether, in the same sample, linkage between OFC and markers on 2p13 could be determined. Evidence for genetic heterogeneity in our family set was apparent, by both pairwise and multipoint linkage analyses. Moreover, lod scores > 3 were found for marker D2S378 when families linked to the 6p23 markers were analyzed. Taken together these results indicate a role for the TGFA, or for another gene physically close to it, and suggest an interaction between two different genes, OFC1 and OFC2, mapped in 6p23 and 2p13, respectively, in the development of the cleft.

Chromosomes, Human, Pair 2↗
PubMed1998

Glycosaminoglycan profile in macrophages exposed to Candida albicans and interleukins.

Glycosaminoglycans (GAG), are extracellular matrix macromolecules that affect the phagocytic properties of macrophages. In order to assess whether the interaction between macrophages and Candida albicans (iCa) provokes changes in the phenotype, we analyzed the GAG profiles in two macrophage lines, ANA-1 (from murine bone-marrow) and BV-2 (from murine brain). We also investigated GAG modulation by interleukin-1alpha (IL-1alpha) and interleukin-6 (IL-6). During iCa treatment and even after the addition of ILs, ANA-1 accumulated less total GAG compared to controls. IL-1 treatment, combined with iCa exposure, induced a decrease in heparan sulfate and chondroitin sulfate chains, and an increase in the hyaluronic acid percentage. IL-6 treatment, with or without iCa, decreased the hyaluronic acid/sulfated GAG ratio. The GAG pattern in BV-2 appears to be different to ANA-1 and iCa exposure does not induce any difference in total GAG. The inhibitory effect induced by ILs on GAG synthesis is less than that observed in ANA-1 and the GAG elution profile is modulated to a lesser extent by treatment with ILs and/or iCa compared to the ANA-1. We suggest that the observed changes in the expression of the individual GAG classes may be responsible for the macrophage functional heterogeneity.

Animals↗
PubMed1998

Role of growth factors on extracellular matrix production by chick embryo fibroblasts in vitro. Antagonist effect of TGF-beta through the control of IL-1 and IL-1Ra secretion.

Growth factors and extracellular matrix (ECM) macromolecules create specific environments that regulate cell proliferation and differentiation during embryonic development. This study had two main aims: (1) to characterize the phenotype of 7- and 13-day-old chick embryo fibroblasts treated with interleukin 1 (IL-1) and interleukin 6 (IL-6) evaluating in particular the neosynthesis of the total proteins and of the fibronectin (FN); (2) to examine the mechanisms through which transforming growth factor beta (TGF-beta) antagonizes the action of IL-1. The results show that protein neosynthesis and secretion is modulated by treatment with IL-1 and IL-6 only in 7-day-old fibroblasts. IL-1 favours cellular accumulation, while IL-6 promotes secretion more. FN, isolated by affinity chromatography and analysed by SDS-PAGE and flurography, is produced in greater concentrations by 7-day-old fibroblasts. Treatment with IL-1 promotes the accumulation of FN in the cellular compartment both at 7 and 13 days, while it stimulates the secretion only in 7-day-old fibroblasts. IL-6 only has a stimulating effect on the processes of accumulation and secretion on 13-day-old fibroblasts. The authors show in addition, that TFG-beta blocks the IL-1 induced inhibitory effect on glycosaminoglycan (GAG) and collagen production, evaluated with [3H]glucosamine and [3H]proline incorporation studies, respectively. The effect is evident when TGF-beta is added either before of with the cytokine. Analysis in cell culture supernatants, using specific ELISA kit and the study of the proliferative responses in mouse thymocytes, showed that TGF-beta induces its antagonist effects through a downregulation of IL-1 and/or an upregulation of IL-1 receptor antagonist protein (IL-1Ra). Considered as a whole the data indicate that the ILs and TGF-beta are involved in the physiological age-dependent accumulation of ECM and that the balance between the secreted cytokine network and IL-1Ra amount, may represent a homeostatic mechanism aimed at controlling normal embyrogenesis.

Animals↗
PubMed1998

Interleukin pattern of Apert fibroblasts in vitro.

