WorldWideScience

Sample records for connective tissue progenitor

  1. Connective tissue cells expressing fibro/adipogenic progenitor markers increase under chronic damage: relevance in fibroblast-myofibroblast differentiation and skeletal muscle fibrosis.

    Science.gov (United States)

    Contreras, Osvaldo; Rebolledo, Daniela L; Oyarzún, Juan Esteban; Olguín, Hugo C; Brandan, Enrique

    2016-06-01

    Fibrosis occurs in skeletal muscle under various pathophysiological conditions such as Duchenne muscular dystrophy (DMD), a devastating disease characterized by fiber degeneration that results in progressive loss of muscle mass, weakness and increased extracellular matrix (ECM) accumulation. Fibrosis is also observed after skeletal muscle denervation and repeated cycles of damage followed by regeneration. The ECM is synthesized largely by fibroblasts in the muscle connective tissue under normal conditions. Myofibroblasts, cells that express α-smooth muscle actin (α-SMA), play a role in many tissues affected by fibrosis. In skeletal muscle, fibro/adipogenic progenitors (FAPs) that express cell-surface platelet-derived growth factor receptor-α (PDGFR-α) and the transcription factor Tcf4 seem to be responsible for connective tissue synthesis and are good candidates for the origin of myofibroblasts. We show that cells positive for Tcf4 and PDGFR-α are expressed in skeletal muscle under normal conditions and are increased in various skeletal muscles of mdx mice, a murine model for DMD, wild type muscle after sciatic denervation and muscle subjected to chronic damage. These cells co-label with the myofibroblast marker α-SMA in dystrophic muscle but not in normal tissue. The Tcf4-positive cells lie near macrophages mainly concentrated in dystrophic necrotic-regenerating foci. The close proximity of Tcf4-positive cells to inflammatory cells and their previously described role in muscle regeneration might reflect an active interaction between these cell types and growth factors, possibly resulting in a muscular regenerative or fibrotic condition.

  2. Assessment of Methods for Rapid Intraoperative Concentration and Selection of Marrow-Derived Connective Tissue Progenitors for Bone Regeneration Using the Canine Femoral Multidefect Model

    Science.gov (United States)

    Luangphakdy, Viviane; Boehm, Cynthia; Pan, Hui; Herrick, James; Zaveri, Phil

    2016-01-01

    Treatment of large bone defects remains an unsolved clinical challenge, despite a wide array of existing bone graft materials and strategies. Local deficiency in osteogenic connective tissue progenitors (CTP-Os) due to tissue loss is one of the central biological barriers to bone regeneration. Density separation (DS) and selective retention (SR) represent two promising methods that can be used intraoperatively to rapidly concentrate cells and potentially select CTP-Os. This project was designed to compare DS and SR using the canine femoral multidefect (CFMD) model. Mineralized cancellous allograft (MCA) was used as a standardized scaffold for cell transplantation. Two experiments were performed using a cohort of six animals in each comparison. In Cohort I, unprocessed bone marrow aspirate (BMA) clot was compared to DS processing. MCA combined with raw BMA or DS processed cells produced a robust and advanced stage of bone regeneration throughout the defect in 4 weeks with reconstitution of hematopoietic marrow. However, the retention of DS processed cells and CTP-Os in the MCA matrix was low compared to BMA clot. In Cohort II, MCA with DS-T cells (addition of calcium chloride thrombin to induce clotting and enhance cell and CTP-O retention) was compared to MCA with SR cells. A mean of 276 ± 86 million nucleated cells and 29,030 ± 10,510 CTP-Os were implanted per defect in the DS-T group. A mean of 76 ± 42 million nucleated cells and 30,266 ± 15,850 CTP-Os were implanted in the SR group. Bone formation was robust and not different between treatments. Histologically, both groups demonstrated regeneration of hematopoietic marrow tissue. However, SR sites contained more hematopoietic vascular tissues, less fibrosis, and less residual allograft, particularly in the intramedullary cavity, suggesting a more advanced stage of remodeling (p = 0.04). These data demonstrate excellent overall performance of DS and SR processing methods. Both methods

  3. Skeletal muscle connective tissue

    DEFF Research Database (Denmark)

    Brüggemann, Dagmar Adeline

    that collagen plays a significant role in determining the tenderness of meat. What are we missing? Therefore, fundamental aspects of connective tissue research have been the centre of attention throughout this thesis. A holistic view has been applied, glancing at this complex tissue which has many facets......  The connective tissue content of skeletal muscle is believed to be the major factor responsible for defining the eating quality of different meat cuts, although attempts to correlate quantifications based on traditional histological methods have not as yet been able to prove this relation....... Collagen, being the major protein in connective tissue, has been extensively investigated with regard to its relation to meat tenderness, but the results have been rather conflicting. Meat from older animals is tougher than that from younger animals, and changes in the properties of the collagen due...

  4. Skeletal muscle connective tissue

    DEFF Research Database (Denmark)

    Brüggemann, Dagmar Adeline

      The connective tissue content of skeletal muscle is believed to be the major factor responsible for defining the eating quality of different meat cuts, although attempts to correlate quantifications based on traditional histological methods have not as yet been able to prove this relation...... that collagen plays a significant role in determining the tenderness of meat. What are we missing? Therefore, fundamental aspects of connective tissue research have been the centre of attention throughout this thesis. A holistic view has been applied, glancing at this complex tissue which has many facets...... in this thesis that alpha-ketoglutarate, a tricarboxylic acid cycle metabolite, has the potential to control the metabolism of this particular tissue. Finally, a new microscopic method is introduced which allows the study of thermal denaturation of fibrillar collagen and myofibers in real time without any label...

  5. Mixed Connective Tissue Disease

    Science.gov (United States)

    ... complicated. Early signs and symptoms often involve the hands. Fingers might swell like sausages, and the fingertips become white and numb. In later stages, some organs — such as the lungs, heart and kidneys — may be affected. There's no cure for mixed connective tissue disease. The signs and ...

  6. Mixed connective tissue disease.

    Science.gov (United States)

    Gunnarsson, Ragnar; Hetlevik, Siri Opsahl; Lilleby, Vibke; Molberg, Øyvind

    2016-02-01

    The concept of mixed connective tissue disease (MCTD) as a separate connective tissue disease (CTD) has persisted for more than four decades. High titers of antibodies targeting the U1 small nuclear ribonucleoprotein particle (U1 snRNP) in peripheral blood are a sine qua non for the diagnosis of MCTD, in addition to distinct clinical features including Raynaud's phenomenon (RP), "puffy hands," arthritis, myositis, pleuritis, pericarditis, interstitial lung disease (ILD), and pulmonary hypertension (PH). Recently, population-based epidemiology data from Norway estimated the point prevalence of adult-onset MCTD to be 3.8 per 100,000 and the mean annual incidence to be 2.1 per million per year, supporting the notion that MCTD is the least common CTD. Little is known about the etiology of MCTD, but recent genetic studies have confirmed that MCTD is a strongly HLA (​human leukocyte antigen)-linked disease, as the HLA profiles of MCTD differ distinctly from the corresponding profiles of ethnically matched healthy controls and other CTDs. In the first section of this review, we provide an update on the clinical, immunological, and genetic features of MCTD and discuss the relationship between MCTD and the other CTDs. Then we proceed to discuss the recent advances in therapy and our current understanding of prognosis and prognostic factors, especially those that are associated with the more serious pulmonary and cardiovascular complications of the disease. In the final section, we discuss some of the key, unresolved questions related to anti-RNP-associated diseases and indicate how these questions may be approached in future studies. Copyright © 2016. Published by Elsevier Ltd.

  7. Induced pluripotent stem cell-derived cardiac progenitors differentiate to cardiomyocytes and form biosynthetic tissues.

    Directory of Open Access Journals (Sweden)

    Nicolas Christoforou

    Full Text Available The mammalian heart has little capacity to regenerate, and following injury the myocardium is replaced by non-contractile scar tissue. Consequently, increased wall stress and workload on the remaining myocardium leads to chamber dilation, dysfunction, and heart failure. Cell-based therapy with an autologous, epigenetically reprogrammed, and cardiac-committed progenitor cell source could potentially reverse this process by replacing the damaged myocardium with functional tissue. However, it is unclear whether cardiac progenitor cell-derived cardiomyocytes are capable of attaining levels of structural and functional maturity comparable to that of terminally-fated cardiomyocytes. Here, we first describe the derivation of mouse induced pluripotent stem (iPS cells, which once differentiated allow for the enrichment of Nkx2-5(+ cardiac progenitors, and the cardiomyocyte-specific expression of the red fluorescent protein. We show that the cardiac progenitors are multipotent and capable of differentiating into endothelial cells, smooth muscle cells and cardiomyocytes. Moreover, cardiac progenitor selection corresponds to cKit(+ cell enrichment, while cardiomyocyte cell-lineage commitment is concomitant with dual expression of either cKit/Flk1 or cKit/Sca-1. We proceed to show that the cardiac progenitor-derived cardiomyocytes are capable of forming electrically and mechanically coupled large-scale 2D cell cultures with mature electrophysiological properties. Finally, we examine the cell progenitors' ability to form electromechanically coherent macroscopic tissues, using a physiologically relevant 3D culture model and demonstrate that following long-term culture the cardiomyocytes align, and form robust electromechanical connections throughout the volume of the biosynthetic tissue construct. We conclude that the iPS cell-derived cardiac progenitors are a robust cell source for tissue engineering applications and a 3D culture platform for pharmacological

  8. Undiagnosed connective tissue diseases

    Science.gov (United States)

    Cavagna, Lorenzo; Codullo, Veronica; Ghio, Stefano; Scirè, Carlo Alberto; Guzzafame, Eleonora; Scelsi, Laura; Rossi, Silvia; Montecucco, Carlomaurizio; Caporali, Roberto

    2016-01-01

    Abstract Among different subgroups of pulmonary arterial hypertension (PAH), those associated with connective tissue diseases (CTDs) have distinct hemodynamic and prognostic features; a correct etiologic diagnosis is thus mandatory. To estimate frequency and prognosis of previously undiagnosed CTDs in a suspect idiopathic (i) PAH cohort. Consecutive patients with PAH confirmed by right heart catheterization referred at the Cardiology Division of our Hospital without a previous rheumatological assessment or the occurrence of other conditions explaining PAH were checked for CTD by a clinical, laboratory, and instrumental evaluation. Survival in each group has also been analyzed. In our study 17 of 49 patients were classified as CTD-PAH, corresponding to a prevalence (95% CI) of 34.7% (21.7–49.6%). ANA positivity had 94% (71.3–99.9%) sensitivity and 78.1% (60–90.7%) specificity for a diagnosis of CTD-PAH; Raynaud phenomenon (RP) showed 83.3% (51.6–97.9%) sensitivity and 100% (90.5–100%) specificity for the diagnosis of Systemic Sclerosis (SSc)-PAH. At diagnosis, SSc patients were older and had a lower creatinine clearance compared with iPAH and other CTD-PAH. After a median follow-up of 44 (2–132) months, 18 of 49 (36.7%) patients died: 31.2% in the iPAH group, 20% in the CTD-, and 58.3% in the SSc-PAH group. Mortality was significantly higher in SSc-PAH (HR 3.32, 1.11–9.95, P <0.05) versus iPAH. We show a high prevalence of undiagnosed CTDs in patients with iPAH without a previous rheumatological assessment. All patients with RP were diagnosed with SSc. Our data stress the importance of a rheumatological assessment in PAH, especially because of the unfavorable prognostic impact of an associated SSc. PMID:27684814

  9. Heritable Disorders of Connective Tissue

    Science.gov (United States)

    ... skin. Epidermolysis bullosa affects the skin, causing blisters. Marfan syndrome can affect the heart, blood vessels, lungs, eyes, ... Disorders of Connective Tissue, Questions and Answers about Marfan Syndrome, Questions and Answers about Marfan Syndrome, Easy-to- ...

  10. Tissue engineering bone using autologous progenitor cells in the peritoneum.

    Science.gov (United States)

    Shen, Jinhui; Nair, Ashwin; Saxena, Ramesh; Zhang, Cheng Cheng; Borrelli, Joseph; Tang, Liping

    2014-01-01

    Despite intensive research efforts, there remains a need for novel methods to improve the ossification of scaffolds for bone tissue engineering. Based on a common phenomenon and known pathological conditions of peritoneal membrane ossification following peritoneal dialysis, we have explored the possibility of regenerating ossified tissue in the peritoneum. Interestingly, in addition to inflammatory cells, we discovered a large number of multipotent mesenchymal stem cells (MSCs) in the peritoneal lavage fluid from mice with peritoneal catheter implants. The osteogenic potential of these peritoneal progenitor cells was demonstrated by their ability to easily infiltrate decalcified bone implants, produce osteocalcin and form mineralized bone in 8 weeks. Additionally, when poly(l-lactic acid) scaffolds loaded with bone morphogenetic protein-2 (a known osteogenic differentiation agent) were implanted into the peritoneum, signs of osteogenesis were seen within 8 weeks of implantation. The results of this investigation support the concept that scaffolds containing BMP-2 can stimulate the formation of bone in the peritoneum via directed autologous stem and progenitor cell responses.

  11. Effect of ionizing radiations on connective tissue

    International Nuclear Information System (INIS)

    Altman, K.I.; Gerber, G.B.

    1980-01-01

    The effects of ionizing radiations on connective tissue in lung, heart, vasculature, kidney, skin, and skeletal tissues are reviewed. Special emphasis is given to the effect of ionizing radiations on vasculo-connective tissue and fibrotic changes following radiation-induced injury to organs and tissues. In order to put the subject matter in proper prospective, the general biochemistry, physiology, and pathology of connective tissue is reviewed briefly together with the participation of connective tissue in disease. The review closes with an assessment of future problems and an enumeration and discussion of important, as yet unanswered questions

  12. Radiotherapy in patients with connective tissue diseases.

    Science.gov (United States)

    Giaj-Levra, Niccolò; Sciascia, Savino; Fiorentino, Alba; Fersino, Sergio; Mazzola, Rosario; Ricchetti, Francesco; Roccatello, Dario; Alongi, Filippo

    2016-03-01

    The decision to offer radiotherapy in patients with connective tissue diseases continues to be challenging. Radiotherapy might trigger the onset of connective tissue diseases by increasing the expression of self-antigens, diminishing regulatory T-cell activity, and activating effectors of innate immunity (dendritic cells) through Toll-like receptor-dependent mechanisms, all of which could potentially lead to breaks of immune tolerance. This potential risk has raised some debate among radiation oncologists about whether patients with connective tissue diseases can tolerate radiation as well as people without connective tissue diseases. Because the number of patients with cancer and connective tissue diseases needing radiotherapy will probably increase due to improvements in medical treatment and longer life expectancy, the issue of interactions between radiotherapy and connective tissue diseases needs to be clearer. In this Review, we discuss available data and evidence for patients with connective tissue diseases treated with radiotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Immuno-Magnetic Isolation and Thermogenic Differentiation of White Adipose Tissue Progenitor Cells.

    Science.gov (United States)

    Babaei, Rohollah; Bayindir-Buchhalter, Irem; Meln, Irina; Vegiopoulos, Alexandros

    2017-01-01

    Appropriate cell models are necessary for the investigation of thermogenic beige adipocyte differentiation from progenitor cells. Here, we describe a primary cell culture method that is based on defined progenitor cells from murine white adipose tissue and aims at minimizing confounding factors including cell heterogeneity and nonphysiological differentiation inducers. Adipocyte progenitor cells are enriched by immuno-magnetic separation, expanded minimally, and induced for beige adipocyte differentiation with carbaprostacyclin, a stable analogue of the endogenous mediator PGI 2 .

  14. Mesenchymal Stromal Cells and Tissue-Specific Progenitor Cells: Their Role in Tissue Homeostasis

    Directory of Open Access Journals (Sweden)

    Aleksandra Klimczak

    2016-01-01

    Full Text Available Multipotent mesenchymal stromal/stem cells (MSCs reside in many human organs and comprise heterogeneous population of cells with self-renewal ability. These cells can be isolated from different tissues, and their morphology, immunophenotype, and differentiation potential are dependent on their tissue of origin. Each organ contains specific population of stromal cells which maintain regeneration process of the tissue where they reside, but some of them have much more wide plasticity and differentiate into multiple cells lineage. MSCs isolated from adult human tissues are ideal candidates for tissue regeneration and tissue engineering. However, MSCs do not only contribute to structurally tissue repair but also MSC possess strong immunomodulatory and anti-inflammatory properties and may influence in tissue repair by modulation of local environment. This paper is presenting an overview of the current knowledge of biology of tissue-resident mesenchymal stromal and progenitor cells (originated from bone marrow, liver, skeletal muscle, skin, heart, and lung associated with tissue regeneration and tissue homeostasis.

  15. Tissue Myeloid Progenitors Differentiate into Pericytes through TGF-β Signaling in Developing Skin Vasculature

    Directory of Open Access Journals (Sweden)

    Tomoko Yamazaki

    2017-03-01

    Full Text Available Mural cells (pericytes and vascular smooth muscle cells are essential for the regulation of vascular networks and maintenance of vascular integrity, but their origins are diverse in different tissues and not known in the organs that arise from the ectoderm, such as skin. Here, we show that tissue-localized myeloid progenitors contribute to pericyte development in embryonic skin vasculature. A series of in vivo fate-mapping experiments indicates that tissue myeloid progenitors differentiate into pericytes. Furthermore, depletion of tissue myeloid cells and their progenitors in PU.1 (also known as Spi1 mutants results in defective pericyte development. Fluorescence-activated cell sorting (FACS-isolated myeloid cells and their progenitors from embryonic skin differentiate into pericytes in culture. At the molecular level, transforming growth factor-β (TGF-β induces pericyte differentiation in culture. Furthermore, type 2 TGF-β receptor (Tgfbr2 mutants exhibit deficient pericyte development in skin vasculature. Combined, these data suggest that pericytes differentiate from tissue myeloid progenitors in the skin vasculature through TGF-β signaling.

  16. Poised Regeneration of Zebrafish Melanocytes Involves Direct Differentiation and Concurrent Replenishment of Tissue-Resident Progenitor Cells.

    Science.gov (United States)

    Iyengar, Sharanya; Kasheta, Melissa; Ceol, Craig J

    2015-06-22

    Efficient regeneration following injury is critical for maintaining tissue function and enabling organismal survival. Cells reconstituting damaged tissue are often generated from resident stem or progenitor cells or from cells that have dedifferentiated and become proliferative. While lineage-tracing studies have defined cellular sources of regeneration in many tissues, the process by which these cells execute the regenerative process is largely obscure. Here, we have identified tissue-resident progenitor cells that mediate regeneration of zebrafish stripe melanocytes and defined how these cells reconstitute pigmentation. Nearly all regeneration melanocytes arise through direct differentiation of progenitor cells. Wnt signaling is activated prior to differentiation, and inhibition of Wnt signaling impairs regeneration. Additional progenitors divide symmetrically to sustain the pool of progenitor cells. Combining direct differentiation with symmetric progenitor divisions may serve as a means to rapidly repair injured tissue while preserving the capacity to regenerate. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Connective Tissue Disease in a Malawian Man

    African Journals Online (AJOL)

    31Ward Round 2. Introduction. We describe a case of systemic connective tissue disease (CTD) in a Malawian man in whom an autoimmune etiology was likely. Autoimmune CTDs ... Case Presentantion. A 17 year-old student was referred to Queen Elizabeth ... X rays of the hands are shown in Figure 2. The most striking.

  18. Expansion of Adult Human Pancreatic Tissue Yields Organoids Harboring Progenitor Cells with Endocrine Differentiation Potential

    Directory of Open Access Journals (Sweden)

    Cindy J.M. Loomans

    2018-03-01

    Full Text Available Summary: Generating an unlimited source of human insulin-producing cells is a prerequisite to advance β cell replacement therapy for diabetes. Here, we describe a 3D culture system that supports the expansion of adult human pancreatic tissue and the generation of a cell subpopulation with progenitor characteristics. These cells display high aldehyde dehydrogenase activity (ALDHhi, express pancreatic progenitors markers (PDX1, PTF1A, CPA1, and MYC, and can form new organoids in contrast to ALDHlo cells. Interestingly, gene expression profiling revealed that ALDHhi cells are closer to human fetal pancreatic tissue compared with adult pancreatic tissue. Endocrine lineage markers were detected upon in vitro differentiation. Engrafted organoids differentiated toward insulin-positive (INS+ cells, and circulating human C-peptide was detected upon glucose challenge 1 month after transplantation. Engrafted ALDHhi cells formed INS+ cells. We conclude that adult human pancreatic tissue has potential for expansion into 3D structures harboring progenitor cells with endocrine differentiation potential. : In the context of β cell replacement therapy for diabetes, de Koning and colleagues describe a 3D culture platform that supports ex vivo expansion of human pancreatic tissue as organoids. These organoids harbor a subpopulation of ALDHhi cells that display proliferative capacity and can differentiate to an endocrine fate. Keywords: pancreas, organoid, human, ALDH, endocrine differentiation, beta cells, insulin, progenitor, fetal, diabetes

  19. Connective tissue: Vascular and hematological (blood) support.

    Science.gov (United States)

    Calvino, Nick

    2003-01-01

    Connective Tissue (CT) is a ubiquitous component of all major tissues and structures of the body (50% of all body protein is CT), including that of the blood, vascular, muscle, tendon, ligament, fascia, bone, joint, IVD's (intervertebral discs) and skin. Because of its ubiquitous nature, CT is an often overlooked component of any essential nutritional program that may address the structure, and/or function of these tissues. The central role of CT in the health of a virtually all cells, tissues, organs, and organ systems, is discussed. General nutritional CT support strategies, as well as specific CT support strategies that focus on blood, vascular, structural system (eg, muscles, tendons, ligaments, fascia, bone, and joints), integument (skin) and inflammatory and immune mediation will be discussed here and will deal with connective tissue dynamics and dysfunction. An overview of the current scientific understanding and possible options for naturally enhancing the structure and function of CT through the application of these concepts will be discussed in this article, with specific attention on the vascular and hematological systems.

  20. Ischemic tissue injury and progenitor cell tropism: significant contributors to the pathogenesis of pterygium.

    Science.gov (United States)

    Kim, Kyoung Woo; Ha, Hyo Shin; Kim, Jae Chan

    2015-03-01

    Pterygium is a common ocular surface disease characterized by triangular wing-like growth consisting of subconjunctival hypertrophic connective tissue. Pterygium is easily complicated by adhesion to the eyelid and diplopia related to motility restriction of the eyeball. Beyond the cosmetic problems, this condition has a catastrophic effect on quality of life. Post-surgical recurrence rates of pterygium excision have been reported to be very high. Therefore, identifying the distinct pathogenic pathways of the disease may lead to new therapeutic strategies with lower risk of treatment failure. Based on the relatively low vascularity and known-predominance of disease occurrence in the nasal conjunctiva of normal eyes, we proposed that hypoxic ischemic injury can elicit the development of pterygium. Here, we review hypoxia-inducible factor (HIF)-1alpha-induced activation of the stromal cell-derived factor-1 (SDF-1)/chemokine receptor type 4 (CXCR4) signaling pathway as a possible mechanism. Supporting this concept of pathogenic mechanism, we also highlight bone marrow-derived progenitor cell tropism as a main contributor to pterygium pathogenesis.

  1. The Progenitor-Remnant Connection of Neutrino-Driven Supernovae Across the Stellar Mass Range

    Science.gov (United States)

    Ertl, Thomas

    2017-11-01

    We perform hydrodynamic supernova (SN) simulations in spherical symmetry for progenitor models with solar metallicity across the stellar mass range from 9.0 to 120 M ⊙ to explore the progenitor-explosion and progenitor-remnant connections based on the neutrino-driven mechanism. We use an approximative treatment of neutrino transport and replace the high-density interior of the neutron star (NS) by an inner boundary condition based on an analytic proto-NS core-cooling model, whose free parameters are chosen to reproduce the observables of SN 1987A and the Crab SN for theoretical models of their progenitor stars. Judging the fate of a massive star, either a neutron star (NS) or a black hole (BH), solely by its structure prior to collapse has been ambiguous. Our work and previous attempts find a non-monotonic variation of successful and failed supernovae with zero-age main-sequence mass. We identify two parameters based on the ``critical luminosity'' concept for neutrino-driven explosions, which in combination allows for a clear separation of exploding and non-exploding cases. Continuing our simulations beyond shock break-out, we are able to determine nucleosynthesis, light curves, explosion energies, and remnant masses. The resulting NS initial mass function has a mean gravitational mass near 1.4 M ⊙. The average BH mass is about 9 M ⊙ if only the helium core implodes, and 14 M ⊙ if the entire pre-SN star collapses. Only ~10% of SNe come from stars over 20 M ⊙, and some of these are Type Ib or Ic.

  2. BIOCOMPATIBILITY OF AZITROMICYN ON CONNECTIVE TISSUE

    Directory of Open Access Journals (Sweden)

    Shafira Kurnia

    2011-01-01

    Full Text Available Background: periodontal disease is commonly caused by bacteria, especially actinomyces actinomycetemcomitans and porphyromonas gingivalis have an abilty enter epithelial cells objectives: to investigate systemic azithromycin as the antibiotic of choice for periodontal disease based on biocomptability test in connective tissue. Material and Methods: BHK 21 cell lines were exposed to 0.025%, 0.050%, 0.075%, and 0.1% azithromycin solution for seven times. Samples were put in incubator for 24 hours. Result: Azitrromycin 0.050%-0.1% showed significant difference between life cells percentage and control, however, azithromycin 0.025% revealed insignificant difference with control. Conclusion: 0.025% azithromycin was considered biocompatible with connective tissue and 0.050% was not.

  3. Pregnancy and autoimmune connective tissue diseases

    Science.gov (United States)

    Marder, Wendy; Littlejohn, Emily A

    2016-01-01

    The autoimmune connective tissue diseases predominantly affect women and often occur during the reproductive years. Thus, specialized issues in pregnancy planning and management are commonly encountered in this patient population. This chapter provides a current overview of pregnancy as a risk factor for onset of autoimmune disease, considerations related to the course of pregnancy in several autoimmune connective tissue diseases, and disease management and medication issues before and during pregnancy and the postpartum period. A major theme that has emerged across these inflammatory diseases is that active maternal disease during pregnancy is associated with adverse pregnancy outcomes, and that maternal and fetal health can be optimized when conception is planned during times of inactive disease and through maintaining treatment regimens compatible with pregnancy. PMID:27421217

  4. Radiological approach to systemic connective tissue diseases

    Energy Technology Data Exchange (ETDEWEB)

    Wiesmann, W.; Schneider, M.

    1988-07-01

    Systemic lupus erythematosus (SLE) and progressive systemic sclerosis (PSS) represent the most frequent manifestations of systemic connective tissue diseases (collagen diseases). Radiological examinations are employed to estimate the extension and degree of the pathological process. In addition, progression of the disease can be verified. In both of the above collagen diseases, specific radiological findings can be observed that permit them to be differentiated from other entities. An algorithm for the adequate radiological work-up of collagen diseases is presented.

  5. Autonomous informational stability in connective tissues.

    Science.gov (United States)

    Brand, R A

    1992-02-01

    No coherent theories currently explain connective tissue stability (i.e. 'memory') as well as spatial and temporal adaptability in the face of continual flux of its constituents. Furthermore, explanations of stability based exclusively upon DNA raise certain inherent problems, particularly with the spatial concordance of somatic tissues. As an alternative explanation, it is hypothesized that while connective tissue cells produce extracellular protein precursors through DNA-dependent processes, the assembly, location, orientation and configuration of the extracellular macromolecules as well as their degree of cell attachment depend primarily upon local micro-environmental conditions and/or self-organization rather than strictly cellular processes. The resulting extracellular matrix (ECM) serves as a time- and spatially-variable filter about each cell to afford a relatively consistent micro-environment for all similar cells, regardless of the more variable macro-environment. By insuring a consistent set of signals to the cell, the filter provides a non-genetic memory complementary to genetic memory. The half-lives of constituent molecules define the duration of the filter, allowing the filter to adapt to new environmental demands, yet to maintain a consistent milieu for the cell. The cell/matrix construct permits local, self-optimizing, non-deterministic tissue autonomy obviating the need to postulate certain intricate mechanisms coordinating spatial morphology and temporal behavior.

  6. Soft tissue engineering with micronized-gingival connective tissues.

    Science.gov (United States)

    Noda, Sawako; Sumita, Yoshinori; Ohba, Seigo; Yamamoto, Hideyuki; Asahina, Izumi

    2018-01-01

    The free gingival graft (FGG) and connective tissue graft (CTG) are currently considered to be the gold standards for keratinized gingival tissue reconstruction and augmentation. However, these procedures have some disadvantages in harvesting large grafts, such as donor-site morbidity as well as insufficient gingival width and thickness at the recipient site post-treatment. To solve these problems, we focused on an alternative strategy using micronized tissue transplantation (micro-graft). In this study, we first investigated whether transplantation of micronized gingival connective tissues (MGCTs) promotes skin wound healing. MGCTs (≤100 µm) were obtained by mincing a small piece (8 mm 3 ) of porcine keratinized gingiva using the RIGENERA system. The MGCTs were then transplanted to a full skin defect (5 mm in diameter) on the dorsal surface of immunodeficient mice after seeding to an atelocollagen matrix. Transplantations of atelocollagen matrixes with and without micronized dermis were employed as experimental controls. The results indicated that MGCTs markedly promote the vascularization and epithelialization of the defect area 14 days after transplantation compared to the experimental controls. After 21 days, complete wound closure with low contraction was obtained only in the MGCT grafts. Tracking analysis of transplanted MGCTs revealed that some mesenchymal cells derived from MGCTs can survive during healing and may function to assist in wound healing. We propose here that micro-grafting with MGCTs represents an alternative strategy for keratinized tissue reconstruction that is characterized by low morbidity and ready availability. © 2017 Wiley Periodicals, Inc.

  7. Aging of tissue-resident adult stem/progenitor cells and their pathological consequences.

    Science.gov (United States)

    Mimeault, M; Batra, S K

    2009-06-01

    The fascinating discovery of tissue-resident adult stem/progenitor cells in recent years led to an explosion of interest in the development of novel stem cell-based therapies for improving the regenerative capacity of these endogenous immature cells or transplanted cells for the repair of damaged and diseased tissues. In counterbalance, a growing body of evidence has revealed that the changes in phenotypic and functional properties of human adult stem/progenitor cells may occur during chronological aging and have severe pathological consequences. Especially, intense oxidative and metabolic stress and chronic inflammation, enhanced telomere attrition and defects in DNA repair mechanisms may lead to severe DNA damages and genomic instability in adult stem/progenitor cells with advancing age that may in turn trigger their replicative senescence and/or programmed cell death. Moreover, the changes in the intrinsic and extrinsic factors involved in the stringent control of self-renewal and multilineage differentiation capacities of these regenerative cells, including deregulated signals from the aged niche, may also contribute to their dysfunctions or loss during chronological aging. This age-associated decline in the regenerative capacity and number of functional adult stem/progenitor cells may increase the risk to develop certain diseases. At opposed end, the telomerase reactivation and accumulation of genetic alterations leading to a down-regulation of numerous tumor suppressor genes concomitant with the enhanced expression of diverse oncogenic products may result in their malignant transformation into cancer-initiating cells. Therefore, the rescue or replacement of aged and dysfunctional endogenous adult stem/progenitor cells or molecular targeting of their malignant counterpart, cancer stem/progenitor cells may constitute potential anti-aging and cancer therapies. These therapeutic strategies could be used for treating diverse devastating premature aging and age

  8. Connective Tissue Disorder-Associated Vasculitis.

    Science.gov (United States)

    Sharma, Aman; Dhooria, Aadhaar; Aggarwal, Ashish; Rathi, Manish; Chandran, Vinod

    2016-06-01

    Vasculitides secondary to connective tissue diseases are classified under the category of 'vasculitis associated with systemic disease' in the revised International Chapel Hill Consensus Conference (CHCC) nomenclature. These secondary vasculitides may affect any of the small, medium or large vessels and usually portend a poor prognosis. Any organ system can be involved and the presentation would vary depending upon that involvement. Treatment depends upon the type and severity of presentation. In this review, we describe secondary vasculitis associated with rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, relapsing polychondritis, systemic sclerosis, Sjogren's syndrome and idiopathic inflammatory myositis, focusing mainly on recent advances in the past 3 years.

  9. Synergistic actions of hematopoietic and mesenchymal stem/progenitor cells in vascularizing bioengineered tissues.

    Directory of Open Access Journals (Sweden)

    Eduardo K Moioli

    Full Text Available Poor angiogenesis is a major road block for tissue repair. The regeneration of virtually all tissues is limited by angiogenesis, given the diffusion of nutrients, oxygen, and waste products is limited to a few hundred micrometers. We postulated that co-transplantation of hematopoietic and mesenchymal stem/progenitor cells improves angiogenesis of tissue repair and hence the outcome of regeneration. In this study, we tested this hypothesis by using bone as a model whose regeneration is impaired unless it is vascularized. Hematopoietic stem/progenitor cells (HSCs and mesenchymal stem/progenitor cells (MSCs were isolated from each of three healthy human bone marrow samples and reconstituted in a porous scaffold. MSCs were seeded in micropores of 3D calcium phosphate (CP scaffolds, followed by infusion of gel-suspended CD34(+ hematopoietic cells. Co-transplantation of CD34(+ HSCs and CD34(- MSCs in microporous CP scaffolds subcutaneously in the dorsum of immunocompromised mice yielded vascularized tissue. The average vascular number of co-transplanted CD34(+ and MSC scaffolds was substantially greater than MSC transplantation alone. Human osteocalcin was expressed in the micropores of CP scaffolds and was significantly increased upon co-transplantation of MSCs and CD34(+ cells. Human nuclear staining revealed the engraftment of transplanted human cells in vascular endothelium upon co-transplantation of MSCs and CD34(+ cells. Based on additional in vitro results of endothelial differentiation of CD34(+ cells by vascular endothelial growth factor (VEGF, we adsorbed VEGF with co-transplanted CD34(+ and MSCs in the microporous CP scaffolds in vivo, and discovered that vascular number and diameter further increased, likely owing to the promotion of endothelial differentiation of CD34(+ cells by VEGF. Together, co-transplantation of hematopoietic and mesenchymal stem/progenitor cells may improve the regeneration of vascular dependent tissues such as bone

  10. Connective Tissue Degeneration: Mechanisms of Palmar Fascia Degeneration (Dupuytren's Disease)

    NARCIS (Netherlands)

    Karkampouna, S.; Kreulen, M.; Obdeijn, M. C.; Kloen, P.; Dorjée, A. L.; Rivellese, F.; Chojnowski, A.; Clark, I.; Kruithof-de Julio, Marianna

    2016-01-01

    Dupuytren's disease is a connective tissue disorder of the hand causing excessive palmar fascial fibrosis with associated finger contracture and disability. The aetiology of the disease is heterogeneous, with both genetic and environmental components. The connective tissue is abnormally infiltrated

  11. Histological properties of intramuscular connective tissues in native ...

    African Journals Online (AJOL)

    The conventional histological study revealed that except the endomysium which was similar in both muscles, the other intramuscular connective tissues' layers varied between leg and breast muscles and were affected by sex. All the connective tissue fibers were observed in all the intramuscular connective tissues of both ...

  12. Application of olfactory tissue and its neural progenitors to schizophrenia and psychiatric research.

    Science.gov (United States)

    Lavoie, Joëlle; Sawa, Akira; Ishizuka, Koko

    2017-05-01

    The goal of this review article is to introduce olfactory epithelium-derived cell/tissue models as a promising surrogate system to study the molecular mechanisms implicated in schizophrenia and other neuropsychiatric disorders. Here, we particularly focus on the utility of their neural progenitors. Recent investigations of the pathophysiology of schizophrenia using olfactory epithelium-derived tissue/cell models have provided insights about schizophrenia-associated alterations in neurodevelopment, stress response, and gene/protein expression regulatory pathways. The olfactory epithelium retains the capacity for lifelong neurogenesis and regeneration, because of the presence of neural stem cells and progenitors. Thus, both mature neurons and neural progenitors can be obtained from the olfactory epithelium without the need for genetic reprogramming and related confounds. Furthermore, the olfactory epithelium is highly scalable resource in translational settings. Here, we also demonstrate recent findings from research using olfactory epithelium-derived tissue/cell models in schizophrenia and other brain disorders. In summary, we propose that the olfactory epithelium is a promising resource to study neural molecular and cellular signatures relevant to the pathology of schizophrenia and other mental disorders.

  13. Tracking of adipose tissue-derived progenitor cells using two magnetic nanoparticle types

    Energy Technology Data Exchange (ETDEWEB)

    Kasten, Annika; Siegmund, Birte J. [Department of Oral and Maxillofacial Surgery, Facial Plastic Surgery, Rostock University Medical Center, Schillingallee 35 D-18057 Rostock (Germany); Grüttner, Cordula [Micromod Partikeltechnologie GmbH, Warnemünde, D-18115 Rostock (Germany); Kühn, Jens-Peter [Department of Radiology and Neuroradiology, Greifswald University Medical Center, D-17475 Greifswald (Germany); Frerich, Bernhard, E-mail: bernhard.frerich@med.uni-rostock.de [Department of Oral and Maxillofacial Surgery, Facial Plastic Surgery, Rostock University Medical Center, Schillingallee 35 D-18057 Rostock (Germany)

    2015-04-15

    Magnetic resonance imaging (MRI) is to be considered as an emerging detection technique for cell tracking experiments to evaluate the fate of transplanted progenitor cells and develop successful cell therapies for tissue engineering. Adipose tissue engineering using adipose tissue-derived progenitor cells has been advocated for the cure of soft tissue defects or for persistent soft tissue augmentation. Adipose tissue-derived progenitor cells were differentiated into the adipogenic lineage and labeled with two different types of magnetic iron oxide nanoparticles in varying concentrations which resulted in a concentration-dependent reduction of gene expression of adipogenic differentiation markers, adiponectin and fatty acid-binding protein 4 (FABP4), whereas the metabolic activity was not altered. As a result, only low nanoparticle concentrations for labeling were used for in vivo experiments. Cells were seeded onto collagen scaffolds and subcutaneously implanted into severe combined immunodeficient (SCID) mice. At 24 h as well as 28 days after implantation, MRI analyses were performed visualizing nanoparticle-labeled cells using T2-weighted sequences. The quantification of absolute volume of the scaffolds revealed a decrease of volume over time in all experimental groups. The distribution of nanoparticle-labeled cells within the scaffolds varied likewise over time. - Highlights: • Adipose tissue-derived stem cells (ASC) were labeled with magnetic iron oxide nanoparticles. • Nanoparticles influenced the adipogenic differentiation of ASC. • Labeled cells were seeded onto collagen scaffolds and implanted in SCID mice. • Nanoparticle-labeled cells were visualized in vivo using T2-weighted sequences. • Volume of collagen scaffolds was decreased over time after implantation.

  14. Tracking of adipose tissue-derived progenitor cells using two magnetic nanoparticle types

    International Nuclear Information System (INIS)

    Kasten, Annika; Siegmund, Birte J.; Grüttner, Cordula; Kühn, Jens-Peter; Frerich, Bernhard

    2015-01-01

    Magnetic resonance imaging (MRI) is to be considered as an emerging detection technique for cell tracking experiments to evaluate the fate of transplanted progenitor cells and develop successful cell therapies for tissue engineering. Adipose tissue engineering using adipose tissue-derived progenitor cells has been advocated for the cure of soft tissue defects or for persistent soft tissue augmentation. Adipose tissue-derived progenitor cells were differentiated into the adipogenic lineage and labeled with two different types of magnetic iron oxide nanoparticles in varying concentrations which resulted in a concentration-dependent reduction of gene expression of adipogenic differentiation markers, adiponectin and fatty acid-binding protein 4 (FABP4), whereas the metabolic activity was not altered. As a result, only low nanoparticle concentrations for labeling were used for in vivo experiments. Cells were seeded onto collagen scaffolds and subcutaneously implanted into severe combined immunodeficient (SCID) mice. At 24 h as well as 28 days after implantation, MRI analyses were performed visualizing nanoparticle-labeled cells using T2-weighted sequences. The quantification of absolute volume of the scaffolds revealed a decrease of volume over time in all experimental groups. The distribution of nanoparticle-labeled cells within the scaffolds varied likewise over time. - Highlights: • Adipose tissue-derived stem cells (ASC) were labeled with magnetic iron oxide nanoparticles. • Nanoparticles influenced the adipogenic differentiation of ASC. • Labeled cells were seeded onto collagen scaffolds and implanted in SCID mice. • Nanoparticle-labeled cells were visualized in vivo using T2-weighted sequences. • Volume of collagen scaffolds was decreased over time after implantation

  15. Ability of stem and progenitor cells in the dental pulp to form hard tissue

    Directory of Open Access Journals (Sweden)

    Akihiro Hosoya, DDS, PhD

    2015-08-01

    Full Text Available Dental pulp has an important ability to form mineralized hard tissue in response to a variety of external stimuli. The formation of mineralized tissue within the pulp cavity has been widely examined in both clinical and animal studies. Despite these studies focusing on the phenomena of reparative dentin and dentin bridge formation, the mechanisms of their induction remain unknown. Recently, several morphological studies revealed that the source of cells for hard tissue formation is the dental pulp itself, even after pulp injury. This finding indicates that the dental pulp tissue contains undifferentiated cells participating in dentin and pulp regeneration. Additionally, stem and progenitor cells isolated from the dental pulp were found to differentiate into odontoblasts as well as osteoblasts. This review presents current evidences for the multipotent ability of dental pulp cells and their usefulness in tissue engineering applications as a cell resource.

  16. Vasculitis associated with connective tissue diseases.

    Science.gov (United States)

    Cozzani, E; Gasparini, G; Papini, M; Burlando, M; Drago, F; Parodi, A

    2015-04-01

    Vasculitis in connective tissue disease (CTD) is quite rare, it is reported in approximately 10% of patients with CTD; systemic lupus erythematosus (SLE) shows the highest association rate. Vessels of any size may be involved, but mainly small vessels vasculitis is reported. At present the classification of these vasculitis is unsatisfactory. According to the 2012 revised International Chapel Hill Consensus Conference, vasculitides secondary to CTD are a well identified entity and are classified under the category of "vasculitis associated with systemic disease". However only lupus vasculitis and rheumatoid vasculitis are explicitly listed, while the remaining are generically included under the heading "others". Petechiae, purpura, gangrene and ulcers are the most frequent cutaneous manifestations that should investigated in order to rule out potentially dangerous systemic involvement, especially if cryoglobulinemic or necrotizing vasculitis are suspected. This review will focus on the cutaneous involvement in CTD associated vasculitis.

  17. Undifferentiated connective tissue dysplasia in adolescents

    Directory of Open Access Journals (Sweden)

    G. Yu. Kalayeva

    2014-01-01

    Full Text Available Objective: to study the spectrum and frequency of dysplasia-dependent and connective tissue dysplasia-associated disorders in adolescents. One hundred and ten 10-to-14-year-old pupils of one of the Leninsk-Kuznetsky schools were examined. The presence and degree of undifferentiated connective tissue dysplasia (UCTD were established according to the phenotypic characters; joint mobility was rated using the standard Beighton methods. The adolescents showed a high prevalence of the signs of UCTD whose degree corresponded to that of joint hypermobility. The latter was accompanied by joint pain in 89 (33,3% adolescents in the study group or concurrent with scoliosis in 77,8% and platypodia in 22,2%. In a control group (я=29, scoliosis and platypodia were 2 and 3,3 times rarer, respectively; complaints of arthralgia were absent. After 3 years, the number of adolescents with platypodia increased up to 33,3% in the study group and up to 10,3% in the control group; that of teenagers with scoliosis did up to 81,5and 41,4%, respectively. A larger number of adolescents with CTD were noted to have vegetovascular disorders, more commonly with parasympathotonia with insufficient autonomic performance support. A great difference was retained in the frequency of myopia and biliary dyskinesia and in the incidence of respiratory infections. Thus, the high prevalence of dysplasia-dependent disorders in adolescents suggests that there is a need for the early detection of the signs of CTD in children to timely implement a package of prevention and health-improvement measures.

  18. Generalized connective tissue disease in Crtap-/- mouse.

    Directory of Open Access Journals (Sweden)

    Dustin Baldridge

    2010-05-01

    Full Text Available Mutations in CRTAP (coding for cartilage-associated protein, LEPRE1 (coding for prolyl 3-hydroxylase 1 [P3H1] or PPIB (coding for Cyclophilin B [CYPB] cause recessive forms of osteogenesis imperfecta and loss or decrease of type I collagen prolyl 3-hydroxylation. A comprehensive analysis of the phenotype of the Crtap-/- mice revealed multiple abnormalities of connective tissue, including in the lungs, kidneys, and skin, consistent with systemic dysregulation of collagen homeostasis within the extracellular matrix. Both Crtap-/- lung and kidney glomeruli showed increased cellular proliferation. Histologically, the lungs showed increased alveolar spacing, while the kidneys showed evidence of segmental glomerulosclerosis, with abnormal collagen deposition. The Crtap-/- skin had decreased mechanical integrity. In addition to the expected loss of proline 986 3-hydroxylation in alpha1(I and alpha1(II chains, there was also loss of 3Hyp at proline 986 in alpha2(V chains. In contrast, at two of the known 3Hyp sites in alpha1(IV chains from Crtap-/- kidneys there were normal levels of 3-hydroxylation. On a cellular level, loss of CRTAP in human OI fibroblasts led to a secondary loss of P3H1, and vice versa. These data suggest that both CRTAP and P3H1 are required to maintain a stable complex that 3-hydroxylates canonical proline sites within clade A (types I, II, and V collagen chains. Loss of this activity leads to a multi-systemic connective tissue disease that affects bone, cartilage, lung, kidney, and skin.

  19. Concomitant multipotent and unipotent dental pulp progenitors and their respective contribution to mineralised tissue formation

    Directory of Open Access Journals (Sweden)

    S Dimitrova-Nakov

    2012-05-01

    Full Text Available Upon in vitro induction or in vivo implantation, the stem cells of the dental pulp display hallmarks of odontoblastic, osteogenic, adipogenic or neuronal cells. However, whether these phenotypes result from genuine multipotent cells or from coexistence of distinct progenitors is still an open question. Furthermore, determining whether a single cell-derived progenitor is capable of undergoing a differentiation cascade leading to tissue repair in situ is important for the development of cell therapy strategies. Three clonal pulp precursor cell lines (A4, C5, H8, established from embryonic ED18 first molars of mouse transgenic for a recombinant plasmid adeno-SV40, were induced to differentiate towards the odonto/osteogenic, chondrogenic or adipogenic programme. Expression of phenotypic markers of each lineage was evaluated by RT-PCR, histochemistry or immunocytochemistry. The clones were implanted into mandibular incisors or calvaria of adult mice. The A4 clone was capable of being recruited towards at least 3 mesodermal lineages in vitro and of contributing to dentin-like or bone formation, in vivo, thus behaving as a multipotent cell. In contrast, the C5 and H8 clones displayed a more restricted potential. Flow cytometric analysis revealed that isolated monopotent and multipotent clones could be distinguished by a differential expression of CD90. Altogether, isolation of these clonal lines allowed demonstrating the coexistence of multipotential and restricted-lineage progenitors in the mouse pulp. These cells may further permit unravelling specificities of the different types of pulp progenitors, hence facilitating the development of cell-based therapies of the dental pulp or other cranio-facial tissues.

  20. The Use of Endothelial Progenitor Cells for the Regeneration of Musculoskeletal and Neural Tissues

    Directory of Open Access Journals (Sweden)

    Naosuke Kamei

    2017-01-01

    Full Text Available Endothelial progenitor cells (EPCs derived from bone marrow and blood can differentiate into endothelial cells and promote neovascularization. In addition, EPCs are a promising cell source for the repair of various types of vascularized tissues and have been used in animal experiments and clinical trials for tissue repair. In this review, we focused on the kinetics of endogenous EPCs during tissue repair and the application of EPCs or stem cell populations containing EPCs for tissue regeneration in musculoskeletal and neural tissues including the bone, skeletal muscle, ligaments, spinal cord, and peripheral nerves. EPCs can be mobilized from bone marrow and recruited to injured tissue to contribute to neovascularization and tissue repair. In addition, EPCs or stem cell populations containing EPCs promote neovascularization and tissue repair through their differentiation to endothelial cells or tissue-specific cells, the upregulation of growth factors, and the induction and activation of endogenous stem cells. Human peripheral blood CD34(+ cells containing EPCs have been used in clinical trials of bone repair. Thus, EPCs are a promising cell source for the treatment of musculoskeletal and neural tissue injury.

  1. Autoimmune connective tissue diseases and vaccination

    Directory of Open Access Journals (Sweden)

    Ewa Więsik-Szewczyk

    2015-12-01

    Full Text Available The idea that infectious agents can induce autoimmune diseases in genetically susceptible subjects has been a matter of discussion for years. Moreover, increased incidence of autoimmune diseases and introduction of prophylactic vaccinations from early childhood suggest that these two trends are linked. In the medical literature and even non-professional media, case reports or events temporally related to vaccination are reported. It raises the issue of vaccination safety. In everyday practice medical professionals, physicians, rheumatologists and other specialists will be asked their opinion of vaccination safety. The decision should be made according to evidence-based medicine and the current state of knowledge. The purpose of this paper is to discuss a potential mechanism which links infections, vaccinations and autoimmunity. We present an overview of published case reports, especially of systemic connective tissue diseases temporally related to vaccination and results from case-nested studies. As yet, no conclusive evidence supports a causal relationship between vaccination and autoimmune diseases. It has to be determined whether the performed studies are sufficiently Epsteinasensitive to detect the link. The debate is ongoing, and new data may be required to explain the pathogenesis of autoimmunity. We would like to underscore the need for prophylactic vaccination in patients with autoimmune rheumatic diseases and to break down the myth that the vaccines are contraindicated in this target group.

  2. Lung involvement in systemic connective tissue diseases

    Directory of Open Access Journals (Sweden)

    Plavec Goran

    2008-01-01

    Full Text Available Background/Aim. Systemic connective tissue diseases (SCTD are chronic inflammatory autoimmune disorders of unknown cause that can involve different organs and systems. Their course and prognosis are different. All of them can, more or less, involve the respiratory system. The aim of this study was to find out the frequency of respiratory symptoms, lung function disorders, radiography and high-resolution computerized tomography (HRCT abnormalities, and their correlation with the duration of the disease and the applied treatment. Methods. In 47 non-randomized consecutive patients standard chest radiography, HRCT, and lung function tests were done. Results. Hypoxemia was present in nine of the patients with respiratory symptoms (20%. In all of them chest radiography was normal. In five of these patients lung fibrosis was established using HRCT. Half of all the patients with SCTD had symptoms of lung involvement. Lung function tests disorders of various degrees were found in 40% of the patients. The outcome and the degree of lung function disorders were neither in correlation with the duration of SCTD nor with therapy used (p > 0.05 Spearmans Ro. Conclusion. Pulmonary fibrosis occurs in about 10% of the patients with SCTD, and possibly not due to the applied treatment regimens. Hypoxemia could be a sing of existing pulmonary fibrosis in the absence of disorders on standard chest radiography.

  3. Tissue engineering and the use of stem/progenitor cells for airway epithelium repair

    Directory of Open Access Journals (Sweden)

    GM Roomans

    2010-06-01

    Full Text Available Stem/progenitor cells can be used to repair defects in the airway wall, resulting from e.g., tumors, trauma, tissue reactions following long-time intubations, or diseases that are associated with epithelial damage. Several potential sources of cells for airway epithelium have been identified. These can be divided into two groups. The first group consists of endogenous progenitor cells present in the respiratory tract. This group can be subdivided according to location into (a a ductal cell type in the submucosal glands of the proximal trachea, (b basal cells in the intercartilaginous zones of the lower trachea and bronchi, (c variant Clara cells (Clarav-cells in the bronchioles and (d at the junctions between the bronchioles and the alveolar ducts, and (e alveolar type II cells. This classification of progenitor cell niches is, however, controversial. The second group consists of exogenous stem cells derived from other tissues in the body. This second group can be subdivided into: (a embryonic stem (ES cells, induced pluripotent stem (iPS cells, or amniotic fluid stem cells, (b side-population cells from bone marrow or epithelial stem cells present in bone marrow or circulation and (c fat-derived mesenchymal cells. Airway epithelial cells can be co-cultured in a system that includes a basal lamina equivalent, extracellular factors from mesenchymal fibroblasts, and in an air-liquid interface system. Recently, spheroid-based culture systems have been developed. Several clinical applications have been suggested: cystic fibrosis, acute respiratory distress syndrome, chronic obstructive lung disease, pulmonary fibrosis, pulmonary edema, and pulmonary hypertension. Clinical applications so far are few, but include subglottic stenosis, tracheomalacia, bronchiomalacia, and emphysema.

  4. Osteoarthritis-derived chondrocytes are a potential source of multipotent progenitor cells for cartilage tissue engineering.

    Science.gov (United States)

    Oda, Tomoyuki; Sakai, Tadahiro; Hiraiwa, Hideki; Hamada, Takashi; Ono, Yohei; Nakashima, Motoshige; Ishizuka, Shinya; Matsukawa, Tetsuya; Yamashita, Satoshi; Tsuchiya, Saho; Ishiguro, Naoki

    2016-10-21

    The natural healing capacity of damaged articular cartilage is poor, rendering joint surface injuries a prime target for regenerative medicine. While autologous chondrocyte or mesenchymal stem cell (MSC) implantation can be applied to repair cartilage defects in young patients, no appropriate long-lasting treatment alternative is available for elderly patients with osteoarthritis (OA). Multipotent progenitor cells are reported to present in adult human articular cartilage, with a preponderance in OA cartilage. These facts led us to hypothesize the possible use of osteoarthritis-derived chondrocytes as a cell source for cartilage tissue engineering. We therefore analyzed chondrocyte- and stem cell-related markers, cell growth rate, and multipotency in OA chondrocytes (OACs) and bone marrow-derived MSCs, along with normal articular chondrocytes (ACs) as a control. OACs demonstrated similar phenotype and proliferation rate to MSCs. Furthermore, OACs exhibited multilineage differentiation ability with a greater chondrogenic differentiation ability than MSCs, which was equivalent to ACs. We conclude that chondrogenic capacity is not significantly affected by OA, and OACs could be a potential source of multipotent progenitor cells for cartilage tissue engineering. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Increased circulating progenitor cells in Alzheimer's disease patients with moderate to severe dementia: evidence for vascular repair and tissue regeneration?

    Science.gov (United States)

    Stellos, Konstantinos; Panagiota, Victoria; Sachsenmaier, Saskia; Trunk, Theresia; Straten, Guido; Leyhe, Thomas; Seizer, Peter; Geisler, Tobias; Gawaz, Meinrad; Laske, Christoph

    2010-01-01

    Cerebrovascular dysfunction is a common finding in patients with Alzheimer's disease (AD) and may contribute to cognitive decline. Abundant evidence suggests that vascular and neuronal repair mechanisms are mediated by circulating progenitor cells in vivo. Whether CD34+ and, specifically, CD34+/CD133+ progenitor cells are involved in the pathophysiology of AD is poorly understood so far. In the present study, peripheral blood concentrations of circulating CD34+/CD133+ and CD34+ progenitor cells were measured in 45 AD patients and in 30 healthy elderly controls by flow cytometry. The severity of dementia was assessed by Mini-Mental Status Examination and Clinical Dementia Rating scale. AD patients were stratified into two groups showing mild (n=17) and moderate to severe (n= 28) dementia. In the present study, AD patients with moderate to severe dementia, but not those with mild dementia, showed significantly increased circulating CD34+/CD133+ and CD34+ progenitor cells compared to healthy elderly controls independent of cardiovascular risk factors and medication. In addition, the number of circulating CD34+/CD133+ progenitor cells in AD patients was significantly inversely correlated with cognitive function, age, and plasma levels of SDF-1, the most potent chemokine for progenitor cells. Our findings suggest a stage-dependent upregulation of circulating CD34+/CD133+ and CD34+ progenitor cells in AD patients, which could take part in tissue healing processes of the brain in AD.

  6. Giant Panda (Ailuropoda melanoleuca Buccal Mucosa Tissue as a Source of Multipotent Progenitor Cells.

    Directory of Open Access Journals (Sweden)

    Hilary M A Prescott

    Full Text Available Since the first mammal was cloned, the idea of using this technique to help endangered species has aroused considerable interest. However, several issues limit this possibility, including the relatively low success rate at every stage of the cloning process, and the dearth of usable tissues from these rare animals. iPS cells have been produced from cells from a number of rare mammalian species and this is the method of choice for strategies to improve cloning efficiency and create new gametes by directed differentiation. Nevertheless information about other stem cell/progenitor capabilities of cells from endangered species could prove important for future conservation approaches and adds to the knowledge base about cellular material that can be extremely limited. Multipotent progenitor cells, termed skin-derived precursor (SKP cells, can be isolated directly from mammalian skin dermis, and human cheek tissue has also been shown to be a good source of SKP-like cells. Recently we showed that structures identical to SKPs termed m-SKPs could be obtained from monolayer/ two dimensional (2D skin fibroblast cultures. Here we aimed to isolate m-SKPs from cultured cells of three endangered species; giant panda (Ailuropoda melanoleuca; red panda (Ailurus fulgens; and Asiatic lion (Panthera leo persica. m-SKP-like spheres were formed from the giant panda buccal mucosa fibroblasts; whereas dermal fibroblast (DF cells cultured from abdominal skin of the other two species were unable to generate spheres. Under specific differentiation culture conditions giant panda spheres expressed neural, Schwann, adipogenic and osteogenic cell markers. Furthermore, these buccal mucosa derived spheres were shown to maintain expression of SKP markers: nestin, versican, fibronectin, and P75 and switch on expression of the stem cell marker ABCG2. These results demonstrate that giant panda cheek skin can be a useful source of m-SKP multipotent progenitors. At present lack of

  7. Giant Panda (Ailuropoda melanoleuca) Buccal Mucosa Tissue as a Source of Multipotent Progenitor Cells.

    Science.gov (United States)

    Prescott, Hilary M A; Manning, Craig; Gardner, Aaron; Ritchie, William A; Pizzi, Romain; Girling, Simon; Valentine, Iain; Wang, Chengdong; Jahoda, Colin A B

    2015-01-01

    Since the first mammal was cloned, the idea of using this technique to help endangered species has aroused considerable interest. However, several issues limit this possibility, including the relatively low success rate at every stage of the cloning process, and the dearth of usable tissues from these rare animals. iPS cells have been produced from cells from a number of rare mammalian species and this is the method of choice for strategies to improve cloning efficiency and create new gametes by directed differentiation. Nevertheless information about other stem cell/progenitor capabilities of cells from endangered species could prove important for future conservation approaches and adds to the knowledge base about cellular material that can be extremely limited. Multipotent progenitor cells, termed skin-derived precursor (SKP) cells, can be isolated directly from mammalian skin dermis, and human cheek tissue has also been shown to be a good source of SKP-like cells. Recently we showed that structures identical to SKPs termed m-SKPs could be obtained from monolayer/ two dimensional (2D) skin fibroblast cultures. Here we aimed to isolate m-SKPs from cultured cells of three endangered species; giant panda (Ailuropoda melanoleuca); red panda (Ailurus fulgens); and Asiatic lion (Panthera leo persica). m-SKP-like spheres were formed from the giant panda buccal mucosa fibroblasts; whereas dermal fibroblast (DF) cells cultured from abdominal skin of the other two species were unable to generate spheres. Under specific differentiation culture conditions giant panda spheres expressed neural, Schwann, adipogenic and osteogenic cell markers. Furthermore, these buccal mucosa derived spheres were shown to maintain expression of SKP markers: nestin, versican, fibronectin, and P75 and switch on expression of the stem cell marker ABCG2. These results demonstrate that giant panda cheek skin can be a useful source of m-SKP multipotent progenitors. At present lack of sample numbers

  8. [Origins and selection of epidermal progenitors and stem cells: a challenge for tissue engineering].

    Science.gov (United States)

    Deshayes, Nathalie; Rathman-Josserand, Michelle

    2008-01-01

    The use of epidermal stem cells and their progeny for tissue engineering and cell therapy represents a source of hope and major interest in view of applications such as replacing the loss of functionality in failing tissues or obtaining physiologic skin equivalents for skin grafting. The use of such cells necessitates the isolation and purification of rare populations of keratinocytes and then increasing their numbers by mass culture. This is not currently possible since part of the specific phenotype of these cells is lost once the cells are placed in culture. Furthermore, few techniques are available to unequivocally detect the presence of skin stem cells and/or their progeny in culture and thus quantify them. Two different sources of stem cells are currently being studied for skin research and clinical applications: skin progenitors either obtained from embryonic stem cells (ESC) or from selection from adult skin tissue. It has been shown that "keratinocyte-like" cells can be derived from ESC; however, the culturing processes must still be optimized to allow for the mass culture of homogeneous populations at a controlled stage of differentiation. The functional characterization of such populations must also be more thoroughly achieved. In order to use stem cells from adult tissues, improvements must be made in order to obtain a satisfactory degree of purification and characterization of this rare population. Distinguishing stem cells from progenitor cells at the molecular level also remains a challenge. Furthermore, stem cell research inevitably requires cultivating these cells outside their physiological environment or niche. It will thus be necessary to better understand the impact of this specific environmental niche on the preservation of the cellular phenotypes of interest.

  9. Pectus excavatum and heritable disorders of the connective tissue

    Directory of Open Access Journals (Sweden)

    Francesca Tocchioni

    2013-09-01

    Full Text Available Pectus excavatum, the most frequent congenital chest wall deformity, may be rarely observed as a sole deformity or as a sign of an underlying connective tissue disorder. To date, only few studies have described correlations between this deformity and heritable connective tissue disorders such as Marfan, Ehlers-Danlos, Poland, MASS (Mitral valve prolapse, not progressive Aortic enlargement, Skeletal and Skin alterations phenotype among others. When concurring with connective tissue disorder, cardiopulmonary and vascular involvement may be associated to the thoracic defect. Ruling out the concomitance of pectus excavatum and connective tissue disorders, therefore, may have a direct implication both on surgical outcome and long term prognosis. In this review we focused on biological bases of connective tissue disorders which may be relevant to the pathogenesis of pectus excavatum, portraying surgical and clinical implication of their concurrence.

