Biomedical subjects

Y Acil

Publications and source records attributed to Y Acil.

12 recordsLinked to original sources

PubMed2006

Diabetes may increase risk for oral cancer through the insulin receptor substrate-1 and focal adhesion kinase pathway.

In light of recent epidemiological studies that associate diabetes mellitus with increased risk for oral cancer, we investigated in diabetic (type I) and normal rats with induced oral squamous cell carcinoma whether the molecular basis for that putative association involves insulin receptor substrate-1 (IRS-1) and focal adhesion kinase (FAK). Fourteen diabetic and 12 normal rats developed cancer after 4-nitroquinoline-N-oxide treatment, while six diabetic and six normal animals were used as controls. Oral sections were studied using monoclonal antibodies against IRS-1 and FAK proteins. Expression of IRS-1 was significantly higher in diabetic than normal rats, but it decreased in diabetic animals with tumor, especially in more advanced stages. FAK expression was significantly higher in rats with cancer in comparison to the ones without it, regardless the diabetes status. These data suggest that the IRS-1/FAK pathway is altered by diabetes resulting in reduced cell adhesion and possibly increasing risk for oral cancer.

Animals↗

PubMed2006

Cell proliferation and apoptosis culminate in early stages of oral oncogenesis.

Markers of cell proliferation (Ki-67 antigen) and apoptosis (Bax, Bcl-2) were studied in an experimental system of induced oral carcinogenesis in Syrian golden hamsters. Thirty-seven animals were divided into one control group and three experimental groups, which were treated with a carcinogen and sacrificed at 10, 14 and 19 weeks after treatment. The histological status of the lesions in the three experimental groups corresponded well with tumour advancement (from oral mucosal dysplasia to moderately differentiated squamous cell carcinoma). Tumour sections were studied using monoclonal antibodies against Bax, Bcl-2 and Ki-67 proteins. Pro-apoptotic Bax expression maintained high levels during all stages of oral carcinogenesis. Anti-apoptotic Bcl-2 expression decreased significantly in dysplastic and early invasion lesions and consequently increased almost to normal tissue level in consequent stages. Finally, Ki-67 expression increased sharply in initial stages of oral carcinogenesis, but significantly decreased in later stages.

Animals↗

PubMed2006

Intraoral lesions associated with sebaceous nevus syndrome.

The sebaceous nevus syndrome describes the rare association of a sebaceous nevus with systemic features such as mental retardation, seizures and colobomas (among others). It is thought to be a cutaneous mosaic inherited as a paradominant trait. Three cases are provided illustrating the intraoral manifestations of the syndrome. The first histological comparison of contiguous mucosal and cutaneous lesions is provided. We also describe the possible association of SFM syndrome with a benign fibrous histiocytic lesion of the mandible. This and other mandibular tumors associated with the sebaceous nevus syndrome may have significant implications for patients. Awareness of the potential presence or development of significant intraoral lesions in association with the sebaceous nevus syndrome is important for those involved in the care of patients with this syndrome.

Abnormalities, Multiple↗

PubMed2005

Innate immunity in human bone.

Bone has exceptional regenerative properties. Oral bone appears to be particularly resistant to infection despite exposure to oral flora, even in circumstances such as oral surgery where the thin mucosal layer covering the bone is disrupted. The goal of this study was to determine whether the innate immune system of antimicrobial peptides exists inside bone. Biopsies of non-infected and chronically infected mandibular bone were harvested from patients during maxillofacial surgical procedures. Bone biopsies from the iliac crest and fibula served as controls. Immunohistochemical staining was performed, directed against the human beta-defensin antimicrobial peptides (hBD) -1, -2 and -3. In addition, cultures of osteoblast-like cells were examined for the presence of each of the three beta-defensins and their mRNA transcripts. All three human beta-defensins were detected within the mineralized bone matrix of chronically infected mandibular bone in the vicinity of the endosteum and osteocytes. hBD-1, -2 and -3 were also found in the cytoplasm of osteocytes. Expression of all three beta-defensins was detected in each of the non-infected bone types including the controls, however, to a lesser degree than that found in the chronically infected mandibular bone. This may reflect upregulation of antimicrobial peptide expression in the presence of chronic infection. Cultures of non-infected osteoblast-like cells were found to express mRNA for each of hBD-1, -2 and -3. Immunohistochemical staining of the cultures was positive for hBD-1 and -2, but not for hBD-3. We provide the first evidence of a previously unrecognized innate immunological function of bone through the demonstration of the presence of the human beta-defensins hBD-1, -2 and -3 in bone.