The phenotype of cultured fibroblasts from patients affected by Apert's syndrome, a rare connective disorder, differs from that of normal cells in its extracellular matrix macromolecule composition (glycosaminoglycans, collagens and fibronectin) and is further modulated by treatment with interleukins (ILs). As the mechanisms responsible for the changes are unknown, we used our recently described model system for Apert periosteal fibroblasts to ascertain whether the pattern of ILs they secrete into the medium is comparable to that of normal fibroblasts. The results obtained by enzyme-linked immunosorbent assay (ELISA) show that the levels of interleukin-1 (IL-1) and interleukin-6 (IL-6) were lower in Apert than in normal media, whereas levels of IL-1 receptor antagonist (IL-1ra), the natural inhibitor of IL-1, were markedly higher. IL-1 specific bio-activity on thymocyte proliferation was also decreased in Apert supernatants. As we provided also evidence that active transforming growth factor beta (TGFbeta1), an IL-1 antagonist, was not secreted in greater amount in Apert media with respect to normals, the enhancement of IL-1ra appeared critical in down-regulating IL-1. Northern blot analysis of cytokine mRNA revealed no detectable IL-1 or IL-6 gene expression in normal fibroblasts, but high amounts of IL-6 mRNA transcripts in Apert cells. As the increased IL-6 gene expression did not translate into a parallel increase of secreted IL-6, the control of IL-6 secretion may be mainly post-transcriptional. Furthermore, the result that a treatment of the cultures with IL-1ra was able to induce a decrease of IL-6 secretion, suggests that the observed decreased secretion of IL-6 may be due to the autocrine action of overproduction of IL-1ra. The observed imbalance in the production of ILs which we show for the first time suggests ILs may be the natural autocrine regulators of ECM production in Apert fibroblasts. We hypothesize that in vitro differences previously reported in fibroblast phenotypes and several clinical features of Apert's syndrome may correlate with different cytokine patterns.

Acrocephalosyndactylia↗
PubMed1998

Characterization of recombinant type II collagen: arthritogenicity and tolerogenicity in DBA/1 mice.

Recombinant human type II collagen (rhCII) was produced using both the HT1080 mammalian cell expression system (rhCIIht) and a baculovirus expression system (rhCIIbac). The biosynthesis of CII requires extensive post-translational modifications, such as the hydroxylation of prolyl and lysyl residues and glycosylation of hydroxylysyl residues. Amino acid analyses indicated that the rhCIIbac was adequately hydroxylated at prolyl residues but underhydroxylated at lysyl residues and underglycosylated compared with tissue-derived hCII, while rhCIIht was hyperhydroxylated and hyperglycosylated at lysyl residues. When the murine collagen-induced arthritis (CIA) model was used to investigate the immunological properties of the two forms of recombinant CII, each induced a high incidence of arthritis following immunization of susceptible mice when emulsified with complete Freund's adjuvant (CFA). However, the severity of the arthritis, as assessed by the number of affected limbs, was significantly higher in mice immunized with rhCIIht than in mice immunized with rhCIIbac. These data indicate that the degree of hydroxylysine glycosylation may play a role in the induction of the arthritogenic response to CII. Each of the recombinant collagens was comparable to tissue-derived hCII in their ability to induce tolerance and suppress arthritis when given as intravenous or oral tolerogens. Taken together, our data suggest that recombinant CII can be prepared in adequate amounts for therapeutic uses and that the material is immunologically comparable to tissue-derived hCII when used to induce tolerance.

Administration, Oral↗
PubMed1998

Diphenylhydantoin affects glycosaminoglycans and collagen production by human fibroblasts from cleft palate patients.

During embryonic development, the proper production of extracellular matrix molecules mediates morphogenetic processes involved in palatogenesis. In the present study, we investigated whether any differences exist in glycosaminoglycan (GAG) and collagen synthesis between palate fibroblasts from infants, with or without cleft palate, in two age ranges. Subsequently, the effects of diphenylhydantoin (PHT), a teratogen known to induce cleft palate in human and mammalian newborns, on extracellular matrix (ECM) production were studied. We found that cleft palate fibroblasts (CPFs) synthesize greater amounts of GAG and collagen than normal fibroblasts (NFs). CPFs produced less cellular hyaluronic acid (HA) and more sulphated GAG. HA was the principal GAG species in the medium, and its percentage was lower in one- to three-year-old CPFs. Cleft palate fibroblasts produced more extracellular chondroitin 4- and 6-sulphate (CS) and dermatan sulphate (DS). Associated with a higher production of sulphated GAG, we observed a higher synthesis of type III and type I collagen with a normal ratio of alpha2(I) to alpha1(I) chains. PHT treatment of NFs reduced collagen and GAG synthesis, with a marked effect on sulphated GAG. The drug changed collagen synthesis, whereas it did not affect GAG production in CPFs whose phenotype may already be impaired. These findings indicate that, in CPFs, modifications in the pattern of ECM components, which are most likely responsible for the anomalous development, persist in infants. In addition, NFs and CPFs with a different phenotype respond differently to PHT treatment.