  10. The decrease in silicon concentration of the connective tissues with age in rats is a marker of connective tissue turnover.

    Science.gov (United States)

    Jugdaohsingh, Ravin; Watson, Abigail I E; Pedro, Liliana D; Powell, Jonathan J

    2015-06-01

    Silicon may be important for bone and connective tissue health. Higher concentrations of silicon are suggested to be associated with bone and the connective tissues, compared with the non-connective soft tissues. Moreover, in connective tissues it has been suggested that silicon levels may decrease with age based upon analyses of human aorta. These claims, however, have not been tested under controlled conditions. Here connective and non-connective tissues were collected and analysed for silicon levels from female Sprague-Dawley rats of different ages (namely, 3, 5, 8, 12, 26 and 43 weeks; n=8-10 per age group), all maintained on the same feed source and drinking water, and kept in the same environment from weaning to adulthood. Tissues (696 samples) were digested in nitric acid and analysed by inductively coupled plasma optical emission spectrometry for total silicon content. Fasting serum samples were also collected, diluted and analysed for silicon. Higher concentrations of silicon (up to 50-fold) were found associated with bone and the connective tissues compared with the non-connective tissues. Although total silicon content increased with age in all tissues, the highest connective tissue silicon concentrations (up to 9.98 μg/g wet weight) were found in young weanling rats, decreasing thereafter with age (by 2-6 fold). Fasting serum silicon concentrations reflected the pattern of connective tissue silicon concentrations and, both measures, when compared to collagen data from a prior experiment in Sprague-Dawley rats, mirrored type I collagen turnover with age. Our findings confirm the link between silicon and connective tissues and would imply that young growing rats have proportionally higher requirements for dietary silicon than mature adults, for bone and connective tissue development, although this was not formally investigated here. However, estimation of total body silicon content suggested that actual Si requirements may be substantially lower than

  11. The decrease in silicon concentration of the connective tissues with age in rats is a marker of connective tissue turnover☆

    Science.gov (United States)

    Jugdaohsingh, Ravin; Watson, Abigail I.E.; Pedro, Liliana D.; Powell, Jonathan J.

    2015-01-01

    Silicon may be important for bone and connective tissue health. Higher concentrations of silicon are suggested to be associated with bone and the connective tissues, compared with the non-connective soft tissues. Moreover, in connective tissues it has been suggested that silicon levels may decrease with age based upon analyses of human aorta. These claims, however, have not been tested under controlled conditions. Here connective and non-connective tissues were collected and analysed for silicon levels from female Sprague–Dawley rats of different ages (namely, 3, 5, 8, 12, 26 and 43 weeks; n = 8–10 per age group), all maintained on the same feed source and drinking water, and kept in the same environment from weaning to adulthood. Tissues (696 samples) were digested in nitric acid and analysed by inductively coupled plasma optical emission spectrometry for total silicon content. Fasting serum samples were also collected, diluted and analysed for silicon. Higher concentrations of silicon (up to 50-fold) were found associated with bone and the connective tissues compared with the non-connective tissues. Although total silicon content increased with age in all tissues, the highest connective tissue silicon concentrations (up to 9.98 μg/g wet weight) were found in young weanling rats, decreasing thereafter with age (by 2–6 fold). Fasting serum silicon concentrations reflected the pattern of connective tissue silicon concentrations and, both measures, when compared to collagen data from a prior experiment in Sprague–Dawley rats, mirrored type I collagen turnover with age. Our findings confirm the link between silicon and connective tissues and would imply that young growing rats have proportionally higher requirements for dietary silicon than mature adults, for bone and connective tissue development, although this was not formally investigated here. However, estimation of total body silicon content suggested that actual Si requirements may be substantially

  12. [Protein-energy malnutrition in patients with connective tissue dysplasia].

    Science.gov (United States)

    Lialiukova, E A

    2013-01-01

    In the conditions of the specialized Center of a dysplasia of a connecting tissue the assessment of an protein--energy malnutrition at 121 patients with signs of a dysplasia of a connecting tissue is carried out. High frequency of an oligotrophy at patients with a dysplasia of a connecting tissue is registered. The I degree of a gipotorofiya is taped at 26.21% of the patients, II degree--at 18.44%, the III degree--at 3.88% of patients.

  13. Micromechanics and constitutive modeling of connective soft tissues.

    Science.gov (United States)

    Fallah, A; Ahmadian, M T; Firozbakhsh, K; Aghdam, M M

    2016-07-01

    In this paper, a micromechanical model for connective soft tissues based on the available histological evidences is developed. The proposed model constituents i.e. collagen fibers and ground matrix are considered as hyperelastic materials. The matrix material is assumed to be isotropic Neo-Hookean while the collagen fibers are considered to be transversely isotropic hyperelastic. In order to take into account the effects of tissue structure in lower scales on the macroscopic behavior of tissue, a strain energy density function (SEDF) is developed for collagen fibers based on tissue hierarchical structure. Macroscopic response and properties of tissue are obtained using the numerical homogenization method with the help of ABAQUS software. The periodic boundary conditions and the proposed constitutive models are implemented into ABAQUS using the DISP and the UMAT subroutines, respectively. The existence of the solution and stable material behavior of proposed constitutive model for collagen fibers are investigated based on the poly-convexity condition. Results of the presented micromechanics model for connective tissues are compared and validated with available experimental data. Effects of geometrical and material parameters variation at microscale on macroscopic mechanical behavior of tissues are investigated. The results show that decrease in collagen content of the connective tissues like the tendon due to diseases leads 20% more stretch than healthy tissue under the same load which can results in connective tissue malfunction and hypermobility in joints. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Optical Clearing in Dense Connective Tissues to Visualize Cellular Connectivity In Situ

    Science.gov (United States)

    Calve, Sarah; Ready, Andrew; Huppenbauer, Christopher; Main, Russell; Neu, Corey P.

    2015-01-01

    Visualizing the three-dimensional morphology and spatial patterning of cells embedded deep within dense connective tissues of the musculoskeletal system has been possible only by utilizing destructive techniques. Here we utilize fructose-based clearing solutions to image cell connectivity and deep tissue-scale patterning in situ by standard confocal microscopy. Optical clearing takes advantage of refractive index matching of tissue and the embedding medium to visualize light transmission through a broad range of bovine and whole mount murine tissues, including cartilage, bone, and ligament, of the head and hindlimb. Using non-destructive methods, we show for the first time intercellular chondrocyte connections throughout the bulk of cartilage, and we reveal in situ patterns of osteocyte processes and the lacunar-canalicular system deep within mineralized cortical bone. Optical clearing of connective tissues is expected to find broad application for the study of cell responses in normal physiology and disease pathology. PMID:25581165

  15. Designing the stem cell microenvironment for guided connective tissue regeneration.

    Science.gov (United States)

    Bogdanowicz, Danielle R; Lu, Helen H

    2017-12-01

    Adult mesenchymal stem cells (MSCs) are an attractive cell source for regenerative medicine because of their ability to self-renew and their capacity for multilineage differentiation and tissue regeneration. For connective tissues, such as ligaments or tendons, MSCs are vital to the modulation of the inflammatory response following acute injury while also interacting with resident fibroblasts to promote cell proliferation and matrix synthesis. To date, MSC injection for connective tissue repair has yielded mixed results in vivo, likely due to a lack of appropriate environmental cues to effectively control MSC response and promote tissue healing instead of scar formation. In healthy tissues, stem cells reside within a complex microenvironment comprising cellular, structural, and signaling cues that collectively maintain stemness and modulate tissue homeostasis. Changes to the microenvironment following injury regulate stem cell differentiation, trophic signaling, and tissue healing. Here, we focus on models of the stem cell microenvironment that are used to elucidate the mechanisms of stem cell regulation and inspire functional approaches to tissue regeneration. Recent studies in this frontier area are highlighted, focusing on how microenvironmental cues modulate MSC response following connective tissue injury and, more importantly, how this unique cell environment can be programmed for stem cell-guided tissue regeneration. © 2017 New York Academy of Sciences.

  16. Hypericin-mediated selective photomodification of connective tissues

    Energy Technology Data Exchange (ETDEWEB)

    Hovhannisyan, V., E-mail: hovv@phys.ntu.edu.tw; Guo, H. W.; Chen, Y. F., E-mail: yfchen@phys.ntu.edu.tw [Department of Physics, National Taiwan University, Taipei 106, Taiwan (China); Hovhannisyan, A. [Multimedia and Programming, European Regional Education Academy, Yerevan 0037 (Armenia); Ghukasyan, V. [Neuroscience Center, University of North Carolina at Chapel Hill, North Carolina 27514 (United States); Dong, C. Y., E-mail: cydong@phys.ntu.edu.tw [Department of Physics, National Taiwan University, Taipei 106, Taiwan (China); Center for Quantum Science and Engineering, National Taiwan University, Taipei 106, Taiwan (China)

    2014-12-29

    Controllable modification of biological molecules and supramolecular components of connective tissue are important for biophysical and biomedical applications. Through the use of second harmonic generation imaging, two-photon fluorescence microscopy, and spectrofluorimetry, we found that hypericin, a natural pigment, induces photosensitized destruction of collagen fibers but does not affect elastic fibers and lipids in chicken tendon, skin, and blood vessels. We demonstrated the dynamics and efficiency of collagen photomodification and investigated mechanisms of this processes. Our results suggest that hypericin–mediated photoprocesses in biological tissues may be useful in biomedical applications that require selective modification of connective tissues.

  17. Oral manifestations of connective tissue disease and novel therapeutic approaches.

    Science.gov (United States)

    Heath, Kenisha R; Rogers, Roy S; Fazel, Nasim

    2015-10-16

    Connective tissue diseases such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and Sjögren syndrome (SS) have presented many difficulties both in their diagnosis and treatment. Known causes for this difficulty include uncertainty of disease etiology, the multitude of clinical presentations, the unpredictable disease course, and the variable cell types, soluble mediators, and tissue factors that are believed to play a role in the pathogenesis of connective tissue diseases. The characteristic oral findings seen with these specific connective tissue diseases may assist with more swift diagnostic capability. Additionally, the recent use of biologics may redefine the success rate in the treatment and management of the disease. In this review we describe the oral manifestations associated with SLE, SSc, and SS and review the novel biologic drugs used to treat these conditions.

  18. Micromechanical modeling of rate-dependent behavior of Connective tissues.

    Science.gov (United States)

    Fallah, A; Ahmadian, M T; Firozbakhsh, K; Aghdam, M M

    2017-03-07

    In this paper, a constitutive and micromechanical model for prediction of rate-dependent behavior of connective tissues (CTs) is presented. Connective tissues are considered as nonlinear viscoelastic material. The rate-dependent behavior of CTs is incorporated into model using the well-known quasi-linear viscoelasticity (QLV) theory. A planar wavy representative volume element (RVE) is considered based on the tissue microstructure histological evidences. The presented model parameters are identified based on the available experiments in the literature. The presented constitutive model introduced to ABAQUS by means of UMAT subroutine. Results show that, monotonic uniaxial test predictions of the presented model at different strain rates for rat tail tendon (RTT) and human patellar tendon (HPT) are in good agreement with experimental data. Results of incremental stress-relaxation test are also presented to investigate both instantaneous and viscoelastic behavior of connective tissues. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Tumors of the connective and supporting tissues

    International Nuclear Information System (INIS)

    Suit, Herman

    1995-01-01

    There has been a continuous acceleration of medical/scientific inquiry and of actual improvements in management of patients with neoplasms of the mesenchymal tissues over the last four decades. The number of publications in this field has increased from 1140 in 1970 and then to 1700 in 1990. Important advances discussed over this period include: establishment of sarcoma teams in major oncology centers; staging systems for both soft tissue and osseous sarcomas; demonstration of genetic determinants in the development of, at least, some of the sarcomas; the revolutionary change in quality of diagnostic imaging by the introduction of CT and MRI; use of immunohistochemistry in diagnostic pathology; the drastic gains in survival of patients with osteogenic sarcoma, Ewing's sarcoma and rhabdomyosarcoma due to the efficacy of multi-drug and multi-cycle chemotherapy protocols; major advances in surgical techniques which have made limb salvage practical; cell lines derived from human sarcomas have been shown to have in vitro radiation sensitivity comparable to that of cell lines from epithelial tumors; the combination of conservative surgery and moderate doses of radiation yields local control and survival results equivalent to that of radical surgery with a much improved functional and cosmetic outcome; intra-operative electron beam radiation therapy improves the outcome of patients with retroperitoneal sarcomas when given after grossly complete resection combined with external beam radiation therapy (pre- or post-operatively); radiation is a highly effective alternative to extensive surgery for desmoid tumors; local control of giant cell tumors by modern radiation techniques is ∼ 80% and the incidence of radiation induced tumors at 10 years is ∼ 3%; to decrease the incidence of radiation induced sarcoma, resection has replaced radiation in the management of selected patients with primary Ewing's sarcoma when the response to chemotherapy has been excellent and the

  20. Keratoconus as a manifestation of connective tissue dysplasia

    Directory of Open Access Journals (Sweden)

    M. M. Bikbov

    2015-01-01

    Full Text Available Common association of keratoconus and connective tissue dysplasia indicates that these disorders possibly share etiology and pathogenesis. Connective tissue dysplasia is characterized by the decrease in certain types of collagen, abnormalities of their proportion, alteration of collagen synthesis and assembly, immature collagen synthesis, abnormalities of collagen fiber structure, defects of type III collagen synthesis, peptidase deficiency, and increase in pro-collagen as compared with collagen. The latter accounts for immature collagen level increase in tissues and organs and systemic congenital laxity of connective tissue. This results in the abnormalities of biomechanical properties of organs and tissues which are composed of collagen fibers. Corneal stroma consists of collagen fibers and glycoprotein matrix. Hence, quantitative and qualitative changes in connective tissue dysplasia affect corneal biomechanics. Abnormalities of collagen fibril orientation result in their reorganization thus influencing corneal shape and transparency. In keratoconus, decreased total collagen and type I, type III, and type IV collagen, increased type XV collagen, and abnormalities of their proportion in corneal stroma as well as allele differences in COL4A3 and CoL4A4 genes encoding 2 of 6 α-chains of type IV collagen were demonstrated. Nucleotide polymorphisms in LOX genes encoding lysyl oxidase and lysyl oxidase-like enzymes which are responsible for cross-linking of collagen polypeptide chains (and, therefore, mechanical strength of fibrils were revealed as well. LOX gene deficiency that accounts for systemic biomechanical abnormalities was also recognized in certain connective tissue dysplasia. Further studies will provide early diagnosis and pathogenically target therapy of genetic disorders associated with tissue abnormalities 

  1. Construction of tissue-engineered heart valves by using decellularized scaffolds and endothelial progenitor cells.

    Science.gov (United States)

    Fang, Ning-Tao; Xie, Shang-Zhe; Wang, Song-Mei; Gao, Hong-Yang; Wu, Chun-Gen; Pan, Luan-Feng

    2007-04-20

    Tissue-engineered heart valves have the potential to overcome the limitations of present heart valve replacements. This study was designed to develop a tissue engineering heart valve by using human umbilical cord blood-derived endothelial progenitor cells (EPCs) and decellularized valve scaffolds. Decellularized valve scaffolds were prepared from fresh porcine heart valves. EPCs were isolated from fresh human umbilical cord blood by density gradient centrifugation, cultured for 3 weeks in EGM-2-MV medium, by which time the resultant cell population became endothelial in nature, as assessed by immunofluorescent staining. EPC-derived endothelial cells were seeded onto the decellularized scaffold at 3 x 10(6) cells/cm(2) and cultured under static conditions for 7 days. Proliferation of the seeded cells on the scaffolds was detected using the MTT assay. Tissue-engineered heart valves were analyzed by HE staining, immunofluorescent staining and scanning electron microscopy. The anti-thrombogenic function of the endothelium on the engineered heart valves was evaluated by platelet adhesion experiments and reverse transcription-polymerase chain reaction (RT-PCR) analysis for the expression of endothelial nitric oxide synthase (eNOS) and tissue-type plasminogen activator (t-PA). EPC-derived endothelial cells showed a histolytic cobblestone morphology, expressed specific markers of the endothelial cell lineage including von Willebrand factor (vWF) and CD31, bound a human endothelial cell-specific lectin, Ulex Europaeus agglutinin-1 (UEA-1), and took up Dil-labeled low density lipoprotein (Dil-Ac-LDL). After seeding on the decellularized scaffold, the cells showed excellent metabolic activity and proliferation. The cells formed confluent endothelial monolayers atop the decellularized matrix, as assessed by HE staining and immunostaining for vWF and CD31. Scanning electron microscopy demonstrated the occurrence of tight junctions between cells forming the confluent monolayer

  2. 3D Normal Human Neural Progenitor Tissue-Like Assemblies: A Model of Persistent VZV Infection

    Science.gov (United States)

    Goodwin, Thomas J.

    2013-01-01

    Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus that causes varicella upon primary infection, establishes latency in multiple ganglionic neurons, and can reactivate to cause zoster. Live attenuated VZV vaccines are available; however, they can also establish latent infections and reactivate. Studies of VZV latency have been limited to the analyses of human ganglia removed at autopsy, as the virus is strictly a human pathogen. Recently, terminally differentiated human neurons have received much attention as a means to study the interaction between VZV and human neurons; however, the short life-span of these cells in culture has limited their application. Herein, we describe the construction of a model of normal human neural progenitor cells (NHNP) in tissue-like assemblies (TLAs), which can be successfully maintained for at least 180 days in three-dimensional (3D) culture, and exhibit an expression profile similar to that of human trigeminal ganglia. Infection of NHNP TLAs with cell-free VZV resulted in a persistent infection that was maintained for three months, during which the virus genome remained stable. Immediate-early, early and late VZV genes were transcribed, and low-levels of infectious VZV were recurrently detected in the culture supernatant. Our data suggest that NHNP TLAs are an effective system to investigate long-term interactions of VZV with complex assemblies of human neuronal cells.

  3. Electrical impedance along connective tissue planes associated with acupuncture meridians

    Directory of Open Access Journals (Sweden)

    Hammerschlag Richard

    2005-05-01

    Full Text Available Abstract Background Acupuncture points and meridians are commonly believed to possess unique electrical properties. The experimental support for this claim is limited given the technical and methodological shortcomings of prior studies. Recent studies indicate a correspondence between acupuncture meridians and connective tissue planes. We hypothesized that segments of acupuncture meridians that are associated with loose connective tissue planes (between muscles or between muscle and bone visible by ultrasound have greater electrical conductance (less electrical impedance than non-meridian, parallel control segments. Methods We used a four-electrode method to measure the electrical impedance along segments of the Pericardium and Spleen meridians and corresponding parallel control segments in 23 human subjects. Meridian segments were determined by palpation and proportional measurements. Connective tissue planes underlying those segments were imaged with an ultrasound scanner. Along each meridian segment, four gold-plated needles were inserted along a straight line and used as electrodes. A parallel series of four control needles were placed 0.8 cm medial to the meridian needles. For each set of four needles, a 3.3 kHz alternating (AC constant amplitude current was introduced at three different amplitudes (20, 40, and 80 μAmps to the outer two needles, while the voltage was measured between the inner two needles. Tissue impedance between the two inner needles was calculated based on Ohm's law (ratio of voltage to current intensity. Results At the Pericardium location, mean tissue impedance was significantly lower at meridian segments (70.4 ± 5.7 Ω compared with control segments (75.0 ± 5.9 Ω (p = 0.0003. At the Spleen location, mean impedance for meridian (67.8 ± 6.8 Ω and control segments (68.5 ± 7.5 Ω were not significantly different (p = 0.70. Conclusion Tissue impedance was on average lower along the Pericardium meridian, but not

  4. Prospective isolation of human embryonic stem cell-derived cardiovascular progenitors that integrate into human fetal heart tissue.

    Science.gov (United States)

    Ardehali, Reza; Ali, Shah R; Inlay, Matthew A; Abilez, Oscar J; Chen, Michael Q; Blauwkamp, Timothy A; Yazawa, Masayuki; Gong, Yongquan; Nusse, Roeland; Drukker, Micha; Weissman, Irving L

    2013-02-26

    A goal of regenerative medicine is to identify cardiovascular progenitors from human ES cells (hESCs) that can functionally integrate into the human heart. Previous studies to evaluate the developmental potential of candidate hESC-derived progenitors have delivered these cells into murine and porcine cardiac tissue, with inconclusive evidence regarding the capacity of these human cells to physiologically engraft in xenotransplantation assays. Further, the potential of hESC-derived cardiovascular lineage cells to functionally couple to human myocardium remains untested and unknown. Here, we have prospectively identified a population of hESC-derived ROR2(+)/CD13(+)/KDR(+)/PDGFRα(+) cells that give rise to cardiomyocytes, endothelial cells, and vascular smooth muscle cells in vitro at a clonal level. We observed rare clusters of ROR2(+) cells and diffuse expression of KDR and PDGFRα in first-trimester human fetal hearts. We then developed an in vivo transplantation model by transplanting second-trimester human fetal heart tissues s.c. into the ear pinna of a SCID mouse. ROR2(+)/CD13(+)/KDR(+)/PDGFRα(+) cells were delivered into these functioning fetal heart tissues: in contrast to traditional murine heart models for cell transplantation, we show structural and functional integration of hESC-derived cardiovascular progenitors into human heart.

  5. Alveolar ridge augmentation by connective tissue grafting using a pouch method and modified connective tissue technique: A prospective study

    Directory of Open Access Journals (Sweden)

    Ashish Agarwal

    2015-01-01

    Full Text Available Background: Localized alveolar ridge defect may create physiological and pathological problems. Developments in surgical techniques have made it simpler to change the configuration of a ridge to create a more aesthetic and more easily cleansable shape. The purpose of this study was to compare the efficacy of alveolar ridge augmentation using a subepithelial connective tissue graft in pouch and modified connective tissue graft technique. Materials and Methods: In this randomized, double blind, parallel and prospective study, 40 non-smoker individuals with 40 class III alveolar ridge defects in maxillary anterior were randomly divided in two groups. Group I received modified connective tissue graft, while group II were treated with subepithelial connective tissue graft in pouch technique. The defect size was measured in its horizontal and vertical dimension by utilizing a periodontal probe in a stone cast at base line, after 3 months, and 6 months post surgically. Analysis of variance and Bonferroni post-hoc test were used for statistical analysis. A two-tailed P < 0.05 was considered to be statistically significant. Results: Mean values in horizontal width after 6 months were 4.70 ± 0.87 mm, and 4.05 ± 0.89 mm for group I and II, respectively. Regarding vertical heights, obtained mean values were 4.75 ± 0.97 mm and 3.70 ± 0.92 mm for group I and group II, respectively. Conclusion: Within the limitations of this study, connective tissue graft proposed significantly more improvement as compare to connective tissue graft in pouch.

  6. Use of human umbilical cord blood-derived progenitor cells for tissue-engineered heart valves.

    Science.gov (United States)

    Sodian, Ralf; Schaefermeier, Philipp; Abegg-Zips, Sybille; Kuebler, Wolfgang M; Shakibaei, Mehdi; Daebritz, Sabine; Ziegelmueller, Johannes; Schmitz, Christoph; Reichart, Bruno

    2010-03-01

    Tissue engineering of autologous heart valves with the potential to grow and to remodel represents a promising concept. Here we describe the use of cryopreserved umbilical cord blood-derived CD133(+) cells as a single cell source for the tissue engineering of heart valves. After expansion and differentiation of CD133(+) cells, phenotypes were analyzed by immunohistochemistry and cryopreserved. Heart valve scaffolds fabricated from a biodegradable polymer (n = 8) were seeded with blood-derived myofibroblasts and subsequently coated with blood-derived endothelial cells. Afterward, the heart valve constructs were grown in a pulse duplicator system. Analysis of all heart valves, including histology, immunohistochemistry, electron microscopy, fluorescence imaging, and biochemical and biomechanical examination, was performed. The tissue-engineered heart valves showed endothelialized layered tissue formation including connective tissue between the inside and the outside of the scaffold. The notion of an intact endothelial phenotype was substantiated by fluorescence imaging studies of cellular nitric oxide production and Ca(2+) signaling. Electron microscopy showed that the cells had grown into the pores and formed a confluent tissue layer. Biochemical examination showed extracellular matrix formation (77% +/- 9% collagen of human pulmonary leaflet tissue [HPLT], 85% +/- 61% glycosaminoglycans of HPLT and 67% +/- 17% elastin of HPLT). Importantly, this study demonstrates in vitro generation of viable human heart valves based on CD133(+) cells derived from umbilical cord blood. These findings constitute a significant step forward in the development of new clinical strategies for the treatment of congenital defects. 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  7. Trophic factors from adipose tissue-derived multi-lineage progenitor cells promote cytodifferentiation of periodontal ligament cells

    Energy Technology Data Exchange (ETDEWEB)

    Sawada, Keigo [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Takedachi, Masahide, E-mail: takedati@dent.osaka-u.ac.jp [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Yamamoto, Satomi; Morimoto, Chiaki; Ozasa, Masao; Iwayama, Tomoaki [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan); Lee, Chun Man [Medical Center for Translational Research, Osaka University Hospital, Osaka (Japan); Okura, Hanayuki; Matsuyama, Akifumi [Research on Disease Bioresources, Platform of Therapeutics for Rare Disease, National Institute of Biomedical Innovation, Osaka (Japan); Kitamura, Masahiro; Murakami, Shinya [Department of Periodontology, Osaka University Graduate School of Dentistry, Osaka (Japan)

    2015-08-14

    Stem and progenitor cells are currently being investigated for their applicability in cell-based therapy for periodontal tissue regeneration. We recently demonstrated that the transplantation of adipose tissue-derived multi-lineage progenitor cells (ADMPCs) enhances periodontal tissue regeneration in beagle dogs. However, the molecular mechanisms by which transplanted ADMPCs induce periodontal tissue regeneration remain to be elucidated. In this study, trophic factors released by ADMPCs were examined for their paracrine effects on human periodontal ligament cell (HPDL) function. ADMPC conditioned medium (ADMPC-CM) up-regulated osteoblastic gene expression, alkaline phosphatase activity and calcified nodule formation in HPDLs, but did not significantly affect their proliferative response. ADMPCs secreted a number of growth factors, including insulin-like growth factor binding protein 6 (IGFBP6), hepatocyte growth factor and vascular endothelial growth factor. Among these, IGFBP6 was most highly expressed. Interestingly, the positive effects of ADMPC-CM on HPDL differentiation were significantly suppressed by transfecting ADMPCs with IGFBP6 siRNA. Our results suggest that ADMPCs transplanted into a defect in periodontal tissue release trophic factors that can stimulate the differentiation of HPDLs to mineralized tissue-forming cells, such as osteoblasts and cementoblasts. IGFBP6 may play crucial roles in ADMPC-induced periodontal regeneration. - Highlights: • ADMPC-derived humoral factors stimulate cytodifferentiation of HPDLs. • ADMPCs secret growth factors including IGFBP6, VEGF and HGF. • IGFBP6 is involved in the promotion effect of ADMPC-CM on HPDL cytodifferentiation.

  8. Trophic factors from adipose tissue-derived multi-lineage progenitor cells promote cytodifferentiation of periodontal ligament cells

    International Nuclear Information System (INIS)

    Sawada, Keigo; Takedachi, Masahide; Yamamoto, Satomi; Morimoto, Chiaki; Ozasa, Masao; Iwayama, Tomoaki; Lee, Chun Man; Okura, Hanayuki; Matsuyama, Akifumi; Kitamura, Masahiro; Murakami, Shinya

    2015-01-01

    Stem and progenitor cells are currently being investigated for their applicability in cell-based therapy for periodontal tissue regeneration. We recently demonstrated that the transplantation of adipose tissue-derived multi-lineage progenitor cells (ADMPCs) enhances periodontal tissue regeneration in beagle dogs. However, the molecular mechanisms by which transplanted ADMPCs induce periodontal tissue regeneration remain to be elucidated. In this study, trophic factors released by ADMPCs were examined for their paracrine effects on human periodontal ligament cell (HPDL) function. ADMPC conditioned medium (ADMPC-CM) up-regulated osteoblastic gene expression, alkaline phosphatase activity and calcified nodule formation in HPDLs, but did not significantly affect their proliferative response. ADMPCs secreted a number of growth factors, including insulin-like growth factor binding protein 6 (IGFBP6), hepatocyte growth factor and vascular endothelial growth factor. Among these, IGFBP6 was most highly expressed. Interestingly, the positive effects of ADMPC-CM on HPDL differentiation were significantly suppressed by transfecting ADMPCs with IGFBP6 siRNA. Our results suggest that ADMPCs transplanted into a defect in periodontal tissue release trophic factors that can stimulate the differentiation of HPDLs to mineralized tissue-forming cells, such as osteoblasts and cementoblasts. IGFBP6 may play crucial roles in ADMPC-induced periodontal regeneration. - Highlights: • ADMPC-derived humoral factors stimulate cytodifferentiation of HPDLs. • ADMPCs secret growth factors including IGFBP6, VEGF and HGF. • IGFBP6 is involved in the promotion effect of ADMPC-CM on HPDL cytodifferentiation

  9. Investigation of The Effects of Connective Tissue Mobilisation on ...

    African Journals Online (AJOL)

    Aim: This study was planned to investigate the effects of connective tissue mobilization (CTM) on quality of life and emotional status in healthy subjects. Design; Prospective trial, Setting; Treatment and Population. The study was conducted on 100 volunteers (students). Students in second class were in CTM group (20,49±1 ...

  10. SECONDARY PULMONARY ARTERIAL HYPERTENSION IN SYSTEMIC DISEASES OF CONNECTIVE TISSUE

    Directory of Open Access Journals (Sweden)

    N. A. Shostak

    2016-01-01

    Full Text Available Modern definition of pulmonary arterial hypertension (PAH as well as data on prevalence and incidence of secondary PAH in systemic disease of connective tissue is presented,  including data of USA, France and Scotland registers. The main chains of pathogenesis, classification approaches, clinical features and diagnostics are described. 

  11. SECONDARY PULMONARY ARTERIAL HYPERTENSION IN SYSTEMIC DISEASES OF CONNECTIVE TISSUE

    Directory of Open Access Journals (Sweden)

    N. A. Shostak

    2009-01-01

    Full Text Available Modern definition of pulmonary arterial hypertension (PAH as well as data on prevalence and incidence of secondary PAH in systemic disease of connective tissue is presented,  including data of USA, France and Scotland registers. The main chains of pathogenesis, classification approaches, clinical features and diagnostics are described. 

  12. Basic Components of Connective Tissues and Extracellular Matrix

    DEFF Research Database (Denmark)

    Halper, Jaroslava; Kjær, Michael

    2014-01-01

    of specific organ systems, but they also provide a scaffold for elastogenesis in elastic tissues. Fibrillin is important for the assembly of elastin into elastic fibers. Mutations in the fibrillin-1 gene are closely associated with Marfan syndrome. Fibulins are tightly connected with basement membranes...

  13. On the connective tissue regulator Follistatin-like 1

    NARCIS (Netherlands)

    Sylva, M.

    2014-01-01

    Even though for many years the molecular mechanisms underlying cardiac development have been studied, the majority of cardiac defects remain unexplained. Defects in the cardiac connective tissue component result in a large proportion of heart defects such as valve and septal defects. Previous

  14. Possibility of laboratory assessment of the state of connective tissue

    Directory of Open Access Journals (Sweden)

    G. A. Berezovskaya

    2015-01-01

    Full Text Available This article deals with the possibilities of laboratory assessment of the state of the connective tissue. It contains brief information about its structure, functions and roles of the various components in the development of pathological processes, and provides laboratory diagnostic methods of these changes.

  15. Overview of the radiology of connective tissue disorders in children

    Energy Technology Data Exchange (ETDEWEB)

    Hanlon, R.; King, S

    2000-02-01

    This review article describes the imaging finding of the connective tissue disorders in children. The radiological features of the following conditions are described; the spondyloarthropathics, systemic lupus erythematosus (SLE), dermatomyositis, scleroderma, the vasculitides, Kawasaki disease, synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO), and focal myositis. The features on several integrated imaging techniques are described.

  16. Clinical application of tissue engineered human heart valves using autologous progenitor cells.

    Science.gov (United States)

    Cebotari, Serghei; Lichtenberg, Artur; Tudorache, Igor; Hilfiker, Andres; Mertsching, Heike; Leyh, Rainer; Breymann, Thomas; Kallenbach, Klaus; Maniuc, Liviu; Batrinac, Aurel; Repin, Oleg; Maliga, Oxana; Ciubotaru, Anatol; Haverich, Axel

    2006-07-04

    Tissue engineering (TE) of heart valves reseeded with autologous cells has been successfully performed in vitro. Here, we report our first clinical implantation of pulmonary heart valves (PV) engineered with autologous endothelial progenitor cells (EPCs) and the results of 3.5 years of follow-up. Human PV allografts were decellularized (Trypsin/EDTA) and resulting scaffolds reseeded with peripheral mononuclear cells isolated from human blood. Positive stain for von Willebrand factor, CD31, and Flk-1 was observed in monolayers of cells cultivated and differentiated on the luminal surface of the scaffolds in a dynamic bioreactor system for up to 21 days, indicating endothelial nature. PV reseeded with autologous cells were implanted into 2 pediatric patients (age 13 and 11) with congenital PV failure. Postoperatively, a mild pulmonary regurgitation was documented in both children. Based on regular echocardiographic investigations, hemodynamic parameters and cardiac morphology changed in 3.5 years as follows: increase of the PV annulus diameter (18 to 22.5 mm and 22 to 26 mm, respectively), decrease of valve regurgitation (trivial/mild and trivial, respectively), decrease (16 to 9 mm Hg) or a increase (8 to 9.5 mm Hg) of mean transvalvular gradient, remained 26 mm or decreased (32 to 28 mm) right-ventricular end-diastolic diameter. The body surface area increased (1.07 to 1.42 m2 and 1.07 to 1.46 m2, respectively). No signs of valve degeneration were observed in both patients. TE of human heart valves using autologous EPC is a feasible and safe method for pulmonary valve replacement. TE valves have the potential to remodel and grow accordingly to the somatic growth of the child.

  17. iPS Cells Reprogrammed From Human Mesenchymal-Like Stem/Progenitor Cells of Dental Tissue Origin

    Science.gov (United States)

    2010-01-01

    Generation of induced pluripotent stem (iPS) cells holds a great promise for regenerative medicine and other aspects of clinical applications. Many types of cells have been successfully reprogrammed into iPS cells in the mouse system; however, reprogramming human cells have been more difficult. To date, human dermal fibroblasts are the most accessible and feasible cell source for iPS generation. Dental tissues derived from ectomesenchyme harbor mesenchymal-like stem/progenitor cells and some of the tissues have been treated as biomedical wastes, for example, exfoliated primary teeth and extracted third molars. We asked whether stem/progenitor cells from discarded dental tissues can be reprogrammed into iPS cells. The 4 factors Lin28/Nanog/Oct4/Sox2 or c-Myc/Klf4/Oct4/Sox2 carried by viral vectors were used to reprogram 3 different dental stem/progenitor cells: stem cells from exfoliated deciduous teeth (SHED), stem cells from apical papilla (SCAP), and dental pulp stem cells (DPSCs). We showed that all 3 can be reprogrammed into iPS cells and appeared to be at a higher rate than fibroblasts. They exhibited a morphology indistinguishable from human embryonic stem (hES) cells in cultures and expressed hES cell markers SSEA-4, TRA-1-60, TRA-1-80, TRA-2-49, Nanog, Oct4, and Sox2. They formed embryoid bodies in vitro and teratomas in vivo containing tissues of all 3 germ layers. We conclude that cells of ectomesenchymal origin serve as an excellent alternative source for generating iPS cells. PMID:19795982

  18. Human adipose tissue-derived tenomodulin positive subpopulation of stem cells: A promising source of tendon progenitor cells.

    Science.gov (United States)

    Gonçalves, A I; Gershovich, P M; Rodrigues, M T; Reis, R L; Gomes, M E

    2018-03-01

    Cell-based therapies are of particular interest for tendon and ligament regeneration given the low regenerative potential of these tissues. Adipose tissue is an abundant source of stem cells, which may be employed for the healing of tendon lesions. However, human adult multipotent adipose-derived stem cells (hASCs) isolated from the stromal vascular fraction of adipose tissue originate highly heterogeneous cell populations that hinder their use in specific tissue-oriented applications. In this study, distinct subpopulations of hASCs were immunomagnetic separated and their tenogenic differentiation capacity evaluated in the presence of several growth factors (GFs), namely endothelial GF, basic-fibroblast GF, transforming GF-β1 and platelet-derived GF-BB, which are well-known regulators of tendon development, growth and healing. Among the screened hASCs subpopulations, tenomodulin-positive cells were shown to be more promising for tenogenic applications and therefore this subpopulation was further studied, assessing tendon-related markers (scleraxis, tenomodulin, tenascin C and decorin) both at gene and protein level. Additionally, the ability for depositing collagen type I and III forming extracellular matrix structures were weekly assessed up to 28 days. The results obtained indicated that tenomodulin-positive cells exhibit phenotypical features of tendon progenitor cells and can be biochemically induced towards tenogenic lineage, demonstrating that this subset of hASCs can provide a reliable source of progenitor cells for therapies targeting tendon regeneration. Copyright © 2017 John Wiley & Sons, Ltd.

  19. A Framework for Modelling Connective Tissue Changes in VIIP Syndrome

    Science.gov (United States)

    Ethier, C. R.; Best, L.; Gleason, R.; Mulugeta, L.; Myers, J. G.; Nelson, E. S.; Samuels, B. C.

    2014-01-01

    Insertion of astronauts into microgravity induces a cascade of physiological adaptations, notably including a cephalad fluid shift. Longer-duration flights carry an increased risk of developing Visual Impairment and Intracranial Pressure (VIIP) syndrome, a spectrum of ophthalmic changes including posterior globe flattening, choroidal folds, distension of the optic nerve sheath, kinking of the optic nerve and potentially permanent degradation of visual function. The slow onset of changes in VIIP, their chronic nature, and the similarity of certain clinical features of VIIP to ophthalmic findings in patients with raised intracranial pressure strongly suggest that: (i) biomechanical factors play a role in VIIP, and (ii) connective tissue remodeling must be accounted for if we wish to understand the pathology of VIIP. Our goal is to elucidate the pathophysiology of VIIP and suggest countermeasures based on biomechanical modeling of ocular tissues, suitably informed by experimental data, and followed by validation and verification. We specifically seek to understand the quasi-homeostatic state that evolves over weeks to months in space, during which ocular tissue remodeling occurs. This effort is informed by three bodies of work: (i) modeling of cephalad fluid shifts; (ii) modeling of ophthalmic tissue biomechanics in glaucoma; and (iii) modeling of connective tissue changes in response to biomechanical loading.

  20. Cell-Cell Connection Enhances Proliferation and Neuronal Differentiation of Rat Embryonic Neural Stem/Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Qian Jiao

    2017-07-01

    Full Text Available Cell-cell interaction as one of the niche signals plays an important role in the balance of stem cell quiescence and proliferation or differentiation. In order to address the effect and the possible mechanisms of cell-cell connection on neural stem/progenitor cells (NSCs/NPCs proliferation and differentiation, upon passaging, NSCs/NPCs were either dissociated into single cell as usual (named Group I or mechanically triturated into a mixture of single cell and small cell clusters containing direct cell-cell connections (named Group II. Then the biological behaviors including proliferation and differentiation of NSCs/NPCs were observed. Moreover, the expression of gap junction channel, neurotrophic factors and the phosphorylation status of MAPK signals were compared to investigate the possible mechanisms. Our results showed that, in comparison to the counterparts in Group I, NSCs/NPCs in Group II survived well with preferable neuronal differentiation. In coincidence with this, the expression of connexin 45 (Cx45, as well as brain derived neurotrophic factor (BDNF and neurotrophin 3 (NT-3 in Group II were significantly higher than those in Group I. Phosphorylation of ERK1/2 and JNK2 were significantly upregulated in Group II too, while no change was found about p38. Furthermore, the differences of NSCs/NPCs biological behaviors between Group I and II completely disappeared when ERK and JNK phosphorylation were inhibited. These results indicated that cell-cell connection in Group II enhanced NSCs/NPCs survival, proliferation and neuronal differentiation through upregulating the expression of gap junction and neurotrophic factors. MAPK signals- ERK and JNK might contribute to the enhancement. Efforts for maintaining the direct cell-cell connection are worth making to provide more favorable niches for NSCs/NPCs survival, proliferation and neuronal differentiation.

  1. Mapping by monoclonal antibody detection of glycosaminoglycans in connective tissues

    DEFF Research Database (Denmark)

    Couchman, J R; Caterson, B; Christner, J E

    1984-01-01

    organizations on the GAG molecule endowed by the sulphate groups. So far, it has not been possible to identify and map chondroitins of differing sulphation in tissues, but we have now raised three monoclonal antibodies which specifically recognize unsulphated, 4-sulphated and 6-sulphated chondroitin...... of the glycosaminoglycan (GAG), particularly with respect to self-association and interactions with other extracellular matrix components. Interactions with specific molecules from different connective tissue types, such as the collagens and their associated glycoproteins, could be favoured by particular charge...

  2. A Histopathological Study of Pulmonary Hypertension in Connective Tissue Disease

    Directory of Open Access Journals (Sweden)

    Nobuhito Sasaki

    2011-01-01

    Full Text Available Connective tissue diseases (CTD, such as systemic sclerosis (SSc, systemic lupus erythematosus (SLE, and mixed connective tissue disease (MCTD, develop pulmonary hypertension (PH. Generally all PH cases associated with any CTD are classified into the same PH group. However, histological examination shows both common and specific lesions for each disease. In patients with SLE, fibrosis is generally rare and mild. The findings of PH in SLE are similar to those in primary pulmonary hypertension. Many cases of SSc are accompanied by fibrosis. MCTD is rather close to SSc. Arterial and arteriolar lesions of MCTD are characterized by fibrous intimal thickening. In this review, we describe the pathological features of PH associated with each CTD.

  3. [Second degree atrioventricular block in mixed connective tissue disease].

    Science.gov (United States)

    Vinsonneau, U; Delluc, A; Bergez, C; Caumes, D; Talarmin, F

    2005-08-01

    Mixed connective tissue disease (MCTD) is characterized by overlapping features of progressive systemic sclerosis, dermatomyositis and systemic lupus erythematosus, and by high rate of antibodies to an extractable nuclear antigen ribonucleoprotein. Cardiac manifestations in MTCD are rare. A 58 years old man was admitted for mild fever, a impairment of the general status, muscular pain and a Raynaud's phenomenon. Biologic abnormalities were an inflammatory syndrome, elevated serum CPK and high rate anti-RNP antibodies. Diagnosis of mixed connective tissue disease was made. Shortly after, a Wenckebach atrioventricular block occurred. Systemic corticosteroids were efficient. Heart blocks are rarely described in MCTD. Three cases have been reported. It's a systemic complication resulting of an inflammatory process often responsive to steroids.

  4. Mechanism of endothelial progenitor cell recruitment into neo-vessels in adjacent non-tumor tissues in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Yu, De-cai; Chen, Jun; Sun, Xi-tai; Zhuang, Lin-yuan; Jiang, Chun-ping; Ding, Yi-tao

    2010-01-01

    We investigated the distribution and clinical significance of mobilized endothelial progenitor cells (EPCs) in hepatocellular carcinoma (HCC). We found that many more EPCs were recruited to nonmalignant liver tissue (especially into adjacent non-tumor tissues (AT)) than to tumor vessels. These results suggest that the mechanism underlying the recruitment of EPCs into microvessels in AT merits further investigation Angiogenic factors were detected in three tissue microarrays comprising normal liver, paired tumor tissue (TT) and AT from 105 patients (who had undergone hepatectomy for HCC) using immunohistochemistry. Also, the number of EPCs (positive for Sca-1, Flk-1 and c-Kit) in the blood and liver of cirrhotic mice were determined by flow cytometry and immunohistochemistry. The distribution of these labeled EPCs in tumor and non-tumor tissues was then studied. The results from the tissue microarrays showed that the expression levels of VEGF-A, bFGF, TGF-β, MCP-1, TSP-1, MMP-9, TIMP-2, and endostatin were significantly higher in AT than in either normal liver or TT (p < 0.05), but no significant difference was found in the expression levels of COX-2 and NOS-2 between AT and TT. The expression of VEGF-A, bFGF, TGF-β, MCP-1, TSP-1, MMP-9, TIMP-2, endostatin, COX-2, and NOS-2 in normal liver tissue was weaker than that in AT or TT. In cirrhotic mice, the number of circulating endothelial progenitor cells gradually increased, before decreasing again. In this mouse model, increased numbers of EPCs were recruited and homed specifically to the cirrhotic liver. Both liver cirrhosis and HCC led to increased expression of pro-angiogenic factors, which resulted in the recruitment of EPCs into AT. Also, EPCs were mobilized, recruited and homed to cirrhotic liver. The unique pathology of HCC coupled with liver cirrhosis may, therefore, be associated with the distribution and function of EPCs

  5. [Connective tissue diseases in hospital practice in Ouagadougou (Burkina Faso)].

    Science.gov (United States)

    Ouédraogo, D D; Korsaga-Somé, N; Zabsonné Tiendrébéogo, J; Tiéno, H; Kaboré, H; Niamba, P; Drabo, J

    2014-01-01

    To describe the semiological and immunological features of connective tissue diseases seen at the Yalgado Ouédraogo University Hospital in Ouagadougou. A retrospective study reviewed the records of patients seen in the hospital dermatology and internal medicine departments from January 1, 2004, through December 31, 2009 and diagnosed with systemic lupus erythematosus (SLE), systemic sclerosis (ScS), dermatopolymyositis (DPM), primary Gougerot-Sjögren disease (GS), polymyositis (PM) or indeterminate connective tissue disease (ICTD) meeting the criteria of the American College of Rheumatology. The study included 42 patients, 36 women and 6 men. Their mean age was 41.2 years ±11.97 (range: 15-75). SLE was the diagnosis for 10 patients, ScS for 14, DPM for 7, primary GS for 1, PM for 1, and ICTD for 9. Hematologic (93%), cutaneous (88%), and rheumatologic (81%) abnormalities were the most frequent manifestations. The specific auto-antibodies associated with SLE patients were: anti-native DNA (3/6), anti-Sm (3/6), anti-RNP (3/6), and anti-SSA (4/6); anti-Scl 70 antibodies were present in 5 patients with ScS. Connective tissue diseases seem to be rare in Africa, south of the Sahara. However, the very fragmentary studies and the weak healthcare coverage do not allow any definitive conclusions.

  6. Management of peri-implant soft tissue defect with connective tissue graft - A case report

    Directory of Open Access Journals (Sweden)

    Mohinder Panwar

    2017-01-01

    Full Text Available The use of dental implants to replace missing and nonrestorable teeth has increased significantly in the past two decades. The health of peri-implant tissues plays an important role in the long-term success of dental implants. Soft tissue dehiscence around dental implants has frequently been reported which may lead to poor oral hygiene, plaque accumulation, inflamed gingiva, compromised esthetics, and further progression to peri-implantitis. The coverage of exposed implants is aimed to provide adequate keratinized tissue around dental implant. Complete coverage of mucosal defect around the dental implants is still a challenging prospect. This case report describes correction of soft tissue defect and building up of keratinized tissue in relation to implant in the maxillary right first premolar region with subepithelial connective tissue graft along with coronally advanced flap.

  7. Marine-derived collagen biomaterials from echinoderm connective tissues.

    Science.gov (United States)

    Ferrario, Cinzia; Leggio, Livio; Leone, Roberta; Di Benedetto, Cristiano; Guidetti, Luca; Coccè, Valentina; Ascagni, Miriam; Bonasoro, Francesco; La Porta, Caterina A M; Candia Carnevali, M Daniela; Sugni, Michela

    2017-07-01

    The use of marine collagens is a hot topic in the field of tissue engineering. Echinoderms possess unique connective tissues (Mutable Collagenous Tissues, MCTs) which can represent an innovative source of collagen to develop collagen barrier-membranes for Guided Tissue Regeneration (GTR). In the present work we used MCTs from different echinoderm models (sea urchin, starfish and sea cucumber) to produce echinoderm-derived collagen membranes (EDCMs). Commercial membranes for GTR or soluble/reassembled (fibrillar) bovine collagen substrates were used as controls. The three EDCMs were similar among each other in terms of structure and mechanical performances and were much thinner and mechanically more resistant than the commercial membranes. Number of fibroblasts seeded on sea-urchin membranes were comparable to the bovine collagen substrates. Cell morphology on all EDCMs was similar to that of structurally comparable (reassembled) bovine collagen substrates. Overall, echinoderms, and sea urchins particularly, are alternative collagen sources to produce efficient GTR membranes. Sea urchins display a further advantage in terms of eco-sustainability by recycling tissues from food wastes. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Marine-derived collagen biomaterials from echinoderm connective tissues

    KAUST Repository

    Ferrario, Cinzia

    2016-03-31

    The use of marine collagens is a hot topic in the field of tissue engineering. Echinoderms possess unique connective tissues (Mutable Collagenous Tissues, MCTs) which can represent an innovative source of collagen to develop collagen barrier-membranes for Guided Tissue Regeneration (GTR). In the present work we used MCTs from different echinoderm models (sea urchin, starfish and sea cucumber) to produce echinoderm-derived collagen membranes (EDCMs). Commercial membranes for GTR or soluble/reassembled (fibrillar) bovine collagen substrates were used as controls. The three EDCMs were similar among each other in terms of structure and mechanical performances and were much thinner and mechanically more resistant than the commercial membranes. Number of fibroblasts seeded on sea-urchin membranes were comparable to the bovine collagen substrates. Cell morphology on all EDCMs was similar to that of structurally comparable (reassembled) bovine collagen substrates. Overall, echinoderms, and sea urchins particularly, are alternative collagen sources to produce efficient GTR membranes. Sea urchins display a further advantage in terms of eco-sustainability by recycling tissues from food wastes.

  9. HEREDITARY CONNECTIVE TISSUE DISORDERS: NOMENCLATURE AND DIAGNOSTIC ALGORITHM

    Directory of Open Access Journals (Sweden)

    A. V. Klemenov

    2015-01-01

    Full Text Available Hereditary connective tissue disorders (HCTDs are a genetically and clinically diverse group of diseases, which encompasses common congenital disorders of fibrous connective tissue structures. Out of the whole variety of the clinical manifestations of NCTDs, only differentiated monogenic syndromes with the agreed guidelines for their diagnosis have been long the focus of the medical community’s attention. Many unclassified forms of the pathology (dysplasia phenotypes have been disregarded while assessing a person’s prognosis and defining treatment policy. With no clear definition of NCTDs or their approved diagnostic algorithm, it is difficult to study their real prevalence in the population, to compare literature data, and to constructively discuss various scientific and practical aspects of this disease. Efforts to systematize individual clinical types of NCTD and to formulate their diagnostic criteria are set forth in the All-Russian Research Society Expert Committee national guidelines approved in 2009 and revised in 2012. The paper gives current views on the nomenclature of NCTDs, considers diagnostic criteria for both classified monogenic syndromes (Marfan's syndrome, Ehlers–Danlos' syndrome, MASS phenotype, primary mitral valve prolapse, joint hypermobility syndrome and unclassified dysplasia phenotypes (MASS-like phenotype, marfanoid appearance, Ehlers–Danlos-like phenotype, benign joint hypermobility syndrome, unclassified phenotype. The above abnormalities are presented as a continuous list drawn up in the decreasing order of the degree of their clinical manifestations and prognostic value (the phenotypic continuum described by M.J. Glesby and R.E. Pyentz: from monogenic syndromes through dysplasia phenotypes to an unclassified phenotype. Emphasis is laid on the clinical NCTD identification difficulties associated with the lack of specificity of external and visceral markers of connective tissue asthenia and with the certain

  10. Purpura fulminans in a patient with mixed connective tissue disease.

    LENUS (Irish Health Repository)

    Murad, Aizuri A

    2013-01-01

    A 43-year-old lady was admitted to the intensive care unit with sepsis. She had a history of mixed connective tissue disease, Raynaud\\'s syndrome and hypothyroidism. 2 days later, she developed a purpuric rash on her face and extremities with a livedoid background. Few days later, her distal fingers and toes became gangrenous which then had to be amputated. Laboratory investigations showed that she was coagulopathic and had multiple organ dysfunctions. Antiphospholipid antibodies were negative; however, protein C and antithrombin III levels were low. A skin biopsy showed fibrinoid necrosis in the vessel wall with microthrombi and red-cell extravasation. A diagnosis of purpura fulminans was made.

  11. Neoliberalism as the "Connective Tissue" of Contemporary Capitalism

    Directory of Open Access Journals (Sweden)

    Giulio Moini

    2016-09-01

    Full Text Available What can we understand better about contemporary economic, social, political and cultural processes using the category of neoliberalism? What can it add to an understanding of the present existing forms of social organization? The article tries to answer these main questions in theoretical terms considering the arguments of those who claim to have stopped using the concept and of those who, on the contrary, sus-tain its theoretical value. Neoliberalism is considered as the "connective tissue" of contemporary capitalism, which is able to shape historically significant links between processes, ideas and practices re-garding not only different sub-social systems (political, economic, cultural, etc., but also diverse scales of action (from global to local scale and vice versa. For this "ontological" reason the concept of neoliberalism seems to show an epistemological relevance, which rests on the capacity of this concept to disclose the interconnections not only between different phenomena, but also between each of them and a more general fabric of contemporary society. This regards especially functional relationships between the ontic and ontological dimensions of neoliberalism and contemporary capitalism. For this purpose the concept of neoliberalism as a "connective tissue" shows potential analytical advantages

  12. Hypertrophic Cardiomyopathy and Connective Tissue Dysplasia Syndrome: Comorbidity Variants

    Directory of Open Access Journals (Sweden)

    Yu. N. Belenkov

    2016-01-01

    Full Text Available Aim. To study the structure of co-morbidities, especially connective tissue undifferentiated dysplasia syndrome (CTDS, in patients with hypertrophic cardiomyopathy (HCM to develop an algorithm of complex examination of patients.Material and methods. Patients with HCM (n=186; 88 men and 78 women were examined. The diagnosis of HCM was based on current guidelines; molecular genetic study was performed in the absence of phenotypic manifestations. Echocardiography and standard examination of cardiac patient were performed in all patients to identify comorbidities. Genotyping of polymorphisms of 12 modifying genes was performed in 61 patients and 61 people in the control group.Results. HCM was most often associated with uterine myoma (52%, cardiac and extracardiac congenital malformations (50%, and thyroid diseases (37%. Combination of HCM with different variants of connective tissue dysplasia was found in 17% of patients (mitral valve prolapse – 6.3%, tricuspid valve prolapse – 2.7%, supplemental chords – 4.5%, bivalve aortic disease – 1.8%, increased left ventricular trabeculation – 3.6%, atrial septal aneurysm – 3.6%, membranous ventricular septal defect – 1.8%.Conclusion. CTDS is one of the most often associated disorders in patients with HCM. The study of the association of CTDS and HCM, the nature of their genetic structure and similarity of pathogenesis require further study.

  13. Cell-based and biomaterial approaches to connective tissue repair

    Science.gov (United States)

    Stalling, Simone Suzette

    Connective tissue injuries of skin, tendon and ligament, heal by a reparative process in adults, filling the wound site with fibrotic, disorganized scar tissue that poorly reflects normal tissue architecture or function. Conversely, fetal skin and tendon have been shown to heal scarlessly. Complete regeneration is not intrinsically ubiquitous to all fetal tissues; fetal diaphragmatic and gastrointestinal injuries form scars. In vivo studies suggest that the presence of fetal fibroblasts is essential for scarless healing. In the orthopaedic setting, adult anterior cruciate ligament (ACL) heals poorly; however, little is known about the regenerative capacity of fetal ACL or fetal ACL fibroblasts. We characterized in vitro wound healing properties of fetal and adult ACL fibroblasts demonstrating that fetal ACL fibroblasts migrate faster and elaborate greater quantities of type I collagen, suggesting the healing potential of the fetal ACL may not be intrinsically poor. Similar to fetal ACL fibroblasts, fetal dermal fibroblasts also exhibit robust cellular properties. We investigated the age-dependent effects of dermal fibroblasts on tendon-to-bone healing in rat supraspinatus tendon injuries, a reparative injury model. We hypothesized delivery of fetal dermal fibroblasts would increase tissue organization and mechanical properties in comparison to adult dermal fibroblasts. However, at 1 and 8 weeks, the presence of dermal fibroblasts, either adult or fetal, had no significant effect on tissue histology or mechanical properties. There was a decreasing trend in cross-sectional area of repaired tendons treated with fetal dermal fibroblasts in comparison to adult, but this finding was not significant in comparison to controls. Finally, we synthesized a novel polysaccharide, methacrylated methylcellulose (MA-MC), and fabricated hydrogels using a well-established photopolymerization technique. We characterized the physical and mechanical properties of MA-MC hydrogels in

  14. Mobilization of Circulating Vascular Progenitors in Cancer Patients Receiving External Beam Radiation in Response to Tissue Injury

    International Nuclear Information System (INIS)

    Allan, David S.; Morgan, Scott C.; Birch, Paul E.; Yang, Lin; Halpenny, Michael J.; Gunanayagam, Angelo; Li Yuhua; Eapen, Libni

    2009-01-01

    Purpose: Endothelial-like vascular progenitor cells (VPCs) are associated with the repair of ischemic tissue injury in several clinical settings. Because the endothelium is a principal target of radiation injury, VPCs may be important in limiting toxicity associated with radiotherapy (RT) in patients with cancer. Methods and Materials: We studied 30 patients undergoing RT for skin cancer (n = 5), head-and-neck cancer (n = 15), and prostate cancer (n = 10) prospectively, representing a wide range of irradiated mucosal volumes. Vascular progenitor cell levels were enumerated from peripheral blood at baseline, midway through RT, at the end of treatment, and 4 weeks after radiation. Acute toxicity was graded at each time point by use of the National Cancer Institute's Common Toxicity Criteria, version 3.0. Results: Significant increases in the proportion of CD34 + /CD133 + VPCs were observed after completion of RT, from 0.012% at baseline to 0.048% (p = 0.029), and the increase in this subpopulation was most marked in patients with Grade 2 peak toxicity or greater after RT (p = 0.034). Similarly, CD34 + /vascular endothelial growth factor receptor 2-positive VPCs were increased after the completion of radiation therapy in comparison to baseline (from 0.014% to 0.027%, p = 0.043), and there was a trend toward greater mobilization in patients with more significant toxicity (p = 0.08). The mobilization of CD34 + hematopoietic stem cells did not increase after treatment (p = 0.58), and there was no relationship with toxicity. Conclusions: We suggest that VPCs may play an important role in reducing radiation-induced tissue damage. Interventions that increase baseline VPC levels or enhance their mobilization and recruitment in response to RT may prove useful in facilitating more rapid and complete tissue healing.

  15. Molecular constituents of the extracellular matrix in rat liver mounting a hepatic progenitor cell response for tissue repair

    DEFF Research Database (Denmark)

    Vestentoft, Peter Siig; Jelnes, Peter; Andersen, Jesper Bøje

    2013-01-01

    BackgroundTissue repair in the adult mammalian liver occurs in two distinct processes, referred to as the first and second tiers of defense. We undertook to characterize the changes in molecular constituents of the extracellular matrix when hepatic progenitor cells (HPCs) respond in a second tier...... and compared the transcriptional signatures in untreated rat liver (control) with those from livers of day 1, day 5 and day 9 post hepatectomy in both protocols. Numerous transcripts encoding specific subunits of collagens, laminins, integrins, and various other extracellular matrix structural components were...... strong correlation with Krt1- 19, a well-established marker of a ductular/HPC reaction. Furthermore, a significant up-modulation and very strong correlation between the transcriptional profiles of Krt1-19 and St14 encoding matriptase, a component of a novel protease system, was found in the second tier...

  16. Connective tissue representation for detection of microcalcifications in digital mammograms

    Science.gov (United States)

    McLoughlin, Kristin J.; Bones, Philip J.; Kovesi, Peter

    2002-05-01

    Microcalcification clusters appear as an early sign of breast cancer and play an important role in interpreting mammograms. Progress is reported towards an automated computer aided detection system for clustered microcalcifications utilizing two image feature parameters: local contrast and shape. The use of a shape parameter is necessary to distinguish thin patches of connective tissue from microcalcifications. Two shape parameter techniques are compared in the segmentation of 15 digital mammogram images. The first technique implements the linear Hough transform, while the second uses image phase information in the Fourier domain. In both cases labeling of the image is performed by a deterministic relaxation scheme, in which both image data dn prior beliefs are weighted simultaneously. Similar segmentation results are obtained for each shape parameter technique however the execution time for the phase method is approximately one quarter that for the Hough method. Both techniques offer an improvement over segmentation results obtained without the shape parameter.

  17. Developmental competence of oocytes isolated from surplus medulla tissue in connection with cryopreservation of ovarian tissue for fertility preservation

    DEFF Research Database (Denmark)

    Wilken-Jensen, Helle N; Kristensen, Stine G; Jeppesen, Janni V

    2014-01-01

    OBJECTIVE: Evaluating the developmental competence of immature oocytes collected from surplus medulla tissue in connection with ovarian tissue cryopreservation for fertility preservation. DESIGN: Cohort comparative study. SETTING: University laboratory in Denmark from 2011-2012. POPULATION: 69...

  18. Monocytes/macrophages cooperate with progenitor cells during neovascularization and tissue repair: conversion of cell columns into fibrovascular bundles.

    Science.gov (United States)

    Anghelina, Mirela; Krishnan, Padma; Moldovan, Leni; Moldovan, Nicanor I

    2006-02-01

    The potential of monocytes/macrophages (MC/Mph) to contribute to neovascularization has recently become a topic of intense scrutiny. Here, we characterized the behavior of MC/Mph in cellular infiltrates, with emphasis on their spatial organization and localization in newly formed microvessels. To this end, we studied MC/Mph migration and assembly in basic fibroblast growth factor-supplemented Matrigel plugs placed in transgenic Tie2-beta-galactosidase mice for up to 4 weeks. In these plugs, along with Nile Red-positive adipocytes, we found MC/Mph distributed in cell cords, also containing various mature and progenitor tissue cells; and functional Tie2-positive or -negative microvessels embedded in bundles of fibrillar collagen surrounded by F4/80-positive MC/Mph. At earlier stages of infiltration, we found tubular destruction of the matrix (tunnels) and MC/Mph-lined capillary-like structures occasionally containing erythrocytes, indicating their propensity for endothelial trans-differentiation. We also analyzed in vitro the MCP-1-induced chemotactic migration of fluorescently labeled peritoneal MC/Mph incorporated in Matrigel-containing fluorescent protease substrates. Many of these MC/Mph produced MMP-12- and TIMP-1-dependent tunnels coupled with acquisition of a lumen. In conclusion, long-term implantation of Matrigel plugs qualifies as a novel experimental model of tissue regeneration, in which neovascularization intimately couples with fibrosis and organogenesis and in which cells of MC/Mph phenotype play a key structural role.