Alkaline Phosphatase↗

PubMed2005

Heat shock induces the synthesis of the inflammatory mediator leukotriene B4 in human pulp cells.

AIM: To measure the synthesis of leukotriene B4 (LTB4) in cultures of human dental pulp cells induced by heat shock. METHODOLOGY: Primary pulp cells (PC) and dental pulp stem cells (DPSC) were cultivated under appropriate conditions. For the characterization of PC the expression of dentine sialophosphoprotein (DSPP) was evaluated by reverse transcription-polymerase chain reaction. Thermal stimulation of cell cultures was performed at temperatures of 37, 38, 39, 40, 42 and 45 degrees C for stimulation times of 5 and 30 s. LTB4 was quantified by reversed-phase high-performance chromatography and differences between the LTB4 concentrations of controls and heat stimulated cells were analysed with Friedman analysis of variances by ranks and multiple comparisons (P < 0.05). RESULTS: Both cell cultures expressed DSPP under the conditions of the present experiment. The analysis revealed significantly enhanced LTB4 synthesis following thermal stimulations at 38, 39, 40, 42 and 45 degrees C compared with unstimulated controls for both PC and DPSC. CONCLUSION: The present study demonstrated the capability of pulp cells to synthesize the arachidonic acid mediator LTB4 in response to heat shock. LTB4 has the capacity to induce inflammatory reactions and to sensitise afferent nociceptive nerve endings. LTB4 synthesis is induced by minor temperature changes, which are relevant for various clinical situations.

Cells, Cultured↗

PubMed2004

Prefabrication of vascularized bone grafts using recombinant human osteogenic protein-1--part 3: dosage of rhOP-1, the use of external and internal scaffolds.

In a previous study vascularized bone grafts were prefabricated with recombinant human osteogenic protein-1 (rhOP-1) using blocks of xenogenic bone mineral (BioOss) as scaffolds. The present study addressed the dosage of rhOP-1 and the combination of an external (mould) and internal scaffold (granular BioOss). In five Göttingen minipigs six prefabrication sites in the latissimus dorsi muscles were randomly assigned to groups a-f. Moulds were prepared by shaping collagen/polylactide membranes in a cylindrical form which was filled with 1g BioOss granules and rhOP-1 (a: 0; b: 50; c, f, e: 250; d: 1000 microg of rhOP-1, a-e: cylinder open to muscle, e cylinder perforated, f: cylinder open to subcutaneous fat). After 6 weeks a dose dependency of bone density (a-d: 0%; 9.4%; 15.8%; 31.1%) and vessel density (a-d: 0.3; 2.4; 7.9; 25.4 counts/view) was observed histomorphometrically. Muscular surrounding was advantageous to subcutaneous tissue. Perforations of the membranes increased vessel density and did not impair bone formation. Bone density decreased in the proximity of the polylactide membranes. The membrane material was too soft and partly collapsed and therefore needs not to be reconsidered. The use of BioOss granules with 1000 microg rhOP-1 per gram proved to be a suitable concept for prefabrication of bone transplants.

Absorbable Implants↗

PubMed1997

Antiinflammatory and antifibrotic properties of colchicine: implications for idiopathic pulmonary fibrosis.