Cells, Cultured↗
PubMed1998

A contribution to the regulation of proteoglycan production: modulation by TGF alpha, TGF beta and IL-1 of glycosaminoglycan biosynthesis on beta-D-xyloside in chick embryo fibroblasts.

In order to elucidate the mechanisms determining the variability in the proteoglycan structure and the factors involved in this determination, we treated chick embryo skin fibroblasts with beta-D-xyloside to obtain glycosaminoglycan chains deprived of core proteins, and with different cytokines (transforming growth factor alpha and beta, interleukin-1) to produce variability. The different cytokines specifically regulate both cellular and extracellular amount and composition of glycosaminoglycans. Beta-D-xyloside treatment does not change protein content and protein synthesis, whereas it increases overall extracellular sulphated glycosaminoglycan production, heparan sulphate and chondroitin sulphate content, and reduces that of dermatan sulphate. This indicates that the core protein regulates quantitative proteoglycan production, and probably directs (with appropriate signals) the core oligosaccharide bound to it to the right synthesizing enzymes. The modulatory action of the different cytokines on sulphated glycosaminoglycan production and classes remains, even though the core protein is absent. This indicates that the cytokines also act on the glycosyltransferases. Our results suggest that the proteoglycan production may be subject to a double control, one of which is at the level of the core protein and the other, mediated by environmental signals, at the level of glycosaminoglycan synthesizing enzymes.

Animals↗
PubMed1997

Involvement of polyamines in the action of transforming growth factor beta and interleukin-1 on cultured chick embryo fibroblasts.

In this study we have examined the relationship between growth factor-induced proliferation and ODC/polyamine levels. TGF beta promotes cell growth and enhances [3H]-thymidine incorporation in chick embryo fibroblasts maintained in a serum-depleted medium. The action on DNA synthesis declines in the second day of treatment. IL-1 does not affect proliferation or [3H]-thymidine incorporation either when it is added alone or in combination with TGF beta. The response of the cells to TGF beta is associated with a significant stimulation of ODC activity and Put, Spd levels together with an enhancement of the Spd/polyamines ratio. IL-1, which does not act on cell proliferation, fails to activate ODC and to increase polyamine levels, thus indicating that the ODC/polyamine system is most likely to be an important link in the chain of events that leads to growth factor-induced proliferation.

Animals↗
PubMed1997

Improving cancer prevention at the worksite: how are Belgian companies dealing with smoking regulations?

Little is known about the impact of smoking policy on companies' policies related to smoking in Belgium. The study was designed in order to compare the companies' policies related to smoking (CPRS) in 1990 and in 1993. During this 3 year period, numerous information and regulation inputs (media, brochures) were aimed at companies to regulate smoking behavior in the workplace, so as to reduce the risks of passive smoking. A short questionnaire was mailed to 3543 Belgian companies in October 1990 and in June 1993 to assess: designation of smoke free areas (SFA); willingness to offer a worksite information program (WIP); willingness to offer a worksite smoking cessation program (WSCP); willingness to subsidize a WSCP; willingness to offer a WSCP during working hours; willingness to offer a meeting room for a WSCP and actual organization of a WSCP. In 1990, 773 companies (22%) and in 1993, 890 companies (25%) responded to the questionnaire. The results showed that small companies and companies with a high blue/white collar ratio were less able to implement health policy recommendations. A total of 325 (9%) companies responded to the 1990 and 1993 questionnaires. Comparison of 1990 and 1993 dataset showed that during this 3 year period, no major changes occurred for a majority of companies. Amongst the small positive changes, only the designation of smoke free areas and the organization of a small number of WSCP was observed. The conclusion is that despite inputs, little impact on smoking policies is noticeable. Strategies designed to intensify inputs and to promote implementation of regulation of WSCP should therefore further be studied.

Belgium↗
PubMed1997

Apert's syndrome: differential in vitro production of matrix macromolecules and its regulation by interleukins.