  19. The synergistic effect of bone forming peptide-1 and endothelial progenitor cells to promote vascularization of tissue engineered bone.

    Science.gov (United States)

    Wang, Huaixi; Cheng, Hao; Tang, Xiangyu; Chen, Jingyuan; Zhang, Jun; Wang, Wei; Li, Wenkai; Lin, Guanlin; Wu, Hua; Liu, Chaoxu

    2018-04-01

    Large segmental bone defect repair remains a challenge in orthopedic surgeries. The tissue engineered bone graft will be a promising approach if vascularization of the graft is realized. In this study, beta-tricalcium phosphate (β-TCP) scaffold incorporated with bone forming peptide-1 (BFP-1) was fabricated. Endothelial progenitor cells (EPCs) were introduced as well. We investigated the effect of BFP-1 on the proliferation, differentiation, and angiogenic functions of EPCs. Additionally, segmental femur bone defect was created in rabbits. Prevascularized β-TCP scaffold was constructed and implanted into the bone defect. The vascularization and bone formation were evaluated after 4 and 12 weeks. The results showed that BFP-1 promoted the angiogenesis of EPCs through activating the activin receptor-like kinase-1/Smad pathway. The prevascularized tissue engineered bone graft enhanced capillary vessel in-growth and new bone formation. Significantly higher values of vascularization and radiographic grading scores were observed in groups involving EPCs and BFP-1, compared to β-TCP scaffold alone. In conclusion, the synergy between EPCs and BFP-1 improved the vascularization and new bone regeneration, which has great potentials in clinical applications. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1008-1021, 2018. © 2017 Wiley Periodicals, Inc.

  20. Endothelial progenitor cells as a sole source for ex vivo seeding of tissue-engineered heart valves.

    Science.gov (United States)

    Sales, Virna L; Mettler, Bret A; Engelmayr, George C; Aikawa, Elena; Bischoff, Joyce; Martin, David P; Exarhopoulos, Alexis; Moses, Marsha A; Schoen, Frederick J; Sacks, Michael S; Mayer, John E

    2010-01-01

    We investigated whether circulating endothelial progenitor cells (EPCs) can be used as a cell source for the creation of a tissue-engineered heart valve (TEHV). Trileaflet valved conduits were fabricated using nonwoven polyglycolic acid/poly-4-hydroxybutyrate polymer. Ovine peripheral blood EPCs were dynamically seeded onto a valved conduit and incubated for 7, 14, and 21 days. Before seeding, EPCs were shown to express CD31(+), eNOS(+), and VE-Cadherin(+) but not alpha-smooth muscle actin. Histological analysis demonstrated relatively homogenous cellular ingrowth throughout the valved conduit. TEHV constructs revealed the presence of endothelial cell (EC) markers and alpha-smooth muscle actin(+) cells comparable with native valves. Protein levels were comparable with native valves and exceeded those in unseeded controls. EPC-TEHV demonstrated a temporal pattern of matrix metalloproteinases-2/9 expression and tissue inhibitors of metalloproteinase activities comparable to that of native valves. Mechanical properties of EPC-TEHV demonstrated significantly greater stiffness than that of the unseeded scaffolds and native valves. Circulating EPC appears to have the potential to provide both interstitial and endothelial functions and could potentially serve as a single-cell source for construction of autologous heart valves.

  1. METABOLIC CHANGES OF CONNECTIVE TISSUE IN CHILDREN WITH BONE CYST

    Directory of Open Access Journals (Sweden)

    O. M. Magomedov

    2013-10-01

    Full Text Available The results of the study of diagnostically important metabolism parameters in patients with bone cysts in different stages of the disease are presented. It is shown that an increase activity of protein banding collagenase, alkaline phosphatase and also of hydroxyproline, glycosaminoglycans contents due to lower levels of calcium and inorganic phosphate levels increase in blood serum are expressed in a stage osteolysis than the step of separating. Decreasing the amount of glycosaminoglycans and collagen in bone indicates an intensification of catabolic processes in the connective tissue matrix. Diagnostically important indicators of the degree of disturbance of bone metabolism are the level of collagen, proteoglycans and activity of marker enzymes — collagenase and alkaline phosphatase. Based on the evaluation of sensitivity, specificity and diagnostic efficiency of the obtained results, we can recommend the threshold values of the investigated parameters of basic organic components and mineral metabolism of bone for the differential diagnosis of stages of bone cysts in children, which will serve as a basis for the development of appropriate diagnostic tests.

  2. Pelvic organ prolapse and connective tissue abnormalities in Korean women.

    Science.gov (United States)

    Bai, Sang Wook; Choe, Byung Hoon; Kim, Jeong Yeon; Park, Ki Hyun

    2002-03-01

    To evaluate the relationship between pelvic organ prolapse in Korean women and joint hypermobility, which suggests a metabolic collagen fiber abnormality. Between March 1998 and March 2000, we investigated 55 patients with prolapse. The prevalence of joint hypermobility, by measuring finger extension angle, and the proportion of patients with joint hypermobility were measured in patients with pelvic organ prolapse and benign gynecologic patients (control group). In middle-aged women (40-59 years), the average finger extension angles were higher in the POP group than in the control group (50.04 +/- 9.70 degrees vs. 39.50 +/- 12.19 degrees, respectively; P .05). The prevalence of joint hypermobility was higher in the POP group and with advanced POP stage (III, IV) than in the control group and early POP stage (I, II). Our results suggest that intrinsic connective tissue abnormality is related to the development of pelvic organ prolapse. Further study involving more patients with pelvic organ prolapse is warranted, and molecular studies to determine the genetic basis of pelvic organ prolapse are also required to further elucidate this abnormality.

  3. Significance of connective tissue diseases features in pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Vincent Cottin

    2013-09-01

    Full Text Available Interstitial lung disease (ILD can occur in any of the connective tissue diseases (CTD with varying frequency and severity, and an overall long-term prognosis that is less severe than that of idiopathic pulmonary fibrosis (IPF. Because ILD may be the presenting manifestation of CTD and/or the dominant manifestation of CTD, clinical extra-thoracic manifestations should be systematically considered in the diagnostic approach of ILD. When present, autoantibodies strongly contribute to the recognition and classification of the CTD. Patients with clinical extrathoracic manifestations of CTD and/or autoantibodies (especially with a high titer and/or the antibody is considered “highly specific” of an autoimmune condition, but who do not fit with established international CTD criteria may be called undifferentiated CTD or “lung-dominant CTD”. Although it remains to be determined which combination of symptoms and serologic tests best identify the subset of patients with clinically relevant CTD features, available evidence suggests that such patients may have distinct clinical and imaging presentation and may portend a distinct clinical course. However, autoantibodies alone when present in IPF patients do not seem to impact prognosis or management. Referral to a rheumatologist and multidisciplinary discussion may contribute to management of patients with undifferentiated CTD.

  4. Development and clinical course of diseases accompanied by connective tissue dysplasia in children of puberty age

    Directory of Open Access Journals (Sweden)

    Elizarova S.Yu.

    2011-03-01

    Full Text Available The risk of development and clinical course of somatic diseases have been analyzed in the research work. 111 adolescents suffering from connective tissue dysplasia have been under the study. It has been stated that the frequency of somatic diseases among adolescents with connective tissue dysplasia is higher than this frequency among adolescents without such disease. Phenotypic signs of connective tissue dysplasia have been revealed. They are responsible for the development of bronchial asthma and severe stomach ulcer

  5. Connective tissue diseases and noninvasive evaluation of atherosclerosis

    Directory of Open Access Journals (Sweden)

    Ardita G

    2014-06-01

    Full Text Available Giorgio Ardita, Giacomo Failla, Paolo Maria Finocchiaro, Francesco Mugno, Luigi Attanasio, Salvatore Timineri, Michelangelo Maria Di SalvoCardiovascular Department, Angiology Unit, Ferrarotto Hospital, Catania, ItalyAbstract: Connective tissue diseases (CTDs are associated with increased risk of cardiovascular disease due to accelerated atherosclerosis. In patients with autoimmune disorders, in addition to traditional risk factors, an immune-mediated inflammatory process of the vasculature seems to contribute to atherogenesis. Several pathogenetic mechanisms have been proposed, including chronic inflammation and immunologic abnormalities, both able to produce vascular damage. Macrovascular atherosclerosis can be noninvasively evaluated by ultrasound measurement of carotid or femoral plaque. Subclinical atherosclerosis can be evaluated by well-established noninvasive techniques which rely on ultrasound detection of carotid intima-media thickness. Flow-mediated vasodilatation and arterial stiffness are considered markers of endothelial dysfunction and subclinical atherosclerosis, respectively, and have been recently found to be impaired early in a wide spectrum of autoimmune diseases. Carotid intima-media thickness turns out to be a leading marker of subclinical atherosclerosis, and many studies recognize its role as a predictor of future vascular events, both in non-CTD individuals and in CTD patients. In rheumatic diseases, flow-mediated dilatation and arterial stiffness prove to be strongly correlated with inflammation, disease damage index, and with subclinical atherosclerosis, although their prognostic role has not yet been conclusively shown. Systemic lupus erythematosus, rheumatoid arthritis, and likely antiphospholipid syndrome are better associated with premature and accelerated atherosclerosis. Inconclusive results were reported in systemic sclerosis.Keywords: rheumatic disease, subclinical atherosclerosis, arterial stiffness

  6. Ultrasound -Assisted Gene Transfer to Adipose Tissue-Derived Stem/Progenitor Cells (ASCs)

    Science.gov (United States)

    Miyamoto, Yoshitaka; Ueno, Hitomi; Hokari, Rei; Yuan, Wenji; Kuno, Shuichi; Kakimoto, Takashi; Enosawa, Shin; Negishi, Yoichi; Yoshinaka, Kiyoshi; Matsumoto, Yoichiro; Chiba, Toshio; Hayashi, Shuji

    2011-09-01

    In recent years, multilineage adipose tissue-derived stem cells (ASCs) have become increasingly attractive as a promising source for cell transplantation and regenerative medicine. Particular interest has been expressed in the potential to make tissue stem cells, such as ASCs and marrow stromal cells (MSCs), differentiate by gene transfection. Gene transfection using highly efficient viral vectors such as adeno- and sendai viruses have been developed for this purpose. Sonoporation, or ultrasound (US)-assisted gene transfer, is an alternative gene manipulation technique which employs the creation of a jet stream by ultrasonic microbubble cavitation. Sonoporation using non-viral vectors is expected to be a much safer, although less efficient, tool for prospective clinical gene therapy. In this report, we assessed the efficacy of the sonoporation technique for gene transfer to ASCs. We isolated and cultured adipocyets from mouse adipose tissue. ASCs that have the potential to differentiate with transformation into adipocytes or osteoblasts were obtained. Using the US-assisted system, plasmid DNA containing beta-galactosidase (beta-Gal) and green fluorescent protein (GFP) genes were transferred to the ASCs. For this purpose, a Sonopore 4000 (NEPAGENE Co.) and a Sonazoid (Daiichi Sankyo Co.) instrument were used in combination. ASCs were subjected to US (3.1 MHz, 50% duty cycle, burst rate 2.0 Hz, intensity 1.2 W/cm2, exposure time 30 sec). We observed that the gene was more efficiently transferred with increased concentrations of plasmid DNA (5-150 μg/mL). However, further optimization of the US parameters is required, as the gene transfer efficiency was still relatively low. In conclusion, we herein demonstrate that a gene can be transferred to ASCs using our US-assisted system. In regenerative medicine, this system might resolve the current issues surrounding the use of viral vectors for gene transfer.

  7. Patch tracheoplasty in body tissue engineering using collagenous connective tissue membranes (biosheets).

    Science.gov (United States)

    Satake, Ryosuke; Komura, Makoto; Komura, Hiroko; Kodaka, Tetsuro; Terawaki, Kan; Ikebukuro, Kenichi; Komuro, Hiroaki; Yonekawa, Hironobu; Hoshi, Kazuto; Takato, Tsuyoshi; Nakayama, Yasuhide

    2016-02-01

    Collagenous connective tissue membranes (biosheets) are useful for engineering cardiovascular tissue in tissue engineering. The aim was to evaluate the use of biosheets as a potential tracheal substitute material in vivo in a rabbit model. Group 1: Rectangular-shaped Gore-Tex (4×7mm) was implanted into a 3×6mm defect created in the midventral portion of the cervical trachea. Group 2: Rectangular-shaped dermis was implanted into a tracheotomy of similar size. Group 3: Biosheets were prepared by embedding silicone moulds in dorsal subcutaneous pouches in rabbits for 1month. Rectangular-shaped biosheets were implanted into a tracheotomy of similar size in an autologous fashion. All groups (each containing 10 animals) were sacrificed 4weeks after implantation. All materials maintained airway structure for up to 4weeks after implantation. Regenerative cartilage in implanted Biosheets in group 3 was confirmed by histological analysis. Tracheal epithelial regeneration occurred in the internal lumen of group 3. There were significant differences in the amounts of collagen type II and glycosaminoglycan between group 3 and group 1 or 2. We confirm that cartilage can self-regenerate onto an airway patch using Biosheets. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. Mutation of the zebrafish nucleoporin elys sensitizes tissue progenitors to replication stress.

    Directory of Open Access Journals (Sweden)

    Gangarao Davuluri

    2008-10-01

    Full Text Available The recessive lethal mutation flotte lotte (flo disrupts development of the zebrafish digestive system and other tissues. We show that flo encodes the ortholog of Mel-28/Elys, a highly conserved gene that has been shown to be required for nuclear integrity in worms and nuclear pore complex (NPC assembly in amphibian and mammalian cells. Maternal elys expression sustains zebrafish flo mutants to larval stages when cells in proliferative tissues that lack nuclear pores undergo cell cycle arrest and apoptosis. p53 mutation rescues apoptosis in the flo retina and optic tectum, but not in the intestine, where the checkpoint kinase Chk2 is activated. Chk2 inhibition and replication stress induced by DNA synthesis inhibitors were lethal to flo larvae. By contrast, flo mutants were not sensitized to agents that cause DNA double strand breaks, thus showing that loss of Elys disrupts responses to selected replication inhibitors. Elys binds Mcm2-7 complexes derived from Xenopus egg extracts. Mutation of elys reduced chromatin binding of Mcm2, but not binding of Mcm3 or Mcm4 in the flo intestine. These in vivo data indicate a role for Elys in Mcm2-chromatin interactions. Furthermore, they support a recently proposed model in which replication origins licensed by excess Mcm2-7 are required for the survival of human cells exposed to replication stress.

  9. Mesenchymal Stem and Progenitor Cells in Regeneration: Tissue Specificity and Regenerative Potential.

    Science.gov (United States)

    Rohban, Rokhsareh; Pieber, Thomas Rudolf

    2017-01-01

    It has always been an ambitious goal in medicine to repair or replace morbid tissues for regaining the organ functionality. This challenge has recently gained momentum through considerable progress in understanding the biological concept of the regenerative potential of stem cells. Routine therapeutic procedures are about to shift towards the use of biological and molecular armamentarium. The potential use of embryonic stem cells and invention of induced pluripotent stem cells raised hope for clinical regenerative purposes; however, the use of these interventions for regenerative therapy showed its dark side, as many health concerns and ethical issues arose in terms of using these cells in clinical applications. In this regard, adult stem cells climbed up to the top list of regenerative tools and mesenchymal stem cells (MSC) showed promise for regenerative cell therapy with a rather limited level of risk. MSC have been successfully isolated from various human tissues and they have been shown to offer the possibility to establish novel therapeutic interventions for a variety of hard-to-noncurable diseases. There have been many elegant studies investigating the impact of MSC in regenerative medicine. This review provides compact information on the role of stem cells, in particular, MSC in regeneration.

  10. Immunological methods for the detection and determination of connective tissue proteoglycans

    DEFF Research Database (Denmark)

    Caterson, B; Baker, J R; Christner, J E

    1982-01-01

    In this paper we report the use of immunological methods for specifically detecting and determining proteoglycan in cartilage and other connective tissues. Antibodies (polyclonal and monoclonal) have been raised against specific components of cartilage proteoglycan aggregates (i.e., proteoglycan...... surrounding invaginating hair follicles. These immunological procedures are currently being used to complement conventional biochemical analyses of proteoglycans found in different connective tissue matrices....

  11. Mixed connective tissue disease: The King Faisal Specialist Hospital experience

    International Nuclear Information System (INIS)

    Al-Rayes, H.; Al-Sheikh, A.; Al-Dalaan, A.; Al-Saleh, S.

    2002-01-01

    The aim of this study was to assess the clinical presentation, complications and serological analysis of mixed connective tissue disease (MCTD) at King Faisal Specialist Hospital and Research Centre (KFSHRC), and to determine the long-term clinical and immunologic outcomes. This was a retrospective study with prospective follow-up of 18 patients with MCTD who were followed at KFSHRC between 1982 and 1999. The age at onset of the disease ranged from 6 to 44 years, with mean age of 17.9 years. The female to male ratio was 2.5:1 and the mean follow-up time was 5 years. The most frequent presenting symptoms were arthralgia in all patients, Raynaud's phenomenon in 16 patients (88%) and swollen hands in 11 patients (61%). Arthritis was seen in 12 patients in (67%) and definite myositis in 10 patients (58%). The most common skin rashes encountered included lupus-like rash in 8 patients (44%) and cutaneous vasculitis in 5 patients (28%). Pulmonary hypertension occurred in 4 patients (22%). Other clinical manifestations encountered were esophageal hypomotility in 10 patients (56%), myocarditis in 2 patients (11%) and proteinurea in 2 patients (11%), while various neurological manifestations were present in 7 patients (39%). All patients exhibited higher titer of ANA and anti-nRNP antibodies. Five of the 18 patients (28%) had marked reduction in the anti-nRNP during remission. Following treatment, features of inflammation as well as Raynaud's phenomenon and esophageal hypomotility diminished, while pulmonary hypertension persisted. A favorable outcome was observed in 12 patients (67%), 3 patients (17%) had continued active disease, while 3 patients (17%) died, with death related to pulmonary hypertension occurring in 2 patients (11%). The studied patients demonstrated the typical clinical and serological findings of MCTD, which support the correlation between anti-nRNP antibody specificities and MCTD. Autoantibody reactivity against nRNP polypeptides tends to regress during

  12. Gene targeting study reveals unexpected expression of brain-expressed X-linked 2 in endocrine and tissue stem/progenitor cells in mice.

    Science.gov (United States)

    Ito, Keiichi; Yamazaki, Satoshi; Yamamoto, Ryo; Tajima, Yoko; Yanagida, Ayaka; Kobayashi, Toshihiro; Kato-Itoh, Megumi; Kakuta, Shigeru; Iwakura, Yoichiro; Nakauchi, Hiromitsu; Kamiya, Akihide

    2014-10-24

    Identification of genes specifically expressed in stem/progenitor cells is an important issue in developmental and stem cell biology. Genome-wide gene expression analyses in liver cells performed in this study have revealed a strong expression of X-linked genes that include members of the brain-expressed X-linked (Bex) gene family in stem/progenitor cells. Bex family genes are expressed abundantly in the neural cells and have been suggested to play important roles in the development of nervous tissues. However, the physiological role of its individual members and the precise expression pattern outside the nervous system remain largely unknown. Here, we focused on Bex2 and examined its role and expression pattern by generating knock-in mice; the enhanced green fluorescence protein (EGFP) was inserted into the Bex2 locus. Bex2-deficient mice were viable and fertile under laboratory growth conditions showing no obvious phenotypic abnormalities. Through an immunohistochemical analysis and flow cytometry-based approach, we observed unique EGFP reporter expression patterns in endocrine and stem/progenitor cells of the liver, pyloric stomach, and hematopoietic system. Although Bex2 seems to play redundant roles in vivo, these results suggest the significance and potential applications of Bex2 in studies of endocrine and stem/progenitor cells. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Experiment K-7-29: Connective Tissue Studies. Part 3; Rodent Tissue Repair: Skeletal Muscle

    Science.gov (United States)

    Stauber, W.; Fritz, V. K.; Burkovskaya, T. E.; Ilyina-Kakueva, E. I.

    1994-01-01

    Myofiber injury-repair was studied in the rat gastrocnemius following a crush injury to the lower leg prior to flight in order to understand if the regenerative responses of muscles are altered by the lack of gravitational forces during Cosmos 2044 flight. After 14 days of flight, the gastrocnemius muscle was removed from the 5 injured flight rodents and various Earth-based treatment groups for comparison. The Earth-based animals consisted of three groups of five rats with injured muscles from a simulated, tail-suspended, and vivarium as well as an uninjured basal group. The gastrocnemius muscle from each was evaluated by histochemical and immunohistochemical techniques to document myofiber, vascular, and connective tissue alterations following injury. In general the repair process was somewhat similar in all injured muscle samples with regard to extracellular matrix organization and myofiber regeneration. Small and large myofibers were present with a newly organized extracellular matrix indicative of myogenesis and muscle regeneration. In the tail-suspended animals, a more complete repair was observed with no enlarged area of non-muscle cells or matrix material visible. In contrast, the muscle samples from the flight animals were less well differentiated with more macrophages and blood vessels in the repair region but small myofibers and proteoglycans, nevertheless, were in their usual configuration. Thus, myofiber repair did vary in muscles from the different groups, but for the most part, resulted in functional muscle tissue.

  14. Life-long endurance running is associated with reduced glycation and mechanical stress in connective tissue

    DEFF Research Database (Denmark)

    Couppé, Christian; Svensson, René B; Grosset, Jean-Francois

    2014-01-01

    counteract the aging process in connective tissue by reducing age-related accumulation of AGEs. This may not only benefit skin and tendon but also other long-lived protein tissues in the body. Furthermore, it appears that endurance running yields tendon tissue hypertrophy that may serve to lower the stress...

  15. Detection of Connective Tissue Disorders from 3D Aortic MR Images Using Independent Component Analysis

    DEFF Research Database (Denmark)

    Hansen, Michael Sass; Zhao, Fei; Zhang, Honghai

    2006-01-01

    A computer-aided diagnosis (CAD) method is reported that allows the objective identification of subjects with connective tissue disorders from 3D aortic MR images using segmentation and independent component analysis (ICA). The first step to extend the model to 4D (3D + time) has also been taken....... ICA is an effective tool for connective tissue disease detection in the presence of sparse data using prior knowledge to order the components, and the components can be inspected visually. 3D+time MR image data sets acquired from 31 normal and connective tissue disorder subjects at end-diastole (R...

  16. Removal of an amalgam tattoo using a subepithelial connective tissue graft and laser deepithelialization.

    Science.gov (United States)

    Campbell, Casey M; Deas, David E

    2009-05-01

    A 56-year-old female presented for periodontal treatment with a large amalgam tattoo located in alveolar mucosa on the facial aspect of her maxillary central incisors. The lesion had been present for 42 years since having endodontic surgery at teeth #8 and #9 after a traumatic childhood incident. A two-stage surgical approach was used to eliminate the lesion, beginning with a subepithelial connective tissue graft to increase tissue thickness subjacent to the amalgam tattoo. After 6 weeks of healing, the overlying pigmented tissue was removed using laser surgery to expose the underlying grafted connective tissue. After 2 months of healing following laser surgery, the amalgam pigmentation was completely removed, with good color match and an increased width of keratinized tissue at the surgical site. A relatively large amalgam tattoo in the esthetic zone can be adequately removed by a two-stage procedure using grafted palatal connective tissue and laser deepithelialization.

  17. Human adipose-tissue derived stromal cells in combination with hypoxia effectively support ex vivo expansion of cord blood haematopoietic progenitors.

    Directory of Open Access Journals (Sweden)

    Elena R Andreeva

    Full Text Available The optimisation of haematopoietic stem and progenitor cell expansion is on demand in modern cell therapy. In this work, haematopoietic stem/progenitor cells (HSPCs have been selected from unmanipulated cord blood mononuclear cells (cbMNCs due to adhesion to human adipose-tissue derived stromal cells (ASCs under standard (20% and tissue-related (5% oxygen. ASCs efficiently maintained viability and supported further HSPC expansion at 20% and 5% O2. During co-culture with ASCs, a new floating population of differently committed HSPCs (HSPCs-1 grew. This suspension was enriched with СD34+ cells up to 6 (20% O2 and 8 (5% O2 times. Functional analysis of HSPCs-1 revealed cobble-stone area forming cells (CAFCs and lineage-restricted colony-forming cells (CFCs. The number of CFCs was 1.6 times higher at tissue-related O2, than in standard cultivation (20% O2. This increase was related to a rise in the number of multipotent precursors - BFU-E, CFU-GEMM and CFU-GM. These changes were at least partly ensured by the increased concentration of MCP-1 and IL-8 at 5% O2. In summary, our data demonstrated that human ASCs enables the selection of functionally active HSPCs from unfractionated cbMNCs, the further expansion of which without exogenous cytokines provides enrichment with CD34+ cells. ASCs efficiently support the viability and proliferation of cord blood haematopoietic progenitors of different commitment at standard and tissue-related O2 levels at the expense of direct and paracrine cell-to-cell interactions.

  18. Reduction of urinary connective tissue growth factor by Losartan in type 1 patients with diabetic nephropathy

    NARCIS (Netherlands)

    Andersen, S; van Nieuwenhoven, FA; Tarnow, L; Rossing, P; Rossing, K; Wieten, L; Goldschmeding, R; Parving, HH

    Background. Connective tissue growth factor (CTGF) is an important profibrotic cytokine implicated in development of diabetic glomerulosclerosis. Urinary CTGF is reported to be significantly increased in patients with diabetic nephropathy. The present study aimed to investigate the short- and long

  19. The properties of connective tissue membrane and pig skin as raw materials for cooked sausage.

    Science.gov (United States)

    Puolanne, E; Ruusunen, M

    1981-09-01

    Pig skin and epimysial membrane from young bulls were comminuted in a colloid grinder and mixed with water and additives. The resultant mixture was heated in a water bath to give an internal temperature of 72°C, and centrifuged while still hot. Such variations in the amount of water added, the salt content, the phosphate content and the pH value as are possible in cooked sausage heated to over 65°C during processing did not cause marked changes in the amount of water bound by the connective tissues, the amount of dissolved protein or the gel strength of the liquid released from the connective tissues. As the temperature rose the amount of bound water dropped, but the amount of dissolved protein and the gel strength increased. The liquid released from the connective tissue membranes formed a gel at 32°C and re-melted at 49°C. For pig skin, the corresponding temperatures were 23°C and 47°C. On the basis of this study it appears that connective tissue may be important for the water-binding capacity and firmness of cold sausage. The connective tissue membranes obtained from young bulls and pig skin are of roughly equal value in this respect, although the gel formed from connective tissue membrane is tougher. Copyright © 1981. Published by Elsevier Ltd.

  20. CONNECTIVE-TISSUE DISEASE IN PATIENTS PRESENTING WITH RAYNAUDS-PHENOMENON ALONE

    NARCIS (Netherlands)

    Kallenberg, Cees

    1991-01-01

    Raynaud's phenomenon is due to the constriction of small, digital arteries on exposure mainly to cold and may occur in isolation or in relation to connective tissue disease. Is there any connection between the two varieties? Sadly the answer may be yes in a substantial number. Those who go on to

  1. The ratio of ADSCs to HSC-progenitors in adipose tissue derived SVF may provide the key to predict the outcome of stem-cell therapy.

    Science.gov (United States)

    Kilinc, Mehmet Okyay; Santidrian, Antonio; Minev, Ivelina; Toth, Robert; Draganov, Dobrin; Nguyen, Duong; Lander, Elliot; Berman, Mark; Minev, Boris; Szalay, Aladar A

    2018-02-07

    Stromal vascular fraction (SVF) represents an attractive source of adult stem cells and progenitors, holding great promise for numerous cell therapy approaches. In 2017, it was reported that 1524 patients received autologous SVF following the enzymatic digestion of liposuction fat. The treatment was safe and effective and patients showed significant clinical improvement. In a collaborative study, we analyzed SVF obtained from 58 patients having degenerative, inflammatory, autoimmune diseases, and advanced stage cancer. Flow analysis showed that freshly isolated SVF was very heterogeneous and harbored four major subsets specific to adipose tissue; CD34 high CD45 - CD31 - CD146 - adipose-derived stromal/stem cells (ADSCs), CD34 low CD45 + CD206 + CD31 - CD146 - hematopoietic stem cell-progenitors (HSC-progenitors), CD34 high CD45 - CD31 + CD146 + adipose tissue-endothelial cells and CD45 - CD34 - CD31 - CD146 + pericytes. Culturing and expanding of SVF revealed a homogenous population lacking hematopoietic lineage markers CD45 and CD34, but were positive for CD90, CD73, CD105, and CD44. Flow cytometry sorting of viable individual subpopulations revealed that ADSCs had the capacity to grow in adherent culture. The identity of the expanded cells as mesenchymal stem cells (MSCs) was further confirmed based on their differentiation into adipogenic and osteogenic lineages. To identify the potential factors, which may determine the beneficial outcome of treatment, we followed 44 patients post-SVF treatment. The gender, age, clinical condition, certain SVF-dose and route of injection, did not play a role on the clinical outcome. Interestingly, SVF yield seemed to be affected by patient's characteristic to various extents. Furthermore, the therapy with adipose-derived and expanded-mesenchymal stem cells (ADE-MSCs) on a limited number of patients, did not suggest increased efficacies compared to SVF treatment. Therefore, we tested the hypothesis that a certain combination

  2. Effect of connective tissue grafting on peri-implant tissue in single immediate implant sites : A RCT

    NARCIS (Netherlands)

    Zuiderveld, Elise G; Meijer, Henny J A; den Hartog, Laurens; Vissink, Arjan; Raghoebar, Gerry M

    AimTo assess the effect of connective tissue grafting on the mid-buccal mucosal level (MBML) of immediately placed and provisionalized single implants in the maxillofacial aesthetic zone. Materials and methodsSixty patients with a failing tooth were provided with an immediately placed and

  3. Efficacy of Connective Tissue with and without Periosteum in Regeneration of Intrabony Defects

    Directory of Open Access Journals (Sweden)

    Vahid Esfahanian

    2014-12-01

    Full Text Available Background and aims. Connective tissue grafts with and without periosteum is used in regenerative treatments of bone and has demonstrated successful outcomes in previous investigations. The aim of present study was to evaluate the effec-tiveness of connective tissue graft with and without periosteum in regeneration of intrabony defects. Materials and methods. In this single-blind randomized split-mouth clinical trial, 15 pairs of intrabony defects in 15 pa-tients with moderate to advanced periodontitis were treated by periosteal connective tissue graft + ABBM (test group or non-periosteal connective tissue graft + ABBM (control group. Probing pocket depth, clinical attachment level, free gingi-val margin position, bone crestal position, crest defect depth and defect depth to stent were measured at baseline and after six months by surgical re-entry. Data was analyzed by Student’s t-test and paired t-tests (α=0.05. Results. Changes in clinical parameters after 6 months in the test and control groups were as follows: mean of PPD reduc-tion: 3.1±0.6 (P<0.0001; 2.5±1.0 mm (P<0.0001, CAL gain: 2.3±0.9 (P<0.0001; 2.2±1.0 mm (P<0.0001, bone fill: 2.2±0.7 mm (P<0.0001; 2.2±0.7 mm (P<0.0001, respectively. No significant differences in the position of free gingival margin were observed during 6 months compared to baseline in both groups. Conclusion. Combinations of periosteal connective tissue graft + ABBM and non-periosteal connective tissue graft + ABBM were similarly effective in treating intrabony defects without any favor for any group. Connective tissue and perio-steum can be equally effective in regeneration of intrabony defects.

  4. Adipose tissue and sustainable development: a connection that needs protection

    Directory of Open Access Journals (Sweden)

    Angelo eTremblay

    2015-05-01

    Full Text Available Obesity is generally considered as an excess body fat that increases the risk to develop ergonomic, metabolic and psychosocial problems. As suggested in this paper, body fat gain is also a protective adaptation that prevents body lipotoxicity, contributes to the secretion of molecules involved in metabolic regulation, and dilutes lipid soluble persistent organic pollutants (POPs. Recent literature shows that this protective role of adipose tissue is more solicited in a modern context in which unsuspected factors can affect energy balance to a much greater extent than what is generally perceived by health care professionals. These factors include short sleep duration, demanding mental work, and chemical pollution whose impact is more detectable in a context dominated by economic productivity and competitiveness. Since these factors might also include the increase in atmospheric CO2, it is likely that obesity prevention will need the support of a promotion in sustainable development, whether it is for human health and well-being or global ecological protection.

  5. Facial gingival tissue stability after connective tissue graft with single immediate tooth replacement in the esthetic zone: consecutive case report.

    Science.gov (United States)

    Kan, Joseph Y K; Rungcharassaeng, Kitichai; Morimoto, Taichiro; Lozada, Jaime

    2009-11-01

    The present consecutive case report evaluated facial gingival tissue stability after immediate tooth replacement with connective tissue grafting in the esthetic zone. The implant success rate and peri-implant tissue response were also recorded. A total of 20 consecutive patients with a mean age of 52.3 years (range 28 to 71), who had undergone 20 single immediate tooth replacement with connective tissue grafting, were evaluated clinically and radiographically at the preoperative examination, immediately after implant placement and provisionalization with connective tissue grafting, and at the latest follow-up appointment. The data were analyzed using the t test and Wilcoxon signed rank test at a significance level of alpha = .05. At the preoperative examination, a thick gingival biotype was observed in 8 patients and a thin gingival biotype in 12. At a mean follow-up of 2.15 years (range 1 to 4), all implants were functioning and exhibited a thick biotype. At the latest follow-up appointment, no significant differences (P > .05) were found between the initially thick and thin gingival biotypes in the mean mesial marginal bone level changes (-0.53 versus -0.55 mm), the mean distal marginal bone level changes (-0.50 versus -0.44 mm), and the mean facial gingival level changes (+0.23 mm versus +0.06 mm). The frequency distribution of the papilla index score showed that peri-implant papillae were well preserved at the latest follow-up visit. With proper 3-dimensional implant positioning and bone grafting into the implant-socket gap, the facial gingival level can be maintained after connective tissue grafting with single immediate tooth replacement, regardless of the initial gingival biotype, indicating that the thin gingival biotype can be converted to the thick gingival biotype morphologically and behaviorally with this procedure. Nevertheless, careful patient selection and treatment planning, as well as immaculate execution by skillful clinicians, are required to

  6. Efficient Generation of Human Embryonic Stem Cell-Derived Cardiac Progenitors Based on Tissue-Specific Enhanced Green Fluorescence Protein Expression

    Science.gov (United States)

    Szebényi, Kornélia; Péntek, Adrienn; Erdei, Zsuzsa; Várady, György; Orbán, Tamás I.; Sarkadi, Balázs

    2015-01-01

    Cardiac progenitor cells (CPCs) are committed to the cardiac lineage but retain their proliferative capacity before becoming quiescent mature cardiomyocytes (CMs). In medical therapy and research, the use of human pluripotent stem cell-derived CPCs would have several advantages compared with mature CMs, as the progenitors show better engraftment into existing heart tissues, and provide unique potential for cardiovascular developmental as well as for pharmacological studies. Here, we demonstrate that the CAG promoter-driven enhanced green fluorescence protein (EGFP) reporter system enables the identification and isolation of embryonic stem cell-derived CPCs. Tracing of CPCs during differentiation confirmed up-regulation of surface markers, previously described to identify cardiac precursors and early CMs. Isolated CPCs express cardiac lineage-specific transcripts, still have proliferating capacity, and can be re-aggregated into embryoid body-like structures (CAG-EGFPhigh rEBs). Expression of troponin T and NKX2.5 mRNA is up-regulated in long-term cultured CAG-EGFPhigh rEBs, in which more than 90% of the cells become Troponin I positive mature CMs. Moreover, about one third of the CAG-EGFPhigh rEBs show spontaneous contractions. The method described here provides a powerful tool to generate expandable cultures of pure human CPCs that can be used for exploring early markers of the cardiac lineage, as well as for drug screening or tissue engineering applications. PMID:24734786

  7. Morphometric Analysis of Connective Tissue Sheaths of Sural Nerve in Diabetic and Nondiabetic Patients

    Directory of Open Access Journals (Sweden)

    Braca Kundalić

    2014-01-01

    Full Text Available One of the most common complications of diabetes mellitus is diabetic neuropathy. It may be provoked by metabolic and/or vascular factors, and depending on duration of disease, various layers of nerve may be affected. Our aim was to investigate influence of diabetes on the epineurial, perineurial, and endoneurial connective tissue sheaths. The study included 15 samples of sural nerve divided into three groups: diabetic group, peripheral vascular disease group, and control group. After morphological analysis, morphometric parameters were determined for each case using ImageJ software. Compared to the control group, the diabetic cases had significantly higher perineurial index (P<0.05 and endoneurial connective tissue percentage (P<0.01. The diabetic group showed significantly higher epineurial area (P<0.01, as well as percentage of endoneurial connective tissue (P<0.01, in relation to the peripheral vascular disease group. It is obvious that hyperglycemia and ischemia present in diabetes lead to substantial changes in connective tissue sheaths of nerve, particularly in peri- and endoneurium. Perineurial thickening and significant endoneurial fibrosis may impair the balance of endoneurial homeostasis and regenerative ability of the nerve fibers. Future investigations should focus on studying the components of extracellular matrix of connective tissue sheaths in diabetic nerves.

  8. Connective tissue regeneration in skeletal muscle after eccentric contraction-induced injury.

    Science.gov (United States)

    Mackey, Abigail L; Kjaer, Michael

    2017-03-01

    Human skeletal muscle has the potential to regenerate completely after injury induced under controlled experimental conditions. The events inside the myofibers as they undergo necrosis, followed closely by satellite cell-mediated myogenesis, have been mapped in detail. Much less is known about the adaptation throughout this process of both the connective tissue structures surrounding the myofibers and the fibroblasts, the cells responsible for synthesizing this connective tissue. However, the few studies investigating muscle connective tissue remodeling demonstrate a strong response that appears to be sustained for a long time after the major myofiber responses have subsided. While the use of electrical stimulation to induce eccentric contractions vs. voluntary eccentric contractions appears to lead to a greater extent of myofiber necrosis and regenerative response, this difference is not apparent when the muscle connective tissue responses are compared, although further work is required to confirm this. Pharmacological agents (growth hormone and angiotensin II type I receptor blockers) are considered in the context of accelerating the muscle connective tissue adaptation to loading. Cautioning against this, however, is the association between muscle matrix protein remodeling and protection against reinjury, which suggests that a (so far undefined) period of vulnerability to reinjury may exist during the remodeling phases. The role of individual muscle matrix components and their spatial interaction during adaptation to eccentric contractions is an unexplored field in human skeletal muscle and may provide insight into the optimal timing of rest vs. return to activity after muscle injury. Copyright © 2017 the American Physiological Society.

  9. Connective tissue injury in calf muscle tears and return to play: MRI correlation.

    Science.gov (United States)

    Prakash, Ashutosh; Entwisle, Tom; Schneider, Michal; Brukner, Peter; Connell, David

    2017-10-26

    The aim of our study was to assess a group of patients with calf muscle tears and evaluate the integrity of the connective tissue boundaries and interfaces. Further, we propose a novel MRI grading system based on integrity of the connective tissue and assess any correlation between the grading score and time to return to play. We have also reviewed the anatomy of the calf muscles. We retrospectively evaluated 100 consecutive patients with clinical suspicion and MRI confirmation of calf muscle injury. We evaluated each calf muscle tear with MRI for the particular muscle injured, location of injury within the muscle and integrity of the connective tissue structure at the interface. The muscle tears were graded 0-3 depending on the degree of muscle and connective tissue injury. The time to return to play for each patient and each injury was found from the injury records and respective sports doctors. In 100 patients, 114 injuries were detected. Connective tissue involvement was observed in 63 out of 100 patients and failure (grade 3 injury) in 18. Mean time to return to play with grade 0 injuries was 8 days, grade 1 tears was 17 days, grade 2 tears was 25 days and grade 3 tears was 48 days (pcalf muscle tears. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. Cells of the connective tissue differentiate and migrate into pollen sacs

    Science.gov (United States)

    Iqbal, M. C. M.; Wijesekara, Kolitha B.

    2002-01-01

    In angiosperms, archesporial cells in the anther primordium undergo meiosis to form haploid pollen, the sole occupants of anther sacs. Anther sacs are held together by a matrix of parenchyma cells, the connective tissue. Cells of the connective tissue are not known to differentiate. We report the differentiation of parenchyma cells in the connective tissue of two Gordonia species into pollen-like structures (described as pseudopollen), which migrate into the anther sacs before dehiscence. Pollen and pseudopollen were distinguishable by morphology and staining. Pollen were tricolpate to spherical while pseudopollen were less rigid and transparent with a ribbed surface. Both types were different in size, shape, staining and surface architecture. The ratio of the number of pseudopollen to pollen was 1:3. During ontogeny in the connective tissue, neither cell division nor tetrad formation was observed and hence pseudopollen were presumed to be diploid. Only normal pollen germinated on a germination medium. Fixed preparations in time seemed to indicate that pseudopollen migrate from the connective tissue into the anther sac.

  11. Remodeling of the Connective Tissue Microarchitecture of the Lamina Cribrosa in Early Experimental Glaucoma

    Science.gov (United States)

    Roberts, Michael D.; Grau, Vicente; Grimm, Jonathan; Reynaud, Juan; Bellezza, Anthony J.; Burgoyne, Claude F.; Downs, J. Crawford

    2009-01-01

    Purpose To characterize the trabeculated connective tissue microarchitecture of the lamina cribrosa (LC) in terms of total connective tissue volume (CTV), connective tissue volume fraction (CTVF), predominant beam orientation, and material anisotropy in monkeys with early experimental glaucoma (EG). Methods The optic nerve heads from three monkeys with unilateral EG and four bilaterally normal monkeys were three dimensionally reconstructed from tissues perfusion fixed at an intraocular pressure of 10 mm Hg. A three-dimensional segmentation algorithm was used to extract a binary, voxel-based representation of the porous LC connective tissue microstructure that was regionalized into 45 subvolumes, and the following quantities were calculated: total CTV within the LC, mean and regional CTVF, regional predominant beam orientation, and mean and regional material anisotropy. Results Regional variation within the laminar microstructure was considerable within the normal eyes of all monkeys. The laminar connective tissue was generally most dense in the central and superior regions for the paired normal eyes, and laminar beams were radially oriented at the periphery for all eyes considered. CTV increased substantially in EG eyes compared with contralateral normal eyes (82%, 44%, 45% increases; P < 0.05), but average CTVF changed little (−7%, 1%, and −2% in the EG eyes). There were more laminar beams through the thickness of the LC in the EG eyes than in the normal controls (46%, 18%, 17% increases). Conclusions The substantial increase in laminar CTV with little change in CTVF suggests that significant alterations in connective and nonconnective tissue components in the laminar region occur in the early stages of glaucomatous damage. PMID:18806292

  12. Pre-irradiation of tissue culture flasks leads to diminished stem and progenitor cell production in long-term bone marrow cultures

    International Nuclear Information System (INIS)

    Rooney, P.; Wright, E.G.

    1993-01-01

    Empty plastic tissue culture flasks were exposed to X-irradiation doses of 0.3-10.0 Gy, prior to the establishment of long-term bone marrow cultures. During the course of a 10 week culture period, all irradiated plastic flasks exhibited a dramatic decrease in the number of both haemopoietic stem cells and myeloid progenitor cells, in the non-adherent layer, when compared with controls. This decrease was not due to a decrease in the number of non-adherent cells produced. Histological examination of non-adherent cells showed an increase in mature granulocytic cells with few blast cells. Morphologically, the adherent layers of irradiated flasks demonstrated a delay in appearance or absence of fat cell production. X-irradiation of glass tissue culture flasks had no deleterious effect. (author)

  13. Association between antinuclear antibody titers and connective tissue diseases in a Rheumatology Department.

    Science.gov (United States)

    Menor Almagro, Raúl; Rodríguez Gutiérrez, Juan Francisco; Martín-Martínez, María Auxiliadora; Rodríguez Valls, María José; Aranda Valera, Concepción; de la Iglesia Salgado, José Luís

    To determine the dilution titles at antinuclear antibodies (ANA) by indirect immunofluorescence observed in cell substrate HEp-2 and its association with the diagnosis of systemic connective tissue disease in ANA test requested by a Rheumatology Unit. Samples of patients attended for the first time in the rheumatology unit, without prior ANA test, between January 2010 and December 2012 were selected. The dilution titers, immunofluorescence patterns and antigen specificity were recorded. In January 2015 the diagnosis of the patients were evaluated and classified in systemic disease connective tissue (systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, undifferentiated connective, antiphospholipid syndrome, mixed connective tissue and inflammatory myophaty) or not systemic disease connective tissue. A total of 1282 ANA tests requested by the Rheumatology Unit in subjects without previous study, 293 were positive, predominance of women (81.9%). Patients with systemic connective tissue disease were recorded 105, and 188 without systemic connective tissue disease. For 1/640 dilutions the positive predictive value in the connective was 73.3% compared to 26.6% of non-connective, and for values ≥1/1,280 85% versus 15% respectively. When performing the multivariate analysis we observed a positive association between 1/320 dilution OR 3.069 (95% CI: 1.237-7.614; P=.016), 1/640 OR 12.570 (95% CI: 3.659-43.187; P=.000) and ≥1/1,280 OR 42.136 (95% CI: 8.604-206.345; P=.000). These results show association titles dilution ≥1/320 in ANA's first test requested by a Rheumatology Unit with patients with systemic connective tissue disease. The VPP in these patients was higher than previous studies requested by other medical specialties. This may indicate the importance of application of the test in a targeted way. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  14. Human adipose CD34+ CD90+ stem cells and collagen scaffold constructs grafted in vivo fabricate loose connective and adipose tissues.

    Science.gov (United States)

    Ferraro, Giuseppe A; De Francesco, Francesco; Nicoletti, Gianfranco; Paino, Francesca; Desiderio, Vincenzo; Tirino, Virginia; D'Andrea, Francesco

    2013-05-01

    Stem cell based therapies for the repair and regeneration of various tissues are of great interest for a high number of diseases. Adult stem cells, instead, are more available, abundant and harvested with minimally invasive procedures. In particular, mesenchymal stem cells (MSCs) are multi-potent progenitors, able to differentiate into bone, cartilage, and adipose tissues. Human adult adipose tissue seems to be the most abundant source of MSCs and, due to its easy accessibility; it is able to give a considerable amount of stem cells. In this study, we selected MSCs co-expressing CD34 and CD90 from adipose tissue. This stem cell population displayed higher proliferative capacity than CD34(-) CD90(-) cells and was able to differentiate in vitro into adipocytes (PPARγ(+) and adiponectin(+)) and endothelial cells (CD31(+) VEGF(+) Flk1(+)). In addition, in methylcellulose without VEGF, it formed a vascular network. The aim of this study was to investigate differentiation potential of human adipose CD34(+) /CD90(+) stem cells loaded onto commercial collagen sponges already used in clinical practice (Gingistat) both in vitro and in vivo. The results of this study clearly demonstrate that human adult adipose and loose connective tissues can be obtained in vivo, highlighting that CD34(+) /CD90 ASCs are extremely useful for regenerative medicine. Copyright © 2012 Wiley Periodicals, Inc.

  15. Polydopamine deposition with anodic oxidation for better connective tissue attachment to transmucosal implants.

    Science.gov (United States)

    Teng, F; Chen, H; Xu, Y; Liu, Y; Ou, G

    2018-04-01

    Nowadays, most designs for the transmucosal surface of implants are machined-smooth. However, connective tissue adhered to the smooth surface of an implant has poor mechanical resistance, which can render separation of tissue from the implant interface and induce epithelial downgrowth. Modification of the transmucosal surface of implants, which can help form a good seal of connective tissue, is therefore desired. We hypothesized that anodic oxidation (AO) and polydopamine (PD) deposition could be used to enhance the attachment between an implant and peri-implant connective tissue. We tested this hypothesis in the mandibles of Beagle dogs. AO and PD were used to modify the transmucosal region of transmucosal implants (implant neck). The surface microstructure, surface roughness and elemental composition were investigated in vitro. L929 mouse fibroblasts were cultured to test the effect of PD on cell adhesion. Six Beagle dogs were used for the in vivo experiment (n = 6 dogs per group). Three months after building the edentulous animal model, four groups of implants (control, AO, PD and AO + PD) were inserted. After 4 months of healing, samples were harvested for histometric analyses. The surfaces of anodized implant necks were overlaid with densely distributed pores, 2-7 μm in size. On the PD-modified surfaces, N1s, the chemical bond of nitrogen in PD, was detected using X-ray photoelectron spectroscopy. L929 developed pseudopods more quickly on the PD-modified surfaces than on the surfaces of the control group. The in vivo experiment showed a longer connective tissue seal and a more coronally located peri-implant soft-tissue attachment in the AO + PD group than in the control group (P < .05). The modification of AO + PD on the implant neck yielded better attachment between the implant and peri-implant connective tissue. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Energy expenditure associated with softening and stiffening of echinoderm connective tissue.

    Science.gov (United States)

    Motokawa, Tatsuo; Sato, Eriko; Umeyama, Kenichi

    2012-04-01

    Catch connective tissue of echinoderms at rest (in the standard state) either stiffens or softens in response to different kinds of stimulation. The energy consumption associated with the changes was estimated by measurement of the oxygen consumption rate (VO(2)) in three types of connective tissues-echinoid catch apparatus (CA), holothuroid body-wall dermis (HD), and asteroid body-wall dermis (AD). Mechanical stimulation by repetitive compression (10%-15% strain), which increased viscosity measured by creep tests, was employed for inducing the stiff state. Noradrenaline (10(-3) mol l(-1)), which decreased viscosity of CA, and static 80% compressive strain, which decreased viscosity of HD, were used to induce the soft state in the respective tissues. The VO(2) (in μl/g/h) values of the standard state were 2.91 (CA), 1.41 (HD), and 0.56 (AD), which were less than 1/4 of the VO(2) of the resting body-wall muscle of the starfish. The VO(2) of the stiff state was about 1.5 times greater than that of the standard state in all types of connective tissues. The VO(2) of the soft state was 3.4 (CA)-9.1 (HD) times greater than that of the standard state. The economical nature of catch connective tissue in posture maintenance is discussed.

  17. Specific features of urinary system diseases in children with connective tissue dysplasia

    Directory of Open Access Journals (Sweden)

    T. A. Kryganova

    2015-01-01

    Full Text Available Urinary system diseases in children with differentiated connective tissue dysplasia have not been adequately investigated and the available information is extremely scarce. The diseases represent mainly minimal change disease as orthostatic proteinuria, microscopic hematuria, metabolic disturbances, structural (nephroptosis and vascular abnormalities (aneurysms. Undifferentiated connective tissue dysplasia is an abnormality that is being actively explored by Russian investigators. Multiple organ dysfunctions attract the attention of physicians in many specialties, including nephrologists. Urinary system diseases as recurrent urinary tract infections, renal and calicopeMc malformations, bladder diseases, and severe congenital anomalies of the kidney and urinary tract (CAKUT are often accompanied by the manifestations of connective tissue dysplasia. A number of authors have identified connective tissue disease markers (matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases, transforming growth factor-p etc. to evaluate sclerotic processes in the kidneys. There are single studies of these markers in Alport syndrome or au-tosomal dominant polycystic kidney disease while such data on the differentiated types of dysplasia (Ehlers-Danlos syndrome, Marfan's syndrome are unavailable.

  18. Segmentation of Connective Tissue in Meat from Microtomography Using a Grating Interferometer

    DEFF Research Database (Denmark)

    Einarsdottir, Hildur; Ersbøll, Bjarne Kjær; Larsen, Rasmus

    It has been demonstrated that phase contrast imaging provides superior contrast of soft tissues in biological material over typical absorption tomography [1-2]. In meat science, this imaging modality can provide valuable information of the effects of heat treatment on muscle tissue. Although......, relative volume and the statistics of the electron density of the connective tissue could prove useful for understanding the structural changes occurring in the meat sample due to heat treatment. In this study a two step segmentation algorithm was implemented in order to segment connective tissue from...... phase contrast microtomograms obtained by a gratinginterferometer. This segmentation has previously been demonstrated for the segmentation of the optic nerve head from microscopic images of stained slices [3]. The first step is to model the data as a mixture of Gaussians using an expectation...

  19. A cGMP-applicable expansion method for aggregates of human neural stem and progenitor cells derived from pluripotent stem cells or fetal brain tissue.

    Science.gov (United States)

    Shelley, Brandon C; Gowing, Geneviève; Svendsen, Clive N

    2014-06-15

    A cell expansion technique to amass large numbers of cells from a single specimen for research experiments and clinical trials would greatly benefit the stem cell community. Many current expansion methods are laborious and costly, and those involving complete dissociation may cause several stem and progenitor cell types to undergo differentiation or early senescence. To overcome these problems, we have developed an automated mechanical passaging method referred to as "chopping" that is simple and inexpensive. This technique avoids chemical or enzymatic dissociation into single cells and instead allows for the large-scale expansion of suspended, spheroid cultures that maintain constant cell/cell contact. The chopping method has primarily been used for fetal brain-derived neural progenitor cells or neurospheres, and has recently been published for use with neural stem cells derived from embryonic and induced pluripotent stem cells. The procedure involves seeding neurospheres onto a tissue culture Petri dish and subsequently passing a sharp, sterile blade through the cells effectively automating the tedious process of manually mechanically dissociating each sphere. Suspending cells in culture provides a favorable surface area-to-volume ratio; as over 500,000 cells can be grown within a single neurosphere of less than 0.5 mm in diameter. In one T175 flask, over 50 million cells can grow in suspension cultures compared to only 15 million in adherent cultures. Importantly, the chopping procedure has been used under current good manufacturing practice (cGMP), permitting mass quantity production of clinical-grade cell products.

  20. Effect of connective tissue grafting on peri-implant tissue in single immediate implant sites: A RCT.

    Science.gov (United States)

    Zuiderveld, Elise G; Meijer, Henny J A; den Hartog, Laurens; Vissink, Arjan; Raghoebar, Gerry M

    2018-02-01

    To assess the effect of connective tissue grafting on the mid-buccal mucosal level (MBML) of immediately placed and provisionalized single implants in the maxillofacial aesthetic zone. Sixty patients with a failing tooth were provided with an immediately placed and provisionalized implant. During implant placement, patients randomly received either a connective tissue graft from the maxillary tuberosity (n = 30, test group) or no graft (n = 30, control group). Follow-up visits were at one (T 1 ) and twelve months (T 12 ) after final crown placement. The primary outcome measure was any change in MBML compared to the pre-operative situation. In addition, gingival biotype, aesthetics (using the Pink Esthetic Score-White Esthetic Score), marginal bone level, soft tissue peri-implant parameters and patient satisfaction were assessed. The mean MBML change at T 12 was -0.5 ± 1.1 mm in the control group and 0.1 ± 0.8 mm in the test group (p = .03). No significant differences regarding other outcome variables were observed, neither was gingival biotype associated with a gain or loss in MBML. This one-year study shows that connective tissue grafting in single, immediately placed and provisionalized implants leads to less recession of the peri-implant soft tissue at the mid-buccal aspect, irrespective of the gingival biotype (www.trialregister.nl: TC3815). © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Therapeutic efficacy of guided tissue regeneration and connective tissue autotransplants with periosteum in the management of gingival recession

    Directory of Open Access Journals (Sweden)

    Jovičić Bojan

    2008-01-01

    Full Text Available Background/Aim. Gingival recession progression in clinical practice as an ethiological factor of periodontal diseases, and symptoms of the disease have caused the development of various surgical procedures and techniques of the reconstruction of periodontal defects. The aim of this study was to verify efficacy of surgical procedures that include connective tissue autotransplants with periosteum and guided tissue regeneration for the treatment of gingival recession. Methods. The study included 20 teet with gingival recession, Müller class II and III. Ten teeth with gingival recession were treated with resorptive membrane and coronary guided surgical flap (GTR group. On the contralateral side 10 teeth with gingival recession were treated with connective tissue autotransplants with periosteum in combination with coronary guided surgical flap (TVT group. We measured the degree of epithelial attachment (DEA, width of subgingival curettage (WGC and vertical deepness of recession (VDR. For statistical significance we used Student's ttest. Results. The study revealed statistical significance in reducing VDR by both used treatments. Root deepness in GTR and TVT group was 63.5%, and 90%, respectively. With both surgical techniques we achieved coronary dislocation of the epithelial attachment, larger zone of gingival curettage, and better oral hygiene. Conclusion. Current surgical techniques are effective in the regeneration of deep periodontal spaces and the treatment of gingival recession. Significantly better results were achieved with the used coronary guided surgical flap than with guided tissue regeneration.

  2. Migraine with Ischemic Stroke in a Young Male with Hyperhomocysteinemia and Connective Tissue Dysplasia

    Directory of Open Access Journals (Sweden)

    S.K. Yevtushenko

    2014-08-01

    Full Text Available Case report of migraine with ischemic stroke on the background of hyperhomocysteinemia in a young male with connective tissue dysplasia is given in the article. The clinical picture, results of magnetic resonance imaging, tomography, genetic and somatic examination are described.

  3. Mineralization/Anti-Mineralization Networks in the Skin and Vascular Connective Tissues

    OpenAIRE

    Li, Qiaoli; Uitto, Jouni

    2013-01-01

    Ectopic mineralization has been linked to several common clinical conditions with considerable morbidity and mortality. The mineralization processes, both metastatic and dystrophic, affect the skin and vascular connective tissues. There are several contributing metabolic and environmental factors that make uncovering of the precise pathomechanisms of these acquired disorders exceedingly difficult. Several relatively rare heritable disorders share phenotypic manifestations similar to those in ...

  4. Tenascin-Y, a component of distinctive connective tissues, supports muscle cell growth.

    Science.gov (United States)

    Hagios, C; Brown-Luedi, M; Chiquet-Ehrismann, R

    1999-12-15

    Chicken tenascin-Y is an extracellular matrix protein most closely related to the mammalian tenascin-X. It is highly expressed in the connective tissue of skeletal muscle (C. Hagios, M. Koch, J. Spring, M. Chiquet, and R. Chiquet-Ehrismann, 1996, J. Cell Biol. 134, 1499-1512). Here we demonstrate the presence of tenascin-Y in specific areas of the connective tissues in developing lung, kidney, and skin. In skin tenascin-Y shows a complementary expression pattern to tenascin-C, whereas in the lung and kidney the sites of expression are partly overlapping. Tenascin-Y is also present in embryonic skeletal muscle where it is expressed in the developing connective tissue in between the muscle fibers. This connective tissue is also the major site of alpha5 integrin expression. We purified recombinantly expressed tenascin-Y and tested its effect on cell adhesion and its influence on muscle cell growth and differentiation. C2C12 myoblasts were able to adhere to tenascin-Y and showed extensive formation of actin-rich processes without generation of stress fibers. Furthermore, we found that tenascin-Y influenced cell morphology of chick embryo fibroblasts over prolonged times in culture and that it supports primary muscle cell growth and restricts muscle cell differentiation. Copyright 1999 Academic Press.

  5. Pulmonary hypertension in connective tissue disease - Report of three cases and review of the literature

    NARCIS (Netherlands)

    L.C. Pronk (Linda); A.J.G. Swaak (Antonius)

    1991-01-01

    textabstractPatients with connective tissue disease (CTD) who are prone to developed isolated pulmonary hypertension (PH) are primarily young females with a history of Raynaud's phenomenon associated with an exertional dyspnoea. From the start of the disease, pulmonary function tests show a

  6. Regulatory mechanism and research progress of connective tissue growth factor in diabetic retinopathy

    Directory of Open Access Journals (Sweden)

    Xi-Da Liang

    2016-04-01

    Full Text Available Diabetic retinopathy is one of the microvascular abnormal diseases. In the late stage of disease progression, the antibody of vascular endothelial growth factor can significantly inhibit the formation of new blood vessels and improve macular edema, which is widely used in clinical. However, the aggravation of pro-fibrotic influence after long-term treated by the medicine also attracts a wide range of attention. Connective tissue growth factor, as an important cytokine in intraocular fibrosis, over expressed after treated by the drug, is considered to be one of the most important factors in the side effect of the drug, and is also a potential therapeutic target. After finishing the current research, the regulation mechanism of connective tissue growth factor, includes two ways, regulation of gene expression and direct binding to other cell factors or receptors. Because of its special four module structure, it has many kinds of cell factor specific binding sites, and its regulation mode is more dependent on the latter, which promotes or inhibits the expression of several important cytokine pathways. In diabetic retinopathy, its expression goes throughout the disease process. The accumulation of connective tissue growth factor plays an important role in promoting the thickening of basement membrane and the formation of new blood vessels in the early stage of the clinical stage and the formation of the new blood vessels. In this paper, the regulatory mechanism of connective tissue growth factor and the research progress of this factor in DR are systematically expounded.