The ancient drug colchicine has repeatedly been proposed as a novel drug for therapy of pulmonary fibrosis. The present study was undertaken to add to the knowledge on colchicine's antiinflammatory and antifibrotic properties and thus help determine its actual rank in the treatment of pulmonary fibrosis. In vitro cell culture experiments with stimulated and unstimulated normal donor peripheral blood mononuclear cells (PMNC) and a human lung fibroblast cell line (WI-38) were used to determine the effects of colchicine on PMNC cytokine release (interleukin-6 and tumor necrosis factor-alpha) as well as on fibroblast proliferation and collagen synthesis rates. Reverse transcriptase polymerase chain amplifications of alpha 1 (III) collagen were done to detect collagen messenger ribonucleic acid (mRNA) expression. Colchicine did not significantly modulate tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) release of PMNC. Colchicine inhibited fibroblast proliferation and total collagen synthesis significantly at concentrations obtainable in serum in vivo. Transcription of the alpha 1 (III) collagen gene into mRNA continued under colchicine. We conclude that colchicine is a potent in vitro inhibitor of fibroblast functions in terms of proliferation and collagen synthesis. The mechanism of collagen inhibition is more likely an inhibition of cellular collagen secretion than a switch off of collagen mRNA transcription. On the other hand, although colchicine is known to inhibit many leukocyte functions, it is a poor inhibitor of cytokines known to be important for fibrogenesis (e.g. IL-6, TNF-alpha, IL-1, platelet-derived growth factor, and transforming growth factor-beta). This makes colchicine, at least from a theoretical standpoint and as concluded from in vitro studies, a preferable candidate for a combined therapeutic strategy.

Cells, Cultured↗

PubMed1997

Glycosylation of human bone collagen I in relation to lysylhydroxylation and fibril diameter.

Posttranslational modifications (lysylhydroxylation, glycosylation, and crosslink formation) of collagen I and the trabecular bone volume (TBV) as well as the supramolecular organization of human vertebrae were studied by analyzing vertebral bones of 55 individuals (22-93 years of age). The degree of lysylhydroxylation of both a-chains of collagen I showed a significant inverse correlation with the TBV, while only a weak correlation between lysylhydroxylation of alpha2(I) and the age of the donor was observed. The degree of glycosylation of collagen I was significantly correlated with both the level of lysylhydroxylation and the degree of osteopenia. Electron microscopic evaluation did not show any relationship between the level of collagen glycosylation and the diameter of in vivo formed fibrils or in vitro formed fibrillar aggregates. In our study the molar ratio of the mature collagen crosslinks, pyridinoline and deoxypyridinoline, showed a slight tendency to be higher, in particular in the samples with a high level of lysylhydroxylation. This ratio was recently found to be significantly increased in avian osteoporotic bone. Our data suggest that the increased level of lysylhydroxylation in human osteopenia is related to the glycosylation of collagen I, while it seems to have little impact on the formation of the mature, non-reducible collagen crosslinks investigated. Based on our observations it appears unlikely that the different diameters of collagen fibrils contribute greatly to the reduced biomechanical stability reported for overhydroxylated, osteopenic bone tissue.

Adult↗

PubMed1995

Transforming growth factor beta 1 influences lysyl hydroxylation of collagen I and reduces steady-state levels of lysyl hydroxylase mRNA in human osteoblast-like cells.

Transforming growth factor beta 1 (TGF-beta 1) is an osteotropic growth factor that is found in substantial concentration in bone. The authors studied the influence of TGF-beta 1 on the modification of lysine residues of collagen I. The degree of lysyl hydroxylation and lysyl glycosylation of newly synthesized collagen as well as steady-state levels of mRNA for both lysyl hydroxylase and collagens I and III were determined in human osteoblast-like cells in vitro. In normal human osteoblasts lysyl hydroxylation was decreased by TGF-beta 1 particularly in the collagen alpha 2-chain. This effect was paralleled by an increase in lysyl residues, whereas glycosylation was not affected. The mRNA for lysyl hydroxylase was reduced by one-third under the influence of TGF-beta 1. Additionally, the mRNAs for both procollagen I alpha-chains were stimulated by TGF-beta 1, whereas pro alpha 1 (III)-mRNA showed a decrease. Changes in the local regulatory activity of TGF-beta 1 may play a role in matrix maturation such as collagen type production and lysyl hydroxylation, the latter being altered in various pathological conditions, e.g. in generalized osteopenia.