During embryonic development, variations in the composition of the extracellular matrix (ECM) macromolecules influence bone tissue differentiation. We present novel findings on the in vitro phenotypic expression of periosteal fibroblasts obtained from patients affected by Apert's syndrome, a rare craniofacial malformation, and the effects that interleukins (ILs) induce on the phenotype. Apert fibroblasts synthesized greater quantities of glycosaminoglycans (GAGs) and intracellular type I collagen, and also produced more type III collagen and fibronectin. The amount of hyaluronic acid (HA) secreted by Apert fibroblasts was much higher than that secreted by normal fibroblasts, but, as the absolute values of heparan sulphate (HS), chondroitin sulphate (CS) and dermatan sulphate (DS) also rose in Apert media, the HA-sulphated GAG ratio was similar in the media obtained from both populations. Both ILs triggered elevations of HA in normal cells, although relative percentage secretion remained unaltered, but significantly reduced HA secretion by Apert cells. IL-1 significantly increased CS in normal and Apert media, whereas IL-6 enhanced HS and DS in media of both populations. HA-sulphated GAG ratio decreased in Apert media after IL treatment. Both ILs boosted fibronectin production by Apert fibroblasts, whereas IL-1 increased type III but not type I collagen. Taken together, these data demonstrate that the synthesis and secretion of ECM macromolecules are markedly altered in Apert fibroblasts. The fact that treatment with ILs further modifies the Apert phenotype suggests that ILs may be implicated in the pathophysiology of the malformations during skull morphogenesis.

Acrocephalosyndactylia↗
PubMed1997

Glycosaminoglycan metabolism and cytokine release in normal and otosclerotic human bone cells interleukin-1 treated.

Glycosaminoglycans (GAGs), normal components of the extracellular matrix (ECM), and the glycosidases, that degrade them, play a key role in the bone remodelling process. The effects of interleukin-1 alpha (IL-1 alpha) on GAG metabolism in normal and otosclerotic human bone cells as well as its capacity to modulate IL-1 alpha, IL-1 beta and IL-6 secretion in both populations was analyzed. The amount of radiolabeled GAGs was lower in otosclerotic than in normal bone cells. IL-1 alpha reduced newly synthesized cellular and extracellular GAGs in normal cells, but only those of the cellular compartment in otosclerotic bone cells. It depressed heparan sulphate (HS) more in normal cells and chondroitin sulphate (CS) more in otosclerotic bone cells. The HA/total sulphated GAG ratio was shifted in favour of the latter in otosclerotic cells, whereas the opposite effect was seen after IL-1 alpha treatment. There was little difference in the beta-D-glucuronidase levels of the normal and pathological cells, while beta-N-acetyl-D-glucosaminidase was significantly increased in otosclerotic bone cells. As the activity of neither enzyme was modified by treatment with IL-1 alpha, the cytokine seems to exert its influences on GAG synthesis rather than on the degradation process. IL-1 alpha, IL-1 beta and IL-6 secretion was markedly higher in otosclerotic cells. IL-1 alpha modulated the secretion of each interleukin differently, thus resulting in a cytokine cascade that may act in autocrine/paracrine manner on target cells. The authors suggest that changes in the cytokine network may have a specific, yet still unknown, role during normal and pathological osteogenesis.

Bone and Bones↗
PubMed1996

Collagen synthesis and cell growth in chick embryo fibroblasts: influence of colchicine, cytochalasin B and concanavalin A.

Culturing of chick embryo fibroblasts in the presence of colchicine or cytochalasin B with and without concanavalin A (Con A) demonstrated that colchicine induces greater neosynthesis of endocellular type I collagen, whereas cytochalasin B boosts secretion. The effects are modified by the addition of Con A, which increases alpha 2 more than a1 chain production. 3H-thymidine incorporation is unaffected by cytochalasin B, but stimulated by colchicine. Con A neutralizes the stimulatory action of colchicine. It would therefore seem that Con A exerts transmembrane control of effects induced by colchicine and cytochalasin B by binding to cell surface receptors and so triggering rearrangement of the cytoskeleton.

Actins↗
PubMed1996

Effects of interleukins on Crouzon fibroblast phenotype in vitro. Release of cytokines and IL-6 mRNA expression.

In Crouzon's syndrome, the cranial morphogenic processes are altered due to the early fusion of the facial and basal cranial bones. Evidence that Crouzon fibroblasts have an altered phenotype which is modulated by interleukin 1 (IL-1) and interleukin 6 (IL-6) is provided. [3H]Thymidine incorporation and cell count studies showed that Crouzon fibroblasts have an accelerated proliferation rate. [3H]Glucosamine incorporation studies, followed by chromatography analysis of culture medium samples, revealed that the various classes of glycosaminoglycans (GAG) secreted into the medium were differently distributed in Crouzon and normal fibroblasts. Crouzon fibroblasts secreted less total GAG, particularly hyaluronic acid (HA) and heparan sulfate (HS), but a relatively greater quantity of chondroitin sulfate. Type I and III collagen were raised in Crouzon fibroblast medium whereas the concentration of fibronectin was lower than in normal cells. Interleukin treatment induced changes in cell growth and neosynthesis of extracellular matrix macromolecules. Both IL-1 and IL-6 stimulated proliferation of Crouzon fibroblasts, whereas only IL-6 increased [3H]thymidine incorporation in normal cells. IL-1 provided a drop in HA and a rise in GAG sulfates in normal fibroblasts, but caused an opposite effect in Crouzon fibroblasts. Type I collagen and fibronectin secretions are differently modulated by the cytokines in the two populations. Moreover, level of IL-1 able to stimulate [3H] thymidine incorporation into mouse thymocytes, and level of IL-1 receptor antagonist (IL-1ra), as determined by ELISA, were higher in pathological than in normal fibroblasts. Also evidence that levels of IL-1 alpha and IL-6 proteins measured by ELISA and also IL-6 mRNA expression are enhanced in Crouzon fibroblasts is provided. These novel data suggested that, in Crouzon's syndrome, the modifications in the relative concentrations of the extracellular matrix (ECM) components associated with the abnormal cytokine networks may alter the balance of the microenvironment where the morphogenic events take place.