  7. In situ bone tissue engineering via ultrasound-mediated gene delivery to endogenous progenitor cells in mini-pigs

    Science.gov (United States)

    Bez, Maxim; Sheyn, Dmitriy; Tawackoli, Wafa; Avalos, Pablo; Shapiro, Galina; Giaconi, Joseph C.; Da, Xiaoyu; Ben David, Shiran; Gavrity, Jayne; Awad, Hani A.; Bae, Hyun W.; Ley, Eric J.; Kremen, Thomas J.; Gazit, Zulma; Ferrara, Katherine W.; Pelled, Gadi; Gazit, Dan

    2017-01-01

    More than 2 million bone-grafting procedures are performed each year using autografts or allografts. However, both options carry disadvantages, and there remains a clear medical need for the development of new therapies for massive bone loss and fracture nonunions. We hypothesized that localized ultrasound-mediated, microbubble-enhanced therapeutic gene delivery to endogenous stem cells would induce efficient bone regeneration and fracture repair. To test this hypothesis, we surgically created a critical-sized bone fracture in the tibiae of Yucatán mini-pigs, a clinically relevant large animal model. A collagen scaffold was implanted in the fracture to facilitate recruitment of endogenous mesenchymal stem/progenitor cells (MSCs) into the fracture site. Two weeks later, transcutaneous ultrasound-mediated reporter gene delivery successfully transfected 40% of cells at the fracture site, and flow cytometry showed that 80% of the transfected cells expressed MSC markers. Human bone morphogenetic protein-6 (BMP-6) plasmid DNA was delivered using ultrasound in the same animal model, leading to transient expression and secretion of BMP-6 localized to the fracture area. Micro–computed tomography and biomechanical analyses showed that ultrasound-mediated BMP-6 gene delivery led to complete radiographic and functional fracture healing in all animals 6 weeks after treatment, whereas nonunion was evident in control animals. Collectively, these findings demonstrate that ultrasound-mediated gene delivery to endogenous mesenchy-mal progenitor cells can effectively treat nonhealing bone fractures in large animals, thereby addressing a major orthopedic unmet need and offering new possibilities for clinical translation. PMID:28515335

  8. Selective reactivation of human herpesvirus 6 in patients with autoimmune connective tissue diseases.

    Science.gov (United States)

    Broccolo, Francesco; Drago, Francesco; Cassina, Giulia; Fava, Andrea; Fusetti, Lisa; Matteoli, Barbara; Ceccherini-Nelli, Luca; Sabbadini, Maria Grazia; Lusso, Paolo; Parodi, Aurora; Malnati, Mauro S

    2013-11-01

    Viral infections have been associated with autoimmune connective tissue diseases. To evaluate whether active infection by Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus (HHV)-6, -7, -8, as well as parvovirus B19 (B19V) occur in patients with autoimmune connective tissue diseases, viral DNA loads were assessed in paired samples of serum and peripheral blood mononuclear cells (PBMCs) of 115 patients affected by different disorders, including systemic sclerosis, systemic, and discoid lupus erythematosus, rheumatoid arthritis, and dermatomyositis. Two additional groups, patients affected by inflammatory diseases (n=51) and healthy subjects (n=58) were studied as controls. The titers of anti-HHV-6 and anti-EBV antibodies were also evaluated. Cell-free HHV-6 serum viremia was detected in a significantly higher proportion of connective tissue diseases patients compared to controls (P<0.0002); a significant association between HHV-6 reactivation and the active disease state was found only for lupus erythematosus (P=0.021). By contrast, the rate of cell-free EBV viremia was similar in patients and controls groups. Cell-free CMV, HHV-8, and B19V viremia was not detected in any subject. Anti-HHV-6 and anti-EBV early antigen IgG titers were both significantly higher in autoimmune diseases patients as compared to healthy controls, although they were not associated with the presence of viremia. EBV, HHV-6, -7 prevalence and viral load in PBMCs of patients with connective tissue diseases and controls were similar. These data suggest that HHV-6 may act as a pathogenic factor predisposing patients to the development of autoimmune connective tissue diseases or, conversely, that these disorders may predispose patients to HHV-6 reactivation. © 2013 Wiley Periodicals, Inc.

  9. Sjögren's syndrome: An underdiagnosed condition in mixed connective tissue disease

    Directory of Open Access Journals (Sweden)

    Fany Solange Usuba

    2014-03-01

    Full Text Available OBJECTIVE: To determine the prevalence of sicca symptoms, dry eye, and secondary Sjögren's syndrome and to evaluate the severity of dry eye in patients with mixed connective tissue disease. METHODS: In total, 44 consecutive patients with mixed connective tissue disease (Kasukawa's criteria and 41 healthy controls underwent Schirmer's test, a tear film breakup time test, and ocular surface staining to investigate dry eye. In addition, the dry eye severity was graded. Ocular and oral symptoms were assessed using a structured questionnaire. Salivary gland scintigraphy was performed in all patients. Classification of secondary Sjögren's syndrome was assessed according to the American-European Consensus Group criteria. RESULTS: The patients and controls had comparable ages (44.7±12.4 vs. 47.2±12.2 years and frequencies of female gender (93 vs. 95% and Caucasian ethnicity (71.4 vs. 85%. Ocular symptoms (47.7 vs. 24.4% and oral symptoms (52.3 vs. 9.7% were significantly more frequent in patients than in controls. Fourteen (31.8% patients fulfilled Sjögren's syndrome criteria, seven of whom (50% did not have this diagnosis prior to study inclusion. A further comparison of patients with mixed connective tissue disease with or without Sjögren's syndrome revealed that the former presented significantly lower frequencies of polyarthritis and cutaneous involvement than did the patients without Sjögren's syndrome. Moderate to severe dry eye was found in 13 of 14 patients with mixed connective tissue disease and Sjögren's syndrome (92.8%. CONCLUSIONS: Sjögren's syndrome, particularly with moderate to severe dry eye, is frequent in patients with mixed connective tissue disease. These findings alert the physician regarding the importance of the appropriate diagnosis of this syndrome in such patients.

  10. Ultrasound evidence of altered lumbar connective tissue structure in human subjects with chronic low back pain.

    Science.gov (United States)

    Langevin, Helene M; Stevens-Tuttle, Debbie; Fox, James R; Badger, Gary J; Bouffard, Nicole A; Krag, Martin H; Wu, Junru; Henry, Sharon M

    2009-12-03

    Although the connective tissues forming the fascial planes of the back have been hypothesized to play a role in the pathogenesis of chronic low back pain (LBP), there have been no previous studies quantitatively evaluating connective tissue structure in this condition. The goal of this study was to perform an ultrasound-based comparison of perimuscular connective tissue structure in the lumbar region in a group of human subjects with chronic or recurrent LBP for more than 12 months, compared with a group of subjects without LBP. In each of 107 human subjects (60 with LBP and 47 without LBP), parasagittal ultrasound images were acquired bilaterally centered on a point 2 cm lateral to the midpoint of the L2-3 interspinous ligament. The outcome measures based on these images were subcutaneous and perimuscular connective tissue thickness and echogenicity measured by ultrasound. There were no significant differences in age, sex, body mass index (BMI) or activity levels between LBP and No-LBP groups. Perimuscular thickness and echogenicity were not correlated with age but were positively correlated with BMI. The LBP group had approximately 25% greater perimuscular thickness and echogenicity compared with the No-LBP group (ANCOVA adjusted for BMI, p<0.01 and p<0.001 respectively). This is the first report of abnormal connective tissue structure in the lumbar region in a group of subjects with chronic or recurrent LBP. This finding was not attributable to differences in age, sex, BMI or activity level between groups. Possible causes include genetic factors, abnormal movement patterns and chronic inflammation.

  11. Histopathological approach to patterns of interstitial pneumonia in patient with connective tissue disorders.

    Science.gov (United States)

    Nicholson, Andrew G; Colby, Thomas V; Wells, Athol U

    2002-03-01

    It is well established that some patients with connective tissue disorders will suffer from pulmonary disease at some stage in their disease progression. This article concentrates on the interstitial pneumonias, seen in association with most types of connective tissue disorder, particularly in the ligh of non-specific interstitial pneumonia (NSIP) being recognised as a distinct histological pattern. Most published articles on this subject precede recognition of NSIP and, as such, the relative incidence of patterns of interstitial pneumonia, as defined by the International Consensus Classification Committee for Interstitial Lung Disease (ICCILD), as well as the clinical and prognostic significance of these patterns is undergoing further scrutiny. In this review, the recognised histological patterns, namely usual interstitial pneumonia (UIP), non-specific interstitial pneumonia (NSIP), diffuse alveolar damage (DAD), organising pneumonia (OP), reactive pulmonary lymphoid hyperplasia, desquamative interstitial pneumonia (DIP) and respiratory bronchiolitis-associated interstitial lung disease (RBILD) are reviewed systematically in relation to the various subgroups of connective tissue disorders. As yet, there are few published studies, but current evidence suggests that many cases previously classified as fibrosing alveolitis are likely to show a pattern of NSIP rather than UIP, particularly in relation to systemic sclerosis. The histological pattern of usual interstitial pneumonia, the most frequently seen pattern in biopsies from patients with idiopathic pulmonary fibrosis/cryptogenic fibrosing alveolitis, appears to be comparatively rare. Furthermore, any biopsy showing a combination of histological patterns, a pattern of non-specific interstitial pneumonia or a pattern of lymphoid interstitial pneumonia/follicular bronchiolitis should be thoroughly investigated for a background connective tissue disorder, if previously unsuspected. Finally, the recently published

  12. Oxidative stress and CCN1 protein in human skin connective tissue aging

    Directory of Open Access Journals (Sweden)

    Zhaoping Qin

    2016-06-01

    Full Text Available Reactive oxygen species (ROS is an important pathogenic factor involved in human aging. Human skin is a primary target of oxidative stress from ROS generated from both extrinsic and intrinsic sources, like ultraviolet irradiation (UV and endogenous oxidative metabolism. Oxidative stress causes the alterations of collagen-rich extracellular matrix (ECM, the hallmark of skin connective tissue aging. Age-related alteration of dermal collagenous ECM impairs skin structural integrity and creates a tissue microenvironment that promotes age-related skin diseases, such as poor wound healing and skin cancer. Here, we review recent advances in our understanding of oxidative stress and CCN1 protein (first member of CCN family proteins, a critical mediator of oxidative stress-induced skin connective tissue aging.

  13. Use of a subepithelial connective tissue graft to treat an area pigmented with graphite.

    Science.gov (United States)

    Phillips, Gregory E; John, Vanchit

    2005-09-01

    Pigmentations of the oral cavity are commonly noted in clinical practice and may have physiologic, non-physiologic, or pathologic etiologies. The most common non-physiologic localized pigmentation is the amalgam tattoo; another, less common, non-physiologic pigmentation is the graphite tattoo. Graphite tattoos may easily be confused with amalgam tattoos but have only infrequently been reported in the literature. This case report discusses a patient with a localized pigmented lesion involving the free gingiva, attached gingiva, and alveolar mucosa. The patient was referred for esthetic enhancement of the area in question. Dental history revealed trauma to the area involving falling on a pencil as a child. The lesion was excised and submitted for histologic examination; a subepithelial connective tissue graft was harvested and utilized to prevent an esthetic defect. Histologic evaluation confirmed graphite within the soft tissue as the etiology of the discoloration. At the 2-month postoperative appointment, a highly esthetic outcome was obtained utilizing a connective tissue graft. Although less common than the amalgam tattoo, the graphite tattoo may be encountered in the course of routine dental examinations and should be included in a differential diagnosis of any localized pigmented lesion. Although histologic evaluation is necessary to rule out pathology, if the dental history is consistent with the clinical impression of a nonpathologic lesion, such as the graphite tattoo in this case report, treatment with an autogenous connective tissue graft at the time of excision can produce a highly esthetic result and avoid additional surgical procedures in the future.

  14. Treatment of amalgam tattoo with a subepithelial connective tissue graft and acellular dermal matrix.

    Science.gov (United States)

    Thumbigere-Math, Vivek; Johnson, Deborah K

    2014-04-01

    A 54-year-old female was referred for management of a large amalgam tattoo involving the alveolar mucosa between teeth #6 and #9. The lesion had been present for over 20 years following endodontic treatment of teeth #7 and #8. A two-stage surgical approach was used to remove the pigmentation, beginning with removal of amalgam fragments from the underlying bone and placement of a subepithelial connective tissue graft and acellular dermal matrix to increase soft tissue thickness subadjacent to the amalgam. Following 7 weeks of healing, gingivoplasty was performed to remove the overlying pigmented tissue. At the 21-month follow-up appointment, the patient exhibited naturally appearing soft tissue with no evidence of amalgam tattoo.

  15. FEATURES OF CLINICAL COURSE OF GASTROESOPHAGEAL REFLUX DISEASE IN NEWLY RECRUITED WITH CONNECTIVE TISSUE UNDIFFERENTIATED DYSPLASIA SYNDROME

    Directory of Open Access Journals (Sweden)

    E.I. Kashkina

    2008-12-01

    Full Text Available The presence of connective tissue undifferentiated dysplasia syndrome against a background of psychological stress at newly recruited can promote the risk of gastroesophageal reflux disease occurrence. To the utmost, correlation between the gastroesophageal reflux disease and such manifestations of connective tissue undifferentiated dysplasia syndrome as asthenic constitution, chest deformation, Gothic palate and hypermobility of joints was found

  16. Connective tissue regeneration in skeletal muscle after eccentric contraction-induced injury

    DEFF Research Database (Denmark)

    Mackey, Abigail Louise; Kjaer, Michael

    2017-01-01

    to be sustained for a long time after the major myofibre responses have subsided. While the use of electrical stimulation to induce eccentric contractions versus voluntary eccentric contractions appears to lead to a greater extent of myofibre necrosis and regenerative response, this difference is not apparent...... when the muscle connective tissue responses are compared, although further work is required to confirm this. Pharmacological agents (growth hormone and angiotensin II type I receptor blockers) are considered in the context of accelerating the muscle connective tissue adaptation to loading. Cautioning...... interaction during adaptation to eccentric contractions is an unexplored field in human skeletal muscle and may provide insight into the optimal timing of rest vs. return to activity after muscle injury....

  17. [Biochemical indices of connective tissue metabolism in patients with chronic hepatitis B and C].

    Science.gov (United States)

    Martynovich, T L; Magomedov, S

    2013-09-01

    37 patients with chronic hepatitis B and C were examined. Patients were divided into 3 groups depending on the degree of connective tissue dysplasia. We investigated: free and protein-bounded hydroxyproline, collagenase activity, total alkaline phosphatase and its bone fraction, creatinine, calcium and phosphorus content in the blood serum and urine. It has been found the dependence of collagen synthesis from the state of connective tissue. The higher is the degree of dysplasia, the more intensive is the process of collagen synthesis (P < 0.05). The index of corellation between protein-bounded and free fraction can be used as a biochemical marker for determination the stage of pathological process in the liver and for monitoring the effectiveness of therapy.

  18. A Case of ANCA Negative Pauci-immune Crescentic Glomerulonephritis in Mixed Connective Tissue Disease

    Directory of Open Access Journals (Sweden)

    Neena Mampilly

    2015-04-01

    Full Text Available Pauci-immune crescentic glomerulonephritis (CrGN is one of the most common causes of rapidly progressive glomerulonephritis. The majority of patients with pauciimmune CrGN have circulating antineutrophil cytoplasmic autoantibodies (ANCA. Approximately 10% of systemic vasculitides patients test negative for ANCA. Majority of the ANCA negative pauciimmune CrGN described in the literature have not shown associations with connective tissue diseases. Only isolated case reports of associations with systemic lupus erythematosus and scleroderma have been described. We report the case of a 24 yr lady who was diagnosed to have a pauciimmune crescentic glomerulonephritis on renal biopsy, and was found to be ANCA negative. Subsequently her collagen profile revealed a mixed connective tissue disease, even though she did not have any other systemic manifestations of the disease at presentation. We presume that antiendothelial antibodies (AECA may have a role in the pathogenesis of the disease.

  19. Scleroderma renal crisis in a case of mixed connective tissue disease

    Directory of Open Access Journals (Sweden)

    Mukul Vij

    2014-01-01

    Full Text Available Mixed connective tissue disease (MCTD is an overlap syndrome first defined in 1972 by Sharp et al. In this original study, the portrait emerged of a connective tissue disorder sharing features of systemic lupus erythematosus, systemic sclerosis (scleroderma and polymyositis. Scleroderma renal crisis (SRC is an extremely infrequent but serious complication that can occur in MCTD. The histologic picture of SRC is that of a thrombotic micro-angiopathic process. Renal biopsy plays an important role in confirming the clinical diagnosis, excluding overlapping/superimposed diseases that might lead to acute renal failure in MCTD patients, helping to predict the clinical outcome and optimizing patient management. We herewith report a rare case of SRC in a patient with MCTD and review the relevant literature.

  20. [CONNECTIVE TISSUE METABOLIC FEATURES IN CLIMACTERIC SYNDROME'S PATIENTS WITH VARIOUS TYPES OF MENOPAUSE].

    Science.gov (United States)

    Gryshchenko, O; Vasylieva, I; Gryshchuk, K

    2017-04-01

    The purpose of the study was investigation of the connective tissue metabolic features among women with menopausal syndrome (MS) and MS, in which the arthropathic syndrome is leading and comparative analysis of the connective tissue indicators exchange during menopause caused in a surgical and natural way. We examined 70 women in total, menopause duration they accounted for 1,95±1,1 years, it came both as natural, and as a result of a surgery. The main group included 40 women with MS with leading arthropathic syndrome. The patients' modified menopausal index was calculated (MMI), the functional condition of the joints was assessed on a scale-questionnaire with the calculation of the clinical-functional index of WOMAC; the quantitative content and qualitative composition of glycosaminoglycans in the serum, the urinary excretion of hydroxyproline and uronic acids were determined. To determine the degree of deviation from the control (standard) indicators was used non-parametric Mann-Whitney criterion and factor analysis (main components method). It was revealed that all patients have an increased content of glycosaminoglycans and glycoprotein in the blood, which corresponds to the general age-related rearrangement of connective tissue metabolism, but the patients of the main group have more expressed indictors, which corresponds to more severe dystrophic changes and the severity of clinical symptoms. Redistribution of the fractional composition of glycosaminoglycans towards the increase of chondroitin-6 sulfate in patients of the main group indicates the presence of pre-emptive destruction of cartilage. The arthropathic syndrome availability also confirms the significant reduction CI-6s / CI-4s ratio and an increased content of chondroitin sulfates. Patients with a natural type of menopause showed more pronounced changes in connective tissue metabolites, in contrast to patients with surgical menopause еhat indicates a longer and more invasive pathologic course of

  1. Treatment of multiple gingival recessions adopting modified tunnel subepithelial connective tissue graft technique

    OpenAIRE

    Jagmohan Singh; Vipin Bharti

    2014-01-01

    Gingival recession related to periodontal disease or developmental problems can result in root sensitivity, root caries, and esthetically unacceptable root exposures. In the past, multiple surgical procedures have been proposed to obtain root coverage on exposed buccal root surfaces. There has been great interest in the treatment of gingival recession defects, especially with subepithelial connective-tissue grafting (SCTG). Recent advances have focused on SCTG by the tunnel technique. This ar...

  2. Anti-Nuclear antibodies: Current concepts and future direction for diagnosing connective tissue disease

    OpenAIRE

    K Gautam

    2015-01-01

    Identification of antinuclear antibodies has been used for the diagnosis of connective tissue diseases for more than fifty years. Indirect immunofluorescence on human epithelial (HEp-2) cells is considered the gold standard screening method for the detection of antinuclear autoantibodies. As the demand of ANA testing increased, the need for automation and standardization has also come forth. A high level of false positive and false negative cases is seen in various populations making it diffi...

  3. Systemic Lupus Erythematosus and Systemic Autoimmune Connective Tissue Disorders behind Recurrent Diastolic Heart Failure

    Directory of Open Access Journals (Sweden)

    Luis Miguel Blasco Mata

    2012-01-01

    Full Text Available Diastolic heart failure (DHF remains unexplained in some patients with recurrent admissions after full investigation. A study was directed for screening SLE and systemic autoimmune connective tissue disorders in recurrent unexplained DHF patients admitted at a short-stay and intermediate care unit. It was found that systemic autoimmune conditions explained 11% from all of cases. Therapy also prevented new readmissions. Autoimmunity should be investigated in DHF.

  4. Intravenous iloprost in the combination therapy of vascular disorders in patients with systemic connective tissue diseases

    Directory of Open Access Journals (Sweden)

    Aleksandr Vitalyevich Volkov

    2013-01-01

    Full Text Available Systemic connective tissue diseases, systemic scleroderma in particular, constitute a group of diseases in which vascular disorders underlying diverse clinical manifestations are one of the pathogenetic components. Raynaud 's syndrome and ulceration are the most common symptoms of these diseases, which influence quality of life in patients and require constant drug therapy. The paper discusses the authors' clinical experience with intravenous iloprost used in the combination therapy of the vascular manifestations of systemic scleroderma and systemic lupus erythematosus.

  5. Connective tissue graft vs. emdogain: A new approach to compare the outcomes.

    Science.gov (United States)

    Sayar, Ferena; Akhundi, Nasrin; Gholami, Sanaz

    2013-01-01

    The aim of this clinical trial study was to clinically evaluate the use of enamel matrix protein derivative combined with the coronally positioned flap to treat gingival recession compared to the subepithelial connective tissue graft by a new method to obtain denuded root surface area. Thirteen patients, each with two or more similar bilateral Miller class I or II gingival recession (40 recessions) were randomly assigned to the test (enamel matrix protein derivative + coronally positioned flap) or control group (subepithelial connective tissue graft). Recession depth, width, probing depth, keratinized gingival, and plaque index were recorded at baseline and at one, three, and six months after treatment. A stent was used to measure the denuded root surface area at each examination session. Results were analyzed using Kolmogorov-Smirnov, Wilcoxon, Friedman, paired-sample t test. The average percentages of root coverage for control and test groups were 63.3% and 55%, respectively. Both groups showed significant keratinized gingival increase (P 0.05). The results of Friedman test were significant for clinical indices (P < 0.05), except for probing depth in control group (P = 0.166). Enamel matrix protein derivative showed the same results as subepithelial connective tissue graft with relatively easy procedure to perform and low patient morbidity.

  6. Isolated Ro52 Antibodies as Immunological Marker of a Mild Phenotype of Undifferentiated Connective Tissue Diseases

    Directory of Open Access Journals (Sweden)

    Ana Alonso-Larruga

    2017-01-01

    Full Text Available The term undifferentiated connective tissue disease (UCTD is used to describe undiagnosed patients that do not fulfill classification criteria for definite connective tissue disease (Systemic Lupus, Systemic Sclerosis, Sjögren Syndrome, and Dermatomyositis/Polymyositis. It is important to find serological markers as predictors of the evolution or severity of these diseases. The objective of this retrospective study was to investigate if there was a milder subgroup of UCTD with a special clinical profile consisting only in the presence of anti-Ro52 autoantibodies. Immunological and clinical records of 62 patients attending the hospital during 30 months were studied. Results showed a target population formed by mostly women, aged between 40 and 80 years at the moment of the study, with a registered age of onset between 40 and 60 years. Speckled pattern was the most frequent pattern found by indirect immunofluorescence. Given the obtained results and keeping in mind possible limitations because of sample size, isolated positive anti-Ro52 autoantibodies seem to lead to a benign effect in terms of evolution of the disease. As a future objective, the follow-up of these patients should be necessary to investigate new clinical symptoms, serological markers, or development of a definite connective tissue disease over time.

  7. Immediate single tooth replacement with subepithelial connective tissue graft using platform switching implants: a case series.

    Science.gov (United States)

    Chung, Seunghwan; Rungcharassaeng, Kitichai; Kan, Joseph Y K; Roe, Phillip; Lozada, Jaime L

    2011-10-01

    This case series evaluated the facial gingival stability following single immediate tooth replacement in conjunction with subepithelial connective tissue graft (SCTG). Implant success rate and peri-implant tissue response were also reported. Ten patients (6 male, 4 female), with a mean age of 52.1 (range = 22.7 to 67.1) years, underwent immediate implant placement and provisionalization with SCTG and were evaluated clinically and radiographically at presurgery (T0), at the time of immediate tooth replacement and SCTG (T1), and 3 months (T2), 6 months (T3), and 12 months (T4) after surgery. Data were analyzed using the Friedman and Wilcoxon signed-ranks tests at the significance level of α = .05. At 1 year, 9 of 10 implants remained osseointegrated with the overall mean marginal bone change of -0.31 mm and a mean facial gingival level change of -0.05 mm. The modified plaque index scores showed that patients were able to maintain a good level of hygiene throughout the study. The papilla index score indicated that at T4, more than 50% of the papilla fill was observed in 89% of all sites. When proper 3-dimensional implant position is achieved and bone graft is placed into the implant-socket gap, favorable success rate and peri-implant tissue response of platform switching implants can be achieved following immediate tooth replacement in conjunction with subepithelial connective tissue graft.

  8. [Fungal invasion of connective tissue in patients with gingival-periodontal disease].

    Science.gov (United States)

    Rubio, Nicolás Agustín; Puia, Sebastian; Toranzo, Silvia; Brusca, María Isabel

    2015-01-01

    In the last few years unusual microorganisms have been isolated from subgingival biofilm, as possible initiators or contributors to periodontal disease, especially in patients who show no improvement during treatment. To study the Candida invasion of the connective tissue in relation to subgingival biofilm presence. A total of 55 immunocompetent patients of both sexes, between 21 and 55 years of age, non-smokers, without previous antimicrobial treatment, suffering periodontal diseases, were studied. Soft tissues, supragingival and subgingival plaque samples, and periodontal pocket biopsies were taken. Microscopic studies, cultures, assimilation profiles, and DNA amplifications were performed. In 35% of the samples, different species of Candida were isolated in cultures, especially Candida albicans. Hyphae invasions in the connective tissue were observed, in association with anaerobic microorganisms (Porphyromonas gingivalis, Prevotella intermedia and Aggregatibacter actinomycetemcomitans) in patients with periodontitis. Different species of Candida could be part of the periodontal plaque and could play an important role in the adherence to soft tissues, allowing deep invasion. They also could infect gingival pockets in patients with gingivitis, even in healthy locations, playing a commensal or opportunist role. Copyright © 2011 Revista Iberoamericana de Micología. Published by Elsevier Espana. All rights reserved.

  9. Energy metabolism disorders in rat salivary glands tissues in connection with chronic sodium nitrate intoxication.

    Science.gov (United States)

    Avetikov, D; Bondarenko, V; Danylchenko, S; Pronina, E; Stavytskyi, S

    2014-12-01

    The purpose of the research was the study of nitrite impact on energy metabolism in salivary gland tissues in connection with chronic nitrate intoxication. The study has been carried out on 100 Wistar rats, weighing 160-250 g, which were divided into following groups: the 1st group consisted of intact rodents (control); the 2nd group consisted of experimental rodents, where chronic nitrate intoxication has been reproduced during 14, 30, 60 and 90 days. Intoxication leads to hypoxia, which complications cause tissue hypoxia. Has been established that prolonged intake of nitrates in low doses leads to their accumulation in salivary glands tissues all these result in derangement of metabolism at the intermembrane cellular level. At the same time energy metabolism in salivary glands is inhibited, resulting in their dysfunction at the excretory and endocrine levels.

  10. Production and characterization of monoclonal antibodies directed against connective tissue proteoglycans

    DEFF Research Database (Denmark)

    Caterson, B; Christner, J E; Baker, J R

    1985-01-01

    attached to the proteoglycan core protein after chondroitinase digestion of the proteoglycan (i.e., delta-unsaturated 4- and 6-sulfated and unsulfated chondroitin sulfate on the proteoglycan core). The antibody recognizing keratan sulfate has been used to demonstrate the presence of a keratan sulfate...... distribution of 4- and 6-sulfated and unsulfated proteoglycans in tissue sections of cartilage and other noncartilaginous tissues. Digestion with chondroitinase ABC or ACII can be used to differentiate between chondroitin sulfate and dermatan sulfate proteoglycan in different connective tissues. In addition......, the presence of a 6-sulfated chondroitin sulfate proteoglycan that is associated with membranes surrounding nerve and muscle fiber bundles is described. Monoclonal antibodies were also raised against the link protein(s) of cartilage proteoglycan aggregate. They have been used in peptide map analyses of link...

  11. Epidemiology of Mixed Connective Tissue Disease, 1985-2014: A Population-Based Study.

    Science.gov (United States)

    Ungprasert, Patompong; Crowson, Cynthia S; Chowdhary, Vaidehi R; Ernste, Floranne C; Moder, Kevin G; Matteson, Eric L

    2016-12-01

    To characterize the epidemiology of mixed connective tissue disease (MCTD) from 1983 to 2014. An inception cohort of patients with incident MCTD in 1985-2014 in Olmsted County, Minnesota was identified based on comprehensive individual medical record review. Diagnosis of MCTD required fulfillment of at least 1 of the 4 widely accepted diagnostic criteria without fulfillment of classification criteria for other connective tissue diseases. Data were collected on demographic characteristics, clinical presentation, laboratory investigations, and mortality. A total of 50 incident cases of MCTD were identified (mean age 48.1 years and 84% were female). The annual incidence of MCTD was 1.9 per 100,000 population. Raynaud's phenomenon was the most common initial symptoms (50%), followed by arthralgia (30%) and swollen hands (16%). The diagnosis was frequently delayed with the median time from first symptom to fulfillment of criteria of 3.6 years. At fulfillment of criteria, arthralgia was the most prevalent manifestation (86%), followed by Raynaud's phenomenon (80%), swollen hands (64%), leukopenia/lymphopenia (44%), and heartburn (38%). Evolution to other connective tissue occurred infrequently with a 10-year rate of evolution of 8.5% and 6.3% for systemic lupus erythematosus and systemic sclerosis, respectively. The overall mortality was not different from the general population with a standardized mortality ratio of 1.1 (95% confidence interval 0.4-2.6). This study was the first population-based study of MCTD to provide a complete picture of epidemiology and clinical characteristics of MCTD. MCTD occurred in about 2 persons per 100,000 per year. Evolution to other connective diseases occurred infrequently and the mortality was not affected. © 2016, American College of Rheumatology.

  12. Histological changes in connective tissue of rat tails after bipolar radiofrequency treatment.

    Science.gov (United States)

    Beltrán-Frutos, E; Bernal-Mañas, C M; Navarro, S; Zuasti, A; Ferrer, C; Canteras, M; Seco-Rovira, V; García-Collado, A J; Pastor, L M

    2012-09-01

    Radiofrequency (RF) has been included in the techniques used in aesthetic surgery/medicine. To date, no studies have performed a histological assessment of changes in the tissue after application of bipolar radiofrequency (BRF) with low energy and frequency. The aim of this study was to examine changes that are produced in connective tissue, principally in the fibroblasts, following BRF treatment. Four groups of rats received a different number of RF sessions (1, 2, 3 and 5). The following parameters were determined: the number of fibroblasts/unit area (FA), the proliferation index (PI), the Heat shock Protein 47 index (HSPI) and the percentage of connective tissue (PC). For statistical analysis, two subgroups (A and B) were made for the variables FA, PI and PC, and another two subgroups (C and D) for the variable HSPI. Significant differences for FA, PI and PC were observed between subgroups A and B, FA and PI having higher values in A, while PC had higher values in B. The HSPI in subgroup C showed significantly higher values than in D. Low energy and frequency BRF led to an increase in the number, proliferation and biosynthetic activity of fibroblasts. The resulting stress suffered by fibroblasts as a result of heat may be associated with the phenomenon of hormesis.

  13. State-of-the-Art Imaging of the Lung for Connective Tissue Disease (CTD).

    Science.gov (United States)

    Ohno, Yoshiharu; Koyama, Hisanobu; Yoshikawa, Takeshi; Seki, Shinichiro

    2015-12-01

    Involvement of the respiratory system is common in connective tissue diseases (CTDs), and the resultant lung injury can affect every part of the lung: the pleura, alveoli, interstitium, vasculature, lymphatic tissue, and large and/or small airways. Most of the parenchymal manifestations of CTD are similar to those found in interstitial lung diseases (ILDs), especially idiopathic interstitial pneumonias, and can be classified using the same system. Although there is some overlap, each CTD is associated with a characteristic pattern of pulmonary involvement. For this reason, thin-section CT as well as pulmonary function tests and serum markers are utilized for diagnosis, disease severity assessment, and therapeutic efficacy evaluation of ILD associated with CTD. In addition, newly developed pulmonary magnetic resonance imaging (MRI) procedures have been recommended as useful alternative imaging options for patients with CTD. This review article will (1) address radiological findings for chest radiography and conventional or thin-section CT currently used for six major types of CTD, rheumatoid arthritis, scleroderma (progressive systemic sclerosis), polymyositis/dermatomyositis, systemic lupus erythematosus, Sjögren syndrome and mixed connective tissue disease; (2) briefly deal with radiation dose reduction for thin-section CT examination; and (3) discuss clinically applicable or state-of-the-art MR imaging for CTD patients.

  14. Tissue engineering approaches to develop decellularized tendon matrices functionalized with progenitor cells cultured under undifferentiated and tenogenic conditions

    Directory of Open Access Journals (Sweden)

    Daniele D’Arrigo

    2017-11-01

    Full Text Available Tendon ruptures and retractions with an extensive tissue loss represent a major clinical problem and a great challenge in surgical reconstruction. Traditional approaches consist in autologous or allogeneic grafts, which still have some drawbacks. Hence, tissue engineering strategies aimed at developing functionalized tendon grafts. In this context, the use of xenogeneic tissues represents a promising perspective to obtain decellularized tendon grafts. This study is focused on the identification of suitable culture conditions for the generation of reseeded and functional decellularized constructs to be used as tendon grafts. Equine superficial digital flexor tendons were decellularized, reseeded with mesenchymal stem cells (MSCs from bone marrow and statically cultured in two different culture media to maintain undifferentiated cells (U-MSCs or to induce a terminal tenogenic differentiation (T-MSCs for 24 hours, 7 and 14 days. Cell viability, proliferation, morphology as well as matrix deposition and type I and III collagen production were assessed by means of histological, immunohistochemical and semi-quantitative analyses. Results showed that cell viability was not affected by any culture conditions and active proliferation was maintained 14 days after reseeding. However, seeded MSCs were not able to penetrate within the dense matrix of the decellularized tendons. Nevertheless, U-MSCs synthesized a greater amount of extracellular matrix rich in type I collagen compared to T-MSCs. In spite of the inability to deeply colonize the decellularized matrix in vitro, reseeding tendon matrices with U-MSCs could represent a suitable method for the functionalization of biological constructs, considering also any potential chemoattractant capability of the newly deposed extracellular matrix to recruit resident cells. This bioengineering approach can be exploited to produce functionalized tendon constructs for the substitution of large tendon defects.

  15. Preclinical Evaluation of the Immunomodulatory Properties of Cardiac Adipose Tissue Progenitor Cells Using Umbilical Cord Blood Mesenchymal Stem Cells: A Direct Comparative Study

    Directory of Open Access Journals (Sweden)

    Isaac Perea-Gil

    2015-01-01

    Full Text Available Cell-based strategies to regenerate injured myocardial tissue have emerged over the past decade, but the optimum cell type is still under scrutiny. In this context, human adult epicardial fat surrounding the heart has been characterized as a reservoir of mesenchymal-like progenitor cells (cardiac ATDPCs with potential clinical benefits. However, additional data on the possibility that these cells could trigger a deleterious immune response following implantation are needed. Thus, in the presented study, we took advantage of the well-established low immunogenicity of umbilical cord blood-derived mesenchymal stem cells (UCBMSCs to comparatively assess the immunomodulatory properties of cardiac ATDPCs in an in vitro allostimulatory assay using allogeneic mature monocyte-derived dendritic cells (MDDCs. Similar to UCBMSCs, increasing amounts of seeded cardiac ATDPCs suppressed the alloproliferation of T cells in a dose-dependent manner. Secretion of proinflammatory cytokines (IL6, TNFα, and IFNγ was also specifically modulated by the different numbers of cardiac ATDPCs cocultured. In summary, we show that cardiac ATDPCs abrogate T cell alloproliferation upon stimulation with allogeneic mature MDDCs, suggesting that they could further regulate a possible harmful immune response in vivo. Additionally, UCBMSCs can be considered as valuable tools to preclinically predict the immunogenicity of prospective regenerative cells.

  16. Functional anatomy of the levator palpebrae superioris muscle and its connective tissue system.

    Science.gov (United States)

    Ettl, A; Priglinger, S; Kramer, J; Koornneef, L

    1996-01-01

    AIMS/BACKGROUND: The connective tissue system of the levator palpebrae superioris muscle (LPS) consists of the septa surrounding its muscle sheath, the superior transverse ligament (STL) commonly referred to as 'Whitnall's ligament' and the common sheath which is the fascia between the LPS and the superior rectus muscle (SRM). The anterior band-like component of the common sheath is called transverse superior fascial expansion (TSFE) of the SRM and LPS. It mainly extends from the connective tissue of the trochlea to the fascia of the lacrimal gland. A detailed description of the relation between the LPS and its connective tissue is presented. Furthermore, the course of the LPS in the orbit is described. The study was conducted to provide a morphological basis for biomechanical and clinical considerations regarding ptosis surgery. METHODS: Postmortem dissections were performed in 16 orbits from eight cadavers. The microscopical anatomy was demonstrated in six formalin preserved orbits from six cadavers which had been sectioned in the frontal and sagittal plane and stained with haematoxylin and azophloxin. Surface coil magnetic resonance imaging in the sagittal and coronal plane was performed in five orbits from five normal volunteers using a T1 weighted spin echo sequence. RESULTS: The STL and the TSFE surround the LPS to form a fascial sleeve around the muscle which has attachments to the medial and lateral orbital wall. The TSFE, which is thicker than the STL, blends with Tenon's capsule. The STL and the fascial sheath of the LPS muscle are suspended from the orbital roof by a framework of radial connective tissue septa. MR images show that the TSFE is located between the anterior third of the superior rectus muscle and the segment of the LPS muscle where it changes its course from upwards to downwards. In this area, the LPS reaches its highest point in the orbit (culmination point). The culmination point is located a few millimetres posterior to the equator and

  17. Midterm outcome of valve-sparing aortic root replacement in inherited connective tissue disorders.

    Science.gov (United States)

    Tanaka, Hiroshi; Ogino, Hitoshi; Matsuda, Hitoshi; Minatoya, Kenji; Sasaki, Hiroaki; Iba, Yutaka

    2011-11-01

    This study determined the midterm outcome of valve-sparing aortic root replacement for patients with inherited connective tissue disorders. From 1993 to 2008, 94 patients underwent valve-sparing aortic root replacement. Sixty patients (64%), average age 33 years (range, 15 to 61 years), had inherited connective tissue disorders: Marfan syndrome, 54 (92%); Loeys-Dietz syndrome, 5 (8%); and smooth muscle α-actin (ACTA2) mutation in 1. Median preoperative sinus diameter was 52 mm (range, 42 to 76 mm), and moderate/severe aortic regurgitation was present in 14 (23%). Seven (12%, 1993 to 1999) underwent remodeling procedures, and 53 had reimplantation procedures. Cusp repair was performed in 4. Median follow-up was 55 months (range, 1 to 149 months). There were 15 patients in the early term (1993 to 2000) and 45 in the late term (2001 to 2008). Four late deaths occurred (cardiac, 3; aortic, 1), with 10-year survival of 86%. Rates of freedom from aortic valve replacement at 5 and 10 years were 85% and 58% in remodeling and 96% and 58% in reimplantation. Risk factors for reoperations were postprocedure intraoperative aortic insufficiency greater than mild (p = 0.046), remodeling procedure (p = 0.016), and early term (p = 0.0002). One patient (2%) with none/trivial postprocedure aortic insufficiency required aortic valve replacement. Freedom from reoperation in patients with none/trivial postprocedure aortic insufficiency at 5 and 10 years was 100% and 67%. Meticulous control of aortic insufficiency during operation would bring favorable midterm durability in valve-sparing aortic root replacement using a reimplantation technique, even in patients with inherited connective tissue disorders. Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  18. A STUDY OF MUCOCUTANEOUS MANIFESTATIONS IN AUTOIMMUNE CONNECTIVE TISSUE DISORDERS AT TERTIARY CARE CENTRE

    Directory of Open Access Journals (Sweden)

    Manisha Jethwa

    2017-06-01

    Full Text Available BACKGROUND Our aim was to study the clinical and immunological profile of patients with newly detected connective tissue disease presented to a tertiary care centre. MATERIALS AND METHODS The study involved 51 patients with newly-detected Systemic Lupus Erythematosus (SLE (fulfilling the revise SLICC criteria for SLE and Systemic Sclerosis (SS, Mixed Connective Tissue Disease (MCTD, etc. attending Sir. T. Hospital, Bhavnagar, between January 2013 and December 2016. All patients were assessed for clinical features and immunological profile. RESULTS Out of the 51 patients, 30 having SLE, 10 having SS, 9 with MCTD, 1 with dermatomyositis and 1 with Rowell’s syndrome. Among them, 47 were females and 4 were males. The mean age at presentation was between 15-25 years. The LE-specific skin lesions were noted as malar rash in 25 patients (83%, subacute and acute lupus rashes (80% and discoid rash (13%. Among LE-nonspecific lesions, non-scarring alopecia was most common followed by oral ulcers, Raynaud’s phenomenon, joint pain, scarring alopecia, erythema multiforme, livedo reticularis, vasculitic lesions, urticaria and calcinosis cutis were seen. In MCTD, muscle weakness was common finding. In systemic sclerosis, hide-bound skin and decreases mouth opening were seen in all cases and Raynaud’s phenomenon, joint pain, hair loss, calcinosis cutis and respiratory system involvement were other features. Serum ANA was positive in 76% while negative in 3.8% of individuals. The most common pattern observed in ANA profile was speckled (56% followed by homogenous (32% and nucleolar (28%. CONCLUSION There is diversity in clinical presentation of autoimmune connective tissue disease with regards to their genetic and environmental backgrounds. Cutaneous features are utmost important having diagnostic and prognostic value as well.

  19. Human adipose tissue-derived multilineage progenitor cells exposed to oxidative stress induce neurite outgrowth in PC12 cells through p38 MAPK signaling

    Directory of Open Access Journals (Sweden)

    Moriyama Mariko

    2012-08-01

    Full Text Available Abstract Background Adipose tissues contain populations of pluripotent mesenchymal stem cells that also secrete various cytokines and growth factors to support repair of damaged tissues. In this study, we examined the role of oxidative stress on human adipose-derived multilineage progenitor cells (hADMPCs in neurite outgrowth in cells of the rat pheochromocytoma cell line (PC12. Results We found that glutathione depletion in hADMPCs, caused by treatment with buthionine sulfoximine (BSO, resulted in the promotion of neurite outgrowth in PC12 cells through upregulation of bone morphogenetic protein 2 (BMP2 and fibroblast growth factor 2 (FGF2 transcription in, and secretion from, hADMPCs. Addition of N-acetylcysteine, a precursor of the intracellular antioxidant glutathione, suppressed the BSO-mediated upregulation of BMP2 and FGF2. Moreover, BSO treatment caused phosphorylation of p38 MAPK in hADMPCs. Inhibition of p38 MAPK was sufficient to suppress BMP2 and FGF2 expression, while this expression was significantly upregulated by overexpression of a constitutively active form of MKK6, which is an upstream molecule from p38 MAPK. Conclusions Our results clearly suggest that glutathione depletion, followed by accumulation of reactive oxygen species, stimulates the activation of p38 MAPK and subsequent expression of BMP2 and FGF2 in hADMPCs. Thus, transplantation of hADMPCs into neurodegenerative lesions such as stroke and Parkinson’s disease, in which the transplanted hADMPCs are exposed to oxidative stress, can be the basis for simple and safe therapies.

  20. Contraction mode and whey protein intake affect the synthesis rate of intramuscular connective tissue

    DEFF Research Database (Denmark)

    Holm, Lars; Klejs Rahbek, Stine; Farup, Jean

    2016-01-01

    IntroductionIn this study we investigated the impact of whey protein hydrolysate and maltodextrin (WPH) intake on intramuscular connective tissue (IMCT) protein fractional synthesis rate (FSR) after maximal shortening and lengthening contractions. Methods Twenty young men were randomized to receive...... either WPH or maltodextrin [carbohydrate (CHO)] immediately after completion of unilateral shortening and lengthening knee extensions. Ring-13C6-phenylalanine was infused, and muscle biopsies were obtained. IMCT protein FSR was measured at 1–5, as well as 1–3 and 3–5 hours after contractions and nutrient...

  1. Cardiac rhythm disturbance in athletes with cardiac connective tissue dysplasia syndrome

    Directory of Open Access Journals (Sweden)

    Shahrjerdi Sh

    2007-06-01

    Full Text Available Background: Cardiac connective tissue dysplasia syndrome consists of mitral valve prolapse (MVP, anomalously located chordae tendinae of the left ventricle, or a combination of the two. MVP is marked by the displacement of an abnormally thickened mitral valve leaflet into the left atrium during systole. The nonclassic form of MVP carries a low risk of complications. Patients with severe classic MVP can suffer from mitral regurgitation (MR, infective endocarditis, and, infrequently, sudden death from cardiac arrest. Anomalously located left ventricular chordae tendinae are fibrous or fibromuscular bands that stretch across the left ventricle from the septum to the free wall. They have been associated with murmurs and arrhythmias. The purpose of this study is to assess the performance, as measured by the physical working capacity (PWC170 and maximal oxygen consumption (VO2 max, in athletes with cardiac connective tissue dysplasia syndrome. Methods: Of the 183 male athletes studied, 158 had cardiac connective tissue dysplasia syndrome and 25 were normal, healthy controls. Their mean age was 16.23 (± 5.48 years and mean training time was 5.2 (±- 4.6 years. Athletes with cardiac connective tissue dysplasia syndrome were divided to four groups. Group 1 consisted of those with MVP; Group 2 had patients with an additional cord in left ventricle; Group 3 was made up of athletes with a combination of MVP and additional cord; Group 4 contained athletes with a combination of MVP and MR. All sportsmen were studied by echocardiograph, veloergometer, and those with arrhythmias were studied and recorded using a Holter monitor. Results: The most common form of this syndrome in our study groups was MVP. The PWC170and VO2 max among the athletes with the combination of MVP+MR (Group 4 was lower than that of athletes in other groups (P<0.05. The most common arrhythmia among the athletes with anomalously located left ventricular chordae, Group 2, was Wolf

  2. Autoradiographic study of 3H-proline incorporation by rat periodontal ligament, gingival connective tissue and dental pulp

    International Nuclear Information System (INIS)

    Kameyama, Y.

    1975-01-01

    The rates of 3 H-proline incorporation by the rat periodontal ligament, the gingival connective tissue and the dental pulp were studied by autoradiography. The rate of 3 H-proline incorporation by the periodontal ligament was 2.8 times higher than by the gingival connective tissue and 5 times higher than by the dental pulp. These differences were significant (p 3 H-proline incorporation by the periodontal ligament was significantly different (p 3 H-proline incorporation. The ratio of the rates of 3 H-proline incorporation by the three tissues did not correlate with the ratio of the cellular densities in the same three tissues. (author)

  3. 23Na+- and 39K+-NMR studies of cation-polyanion interactions in vascular connective tissue

    International Nuclear Information System (INIS)

    Siegel, G.; Walter, A.; Bostanjoglo, M.

    1987-01-01

    The ion binding properties of vascular connective tissue as well as of substances derived therefrom were studied in dependence on cation concentration by NMR and atomic absorption techniques. 16 refs.; 8 figs

  4. Meat Science and Muscle Biology Symposium: manipulating meat tenderness by increasing the turnover of intramuscular connective tissue.

    Science.gov (United States)

    Purslow, P P; Archile-Contreras, A C; Cha, M C

    2012-03-01

    Controlled reduction of the connective tissue contribution to cooked meat toughness is an objective that would have considerable financial impact in terms of added product value. The amount of intramuscular connective tissue in a muscle appears connected to its in vivo function, so reduction of the overall connective tissue content is not thought to be a viable target. However, manipulation of the state of maturity of the collagenous component is a biologically viable target; by increasing connective tissue turnover, less mature structures can be produced that are functional in vivo but more easily broken down on cooking at temperatures above 60°C, thus improving cooked meat tenderness. Recent work using cell culture models of fibroblasts derived from muscle and myoblasts has identified a range of factors that alter the activity of the principal enzymes responsible for connective tissue turnover, the matrix metalloproteinases (MMP). Fibroblasts cultured from 3 different skeletal muscles from the same animal show different cell proliferation and MMP activity, which may relate to the different connective tissue content and architecture in functionally different muscles. Expression of MMP by fibroblasts is increased by vitamins that can counter the negative effects of oxidative stress on new collagen synthesis. Preliminary work using in situ zymography of myotubes in culture also indicates increased MMP activity in the presence of epinephrine and reactive oxidative species. Comparison of the relative changes in MMP expression from muscle cells vs. fibroblasts shows that myoblasts are more responsive to a range of stimuli. Muscle cells are likely to produce more of the total MMP in muscle tissue as a whole, and the expression of latent forms of the enzymes (i.e., pro-MMP) may vary between oxidative and glycolytic muscle fibers within the same muscle. The implication is that the different muscle fiber composition of different muscles eaten as meat may influence the

  5. Undifferentiated connective tissue disease presenting with prevalent interstitial lung disease: Case report and review of literature

    Directory of Open Access Journals (Sweden)

    Sfriso Paolo

    2011-06-01

    Full Text Available Abstract Undifferentiated connective tissue diseases (UCTDs are clinical entities characterised by signs and symptoms suggestive of a systemic autoimmune disease, which do not fulfil the diagnostic criteria for a defined connective tissue disease. Lung involvement can complicate the course and management of the disease, often determining a worse outcome. Respiratory dysfunction as the first clinical manifestation has seldom been reported. We describe a case of a female patient who developed significant respiratory dysfunction as the principal clinical sign. Video-assisted thoracoscopy was performed and a histological pattern of nonspecific interstitial pneumonia (NSIP was found. A pathological diagnosis suggested careful follow-up with extensive immunological screening which then detected Raynaud's phenomenon and positivity of antinuclear antibodies. After a multidisciplinary discussion (pneumologist, radiologist, pathologist and rheumatologist a final diagnosis of NSIP associated with UCTD was made. The diagnosis of UCTD should be considered when NSIP is diagnosed even in cases with evident first clinical manifestations of severe respiratory dysfunction. A multidisciplinary approach in the field of interstitial lung disease with NSIP, also including rheumatologic expertise, is fundamental to achieve a prompt and correct diagnosis.

  6. Influence of surface modified dental implant abutments on connective tissue attachment: A systematic review.

    Science.gov (United States)

    Blázquez-Hinarejos, Mónica; Ayuso-Montero, Raúl; Jané-Salas, Enric; López-López, José

    2017-08-01

    Determine whether surface modified prosthetic abutments for dental implants influence connective tissue attachment to the implant-abutment system. A systematic review was conducted using the MEDLINE-PubMed database, with two independent reviewers filtering the titles and abstracts. Two reviewers assessed all potentially relevant articles. An assessment was carried out on the level of evidence of the research according to the guidelines of the Oxford Centre for Evidence-Based Medicine (OCEBM). After an initial search, 109 potentially relevant articles were found. After reading the titles and abstracts, 99 articles were excluded because the surface treatment was limited to the implant and not to the abutment, or because different materials were analysed instead of surface treatments; 28 were also duplicate articles. An additional 6 research studies were included that were of interest and were found by reading the references of the included articles. The studies included are: 7 in vitro studies, 5 experimental studies in animals, 2 clinical trials in humans and 2 clinical cases. Surface modification for prosthetic abutments on dental implants can achieve connective tissue attachment to the abutment; however, more studies should be conducted in humans to obtain more and better evidence of these results. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Evaluation of an automated connective tissue disease screening assay in Korean patients with systemic rheumatic diseases.

    Directory of Open Access Journals (Sweden)

    Seri Jeong

    Full Text Available This study aimed to evaluate the diagnostic utilities of the automated connective tissues disease screening assay, CTD screen, in patients with systemic rheumatic diseases. A total of 1093 serum samples were assayed using CTD screen and indirect immunofluorescent (IIF methods. Among them, 162 were diagnosed with systemic rheumatic disease, including rheumatoid arthritis (RA, systemic lupus erythematosus (SLE, and mixed connective tissue disease (MCT. The remaining 931 with non-systemic rheumatic disease were assigned to the control group. The median ratios of CTD screen tests were significantly higher in the systemic rheumatic disease group than in the control group. The positive likelihood ratios of the CTD screen were higher than those of IIF in patients with total rheumatic diseases (4.1 vs. 1.6, including SLE (24.3 vs. 10.7. The areas under the receiver operating characteristic curves (ROC-AUCs of the CTD screen for discriminating total rheumatic diseases, RA, SLE, and MCT from controls were 0.68, 0.56, 0.92 and 0.80, respectively. The ROC-AUCs of the combinations with IIF were significantly higher in patients with total rheumatic diseases (0.72 and MCT (0.85 than in those of the CTD screen alone. Multivariate analysis indicated that both the CTD screen and IIF were independent variables for predicting systemic rheumatic disease. CTD screen alone and in combination with IIF were a valuable diagnostic tool for predicting systemic rheumatic diseases, particularly for SLE.

  8. SCREENING METHOD OF THE DYSPLASIA OF THE CONNECTIVE TISSUE IN ADOLESCENTS

    Directory of Open Access Journals (Sweden)

    G. Y. Kalaeva

    2016-01-01

    Full Text Available ABSTRACT Aim of the study is to develop the diagnostic checklist based on the incidence and significance analysis of the external features of the dysplasia of the connective tissue (DCT for its screening and assessment of its prevalence in the adolescents’ population.Materials and methods.110 adolescents (aged from 10 to 14 years were examined, 81 of them had the dysplasia of the connective tissue (the first group. The second group was presented by 29 adolescents without DCT. The presence and degree of manifestation of DCT were established according to the criterions of Kadurina T. I., Gorbunova V.N. (2009, Т. Milkovska–Dimitrova (1987. There were the physical, laboratory and instrumental examination. Statistical processing of the results was carried out using Statistica 6.0 program and IBM SPSS Statistics 20.0. The diagnostic efficiency of the developed checklist was appreciated by means of the receiver operating characteristic curve (ROC curve. Results. The frequent occurrence of the DCT’s external features in adolescents was identified. The diagnostic checklist was developed. It was consisted of 12 items with illustrations, allowing readily identification of the dysplastic phenotype presence with diagnostic sensitivity 81.5% and specificity 79.3%. This checklist can be recommended as for the population studies, as for screening about DCT in adolescents during the primary outpatient pediatrician attendance. In the positive result of the screening it is necessary the further checkup to detect the organ changes and diagnosis updating. 

  9. Relationship between aneurism of ascending part of aorta and syndrome of connective tissue dysplasia

    Directory of Open Access Journals (Sweden)

    Osovska N.Yu.

    2014-11-01

    Full Text Available The paper identifies the main reasons for the development of an aneurysm of the ascending aorta and predictors of its complications in patients of all ages. To determine the cause and age-associated risk factors for aneurysms there were examined 154 patients with the presence of the expansion of the root and / or ascending aorta of more than 40 mm, according to echocardiographic examination. Patients were divided into 4 categories by age: 18-29 years, 30-44 years 45-59 years 60-74 years. Instrumental methods of examination: echocardiography, ECG, ECG monitoring and blood pressure, heart rate variability, ultrasound of internal organs were used. Syndrome of connective tissue dysplasia was established according to the criteria of the working group of the British Society of Rheumatology. Joint hypermobility syndrome was determined according to the Brayton criteria. Statistical processing was carried out by methods of variation statistic program StatSoft "Statistica" v.10.0. It was established that in young and middle aged patients the cause of aneurysm of ascending aorta more often is connective tissue dysplasia syndrome. In older patients the main cause of aneurysm of ascending aorta is associated with left ventricular hypertrophy and decreased contractile function of the heart.

  10. Evaluation of muscular lesions in connective tissue diseases: thallium 201 muscular scans

    International Nuclear Information System (INIS)

    Guillet, G.; Guillet, J.; Sanciaume, C.; Maleville, J.; Geniaux, M.; Morin, P.

    1988-01-01

    We performed thallium 201 muscle scans to assess muscular involvement in 40 patients with different connective tissue diseases (7 with dermatomyositis, 7 with systemic lupus erythematosus, 12 with progressive systemic scleroderma, 2 with calcinosis, Raynaud's phenomenon, esophageal involvement, sclerodactyly, and telangiectasia (CREST) syndrome, 3 with monomelic scleroderma, 6 with morphea, and 3 with Raynaud's disease). Only 12 of these patients complained of fatigability and/or myalgia. Electromyography was performed and serum levels of muscle enzymes were measured in all patients. Comparison of thallium 201 exercise recording with the other tests revealed that scan sensitivity is greater than electromyographic and serum muscle enzymes levels. Thallium 201 scans showed abnormal findings in 32 patients and revealed subclinical lesions in 18 patients, while electromyography findings were abnormal in 25 of these 32 patients. Serum enzyme levels were raised in only 8 patients. Thallium 201 scanning proved to be a useful guide for modifying therapy when laboratory data were conflicting. It was useful to evaluate treatment efficacy. Because our data indicate a 100% positive predictive value, we believe that thallium 201 scanning should be advised for severe systemic connective tissue diseases with discordant test results

  11. Evaluation of muscular lesions in connective tissue diseases: thallium 201 muscular scans

    Energy Technology Data Exchange (ETDEWEB)

    Guillet, G.; Guillet, J.; Sanciaume, C.; Maleville, J.; Geniaux, M.; Morin, P.

    1988-04-01

    We performed thallium 201 muscle scans to assess muscular involvement in 40 patients with different connective tissue diseases (7 with dermatomyositis, 7 with systemic lupus erythematosus, 12 with progressive systemic scleroderma, 2 with calcinosis, Raynaud's phenomenon, esophageal involvement, sclerodactyly, and telangiectasia (CREST) syndrome, 3 with monomelic scleroderma, 6 with morphea, and 3 with Raynaud's disease). Only 12 of these patients complained of fatigability and/or myalgia. Electromyography was performed and serum levels of muscle enzymes were measured in all patients. Comparison of thallium 201 exercise recording with the other tests revealed that scan sensitivity is greater than electromyographic and serum muscle enzymes levels. Thallium 201 scans showed abnormal findings in 32 patients and revealed subclinical lesions in 18 patients, while electromyography findings were abnormal in 25 of these 32 patients. Serum enzyme levels were raised in only 8 patients. Thallium 201 scanning proved to be a useful guide for modifying therapy when laboratory data were conflicting. It was useful to evaluate treatment efficacy. Because our data indicate a 100% positive predictive value, we believe that thallium 201 scanning should be advised for severe systemic connective tissue diseases with discordant test results.

  12. Leucine Supplementation Accelerates Connective Tissue Repair of Injured Tibialis Anterior Muscle

    Directory of Open Access Journals (Sweden)

    Marcelo G. Pereira

    2014-09-01

    Full Text Available This study investigated the effect of leucine supplementation on the skeletal muscle regenerative process, focusing on the remodeling of connective tissue of the fast twitch muscle tibialis anterior (TA. Young male Wistar rats were supplemented with leucine (1.35 g/kg per day; then, TA muscles from the left hind limb were cryolesioned and examined after 10 days. Although leucine supplementation induced increased protein synthesis, it was not sufficient to promote an increase in the cross-sectional area (CSA of regenerating myofibers (p > 0.05 from TA muscles. However, leucine supplementation reduced the amount of collagen and the activation of phosphorylated transforming growth factor-β receptor type I (TβR-I and Smad2/3 in regenerating muscles (p < 0.05. Leucine also reduced neonatal myosin heavy chain (MyHC-n (p < 0.05, increased adult MyHC-II expression (p < 0.05 and prevented the decrease in maximum tetanic strength in regenerating TA muscles (p < 0.05. Our results suggest that leucine supplementation accelerates connective tissue repair and consequent function of regenerating TA through the attenuation of TβR-I and Smad2/3 activation. Therefore, future studies are warranted to investigate leucine supplementation as a nutritional strategy to prevent or attenuate muscle fibrosis in patients with several muscle diseases.

  13. Irradiation by pulsed Nd:YAG laser induces the production of extracellular matrix molecules by cells of the connective tissues: a tool for tissue repair

    Science.gov (United States)

    Monici, Monica; Basile, Venere; Cialdai, Francesca; Romano, Giovanni; Fusi, Franco; Conti, Antonio

    2008-04-01

    Many studies demonstrated that mechanical stress is a key factor for tissue homeostasis, while unloading induce loss of mass and impairment of function. Because of their physiological function, muscle, connective tissue, bone and cartilage dynamically interact with mechanical and gravitational stress, modifying their properties through the continuous modification of their composition. Indeed, it is known that mechanical stress increases the production of extracellular matrix (ECM) components by cells, but the mechanotransduction mechanisms and the optimal loading conditions required for an optimal tissue homeostasis are still unknown. Considering the importance of cell activation and ECM production in tissue regeneration, a proper use of mechanical stimulation could be a powerful tool in tissue repair and tissue engineering. Studies exploring advanced modalities for supplying mechanical stimuli are needed to increase our knowledge on mechanobiology and to develop effective clinical applications. Here we describe the effect of photomechanical stress, supplied by a pulsed Nd:YAG laser on ECM production by cells of connective tissues. Cell morphology, production of ECM molecules (collagens, fibronectin, mucopolysaccharides), cell adhesion and cell energy metabolism have been studied by using immunofluorescence and autofluorescence microscopy. The results show that photomechanical stress induces cytoskeleton remodelling, redistribution of membrane integrins, increase in production of ECM molecules. These results could be of consequence for developing clinical protocols for the treatment of connective tissue dideases by pulsed Nd:YAG laser.

  14. Vegetative status characteristics in children with neurological pathology on the background of undifferentiated connective tissue dysplasia

    Directory of Open Access Journals (Sweden)

    Tyazka O.V.

    2016-03-01

    Full Text Available Background. Disorders of the autonomic nervous system are the most common pathological conditions detected in 20% - 85% of children and adolescents according to different authors' data. Assessment of the vegetative status in the period of intensive growth and differentiation of organs and tissues that is characteristic of childhood is of great practical importance. Identification of vegetative dysregulation is an important diagnostic measure in children's health status evaluation especially in patients with undifferentiated connective tissue dysplasia (UNDCT taking into account its genetic determinism and debut in childhood. Genetically determined biochemical disorders in the connective tissue followed by formation of characteristic pathological substrates cause dysregulation of sympathoadrenal system and correlate with UNDCT severity degree. Material and methods. There were 100 children aged from 5 to 16 years engaged in the investigation. All of them were treated in the neurological department of the City clinical hospital №4. All patients were divided into two groups: basic group, which included 50 children with neurological disorders and UNDC, and control one, which consisted of 50 children with neurological disorders without UNDCT. The survey included obstetric history analysis, anthropometry to determine the ratio of longitudinal and transverse dimensions (the index of Vervica; clinical and neurological examination (study of reflex&motor areas, sensory function, coordination; laboratory methods (clinical blood count and biochemical blood tests to determine the level of potassium and calcium ions, instrumental methods (electroencephalography, rheoencephalography, magnetic resonance imaging of the brain. Osokina's table was used for baseline autonomic tone assessment. The evaluation was conducted by counting the number of signs. Subsequently was performed the summation of the scores with the determination of the percentage of predominant

  15. Postulating a role for connective tissue elements in inferior oblique muscle overaction (an American Ophthalmological Society thesis).