Adult↗

PubMed1994

A unique antigenic determinant on collagen II closely associated with age related abnormal modification.

During aging, a variety of proteins undergo a non-enzymatic modification, such as oxidation, attachment of lipid peroxide, and glycation. In particular, the long-lived extracellular matrix proteins in connective tissue may be common targets for this kind of modification which, in turn, is involved in the pathogenesis of age related diseases. In the present study, we demonstrate that the age related modification on collagen II generates (a) new epitope(s). Furthermore, we established an immunochemical assay which is specifically suited to monitor the extent of abnormal modification of collagen II.

Adolescent↗

PubMedDate not supplied

Growth and transplantation of a custom vascularised bone graft in a man.

BACKGROUND: A major goal of research in bone transplantation is the ability to avoid creation of secondary bone defects. We aimed to repair an extended mandibular discontinuity defect by growth of a custom bone transplant inside the latissimus dorsi muscle of an adult male patient. METHODS: Three-dimensional computed tomography (CT) scanning and computer-aided design techniques were used to produce an ideal virtual replacement for the mandibular defect. These data were used to create a titanium mesh cage that was filled with bone mineral blocks and infiltrated with 7 mg recombinant human bone morphogenetic protein 7 and 20 mL of the patient's bone marrow. Thus prepared, the transplant was implanted into the latissimus dorsi muscle and 7 weeks later transplanted as a free bone-muscle flap to repair the mandibular defect. FINDINGS: In-vivo skeletal scintigraphy showed bone remodelling and mineralisation inside the mandibular transplant both before and after transplantation. CT provided radiological evidence of new bone formation. Postoperatively, the patient had an improved degree of mastication and was satisfied with the aesthetic outcome of the procedure. INTERPRETATION: Heterotopic bone induction to form a mandibular replacement inside the latissimus dorsi muscle in a human being is possible. This technique allows for a lower operative burden compared with conventional techniques by avoiding creation of a secondary bone defect. It also provides a good three-dimensional outcome.

Activin Receptors, Type I↗

PubMedDate not supplied

Purification and substrate specificity of two cysteine proteinases of Giardia lamblia.

The proteinase activity present in homogenates of trophozoites of Giardia lamblia, active on azocasein and urea-denaturated hemoglobin, was separated into two different enzymes by a series of purification procedures. These procedures included gel filtration on Fractogel TSK HW-55 (F), organomercurial agarose affinity chromatography, and ion exchange chromatography on DEAE-cellulose. By chromatography on Sephadex G-100, two purified enzymes exhibited relative molecular weights of Mr = 95,000 and 35,000 +/- 10%, respectively. On the basis of inhibition by thiol reagents and abrogation of this effect by dithiothreitol and cysteine, they were identified as cysteine proteinases. Proteinase I (Mr = 95,000) and proteinase II (Mr = 35,000) were active against the beta-chain of insulin releasing characteristic fragments. However, differences in substrate specificities of the two enzymes could be observed by using synthetic peptides that represent sequences 1-6, 8-18, and 20-30 of the insulin beta-chain. Furthermore, the synthetic tetrapeptides Arg-Gly-Phe-Phe, Arg-Gly-Leu-Hyp, and Arg-Arg-Phe-Phe were hydrolyzed by the two proteinases releasing Phe-Phe and Leu-Hyp, respectively. Compared with Arg-Gly-Phe-Phe, the rates of hydrolysis of Arg-Gly-Leu-Hyp and Arg-Arg-Phe-Phe at substrate concentrations of 1 mM were 91% and 63% (proteinase I) and 80% and 57% (proteinase II), respectively.

Amino Acid Sequence↗