Adolescent↗
PubMed1995

Microgravity and hypergravity effects on collagen biosynthesis of human dermal fibroblasts.

Astronauts experiencing long periods of space flight suffer from severe loss of bone tissue, particularly in those bones that carry the body weight under normal gravity. It is assumed that the lack of mechanical load decreases connective tissue biosynthesis in bone-forming cells. To test this assumption, quantitative and qualitative aspects of collagen synthesis under microgravity, normal gravity, and hypergravity conditions were investigated by incubating human fibroblast cultures with [3H]-proline for 4, 7, 10, and 20 h during the Spacelab D2-mission in 1993. Quantitative analysis revealed an increase of collagen synthesis under microgravity conditions, being up to 143% higher than in 1 g controls. In contrast, hypergravity samples showed a decrease in collagen synthesis with increasing g, being at the 13% level at 10 g. The relative proportion of collagen in total synthesized protein showed a slight decrease with increasing g. The secretion of collagen by the cells, proline hydroxylation of individual collagen alpha-chains, and the relative proportions of synthesized collagens I, III, and V were not affected under any of the applied conditions.

Adult↗
PubMed1995

Composition and posttranslational modification of individual collagen chains from osteosarcomas and osteofibrous dysplasias.

The composition of collagen was analyzed and the degree of lysyl hydroxylation of individual collagen chains was determined in four osteosarcomas and two osteofibrous dysplasias. In addition, the tumor proliferation (number of mitoses, proliferating-nuclear-antigen-positive cells, MIB) as well as the response to chemotherapy (morphological regression grade) were checked. All tumors contained a high proportion of collagen III and, in all but one osteosarcoma, pepsin-extracted collagens I and III were overmodified. Furthermore, the proportion of diglycosides in collagen I was about four times higher than in controls. The collagen composition and modification resembled those of bones at early stages of human development. One osteosarcoma and both osteofibrous dysplasias were in the normal range of lysyl hydroxylation. There was no correlation between the collagen properties and the histopathological marker of tumor proliferation.

Adolescent↗
PubMed1995

Gravity effects on connective tissue biosynthesis by cultured mesenchymal cells.

Quantitative and qualitative aspects of collagen synthesis under microgravity, normal gravity and hypergravity conditions were investigated during the spacelab D-2 mission by incubating human fibroblast cultures with [3H]-proline for 0, 4, 7, 10 and 20 hours. Quantitative analysis revealed an increase of collagen synthesis under microgravity conditions, being 40% higher than 1g controls. Hypergravity samples at 1.44g, 6.6g and 10g showed a decrease in collagen synthesis with increasing g, being down to about 15% at 10g. The relative proportion of collagen from total protein synthesized, the secretion of collagen by the cells, proline hydroxylation of individual collagen alpha-chains and the relative proportions of collagens I, III and V synthesized were not affected at any of the applied conditions.

Cells, Cultured↗
PubMed1995

Hydroxylation of collagen type I: evidence that both lysyl and prolyl residues are overhydroxylated in osteogenesis imperfecta.

The composition of the collagens secreted into the media of fibroblast cultures of 39 patients with osteogenesis imperfecta (OI) was the same in controls and OI cultures. An abnormal migration pattern of collagens upon SDS-PAGE was evident in one third of the cultures investigated. Lysyl and prolyl hydroxylation of HPLC-purified alpha 1(I) chains was elevated in about 60% of cultures. The degree of hydroxylation was highest in the lethal forms. The extent of lysyl and prolyl hydroxylation showed a strong correlation (r = 0.74, P < 0.001). While high levels of hydroxylation are frequently observed in OI patients, a direct correlation between lysyl or prolyl hydroxylation and fracture rate or growth retardation could not be established.

Adolescent↗