    Science.gov (United States)

    Stager, David; McLoon, Linda K; Felius, Joost

    2013-09-01

    To compare the localization and density of collagens I, IV, VI, and elastin, the major protein components of connective tissue, in the inferior oblique muscle of patients with overelevation in adduction and in controls and to characterize changes that develop following surgery. Biomechanical studies suggest that the connective tissue matrix plays a critical role in extraocular muscle function, determining tensile strength and force transmission during contraction. Prospective laboratory-based case-control study of inferior oblique muscle specimens from 31 subjects: 16 with primary inferior oblique overaction, 6 with craniofacial dysostosis, and 9 normal controls. Collagen I, IV, VI, and elastin were localized and quantified using immunohistochemical staining. Densities were compared using analysis of variance and post hoc comparisons. In primary inferior oblique overaction, all connective tissue components in unoperated specimens were elevated compared to controls (P.27) but increased collagen I. In unoperated craniofacial dysostosis specimens, only elastin was elevated (P=.03), whereas density of collagens IV and VI was lower in previously operated vs unoperated specimens (P=.015). Elevated collagen and elastin levels in the cohort with primary inferior oblique overaction are consistent with the clinical finding of muscle stiffness. Contrarily, normal connective tissue densities in craniofacial dysostosis support the hypothesis that overelevation in this group reflects anomalous muscle vectors rather than tissue changes. Surgical intervention was associated with changes in the connective tissue matrix in both cohorts. These results have ramifications for treating patients with overelevation in adduction.

  16. MINIMALLY INVASIVE SINGLE FLAP APPROACH WITH CONNECTIVE TISSUE WALL FOR PERIODONTAL REGENERATION

    Directory of Open Access Journals (Sweden)

    Kamen Kotsilkov

    2017-09-01

    Full Text Available INTRODUCTION: The destructive periodontal diseases are among the most prevalent in the human population. In some cases, bony defects are formed during the disease progression, thus sustaining deep periodontal pockets. The reconstruction of these defects is usually done with the classical techniques of bone substitutes placement and guided tissue regeneration. The clinical and histological data from the recent years, however, demonstrate the relatively low regenerative potential of these techniques. The contemporary approaches for periodontal regeneration rely on minimally invasive surgical protocols, aimed at complete tissue preservation in order to achieve and maintain primary closure and at stimulating the natural regenerative potential of the periodontal tissues. AIM: This presentation demonstrates the application of a new, minimally invasive, single flap surgical technique for periodontal regeneration in a clinical case with periodontitis and a residual deep intrabony defect. MATERIALS AND METHODS: A 37 years old patient presented with chronic generalised periodontitis. The initial therapy led to good control of the periodontal infection with a single residual deep periodontal pocket medially at 11 due to a deep intrabony defect. A single flap approach with an enamel matrix derivate application and a connective tissue wall technique were performed. The proper primary closure was obtained. RESULT: One month after surgery an initial mineralisation process in the defect was detected. At the third month, a complete clinical healing was observed. The radiographic control showed finished bone mineralisation and periodontal space recreation. CONCLUSION: In the limitation of the presented case, the minimally invasive surgical approach led to complete clinical healing and new bone formation, which could be proof for periodontal regeneration.

  17. Biocompatibility of a new nanomaterial based on calcium silicate implanted in subcutaneous connective tissue of rats

    Directory of Open Access Journals (Sweden)

    Petrović Violeta

    2012-01-01

    Full Text Available The aim of the study was to investigate rat connective tissue response to a new calcium silicate system 7, 15, 30 and 60 days after implantation. Twenty Wistar albino male rats received two tubes half-filled with a new calcium silicate system (NCSS or MTA in subcutaneous tissue. The empty half of the tubes served as controls. Five animals were sacrificed after 7, 15, 30 and 60 days and samples of the subcutaneous tissue around implanted material were submitted to histological analysis. The intensity of inflammation was evaluated based on the number of inflammatory cells present. Statistical analysis was performed using one way ANOVA and Holm Sidak's multiple comparison tests. Mild to moderate inflammatory reaction was observed after 7, 15 and 30 days around a NCSS while mild inflammatory reaction was detected after 60 days of implantation. In the MTA group, mild to moderate inflammatory reaction was found after 7 and 15 days while mild inflammatory reaction was present after 30 and 60 days. There was no statistically significant difference in the intensity of inflammatory reactions between the tested materials and control groups in any experimental period (ANOVA p>0.05. Regarding the intensity of inflammatory reactions at different experimental periods, a statistically significant difference was observed between 7 and 30 days, 7 and 60 days and 15 to 60 days for both materials. For the controls, a statistically significant difference was found between 7 and 60 days and 15 and 60 days of the experiment (Holm Sidak < p 0.001. Subcutaneous tissue of rats showed good tolerance to a new calcium silicate system. Inflammatory reaction was similar to that caused by MTA. [Projekat Ministarstva nauke Republike Srbije, br. 172026

  18. Matriptase activation connects tissue factor-dependent coagulation initiation to epithelial proteolysis and signaling.

    Science.gov (United States)

    Le Gall, Sylvain M; Szabo, Roman; Lee, Melody; Kirchhofer, Daniel; Craik, Charles S; Bugge, Thomas H; Camerer, Eric

    2016-06-23

    The coagulation cascade is designed to sense tissue injury by physical separation of the membrane-anchored cofactor tissue factor (TF) from inactive precursors of coagulation proteases circulating in plasma. Once TF on epithelial and other extravascular cells is exposed to plasma, sequential activation of coagulation proteases coordinates hemostasis and contributes to host defense and tissue repair. Membrane-anchored serine proteases (MASPs) play critical roles in the development and homeostasis of epithelial barrier tissues; how MASPs are activated in mature epithelia is unknown. We here report that proteases of the extrinsic pathway of blood coagulation transactivate the MASP matriptase, thus connecting coagulation initiation to epithelial proteolysis and signaling. Exposure of TF-expressing cells to factors (F) VIIa and Xa triggered the conversion of latent pro-matriptase to an active protease, which in turn cleaved the pericellular substrates protease-activated receptor-2 (PAR2) and pro-urokinase. An activation pathway-selective PAR2 mutant resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cells co-expressed pro-matriptase, and matriptase transactivation was necessary for efficient cleavage and activation of wild-type PAR2 by physiological concentrations of TF:FVIIa and FXa. The coagulation initiation complex induced rapid and prolonged enhancement of the barrier function of epithelial monolayers that was dependent on matriptase transactivation and PAR2 signaling. These observations suggest that the coagulation cascade engages matriptase to help coordinate epithelial defense and repair programs after injury or infection, and that matriptase may contribute to TF-driven pathogenesis in cancer and inflammation.

  19. Treatment of multiple gingival recessions adopting modified tunnel subepithelial connective tissue graft technique

    Directory of Open Access Journals (Sweden)

    Jagmohan Singh

    2014-01-01

    Full Text Available Gingival recession related to periodontal disease or developmental problems can result in root sensitivity, root caries, and esthetically unacceptable root exposures. In the past, multiple surgical procedures have been proposed to obtain root coverage on exposed buccal root surfaces. There has been great interest in the treatment of gingival recession defects, especially with subepithelial connective-tissue grafting (SCTG. Recent advances have focused on SCTG by the tunnel technique. This article highlights the esthetic results obtained by adopting a modification of the tunnel technique using a single vertical incision along with autologous SCTG in the management of multiple adjacent Miller Class-II gingival recessions. A single vertical incision was used along with tunnel preparation for the facile placement of SCTG into the prepared tunnel. After 6 months of follow-up, the clinical condition was stable with satisfactory root coverage outcome. An excellent esthetical outcome was achieved and the patient was satisfied with the result.

  20. Molecular and Genetic Basis of Hereditary Connective-Tissue Diseases Accompanied by Frequent Fractures

    Directory of Open Access Journals (Sweden)

    G. T. Yakhyaeva

    2016-01-01

    Full Text Available Frequent bone fractures in infancy require the elimination of a large number (> 100 of genetic disorders. The modern diagnostic method of hereditary diseases characterized by debilitating course is a new generation sequencing. The article presents the results of molecular-genetic study conducted in 18 patients with clinical symptoms of connective tissue disorders. 10 (56% patients had mutations in the genes encoding type I collagen chains, leading to the development of osteogenesis imperfecta, 5 (28% — mutations in IV and V type collagen genes that are responsible for the development of Ehlers-Danlos syndrome. 3 (17% patients had mutations in the gene encoding fibrillin-1 protein, deficiency of which is manifested by Marfan syndrome. However, the correlation between patient's phenotype and discovered mutations in the investigated gene is established not in all cases.

  1. Anti-Nuclear antibodies: Current concepts and future direction for diagnosing connective tissue disease

    Directory of Open Access Journals (Sweden)

    K Gautam

    2015-03-01

    Full Text Available Identification of antinuclear antibodies has been used for the diagnosis of connective tissue diseases for more than fifty years. Indirect immunofluorescence on human epithelial (HEp-2 cells is considered the gold standard screening method for the detection of antinuclear autoantibodies. As the demand of ANA testing increased, the need for automation and standardization has also come forth. A high level of false positive and false negative cases is seen in various populations making it difficult to take clinical decisions. Newer technologies were introduced for the antibody detection to ensure high sensitivity and specificity. This article intends to provide an overview of the concepts on ANA testing, the different diagnostic methods available, the various patterns and clinical utility, the clinical guidelines to be followed, the drawbacks and what lies ahead in the future of ANA testing.Journal of Pathology of Nepal (2015 Vol. 5, 766-773

  2. Paraquat increases connective tissue growth factor expression and impairs lung fibroblast proliferation and viscoelasticity.

    Science.gov (United States)

    Zhang, N; Xie, Y-P; Pang, L; Zang, X-X; Wang, J; Shi, D; Wu, Y; Liu, X-L; Wang, G-H

    2014-12-01

    This in vitro study was designed to investigate the molecular mechanisms of paraquat-induced damage using cultured human fetal lung fibroblasts (MRC-5 cells), in order to promote the development of improved therapies for paraquat poisoning. Paraquat's effects on proliferation were examined by flow cytometry, on viscoelasticity by the micropipette aspiration technique, and on connective tissue growth factor (CTGF) expression by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Paraquat was found to significantly reduce the proliferation index of MRC-5 cells in a concentration-dependent manner (p paraquat led to a significant and time-dependent increase in CTGF expression (p paraquat-induced lung fibrosis but may represent useful targets of improved molecular-based therapies for paraquat poisoning. © The Author(s) 2014.

  3. Two-years therapy with bosentan of pulmonary arterial hypertension related to connective tissue diseases

    Directory of Open Access Journals (Sweden)

    M. Rizzo

    2011-09-01

    Full Text Available Objective: Pulmonary arterial hypertension (PAH is a rare but severe complication of connective tissue diseases (CTD, with a negative impact on patients survival. Bosentan, a receptor antagonist of endothelin, has been proved effective for the treatment of PAH. The aim of this study was to evaluate the effects and the safety of bosentan administered for 2 years in a group of patients with PAH related to CTD. Methods: Twelve patients with PAH related to systemic sclerosis (8 cases, SLE (2 cases, mixed connective tissue disease (1 case and polymyositis (1 case attending the Rheumatology Unit of Padova University were treated with bosentan for two years. Distance walked in 6 minutes, right ventricular systolic pressure and mean pulmonary artery pressure estimated by doppler echocardiography were evaluated at baseline and after 6, 12, 18 and 24 months of treatment. Safety was assessed by laboratory tests performed every two months. Results: During bosentan treatment, a significant decrease of right ventricular systolic pressure was observed after 6, 12, 18 and 24 months in comparison to baseline, whereas pulmonary artery mean pressure remained unchanged. Distance walked in 6 minutes slightly increased after 6 and 12 months, but significantly decreased after 18 and 24 months, mostly because complications of CTD which compromised the ability to walk arose in 4 patients. Adverse events related to bosentan were observed in 2 cases. Conclusions: Bosentan has been demonstrated effective in reducing pulmonary arterial pressure in a two-year period of treatment. Exercise capacity improved only in the first year of therapy and worsened thereafter, suggesting the opportunity of a combination therapy for a long-term treatment of PAH related to CTD.

  4. Pharmacological treatment in calcinosis cutis associated with connective-tissue diseases.

    Science.gov (United States)

    Dima, Alina; Balanescu, P; Baicus, C

    2014-01-01

    Dystrophic calcinosis cutis is a common manifestation in connective tissue diseases, but there's still no consensus on treatment. The purpose of this review is to discuss the current pharmacological options of treatment in calcinosis cutis related to rheumatic diseases. We performed an extensive MEDLINE search of articles from 1970 to January 2014 using the index word "calcinosis" and the co-indexing terms "treatment", "calcium channel blocker", "diltiazem", "nifedipine", "verapamil", "amlodipine", "anticoagulant", "warfarin", "bisphosphonate", "etidronate", "pamidronate", "alendronate", "risedronate", "aluminum hydroxide", "probenecid", "antibiotic", "tetracycline", "minocycline", "ceftriaxone", "colchicine", "intravenous immunoglobulin", "sodium thiosulfate", "TNF-alpha inhibitors", "infliximab", "rituximab", "thalidomide", "corticosteroids", "stem cell transplantation". Diltiazem is recommended by some authors as first-line approach in calcinosis cutis and is also the therapeutic principal referred by the largest number of available publications. It seems to be efficient in more than half of the reported cases. There remain, however, a significant number of patients in which another solution must be found. The general trends observed over time are of switching the search of solutions in dystrophic calcinosis cutis related to connective tissue diseases, from therapies on calcium metabolism to therapies for the underlying disease. The new options available in the management of calcinosis cutis, like biological therapies or intravenous immunoglobulin, seem to be promising, but not universally successful. In children with severe forms, hematopoietic stem cell transplantation can also be taken into consideration. Data for all therapies proposed in calcinosis cutis is generally reported in single cases and small case series and so, the existent data is all yielding a low level of evidence.

  5. Smooth muscle myosin regulation by serum and cell density in cultured rat lung connective tissue cells.

    Science.gov (United States)

    Babij, P; Zhao, J; White, S; Woodcock-Mitchell, J; Mitchell, J; Absher, M; Baldor, L; Periasamy, M; Low, R B

    1993-08-01

    RNA and protein analyses were used to detect expression of SM1 and SM2 smooth muscle myosin heavy chain (MHC) in cultured adult rat lung connective tissue cells (RL-90). Smooth muscle MHC mRNA expression in confluent cells grown in 10% serum was approximately 50% of the level in adult stomach. Similar results were obtained in cells cultured at low density (25% confluency) in 1% serum. However, in low-density cultures transferred to 10% serum for 24 h, the level of MHC mRNA decreased to approximately 20% of that in adult stomach. Smooth muscle alpha-actin showed a pattern of expression similar to that for smooth muscle MHC. Expression of nonmuscle MHC-A mRNA was higher in all culture conditions compared to stomach. MHC-A mRNA expression was less in low-density cultures in low serum and increased when low-density cultures were transferred to 10% serum for 24 h. MHC-B mRNA expression was less in low- vs. high-density cultures. In contrast to MHC-A, however, MHC-B mRNA expression in low-density cultures was higher in low serum. Immunofluorescence and immunoblotting with SM1-specific antibody demonstrated the presence of the SM1 protein isoform as well as reactivity to a protein band migrating slightly faster than SM2. These results demonstrate that cultured rat lung connective tissue cells express smooth muscle MHC and that expression is modulated by culture conditions.

  6. Undifferentiated connective tissue disease and interstitial lung disease: Trying to define patterns.

    Science.gov (United States)

    Alberti, María Laura; Paulin, Francisco; Toledo, Heidegger Mateos; Fernández, Martín Eduardo; Caro, Fabián Matías; Rojas-Serrano, Jorge; Mejía, Mayra Edith

    To identify clinical or immunological features in patients with undifferentiated connective tissue disease (UCTD) associated interstitial lung disease (ILD), in order to group them and recognize different functional and high resolution computed tomography (HRCT) behavior. Retrospective cohort study. Patients meeting Kinder criteria for UCTD were included. We defined the following predictive variables: 'highly specific' connective tissue disease (CTD) manifestations (Raynaud's phenomenon, dry eyes or arthritis), high antinuclear antibody (ANA) titer (above 1: 320), and 'specific' ANA staining patterns (centromere, cytoplasmic and nucleolar patterns). We evaluated the following outcomes: change in the percentage of the predicted forced vital capacity (FVC%) during the follow-up period, and HRCT pattern. Sixty-six patients were included. Twenty-nine (43.94%) showed at least one 'highly specific' CTD manifestation, 16 (28.57%) had a 'specific' ANA staining pattern and 29 (43.94%) high ANA titer. Patients with 'highly specific' CTD manifestations were younger (mean [SD] 52 years [14.58] vs 62.08 years [9.46], P<.001), were more likely men (10.34% vs 48.65%, P<.001) and showed a smaller decline of the FVC% (median [interquartile range] 1% [-1 to 10] vs -6% [-16 to -4], P<.006). In the multivariate analysis, the presence of highly specific manifestations was associated with improvement in the FVC% (B coefficient of 13.25 [95% confidence interval, 2.41 to 24.09]). No association was observed in relation to the HRCT pattern. The presence of 'highly specific' CTD manifestations was associated with female sex, younger age and better functional behavior. These findings highlight the impact of the clinical features in the outcome of patients with UCTD ILD. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  7. [Long-term outcome of aortic valve sparing procedures in connective tissue disorders].

    Science.gov (United States)

    Tanaka, Hiroshi; Ogino, H; Matsuda, H; Minatoya, K; Sasaki, N

    2009-10-01

    The aim of this study is to determine the long-term outcome of aortic valve sparing procedures for patients having connective tissue disorder. Between 1993 and 2008, the aortic valve sparing surgery was performed in 94 patients having aortic root dilatation. Eighty patients of them (37.2 +/- 13.4 years, 50 male) had cystic medial necrosis in the aortic wall, which was confirmed the pathological examination. We reviewed these patients. Sixty percent (48/80) had Marfan syndrome, 5% (4/80) had Loeyz-Dietz syndrome, 2% (2/80) had bicuspid aortic valve, and 11% (9/80) had aortic dissection. Our reimplantation procedure has been refined as followed: with a tube graft in 41, a tube graft with creation of neo-sinuses in 11, and a Valsalva graft in 14. Fourteen patients underwent the remodeling procedure. The follow-up rate was 100% with the duration of 3.7+/- 3.4 years. There were no operative death but six late deaths. Seventeen (21.3%) patients required aortic valve replacement, for recurrent aortic insufficiency in 13 and infection in 4. Freedom from reoperation was 80%, 43%, and freedom from moderate or severe aortic insufficiency was 80%, 54%, at 5 and 10 years, respectively. Pathological findings of the aortic valve obtained in the reoperations showed elongation and prolapse of the aortic valve due to myxomatous degeneration and fibrous thickening caused by aortic insufficiency. Even in connective tissue disorders, aortic valve sparing operation is associated with acceptable long-term durability, although cusp degeneration resulting in recurrent aortic insufficiency might be progressive.

  8. Cutaneous manifestations of mixed connective tissue disease: Study from a tertiary care hospital in Eastern India

    Directory of Open Access Journals (Sweden)

    Sumit Sen

    2014-01-01

    Full Text Available Context: Mixed connective tissue disorder is an uncommon disease. Some scientists are reluctant to recognize it as a separate entity. Some others have defined this ailment. Cutaneous features of this condition are unique. Researchers from India have described these features to relate to those described in the studies from other parts of the globe. Aims: This study aims to delineate the skin manifestations of clearly defined mixed connective tissue disease (MCTD patients, to compare them with those established as overlap syndrome, and to relate them with studies from other parts of the globe. Settings and Design: Successive patients who fulfilled the specific criteria for MCTD presenting in the skin outpatient department of a tertiary care hospital in eastern India were clinically examined from 2009 for 3 years. Materials and Methods: The number of participants was 23 and the dermatological features of these were compared with 22 patients with overlap syndrome. The antibody to uridine-rich U1 ribonucleoprotein was measured for all patients. Statistical Analysis Used: SPSS (Version 17 and MedCalc (Version 11.6. Results: The Male: Female ratio among the MCTD patients was 1:6.67 and that of the overlap syndrome was 1:10. Twenty patients of the MCTD group presented with synovitis as against only seven in the overlap group. Raynaud′s phenomenon was present in some of the subjects. Puffy fingers were rare in our study. Facial numbness was reported by four of those suffering from MCTD. Antinuclear antibody (ANA was essentially of a speckled pattern in this disease Conclusions: Cutaneous indicators of MCTD are distinct from overlap syndrome. Knowledge of these manifestations prevalent in a region may lead to early diagnosis of the disease.

  9. Connective Tissue Reflex Massage for Type 2 Diabetic Patients with Peripheral Arterial Disease: Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Adelaida María Castro-Sánchez

    2011-01-01

    Full Text Available The objective of this study was to evaluate the efficacy of connective tissue massage to improve blood circulation and intermittent claudication symptoms in type 2 diabetic patients. A randomized, placebo-controlled trial was undertaken. Ninety-eight type 2 diabetes patients with stage I or II-a peripheral arterial disease (PAD (Leriche-Fontaine classification were randomly assigned to a massage group or to a placebo group treated using disconnected magnetotherapy equipment. Peripheral arterial circulation was determined by measuring differential segmental arterial pressure, heart rate, skin temperature, oxygen saturation and skin blood flow. Measurements were taken before and at 30 min, 6 months and 1 year after the 15-week treatment. After the 15-week program, the groups differed (P<.05 in differential segmental arterial pressure in right lower limb (lower one-third of thigh, upper and lower one-third of leg and left lower limb (lower one-third of thigh and upper and lower one-third of leg. A significant difference (P<.05 was also observed in skin blood flow in digits 1 and 4 of right foot and digits 2, 4 and 5 of left foot. ANOVA results were significant (P<.05 for right and left foot oxygen saturation but not for heart rate and temperature. At 6 months and 1 year, the groups differed in differential segmental arterial pressure in upper third of left and right legs. Connective tissue massage improves blood circulation in the lower limbs of type 2 diabetic patients at stage I or II-a and may be useful to slow the progression of PAD.

  10. Anti-Ku antibodies in connective tissue diseases: clinical and serological evaluation of 14 patients.

    Science.gov (United States)

    Franceschini, Franco; Cavazzana, Ilaria; Generali, Daniele; Quinzanini, Marzia; Viardi, Luigi; Ghirardello, Anna; Doria, Andrea; Cattaneo, Roberto

    2002-07-01

    To assess the clinical and serological associations of anti-Ku antibodies. Fourteen patients with anti-Ku antibody detected by counterimmunoelectrophoresis (CIE) and immunoblot (IB) were retrospectively evaluated. Patients (13 women, one man) had a mean age of 60.3 years (range 19-83). Seven patients had overlap syndromes: 5 polymyositis/scleroderma (PM/SSc), one systemic lupus erythematosus (SLE)/SSc/PM, and one SLE/PM. Three additional patients had undifferentiated connective tissue disease, 2 primary Sjögren's syndrome (SS), one psoriatic arthritis, and one SSc. The clinical manifestations most frequently recorded were arthralgias (86%), myositis (50%) and Raynaud's phenomenon (78.6%). Five patients had esophageal dysmotility, while 6 showed interstitial pulmonary fibrosis (4 of them with reduced DLCO). No case of pulmonary hypertension was observed. All patients had very high titer of ANA with speckled and nucleolar pattern. All the sera were positive for anti-Ku antibodies by CIE: all but one were confirmed by IB. Eight sera contained isolated antibodies to Ku proteins: both subunits were recognized in 7 cases, while isolate reactivity to the 70 kDa protein was detected in one case. Five sera contained additional antibody specificities: anti-Ro 60 kDa in 4 cases, and anti-La/SSB, anti-SL, and anti-PM-Scl in one case each. Anti-Ku antibody is found in a wide spectrum of connective tissue diseases including overlap syndromes with SSc and myositis. Raynaud's phenomenon and muscular and joint involvement are the most frequent clinical features associated with anti-Ku antibodies, which are frequently detected in association with anti-Ro/SSA and/or other antinuclear specificities.

  11. [CLINICAL CHARACTERISTICS OF CONGENITAL HEART DISEASES ASSOCIATED WITH CONNECTIVE TISSUE DISPLASIA AT CHILDREN LIVING IN EAST REGION OF KAZAKHSTAN].

    Science.gov (United States)

    Madiyeva, M; Rymbayeva, T

    2017-11-01

    The frequency of the combination of congenital heart defects (CHD) and connective tissue dysplasia remains poorly understood. And connective tissue dysplasia enhance severity the clinical of CHD. The aim of the study was to conduct a clinical and laboratory analysis of combinations of congenital heart defects and connective tissue dysplasia in children of Semey and to determine the risk for the development of these pathologies. The object of the study is the children of Semey (East Kazakhstan) aged 1-14 with congenital heart defects (CHD), with connective tissue dysplasia, healthy children and their mothers. Definition complex clinical and laboratory studies in children with CHD and connective tissue dysplasia, and their mothers. In children with CHD, the frequency of external and visceral signs of dysplasia was high. In 88.1% of cases in children with CHD was diagnosed 2-3 degrees of dysplasia. Was found difference in the microelement composition of blood serum and of hemostasis in children with CHD were expressed by hypofibrinogenemia, hypocalcemia, hypomagnesemia. Excess of the frequency of signs of dysplasia in mothers over the control group to consider dysplasia as a factor that influences the clinical of CHD.

  12. Diagnosis of Protein Losing Enteropathy in connective Tissue Diseases with 99mTc-human Serum Albumin(Hsa)

    International Nuclear Information System (INIS)

    Won, Kyoung Sook; Oh, Yeong Seok; Bang, Shin Ho; Park, Won

    1993-01-01

    Anterior abdominal scintigraphy after intravenous injection of 99m Tc-human serum albumin ( 99m Tc-HSA 20 mCi) was done in 16 patients with connective tissue diseases and 15 healthy control patients. Patients with proteinuria or hepatopathy were excluded. 1) 7(44%) patients among 16 connective tissue disease patients without the apparent evidence of external protein loss showed abnormal intestinal accumulation of albumin. 6 patients with positive albumin scintigraphy showed hypoalbuminaemia. 2) There was no false positive scintigraphic finding in control group. 3) The serum albumin level in connective tissue disease patients (3.1 ± 0.6 g/dl, n=16) was lower than control patients(3.9 ± 0.3 g/dl, n=15) (p 99m Tc-HSA scan(2.8 ± 0.6 g/dl, n=7) than the connective tissue disease patients with negative scan(3.3 ± 0.3 g/dl, n=9) (p 99m Tc-HSA scan also must be validated by more extended study and comparison with the quantitative study such as stool α -1 antitrypsin measurement. There must be a reevaluation of PLE in various diseases especially in connective tissue diseases with easy, fast, economical, and noninvasive method.

  13. Biocompatibility Evaluation of EndoSequence Root Repair Paste in the Connective Tissue of Rats.

    Science.gov (United States)

    Taha, Nessrin A; Safadi, Rima A; Alwedaie, Manal S

    2016-10-01

    The aim of this study was to evaluate the subcutaneous connective tissue response to EndoSequence root repair paste (Brasseler, Savannah, GA) compared with mineral trioxide aggregate (MTA). Thirty-six Wistar rats each received 3 sterile tubes, containing 1 of the tested materials and control. The animals were killed 1, 3 and 6 weeks after implantation. The specimens were evaluated histologically for type of inflammation, intensity and extent of inflammatory cells, foreign body reaction, fibrous capsule thickness, perivascular fragments, calcific deposits and vascular congestion. EndoSequence provoked severe inflammation after 1 week, which was significantly different from MTA and control (P ˂ .05), with fragmented particles and foreign body reaction. MTA showed tissue-tolerance features almost comparable to control. EndoSequence was significantly more irritating than MTA and control at 1 and 3 weeks in terms of severity and extent of inflammation. After 6 weeks it displayed more biocompatible characteristics. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

  14. Activated alveolar epithelial cells initiate fibrosis through autocrine and paracrine secretion of connective tissue growth factor.

    Science.gov (United States)

    Yang, Jibing; Velikoff, Miranda; Canalis, Ernesto; Horowitz, Jeffrey C; Kim, Kevin K

    2014-04-15

    Fibrogenesis involves a pathological accumulation of activated fibroblasts and extensive matrix remodeling. Profibrotic cytokines, such as TGF-β, stimulate fibroblasts to overexpress fibrotic matrix proteins and induce further expression of profibrotic cytokines, resulting in progressive fibrosis. Connective tissue growth factor (CTGF) is a profibrotic cytokine that is indicative of fibroblast activation. Epithelial cells are abundant in the normal lung, but their contribution to fibrogenesis remains poorly defined. Profibrotic cytokines may activate epithelial cells with protein expression and functions that overlap with the functions of active fibroblasts. We found that alveolar epithelial cells undergoing TGF-β-mediated mesenchymal transition in vitro were also capable of activating lung fibroblasts through production of CTGF. Alveolar epithelial cell expression of CTGF was dramatically reduced by inhibition of Rho signaling. CTGF reporter mice demonstrated increased CTGF promoter activity by lung epithelial cells acutely after bleomycin in vivo. Furthermore, mice with lung epithelial cell-specific deletion of CTGF had an attenuated fibrotic response to bleomycin. These studies provide direct evidence that epithelial cell activation initiates a cycle of fibrogenic effector cell activation during progressive fibrosis. Therapy targeted at epithelial cell production of CTGF offers a novel pathway for abrogating this progressive cycle and limiting tissue fibrosis.

  15. Comparative Anatomy of the Subsynovial Connective Tissue in the Carpal Tunnel of the Rat, Rabbit, Dog, Baboon, and Human

    OpenAIRE

    Ettema, Anke M.; Zhao, Chunfeng; An, Kai-Nan; Amadio, Peter C.

    2006-01-01

    The tenosynovium in the human carpal tunnel is connected to the flexor tendons and the median nerve by the subsynovial connective tissue (SSCT). The most common histological finding in carpal tunnel syndrome (CTS), a compression neuropathy of the median nerve, is noninflammatory fibrosis of the SSCT. The relationship, if any, between the fibrosis and nerve pathology is unknown, although some have speculated that a change in the SSCT volume or stiffness might be the source of the compression. ...

  16. The serum levels of connective tissue growth factor in patients with systemic lupus erythematosus and lupus nephritis.

    Science.gov (United States)

    Wang, F-M; Yu, F; Tan, Y; Liu, G; Zhao, M-H

    2014-06-01

    The expression of connective tissue growth factor mRNA in human kidneys may serve as an early marker for lupus nephritis progression. Therefore, we speculated that connective tissue growth factor may be involved in the pathogenesis of systemic lupus erythematosus and lupus nephritis. In this study, we set out to investigate the associations between serum connective tissue growth factor levels and clinicopathological features of patients with systemic lupus erythematosus and lupus nephritis. Serum samples from patients with non-renal systemic lupus erythematosus, renal biopsy-proven lupus nephritis and healthy control subjects were detected by enzyme-linked immunosorbent assay for serum connective tissue growth factor levels. The associations between connective tissue growth factor levels and clinicopathological features of the patients were further analysed. The levels of serum connective tissue growth factor in patients with non-renal systemic lupus erythematosus and lupus nephritis were both significantly higher than those in the normal control group (34.14 ± 12.17 ng/ml vs. 22.8 ± 3.0 ng/ml, plupus erythematosus and lupus nephritis group (34.14 ± 12.17 ng/ml vs. 44.1 ± 46.8 ng/ml, p = 0.183). Serum connective tissue growth factor levels were significantly higher in lupus nephritis patients with the following clinical manifestations, including anaemia (51.3 ± 51.4 ng/ml vs. 23.4 ± 9.7 ng/ml, plupus nephritis (63.3 ± 63.4 ng/ml vs. 38.3 ± 37.9 ng/ml, p = 0.035, respectively). Serum connective tissue growth factor levels were negatively associated with estimated glomerular filtration rate (r = -0.46, plupus nephritis (plupus and correlated with chronic renal interstitial injury and doubling of serum creatinine in patients with lupus nephritis. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  17. Longitudinal analysis of quality of life in patients with undifferentiated connective tissue diseases

    Directory of Open Access Journals (Sweden)

    Iudici M

    2017-02-01

    Full Text Available Michele Iudici, Rosaria Irace, Antonella Riccardi, Giovanna Cuomo, Serena Vettori, Gabriele Valentini Rheumatology Section, Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy Introduction/objectives: To prospectively assess the quality of life (QoL of patients affected by undifferentiated connective tissue diseases (UCTDs and to identify factors associated with changes over time.Patients and methods: A total of 46 consecutive UCTD patients completed the Short-Form 36 (SF-36 questionnaire at presentation and then yearly. At each 6-month visit, all patients underwent a detailed history taking and a laboratory and physical assessment, in order to follow the evolution of the disease over time and to assess the the co-existence of fibromyalgia.Results: At presentation, scores lower than the average of the general population were detected in 34 (74% and 41 (89% patients in the physical and mental domains, respectively. No difference between patients with and without Raynaud’s phenomenon was detected. Fibromyalgia was the only independent variable associated with an impaired physical component summary score (p = 0.0009. No patient feature was found to be associated with the basal mental component summary score. During 24 months of follow-up, a significant improvement (ie, a change ≥5 from baseline in physical component summary and mental component summary scores was observed in 14 (33.3% and 20 (43.4% patients, respectively. Patients who significantly improved in the physical domain more frequently had a history of glucocorticoids intake (p < 0.001, while those who improved in the mental component more frequently had a history of either glucocorticoids (p = 0.043 or immunosuppressors (p = 0.037 intake during follow-up.Conclusion: UCTD patients perceive a worse QoL, regardless of Raynaud’s phenomenon Fibromyalgia is one of the major contributors of physical QoL, whereas no factor influencing

  18. Transplanting oligodendrocyte progenitors into the adult CNS

    International Nuclear Information System (INIS)

    Franklin, R.J.M.; Blakemore, W.F.; Cambridge Univ.

    1997-01-01

    This review covers a number of aspects of the behaviour of oligodendrocyte progenitors following transplantation into the adult CNS. First, an account is given of the ability of transplanted oligodendrocyte progenitors, grown in tissue culture in the presence of PDGF and bFGF, to extensively remyelinate focal areas of persistent demyelination. Secondly, we describe how transplanted clonal cell lines of oligodendrocyte progenitors will differentiate in to astrocytes as will oligodendrocytes following transplantation into pathological environments in which both oligodendrocytes and astrocytes are absent, thereby manifesting the bipotentially demonstrable in vitro but not during development. Finally, a series of studies examining the migratory behaviour of transplanted oligodendrocyte progenitors (modelled using the oligodendrocyte progenitor cell line CG4) are described. (author)

  19. Reconstruction of the interdental papilla with an underlying subepithelial connective tissue graft: technical considerations and case reports.

    Science.gov (United States)

    Carranza, Nelson; Zogbi, Carim

    2011-01-01

    This article introduces a surgical technique developed to achieve soft tissue augmentation of the interproximal space. The technique was designed to minimize surgical trauma and blockage of blood supply to the existing papilla by accessing the papillary area through vertical incisions and by elevating a single full-thickness flap without disrupting the papillary bridge. A free connective tissue graft was placed beneath the undermined papilla and secured with sutures. Advantages and variations of the technique are discussed.

  20. Serum B cell-activating factor (BAFF) level in connective tissue disease associated interstitial lung disease.

    Science.gov (United States)

    Hamada, Tsutomu; Samukawa, Takuya; Kumamoto, Tomohiro; Hatanaka, Kazuhito; Tsukuya, Go; Yamamoto, Masuki; Machida, Kentaro; Watanabe, Masaki; Mizuno, Keiko; Higashimoto, Ikkou; Inoue, Yoshikazu; Inoue, Hiromasa

    2015-09-30

    Interstitial lung diseases (ILDs) are common in patients with connective tissue diseases (CTDs). Although the diagnosis of an underlying CTD in ILD (CTD-ILD) affects both prognosis and treatment, it is sometimes difficult to distinguish CTD-ILD from chronic fibrosing interstitial pneumonia (CFIP). B cell-activating factor belonging to the tumour necrosis factor family (BAFF) plays a crucial role in B cell development, survival, and antibody production. We examined serum levels of BAFF, surfactant protein D (SP-D), and Krebs von den Lungen-6 (KL-6) in 33 patients with CTD-ILD, 16 patients with undifferentiated CTD-ILD, 19 patients with CFIP, and 26 healthy volunteers. And we analysed the relationship between serum BAFF levels and pulmonary function, as well as the expression of BAFF in the lung tissue of patients with CTD-ILD. Serum levels of BAFF were significantly higher in CTD-ILD patients compared to healthy subjects and CFIP patients. However, there were no significant differences in serum levels of SP-D and KL-6. Furthermore, serum BAFF levels in CTD-ILD patients were inversely correlated with pulmonary function. BAFF was strongly expressed in the lungs of CTD-ILD patients, but weakly in normal lungs. This is the first study to demonstrate that serum BAFF levels were significantly higher in CTD-ILD patients compared to healthy subjects and CFIP patients. Furthermore, serum BAFF levels were correlated with pulmonary function. We consider that serum BAFF levels in patients with CTD-ILD reflect the presence of ILDs disease activity and severity. These finding suggest that BAFF may be a useful marker for distinguishing CTD-ILD from CFIP.

  1. Effects of x-ray irradiation on mast cells and mastocalcergy in the connective tissue

    International Nuclear Information System (INIS)

    Song, H. Y.; Rhee, S. J.; Son, M. H.; Choi, K. C.

    1982-01-01

    Experiments were performed to observe the influence of x-ray irradiation on mast cells and mastocalcergy in rats. Animals were irradiated single dose of x-ray. X-ray irradiation was applied to the whole body in doses either 100 rads or 150 rads (Cobalt-60 Teletherapy Unit). One day after irradiation the rats were injected lead acetate intravenously, followed by injection of compound 48/80 in the back subcutaneously. Animals were killed by decapitation at intervals, 1 hour, 5 hours, 1 day and 6 day after subcutaneous injection. Specimens of the abdominal and back skin were fixed in alcohol formol solution and stained with the following methods; H-E for observation of pathological changes of tissues, toluidine blue for demonstration of mast cells, von Kossa-azure A for demonstration of carbonate and phosphate, and chloranilic acid for demonstration of calcium. The following conclusions were obtained. Calciphylatic wheals are large size in the control group, medium size in 100 rads irradiation group and small size in 150 rads irradiation group. In x-ray irradiation groups the number of mast cells decreases more in the 150 rads than in the 100 rads irradiation. In the 100 rads x-ray irradiation group, histochemical study of the injection sites showed that calcium impregnated to mast cell granules and connective tissue fibers in 1 days after subcutaneous injection. The morphogenesis of this calcinosis was the same in the rat of 5 hour after subcutaneous injection of the control group. Whereas, 1 day after subcutaneous injection in 150 rads x-ray irradiation group calcium deposited more slightly than other groups

  2. Intramuscular connective tissue differences in spastic and control muscle: a mechanical and histological study.

    Directory of Open Access Journals (Sweden)

    Marije de Bruin

    Full Text Available Cerebral palsy (CP of the spastic type is a neurological disorder characterized by a velocity-dependent increase in tonic stretch reflexes with exaggerated tendon jerks. Secondary to the spasticity, muscle adaptation is presumed to contribute to limitations in the passive range of joint motion. However, the mechanisms underlying these limitations are unknown. Using biopsies, we compared mechanical as well as histological properties of flexor carpi ulnaris muscle (FCU from CP patients (n = 29 and healthy controls (n = 10. The sarcomere slack length (mean 2.5 µm, SEM 0.05 and slope of the normalized sarcomere length-tension characteristics of spastic fascicle segments and single myofibre segments were not different from those of control muscle. Fibre type distribution also showed no significant differences. Fibre size was significantly smaller (1933 µm2, SEM 190 in spastic muscle than in controls (2572 µm2, SEM 322. However, our statistical analyses indicate that the latter difference is likely to be explained by age, rather than by the affliction. Quantities of endomysial and perimysial networks within biopsies of control and spastic muscle were unchanged with one exception: a significant thickening of the tertiary perimysium (3-fold, i.e. the connective tissue reinforcement of neurovascular tissues penetrating the muscle. Note that this thickening in tertiary perimysium was shown in the majority of CP patients, however a small number of patients (n = 4 out of 23 did not have this feature. These results are taken as indications that enhanced myofascial loads on FCU is one among several factors contributing in a major way to the aetiology of limitation of movement at the wrist in CP and the characteristic wrist position of such patients.

  3. Transcription factor scleraxis vitally contributes to progenitor lineage direction in wound healing of adult tendon in mice.

    Science.gov (United States)

    Sakabe, Tomoya; Sakai, Keiko; Maeda, Toru; Sunaga, Ataru; Furuta, Nao; Schweitzer, Ronen; Sasaki, Takako; Sakai, Takao

    2018-03-05

    Tendon is a dense connective tissue that transmits high mechanical forces from skeletal muscle to bone. The transcription factor scleraxis (Scx) is a highly specific marker of both precursor and mature tendon cells (tenocytes). Mice lacking scx exhibit a specific and virtually complete loss of tendons during development. However, the functional contribution of Scx to wound healing in adult tendon has not yet been fully characterized. Here, using ScxGFP-tracking and loss-of-function systems, we show in an adult mouse model of Achilles tendon injury that paratenon cells, representing a stem cell antigen-1 (Sca-1)-positive and Scx-negative progenitor subpopulation, display Scx induction, migrate to the wound site, and produce extracellular matrix (ECM) to bridge the defect, whereas resident tenocytes exhibit a delayed response. Scx induction in the progenitors is initiated by transforming growth factor β (TGF-β)-signaling. Scx-deficient mice had migration of Sca-1-positive progenitor cell to the lesion site, but impaired ECM assembly to bridge the defect. Mechanistically, scx-null progenitors displayed higher chondrogenic potential with up-regulation of SRY-box 9 (Sox9) coactivator PPAR-gamma coactivator 1α (PGC-1α) in vitro, and knock-in analysis revealed that forced-expression of full-length scx significantly inhibited sox9 expression. Accordingly, scx-null wounds formed cartilage-like tissues that developed ectopic ossification. Our findings indicate a critical role of Scx in a progenitor-cell-lineage in wound healing of adult mouse tendon. These progenitor cells could represent targets in strategies to facilitate tendon repair. We propose that this lineage-regulatory mechanism in tissue progenitors could apply to a broader set of tissues or biological systems in the body. Published under license by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Evaluation of single-tooth replacement by an immediate implant covered with connective tissue graft as a biologic barrier.

    Science.gov (United States)

    Jyothi, S G; Triveni, M G; Mehta, D S; Nandakumar, K

    2013-05-01

    The aim of the present study was to evaluate the survival rate of Screw-Vent(®) immediate implants augmented with sub epithelial connective tissue graft for single-tooth replacement for 1 year. Ten patients (five men and five women), with the mean age of 25.3 years, were consecutively treated on the out-patient basis by the placement of Screw-Vent(®) dental implants in to the fresh extraction sockets in association of augmentation with sub epithelial connective tissue graft harvested from the palate, supporting single crowns. The clinical and radiographic parameters were recorded to evaluate the peri-implant soft tissue health and marginal bone loss, respectively, for each patient at baseline and at every 3 months interval for 1 year. The 1 year cumulative survival rate of Screw-Vent(®) dental implants was 100% for all 10 patients. Statistical analysis demonstrated highly significant values indicating an improvement in peri-implant soft tissue parameters in terms of peri-implant aesthetic parameters, which estimated the keratinized mucosa width. Statistically, non-significant marginal bone loss or gain indicated stable condition in hard tissue parameters. Single-tooth replacement by Screw-Vent(®) dental implants in to a fresh extraction socket, in association with guided bone regeneration using autologous connective tissue graft is a predictable treatment as demonstrated by the 100% implant survival rates and appreciable increase in the width of the keratinized mucosa at 1 year follow up.

  5. Evaluation of alteration in mucogingival line location following use of subepithelial connective tissue graft

    Directory of Open Access Journals (Sweden)

    Saber Fariba

    2010-01-01

    Full Text Available Aim and Objective : The aim of this study is to evaluate the positional changes that occur in mucogingival line following the use of subepithelial connective tissue graft (SCTG. Materials and Methods : In 19 Miller class I or II gingival recession defects, distance between mucogingival line (MGL and cemento-enamel junction, also width of keratinized and attached gingiva, and clinical attachment level were measured. SCTG were used for covering the exposed roots. A fore mentioned parameters were repeated at 3, 6 and 12 months after surgery and alterations were measured. Paired t test was used to analyze the results. Results : MGL had been moved in coronal direction (4.39 ± 0.77 mm on average during surgical approach. After 1 year, MGL shifted 2.11 ± 0.7 mm apically. In accordance with this apical shift, a significant increase in the width of keratinized and attached gingival width (2.89 ± 0.63 mm and 2.82 ± 0.5 mm, respectively was seen (P < 0.05. Conclusion : MGL tended to revert back to its original position following the use of SCTG, and this reversion is accompanied with an increase in the keratinized and attached gingival width.

  6. Invasive pulmonary fungal infections in patients with connective tissue disease: a retrospective study from northern China

    Directory of Open Access Journals (Sweden)

    H.F. Ge

    Full Text Available Invasive pulmonary fungal infection (IPFI is a potentially fatal complication in patients with connective tissue disease (CTD. The current study aimed to uncover the clinical characteristics and risk factors of patients with IPFI-CTD. The files of 2186 CTD patients admitted to a single center in northern China between January 2011 and December 2013 were retrospectively reviewed. A total of 47 CTD patients with IPFI were enrolled into this study and assigned to the CTD-IPFI group, while 47 uninfected CTD patients were assigned to the control group. Clinical manifestations were recorded, and risk factors of IPFI were calculated by stepwise logistical regression analysis. Forty-seven (2.15% CTD patients developed IPFI. Systemic lupus erythematosus patients were responsible for the highest proportion (36.17% of cases with IPFI. Candida albicans (72.3% accounted for the most common fungal species. CTD-IPFI patients had significantly elevated white blood cell count, erythrocyte sedimentation rate, C-reactive protein and fasting glucose values compared to controls (P<0.05. Cough, sputum and blood in phlegm were the most common symptoms. Risk factors of IPFI in CTD included maximum prednisone dose ≥30 mg/day within 3 months prior to infection, anti-microbial drug therapy, and interstitial pneumonia. CTD patients who have underlying interstitial pneumonia, prior prednisone or multiple antibiotics, were more likely to develop IPFI.

  7. Differential protective effects of connective tissue growth factor against Aβ neurotoxicity on neurons and glia.

    Science.gov (United States)

    Yang, Cheng-Ning; Wu, Min-Fang; Liu, Chung-Chih; Jung, Wei-Hung; Chang, Yu-Chin; Lee, Wang-Pao; Shiao, Young-Ji; Wu, Chia-Lin; Liou, Horng-Huei; Lin, Sze-Kwan; Chan, Chih-Chiang

    2017-10-15

    Impaired clearance of amyloid-β peptide (Aβ) leads to abnormal extracellular accumulation of this neurotoxic protein that drives neurodegeneration in sporadic Alzheimer's disease (AD). Connective tissue growth factor (CTGF/CCN2) expression is elevated in plaque-surrounding astrocytes in AD patients. However, the role of CTGF in AD pathogenesis remains unclear. Here we characterized the neuroprotective activity of CTGF. We found that CTGF facilitated Aβ uptake and subsequent degradation within primary glia and neuroblastoma cells. CTGF enhanced extracellular Aβ degradation via membrane-bound matrix metalloproteinase-14 (MMP14) in glia and extracellular MMP13 in neurons. In the brain of a Drosophila AD model, glial-expression of CTGF reduced Aβ deposits, improved locomotor function, and rescued memory deficits. Neuroprotective potential of CTGF against Aβ42-induced photoreceptor degeneration was disrupted through silencing MMPs. Therefore, CTGF may represent a node for potential AD therapeutics as it intervenes in glia-neuron communication via specific MMPs to alleviate Aβ neurotoxicity in the central nervous system. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. Suppression of estrogen receptor transcriptional activity by connective tissue growth factor.

    Directory of Open Access Journals (Sweden)

    Long Cheng

    Full Text Available Secreted growth factors have been shown to stimulate the transcriptional activity of estrogen receptors (ER that are responsible for many biological processes. However, whether these growth factors physically interact with ER remains unclear. Here, we show for the first time that connective tissue growth factor (CTGF physically and functionally associates with ER. CTGF interacted with ER both in vitro and in vivo. CTGF interacted with ER DNA-binding domain. ER interaction region in CTGF was mapped to the thrombospondin type I repeat, a cell attachment motif. Overexpression of CTGF inhibited ER transcriptional activity as well as the expression of estrogen-responsive genes, including pS2 and cathepsin D. Reduction of endogenous CTGF with CTGF small interfering RNA enhanced ER transcriptional activity. The interaction between CTGF and ER is required for the repression of estrogen-responsive transcription by CTGF. Moreover, CTGF reduced ER protein expression, whereas the CTGF mutant that did not repress ER transcriptional activity also did not alter ER protein levels. The results suggested the transcriptional regulation of estrogen signaling through interaction between CTGF and ER, and thus may provide a novel mechanism by which cross-talk between secreted growth factor and ER signaling pathways occurs.

  9. [Gastroesophageal reflux disease and connective tissue dysplasia in aspect of premorbid and comorbid disorders].

    Science.gov (United States)

    Dzhulaĭ, G S; Sekareva, E V; Dzhulaĭ, T E

    2014-01-01

    To investigate the phenotypic and visceral signs of connective tissue dysplasia (CTD) and comorbid diseases of the digestive system in gastroesophageal reflux disease (GERD) patients with different types of esophageal reflux as the predictors of its variants. In 124 patients with GERD the clinical features, phenotypic and visceral signs of undifferentiated CTD were studied in details. In 82.0% of patients with GERD associated with gastroesophageal type of reflux (GER) phenotypic and especially visceral signs of STD were detected, mainly in the form of cardiochalasia and hiatal hernia. In patients with duodenogastroesophageal reflux symptoms (DGER) the signs of STD were marked in 42.0% of cases, mostly in the form of biliary tract structure abnormalities. The risk of GERD associated with prevalence of GER, was 11.9 times higher in the presence of diagnostically meaningful combination of 6 or more signs of STD than in patients with DGER. Realization of predictor options in GER occurs in the preference of sharp, acidic foods, spices, taking medications that reduce lower esophageal sphincter tone. GERD, associated with DGER, is formed in patients with family history of diseases of the biliary tract and in the preference of food rich of calories. Study of STD symptoms as predictors of structural development of GERD and its variants is prospective to predict disease, choice of profession and eating behavior, primarily in young adults.

  10. The Microbiome in Connective Tissue Diseases and Vasculitides: An Updated Narrative Review

    Directory of Open Access Journals (Sweden)

    Rossella Talotta

    2017-01-01

    Full Text Available Objective. To provide a narrative review of the most recent data concerning the involvement of the microbiome in the pathogenesis of connective tissue diseases (CTDs and vasculitides. Methods. The PubMed database was searched for articles using combinations of words or terms that included systemic lupus erythematosus, systemic sclerosis, autoimmune myositis, Sjögren’s syndrome, undifferentiated and mixed CTD, vasculitis, microbiota, microbiome, and dysbiosis. Papers from the reference lists of the articles and book chapters were reviewed, and relevant publications were identified. Abstracts and articles written in languages other than English were excluded. Results. We found some evidence that dysbiosis participates in the pathogenesis of systemic lupus erythematosus, systemic sclerosis, Sjögren’s syndrome, and Behçet’s disease, but there are still few data concerning the role of dysbiosis in other CTDs or vasculitides. Conclusions. Numerous studies suggest that alterations in human microbiota may be involved in the pathogenesis of inflammatory arthritides as a result of the aberrant activation of the innate and adaptive immune responses. Only a few studies have explored the involvement of dysbiosis in other CTDs or vasculitides, and further research is needed.

  11. 2009 ESC/ERS Pulmonary Hypertension Guidelines and Connective Tissue Disease

    Directory of Open Access Journals (Sweden)

    Norifumi Nakanishi

    2011-01-01

    PAH is a common and fatal complication of connective tissue disease (CTD, but pulmonary hypertension in CTD consists of PAH, pulmonary hypertension caused by myocardial involvement, pulmonary veno-occlusive disorder, pulmonary hypertension due to interstitial lung disease. PAH has been studied widely in SSc and the estimated prevalence of 7-12%. Treatment of CTD associated PAH (CTD-PAH consists of general therapeutic options and specific treatment. Specific treatment of CTD-PAH patients is targeted to produce vasodilatation. Calcium channel blockers (CCBs are indicated in cases where a sufficient decrease in pulmonary arterial pressure is seen in vasoreactivity testing. If vasoreactivity is absent in CTD-PAH patients, the treatment consists of the endothelin receptor antagonists, the prostacyclin analogues and phosphodiesterase-type 5 inhibitors. Few data are available to support the use of immunosuppression in CTD-PAH. However, some case reports suggested that a minority of CTD-PAH patients could benefit from immunosuppressive therapy. The treatment of CTD-PAH patients may differ from the treatment of idiopathic PAH.

  12. Long-term effects of ionizing radiation on the rat spinal cord: intramedullary connective tissue formation

    International Nuclear Information System (INIS)

    Gilmore, S.A.

    1973-01-01

    Light microscopy was used to evaluate the effects of ionizing radiation on spinal cords of rats irradiated when three days of age and killed at intervals up to 28 months after irradiation. The amounts of x-rays administered (2,000 R; 1,000 R; 500 R) were those which had been demonstrated by short-term studies to cause either no histopathologic changes or only transient, reparable alterations. The most significant and previously unreported finding was the development, usually restricted to the gray matter, of elongated, spindle-shaped cells that produce prodigious amounts of fibers clearly demonstrated by the Wilder's reticular stain. In cases where extensive cellular development had occurred, these cells were oriented around the perikarya of the large ventral motor neurons and formed a well-developed capsule of reticular fibers. This phenomenon occurred more frequently in rats receiving the greater amounts of radiation and killed 12 months or more after exposure. The other observation of interest was the development of lesser amounts of connective tissue-producing cells in the dorsal gray matter, where these cells were seen initially in the substantia gelatinosa. The significance of these changes is discussed in relation to previously reported long-term effects of ionizing radiation on the central nervous system

  13. Thrombotic Thrombocytopenic Purpura Associated with Mixed Connective Tissue Disease: A Case Report

    Directory of Open Access Journals (Sweden)

    João Tadeu Damian Souto Filho

    2011-01-01

    Full Text Available Thrombotic thrombocytopenic purpura (TTP is a multisystemic disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia, which may be accompanied by fever, renal, or neurologic abnormalities. Cases are divided into acute idiopathic TTP and secondary TTP. Autoimmune diseases, especially systemic lupus erythematosus, in association with TTP have been described so far in many patients. In contrast, TTP occurring in a patient with mixed connected tissue disease (MCTD is extremely rare and has only been described in nine patients. We describe the case of a 42-year-old female with MCTD who developed thrombocytopenia, microangiopathic hemolytic anemia, fever, and neurological symptoms. The patient had a good clinical evolution with infusion of high volume of fresh frozen plasma, steroid therapy, and support in an intensive care unit. Although the occurrence of TTP is rare in MCTD patients, it is important to recognize TTP as a cause of thrombocytopenia and hemolytic anemia in any patient with autoimmune diseases. Prompt institution of treatment remains the cornerstone of treatment of TTP even if plasma exchange is not available like what frequently happens in developing countries.

  14. Delayed-type hypersensitivity to metals in connective tissue diseases and fibromyalgia.

    Science.gov (United States)

    Bjørklund, Geir; Dadar, Maryam; Aaseth, Jan

    2018-02-01

    Rheumatic diseases include a group of autoimmune disorders with environmental and genetic etiology that are characterized as a subgroup of connective tissue diseases (CTD). Rheumatoid arthritis (RA) often involves the small joints of the hands in a symmetrical fashion that can lead to loss of joint function, and RA, as well as Sjögren's syndrome (SS) and other rheumatic diseases, are often accompanied by sensitivity to metals. Numerous investigations on metal sensitivity were evaluated in this review. A detailed metal exposure history was collected by different evaluation of studies. In all subjects, the main source of metal exposure was nickel, mercury, gold, palladium, titanium, and chromium. All of SLE (systemic lupus erythematosus), RA and SS patients appeared to have an increased frequency of metal delayed-type hypersensitivity (DTH) (Type IV allergy). As dental restorative materials release minor amounts of their metals (including mercury, gold, and nickel), many adults are commonly exposed to these metal ions by vapor or corrosion into saliva. Metal-related DTH in these patients will induce an inflammatory response. Such inflammations are important factors in CTD progress. It is hypothesized that metal-specific T cell reactivity can act as an etiological agent in the propagation and chronification of rheumatic inflammation. The key responses of metal delayed-type hypersensitivity in autoimmunity are precipitating as an appealing challenge for further investigations. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Ectopic mineralization disorders of the extracellular matrix of connective tissue: Molecular genetics and pathomechanisms of aberrant calcification

    Science.gov (United States)

    Li, Qiaoli; Jiang, Qiujie; Uitto, Jouni

    2013-01-01

    Ectopic mineralization of connective tissues is a complex process leading to deposition of calcium phosphate complexes in the extracellular matrix, particularly affecting the skin and the arterial blood vessels and common in age-associated disorders. A number of initiating and contributing metabolic and environmental factors are linked to aberrant mineralization in these diseases, making the identification of precise pathomechanistic pathways exceedingly difficult. However, there has been significant recent progress in understanding the ectopic mineralization processes through study of heritable single-gene disorders, which have allowed identification of discreet pathways and contributing factors leading to aberrant connective tissue mineralization. These studies have provided support for the concept of an intricate mineralization/anti-mineralization network present in peripheral connective tissues, providing a perspective to development of pharmacologic approaches to limit the phenotypic consequences of ectopic mineralization. This overview summarizes the current knowledge of ectopic heritable mineralization disorders, with accompanying animal models, focusing on pseudoxanthoma elasticum and generalized arterial calcification of infancy, two autosomal recessive diseases manifesting with extensive connective tissue mineralization in the skin and the cardiovascular system. PMID:23891698

  16. Cytoenzymology and 3H-thymidine uptake of retro-ocular connective tissue cultures in experimental endocrino-exophthalmos.

    Science.gov (United States)

    Vaida, E; Petrescu, R; Ghinea, E; Stefaneanu, L

    1976-01-01

    The in vitro retro-ocular connective tissue cultures from guinea pigs with endocrine exophthalmos were studied before and after retro-ocular treatment with cortisol and hyaluronidase. Both cortisol and hyaluronidase inhibited the cell proliferation, the cytoenzymic activities of oxydoreductases, the 3H-thymidine uptake, the number of mitoses and the protein content of cultivated cells.

  17. External thoracic duct-venous shunt in conscious pigs for long term studies of connective tissue metabolites in lymph

    DEFF Research Database (Denmark)

    Jensen, L T; Olesen, H P; Risteli, J

    1990-01-01

    An experimental animal model for lymph studies is described. Thoracic duct-venous shunt was established in 12 pigs. Shunt patency averaged 5.5 days. The composition of connective tissue metabolites in lymph and serum were investigated during a standardized surgical operation (thoracotomy) under g...

  18. Characterization of connective tissue growth factor expression in primary cultures of human tubular epithelial cells: modulation by hypoxia

    NARCIS (Netherlands)

    Kroening, Sven; Neubauer, Emily; Wullich, Bernd; Aten, Jan; Goppelt-Struebe, Margarete

    2010-01-01

    Kroening S, Neubauer E, Wullich B, Aten J, Goppelt-Struebe M. Characterization of connective tissue growth factor expression in primary cultures of human tubular epithelial cells: modulation by hypoxia. Am J Physiol Renal Physiol 298:F796-F806, 2010. First published December 23, 2009;

  19. [Features of fluor intoxication development in patients with nondifferentiated connective tissue dysplasia and physical therapy methods for these patients].

    Science.gov (United States)

    Tereshina, L G; Budkar', L N; Obukhova, T Iu; Bugaeva, I V; Karpova, E A

    2013-01-01

    The article covers results of studies concerning time of fluorosis development in patients with signs of connective tissue dysplasia syndrome (CTDS). if compared with patients without CTDS, and of studies concerning hyperostosis coefficient in accordance with presence or absence of CTDS. Efficiency of physical therapy and balneotherapy for these patients are also reported by the authors.

  20. Experiment K-6-02. Biomedical, biochemical and morphological alterations of muscle and dense, fibrous connective tissues during 14 days of spaceflight

    Science.gov (United States)

    Vailas, A.; Zernicke, R.; Grindeland, R.; Kaplanski, A.

    1990-01-01

    Findings on the connective tissue response to short-term space flight (12 days) are discussed. Specifically, data regarding the biochemical, biomechanical and morphological characteristics of selected connective tissues (humerus, vertebral body, tendon and skeletal muscle) of growing rats is given. Results are given concerning the humerus cortical bone, the vertebral bone, nutritional effects on bone biomechanical properties, and soft tense fiber connective tissue response.

  1. The clinical and pathological characteristics of nephropathies in connective tissue diseases in the Japan Renal Biopsy Registry (J-RBR).

    Science.gov (United States)

    Ichikawa, Kazunobu; Konta, Tsuneo; Sato, Hiroshi; Ueda, Yoshihiko; Yokoyama, Hitoshi

    2017-12-01

    In connective tissue diseases, a wide variety of glomerular, tubulointerstitial, and vascular lesions of the kidney are observed. Nonetheless, recent information is limited regarding renal lesions in connective tissue diseases, except in systemic lupus erythematosus (SLE). In this study, we used a nationwide database of biopsy-confirmed renal diseases in Japan (J-RBR) (UMIN000000618). In total, 20,523 registered patients underwent biopsy between 2007 and 2013; from 110 patients with connective tissue diseases except SLE, we extracted data regarding the clinico-pathological characteristics of the renal biopsy. Our analysis included patients with rheumatoid arthritis (RA) (n = 52), Sjögren's syndrome (SjS) (n = 35), scleroderma (n = 10), mixed connective tissue disease (MCTD; n = 5), anti-phospholipid syndrome (APS; n = 3), polymyositis/dermatomyositis (PM/DM; n = 1), Behçet's disease (n = 1) and others (n = 3). The clinico-pathological features differed greatly depending on the underlying disease. The major clinical diagnosis was nephrotic syndrome in RA; chronic nephritic syndrome with mild proteinuria and reduced renal function in SjS; rapidly progressive nephritic syndrome in scleroderma. The major pathological diagnosis was membranous nephropathy (MN) and amyloidosis in RA; tubulointerstitial nephritis in SjS; proliferative obliterative vasculopathy in scleroderma; MN in MCTD. In RA, most patients with nephrosis were treated using bucillamine, and showed membranous nephropathy. Using the J-RBR database, our study revealed that biopsy-confirmed cases of connective tissue diseases such as RA, SjS, scleroderma, and MCTD show various clinical and pathological characteristics, depending on the underlying diseases and the medication used.

  2. Peri-implant tissue response following connective tissue and bone grafting in conjunction with immediate single-tooth replacement in the esthetic zone: a case series.

    Science.gov (United States)

    Tsuda, Hirotaka; Rungcharassaeng, Kitichai; Kan, Joseph Y K; Roe, Phillip; Lozada, Jaime L; Zimmerman, Grenith

    2011-01-01

    This case series evaluated the peri-implant tissue response following extraction and immediate placement and restoration of an implant in conjunction with subepithelial connective tissue grafting (SCTG) and bone grafting in the esthetic zone. Implant success rates and the peri-implant tissue response were also reported. Ten patients (four men, six women) with a mean age of 48 years (range, 35 to 70) underwent extraction and immediate tooth replacement with SCTG and were evaluated clinically and radiographically presurgically (T0), immediately after immediate tooth replacement and SCTG (T1), and at 3 months (T2), 6 months (T3), and 12 months (T4) after surgery. Data was analyzed using Friedman and Wilcoxon signed-ranks tests at the significance level of a = .05. At 1 year, all implants remained osseointegrated, with an overall mean marginal bone change of +0.10 mm and a mean facial gingival level change of -0.05 mm. Modified Plaque Index scores showed that patients were able to maintain a good level of hygiene throughout the study. Papilla Index scores indicated that at T4, more than 50% papilla fill was observed in 80% of all sites. The results of this case series suggest that, in addition to a favorable implant success rate and peri-implant tissue response, the facial gingival level around single immediately placed implants can also be maintained following connective tissue grafting when proper three-dimensional implant positioning is achieved and bone is grafted into the implant-socket gap.

  3. [Connective tissue growth factors, CTGF and Cyr61 in drug-induced gingival overgrowth--an animal model].

    Science.gov (United States)

    Ciobanică, Mihaela; Cianga, Corina; Căruntu, Irina-Draga; Grigore, Georgiana; Cianga, P

    2008-01-01

    Human gingival overgrowth may occur as a side effect of chronic administration of some therapeutic agents. The mechanisms responsible for the gingival tissues lesions, fibrosis and inflamation, involve an impaired balance between the production and the degradation of type I collagen. It has been demonstrated that CCN2/CTGF, a connective tissue growth factor, is highly expressed in the gingival tissues and positively correlated with the degree of fibrosis in the drug-induced gingival overgrowth. The aim of this study was to identify the presence and localization of CCN2/CTGF and CCN1/Cyr61, members of the same molecular family, in gingival tissues of cyclosporin A- and nifedipine-treated rats, by immunohistochemistry. Staining was evaluated with light microscope and the results show cellular and extracellular CTGF in nifedipin gingival overgrowth tissues with intensity of labeling higher compared to the CsA gingival overgrowth tissues or the controls. The staining for Cyr61 shows its intracellular localization with no diference of labeling intensity between drug-induced gingival overgrowth and normal tissues. Also, we were interested in the gingival TGF-â expression in those animals. We didn't find any commercial anti-rat TGF antibody and our anti-human antibody shows no cross-reactivity with rat tissues. The data from our study sustain the involvement of CTGF and Cyr61 as growth factors in the gingival tissues and the CTGF association with drug-induced gingival overgrowth.

  4. PECULIARITIES OF INTERCELLULAR SUBSTANCE METABOLISM OF PATIENTS WITH OSTEOARTHRITIS AND CONNECTIVE TISSUE DYSPLASIA

    Directory of Open Access Journals (Sweden)

    A. V. Tyurin

    2015-01-01

    Full Text Available Objective of work: to study the peculiarities of intercellular substance metabolism of patients with osteoarthritis (OA and connective tissue dysplasia (CTD.Materials and methods. 95 female patients with OA take part in the study; 70 of them have signs of CTD. Inclusion criteria: female sex, age from 20 to 60 y.o., OA diagnosed on the basis of criteria of the American Association of Rheumatology. Exclusion criteria: injury of the lower extremities in medical history, systemic connective tissue diseases, ovariectomy, prolonged (over 6 months intake of glucocorticoid hormones. 50 almost healthy women were included into the reference group. Study of clinical phenomena of the CTD of patients with OA was performed, as well as the study of levels of cartilage oligomeric matrix protein (COMP and glycosaminoglycans (GAGs in the blood serum.Results. In 500 of patients examined, OA was revealed with 95 cases (19 % including combinations with CTD in 70 cases (14 %. Polyosteoarthrosis was revealed with 38 (40 % patients, isolated gonarthrosis was revealed with 30 (31.5 % patients, coxarthrosis was revealed with 20 (21 % patients, and osteoarthritis of ankle joints was revealed with 7 (7.3 % patients. Increasing of the COMP concetration was revealed with patients with combined pathology of up to 24.15 ± 11.35 μm/l, with OA – up to 18.26 ± 6.35 μm/l, with CTD – up to 14.32 ± 3.96 μm/l. Maximum variability of indicators was marked in the group of people with the combination of OA and CTD. Serum GAG concentrations were increased with female patients with the combined pathology and isolated OA of up to 53.65 ± 21.5 and 46.96 ± 15.82 μm/l, respectively. No increasing of GAG concentration was revealed with patients with CTD.Conclusion. Increasing of the intercellular substance metabolism is observed with persons that suffer from CTD. To a greater degree, CTD affects the state of the fibrillar component of the intercellular substance as

  5. PECULIARITIES OF INTERCELLULAR SUBSTANCE METABOLISM OF PATIENTS WITH OSTEOARTHRITIS AND CONNECTIVE TISSUE DYSPLASIA

    Directory of Open Access Journals (Sweden)

    A. V. Tyurin

    2014-01-01

    Full Text Available Objective of work: to study the peculiarities of intercellular substance metabolism of patients with osteoarthritis (OA and connective tissue dysplasia (CTD.Materials and methods. 95 female patients with OA take part in the study; 70 of them have signs of CTD. Inclusion criteria: female sex, age from 20 to 60 y.o., OA diagnosed on the basis of criteria of the American Association of Rheumatology. Exclusion criteria: injury of the lower extremities in medical history, systemic connective tissue diseases, ovariectomy, prolonged (over 6 months intake of glucocorticoid hormones. 50 almost healthy women were included into the reference group. Study of clinical phenomena of the CTD of patients with OA was performed, as well as the study of levels of cartilage oligomeric matrix protein (COMP and glycosaminoglycans (GAGs in the blood serum.Results. In 500 of patients examined, OA was revealed with 95 cases (19 % including combinations with CTD in 70 cases (14 %. Polyosteoarthrosis was revealed with 38 (40 % patients, isolated gonarthrosis was revealed with 30 (31.5 % patients, coxarthrosis was revealed with 20 (21 % patients, and osteoarthritis of ankle joints was revealed with 7 (7.3 % patients. Increasing of the COMP concetration was revealed with patients with combined pathology of up to 24.15 ± 11.35 μm/l, with OA – up to 18.26 ± 6.35 μm/l, with CTD – up to 14.32 ± 3.96 μm/l. Maximum variability of indicators was marked in the group of people with the combination of OA and CTD. Serum GAG concentrations were increased with female patients with the combined pathology and isolated OA of up to 53.65 ± 21.5 and 46.96 ± 15.82 μm/l, respectively. No increasing of GAG concentration was revealed with patients with CTD.Conclusion. Increasing of the intercellular substance metabolism is observed with persons that suffer from CTD. To a greater degree, CTD affects the state of the fibrillar component of the intercellular substance as

  6. Management of Raynaud's Phenomenon in the Patient with Connective Tissue Disease.

    Science.gov (United States)

    Chatterjee, Soumya

    2010-04-01

    Raynaud's phenomenon is characterized by intense vasospasm of digital arteries on cold exposure or with emotional stress, leading to well-defined color changes of digital skin. It may be primary (Raynaud's disease) or secondary to an underlying condition, including autoimmune rheumatic diseases. Although Raynaud's disease is predominantly a vasospastic condition, Raynaud's phenomenon in connective tissue diseases often is a result of an underlying vaso-occlusive process. As a result, the manifestations are more severe and persistent and often warrant pharmacologic therapy. Dihydropyridine calcium channel blockers are by far the most commonly studied and prescribed class of agents for the treatment of Raynaud's phenomenon. There is some evidence for the efficacy of other classes of drugs, such as topical nitrates, α-antagonists, angiotensin receptor blockers, selective serotonin reuptake inhibitors, and pentoxifylline. However, the data on the efficacy of these agents are not as convincing, and they are not proven to be more effective than calcium channel blockers. Hence, their place in the therapy of Raynaud's phenomenon is limited to patients who fail to respond adequately to or are unable to tolerate calcium channel blockers. More expensive second-line agents, such as phosphodiesterase-5 inhibitors, endothelin receptor antagonists, and intravenous prostanoids, are reserved for refractory cases of secondary Raynaud's phenomenon with severe digital ischemia leading to ulceration or gangrene. These drugs may be used in isolation or as adjunct therapy to the first-line agents. Chemical and/or surgical sympathectomy may be considered if sympathetically driven digital ischemia is severe and resistant to pharmacologic intervention. These procedures may temporarily reverse the digital ischemia and help tide over the crisis, whereas the improvement thus achieved can be maintained by continuing medical therapy. In cases of ischemic digital ulceration, it is important to

  7. Original paper Influence of biologic therapy on growth in children with chronic inflammatory connective tissue diseases

    Directory of Open Access Journals (Sweden)

    Joanna Świdrowska

    2015-04-01

    Full Text Available Objectives: Connective tissue diseases (CTD are a heterogeneous group of chronic inflammatory conditions. One of their complications in children is the inhibition of growth velocity. Due to direct inflammation within the musculoskeletal system as well as glucocorticoid therapy, this feature is the most essential and is mainly expressed in the course of juvenile spondyloarthropathies and juvenile idiopathic arthritis (JIA. Duration of the disease, but predominantly the activity of the inflammatory process, seems to have a significant impact on the abnormal growth profile in children. Effective biological therapy leads to improvement of the patient’s clinical condition and also, through the extinction of disease activity and reduction of daily doses of glucocorticosteroids (GCS, it gradually accelerates and normalizes the growth rate in children with CTD. Our objective was to evaluate the impact of biological therapy on growth in children with chronic inflammatory CTD. Material and methods: Data from 24 patients with CTD treated with tumor necrosis factor--blockers (etanercept, adalimumab, golimumab and an interleukin-6 receptor blocker (tocilizumab were reviewed at the time of disease onset, biological treatment initiation and at least 12 up to 24 months onwards. The rate of growth was correlated with the daily doses of GCS, and the type and duration of biological therapy. Results : Patient median height, measured as the change in height standard deviation score, was 0.36 ±1.07 at disease onset and –0.13 ±1.02 at biologic therapy initiation. The growth velocity accelerated in 17 patients (70.1% during the biological treatment. Mean height-SDS improvement between biological treatment initiation up to two years was 0.51 ±0.58. In 47% of patients daily doses of GCS were reduced to 0 mg/kg/day. Conclusions : In the treatment of CTD, biological agents restore growth velocity not only by inflammation inhibition, but also through limiting GCS

  8. [Three dimensional structure of the connective tissue papillae of the tongue in Suncus murinus].

    Science.gov (United States)

    Kobayashi, K; Miyata, K; Iwasaki, S; Takahashi, K

    1989-08-01

    The surface structure of the connective tissue papillae (CP) of Suncus murinus tongue was observed by SEM after fixing with Karnovsky's fixative and removal of the epithelial cell layer with 3N or 8N HCl. On the surface of the slender conical tongue, there are densely distributed filiform papillae among which fungiform papillae are seen sporadically. A pair of vallate papillae are situated in the posterior region of the tongue. Filiform papillae appear somewhat different externally depending on the dorsal surface of the anterior tongue. At the tip of the tongue, filiform papillae are of a slender conical shape and have a slight depression in the anterior basal portion. The CP of these is seen as a spherical protrusion on which a shallow groove runs in the anteroposterior direction. In the middle region, somewhat large filiform papillae contain CP having one or two small round head-like structures on each spherical protrusion. These head-like structures are increased in number in the posterior region. In the most posterior region of the anterior tongue, there are distributed large filiform papillae having several slender protrusions that surround a basal anterior depression. These large branched filiform papillae have a glove finger like CP. Small conical filiform papillae are distributed in the posterior marginal region of the anterior tongue which have CP of a horse-shoe like protrusion that opens in the anterior direction. Spherical fungiform papillae have CP which are thick columnar in shape with many lateral thin folds running vertically and having a round depression on the top of each. CP of the vallate papillae appear as a beehive like structure.(ABSTRACT TRUNCATED AT 250 WORDS)

  9. Volumetric imaging of oral epithelial neoplasia by MPM-SHGM: epithelial connective tissue interface (Conference Presentation)

    Science.gov (United States)

    Pal, Rahul; Yang, Jinping; Qiu, Suimin; Resto, Vicente; McCammon, Susan; Vargas, Gracie

    2016-03-01

    The majority of oral cancers are comprised of oral squamous cell carcinoma in which neoplastic epithelial cells invade across the epithelial connective tissue interface (ECTI). Invasion is preceded by a multi-component process including epithelial hyperproliferation, loss of cell polarity, and remodeling of the extracellular matrix. Multiphoton Autofluorescence Microscopy (MPAM) and Second Harmonic Generation Microscopy (SHGM) show promise for revealing indicators of neoplasia. In particular, volumetric imaging by these methods can reveal aspects of the 3D microstructure that are not possible by other methods and which could both further our understanding of neoplastic transformation and be explored for development of diagnostic approaches in this disease having only 55% 5-year survival rate. MPAM-SHG were applied to reveal the 3D structure of the critical ECTI interface that plays an integral part toward invasion. Epithelial dysplasia was induced in an established hamster model. MPAM-SHGM was applied to lesion sites, using 780 nm excitation (450-600nm emission) for autofluroescence of cellular and extracellular components; 840 nm using 420 nm bandpass filter for SHG. The ECTI surface was identified as the interface at which SHG signal began following the epithelium and was modeled as a 3D surface using Matlab. ECTI surface area and cell features at sites of epithelial expansion where ECTI was altered were measured; Imaged sites were biopsied and processed for histology. ROC analysis using ECTI image metrics indicated the ability to delineate normal from neoplasia with high sensitivity and specificity and it is noteworthy that inflammation did not significantly alter diagnostic potential of MPAM-SHGM .

  10. Connective Tissue Growth Factor Promotes Pulmonary Epithelial Cell Senescence and Is Associated with COPD Severity.

    Science.gov (United States)

    Jang, Jun-Ho; Chand, Hitendra S; Bruse, Shannon; Doyle-Eisele, Melanie; Royer, Christopher; McDonald, Jacob; Qualls, Clifford; Klingelhutz, Aloysius J; Lin, Yong; Mallampalli, Rama; Tesfaigzi, Yohannes; Nyunoya, Toru

    2017-04-01

    The purpose of this study was to determine whether expression of connective tissue growth factor (CTGF) protein in chronic obstructive pulmonary disease (COPD) is consistent in humans and animal models of COPD and to investigate the role of this protein in lung epithelial cells. CTGF in lung epithelial cells of ex-smokers with COPD was compared with ex-smokers without COPD by immunofluorescence. A total of twenty C57Bl/6 mice and sixteen non-human primates (NHPs) were exposed to cigarette smoke (CS) for 4 weeks. Ten mice of these CS-exposed mice and eight of the CS-exposed NHPs were infected with H3N2 influenza A virus (IAV), while the remaining ten mice and eight NHPs were mock-infected with vehicle as control. Both mRNA and protein expression of CTGF in lung epithelial cells of mice and NHPs were determined. The effects of CTGF overexpression on cell proliferation, p16 protein, and senescence-associated β-galactosidase (SA-β-gal) activity were examined in cultured human bronchial epithelial cells (HBECs). In humans, CTGF expression increased with increasing COPD severity. We found that protein expression of CTGF was upregulated in lung epithelial cells in both mice and NHPs exposed to CS and infected with IAV compared to those exposed to CS only. When overexpressed in HBECs, CTGF accelerated cellular senescence accompanied by p16 accumulation. Both CTGF and p16 protein expression in lung epithelia are positively associated with the severity of COPD in ex-smokers. These findings show that CTGF is consistently expressed in epithelial cells of COPD lungs. By accelerating lung epithelial senescence, CTGF may block regeneration relative to epithelial cell loss and lead to emphysema.

  11. Undiagnosed connective tissue diseases: High prevalence in pulmonary arterial hypertension patients.

    Science.gov (United States)

    Cavagna, Lorenzo; Codullo, Veronica; Ghio, Stefano; Scirè, Carlo Alberto; Guzzafame, Eleonora; Scelsi, Laura; Rossi, Silvia; Montecucco, Carlomaurizio; Caporali, Roberto

    2016-09-01

    Among different subgroups of pulmonary arterial hypertension (PAH), those associated with connective tissue diseases (CTDs) have distinct hemodynamic and prognostic features; a correct etiologic diagnosis is thus mandatory.To estimate frequency and prognosis of previously undiagnosed CTDs in a suspect idiopathic (i) PAH cohort.Consecutive patients with PAH confirmed by right heart catheterization referred at the Cardiology Division of our Hospital without a previous rheumatological assessment or the occurrence of other conditions explaining PAH were checked for CTD by a clinical, laboratory, and instrumental evaluation. Survival in each group has also been analyzed.In our study 17 of 49 patients were classified as CTD-PAH, corresponding to a prevalence (95% CI) of 34.7% (21.7-49.6%). ANA positivity had 94% (71.3-99.9%) sensitivity and 78.1% (60-90.7%) specificity for a diagnosis of CTD-PAH; Raynaud phenomenon (RP) showed 83.3% (51.6-97.9%) sensitivity and 100% (90.5-100%) specificity for the diagnosis of Systemic Sclerosis (SSc)-PAH. At diagnosis, SSc patients were older and had a lower creatinine clearance compared with iPAH and other CTD-PAH. After a median follow-up of 44 (2-132) months, 18 of 49 (36.7%) patients died: 31.2% in the iPAH group, 20% in the CTD-, and 58.3% in the SSc-PAH group. Mortality was significantly higher in SSc-PAH (HR 3.32, 1.11-9.95, P <0.05) versus iPAH.We show a high prevalence of undiagnosed CTDs in patients with iPAH without a previous rheumatological assessment. All patients with RP were diagnosed with SSc. Our data stress the importance of a rheumatological assessment in PAH, especially because of the unfavorable prognostic impact of an associated SSc.

  12. Increased frequency of delayed type hypersensitivity to metals in patients with connective tissue disease.

    Science.gov (United States)

    Stejskal, Vera; Reynolds, Tim; Bjørklund, Geir

    2015-01-01

    Connective tissue disease (CTD) is a group of inflammatory disorders of unknown aetiology. Patients with CTD often report hypersensitivity to nickel. We examined the frequency of delayed type hypersensitivity (DTH) (Type IV allergy) to metals in patients with CTD. Thirty-eight patients; 9 with systemic lupus erythematosus (SLE), 16 with rheumatoid arthritis (RA), and 13 with Sjögren's syndrome (SS) and a control group of 43 healthy age- and sex-matched subjects were included in the study. A detailed metal exposure history was collected by questionnaire. Metal hypersensitivity was evaluated using the optimised lymphocyte transformation test LTT-MELISA(®) (Memory Lymphocyte Immuno Stimulation Assay). In all subjects, the main source of metal exposure was dental metal restorations. The majority of patients (87%) had a positive lymphocyte reaction to at least one metal and 63% reacted to two or more metals tested. Within the control group, 43% of healthy subjects reacted to one metal and only 18% reacted to two or more metals. The increased metal reactivity in the patient group compared with the control group was statistically significant (Pnickel, mercury, gold and palladium. Patients with SLE, RA and SS have an increased frequency of metal DTH. Metals such as nickel, mercury and gold are present in dental restorative materials, and many adults are therefore continually exposed to metal ions through corrosion of dental alloys. Metal-related DTH will cause inflammation. Since inflammation is a key process in CTDs, it is possible that metal-specific T cell reactivity is an etiological factor in their development. The role of metal-specific lymphocytes in autoimmunity remains an exciting challenge for future studies. Copyright © 2015 Elsevier GmbH. All rights reserved.

  13. Pulmonary hypertension not a major feature of early mixed connective tissue disease: A prospective clinicoserological study

    Directory of Open Access Journals (Sweden)

    Haroon N

    2005-01-01

    Full Text Available Background: Mixed connective tissue disease (MCTD has features common to lupus, scleroderma and myositis with high levels of antibodies to U1 ribonucleoprotein (U1 RNP. Identification of a high incidence of pulmonary artery hypertension (PAH has changed its prospect. We report the largest series from India. Settings and Design: Rheumatology unit of a tertiary care centre in India; prospective. Materials and Methods: Patients seen between January 2002 and June 2004, satisfying the Kasukawa criteria were enrolled. All patients had a complete laboratory work-up including pulmonary function test, 2-D echocardiography, and Schirmer′s test, antinuclear antibodies (ANA and antibodies to extractable nuclear antigens. HRCT of chest was done where indicated. All patients were given standard treatment and followed up regularly. Results: Out of 1500 patients, thirteen (one male were diagnosed to have MCTD. The median follow-up period was 18 months [Interquartile range (IQR 12-22]. The median age of onset of symptoms was 36 years (IQR 22-39 and the median duration of disease was three years (IQR 1.75-4. The most common manifestation was polyarthritis followed by puffy fingers. Sjogren′s syndrome, dysphagia and interstitial lung disease, was present in four, three and two patients respectively. Two patients each had myositis and migraine. None had PAH, serositis or renal involvement. Arthritis, puffy fingers and RaynaudÆs phenomenon were the most common manifestations at onset. All patients were positive for ANA and anti U1 RNP. Two patients each had antibodies to Sm and SSA. Response to treatment also was noted. Conclusion: Pulmonary artery hypertension is not common in early MCTD.

  14. Prenatal administration of retinoic acid upregulates connective tissue growth factor in the nitrofen CDH model.

    Science.gov (United States)

    Ruttenstock, Elke Maria; Doi, Takashi; Dingemann, Jens; Puri, Prem

    2011-06-01

    Recent studies have suggested that retinoids may be involved in the molecular mechanisms of pulmonary hypoplasia (PH) in congenital diaphragmatic hernia (CDH). Connective tissue growth factor (CTGF) plays a key role in foetal lung development and remodelling during later gestation. CTGF knockout mice exhibit PH with similar characteristics to the human and nitrofen-induced PH. Prenatal administration of retinoic acid (RA) has been shown to stimulate alveologenesis in nitrofen-induced PH. In vitro studies have revealed that RA can induce CTGF gene expression. We hypothesized that pulmonary gene expression of CTGF is downregulated during the later stages of lung development, and that prenatal administration of RA upregulates CTGF in the nitrofen CDH model. Pregnant rats were exposed to either olive oil or nitrofen on day 9 (D9) of gestation. RA was given intraperitoneally on D18, D19 and D20. Foetuses were harvested on D21 and divided into control, CDH, control + RA and CDH + RA group. Pulmonary CTGF gene and protein expression levels were determined using RT-PCR and immunohistochemistry. On D21, CTGF relative mRNA expression levels were significantly downregulated in CDH group compared to controls. After RA treatment, expression levels of CTGF were significantly upregulated in CDH + RA and control + RA compared to the CDH group. Immunohistochemical studies confirmed these results. Downregulation of pulmonary CTGF gene and protein expression during later stages of lung development may interfere with normal alveologenesis in the nitrofen CDH model. Upregulation of CTGF pulmonary gene expression after prenatal RA treatment may promote lung growth by promoting alveologenesis in the nitrofen-induced CDH model.

  15. Regulatory T Cell Dysfunction in Idiopathic, Heritable and Connective Tissue-Associated Pulmonary Arterial Hypertension.

    Science.gov (United States)

    Huertas, Alice; Phan, Carole; Bordenave, Jennifer; Tu, Ly; Thuillet, Raphaël; Le Hiress, Morane; Avouac, Jérôme; Tamura, Yuichi; Allanore, Yannick; Jovan, Roland; Sitbon, Olivier; Guignabert, Christophe; Humbert, Marc

    2016-06-01

    Pulmonary arterial hypertension (PAH) encompasses a group of conditions with distinct causes. Immunologic disorders are common features of all forms of PAH and contributes to both disease susceptibility and progression. Regulatory T lymphocytes (Treg) are dysfunctional in patients with idiopathic PAH (iPAH) in a leptin-dependent manner. However, it is not known whether these abnormalities are specific to iPAH. Hence, we hypothesized that (1) Treg dysfunction is also present in heritable (hPAH) and connective tissue disease-associated PAH (CTD-PAH); (2) defective leptin-dependent signaling is present in hPAH and CTD-PAH and could contribute to Treg dysfunction; (3) modulating the leptin axis in vivo could protect against Treg dysfunction; and (4) restoration of Treg activity could limit or reverse experimental chronic hypoxia-induced pulmonary hypertension in vivo. We analyzed 62 patients with PAH (30 with iPAH, 18 with hPAH, and 14 with CTD-PAH), 7 patients with CTD without PAH, and 20 healthy control subjects. Our results indicate that Treg are dysfunctional in all PAH forms tested, as well as in patients with CTD without PAH. Importantly, the leptin axis is crucial in Treg dysfunction in patients with iPAH and those with CTD (with or without PAH), whereas in patients with hPAH, Treg are altered in a leptin-independent manner. We found that leptin receptor-deficient rats, which develop less severe hypoxia-induced pulmonary hypertension, are protected against decreased Treg function after hypoxic exposure. Taken together, our results suggest that Treg dysfunction is common to all forms of PAH and may contribute to the development and the progression of the disease. Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.

  16. Connective tissue growth factor is not necessary for haze formation in excimer laser wounded mouse corneas.

    Directory of Open Access Journals (Sweden)

    Xiaodi Feng

    Full Text Available We sought to determine if connective tissue growth factor (CTGF is necessary for the formation of corneal haze after corneal injury. Mice with post-natal, tamoxifen-induced, knockout of CTGF were subjected to excimer laser phototherapeutic keratectomy (PTK and the corneas were allowed to heal. The extent of scaring was observed in non-induced mice, heterozygotes, and full homozygous knockout mice and quantified by macrophotography. The eyes from these mice were collected after euthanization for re-genotyping to control for possible Cre-mosaicism. Primary corneal fibroblasts from CTGF knockout corneas were established in a gel plug assay. The plug was removed, simulating an injury, and the rate of hole closure and the capacity for these cells to form light reflecting cells in response to CTGF and platelet-derived growth factor B (PDGF-B were tested and compared to wild-type cells. We found that independent of genotype, each group of mice was still capable of forming light reflecting haze in the cornea after laser ablation (p = 0.40. Results from the gel plug closure rate in primary cell cultures of knockout cells were not statistically different from serum starved wild-type cells, independent of treatment. Compared to the serum starved wild-type cells, stimulation with PDGF-BB significantly increased the KO cell culture's light reflection (p = 0.03. Most interestingly, both reflective cultures were positive for α-SMA, but the cellular morphology and levels of α-SMA were distinct and not in proportion to the light reflection seen. This new work demonstrates that corneas without CTGF can still form sub-epithelial haze, and that the light reflecting phenotype can be reproduced in culture. These data support the possibilities of growth factor redundancy and that multiple pro-haze pathways exist.

  17. [The connective tissues, from the origin of the concept to its "Maturation" to extracellular matrix. Application to ocular tissues. Contribution to the history of medical sciences].

    Science.gov (United States)

    Labat-Robert, J; Robert, L; Pouliquen, Y

    2011-06-01

    The "Tissue" concept emerged apparently in the medical literature at about the French revolution, during the second half of the 18(th) century. It was found in the texts written by the physicians of Béarn and Montpellier, the Bordeu-s and also by the famous physician, Felix Vicq d'Azyr, the last attending physician of the queen Marie-Antoinette, "Bordeu et al. (1775) et Pouliquen (2009)". It was elaborated into a coherent doctrine somewhat later by Xavier Bichat, considered as the founder of modern pathological anatomy, Bichat. With the advent of histochemistry, from the beginning of the 20(th) century, several of the principal macromolecular components of connective tissues, collagens, elastin, "acid mucopolysaccharides" (later glycosaminoglycans and proteoglycans) and finally structural glycoproteins were characterized. These constituents of connective tissues were then designated as components of the extracellular matrix (ECM), closely associated to the cellular components of these tissues by adhesive (structural) glycoproteins as fibronectin, several others and cell receptors, "recognising" ECM-components as integrins, the elastin-receptor and others. This molecular arrangement fastens cells to the ECM-components they synthesize and mediates the exchange of informations between the cells to the ECM (inside-out) and also from the ECM-components to the cells (outside-in). This macromolecular arrangement is specific for each tissue as a result of the differentiation of their cellular components. It is also the basis and condition of the fulfillment of the specific functions of differentiated tissues. This is a short description of the passage of the "tissue" concept from its vague origin towards its precise identification at the cellular and molecular level up to the recognition of its functional importance and its establishment as an autonomous science. This can be considered as a new example of the importance of metaphors for the progress of science, Keller

  18. Comparison of rat connective tissue reaction to two types of foreign and Iranian white Mineral Trioxide Aggregate

    Directory of Open Access Journals (Sweden)

    Vosough Hosseini S.

    2008-11-01

    Full Text Available "nBackground and Aim: Three Dimensional obturation of root canal is one of the main goals of root canal therapy to preserve health or reach the regeneration or healing of periapical tissues. Root end filling materials are used in numerous situations to reach the mentioned goals. One of the common root end- filling materials is mineral trioxide aggregate (MTA which the foreign and Iranian ones are different in their prices. The aim of this study was to compare the rat connective tissue reaction to Iranian and foreign MTA. "nMaterials and Methods: This was an animal study in which 40 rats were divided into 5 groups of each 8. The polyethylene tubes filled with foreign (Pro Root MTA and Iranian (Root MTA white MTA and were implanted in subcutaneous connective tissue. Similarly, the empty tubes were inserted in subcutaneous connective tissue as control group. The samples were examined histologically after 7, 14, 30, 60 and 90 days and were scored as followings: 0, was characterized to samples without inflammatory cells; without inflammatory reaction 1, for samples with less than 25 inflammatory cells; mild inflammatory reaction. 2, for samples with 25 to 125 inflammatory cells; moderate inflammatory reaction and 3, for ones with more than 125 inflammatory cells; severe inflammatory reaction. The data were analyzed using Kruskal-Wallis test and p<0.05 was considered as the level of significance. "nResults: In general, inflammatory reactions were reduced in all groups. Experimental groups had moderate to severe inflammation in the 7th day which had significant difference with the control group having mild to moderate inflammation (p=0.04. There was not any significant differences between experimental and control group in 14th, 30th, 60th and 90th days (p>0.05. "nConclusion: Based on the findings of this investigation, inflammatory subcutaneous connective tissue reaction to Iranian (Root MTA and foreign (Pro Root MTA MTA was the same.

  19. JAK-STAT and AKT pathway-coupled genes in erythroid progenitor cells through ontogeny

    Directory of Open Access Journals (Sweden)

    Cokic Vladan P

    2012-06-01

    Full Text Available Abstract Background It has been reported that the phosphatidylinositol 3-kinase (PI3K-AKT signaling pathway regulates erythropoietin (EPO-induced survival, proliferation, and maturation of early erythroid progenitors. Erythroid cell proliferation and survival have also been related to activation of the JAK-STAT pathway. The goal of this study was to observe the function of EPO activation of JAK-STAT and PI3K/AKT pathways in the development of erythroid progenitors from hematopoietic CD34+ progenitor cells, as well as to distinguish early EPO target genes in human erythroid progenitors during ontogeny. Methods Hematopoietic CD34+ progenitor cells, isolated from fetal and adult hematopoietic tissues, were differentiated into erythroid progenitor cells. We have used microarray analysis to examine JAK-STAT and PI3K/AKT related genes, as well as broad gene expression modulation in these human erythroid progenitor cells. Results In microarray studies, a total of 1755 genes were expressed in fetal liver, 3844 in cord blood, 1770 in adult bone marrow, and 1325 genes in peripheral blood-derived erythroid progenitor cells. The erythroid progenitor cells shared 1011 common genes. Using the Ingenuity Pathways Analysis software, we evaluated the network pathways of genes linked to hematological system development, cellular growth and proliferation. The KITLG, EPO, GATA1, PIM1 and STAT3 genes represent the major connection points in the hematological system development linked genes. Some JAK-STAT signaling pathway-linked genes were steadily upregulated throughout ontogeny (PIM1, SOCS2, MYC, PTPN11, while others were downregulated (PTPN6, PIAS, SPRED2. In addition, some JAK-STAT pathway related genes are differentially expressed only in some stages of ontogeny (STATs, GRB2, CREBB. Beside the continuously upregulated (AKT1, PPP2CA, CHUK, NFKB1 and downregulated (FOXO1, PDPK1, PIK3CG genes in the PI3K-AKT signaling pathway, we also observed intermittently

  20. Connective Tissue Growth Factor Transgenic Mouse Develops Cardiac Hypertrophy, Lean Body Mass and Alopecia.

    Science.gov (United States)

    Nuglozeh, Edem

    2017-07-01

    Connective Tissue Growth Factor (CTGF/CCN2) is one of the six members of cysteine-rich, heparin-binding proteins, secreted as modular protein and recognised to play a major function in cell processes such as adhesion, migration, proliferation and differentiation as well as chondrogenesis, skeletogenesis, angiogenesis and wound healing. The capacity of CTGF to interact with different growth factors lends an important role during early and late development, especially in the anterior region of the embryo. CTGF Knockout (KO) mice have several craniofacial defects and bone miss shaped due to an impairment of the vascular system development during chondrogenesis. The aim of the study was to establish an association between multiple modular functions of CTGF and the phenotype and cardiovascular functions in transgenic mouse. Bicistronic cassette was constructed using pIRES expressing vector (Clontech, Palo Alto, CA). The construct harbours mouse cDNA in tandem with LacZ cDNA as a reporter gene under the control of Cytomegalovirus (CMV) promoter. The plasmid was linearised with NotI restriction enzyme, and 50 ng of linearised plasmid was injected into mouse pronucleus for the chimaera production. Immunohistochemical methods were used to assess the colocalisation renin and CTGF as well as morphology and rheology of the cardiovascular system. The chimeric mice were backcrossed against the wild-type C57BL/6 to generate hemizygous (F1) mouse. Most of the offsprings died as a result of respiratory distress and those that survived have low CTGF gene copy number, approximately 40 molecules per mouse genome. The copy number assessment on the dead pups showed 5×10 3 molecules per mouse genome explaining the threshold of the gene in terms of toxicity. Interestingly, the result of this cross showed 85% of the progenies to be positive deviating from Mendelian first law. All F2 progenies died excluding the possibility of establishing the CTGF transgenic mouse line, situation that

  1. PPARgamma-2 and ADRB3 polymorphisms in connective tissue diseases and lipid disorders

    Directory of Open Access Journals (Sweden)

    Grygiel-Górniak B

    2018-03-01

    Full Text Available Bogna Grygiel-Górniak,1 Iwona Ziółkowska-Suchanek,2 Elżbieta Kaczmarek,3 Maria Mosor,2 Jerzy Nowak,2 Mariusz Puszczewicz1 1Department of Rheumatology and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland; 2Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland; 3Department of Bioinformatics and Computational Biology, Poznan University of Medical Sciences, Poznan, Poland Background: The aim of the research genetic study was to investigate the association between variants (C1431T and Pro12Ala of the peroxisome proliferator-activated receptor (PPARgamma-2 gene, Trp64Arg polymorphism of the beta-3-adrenergic receptor gene and lipid profile in Polish population including group of 103 patients with connective tissue disease (CTD and 103 sex- and age-matched controls in context of statin use. Methods: Anthropometric and biochemical parameters were measured by routine methods, followed by genotyping (TagMan® Genotyping Assays, PCR-restriction fragment length polymorphism analysis. Nearly 30% of CTD patients used statins and 10% of the control group. Results: Although there were no differences between alleles and genotypes prevalence between CTD vs control groups, interesting lipid-gene associations were noted in this study. A higher level of triglycerides (TAG and TAG/high-density lipoprotein (HDL ratios was observed in CTD patients compared to controls. Similar differences were noted in CTD and control groups without statin treatment. Atherogenic markers: the atherogenic index of plasma, TAG/HDL and low-density lipoprotein/HDL ratio were low in the analyzed groups. Of the six analyzed polymorphisms, the Pro12Pro or C14131C or Trp64Trp genotypes were related to higher TAG and TAG/HDL ratios in patients with CTD; however, the highest TAG values were observed in the presence of the Trp64Trp genotype. Conclusion: Lipid disorders were present in both groups independent of statin treatment (mixed dyslipidemia and

  2. X-ray and CT signs of connective tissue dysplasia in patients with primarily diagnosed infiltrative pulmonary tuberculosis

    International Nuclear Information System (INIS)

    Sukhanova, L.A.; Sharmazanova, O.P.

    2009-01-01

    The x-ray signs of connective tissue systemic dysplasia (CTSD) in patients with primarily diagnosed pulmonary tuberculosis was investigated. Fifty-four patients (28 med and 26 women aged 18-70) with primarily diagnosed infiltrative pulmonary tuberculosis underwent x-ray study. In patients with infiltration pulmonary tuberculosis CTSD in the lungs manifests by their diminishing, deformity of the lung pattern, high position of the diaphragm cupola, mediastinum shift to the side of the pathology, which is better seen on CT. The degree of CTSD x-ray signs in the lungs depends on the number of phenotypical signs that is the degree of the disease manifestation. CT allows more accurate determining of the signs of connective tissue dysplasia in which tuberculosis develops

  3. Recommendations for obstetric management and principles of cooperation between rheumatologists and obstetricians in systemic connective tissue disease patients

    Directory of Open Access Journals (Sweden)

    Justyna Teliga-Czajkowska

    2014-03-01

    Full Text Available Systemic connective tissue diseases, notably rheumatoid arthritis and systemic lupus erythematosus, frequently affect women of reproductive age. The significant impact of the diseases on the course of pregnancy is well established, and vice versa – the course of systemic connective tissue diseases may be affected by pregnancy. The risk of developing serious pregnancy complications and obstetric failures is markedly higher in the mentioned disease group. The foundation of obstetric success, i.e. giving birth to a healthy child and pregnancy having no effect on the course of a given autoimmune disease, is cooperation between rheumatologists and obstetricians so as to plan procreation at an optimal period and provide accurate pregnancy monitoring. The article delineates recommendations relating to contraception management, obstetric supervision and fetus wellbeing monitoring, from the point of view of the obstetrician.

  4. [Study of collagen and elastic fibers of connective tissue in patients with and without primary inguinal hernia].

    Science.gov (United States)

    Bórquez, Pablo; Garrido, Luis; Manterola, Carlos; Peña, Patricio; Schlageter, Carol; Orellana, Juan José; Ulloa, Hugo; Peña, Juan Luis

    2003-11-01

    There are few studies looking for collagen matrix defects in patients with inguinal bernia. To study the skin connective tissue in patients with and without inguinal bernia. Skin from the surgical wound was obtained from 23 patients with and 23 patients without inguinal bernia. The samples were processed for conventional light microscopy. Collagen fibers were stained with Van Giesson and elastic fibers with Weigert stain. Patients without hernia had compact collagen tracts homogeneously distributed towards the deep dermis. In contrast, patients with hernia had zones in the dermis with thinner and disaggregated collagen tracts. Connective tissue had a lax aspect in these patients. Collagen fiber density was 52% lower in patients with hernia, compared to subjects without hernia. No differences in elastic fiber density or distribution was observed between groups. Patients with inguinal bernia have alterations in skin collagen fiber quality and density.

  5. The risk of sudden death in sport in patients with signs of connective tissue dysplasia (literature review

    Directory of Open Access Journals (Sweden)

    Nekhanevych O.B.

    2013-03-01

    Full Text Available Literature review indicates that, despite the disclosure of a number of causes and mechanisms of sudden death in people performing physical activities, this issue remains relevant today. The main cause of sudden death in sport is pathological conditions and heart diseases. Par¬ticular risk group during follow-up over persons involved in physical activity are those with the presence of small anomalies; this may be a ma¬nifestation of connective tissue dysplasia. With all the variety of affected organs and systems in patients with connective tissue dysplasia, cardio¬vascular disorders are the leading pathology determining the quality and pro¬gnosis of life.

  6. Tissue-resident Sca1+ PDGFRα+ mesenchymal progenitors are the cellular source of fibrofatty infiltration in arrhythmogenic cardiomyopathy [v1; ref status: indexed, http://f1000r.es/17s

    Directory of Open Access Journals (Sweden)

    Ben Paylor

    2013-06-01

    Full Text Available Arrhythmogenic cardiomyopathy (AC is a disease of the heart involving myocardial dystrophy leading to fibrofatty scarring of the myocardium and is associated with an increased risk of both ventricular arrhythmias and sudden cardiac death. It often affects the right ventricle but may also involve the left. Although there has been significant progress in understanding the role of underlying desmosomal genetic defects in AC, there is still a lack of data regarding the cellular processes involved in its progression. The development of cardiac fibrofatty scarring is known to be a principal pathological process associated with ventricular arrhythmias, and it is vital that we elucidate the role of various cell populations involved in the disease if targeted therapeutics are to be developed. The known role of mesenchymal progenitor cells in the reparative process of both the heart and skeletal muscle has provided inspiration for the identification of the cellular basis of fibrofatty infiltration in AC. Here we hypothesize that reparative processes triggered by myocardial degeneration lead to the differentiation of tissue-resident Sca1+ PDGFRα+ mesenchymal progenitors into adipocytes and fibroblasts, which compose the fibrofatty lesions characteristic of AC.

  7. An Evaluation of Collagen Metabolism in Non Human Primates Associated with the Bion 11 Space Program-Markers of Urinary Collagen Turnover and Muscle Connective Tissue

    Science.gov (United States)

    Vailas, Arthur C.; Martinez, Daniel A.

    1999-01-01

    Patients exhibiting changes in connective tissue and bone metabolism also show changes in urinary by-products of tissue metabolism. Furthermore, the changes in urinary connective tissue and bone metabolites precede alterations at the tissue macromolecular level. Astronauts and Cosmonauts have also shown suggestive increases in urinary by-products of mineralized and non-mineralized tissue degradation. Thus, the idea of assessing connective tissue and bone response in spaceflight monkeys by measurement of biomarkers in urine has merit. Other investigations of bone and connective histology, cytology and chemistry in the Bion 11 monkeys will allow for further validation of the relationship of urinary biomarkers and tissue response. In future flights the non-invasive procedure of urinary analysis may be useful in early detection of changes in these tissues. The purpose of this grant investigation was to evaluate mineralized and non-mineralized connective tissue responses of non-human primates to microgravity by the non-invasive analysis of urinary biomarkers. Secondly, we also wanted to assess muscle connective tissue adaptive changes in three weight-bearing skeletal muscles: the soleus, media] gastrocnemius and tibialis anterior by obtaining pre-flight and post-flight small biopsy specimens in collaboration with Dr. V. Reggie Edgerton's laboratory at the University of California at Los Angeles.

  8. Association of HLA-DRB1 alleles with susceptibility to mixed connective tissue disease in Polish patients.

    Science.gov (United States)

    Paradowska-Gorycka, A; Stypińska, B; Olesińska, M; Felis-Giemza, A; Mańczak, M; Czuszynska, Z; Zdrojewski, Z; Wojciechowicz, J; Jurkowska, M

    2016-01-01

    Mixed connective tissue disease (MCTD) is a systemic autoimmune disease, originally defined as a connective tissue inflammatory syndrome with overlapping features of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), polymyositis/dermatomyositis (PM/DM) and systemic sclerosis (SSc), characterized by the presence of antibodies against components of the U1 small nuclear ribonucleoprotein (U1snRNP). The aim of the study was to assess the frequency of (high-resolution-typed) DRB1 alleles in a cohort of Polish patients with MCTD (n = 103). Identification of the variants potentially associated with risk and protection was carried out by comparison with the DKMS Polish Bone Marrow Donor Registry (41306 alleles). DRB1*15:01 (odds ratio (OR): 6.06; 95% confidence interval (CI) 4.55-8.06), DRB1*04 (OR: 3.69; 95% CI 2.69-5.01) and *09:01 (OR: 8.12; 95% CI 2.15-21.75) were identified as risk alleles for MCTD, while HLA-DRB1*07:01 allele was found to be protective (OR: 0.50; 95% CI 0.28-0.83). The carrier frequency of the DRB1*01 was higher in MCTD patients compared with controls, although the differences were not statistically significant. Our results confirm the modulating influence of HLA-DRB1 genotypes on development of connective tissue diseases such as MCTD. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Tissue types (image)

    Science.gov (United States)

    There are 4 basic types of tissue: connective tissue, epithelial tissue, muscle tissue, and nervous tissue. Connective tissue ... and binds them together (bone, blood, and lymph tissues). Epithelial tissue provides a covering (skin, the linings of ...

  10. Markers of Inflammation and Fibrosis in the Orbital Fat/Connective Tissue of Patients with Graves’ Orbitopathy: Clinical Implications

    Directory of Open Access Journals (Sweden)

    Przemyslaw Pawlowski

    2014-01-01

    Full Text Available Purpose. To assess FGF-β, TGF-β, and COX2 expression and immunocompetent cells in the orbital tissue of patients with severe and mild Graves’ orbitopathy. Patients and Methods. Orbital tissue was taken from 27 patients with GO: (1 severe GO (n=18, the mean clinical activity score (CAS being 8.5 (SD 2.5; and (2 mild GO (n=9, the mean CAS being 2.2 (SD 0.8, and from 10 individuals undergoing blepharoplasty. The expression of CD4+, CD8+, CD20+, and CD68 and FGF-β, TGF-β, and COX2 in the orbital tissue was evaluated by immunohistochemical methods. Results. We demonstrated predominant CD4+ T cells in severe GO. CD68 expression was observed in the fibrous connective area of mild GO and was robust in severe GO, while the prominent TGF-β expression was seen in all GO. Increased FGF-β expression was observed in the fibroblasts and adipocytes of severe GO. No expression of COX2 was found in patients with GO. Conclusions. Macrophages and CD4 T lymphocytes are both engaged in the active/severe and long stage of inflammation in the orbital tissue. FGF-β and TGF-β expression may contribute to tissue remodeling, fibrosis, and perpetuation of inflammation in the orbital tissue of GO especially in severe GO.

  11. In Vivo Deletion of the Cebpa +37 kb Enhancer Markedly Reduces Cebpa mRNA in Myeloid Progenitors but Not in Non-Hematopoietic Tissues to Impair Granulopoiesis

    Science.gov (United States)

    Guo, Hong; Cooper, Stacy; Friedman, Alan D.

    2016-01-01

    The murine Cebpa gene contains a +37 kb, evolutionarily conserved 440 bp enhancer that directs high-level expression to myeloid progenitors in transgenic mice. The enhancer is bound and activated by Runx1, Scl, GATA2, C/EBPα, c-Myb, Pu.1, and additional Ets factors in myeloid cells. CRISPR/Cas9-mediated replacement of the wild-type enhancer with a variant mutant in its seven Ets sites leads to 20-fold reduction of Cebpa mRNA in the 32Dcl3 myeloid cell line. To determine the effect of deleting the enhancer in vivo, we now characterize C57BL/6 mice in which loxP sites flank a 688 bp DNA segment containing the enhancer. CMV-Cre mediated germline deletion resulted in diminution of the expected number of viable Enh(f/f);CMV-Cre offspring, with 28-fold reduction in marrow Cebpa mRNA but normal levels in liver, lung, adipose, intestine, muscle, and kidney. Cre-transduction of lineage-negative marrow cells in vitro reduced Cebpa mRNA 12-fold, with impairment of granulocytic maturation, morphologic blast accumulation, and IL-3 dependent myeloid colony replating for >12 generations. Exposure of Enh(f/f);Mx1-Cre mice to pIpC led to 14-fold reduction of Cebpa mRNA in GMP or CMP, 30-fold reduction in LSK, and deletion and confirmed marrow-intrinsic impairment of granulopoiesis and B cell generation with LSK and monocyte lineage expansion. These findings demonstrate a critical role for the +37 kb Cebpa enhancer for hematopoietic-specific Cebpa expression, with enhancer deletion leading to impaired myelopoiesis and potentially preleukemic progenitor expansion. PMID:26937964

  12. Therapeutic efficacy of connective tissue autotransplants with periosteum and platelet rich plasma in the management of gingival recession

    Directory of Open Access Journals (Sweden)

    Jovičić Bojan

    2013-01-01

    Full Text Available Background/Aim. Gingival recession progression in clinical practaice has influenced the development of various surgical procedures and techniques for solving esthetic imperfections and subjective difficulties coused by gingival recession. The aim of this study was to verify efficacy of surgical procedures and to compare both of surgical procedures through the keratinized tissue width. Methods. The study included 20 teeth with gingival recesion, Müller class I and II. Ten teeth with gingival recession were treated with connective tissue autotransplants with periosteum in combination with coronary guided surgical flap (CTG group. On the contralateral side 10 teeth with gingival recession were treated with the same surgical procedures but in combination with platelet-rich plasma (CTGPRP group. We measured the keratinized tissue width. For statistical significance we used the Student's t-test. Results. The study reveled a statistical significance in reducing vertical deepress of recession by both used treatments. Root deepness in CTG and CTG-PRP group was 90% and 93.5%, respectively. With both surgical techniques we achieved larger zone of keratinized gingiva but with a wide zone of keratinized tissue in CTG - the PRP group. Conclusion. The concept regeneration technique with PRP and with the stimulating influence of platele activated growth factors results in the regeneration of deep periodontal tissue as an important prerequisite for the successful treatment of gingival recession.

  13. Development and evaluation of a connective tissue phantom model for subsurface visualization of cancers requiring wide local excision

    Science.gov (United States)

    Samkoe, Kimberley S.; Bates, Brent D.; Tselepidakis, Niki N.; DSouza, Alisha V.; Gunn, Jason R.; Ramkumar, Dipak B.; Paulsen, Keith D.; Pogue, Brian W.; Henderson, Eric R.

    2017-12-01

    Wide local excision (WLE) of tumors with negative margins remains a challenge because surgeons cannot directly visualize the mass. Fluorescence-guided surgery (FGS) may improve surgical accuracy; however, conventional methods with direct surface tumor visualization are not immediately applicable, and properties of tissues surrounding the cancer must be considered. We developed a phantom model for sarcoma resection with the near-infrared fluorophore IRDye 800CW and used it to iteratively define the properties of connective tissues that typically surround sarcoma tumors. We then tested the ability of a blinded surgeon to resect fluorescent tumor-simulating inclusions with ˜1-cm margins using predetermined target fluorescence intensities and a Solaris open-air fluorescence imaging system. In connective tissue-simulating phantoms, fluorescence intensity decreased with increasing blood concentration and increased with increasing intralipid concentrations. Fluorescent inclusions could be resolved at ≥1-cm depth in all inclusion concentrations and sizes tested. When inclusion depth was held constant, fluorescence intensity decreased with decreasing volume. Using targeted fluorescence intensities, a blinded surgeon was able to successfully excise inclusions with ˜1-cm margins from fat- and muscle-simulating phantoms with inclusion-to-background contrast ratios as low as 2∶1. Indirect, subsurface FGS is a promising tool for surgical resection of cancers requiring WLE.

  14. Clinical comparison of guided tissue regeneration, with collagen membrane and bone graft, versus connective tissue graft in the treatment of gingival recessions

    Directory of Open Access Journals (Sweden)

    Haghighati F

    2006-06-01

    Full Text Available Background and Aim: Increasing patient demands for esthetic, put the root coverage procedures in particular attention. Periodontal regeneration with GTR based root coverage methods is the most common treatment used. The purpose of this study was to compare guided tissue regeneration (GTR with collagen membrane and a bone graft, with sub-epithelial connective tissue graft (SCTG, in treatment of gingival recession. Materials and Methods: In this randomized clinical trial study, eleven healthy patients with no systemic diseases who had miller’s class I or II recession defects (gingival recession  2mm were treated with SCTG or GTR using a collagen membrane and a bone graft. Clinical measurements were obtained at baseline and 6 months after surgery. These clinical measurements included recession depth (RD, recession width (RW, probing depth (PD, and clinical attachment level (CAL. Data were analyzed using independent t test with p<0.05 as the limit of significance. Results: Both treatment methods resulted in a statistically significant reduction of recession depth (SCTG=2.3mm, GTR=2.1mm; P<0.0001. CAL gain after 6 months was also improved in both groups (SCG= 2.5mm, GTR=2.1mm, compared to baseline (P<0.0001. No statistical differences were observed in RD, RW, CAL between test and control groups. Root coverage was similar in both methods (SCTG= 74.2%, GTR= 62.6%, P=0.87. Conclusion: Based on the results of this study, the two techniques are clinically comparable. Therefore the use of collagen membrane and a bovine derived xenograft may alleviate the need for connective tissue graft.

  15. Origins of the sympathetic innervation to the nasal-associated lymphoid tissue (NALT): an anatomical substrate for a neuroimmune connection.

    Science.gov (United States)

    Marafetti, Lucas E; Romeo, Horacio E

    2014-11-15

    The participation of sympathetic nerve fibers in the innervation of the nasal-associated lymphoid tissues (NALT) was investigated in hamsters. Vesicular monoamine transporter 2 (VMAT2), an established sympathetic marker, is expressed in all neurons of superior cervical ganglia (SCG). In addition, VMAT2 -immunoreactive nerve fibers were localized in the NALT as well as in adjacent anatomical structures of the upper respiratory tract. Unilateral surgical ablation of the SCG abolished VMAT2 innervation patterns ipsilaterally while the contra lateral side is unaffected. These results provide the anatomical substrate for a neuroimmune connection in the NALT. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Comparative study of the possibility of interdental papilla reconstruction using connective tissue graft with and without Emdogain

    Directory of Open Access Journals (Sweden)

    Soleymani Shayesteh Y.

    2008-04-01

    Full Text Available Background and Aim: Improving esthetics is a major goal in periodontal treatments and specially reconstruction of dental papilla is of great importance. Different techniques have been developed, however the results are not completely predictable. The aim of the present study was to compare the possibility of papilla reconstruction using connective tissue graft with and without Emdogain.Materials and Methods: In this clinical trial, 40 class II lost interdental papilla (Nordland- Tarnow classification in 18 patients (4 male and 14 female were studied. Samples were randomly devided into two groups. Case group was treated by connective tissue graft and emdogain (Straumann-USA and controls were treated using connective tissue graft only. Periodontal parameters including papilla height (PH, periodontal pocket depth (PPD and clinical attachment level (CAL were measured before surgery, and 3 and 6 months after treatment. At the tenth days and 1 month after treatment only the papilla height was measured. Repeated measures analysis was used for data analysis with p<0.05 as the level of significance.Results: In the control group the mean papilla height changed from 3.38 0.89 to 2.85 0.93 on the 3rd month and 2.90 0.95 on the 6th month. The mean PPD changed from 2.8  0.68 to 2.55 0.70 on the 3rd month and 3.06 1.25 on the 6th month. The mean CAL changed from 3.88 1.29 to 3.79 1.25 on the 3rd month and 4.11 1.44 on the 6th month. In test group the mean papilla height changed from 2.98 0.91 to 2.45 1.55 on the 3rd month and 2.55 1.48 on the 6th month. The mean PPD changed from 2.75 1.49 to 2.63 1.38 on the 3rd month and 2.88 1.39 on the 6th month. The mean CAL changed from 3.75 1.24 to 4.01 1.45 on the 3rd month and 4.28 1.63 on the 6th month. These differences were not significant between the studied groups (P>0.05.Conclusion: Based on the results of this study, use of connective tissue with or without emdogain is not effective in interdental papilla

  17. Treatment of a cracked tooth with a resin-ionomer restoration and a connective tissue graft: a case report.

    Science.gov (United States)

    Harris, R J

    2000-12-01

    Treatment of a cracked tooth can be difficult and unpredictable. Quite often, the most predictable treatment possible is simply extraction. This is a case report of the treatment of a cracked tooth with a resin-ionomer restoration and a connective tissue with partial-thickness double pedicle graft. The crack was detected during a routine root coverage procedure using this type of graft. A resin-ionomer was used to repair the crack. Then, the root coverage procedure was completed. Complete root coverage was obtained, including the portion of the root that was repaired. The results remained stable and the tooth treated remained asymptomatic. Clinically, the treatment was a success.

  18. Effect of administration of oral contraceptives in vivo on collagen synthesis in tendon and muscle connective tissue in young women

    DEFF Research Database (Denmark)

    Hansen, M; Miller, B F; Holm, Lars

    2009-01-01

    Women are at greater risk than men for certain kinds of diseases and injuries, which may at least partly be caused by sex hormonal differences. We aimed to test the influence of estradiol in vivo on collagen synthesis in tendon, bone, and muscle. Two groups of young, healthy women similar in age...... concentrations of estradiol and progesterone (control, n = 12). Subjects performed 1 h of one-legged kicking exercise. The next day collagen fractional synthesis rates (FSR) in tendon and muscle connective tissue were measured after a flooding dose of [(13)C]proline followed by biopsies from the patellar tendon...

  19. Basic components of connective tissues and extracellular matrix: elastin, fibrillin, fibulins, fibrinogen, fibronectin, laminin, tenascins and thrombospondins.

    Science.gov (United States)

    Halper, Jaroslava; Kjaer, Michael

    2014-01-01

    Collagens are the most abundant components of the extracellular matrix and many types of soft tissues. Elastin is another major component of certain soft tissues, such as arterial walls and ligaments. Many other molecules, though lower in quantity, function as essential components of the extracellular matrix in soft tissues. Some of these are reviewed in this chapter. Besides their basic structure, biochemistry and physiology, their roles in disorders of soft tissues are discussed only briefly as most chapters in this volume deal with relevant individual compounds. Fibronectin with its muldomain structure plays a role of "master organizer" in matrix assembly as it forms a bridge between cell surface receptors, e.g., integrins, and compounds such collagen, proteoglycans and other focal adhesion molecules. It also plays an essential role in the assembly of fibrillin-1 into a structured network. Laminins contribute to the structure of the extracellular matrix (ECM) and modulate cellular functions such as adhesion, differentiation, migration, stability of phenotype, and resistance towards apoptosis. Though the primary role of fibrinogen is in clot formation, after conversion to fibrin by thrombin, it also binds to a variety of compounds, particularly to various growth factors, and as such fibrinogen is a player in cardiovascular and extracellular matrix physiology. Elastin, an insoluble polymer of the monomeric soluble precursor tropoelastin, is the main component of elastic fibers in matrix tissue where it provides elastic recoil and resilience to a variety of connective tissues, e.g., aorta and ligaments. Elastic fibers regulate activity of TGFβs through their association with fibrillin microfibrils. Elastin also plays a role in cell adhesion, cell migration, and has the ability to participate in cell signaling. Mutations in the elastin gene lead to cutis laxa. Fibrillins represent the predominant core of the microfibrils in elastic as well as non

  20. Collagen XII Contributes to Epicardial and Connective Tissues in the Zebrafish Heart during Ontogenesis and Regeneration.

    Directory of Open Access Journals (Sweden)

    Jan Marro

    Full Text Available Zebrafish heart regeneration depends on cardiac cell proliferation, epicardium activation and transient reparative tissue deposition. The contribution and the regulation of specific collagen types during the regenerative process, however, remain poorly characterized. Here, we identified that the non-fibrillar type XII collagen, which serves as a matrix-bridging component, is expressed in the epicardium of the zebrafish heart, and is boosted after cryoinjury-induced ventricular damage. During heart regeneration, an intense deposition of Collagen XII covers the outer epicardial cap and the interstitial reparative tissue. Analysis of the activated epicardium and fibroblast markers revealed a heterogeneous cellular origin of Collagen XII. Interestingly, this matrix-bridging collagen co-localized with fibrillar type I collagen and several glycoproteins in the post-injury zone, suggesting its role in tissue cohesion. Using SB431542, a selective inhibitor of the TGF-β receptor, we showed that while the inhibitor treatment did not affect the expression of collagen 12 and collagen 1a2 in the epicardium, it completely suppressed the induction of both genes in the fibrotic tissue. This suggests that distinct mechanisms might regulate collagen expression in the outer heart layer and the inner injury zone. On the basis of this study, we postulate that the TGF-β signaling pathway induces and coordinates formation of a transient collagenous network that comprises fibril-forming Collagen I and fiber-associated Collagen XII, both of which contribute to the reparative matrix of the regenerating zebrafish heart.

  1. In vivo and ex vivo methods of growing a liver bud through tissue connection.

    Science.gov (United States)

    Yanagi, Yusuke; Nakayama, Koichi; Taguchi, Tomoaki; Enosawa, Shin; Tamura, Tadashi; Yoshimaru, Koichiro; Matsuura, Toshiharu; Hayashida, Makoto; Kohashi, Kenichi; Oda, Yoshinao; Yamaza, Takayoshi; Kobayashi, Eiji

    2017-10-26

    Cell-based therapy has been proposed as an alternative to orthotopic liver transplantation. The novel transplantation of an in vitro-generated liver bud might have therapeutic potential. In vivo and ex vivo methods for growing a liver bud are essential for paving the way for the clinical translation of liver bud transplantation. We herein report a novel transplantation method for liver buds that are grown in vivo involving orthotopic transplantation on the transected parenchyma of the liver, which showed long engraftment and marked growth in comparison to heterotopic transplantation. Furthermore, this study demonstrates a method for rapidly fabricating scalable liver-like tissue by fusing hundreds of liver bud-like spheroids using a 3D bioprinter. Its system to fix the shape of the 3D tissue with the needle-array system enabled the fabrication of elaborate geometry and the immediate execution of culture circulation after 3D printing-thereby avoiding an ischemic environment ex vivo. The ex vivo-fabricated human liver-like tissue exhibited self-tissue organization ex vivo and engraftment on the liver of nude rats. These achievements conclusively show both in vivo and ex vivo methods for growing in vitro-generated liver buds. These methods provide a new approach for in vitro-generated liver organoids transplantation.

  2. Modelling of Soft Connective Tissues to Investigate Female Pelvic Floor Dysfunctions

    Directory of Open Access Journals (Sweden)

    Aroj Bhattarai

    2018-01-01

    Full Text Available After menopause, decreased levels of estrogen and progesterone remodel the collagen of the soft tissues thereby reducing their stiffness. Stress urinary incontinence is associated with involuntary urine leakage due to pathological movement of the pelvic organs resulting from lax suspension system, fasciae, and ligaments. This study compares the changes in the orientation and position of the female pelvic organs due to weakened fasciae, ligaments, and their combined laxity. A mixture theory weighted by respective volume fraction of elastin-collagen fibre compound (5%, adipose tissue (85%, and smooth muscle (5% is adopted to characterize the mechanical behaviour of the fascia. The load carrying response (other than the functional response to the pelvic organs of each fascia component, pelvic organs, muscles, and ligaments are assumed to be isotropic, hyperelastic, and incompressible. Finite element simulations are conducted during Valsalva manoeuvre with weakened tissues modelled by reduced tissue stiffness. A significant dislocation of the urethrovesical junction is observed due to weakness of the fascia (13.89 mm compared to the ligaments (5.47 mm. The dynamics of the pelvic floor observed in this study during Valsalva manoeuvre is associated with urethral-bladder hypermobility, greater levator plate angulation, and positive Q-tip test which are observed in incontinent females.

  3. Crestal Bone Stability around Implants with Horizontally Matching Connection after Soft Tissue Thickening: A Prospective Clinical Trial.

    Science.gov (United States)

    Linkevicius, Tomas; Puisys, Algirdas; Linkeviciene, Laura; Peciuliene, Vytaute; Schlee, Markus

    2015-06-01

    It has been shown that thin mucosal tissues may be an important factor in crestal bone loss etiology. Thus, it is possible that mucosal tissue thickening with allogenic membrane might reduce crestal bone loss. The purpose of this study was to evaluate how implants with traditional connection maintain crestal bone level after soft tissue thickening with allogenic membrane. One hundred three patients received 103 internal hex implants of 4.6 mm diameter with regular connection. According to gingiva thickness, patients were assigned into A (thin tissues, n = 34), B (thin, thickened with allogenic membrane, n = 35), and C group (thick tissues, n = 34). Groups A and C had one-stage approach, and in group B, implants were placed in two stages. Radiographic examination was performed after implant placement, 2 months after healing, after restoration, and after 1-year follow-up. Crestal bone loss was calculated medially and distally. Significance was set to 0.05. After 1-year follow-up, implants in group A had 1.65 ± 0.08-mm bone loss mesially and 1.81 ± 0.06 mm distally. Group B had 0.31 ± 0.05 mm mesially and 0.34 ± 0.05 mm distally. C group implants experienced bone loss of 0.44 ± 0.06 mm mesially and 0.47 ± 0.07 mm distally. Differences between A and B, and A and C were significant (p = .000) both mesially and distally, whereas differences between B and C were not significant mesially (p = .166) and distally (p = .255). It can be concluded that thin mucosal tissues may cause early crestal bone loss, but their thickening with allogenic membrane may significantly reduce bone resorption. Implants in naturally thick soft tissues experienced minor bone remodeling. © 2013 Wiley Periodicals, Inc.

  4. Clinicopathological evaluation of 164 dental follicles and dentigerous cysts with emphasis on the presence of odontogenic epithelium in the connective tissue. The hypothesis of "focal ameloblastoma"

    NARCIS (Netherlands)

    Meleti, M.; van der Waal, I.

    2013-01-01

    Objectives: Some ameloblastomas presumably originate from odontogenic epithelium within the connective tissue of dental follicles and dentigerous cysts. Therefore, it would seem reasonable to discuss as whether odontogenic epithelium proliferations, frankly displaying ameloblastomatous features

  5. Unusual Glycosaminoglycans from a Deep Sea Hydrothermal Bacterium Improve Fibrillar Collagen Structuring and Fibroblast Activities in Engineered Connective Tissues

    Science.gov (United States)

    Senni, Karim; Gueniche, Farida; Changotade, Sylvie; Septier, Dominique; Sinquin, Corinne; Ratiskol, Jacqueline; Lutomski, Didier; Godeau, Gaston; Guezennec, Jean; Colliec-Jouault, Sylvia

    2013-01-01

    Biopolymers produced by marine organisms can offer useful tools for regenerative medicine. Particularly, HE800 exopolysaccharide (HE800 EPS) secreted by a deep-sea hydrothermal bacterium displays an interesting glycosaminoglycan-like feature resembling hyaluronan. Previous studies demonstrated its effectiveness to enhance in vivo bone regeneration and to support osteoblastic cell metabolism in culture. Thus, in order to assess the usefulness of this high-molecular weight polymer in tissue engineering and tissue repair, in vitro reconstructed connective tissues containing HE800 EPS were performed. We showed that this polysaccharide promotes both collagen structuring and extracellular matrix settle by dermal fibroblasts. Furthermore, from the native HE800 EPS, a low-molecular weight sulfated derivative (HE800 DROS) displaying chemical analogy with heparan-sulfate, was designed. Thus, it was demonstrated that HE800 DROS mimics some properties of heparan-sulfate, such as promotion of fibroblast proliferation and inhibition of matrix metalloproteinase (MMP) secretion. Therefore, we suggest that the HE800EPS family can be considered as an innovative biotechnological source of glycosaminoglycan-like compounds useful to design biomaterials and drugs for tissue engineering and repair. PMID:23612369

  6. Unusual Glycosaminoglycans from a Deep Sea Hydrothermal Bacterium Improve Fibrillar Collagen Structuring and Fibroblast Activities in Engineered Connective Tissues

    Directory of Open Access Journals (Sweden)

    Jean Guezennec

    2013-04-01

    Full Text Available Biopolymers produced by marine organisms can offer useful tools for regenerative medicine. Particularly, HE800 exopolysaccharide (HE800 EPS secreted by a deep-sea hydrothermal bacterium displays an interesting glycosaminoglycan-like feature resembling hyaluronan. Previous studies demonstrated its effectiveness to enhance in vivo bone regeneration and to support osteoblastic cell metabolism in culture. Thus, in order to assess the usefulness of this high-molecular weight polymer in tissue engineering and tissue repair, in vitro reconstructed connective tissues containing HE800 EPS were performed. We showed that this polysaccharide promotes both collagen structuring and extracellular matrix settle by dermal fibroblasts. Furthermore, from the native HE800 EPS, a low-molecular weight sulfated derivative (HE800 DROS displaying chemical analogy with heparan-sulfate, was designed. Thus, it was demonstrated that HE800 DROS mimics some properties of heparan-sulfate, such as promotion of fibroblast proliferation and inhibition of matrix metalloproteinase (MMP secretion. Therefore, we suggest that the HE800EPS family can be considered as an innovative biotechnological source of glycosaminoglycan-like compounds useful to design biomaterials and drugs for tissue engineering and repair.

  7. Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis.

    Science.gov (United States)

    Yang, Zhizhou; Sun, Zhaorui; Liu, Hongmei; Ren, Yi; Shao, Danbing; Zhang, Wei; Lin, Jinfeng; Wolfram, Joy; Wang, Feng; Nie, Shinan

    2015-07-01

    It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson's trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ-treated group. Similarly, PQ treatment of MRC-5 human lung fibroblast cells caused an increase in CTGF in a dose-dependent manner. Furthermore, the addition of CTGF to MRC-5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of α-smooth muscle actin (α-SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ-induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury.

  8. Non-marfan idiopathic medionecrosis (cystic medial necrosis) presenting with multiple visceral artery aneurysms and diffuse connective tissue fragility: Two brothers

    International Nuclear Information System (INIS)

    Kubota, Jun; Tsunemura, Mami; Amano, Shigeko; Tokizawa, Shigemi; Oowada, Susumu; Shinkai, Hiroko; Maehara, Yasunobu; Endo, Keigo

    1997-01-01

    Two brothers with multiple visceral artery aneurysms or dilatations and diffuse connective tissue fragility who did not have clinical features of Marfan syndrome are reported. One presented with retroperitoneal hemorrhage during angiography, and idiopathic medionecrosis was proved by resection of the aneurysms. These cases belong to the heterogeneous group of Marfan syndrome. The angiographical features (multiple dilation of visceral arteries) suggests fragility of connective tissue and is predictive of hazards during and after a catheterization and operation

  9. /sup 239/PuO/sub 2/ aerosol inhalation with emphasis on pulmonary connective tissue modifications

    Energy Technology Data Exchange (ETDEWEB)

    Metivier, H.; Masse, R.; Nobil' e, D.; Lafuma, J.

    1975-09-01

    Inhalation studies were undertaken in which plutonium dioxide (/sup 239/PuO/sub 2/) was administered to either unanesthetized Wistar rats or anaesthetized baboons. In both groups of animals some deaths occurred from acute lung damage resulting from cell necrosis particularly to vascular tissue followed by alveolar oedema. At later stages, marked interstitial pneumonitis and interstitial fibrosis occurred and deaths resulted from respiratory insufficiency preceded by high arterial blood pCO/sub 2/ and low pO/sub 2/. In rats as many as 50% of the animals finally developed lung neoplasms but only two such tumors were found in baboons. Attempts were made to correlate biochemical parameters with observed tissue damage and animal mortality.

  10. Training principles for fascial connective tissues: scientific foundation and suggested practical applications.

    Science.gov (United States)

    Schleip, Robert; Müller, Divo Gitta

    2013-01-01

    Conventional sports training emphasizes adequate training of muscle fibres, of cardiovascular conditioning and/or neuromuscular coordination. Most sports-associated overload injuries however occur within elements of the body wide fascial net, which are then loaded beyond their prepared capacity. This tensional network of fibrous tissues includes dense sheets such as muscle envelopes, aponeuroses, as well as specific local adaptations, such as ligaments or tendons. Fibroblasts continually but slowly adapt the morphology of these tissues to repeatedly applied challenging loading stimulations. Principles of a fascia oriented training approach are introduced. These include utilization of elastic recoil, preparatory counter movement, slow and dynamic stretching, as well as rehydration practices and proprioceptive refinement. Such training should be practiced once or twice a week in order to yield in a more resilient fascial body suit within a time frame of 6-24 months. Some practical examples of fascia oriented exercises are presented. Copyright © 2012 Elsevier Ltd. All rights reserved.

  11. Collagen XII Contributes to Epicardial and Connective Tissues in the Zebrafish Heart during Ontogenesis and Regeneration

    OpenAIRE

    Marro, Jan; Pfefferli, Catherine; de Preux Charles, Anne-Sophie; Bise, Thomas; Ja?wi?ska, Anna

    2016-01-01

    Zebrafish heart regeneration depends on cardiac cell proliferation, epicardium activation and transient reparative tissue deposition. The contribution and the regulation of specific collagen types during the regenerative process, however, remain poorly characterized. Here, we identified that the non-fibrillar type XII collagen, which serves as a matrix-bridging component, is expressed in the epicardium of the zebrafish heart, and is boosted after cryoinjury-induced ventricular damage. Du...

  12. Hormonal modulation of connective tissue homeostasis and sex differences in risk for osteoarthritis of the knee

    Directory of Open Access Journals (Sweden)

    Boyan Barbara D

    2013-02-01

    Full Text Available Abstract Young female athletes experience a higher incidence of ligament injuries than their male counterparts, females experience a higher incidence of joint hypermobility syndrome (a risk factor for osteoarthritis development, and post-menopausal females experience a higher prevalence of osteoarthritis than age-matched males. These observations indicate that fluctuating sex hormone levels in young females and loss of ovarian sex hormone production due to menopause likely contribute to observed sex differences in knee joint function and risk for loss of function. In studies of osteoarthritis, however, there is a general lack of appreciation for the heterogeneity of hormonal control in both women and men. Progress in this field is limited by the relatively few preclinical osteoarthritis models, and that most of the work with established models uses only male animals. To elucidate sex differences in osteoarthritis, it is important to examine sex hormone mechanisms in cells from knee tissues and the sexual dimorphism in the role of inflammation at the cell, tissue, and organ levels. There is a need to determine if the risk for loss of knee function and integrity in females is restricted to only the knee or if sex-specific changes in other tissues play a role. This paper discusses these gaps in knowledge and suggests remedies.

  13. Effect of Th17 and Treg Axis Disorder on Outcomes of Pulmonary Arterial Hypertension in Connective Tissue Diseases

    Directory of Open Access Journals (Sweden)

    Saren Gaowa

    2014-01-01

    Full Text Available This prospective cohort study is to verify the hypothesis that the balance of Th17 and Treg cells frequencies in the peripheral circulation is disturbed in patients with varying degrees of connective tissue diseases-associated pulmonary arterial hypertension (CTD-aPAH and to prove the influence of Th17/Treg imbalance on prognosis. We detected the frequencies and absolute counts of Th17 and Treg cells and related serum cytokines secretion and expressions of key transcription factors in 117 patients with connective tissue diseases (CTD, 53 patients with CTD-aPAH, and 48 healthy volunteers. Moreover, the median value according to levels of Th17/Treg ratios in patients with CTD-aPAH was chosen as basis of group division for survival analysis. CTD-aPAH patients revealed significant increase in peripheral Th17 cells, Th17-related cytokines, and ROR γt mRNA levels. They also presented a significant decrease in Treg cells, Treg-related cytokines, and Foxp3 mRNA levels as compared with CTD patients and healthy controls. More importantly, the Th17/Treg ratio was significantly related to the severity and prognosis of CTD-aPAH. This study indicated that the Th17/Treg axis disorder plays a critical role in CTD-aPAH. Furthermore, the dynamic balance between Th17 and Treg cells was likely to influence prognosis of patients with CTD-aPAH.

  14. Ehlers-Danlos Syndrome, Hypermobility Type: An Underdiagnosed Hereditary Connective Tissue Disorder with Mucocutaneous, Articular, and Systemic Manifestations

    Science.gov (United States)

    Castori, Marco

    2012-01-01

    Ehlers-Danlos syndrome, hypermobility type, constituting a phenotypic continuum with or, perhaps, corresponding to the joint hypermobility syndrome (JHS/EDS-HT), is likely the most common, though the least recognized, heritable connective tissue disorder. Known for decades as a hereditary condition with predominant rheumatologic manifestations, it is now emerging as a multisystemic disorder with widespread manifestations. Nevertheless, the practitioners' awareness of this condition is generally poor and most patients await years or, perhaps, decades before reaching the correct diagnosis. Among the various sites of disease manifestations, skin and mucosae represent a neglected organ where the dermatologist can easily spot diagnostic clues, which consistently integrate joint hypermobility and other orthopedic/neurologic manifestations at physical examination. In this paper, actual knowledge on JHS/EDS-HT is summarized in various sections. Particular attention has been posed on overlooked manifestations, including cutaneous, mucosal, and oropharyngeal features, and early diagnosis techniques, as a major point of interest for the practicing dermatologist. Actual research progresses on JH/EDS-HT envisage an unexpected link between heritable dysfunctions of the connective tissue and a wide range of functional somatic syndromes, most of them commonly diagnosed in the office of various specialists, comprising dermatologists. PMID:23227356

  15. Marginal bone and soft tissue behavior following platform switching abutment connection/disconnection--a dog model study.

    Science.gov (United States)

    Alves, Célia C; Muñoz, Fernando; Cantalapiedra, António; Ramos, Isabel; Neves, Manuel; Blanco, Juan

    2015-09-01

    The effect on the marginal peri-implant tissues following repeated platform switching abutment removal and subsequent reconnection was studied. Six adult female Beagle dogs were selected, and Pm3 and Pm4 teeth, both left and right sides, were extracted and the sites healed for 3 months. At this time, 24 bone level (BL) (Straumann, Basel, Switzerland) Ø 3.3/8 mm implants were placed, 2 in each side on Pm3 and Pm4 regions. In one side (control group), 12 bone level conical Ø 3.6 mm healing abutments and, on the other side (test group), 12 Narrow CrossFit (NC) multibase abutments (Straumann) , Basel, Switzerland) were connected at time of implant surgery. On test group, all prosthetic procedures were carried out direct to multibase abutment without disconnecting it, where in the control group, the multibase abutment was connected/disconnected five times (at 6/8/10/12/14 weeks) during prosthetic procedures. Twelve fixed metal bridges were delivered 14 weeks after implant placement. A cleaning/control appointment was scheduled 6 months after implant placement. The animals were sacrificed at 9 months of the study. Clinical parameters and peri-apical x-rays were registered in every visit. Histomorphometric analysis was carried out for the 24 implants. The distance from multibase abutment shoulder to the first bone implant contact (S-BIC) was defined as the primary histomorphometric parameter. Wilcoxon comparison paired test (n = 6) found no statistically significant differences (buccal P = 0.917; Lingual P = 0.463) between test and control groups both lingually and buccally for S-BIC distance. Only Pm3 buccal aBE-BC (distance from the apical end of the barrier epithelium to the first bone implant contact) (P = 0.046) parameter presented statistically significant differences between test and control groups. Control group presented 0.57 mm more recession than test group, being this difference statistically significant between the two groups (P < 0.001). It can be conclude

  16. Clinical Comparison of Subepithelial Connective Tissue Grafts and Coronally Advanced Flaps with Emdogain in the Treatment of Gingival Recessions

    Directory of Open Access Journals (Sweden)

    F. Haghighati

    2007-03-01

    Full Text Available Objective: The aim of this study was to compare subepithelial connective tissue grafts (SCTG and coronally advanced flaps (CAF with the addition of Emdogain in the treatment of gingival recession.Materials and Methods: This interventional randomized controlled clinical trial involved eleven patients and 31 teeth demonstrating facial recessions of > 2 mm identified as Miller’s class I or II. Recession depth (RD, recession width (RW, probing depth (PD, clinical attachment level (CAL, and keratinized tissue (KT, weremeasured at baseline and at 4, 12 and 24 weeks postoperation. Before surgery the samples were randomized to receive either a CAF with Emdogain (test group or a connective tissue graft (control group. Data were analyzed using independent t-test and univariate analysis of variance.Results: Twenty-four weeks after therapy, the mean root coverage in the test and control cases was 50.24% and 65.82%, respectively. There was no significant difference between the two groups (P=0.759. Within the 24-week follow-up period both procedures resulted in statistically significant improvement in RD, RW and CAL, but not in PD. KT increased 0.7 mm in the SCTG group while it decreased 0.5 mm in the Emdogain group (P<0.05.Conclusion: The SCTG procedure provided better results in comparison to CAF with Emdogain. However the later method is easier and less technique-sensitive. Therefore it can be considered as a possible substitute for the treatment of gingival recessions,especially when increasing KT is not required.

  17. Contribution of collagen and elastin fibers to the mechanical behavior of an abdominal connective tissue.

    Science.gov (United States)

    Levillain, A; Orhant, M; Turquier, F; Hoc, T

    2016-08-01

    The linea alba is a complex structure commonly involved in hernia formation. Knowledge of its mechanical behavior is essential to design suitable meshes and reduce the risk of recurrence. The aim of this study was to investigate the relationships between the mechanical properties of the linea alba and the organization of collagen and elastin fibers. For that purpose, longitudinal and transversal samples were removed from four porcine and three human linea alba, to perform tensile tests under a biphotonic confocal microscope, in each direction. Microscopic observation revealed a tissue composed of two layers, made of transversal collagen fibers in the dorsal side and oblique collagen fibers in the ventral side. This particular architecture led to an anisotropic mechanical behavior, with higher stress in the transversal direction. During loading, oblique fibers of the ventral layer reoriented toward the tensile axis in both directions, while fibers of the dorsal layer remained in the transversal direction. This rotation of oblique fibers progressively increased the stiffness of the tissue and induced a non-linear stress-stretch relation. Elastin fibers formed a layer covering the collagen fibers and followed their movement, suggesting that they ensure their elastic recoil. All of these results demonstrated the strong relationships between the microstructure and the mechanical behavior of the linea alba. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Pulpal progenitors and dentin repair.

    Science.gov (United States)

    Harichane, Y; Hirata, A; Dimitrova-Nakov, S; Granja, I; Goldberg, A; Kellermann, O; Poliard, A

    2011-07-01

    Mesenchymal stem cells are present in the dental pulp. They have been shown to contribute to dentin-like tissue formation in vitro and to participate in bone repair after a mandibular lesion. However, their capacity to contribute efficiently to reparative dentin formation after pulp lesion has never been explored. After pulp exposure, we have identified proliferative cells within 3 zones. In the crown, zone I is near the cavity, and zone II corresponds to the isthmus between the mesial and central pulp. In the root, zone III, near the apex, at a distance from the inflammatory site, contains mitotic stromal cells which may represent a source of progenitor cells. Stem-cell-based strategies are promising treatments for tissue injury in dentistry. Our experiments focused on (1) location of stem cells induced to leave their quiescent state early after pulp injury and (2) implantation of pulp progenitors, a substitute for classic endodontic treatments, paving the way for pulp stem-cell-based therapies.

  19. Real time imaging of human progenitor neurogenesis.

    Directory of Open Access Journals (Sweden)

    Thomas M Keenan

    Full Text Available Human neural progenitors are increasingly being employed in drug screens and emerging cell therapies targeted towards neurological disorders where neurogenesis is thought to play a key role including developmental disorders, Alzheimer's disease, and depression. Key to the success of these applications is understanding the mechanisms by which neurons arise. Our understanding of development can provide some guidance but since little is known about the specifics of human neural development and the requirement that cultures be expanded in vitro prior to use, it is unclear whether neural progenitors obey the same developmental mechanisms that exist in vivo. In previous studies we have shown that progenitors derived from fetal cortex can be cultured for many weeks in vitro as undifferentiated neurospheres and then induced to undergo neurogenesis by removing mitogens and exposing them to supportive substrates. Here we use live time lapse imaging and immunocytochemical analysis to show that neural progenitors use developmental mechanisms to generate neurons. Cells with morphologies and marker profiles consistent with radial glia and recently described outer radial glia divide asymmetrically and symmetrically to generate multipolar intermediate progenitors, a portion of which express ASCL1. These multipolar intermediate progenitors subsequently divide symmetrically to produce CTIP2(+ neurons. This 3-cell neurogenic scheme echoes observations in rodents in vivo and in human fetal slice cultures in vitro, providing evidence that hNPCs represent a renewable and robust in vitro assay system to explore mechanisms of human neurogenesis without the continual need for fresh primary human fetal tissue. Knowledge provided by this and future explorations of human neural progenitor neurogenesis will help maximize the safety and efficacy of new stem cell therapies by providing an understanding of how to generate physiologically-relevant cell types that maintain their

  20. Influence of laser photobiomodulation upon connective tissue remodeling during wound healing.

    Science.gov (United States)

    Medrado, Alena P; Soares, Ana Prates; Santos, Elisângela T; Reis, Sílvia Regina A; Andrade, Zilton A

    2008-09-18

    The modulation of collagen fibers during experimental skin wound healing was studied in 112 Wistar rats submitted to laser photobiomodulation treatment. A standardized 8mm-diameter wound was made on the dorsal skin of all animals. In half of them, 0.2ml of a silica suspension was injected along the border of the wound in order to enhance collagen deposition and facilitate observation. The others received saline as vehicle. The treatment was carried out by means of laser rays from an aluminum-gallium arsenide diode semiconductor with 9mW applied every other day (total dose=4J/cm2) on the borders of the wound. Tissue sections obtained from four experimental groups representing sham-irradiated animals, laser, silica and the association of both, were studied after 3, 7, 10, 15, 20, 30 and 60 days from the laser application. The wounded skin area was surgically removed and submitted to histological, immunohistochemical, ultrastructural, and immunofluorescent studies. Besides the degree and arrangement of collagen fibers and of their isotypes, the degree of edema, the presence of several cell types especially pericytes and myofibroblasts, were described and measured. The observation of Sirius-red stained slides under polarized microscopy revealed to be of great help during the morphological analysis of the collagen tissue dynamic changes. It was demonstrated that laser application was responsible for edema regression and a diminution in the number of inflammatory cells (pobserved in the laser-treated wounds. Collagen deposition was less than expected in silica-treated wounds, and laser treatment contributed to its better differentiation and modulation in all irradiated groups. Thus, laser photobiomodulation was able to induce several modifications during the cutaneous healing process, especially in favoring newly-formed collagen fibers to be better organized and compactedly disposed.

  1. Myocardial connective tissue growth factor (CCN2/CTGF attenuates left ventricular remodeling after myocardial infarction.

    Directory of Open Access Journals (Sweden)

    Jørgen Gravning

    Full Text Available AIMS: Myocardial CCN2/CTGF is induced in heart failure of various etiologies. However, its role in the pathophysiology of left ventricular (LV remodeling after myocardial infarction (MI remains unresolved. The current study explores the role of CTGF in infarct healing and LV remodeling in an animal model and in patients admitted for acute ST-elevation MI. METHODS AND RESULTS: Transgenic mice with cardiac-restricted overexpression of CTGF (Tg-CTGF and non-transgenic littermate controls (NLC were subjected to permanent ligation of the left anterior descending coronary artery. Despite similar infarct size (area of infarction relative to area at risk 24 hours after ligation of the coronary artery in Tg-CTGF and NLC mice, Tg-CTGF mice disclosed smaller area of scar tissue, smaller increase of cardiac hypertrophy, and less LV dilatation and deterioration of LV function 4 weeks after MI. Tg-CTGF mice also revealed substantially reduced mortality after MI. Remote/peri-infarct tissue of Tg-CTGF mice contained reduced numbers of leucocytes, macrophages, and cells undergoing apoptosis as compared with NLC mice. In a cohort of patients with acute ST-elevation MI (n = 42 admitted to hospital for percutaneous coronary intervention (PCI serum-CTGF levels (s-CTGF were monitored and related to infarct size and LV function assessed by cardiac MRI. Increase in s-CTGF levels after MI was associated with reduced infarct size and improved LV ejection fraction one year after MI, as well as attenuated levels of CRP and GDF-15. CONCLUSION: Increased myocardial CTGF activities after MI are associated with attenuation of LV remodeling and improved LV function mediated by attenuation of inflammatory responses and inhibition of apoptosis.

  2. The rate of urinary tract abnormalities and the functional state of kidneys in relation to the degree of connective tissue dysplasia in children

    Directory of Open Access Journals (Sweden)

    T. A. Kryganova

    2016-01-01

    Full Text Available The paper is devoted to the study of the rate of urinary tract abnormalities and kidney functions in children with mild, moderate, and severe connective tissue dysplasia. Severe connective tissue dysplasia was found to prevail in children with urinary tract abnormalities and to be characterized by a variety of urodynamic urinary tract abnormalities. Urinary system infection occurred equally frequently in both patient groups and its rate did not depend on the degree of the dysplasia. Some children with severe connective dysplasia were noted to have diminished renal filtration function. High-grade vesicoureteral reflux, tubular disorders as nocturias, and lowered urine osmolarity were more common in children with severe dysplasia. Hypertension was seen equally often in both patient groups, no matter what the degree of connective tissue dysplasia.

  3. Three-dimensional fine structure of the lingual papillae and their connective tissue cores in the human tongue.

    Science.gov (United States)

    Kobayashi, K; Kumakura, M; Shinkai, H; Ishii, K

    1994-10-01

    The three-dimensional structure of the four types of lingual papillae and their connective tissue cores (CTCs) in the human tongue was studied by scanning electron microscopy after removal of the epithelial cell layer, and was compared to those of other mammalian species. Filiform papillae are densely distributed on the dorsal surface of the anterior two-thirds of the tongue. Each filiform papilla has numerous slender protrusions on the top. After removal of the epithelium, the CTC of the filiform papilla has a columnar primary core with 10-30 rod-shaped small secondary cores surrounding an upper central depression. A few long spine-like protrusions are frequently found in the center of this upper depression. The number, thickness and length of each secondary protrusion of the filiform CTC show some variations at the region distributed on the tongue. Fungiform papillae with spherical heads are scattered among these filiform papillae and are numerous at the anterior margin of the tongue. The CTC of the fungiform papilla shows a coralliform structure with numerous small rod-shaped protrusions on the lateral surface, and its branched top has flat areas with a few small round depressions harboring taste buds. It must be emphasized that human fungiform papilla has some taste buds not only in the young, but also in the adult age. Several to 12 vallate papillae are distributed in front of the terminal groove and had the CTC of pinecone-like structure with numerous small thorns (secondary connective tissue cores). Foliate papillae consist of 10-15 parallel folds at the posterior margin of the tongue. The CTC of the foliate papillae appears as ridges and grooves. Small protrusions are scattered on the surface of the ridges. The underside view of the exfoliated epithelium of the vallate as well as the foliate papillae revealed numerous taste buds arranged in single file in the lateral epithelium. The dorsal surface of the root of the tongue has evenly distributed short rod

  4. Pyrophosphate scintigraphy and other non-invasive methods in the detection of cardiac involvement in some systemic connective tissue diseases

    Energy Technology Data Exchange (ETDEWEB)

    Duska, F.; Bradna, P.; Pospisil, M.; Kubicek, J.; Vizda, J.; Kafka, P.; Palicka, V.; Mazurova, Y.

    1987-02-01

    Thirteen patients with systemic lupus erythematosus, 8 patients with polymyositis, and 6 patients with spondylitis ankylopoetica (Bechterew's disease) underwent clinical cardiologic examination and scintigraphy of the myocardium (/sup 99m/Tc-pyrophosphate), ECG, echocardiography, polygraphy, and their blood pressure was taken. The aim of the study was to ascertain how such a combination of non-invasive examinations can help in recognizing a cardiac involvement. In systemic lupus erythematosus cases one or more positive findings were revealed in 9 patients (69%), in 4 patients all examinations were negative (31%). Four patients (50%) with polymyosits had positive findings. In patients with spondylitis ankylopoetica positive findings occurred in 2 cases (33%). The study has shown that a combination of non-invasive cardiologic methods increases the probability of detecting cardiac involvement in systemic connective tissue diseases.

  5. Lung-dominant connective tissue disease among patients with interstitial lung disease: prevalence, functional stability, and common extrathoracic features

    Directory of Open Access Journals (Sweden)

    Daniel Antunes Silva Pereira

    2015-04-01

    Full Text Available OBJECTIVE: To describe the characteristics of a cohort of patients with lung-dominant connective tissue disease (LD-CTD. METHODS: This was a retrospective study of patients with interstitial lung disease (ILD, positive antinuclear antibody (ANA results (≥ 1/320, with or without specific autoantibodies, and at least one clinical feature suggestive of connective tissue disease (CTD. RESULTS: Of the 1,998 patients screened, 52 initially met the criteria for a diagnosis of LD-CTD: 37% were male; the mean age at diagnosis was 56 years; and the median follow-up period was 48 months. During follow-up, 8 patients met the criteria for a definitive diagnosis of a CTD. The remaining 44 patients comprised the LD-CTD group, in which the most prevalent extrathoracic features were arthralgia, gastroesophageal reflux disease, and Raynaud's phenomenon. The most prevalent autoantibodies in this group were ANA (89% and anti-SSA (anti-Ro, 27%. The mean baseline and final FVC was 69.5% and 74.0% of the predicted values, respectively (p > 0.05. Nonspecific interstitial pneumonia and usual interstitial pneumonia patterns were found in 45% and 9% of HRCT scans, respectively; 36% of the scans were unclassifiable. A similar prevalence was noted in histological samples. Diffuse esophageal dilatation was identified in 52% of HRCT scans. Nailfold capillaroscopy was performed in 22 patients; 17 showed a scleroderma pattern. CONCLUSIONS: In our LD-CTD group, there was predominance of females and the patients showed mild spirometric abnormalities at diagnosis, with differing underlying ILD patterns that were mostly unclassifiable on HRCT and by histology. We found functional stability on follow-up. Esophageal dilatation on HRCT and scleroderma pattern on nailfold capillaroscopy were frequent findings and might come to serve as diagnostic criteria.

  6. The effects of orthodontic movement on a subepithelial connective tissue graft in the treatment of gingival recession.

    Science.gov (United States)

    Tanaka, Orlando Motohiro; Avila, Ana Leticia Rocha; Silva, Gabriela Molina; Añez, Maria Cecilia Galacini; Taffarel, Ivan Pedro

    2010-12-01

    The purpose of this article is to report on the five-year follow-up of a case involving treatment of gingival recession with a subepithelial connective tissue graft prior to orthodontic tooth movement. Gingival recession has a global prevalence that varies from 3 to 100 percent depending on the population studied and the method of analysis. In addition, the frequency of recession seems to be positively correlated with age. Planned orthodontic tooth movement is not necessarily an etiological factor for gingival recession, so long as it does not move the tooth out of its alveolar process. When the tooth is shifted without adequate biomechanical control, bone dehiscence can develop, and the recession can occur as a consequence of the orthodontic treatment. A 19.6-year-old female patient was referred for orthodontic treatment due to severe anterior-inferior dental crowding and a mandibular right lateral incisor in linguoverson and 4.0 mm of gingival recession on the labial surface. Normal gingival architecture was restored with a subepithelial connective tissue graft used to cover the 4.0 mm defect, after which orthodontic treatment repositioned the malposed incisor into its correct occlusal alignment. Individualized torque was applied to the mandibular right central incisor during the orthodontic treatment. The patient was reevaluated five years after completion of the orthodontic treatment. At the five-year recall appointment, the patient exhibited normal tooth alignment and generalized normal gingival architecture; however, 2 mm of gingival recession was noted on the graft site. This case demonstrated that periodontal surgical correction of facial gingival recession with a subepithelial graft may be performed prior to initiating orthodontic treatment.

  7. Selective uptake of boronophenylalanine by glioma stem/progenitor cells

    International Nuclear Information System (INIS)

    Sun, Ting; Zhou, Youxin; Xie, Xueshun; Chen, Guilin; Li, Bin; Wei, Yongxin; Chen, Jinming; Huang, Qiang; Du, Ziwei

    2012-01-01

    The success of boron neutron capture therapy (BNCT) depends on the amount of boron in cells and the tumor/blood and tumor/(normal tissue) boron concentration ratios. For the first time, measurements of boron uptake in both stem/progenitor and differentiated glioma cells were performed along with measurements of boron biodistribution in suitable animal models. In glioma stem/progenitor cells, the selective accumulation of boronophenylalanine (BPA) was lower, and retention of boron after BPA removal was longer than in differentiated glioma cells in vitro. However, boron biodistribution was not statistically significantly different in mice with xenografts. - Highlights: ► Uptake of BPA was analyzed in stem/progenitor and differentiated glioma cells. ► Selective accumulation of BPA was lower in glioma stem/progenitor cells. ► Retention of boron after BPA removal was longer in glioma stem/progenitor cells. ► Boron biodistribution was not statistically different in mice with xenografts.

  8. Prognosis of complicated clinical course of varicose veins of lower extremities on the basis of analysis of phenotypic characteristics of connective tissue dysplasia

    Directory of Open Access Journals (Sweden)

    Tsarev О.А.

    2015-12-01

    Full Text Available Aim: to identify the phenotypic characteristics of indeterminate connective tissue dysplasia, which help to predict the progression of varicose veins of lower extremities and disease recurrence after surgery. Material and Methods. The long-term results of surgical treatment of 60 patients with varicose veins of lower extremities in a 5-year period after phlebectomy were analyzed. The phenotypic characteristics of indeterminate connective tissue dysplasia were researched. 24 patients had recurrence of varicose veins of lower extremities associated with disease progression; 36 patients did not have recurrence of varicose veins of lower extremities. Results. All the patients demonstrated the signs of indeterminate connective tissue dysplasia, whereas their frequency was different. There were specified nine phenotypic characteristics of indeterminate connective tissue dysplasia, which were significantly more frequent for patients with recurrence of varicose vein disease of lower extremities: 1 postural abnormality, 2 flat foot, 3 skin pallor, 4 hyperextension of skin, 5 positive "wrist test", 6 positive "pollex test", 7 diastasis recti abdominis, 8 myopia, 9 hematomas which form quickly. Conclusion. The determined sum of phenotypic characters of indeterminate connective tissue dysplasia allows to predict progression of varicose vein disease of lower extremities, and offers new opportunities for improving the results of surgical treatment via developing special therapeutic measures aimed at improving lifestyle and dysplasia treatment.

  9. Serial analysis of gene expression identifies connective tissue growth factor expression as a prognostic biomarker in gallbladder cancer.

    Science.gov (United States)

    Alvarez, Hector; Corvalan, Alejandro; Roa, Juan C; Argani, Pedram; Murillo, Francisco; Edwards, Jennifer; Beaty, Robert; Feldmann, Georg; Hong, Seung-Mo; Mullendore, Michael; Roa, Ivan; Ibañez, Luis; Pimentel, Fernando; Diaz, Alfonso; Riggins, Gregory J; Maitra, Anirban

    2008-05-01

    Gallbladder cancer (GBC) is an uncommon neoplasm in the United States, but one with high mortality rates. This malignancy remains largely understudied at the molecular level such that few targeted therapies or predictive biomarkers exist. We built the first series of serial analysis of gene expression (SAGE) libraries from GBC and nonneoplastic gallbladder mucosa, composed of 21-bp long-SAGE tags. SAGE libraries were generated from three stage-matched GBC patients (representing Hispanic/Latino, Native American, and Caucasian ethnicities, respectively) and one histologically alithiasic gallbladder. Real-time quantitative PCR was done on microdissected epithelium from five matched GBC and corresponding nonneoplastic gallbladder mucosa. Immunohistochemical analysis was done on a panel of 182 archival GBC in high-throughput tissue microarray format. SAGE tags corresponding to connective tissue growth factor (CTGF) transcripts were identified as differentially overexpressed in all pairwise comparisons of GBC (P SAGE has identified CTGF expression as a predictive biomarker of favorable prognosis in this malignancy. The SAGE libraries from GBC and nonneoplastic gallbladder mucosa are publicly available at the Cancer Genome Anatomy Project web site and should facilitate much needed research into this lethal neoplasm.

  10. Non-alcoholic fatty liver disease connections with fat-free tissues: A focus on bone and skeletal muscle.

    Science.gov (United States)

    Poggiogalle, Eleonora; Donini, Lorenzo Maria; Lenzi, Andrea; Chiesa, Claudio; Pacifico, Lucia

    2017-03-14

    The estimates of global incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) are worrisome, due to the parallel burden of obesity and its metabolic complications. Indeed, excess adiposity and insulin resistance represent two of the major risk factors for NAFLD; interestingly, in the last years a growing body of evidence tended to support a novel mechanistic perspective, in which the liver is at the center of a complex interplay involving organs and systems, other than adipose tissue and glucose homeostasis. Bone and the skeletal muscle are fat- free tissues which appeared to be independently associated with NAFLD in several cross-sectional studies. The deterioration of bone mineral density and lean body mass, leading to osteoporosis and sarcopenia, respectively, are age-related processes. The prevalence of NAFLD also increases with age. Beyond physiological aging, the three conditions share some common underlying mechanisms, and their elucidations could be of paramount importance to design more effective treatment strategies for the management of NAFLD. In this review, we provide an overview on epidemiological data as well as on potential contributors to the connections of NAFLD with bone and skeletal muscle.

  11. Enamel matrix derivative (emdogain) or subepithelial connective tissue graft for the treatment of adjacent multiple gingival recessions: a pilot study.

    Science.gov (United States)

    Alkan, Eylem Ayhan; Parlar, Ates

    2013-01-01

    One treatment approach for achieving healing by regeneration is the application of enamel matrix derivative (EMD) during periodontal surgery. The aim of this randomized clinical study was to compare the efficacy of EMD with a connective tissue graft (CTG) for the treatment of adjacent Miller Class l and II multiple gingival recessions. Twelve systemically healthy subjects with at least two Miller Class I or II multiple gingival recession defects affecting adjacent teeth on both sides of the mouth were enrolled. The surgical protocol was performed for both groups. The 56 recession defects were evaluated for recession depth (RD), recession width (RW), percentage of root coverage (PRC), height of keratinized tissue (HKT), probing depth (PD), and clinical attachment level (CAL). All measurements were repeated at 6 and 12 months. The mean PRC at the final evaluation was 89% ± 17% for the coronally advanced flap (CAF) + EMD group and 93% ± 17% for the CAF + CTG group. Both treatments resulted in statistically significant decreases in RD and RW and increases in HKT at 6 and 12 months. There was also a significant CAL gain for both groups. PD remained shallow over time. The results demonstrated that both procedures were successful in treating Miller Class I and II multiple gingival recessions; however, the greater results of the CAF + CTG group did not reach a statistically significant level.

  12. The zinc transporter SLC39A13/ZIP13 is required for connective tissue development; its involvement in BMP/TGF-beta signaling pathways.

    Directory of Open Access Journals (Sweden)

    Toshiyuki Fukada

    Full Text Available BACKGROUND: Zinc (Zn is an essential trace element and it is abundant in connective tissues, however biological roles of Zn and its transporters in those tissues and cells remain unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that mice deficient in Zn transporter Slc39a13/Zip13 show changes in bone, teeth and connective tissue reminiscent of the clinical spectrum of human Ehlers-Danlos syndrome (EDS. The Slc39a13 knockout (Slc39a13-KO mice show defects in the maturation of osteoblasts, chondrocytes, odontoblasts, and fibroblasts. In the corresponding tissues and cells, impairment in bone morphogenic protein (BMP and TGF-beta signaling were observed. Homozygosity for a SLC39A13 loss of function mutation was detected in sibs affected by a unique variant of EDS that recapitulates the phenotype observed in Slc39a13-KO mice. CONCLUSIONS/SIGNIFICANCE: Hence, our results reveal a crucial role of SLC39A13/ZIP13 in connective tissue development at least in part due to its involvement in the BMP/TGF-beta signaling pathways. The Slc39a13-KO mouse represents a novel animal model linking zinc metabolism, BMP/TGF-beta signaling and connective tissue dysfunction.

  13. Tendon progenitor cells in injured tendons have strong chondrogenic potential: the CD105-negative subpopulation induces chondrogenic degeneration.

    Science.gov (United States)

    Asai, Shuji; Otsuru, Satoru; Candela, Maria Elena; Cantley, Leslie; Uchibe, Kenta; Hofmann, Ted J; Zhang, Kairui; Wapner, Keith L; Soslowsky, Louis J; Horwitz, Edwin M; Enomoto-Iwamoto, Motomi

    2014-12-01

    To study the cellular mechanism of the tendon repair process, we used a mouse Achilles tendon injury model to focus on the cells recruited to the injured site. The cells isolated from injured tendon 1 week after the surgery and uninjured tendons contained the connective tissue progenitor populations as determined by colony-forming capacity, cell surface markers, and multipotency. When the injured tendon-derived progenitor cells (inTPCs) were transplanted into injured Achilles tendons, they were not only integrated in the regenerating area expressing tenogenic phenotype but also trans-differentiated into chondrogenic cells in the degenerative lesion that underwent ectopic endochondral ossification. Surprisingly, the micromass culture of the inTPCs rapidly underwent chondrogenic differentiation even in the absence of exogenous bone morphogenetic proteins or TGFβs. The cells isolated from human ruptured tendon tissues also showed connective tissue progenitor properties and exhibited stronger chondrogenic ability than bone marrow stromal cells. The mouse inTPCs contained two subpopulations one positive and one negative for CD105, a coreceptor of the TGFβ superfamily. The CD105-negative cells showed superior chondrogenic potential in vitro and induced larger chondroid degenerative lesions in mice as compared to the CD105-positive cells. These findings indicate that tendon progenitor cells are recruited to the injured site of tendons and have a strong chondrogenic potential and that the CD105-negative population of these cells would be the cause for chondroid degeneration in injured tendons. The newly identified cells recruited to the injured tendon may provide novel targets to develop therapeutic strategies to facilitate tendon repair. © 2014 AlphaMed Press.

  14. [Mixed connective tissue disease: prevalence and clinical characteristics in African black, study of 7 cases in Gabon and review of the literature].

    Science.gov (United States)

    Missounga, Landry; Ba, Josaphat Iba; Nseng Nseng Ondo, Ingrid Rosalie; Nziengui Madjinou, Maria Ines Carine; Malekou, Doris; Mouendou Mouloungui, Emeline Gracia; Nzengue, Emmanuel Ecke; Boguikouma, Jean Bruno; Kombila, Moussavou

    2017-01-01

    The literature reports that mixed connective tissue disease seems more frequent in the black population and among Asians. This study aims to determine the prevalence of mixed connective tissue disease (MCTD) among connective tissue disorders and all rheumatologic pathologies in a hospital population in Gabon as well as to describe the clinical features of this disease. We conducted a retrospective study by reviewing the medical records of patients treated for mixed connective tissue disease (Kasukawa criteria) and other entities of connective tissue disorders (ACR criteria) in the Division of Rheumatology at the University Hospital in Libreville between January 2010 and December 2015. For each case of MCTD the parameters studied were articular and extra-articular manifestations, anti-U1RNP antibodies levels, patient's evolution. Over a period of 6 years, data were collected by medical records of 7 patients out of 6050 patients and 67 cases of connective tissue disorders, reflecting a prevalence of 0.11% and 10.44% respectively. the 7 patients were women (100%), with an average age of 39.5 years. Articular manifestations included: polyarthritis, myalgias, chubby fingers and Raynaud's phenomenon in 87.5%, 87.5%, 28.6% and 14% respectively. The 7 patients had high anti-U1RNP antibodies levels, ranging between 5 and 35N (N≤ 7 IU). A case of death due to pulmonary arterial hypertension (PAH) was certified. This is the largest case series of MCTD reported in Black Africa. The disease seems to be rare among the black Africans; the reason could be genetic. The demographic and clinical aspects appear similar to those in Caucasians, Asians and Blacks except for a low frequency of Raynaud?s phenomenon among Blacks.

  15. Understanding the effect of pulsed electric fields on thermostability of connective tissue isolated from beef pectoralis muscle using a model system.

    Science.gov (United States)

    Alahakoon, A U; Oey, I; Silcock, P; Bremer, P

    2017-10-01

    Brisket is a low value/tough meat cut that contains a large amount of connective tissue. Conversion of collagen into gelatin during heating reduces the toughness of the connective tissue however this conversion is slow at low cooking temperatures (around 60°C). The objective of this project was to determine the ability of pulsed electric field (PEF) processing to reduce the thermal stability of connective tissue. To achieve this, a novel model system was designed in which connective tissue obtained from beef deep pectotalis muscle (brisket) was exposed to PEF at combinations of electric field strength (1.0 and 1.5kV/cm) and specific energy (50 and 100kJ/kg) within an agar matrix at electrical conductivities representing the electrical conductivity found in brisket. Differential scanning calorimetry showed that PEF treatment significantly (p<0.05) decreased the denaturation temperature of connective tissue compared to untreated samples. Increasing electric field strength and the specific energy increased the Ringer soluble collagen fraction. PEF treated samples showed higher solubilization compared to the untreated samples at both 60°C and 70°C in heat solubility test. SEM examination of PEF treated (at 1.5kV/cm and 100kJ/kg) and untreated samples revealed that PEF appeared to increase the porosity of the connective tissue structure. These finding suggest that PEF processing is a technology that could be used to improve the tenderness and decrease the cooking time of collagen rich, meat cuts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Interleukin-1β Suppresses the Transporter Genes Ank and Ent1 Expression in Stromal Progenitor Cells Retaining Mineralization.

    Science.gov (United States)

    Ezura, Yoichi; Lin, Xin; Hatta, Arina; Izu, Yayoi; Noda, Masaki

    2016-08-01

    Heterotopic ossification (HO) in various tissues evokes clinical problems. Inflammatory responses of the stromal progenitor cells may be involved in its etiology. Previous report indicated that pro-inflammatory cytokines including IL-1β enhanced the in vitro calcification of human mesenchymal stem cells (MSCs), by suppressing the expression of ectonucleotide pyrophosphatase/phosphodiesterase-1 gene (ENPP1). However, possible contribution of other related factors had not been investigated. Here, we investigated the expression of regulators of extracellular pyrophosphate and nucleosides including Enpp1, Nt5e, Ank, Enptds, and Ent1, examining various connective tissue stromal progenitor cells, including bone marrow stromal cells and synovium derived cells from mouse, or bone marrow MSCs from human. Consistent with previous studies, we observed characteristic suppression of the osteoblastic marker genes by IL-1β during the osteogenic culture for 20 days. In addition, we observed a reduced expression of the important transporter genes, Ank and Ent1, whereas the alteration in Enpp1 and Nt5e levels was not always consistent among the cell types. Our results suggest that IL-1β suppresses not only the osteoblastic but also the negative regulators of soft-tissue calcification, including Ank and Ent1 in stromal progenitor cells, which may contribute to the mechanisms of HO in various disorders.

  17. Clinical evaluation of expanded mesh connective tissue graft in the treatment for multiple adjacent gingival recessions in the esthetic zone

    Directory of Open Access Journals (Sweden)

    M Shanmugam

    2015-01-01

    Full Text Available Background: Multiple approaches have been used to replace lost, damaged or diseased gingival tissues. The connective tissue graft (CTG procedure is the golden standard method for root coverage. Although multiple sites often need grafting, the palatal mucosa supplies only a limited area of grafting material. To overcome this limitation, expanded mesh graft provides a method whereby a graft can be stretched to cover a large area. The aim of this study was to evaluate the effectiveness and the predictability of expanded mesh CTG (e-MCTG in the treatment of adjacent multiple gingival recessions. Materials and Methods: Sixteen patients aged 20-50 years contributed to 55 sites, each site falling into at least three adjacent Miller′s Class 1 or Class 2 gingival recession. The CTG obtained from the palatal mucosa was expanded to cover the recipient bed, which was 1.5 times larger than the graft. Clinical measurements were recorded at baseline and 3 months, 12 months postoperatively. Results: A mean coverage of 1.96 mm ± 0.66 mm and 2.22 mm ± 0.68 mm was obtained at the end of 3 rd and 12 th month, respectively. Twelve months after surgery a statistically significant increase in CAL (2.2 mm ± 0.68 mm, P < 0.001 and increasing WKT (1.75 ± 0.78, P < 0.001 were obtained. In 80% of the treated sites, 100% root coverage was achieved (mean 93.5%. Conclusions: The results of this study demonstrated that multiple adjacent recessions were treated by using e-MCTG technique can be applied and highly predictable root coverage can be achieved.

  18. Inhibition of connective tissue growth factor attenuates paraquat-induced lung fibrosis in a human MRC-5 cell line.

    Science.gov (United States)

    Huang, Min; Yang, Huifang; Zhu, Lingqin; Li, Honghui; Zhou, Jian; Zhou, Zhijun

    2016-11-01

    Chronic exposure to Paraquat (PQ) may result in progressive pulmonary fibrosis and subsequent chronic obstructive pulmonary malfunction. Connective tissue growth factor (CTGF) has been proposed as a key determinant in the development of lung fibrosis. We investigated thus whether knock down of CTGF can prevent human lung fibroblasts (MRC-5) activation and proliferation with the subsequent inhibition of PQ-induced fibrosis. MRC-5 was transfected with CTGF-siRNAs and exposed to different concentrations of PQ. The siRNA-silencing efficacy was evaluated using western blotting analyses, qRT-PCR and flow cytometry. Next, the viability and migration of MRC-5 was determined. MMP-2, MMP-9, and TIMP-1 accumulation were quantified to evaluate the lung fibrosis exposure to PQ. Over expression of CTGF mRNA was observed in human MRC-5 cell as early as 6 h following PQ stimulation. CTGF gene expression in MRC-5 cells was substantially reduced by RNAi, which significantly suppressed the expression of the lung fibrosis markers such as tissue inhibitor of metalloproteinase-2 (TIMP-2), Matrix metalloproteinase-2 (MMP-2) and Matrix metalloproteinase-9 (MMP-9) that were stimulated by PQ. Inhibition of CTGF expression suppressed impeded the proliferation and migration ability of MRC-5 cells and resulted in cell-extracellular matrix (ECM) protein accumulation in cells. Our results suggest that CTGF promoted the development of PQ-induced lung fibrosis in collaboration with transforming growth factor β1 (TGFβ1). Furthermore, the observed arresting effects of CTGF knock down during this process suggested that CTGF is the potential target site for preventing PQ-induced pulmonary fibrosis. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1620-1626, 2016. © 2015 Wiley Periodicals, Inc.

  19. Mixed Connective Tissue Disease

    Science.gov (United States)

    ... often involve the hands. Fingers might swell like sausages, and the fingertips become white and numb. In ... swelling to the point where the fingers resemble sausages. Muscle and joint pain. Joints may become deformed, ...

  20. Characterization of fat-connective tissue size distribution in pre-sliced pork hams using multifractal analysis.

    Science.gov (United States)

    Mendoza, Fernando; Valous, Nektarios A; Sun, Da-Wen; Allen, Paul

    2009-12-01

    Fat-connective tissue size distribution (FSD) in hams is a fundamental physical property for its quality assessment. FSD is related to the sensory properties such as texture, taste, quality of raw meat and visual appearance. In this paper we present a tool to carry out the multifractal analysis (MFA) of two-dimensional binary images of pre-sliced pork hams through the calculation of the f(α)-spectra, Rényi (D(q)) dimensions, and associated statistical regressions and parameters. The application is presented for the structural characterization of FSD in three qualities of pork hams (high yield, medium yield and premium quality hams) using image sections of 512×512pixels(2) with a spatial resolution of 0.102mm/pixel. MFA was carried out using the method of moments in the optimized box size range of 32-512pixels for all the ham images using powers of 2, and estimating the probability distribution for moments ranging from -10

  1. CCN2/connective tissue growth factor is essential for pericyte adhesion and endothelial basement membrane formation during angiogenesis.

    Directory of Open Access Journals (Sweden)

    Faith Hall-Glenn

    Full Text Available CCN2/Connective Tissue Growth Factor (CTGF is a matricellular protein that regulates cell adhesion, migration, and survival. CCN2 is best known for its ability to promote fibrosis by mediating the ability of transforming growth factor β (TGFβ to induce excess extracellular matrix production. In addition to its role in pathological processes, CCN2 is required for chondrogenesis. CCN2 is also highly expressed during development in endothelial cells, suggesting a role in angiogenesis. The potential role of CCN2 in angiogenesis is unclear, however, as both pro- and anti-angiogenic effects have been reported. Here, through analysis of Ccn2-deficient mice, we show that CCN2 is required for stable association and retention of pericytes by endothelial cells. PDGF signaling and the establishment of the endothelial basement membrane are required for pericytes recruitment and retention. CCN2 induced PDGF-B expression in endothelial cells, and potentiated PDGF-B-mediated Akt signaling in mural (vascular smooth muscle/pericyte cells. In addition, CCN2 induced the production of endothelial basement membrane components in vitro, and was required for their expression in vivo. Overall, these results highlight CCN2 as an essential mediator of vascular remodeling by regulating endothelial-pericyte interactions. Although most studies of CCN2 function have focused on effects of CCN2 overexpression on the interstitial extracellular matrix, the results presented here show that CCN2 is required for the normal production of vascular basement membranes.

  2. Pericardial tamponade and pancytopenia as the first manifestation of mixed connective tissue disorder and its complete reversal with corticosteroids

    Directory of Open Access Journals (Sweden)

    Ankur Jain

    2014-09-01

    Full Text Available We report a case of a 25-year-old lady who presented to our department with complaints of easy fatigability and shortness of breath since one week. She had a history of Raynaud’s phenomenon. Examination revealed scleroderma like skin changes and pericardial friction rub. Investigations revealed high titer of anti-U1 RNP antibodies along with co-existing pancytopenia. Chest x-ray and echocardiography confirmed pericardial tamponade. Patient was diagnosed as having mixed connective tissue disorder (MCTD and she was started on high dose prednisolone, which led to complete reversal of pancytopenia and pericardial tamponade after 1 month of treatment. There are only 6 reported cases of pericardial tamponade in a patient with MCTD, and none of them had pancytopenia. Present case highlights the need to investigate the patient of pericardial tamponade for MCTD, especially in the presence of pancytopenia and relevant clinical history, as prompt treatment with corticosteroids can avoid invasive procedures like pericardiocentesis.

  3. An unusual association between hemophagocytic lymphohistiocytosis, mixed connective tissue disease, and autoimmune hemolytic anemia: A case report.

    Science.gov (United States)

    Kelkar, Amar H; Shah, Anushi A; Yong, Sherri L; Ahmed, Zohair

    2017-07-01

    In the adult patient, hemophagocytic lymphohistiocytosis (HLH) is uncommon and frequently difficult to diagnose due to its nonspecific presentation and numerous complications. Herein, we present the case of a 25-year-old female who initially presented for evaluation of persistent fevers and fatigue. She was found to have splenomegaly, generalized lymphadenopathy, pancytopenia, and acute hepatic failure. Her course was further complicated by the development of nephrotic syndrome and autoimmune hemolytic anemia (AIHA). Antinuclear antibody and ribonucleoprotein were positive, with concurrent physical examination findings, indicating underlying mixed connective tissue disease (MCTD). Ferritin was greater than 40,000 ng/dL. Viral studies, including hepatitis A, B, and C, cytomegalovirus, and Epstein-Barr virus were negative. On the basis of her clinical presentation, a diagnosis of HLH secondary to MCTD was made. This was later confirmed on liver biopsy. She was started on high-dose prednisone and her symptoms completely resolved. She was then transitioned to azathioprine, hydroxychloroquine, prophylactic antibiotics, and a prednisone taper for long-term management. This case is notable for the association of both AIHA and MCTD with HLH, providing support for a possible relationship between these 3 conditions.

  4. Development of a kinematic model to predict finger flexor tendon and subsynovial connective tissue displacement in the carpal tunnel.

    Science.gov (United States)

    Kociolek, Aaron M; Keir, Peter J

    2015-01-01

    Finger flexor tendinopathies and carpal tunnel syndrome are histologically characterised by non-inflammatory fibrosis of the subsynovial connective tissue (SSCT) in the carpal tunnel, which is indicative of excessive and repetitive shear forces between the finger flexor tendons and SSCT. We assessed flexor digitorum superficialis (FDS) tendon and adjacent SSCT displacements with colour Doppler ultrasound as 16 healthy participants completed long finger flexion/extension movements captured by a motion capture system. FDS tendon displacements fit a second-order regression model based on metacarpophalangeal and proximal interphalangeal joint flexion angles (R(2) = 0.92 ± 0.01). SSCT displacements were 33.6 ± 1.7% smaller than FDS tendon displacements and also fit a second-order regression model (R(2) = 0.89 ± 0.01). FDS tendon and SSCT displacement both correlated with finger joint thickness, enabling participant-specific anthropometric scaling. We propose the current regression models as an ergonomic method to determine relative displacements between the finger flexor tendons and SSCT. Relative displacements between the finger flexor tendons and SSCT provide insight into gliding and friction in the carpal tunnel. Our regression models represent a move towards mechanistic-based ergonomic risk assessment of the wrist/hand. This is a natural evolution of ergonomic methods based on tendon-joint interaction.

  5. Connective Tissue Growth Factor Modulates Adult β-Cell Maturity and Proliferation to Promote β-Cell Regeneration in Mice

    Science.gov (United States)

    Riley, Kimberly G.; Pasek, Raymond C.; Maulis, Matthew F.; Peek, Jennifer; Thorel, Fabrizio; Brigstock, David R.; Herrera, Pedro L.

    2015-01-01

    Stimulation of endogenous β-cell expansion could facilitate regeneration in patients with diabetes. In mice, connective tissue growth factor (CTGF) is expressed in embryonic β-cells and in adult β-cells during periods of expansion. We discovered that in embryos CTGF is necessary for β-cell proliferation, and increased CTGF in β-cells promotes proliferation of immature (MafA−) insulin-positive cells. CTGF overexpression, under nonstimulatory conditions, does not increase adult β-cell proliferation. In this study, we tested the ability of CTGF to promote β-cell proliferation and regeneration after partial β-cell destruction. β-Cell mass reaches 50% recovery after 4 weeks of CTGF treatment, primarily via increased β-cell proliferation, which is enhanced as early as 2 days of treatment. CTGF treatment increases the number of immature β-cells but promotes proliferation of both mature and immature β-cells. A shortened β-cell replication refractory period is also observed. CTGF treatment upregulates positive cell-cycle regulators and factors involved in β-cell proliferation, including hepatocyte growth factor, serotonin synthesis, and integrin β1. Ex vivo treatment of whole islets with recombinant human CTGF induces β-cell replication and gene expression changes consistent with those observed in vivo, demonstrating that CTGF acts directly on islets to promote β-cell replication. Thus, CTGF can induce replication of adult mouse β-cells given a permissive microenvironment. PMID:25392241

  6. Comparative morphology of the lingual papillae and their connective tissue cores in the tongue of the American mink, Neovison vison.

    Science.gov (United States)

    Yoshimura, Ken; Fukue, Yuko; Kishimoto, Ryosuke; Shindo, Junji; Kageyama, Ikuo

    2014-05-01

    We observed the morphology of the lingual papillae (filiform, conical, fungiform, and vallate papillae, and lateral organ) and their connective tissue cores (CTCs) in the American mink (Neovison vison) using light and scanning electron microscopy. Filiform papillae were distributed on the apex linguae and rostral regions of the corpus linguae. Conical papillae were distributed over the caudal region and absent in the radix linguae. Numerous ridges were present in the radix linguae. Four to six vallate papillae were situated at the border between the corpus and radix linguae. Instead of foliate papillae, a pair of lateral organs was situated on the caudal edge of the corpus. The epithelial surface of each filiform papilla consisted of a single main process and 10-12 accessory processes. Notably, filiform papillae in the apex linguae exhibited morphological variation, and some were dome-like and lacked processes. In contrast, filiform papillae on the rostral part were not variable, were extended to a sharp tip, were associated with an eosinophilic stratum corneum, and lacked nuclei. The CTCs of the filiform papillae consisted of a main core and slender accessory cores surrounding a concavity. Those in the apex linguae were similar in appearance and consisted of main and adjacent accessory cores. The fungiform papillae had a dome-like epithelial surface and their CTCs were columnar, with upper concavities and flanges. The simplified lingual morphology of the American mink, particularly in the filiform papillae in the apex linguae, may be influenced by its diet and semiaquatic lifestyle.

  7. Association of Polymorphisms in Connective Tissue Growth Factor and Epidermal Growth Factor Receptor Genes With Human Longevity.

    Science.gov (United States)

    Donlon, Timothy A; Morris, Brian J; He, Qimei; Chen, Randi; Masaki, Kamal H; Allsopp, Richard C; Willcox, D Craig; Tranah, Gregory J; Parimi, Neeta; Evans, Daniel S; Flachsbart, Friederike; Nebel, Almut; Kim, Duk-Hwan; Park, Joobae; Willcox, Bradley J

    2017-08-01

    Growth pathways play key roles in longevity. The present study tested single-nucleotide polymorphisms (SNPs) in the connective tissue growth factor gene (CTGF) and the epidermal growth factor receptor gene (EGFR) for association with longevity. Comparison of allele and genotype frequencies of 12 CTGF SNPs and 41 EGFR SNPs between 440 American men of Japanese ancestry aged ≥95 years and 374 men of average life span revealed association with longevity at the p cases, consistent with heterozygote advantage in living to extreme old age. No associations of the most significant SNPs were observed in whites or Koreans. In conclusion, the present findings indicate that genetic variation in CTGF and EGFR may contribute to the attainment of extreme old age in Japanese. More research is needed to confirm that genetic variation in CTGF and EGFR contributes to the attainment of extreme old age across human populations. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  8. The Architecture of the Connective Tissue in the Musculoskeletal System—An Often Overlooked Functional Parameter as to Proprioception in the Locomotor Apparatus

    Science.gov (United States)

    van der Wal, Jaap

    2009-01-01

    The architecture of the connective tissue, including structures such as fasciae, sheaths, and membranes, is more important for understanding functional meaning than is more traditional anatomy, whose anatomical dissection method neglects and denies the continuity of the connective tissue as integrating matrix of the body. The connective tissue anatomy and architecture exhibits two functional tendencies that are present in all areas of the body in different ways and relationships. In body cavities, the “disconnecting” quality of shaping space enables mobility; between organs and body parts, the “connecting” dimension enables functional mechanical interactions. In the musculoskeletal system, those two features of the connective tissue are also present. They cannot be found by the usual analytic dissection procedures. An architectural description is necessary. This article uses such a methodologic approach and gives such a description for the lateral elbow region. The result is an alternative architectural view of the anatomic substrate involved in the transmission and conveyance of forces over synovial joints. An architectural description of the muscular and connective tissue organized in series with each other to enable the transmission of forces over these dynamic entities is more appropriate than is the classical concept of “passive” force-guiding structures such as ligaments organized in parallel to actively force-transmitting structures such as muscles with tendons. The discrimination between so-called joint receptors and muscle receptors is an artificial distinction when function is considered. Mechanoreceptors, also the so-called muscle receptors, are arranged in the context of force circumstances—that is, of the architecture of muscle and connective tissue rather than of the classical anatomic structures such as muscle, capsules, and ligaments. In the lateral cubital region of the rat, a spectrum of mechanosensitive substrate occurs at the

  9. Comparison of two techniques of harvesting connective tissue and its effects on healing pattern at palate and recession coverage at recipient site.

    Science.gov (United States)

    Pandit, Nymphea; Khasa, Meenakshi; Gugnani, Shalini; Malik, Rajvir; Bali, Deepika

    2016-01-01

    To compare the healing pattern in palate following harvestation of connective tissue graft by two different techniques and to compare the recession coverage at the recipient sites. 30 recession sites with Miller's class I and II recession in 16 patients were recruited for this study. Sites were randomly divided into 2 treatment groups. Group I used Unigraft Knife to harvest the connective tissue whereas in group II patients Langer & Langer techniques was used to harvest the connective tissue graft from the palate. Healing was evaluated at the donor site using- wound size(WS), immediate bleeding (iB) and delayed bleeding (dB), complete wound epithelialization (CE), sensibility disorders (S) and post operative pain (PP) at baseline, 1(st), 4(th), and 12(th) week postoperatively. Recession coverage was assessed by measuring Clinical Attachment Level (CAL), vertical recession (VR), width of keratinized gingiva (KT). On comparison between Group I and II, a statistically significant larger wound size was observed in Group I. CWE was higher in Group II. A non significant difference was observed when SD, and delayed bleeding were compared at all time intervals. A non-significant difference was observed in the clinical parameters at the recipient site. When evaluating the WS and CWE, the Langer and Langer technique was found to be better than the Unigraft knife technique for harvesting the connective tissue graft, whereas both the techniques were found to be effective in root coverage procedure outcomes.

  10. Aberrant immune response with consequent vascular and connective tissue remodeling - causal to scleroderma and associated syndromes such as Raynaud phenomenon and other fibrosing syndromes?

    Science.gov (United States)

    Durmus, Nedim; Park, Sung-Hyun; Reibman, Joan; Grunig, Gabriele

    2016-11-01

    Scleroderma and other autoimmune-induced connective tissue diseases are characterized by dysfunctions in the immune system, connective tissue and the vasculature. We are focusing on systemic sclerosis (SSc)-associated pulmonary hypertension, which remains a leading cause of death with only a 50-60% of 2-year survival rate. Much research and translational efforts have been directed at understanding the immune response that causes SSc and the networked interactions with the connective tissue and the vasculature. One of the unexpected findings was that in some cases the pathogenic immune response in SSc resembles the immune response to helminth parasites. During coevolution, means of communication were developed which protect the host from over-colonization with parasites and which protect the parasite from excessive host responses. One explanation for the geographically clustered occurrence of SSc is that environmental exposures combined with genetic predisposition turn on triggers of molecular and cellular modules that were once initiated by parasites. Future research is needed to further understand the parasite-derived signals that dampen the host response. Therapeutic helminth infection or treatment with parasite-derived response modifiers could be promising new management tools for autoimmune connective tissue diseases.

  11. Aberrant Immune Response with Consequent Vascular and Connective Tissue Remodeling – Causal to Scleroderma and Associated Syndromes such as Raynaud Phenomenon and Other Fibrosing Syndromes ?

    Science.gov (United States)

    Durmus, Nedim; Park, Sung-Hyun; Reibman, Joan; Grunig, Gabriele

    2016-01-01

    Purpose of review Scleroderma and other autoimmune induced connective tissue diseases are characterized by dysfunctions in the immune system, connective tissue and the vasculature. We are focusing on systemic sclerosis (SSc) associated pulmonary hypertension, which remains a leading cause of death with only a 50–60% two-year survival rate. Recent findings Much research and translational efforts have been directed at understanding the immune response that causes SSc and the networked interactions with the connective tissue and the vasculature. One of the unexpected findings was that in some cases the pathogenic immune response in SSc resembles the immune response to helminth parasites. During co-evolution, means of communication were developed which protect the host from over-colonization with parasites and which protect the parasite from excessive host responses. One explanation for the geographically clustered occurrence of SSc is that environmental exposures combined with genetic predisposition turn on triggers of molecular and cellular modules that were once initiated by parasites. Summary Future research is needed to further understand the parasite-derived signals that dampen the host response. Therapeutic helminth infection or treatment with parasite-derived response modifiers could be promising new management tools for autoimmune connective tissue diseases. PMID:27548652

  12. Study of chemical properties and evaluation of collagen in mantle, epidermal connective tissue and tentacle of Indian Squid, Loligo duvauceli Orbigny.

    Science.gov (United States)

    Raman, Maya; Mathew, Saleena

    2014-08-01

    The chemical composition and evaluation of Indian squid (Loligo duvauceli) mantle, epidermal connective tissue and tentacle is investigated in this current study. It is observed that squid mantle contains 22.2% total protein; 63.5% of the total protein is myofibrillar protein. The unique property of squid myofibrillar protein is its water solubility. Squid mantle contains 12.0% total collagen. Epidermal connective tissue has highest amounts of total collagen (17.8%). SDS-PAGE of total collagen identified high molecular weight α-, β- and γ- sub-chains. Amino acid profile analysis indicates that mantle and tentacle contain essential amino acids. Arginine forms a major portion of mantle collagen (272.5 g/100 g N). Isoleucine, glutamic acid and lysine are other amino acids that are found in significantly high amounts in the mantle. Sulphur containing cystine is deficit in mantle collagen. Papain digest of mantle and epidermal connective tissue is rich in uronic acid, while papain digest, collagenase digest and urea digest of epidermal connective tissue has significant amounts of sialic acid (25.2, 33.2 and 99.8 μmol /100 g, respectively). PAS staining of papain digest, collagenase digest and urea digest also identify the association of hexoses with low molecular weight collagen fragments. Histochemical sectioning also emphasized the localized distribution of collagen in epidermal and dermal region and very sparse fibres traverse the myotome bundles.

  13. Uncovering the Number and Clonal Dynamics of Mesp1 Progenitors during Heart Morphogenesis

    Directory of Open Access Journals (Sweden)

    Samira Chabab

    2016-01-01

    Full Text Available The heart arises from distinct sources of cardiac progenitors that independently express Mesp1 during gastrulation. The precise number of Mesp1 progenitors that are specified during the early stage of gastrulation, and their clonal behavior during heart morphogenesis, is currently unknown. Here, we used clonal and mosaic tracing of Mesp1-expressing cells combined with quantitative biophysical analysis of the clonal data to define the number of cardiac progenitors and their mode of growth during heart development. Our data indicate that the myocardial layer of the heart derive from ∼250 Mesp1-expressing cardiac progenitors born during gastrulation. Despite arising at different time points and contributing to different heart regions, the temporally distinct cardiac progenitors present very similar clonal dynamics. These results provide insights into the number of cardiac progenitors and their mode of growth and open up avenues to decipher the clonal dynamics of progenitors in other organs and tissues.

  14. Intracoronary artery transplantation of cardiomyoblast-like cells from human adipose tissue-derived multi-lineage progenitor cells improve left ventricular dysfunction and survival in a swine model of chronic myocardial infarction

    Energy Technology Data Exchange (ETDEWEB)

    Okura, Hanayuki [The Center for Medical Engineering and Informatics, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0879 (Japan); Department of Somatic Stem Cell Therapy and Health Policy, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Saga, Ayami; Soeda, Mayumi [Department of Somatic Stem Cell Therapy and Health Policy, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation, 2-2 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047 (Japan); Miyagawa, Shigeru; Sawa, Yoshiki [Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka 565-0879 (Japan); Daimon, Takashi [Division of Biostatistics, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501 (Japan); Ichinose, Akihiro [Department of Plastic Surgery, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo (Japan); Matsuyama, Akifumi, E-mail: akifumi-matsuyama@umin.ac.jp [The Center for Medical Engineering and Informatics, Osaka University, 2-2 Yamada-oka, Suita, Osaka 565-0879 (Japan); Department of Plastic Surgery, Kobe University Hospital, 7-5-2 Kusunoki-cho, Chuo-ku, Kobe, Hyogo (Japan); RIKEN Program for Drug Discovery and Medical Technology Platforms, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045 (Japan)

    2012-09-07

    Highlights: Black-Right-Pointing-Pointer We administered human CLCs in a swine model of MI via intracoronary artery. Black-Right-Pointing-Pointer Histological studies demonstrated engraftment of hCLCs into the scarred myocardium. Black-Right-Pointing-Pointer Echocardiography showed rescue of cardiac function in the hCLCs transplanted swine. Black-Right-Pointing-Pointer Transplantation of hCLCs is an effective therapeutics for cardiac regeneration. -- Abstract: Transplantation of human cardiomyoblast-like cells (hCLCs) from human adipose tissue-derived multi-lineage progenitor cells improved left ventricular function and survival of rats with myocardial infarction. Here we examined the effect of intracoronary artery transplantation of human CLCs in a swine model of chronic heart failure. Twenty-four pigs underwent balloon-occlusion of the first diagonal branch followed by reperfusion, with a second balloon-occlusion of the left ascending coronary artery 1 week later followed by reperfusion. Four weeks after the second occlusion/reperfusion, 17 of the 18 surviving animals with severe chronic MI (ejection fraction <35% by echocardiography) were immunosuppressed then randomly assigned to receive either intracoronary artery transplantation of hCLCs hADMPCs or placebo lactic Ringer's solution with heparin. Intracoronary artery transplantation was followed by the distribution of DiI-stained hCLCs into the scarred myocardial milieu. Echocardiography at post-transplant days 4 and 8 weeks showed rescue and maintenance of cardiac function in the hCLCs transplanted group, but not in the control animals, indicating myocardial functional recovery by hCLCs intracoronary transplantation. At 8 week post-transplantation, 7 of 8 hCLCs transplanted animals were still alive compared with only 1 of the 5 control (p = 0.0147). Histological studies at week 12 post-transplantation demonstrated engraftment of the pre DiI-stained hCLCs into the scarred myocardium and their expression of

  15. A 10-year institutional experience with open branched graft reconstruction of aortic aneurysms in connective tissue disorders versus degenerative disease.

    Science.gov (United States)

    Hicks, Caitlin W; Lue, Jennifer; Glebova, Natalia O; Ehlert, Bryan A; Black, James H

    2017-11-01

    Aortic reconstruction for complex thoracoabdominal aortic aneurysms (TAAAs) can be challenging, especially in patients with connective tissue disorders (CTDs) in whom tissue fragility is a major concern. Branched graft reconstruction is a more complex operation compared with inclusion patch repair of the aorta but is frequently necessary in patients with CTDs or other pathologies because of anatomic reasons. We describe our institutional experience with open branched graft reconstruction of aortic aneurysms and compare outcomes for patients with CTDs vs degenerative pathologies. We retrospectively analyzed all patients undergoing open aortic reconstruction using branched grafts at our institution between July 2006 and December 2015. Postoperative outcomes, including perioperative morbidity and mortality, midterm graft patency, and the development of new aneurysms, were compared for patients with CTD vs degenerative disease. During the 10-year study period, 137 patients (CTD, 29; degenerative, 108) underwent aortic repair with branched graft reconstruction. CTD patients were significantly younger (39 ± 1.9 vs 68 ± 1.0 years; P disease, coronary artery disease; P degenerative disease. Perioperative mortality (CTD: 10% [n = 3] vs degenerative: 6% [n = 6]; P = .40) and any complication (62% vs 55%; P = .47) were similar between groups. At a median follow-up time of 14.5 months (interquartile range: 6.5, 43.9 months), CTD patients were more likely to develop both new aortic (21%) and nonaortic (14%) aneurysms compared with the degenerative group (7% and 4% for aortic and nonaortic aneurysms, respectively; P = .02). Loss of branch graft patency occurred in 0 of 99 grafts (0%) in CTD patients and in 13 of 167 grafts (7.8%) in degenerative disease patients (P = .005). Loss of branch graft patency occurred most commonly in left renal artery bypass grafts (77%) and was clinically asymptomatic (creatinine: 1.77 ± 0.13 mg/dL currently vs 1.41 ± 0

  16. Expression and functional study of extracellular BMP antagonists during the morphogenesis of the digits and their associated connective tissues.

    Directory of Open Access Journals (Sweden)

    Carlos I Lorda-Diez

    Full Text Available The purpose of this study is to gain insight into the role of BMP signaling in the diversification of the embryonic limb mesodermal progenitors destined to form cartilage, joints, and tendons. Given the importance of extracellular BMP modulators in in vivo systems, we performed a systematic search of those expressed in the developing autopod during the formation of the digits. Here, we monitored the expression of extracellular BMP modulators including: Noggin, Chordin, Chordin-like 1, Chordin-like 2, Twisted gastrulation, Dan, BMPER, Sost, Sostdc1, Follistatin, Follistatin-like 1, Follistatin-like 5 and Tolloid. These factors show differential expression domains in cartilage, joints and tendons. Furthermore, they are induced in specific temporal patterns during the formation of an ectopic extra digit, preceding the appearance of changes that are identifiable by conventional histology. The analysis of gene regulation, cell proliferation and cell death that are induced by these factors in high density cultures of digit progenitors provides evidence of functional specialization in the control of mesodermal differentiation but not in cell proliferation or apoptosis. We further show that the expression of these factors is differentially controlled by the distinct signaling pathways acting in the developing limb at the stages covered by this study. In addition, our results provide evidence suggesting that TWISTED GASTRULATION cooperates with CHORDINS, BMPER, and NOGGIN in the establishment of tendons or cartilage in a fashion that is dependent on the presence or absence of TOLLOID.

  17. Elevated IL-1β levels in anti-Ro/SSA connective tissue diseases patients with prolonged corrected QTc interval.

    Science.gov (United States)

    Pisoni, Cecilia N; Reina, Silvia; Arakaki, Diego; Eimon, Alicia; Carrizo, Carolina; Borda, Enri

    2015-01-01

    Patients with systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS) have increased IL-1β levels. IL-1β and other pro-inflammatory cytokines have a modulating activity on cardiac ion channels and have been associated with increased arrhythmic risk in rheumatoid arthritis patients. Likewise, adult patients with connective tissue diseases (CTDs) may have prolonged QTc intervals associated with the presence of anti-Ro/SSA antibodies. Our objective was to evaluate the presence of serum IL-1β in subjects with CTDs, in relation to the presence of anti-Ro/SSA antibodies and QTc interval duration. 12-lead electrocardiograms (ECG) were performed and blood was withdrawn, measuring electrolytes, IL-1β anti-Ro/SSA antibodies by ELISA in 73 patients with CTDs. 55 patients were anti-Ro/SSA positive and 18 were anti-Ro/SSA negative. Patients with anti-Ro/SSA positive antibodies had a significantly greater median IL-1β serum level: 7.29 (range: 0.17-17.3 pg/ml) compared to patients with anti-Ro/SSA negative antibodies whose median was: 1.67 (range 0.55-4.12 pg/ml) pRo/SSA positive versus 0 (0 %) in anti-Ro/SSA negative patients p=0.05. Median IL-1β levels were: 8.7 (range: 2.69-15.1 pg/ml) in patients with prolonged QTc interval versus median: 5.0 (range: 0.17-17.3 pg/ml) in those with normal QTc interval values (Ro/SSA antibodies and prolonged QTc intervals.

  18. Pulmonary MR imaging with ultra-short TEs: Utility for disease severity assessment of connective tissue disease patients

    International Nuclear Information System (INIS)

    Ohno, Yoshiharu; Nishio, Mizuho; Koyama, Hisanobu; Takenaka, Daisuke; Takahashi, Masaya; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Obara, Makoto; Cauteren, Marc van; Sugimura, Kazuro

    2013-01-01

    Purpose: To evaluate the utility of pulmonary magnetic resonance (MR) imaging with ultra-short echo times (UTEs) at a 3.0 T MR system for pulmonary functional loss and disease severity assessments of connective tissue disease (CTD) patients with interstitial lung disease (ILD). Materials and methods: This prospective study was approved by the institutional review board, and written informed consent was obtained from 18 CTD patients (eight men and ten women) and eight normal subjects with suspected chest disease (three men and five women). All subjects underwent thin-section MDCT, pulmonary MR imaging with UTEs, pulmonary function test and serum KL-6. Regional T2* maps were generated from each MR data set, and mean T2* values were determined from ROI measurements. From each thin-section MDCT data set, CT-based disease severity was evaluated with a visual scoring system. Mean T2* values for normal and CTD subjects were statistically compared by using Student's t-test. To assess capability for pulmonary functional loss and disease severity assessments, mean T2* values were statistically correlated with pulmonary functional parameters, serum KL-6 and CT-based disease severity. Results: Mean T2* values for normal and CTD subjects were significantly different (p = 0.0019) and showed significant correlations with %VC, %DL CO , serum KL-6 and CT-based disease severity of CTD patients (p < 0.05). Conclusion: Pulmonary MR imaging with UTEs is useful for pulmonary functional loss and disease severity assessments of CTD patients with ILD

  19. Interleukin-1 has opposing effects on connective tissue growth factor and tenascin-C expression in human cardiac fibroblasts.

    Science.gov (United States)

    Maqbool, Azhar; Hemmings, Karen E; O'Regan, David J; Ball, Stephen G; Porter, Karen E; Turner, Neil A

    2013-04-24

    Cardiac fibroblasts (CF) play a central role in the repair and remodeling of the heart following injury and are important regulators of inflammation and extracellular matrix (ECM) turnover. ECM-regulatory matricellular proteins are synthesized by several myocardial cell types including CF. We investigated the effects of pro-inflammatory cytokines on matricellular protein expression in cultured human CF. cDNA array analysis of matricellular proteins revealed that interleukin-1α (IL-1α, 10ng/ml, 6h) down-regulated connective tissue growth factor (CTGF/CCN2) mRNA by 80% and up-regulated tenascin-C (TNC) mRNA levels by 10-fold in human CF, without affecting expression of thrombospondins 1-3, osteonectin or osteopontin. Western blotting confirmed these changes at the protein level. In contrast, tumor necrosis factor α (TNFα) did not modulate CCN2 expression and had only a modest stimulatory effect on TNC levels. Signaling pathway inhibitor studies suggested an important role for the p38 MAPK pathway in suppressing CCN2 expression in response to IL-1α. In contrast, multiple signaling pathways (p38, JNK, PI3K/Akt and NFκB) contributed to IL-1α-induced TNC expression. In conclusion, IL-1α reduced CCN2 expression and increased TNC expression in human CF. These observations are of potential value for understanding how inflammation and ECM regulation are linked at the level of the CF. Copyright © 2013 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  20. Clinical and biometrical evaluation of socket preservation using demineralized freeze-dried bone allograft with and without the palatal connective tissue as a biologic membrane.

    Science.gov (United States)

    Moghaddas, Hamid; Amjadi, Mohammad Reza; Naghsh, Narges

    2012-11-01

    Alveolar ridge preservation following tooth extraction has the ability to maintain the ridge dimensions and allow the implant placement in an ideal position fulfilling both functional and aesthetic results. The aim of this study was to evaluate the efficacy of the palatal connective tissue as a biological membrane for socket preservation with demineralized freeze-dried bone allograft (DFDBA). Twelve extraction sites were treated with DFDBA with (case group) and without (control group) using autogenous palatal connective tissue membrane before placement of implants. Alveolar width and height, amount of keratinized tissue, and gingival level were measured at pre-determined points using a surgical stent at two times, the time of socket preservation surgery. In both groups a decrease in all socket dimensions was found. The average decrease in socket width, height, keratinized tissue, and gingival level in case group was 1.16, 0.72, 3.58, and 1.27 mm, and in control group was 2.08, 0.86, 4.52, and 1.58 mm respectively. Statistical analysis showed that decrease in socket width (P = 0.012), keratinized tissue (P ≤ 0.001), and gingival level (P = 0.031) in case group was significantly lower than that of the control group. Results showed no meaningful difference in socket height changes when compared with case and control groups (P = 0.148). Under the limits of this study, connective tissue membrane could preserve socket width, amount of keratinized tissue, and the gingival level more effectively than DFDBA alone.

  1. Reporter-Based Isolation of Developmental Myogenic Progenitors

    Directory of Open Access Journals (Sweden)

    Eyemen Kheir

    2018-04-01

    Full Text Available The formation and activity of mammalian tissues entail finely regulated processes, involving the concerted organization and interaction of multiple cell types. In recent years the prospective isolation of distinct progenitor and stem cell populations has become a powerful tool in the hands of developmental biologists and has rendered the investigation of their intrinsic properties possible. In this protocol, we describe how to purify progenitors with different lineage history and degree of differentiation from embryonic and fetal skeletal muscle by fluorescence-activated cell sorting (FACS. The approach takes advantage of a panel of murine strains expressing fluorescent reporter genes specifically in the myogenic progenitors. We provide a detailed description of the dissection procedures and of the enzymatic dissociation required to maximize the yield of mononucleated cells for subsequent FACS-based purification. The procedure takes ~6–7 h to complete and allows for the isolation and the subsequent molecular and phenotypic characterization of developmental myogenic progenitors.

  2. Mining tissue specificity, gene connectivity and disease association to reveal a set of genes that modify the action of disease causing genes

    Directory of Open Access Journals (Sweden)

    Reverter Antonio

    2008-09-01

    Full Text Available Abstract Background The tissue specificity of gene expression has been linked to a number of significant outcomes including level of expression, and differential rates of polymorphism, evolution and disease association. Recent studies have also shown the importance of exploring differential gene connectivity and sequence conservation in the identification of disease-associated genes. However, no study relates gene interactions with tissue specificity and disease association. Methods We adopted an a priori approach making as few assumptions as possible to analyse the interplay among gene-gene interactions with tissue specificity and its subsequent likelihood of association with disease. We mined three large datasets comprising expression data drawn from massively parallel signature sequencing across 32 tissues, describing a set of 55,606 true positive interactions for 7,197 genes, and microarray expression results generated during the profiling of systemic inflammation, from which 126,543 interactions among 7,090 genes were reported. Results Amongst the myriad of complex relationships identified between expression, disease, connectivity and tissue specificity, some interesting patterns emerged. These include elevated rates of expression and network connectivity in housekeeping and disease-associated tissue-specific genes. We found that disease-associated genes are more likely to show tissue specific expression and most frequently interact with other disease genes. Using the thresholds defined in these observations, we develop a guilt-by-association algorithm and discover a group of 112 non-disease annotated genes that predominantly interact with disease-associated genes, impacting on disease outcomes. Conclusion We conclude that parameters such as tissue specificity and network connectivity can be used in combination to identify a group of genes, not previously confirmed as disease causing, that are involved in interactions with disease causing

  3. Detection of serum anti-B/B’ UsnRNP antibodies in patients with connective tissue diseases by immunoblotting

    Directory of Open Access Journals (Sweden)

    L. Iaccarino

    2011-09-01

    Full Text Available Objective: To investigate the reliability of the immunoblot method in the detection of serum immunoreactivity towards the B/B’ polypeptides of U small nuclear ribonucleoproteins (UsnRNP and to assess the significance of these antibodies in connective tissue disease (CTD patients. Methods: We tested the sera of 348 patients with CTD (101 SLE, 51 systemic sclerosis, 53 primary Sjogren’s syndrome, 27 poly/dermatomyositis, 15 rheumatoid arthritis and 101 overlap CTD, of 31 matched healthy subjects and 13 patients with primary Epstein-Barr virus (EBV infection with high titre IgG anti-EBV antibodies. IgG anti-UsnRNP antibodies were determined by immunoblotting on nuclear extract from Raji cells (an EBV-immortalised human B lymphoid cell line and Jurkat cells (a human T lymphoid cell line. Anti-dsDNA antibodies were detected by indirect immunofluorescence on Crithidia luciliae and anti-ENA by counterimmunoelectrophoresis. Anti-dsDNA activity and avidity were measured in SLE sera by ELISA with Scatchard analysis. Results were statistically analysed by chi-square and Mann-Whitney tests. Results: A high frequency of anti-B/B’ antibodies was found in the sera of CTD patients, confined to SLE (54.4% and overlap CTD with SLE features (55,2%. Anti-B/B’ immune reactivity was closely associated with other anti-UsnRNP specificities, gel precipitating anti-nRNP and anti-P antibodies. Nine out of 15 (60% anti-B/B’ positive/anti-ENA negative lupus sera on Raji blots were confirmed to be positive also on Jurkat blots. The sera from patients with EBV infection provided, on Raji blots, completely different band patterns from those obtained with auto-immune sera. Conclusions. The Sm B/B’ proteins are the predominant or, at least, the most frequently targeted antigens of the UsnRNP auto-immune response in SLE and “lupus-like” overlap CTD. Moreover, anti-B/B’ is diagnostically specific for CTD with SLE features. Immunoblotting on human B lymphoid cells

  4. Masses of supernova progenitors

    International Nuclear Information System (INIS)

    Tinsley, B.M.

    1977-01-01

    The possible nature and masses of supernovae progenitors, and the bearing of empirical results on some unsolved theoretical problems concerning the origin of supernovae, are discussed. The author concentrates on two main questions: what is the lower mass limit for stars to die explosively and what stars initiate type I supernovae. The evidence considered includes local supernova rates, empirical estimates of msub(w) (the upper mass limit for death as a white dwarf), the distributions of supernovae among stellar populations in galaxies and the colors of supernova producing galaxies. (B.D.)

  5. Degradation of connective tissue matrices by macrophages. II. Influence of matrix composition on proteolysis of glycoproteins, elastin, and collagen by macrophages in culture

    Energy Technology Data Exchange (ETDEWEB)

    Jones, P.A. (Univ. of Southern California, Los Angeles); Werb, Z.

    1980-12-01

    Thioglycollate-elicited mouse peritoneal macrophages were cultured in contact with the mixture of extracellular matrix proteins produced by rat smooth muscle cells in culture. Both live macrophages and their conditioned media hydrolyzed glycoproteins, elastin, and collagen. Live macrophages also degraded extracellular connective tissue proteins secreted by endothelial cells and fibroblasts. The glycoproteins in the matrix markedly inhibited the rate of digestion of the other macromolecules, particularly elastin. When plasminogen was added to the matrix, activation of plasminogen to plasmin resulted in the hydrolysis of the glycoprotein components, which then allowed the macrophage elastase easier access to its substrate, elastin. Thus, although plasmin has no direct elastinolytic activity, its presence accelerated the rate of hydrolysis of elastin and therefore the rate of matrix degradation. These findings may be important in an understanding of disease states, such as emphysema and atherosclerosis, that are characterized by the destruction of connective tissue.

  6. Differential diagnosis and diagnostic flow chart of joint hypermobility syndrome/ehlers-danlos syndrome hypermobility type compared to other heritable connective tissue disorders.

    Science.gov (United States)

    Colombi, Marina; Dordoni, Chiara; Chiarelli, Nicola; Ritelli, Marco

    2015-03-01

    Joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT) is an evolving and protean disorder mostly recognized by generalized joint hypermobility and without a defined molecular basis. JHS/EDS-HT also presents with other connective tissue features affecting a variety of structures and organs, such as skin, eye, bone, and internal organs. However, most of these signs are present in variable combinations and severity in many other heritable connective tissue disorders. Accordingly, JHS/EDS-HT is an "exclusion" diagnosis which needs the absence of any consistent feature indicative of other partially overlapping connective tissue disorders. While both Villefranche and Brighton criteria include such an exclusion as a mandatory item, a systematic approach for reaching a stringent clinical diagnosis of JHS/EDS-HT is still lacking. The absence of a consensus on the diagnostic approach to JHS/EDS-HT concerning its clinical boundaries with similar conditions contribute to limit our actual understanding of the pathologic and molecular bases of this disorder. In this review, we revise the differential diagnosis of JHS/EDS-HT with those heritable connective tissue disorders which show a significant overlap with the former and mostly include EDS classic, vascular and kyphoscoliotic types, osteogenesis imperfecta, Marfan syndrome, Loeys-Dietz syndrome, arterial tortuosity syndrome, and lateral meningocele syndrome. A diagnostic flow chart is also offered with the attempt to support the less experienced clinician in stringently recognizing JHS/EDS-HT and stimulate the debate in the scientific community for both management and research purposes. © 2015 Wiley Periodicals, Inc.

  7. Autosomal dominant Marfan-like connective-tissue disorder with aortic dilation and skeletal anomaslies not linked to the Fibrillin genes

    Energy Technology Data Exchange (ETDEWEB)

    Boileau, C.; Coulon, M.; Alexandre, J.-A.; Junien, C. (Laboratorie Central de Biochimie et de Genetique Moleculaire (France)); Jondeau, G.; Delorme, G.; Dubourg, O.; Bourdarias, J.-P. (CHU Ambroise Pare, Boulogne (France)); Babron, M.-C.; Bonaieti-Pellie, C. (INSERM, Chateau de Longchamp, Paris (France)); Sakai, L. (Shriners' Hospital for Crippled Children, Portland, OR (United States)); Melki, J. (Hopital Necker-Enfants Malades, Paris (France))

    1993-07-01

    The authors describe a large family with a connective-tissue disorder that exhibits some of the skeletal and cardiovascular features seen in Marfan syndrome. However, none of the 19 affected individuals displayed ocular abnormalities and therefore did not comply with recognized criteria for this disease. These patients could alternatively be diagnosed as MASS (mitral valve, aorta, skeleton, and skin) phenotype patients or represent a distinct clinical entity, i.e., a new autosomal dominant connective-tissue disorder. The fibrillin genes located on chromosomes 15 and 5 are clearly involved in the classic form of Marfan syndrome and a clinically related disorder (congenital contractural arachnodactyly), respectively. To test whether one of these genes was also implicated in this French family, the authors performed genetic analyses. Blood samples were obtained for 56 family members, and four polymorphic fibrillin gene markers, located on chromosomes 15 (Fib15) and 5 (Fib5), respectively, were tested. Linkage between the disease allele and the markers of these two genes was excluded with lod scores of [minus]11.39 (for Fib15) and [minus]13.34 (for Fib5), at 0 = .001, indicating that the mutation is at a different locus. This phenotype thus represents a new connective-tissue disorder, overlapping but different from classic Marfan syndrome. 33 refs., 1 fig. 2 tabs.

  8. Original paper Assessment of the level of vaccine-induced anti-HBs antibodies in children with inflammatory systemic connective tissue diseases treated with immunosuppression

    Directory of Open Access Journals (Sweden)

    Izabela Szczygielska

    2015-05-01

    Full Text Available Objectives : Protective vaccinations are the most effective method of prevention of type B virus hepatitis. The aim of the study was to determine whether in children receiving immunosuppressive therapy due to inflammatory systemic connective tissue diseases the protective concentration of the anti-HBs antibodies produced after vaccination against type B virus hepatitis in infancy is maintained. Material and methods : The concentration of anti-HBs antibodies was assessed in the sera of 50 children with inflammatory connective tissue diseases – 37 girls (74% and 13 boys (26%, aged 1.5–17.5 years – during the immunosuppressive treatment, which lasted at least 6 months. The control group consisted of 50 healthy children – 28 girls (56% and 22 boys (44% aged 2–17 years. All children were vaccinated in infancy with Engerix B vaccine according to the 0–1–6 months schedule. The antibody concentration of ≥ 10 mIU/ml in patients is regarded as protective. Results: No protective antibody concentrations were found in 25 cases (50% in the group of diseased children and only in 2 children in the control group (4%. Conclusions : The concentration of vaccine-induced antibodies should be assessed in children with inflammatory systemic connective tissue diseases and, in case of the absence of a protective concentration, revaccination should be started. The use of glucocorticosteroids, synthetic and biological disease-modifying antirheumatic drugs is no contraindication to vaccination against hepatitis B.

  9. MicroRNA-145 Inhibits Cell Migration and Invasion and Regulates Epithelial-Mesenchymal Transition (EMT) by Targeting Connective Tissue Growth Factor (CTGF) in Esophageal Squamous Cell Carcinoma.

    Science.gov (United States)

    Han, Qiang; Zhang, Hua-Yong; Zhong, Bei-Long; Wang, Xiao-Jing; Zhang, Bing; Chen, Hua

    2016-10-23

    BACKGROUND This study investigated the mechanism of miR-145 in targeting connective tissue growth factor (CTGF), which affects the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of ESCC cells. MATERIAL AND METHODS A total of 50 ESCC tissues and their corresponding normal adjacent esophageal tissue samples were collected. Then, miR-145 expression in both ESCC clinical specimens and cell lines was detected using quantitative real-time PCR. CTGF protein was detected using immunohistochemistry. Dual luciferase reporter gene assay was employed to assess the effect of miR-145 on the 3'UTR luciferase activity of CTGF. Eca109 cells were transfected with miR-145 mimics and CTGF siRNA, respectively, and changes in cellular proliferation, migration, and invasion were detected via MTT assay, wound-healing assay, and Transwell assay, respectively. Western blotting assay was used to detect the expression of marker genes related to EMT. RESULTS MiR-145 was significantly down-regulated in ESCC tissues and cell lines compared with normal tissues and cell lines (Ptissues was than in normal adjacent esophageal tissues (Ptissues and cell lines, while the protein expression of CTGF exhibited the opposite trend. MiR-145 inhibited the proliferation, migration, invasiveness, and the EMT process of ESCC cells through targeted regulation of CTGF expression.

  10. A novel chemically modified curcumin reduces inflammation-mediated connective tissue breakdown in a rat model of diabetes: periodontal and systemic effects.

    Science.gov (United States)

    Elburki, M S; Moore, D D; Terezakis, N G; Zhang, Y; Lee, H-M; Johnson, F; Golub, L M

    2017-04-01

    levels of inducible MMPs to near-normal levels, but appeared to have no significant effect on the constitutive MMPs required for physiologic connective tissue turnover. In addition to the beneficial effects on periodontal disease, induced both locally and systemically, CMC 2.24 also favorably affected extra-oral connective tissues, skin and skeletal bone. This study supports our hypothesis that CMC 2.24 is a potential therapeutic pleiotropic MMP inhibitor, with both intracellular and extracellular effects, which reduces local and systemic inflammation and prevents hyperglycemia- and bacteria-induced connective tissue destruction. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. High levels of xanthine oxidoreductase in rat endothelial, epithelial and connective tissue cells. A relation between localization and function?

    NARCIS (Netherlands)

    Kooij, A.; Bosch, K. S.; Frederiks, W. M.; van Noorden, C. J.

    1992-01-01

    The localization of xanthine oxidoreductase activity was investigated in unfixed cryostat sections of various rat tissues by an enzyme histochemical method which specifically demonstrates both the dehydrogenase and oxidase forms of xanthine oxidoreductase. High activity was found in epithelial cells

  12. 3D MULTI-MODAL SPATIAL FUZZY SEGMENTATION OF INTRA-MUSCULAR CONNECTIVE AND ADIPOSE TISSUE FROM ULTRA-SHORT TE MR IMAGES OF CALF MUSCLE

    Science.gov (United States)

    Ugarte, Vincent; Sinha, Usha; Malis, Vadim; Csapo, Robert; Sinha, Shantanu

    2016-01-01

    Purpose To develop and evaluate an automated algorithm to segment intramuscular adipose (IMAT) and connective (IMCT) tissue from musculoskeletal MRI images acquired with a dual echo Ultrashort TE (UTE) sequence. Theory and Methods The dual echo images and calculated structure tensor images are the inputs to the multichannel fuzzy cluster mean (MCFCM) algorithm. Modifications to the basic MCFCM include an adaptive spatial term and bias shading correction. The algorithm was tested on digital phantoms simulating IMAT/IMCT tissue under varying conditions of image noise and bias and on ten subjects with varying amounts of IMAT/IMCT. Results The MCFCM including the adaptive spatial term and bias shading correction performed better than the original MCFCM and adaptive spatial MCFCM algorithms. IMAT/IMCT was segmented from the unsmoothed simulated phantom data with a mean Dice coefficient of 0.933 ± 0.001 when contrast-to-noise (CNR) was 140 and bias was varied between 30% and 65%. The algorithm yielded accurate in-vivo segmentations of IMAT/IMCT with a mean Dice coefficient of 0.977 ± 0.066. Conclusion The proposed algorithm is completely automated and yielded accurate segmentation of intramuscular adipose and connective tissue in the digital phantom and in human calf data. PMID:26892499

  13. Growth and maturational changes in dense fibrous connective tissue following 14 days of rhGH supplementation in the dwarf rat

    Science.gov (United States)

    Kyparos, Antonios; Orth, Michael W.; Vailas, Arthur C.; Martinez, Daniel A.

    2002-01-01

    The purpose of this study was to investigate the impact of recombinant human growth hormone (rhGH) on patella tendon (PT), medial collateral ligament (MCL), and lateral collateral ligament (LCL) on collagen growth and maturational changes in dwarf GH-deficient rats. Twenty male Lewis mutant dwarf rats, 37 days of age, were randomly assigned to Dwarf + rhGH (n = 10) and Dwarf + vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt twice daily for 14 days. rhGH administration stimulated dense fibrous connective tissue growth, as demonstrated by significant increases in hydroxyproline specific activity and significant decreases in the non-reducible hydroxylysylpyridinoline (HP) collagen cross-link contents. The increase in the accumulation of newly accreted collagen was 114, 67, and 117% for PT, MCL, and LCL, respectively, in 72 h. These findings suggest that a short course rhGH treatment can affect the rate of new collagen production. However, the maturation of the tendon and ligament tissues decreased 18-25% during the rapid accumulation of de novo collagen. We conclude that acute rhGH administration in a dwarf rat can up-regulate new collagen accretion in dense fibrous connective tissues, while causing a reduction in collagen maturation. Copyright 2002 Elsevier Science Ltd.

  14. Use of cis-[18F]fluoro-proline for assessment of exercise-related collagen synthesis in musculoskeletal connective tissue.

    Directory of Open Access Journals (Sweden)

    Dorthe Skovgaard

    Full Text Available Protein turnover in collagen rich tissue is influenced by exercise, but can only with difficulty be studied in vivo due to use of invasive procedure. The present study was done to investigate the possibility of applying the PET-tracer, cis-[(18F]fluoro-proline (cis-Fpro, for non-invasive assessment of collagen synthesis in rat musculoskeletal tissues at rest and following short-term (3 days treadmill running. Musculoskeletal collagen synthesis was studied in rats at rest and 24 h post-exercise. At each session, rats were PET scanned at two time points following injection of cis-FPro: (60 and 240 min p.i. SUV were calculated for Achilles tendon, calf muscle and tibial bone. The PET-derived results were compared to mRNA expression of collagen type I and III. Tibial bone had the highest SUV that increased significantly (p<0.001 from the early (60 min to the late (240 min PET scan, while SUV in tendon and muscle decreased (p<0.001. Exercise had no influence on SUV, which was contradicted by an increased gene expression of collagen type I and III in muscle and tendon. The clearly, visible uptake of cis-Fpro in the collagen-rich musculoskeletal tissues is promising for multi-tissue studies in vivo. The tissue-specific differences with the highest basal uptake in bone are in accordance with earlier studies relying on tissue incorporation of isotopic-labelled proline. A possible explanation of the failure to demonstrate enhanced collagen synthesis following exercise, despite augmented collagen type I and III transcription, is that SUV calculations are not sensitive enough to detect minor changes in collagen synthesis. Further studies including kinetic compartment modeling must be performed to establish whether cis-Fpro can be used for non-invasive in-vivo assessment of exercise-induced changes in musculoskeletal collagen synthesis.

  15. Lysophosphatidic acid signaling through its receptor initiates profibrotic epithelial cell fibroblast communication mediated by epithelial cell derived connective tissue growth factor.

    Science.gov (United States)

    Sakai, Norihiko; Chun, Jerold; Duffield, Jeremy S; Lagares, David; Wada, Takashi; Luster, Andrew D; Tager, Andrew M

    2017-03-01

    The expansion of the fibroblast pool is a critical step in organ fibrosis, but the mechanisms driving expansion remain to be fully clarified. We previously showed that lysophosphatidic acid (LPA) signaling through its receptor LPA 1 expressed on fibroblasts directly induces the recruitment of these cells. Here we tested whether LPA-LPA 1 signaling drives fibroblast proliferation and activation during the development of renal fibrosis. LPA 1 -deficient (LPA 1 -/- ) or -sufficient (LPA 1 +/+ ) mice were crossed to mice with green fluorescent protein expression (GFP) driven by the type I procollagen promoter (Col-GFP) to identify fibroblasts. Unilateral ureteral obstruction-induced increases in renal collagen were significantly, though not completely, attenuated in LPA 1 -/- Col-GFP mice, as were the accumulations of both fibroblasts and myofibroblasts. Connective tissue growth factor was detected mainly in tubular epithelial cells, and its levels were suppressed in LPA 1 -/- Col-GFP mice. LPA-LPA 1 signaling directly induced connective tissue growth factor expression in primary proximal tubular epithelial cells, through a myocardin-related transcription factor-serum response factor pathway. Proximal tubular epithelial cell-derived connective tissue growth factor mediated renal fibroblast proliferation and myofibroblast differentiation. Administration of an inhibitor of myocardin-related transcription factor/serum response factor suppressed obstruction-induced renal fibrosis. Thus, targeting LPA-LPA 1 signaling and/or myocardin-related transcription factor/serum response factor-induced transcription could be promising therapeutic strategies for renal fibrosis. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

  16. The protein precursors of peptides that affect the mechanics of connective tissue and/or muscle in the echinoderm Apostichopus japonicus.

    Directory of Open Access Journals (Sweden)

    Maurice R Elphick

    Full Text Available Peptides that cause muscle relaxation or contraction or that modulate electrically-induced muscle contraction have been discovered in the sea cucumber Apostichopus japonicus (Phylum Echinodermata; Class Holothuroidea. By analysing transcriptome sequence data, here the protein precursors of six of these myoactive peptides (the SALMFamides Sticho-MFamide-1 and -2, NGIWYamide, stichopin, GN-19 and GLRFA have been identified, providing novel insights on neuropeptide and endocrine-type signalling systems in echinoderms. The A. japonicus SALMFamide precursor comprises eight putative neuropeptides including both L-type and F-type SALMFamides, which contrasts with previous findings from the sea urchin Strongylocentrotus purpuratus where L-type and F-type SALMFamides are encoded by different genes. The NGIWYamide precursor contains five copies of NGIWYamide but, unlike other NG peptide-type neuropeptide precursors in deuterostomian invertebrates, the NGIWYamide precursor does not have a C-terminal neurophysin domain, indicating loss of this character in holothurians. NGIWYamide was originally discovered as a muscle contractant, but it also causes stiffening of mutable connective tissue in the body wall of A. japonicus, whilst holokinins (PLGYMFR and derivative peptides cause softening of the body wall. However, the mechanisms by which these peptides affect the stiffness of body wall connective tissue are unknown. Interestingly, analysis of the A. japonicus transcriptome reveals that the only protein containing the holokinin sequence PLGYMFR is an alpha-5 type collagen. This suggests that proteolysis of collagen may generate peptides (holokinins that affect body wall stiffness in sea cucumbers, providing a novel perspective on mechanisms of mutable connective tissue in echinoderms.

  17. Quantification of the global and local complexity of the epithelial-connective tissue interface of normal, dysplastic, and neoplastic oral mucosae using digital imaging.

    Science.gov (United States)

    Abu Eid, Rasha; Landini, Gabriel

    2003-01-01

    This study aimed at quantifying the complexity of the epithelial-connective tissue interface (ECTI) in human normal mucosa, premalignant, and malignant lesions using fractal geometry. Two approaches were used to describe the complexity of 377 oral mucosa ECTI profiles. The box counting method was used to estimate their global fractal dimension, while local fractal dimensions were estimated using the mass radius relation at various local scales. The ECTI complexity significantly increased from normal through premalignant to malignant profiles in both global and local (over 283 microm) scales. Normal mucosa samples from different sites of the oral cavity also had different degrees of global complexity. Fractal geometry is a useful morphological marker of tissue complexity changes taking place during epithelial malignancy and premalignancy, and we propose it as a quantitative marker of epithelial complexity.

  18. Mouse ES cell-derived hematopoietic progenitor cells.

    Science.gov (United States)

    Kim, Eun-Mi; Manzar, Gohar; Zavazava, Nicholas

    2013-01-01

    Future stem cell-based therapies will benefit from the new discoveries being made on pluripotent stem cells such as embryonic stem (ES) cells and induced pluripotent stem (IPS) cells. Understanding the genes regulating pluripotency has opened new opportunities to generate patient-tailored therapies. However, protocols for deriving progenitor cells of therapeutic grade from these pluripotent stem cells are not yet worked out. In particular the potential of these cells in treating diseases when compared to their adult progenitor counterparts is unknown. This is crucial work that needs to be studied in detail because we will need to determine engraftment potential of these cells and their ability for multi-lineage engraftment in the in vivo setting before any clinical applications. The ability of these cells to engraft is dependent on their expression of cell surface markers which guide their homing patterns. In this review, I discuss murine hematopoietic progenitor cells derived from mouse ES cells. Stem cells in the bone marrow are found in the bone marrow niches. Our knowledge of the bone marrow niches is growing and will ultimately lead to improved clinical transplantation of bone marrow cells. We are, however, a long way in appreciating how hematopoietic progenitor cells migrate and populate lymphoid tissues. One of the variables in generating hematopoietic progenitor cells is that different labs use different approaches in generating progenitor cells. In some cases, the ES cell lines used show some variability as well. The cell culture media used by the different investigators highly influence the maturation level of the cells and their homing patterns. Here, mouse ES cell-derived progenitor cells are discussed.

  19. Biocompatible Silk Noil-Based Three-Dimensional Carded-Needled Nonwoven Scaffolds Guide the Engineering of Novel Skin Connective Tissue.

    Science.gov (United States)

    Chiarini, Anna; Freddi, Giuliano; Liu, Daisong; Armato, Ubaldo; Dal Prà, Ilaria

    2016-08-01

    Retracting hypertrophic scars resulting from healed burn wounds heavily impact on the patients' life quality. Biomaterial scaffolds guiding burned-out skin regeneration could suppress or lessen scar retraction. Here we report a novel silk noil-based three-dimensional (3D) nonwoven scaffold produced by carding and needling with no formic acid exposure, which might improve burn healing. Once wetted, it displays human skin-like physical features and a high biocompatibility. Human keratinocyte-like cervical carcinoma C4-I cells seeded onto the carded-needled nonwovens in vitro quickly adhered to them, grew, and actively metabolized glutamine releasing lactate. As on plastic, they released no proinflammatory IL-1β, although secreting tumor necrosis factor-alpha, an inducer of the autocrine mitogen amphiregulin in such cells. Once grafted into interscapular subcutaneous tissue of mice, carded-needled nonwovens guided the afresh assembly of a connective tissue enveloping the fibroin microfibers and filling the interposed voids within 3 months. Fibroblasts and a few poly- or mononucleated macrophages populated the engineered tissue. Besides, its extracellular matrix contained thin sparse collagen fibrils and a newly formed vascular network whose endothelin-1-expressing endothelial cells grew first on the fibroin microfibrils and later expanded into the intervening matrix. Remarkably, no infiltrates of inflammatory leukocytes and no packed collagen fibers bundles among fibroin microfibers, no fibrous capsules at the grafts periphery, and hence no foreign body response was obtained at the end of 3 months of observation. Therefore, we posit that silk noil-based 3D carded-needled nonwoven scaffolds are tools for translational medicine studies as they could guide connective tissue regeneration at deep burn wounds averting scar retraction with good functional results.

  20. [Structural-morphological changes of the connective tissue of the vaginal mucosa and perineal skin in women with stress urinary incontinence].

    Science.gov (United States)

    Pavlov, V N; Yashchuk, A G; Kazikhinurov, A A; Musin, I I; Zauinullina, R M; Kulavskii, V A; Kazikhinurova, A A

    2017-10-01

    To investigate the morphological and structural changes in the connective tissue of the vaginal mucosa and perineal skin in women with stress urinary incontinence. From 2010 to 2013, 71 patients of reproductive age with stress incontinence were observed. The control group comprised 80 women, who also underwent biopsy of the vaginal mucosa and perineal skin. The sections of specimens were stained by Van Gieson, Mallory and Weigert. In immunohistochemical studies, rabbit antibodies specific for collagen types I, III, and IV were placed on each section. Morphological picture of the perineal skin the study group patients completely confirms the clinical manifestations and results of immunohistochemical test, broadens the notion of structural changes in tissues. According to immunohistochemical and histological examination of the vaginal mucosa, some fibrous elements in the lamina were weakly stained. Due to the decrease in the number of vessels and the destruction of their basal membranes and the basal membrane of the epithelial layer, the amount of type IV collagen was markedly reduced. Elastic fibers in the vaginal mucosa and skin of the perineum together with the collagen fibers are the supporting framework of the skin, and together with the interstitial substance of the above authorities lend elasticity in tension. Studies have shown that stress urinary incontinence may be the result of dysregulation of processes. For this pathology in the lamina propria of the vaginal mucosa and dermal lamina of the skin of the perineum destroyed elastic fibers and changes the ratio of collagen of various types. That is, the predominant type III collagen is type I collagen, as well as in the basal membranes, reduced the number of specific collagen type IV. Mucous membrane of the vagina and perineal skin in women with a stress urinary incontinence is found to exhibit marked pathomorphological changes due to inflammatory, destructive and compensatory-adaptive processes leading to

  1. The Adjunctive Effect of Platelet-Rich Fibrin to Connective Tissue Graft in the Treatment of Buccal Recession Defects: Results of a Randomized, Parallel-Group Controlled Trial.

    Science.gov (United States)

    Keceli, Huseyin Gencay; Kamak, Gulen; Erdemir, Ebru Olgun; Evginer, Mustafa Serdar; Dolgun, Anil

    2015-11-01

    Platelet-rich fibrin (PRF) is an autologous preparation that has encouraging effects in healing and regeneration. The aim of this trial is to evaluate the effectiveness of coronally advanced flap (CAF) + connective tissue graft (CTG) + PRF in Miller Class I and II recession treatment compared to CAF + CTG. Forty patients were treated surgically with either CAF + CTG + PRF (test group) or CAF + CTG (control group). Clinical parameters of plaque index, gingival index, vertical recession (VR), probing depth, clinical attachment level (CAL), keratinized tissue width (KTW), horizontal recession (HR), mucogingival junction localization, and tissue thickness (TT) were recorded at baseline and 3 and 6 months after surgery. Root coverage (RC), complete RC (CRC), attachment gain (AG), and keratinized tissue change (KTC) were also calculated. All individuals completed the entire study period. At baseline, mean VR, HR, CAL, KTW, and TT values were similar (P >0.05). In both groups, all parameters showed significant improvement after treatment (P effect of PRF on recession treatment with CAF + CTG, and additional trials are needed.

  2. Subcutaneous connective tissue reactions to iRoot SP, mineral trioxide aggregate (MTA) Fillapex, DiaRoot BioAggregate and MTA.

    Science.gov (United States)

    Bósio, C C; Felippe, G S; Bortoluzzi, E A; Felippe, M C S; Felippe, W T; Rivero, E R C

    2014-07-01

    To evaluate connective tissue reactions to iRoot SP (Innovative Bioceramics, Vancouver, BC, Canada), mineral trioxide aggregate (MTA) Fillapex (FLPX) (Angelus Soluções Odontológicas, Londrina, Brazil), DiaRoot Bioaggregate (DiaDent Group International, Burnaby, BC, Canada) and white MTA (Angelus, Londrina, Brazil) in Wistar rats. A total of 128 dentine tubes filled with the materials and 32 empty tubes (control) were implanted into 32 rats. After 7, 15, 30 and 90 days (n = 8 per period), the animals were euthanized, and the tissues were processed for histological evaluation using haematoxylin-eosin (H&E) and Von Kossa (VK) staining. Observations were made for cellular inflammatory components and the presence of multinucleated giant cells (MNGC), macrophages and tissue necrosis. Data were analysed by Fisher's exact and Kruskal–Wallis tests (P MTA FLPX and iRoot SP scored higher than the other groups for the variable macrophages (P MTA FLPX scored higher than the other groups for the variable MNGC (P MTA FLPX. VK positivity was observed in areas of necrosis in all groups, except in the control group. The materials were considered biologically acceptable except MTA FLPX, which remained toxic to subcutaneous tissue even after 90 days.

  3. Physical exercise can influence local levels of matrix metalloproteinases and their inhibitors in tendon-related connective tissue

    DEFF Research Database (Denmark)

    Koskinen, S O A; Heinemeier, K M; Olesen, J L

    2004-01-01

    Microdialysis studies indicate that mechanical loading of human tendon tissue during exercise or training can affect local synthesis and degradation of type I collagen. Degradation of collagen and other extracellular matrix proteins is controlled by an interplay between matrix metalloproteinases...... (placed in the peritendinous tissue immediately anterior to the Achilles tendon) before, immediately after, 1 day after, and 3 days after an exercise bout. MMP-2 and MMP-9 were measured in dialysate by gelatin zymography, and amounts were quantified by densitometry in relation to total protein...... in the dialysate. TIMP-1 and TIMP-2 were analyzed by reverse gelatin zymography and semiquantitated visually. Pro-MMP-9 increased markedly after exercise and remained high for 3 days after exercise. Pro-MMP-2 dropped from the basal level immediately after exercise and remained low 1 day after exercise...

  4. 3T3 fibroblasts induce cloned interleukin 3-dependent mouse mast cells to resemble connective tissue mast cells in granular constituency

    International Nuclear Information System (INIS)

    Dayton, E.T.; Pharr, P.; Ogawa, M.; Serafin, W.E.; Austen, K.F.; Levi-Schaffer, F.; Stevens, R.L.

    1988-01-01

    As assessed by ultrastructure, histochemical staining, and T-cell dependency, in vitro-differentiated interleukin 3-dependent mouse mast cells are comparable to the mast cells that reside in the gastrointestinal mucosa but not in the skin or the serosal cavity of the mouse. The authors now demonstrate that when cloned interleukin 3-dependent mast cells are cocultured with mouse skin-derived 3T3 fibroblasts in the presence of WEHI-3 conditioned medium for 28 days, the mast cells acquire the ability to stain with safranin, increase their histamine content ∼ 50-fold and their carboxypeptidase. A content ∼ 100-fold, and augment ∼ their biosynthesis of proteoglycans bearing 35 S-labeled haparin relative to 35 S-labeled chondroitin sulfate glycosaminoglycans. Thus, fibroblasts induce interleukin 3-dependent mouse mast cells to change phenotype from mucosal-like to connective tissue-like, indicating that the biochemical and functional characteristics of this mast cell type are strongly influenced by the connective tissue microenvironment

  5. Magnesium Carbonate‐Containing Phosphate Binder Prevents Connective Tissue Mineralization in Abcc6 −/− Mice–Potential for Treatment of Pseudoxanthoma Elasticum

    Science.gov (United States)

    Li, Qiaoli; LaRusso, Jennifer; Grand‐Pierre, Alix E.; Uitto, Jouni

    2009-01-01

    Abstract Pseudoxanthoma elasticum (PXE) is a heritable disorder characterized by ectopic mineralization of connective tissues primarily in the skin, eyes, and the cardiovascular system. PXE is caused by mutations in the ABCC6 gene. While PXE is associated with considerable morbidity and mortality, there is currently no effective or specific treatment. In this study, we tested oral phosphate binders for treatment of a mouse model of PXE which we have developed by targeted ablation of the corresponding mouse gene (Abcc6 −/−). This “knock‐out” (KO) mouse model recapitulates features of PXE and demonstrates mineralization of a number of tissues, including the connective tissue capsule surrounding vibrissae in the muzzle skin which serves as an early biomarker of the mineralization process. Treatment of these mice with a magnesium carbonate‐enriched diet (magnesium concentration being 5‐fold higher than in the control diet) completely prevented mineralization of the vibrissae up to 6 months of age, as demonstrated by computerized morphometric analysis of histopathology as well as by calcium and phosphate chemical assays. The magnesium carbonate‐enriched diet also prevented the progression of mineralization when the mice were placed on that experimental diet at 3 months of age and followed up to 6 months of age. Treatment with magnesium carbonate was associated with a slight increase in the serum concentration of magnesium, with no effect on serum calcium and phosphorus levels. In contrast, concentration of calcium in the urine was increased over 10‐fold while the concentration of phosphorus was markedly decreased, being essentially undetectable after long‐term (>4 month) treatment. No significant changes were noted in the serum parathyroid hormone levels. Computerized axial tomography scan of bones in mice placed on magnesium carbonate‐enriched diet showed no differences in the bone density compared to mice on the control diet, and chemical assays

  6. Epigenetic Reprogramming of Muscle Progenitors: Inspiration for Clinical Therapies

    Directory of Open Access Journals (Sweden)

    Silvia Consalvi

    2016-01-01

    Full Text Available In the context of regenerative medicine, based on the potential of stem cells to restore diseased tissues, epigenetics is becoming a pivotal area of interest. Therapeutic interventions that promote tissue and organ regeneration have as primary objective the selective control of gene expression in adult stem cells. This requires a deep understanding of the epigenetic mechanisms controlling transcriptional programs in tissue progenitors. This review attempts to elucidate the principle epigenetic regulations responsible of stem cells differentiation. In particular we focus on the current understanding of the epigenetic networks that regulate differentiation of muscle progenitors by the concerted action of chromatin-modifying enzymes and noncoding RNAs. The novel exciting role of exosome-bound microRNA in mediating epigenetic information transfer is also discussed. Finally we show an overview of the epigenetic strategies and therapies that aim to potentiate muscle regeneration and counteract the progression of Duchenne Muscular Dystrophy (DMD.

  7. Use of cis-[18F] fluoro-proline for assessment of exercise-related collagen synthesis in musculoskeletal connective tissue

    DEFF Research Database (Denmark)

    Skovgaard, Dorthe; Kjaer, Andreas; Heinemeier, Katja Maria

    2011-01-01

    Protein turnover in collagen rich tissue is influenced by exercise, but can only with difficulty be studied in vivo due to use of invasive procedure. The present study was done to investigate the possibility of applying the PET-tracer, cis-[(18)F]fluoro-proline (cis-Fpro), for non-invasive assess...... and 240 min p.i). SUV were calculated for Achilles tendon, calf muscle and tibial bone. The PET-derived results were compared to mRNA expression of collagen type I and III. Tibial bone had the highest SUV that increased significantly (p...

  8. Comparative evaluation of a bioabsorbable collagen membrane and connective tissue graft in the treatment of localized gingival recession: A clinical study

    Directory of Open Access Journals (Sweden)

    Harsha Mysore Babu

    2011-01-01

    Full Text Available Background: Gingival recession (GR can result in root sensitivity, esthetic concern to the patient, and predilection to root caries. The purpose of this randomized clinical study was to evaluate (1 the effect of guided tissue regeneration (GTR procedure using a bioabsorbable collagen membrane, in comparison to autogenous subepithelial connective tissue graft (SCTG for root coverage in localized gingival recession defects; and (2 the change in width of keratinized gingiva following these two procedures. Materials and Methods: A total of 10 cases, showing at least two localized Miller′s Class I or Class II gingival recession, participated in this study. In a split mouth design, the pairs of defects were randomly assigned for treatment with either SCTG (SCTG Group or GTR-based collagen membrane (GTRC Group. Both the grafts were covered with coronally advanced flap. Recession depth (RD, recession width (RW, width of keratinized gingiva (KG, probing depth (PD, relative attachment level (RAL, plaque index (PI, and gingival index (GI were recorded at baseline, 3 and 6 months postoperatively. Results: Six months following root coverage procedures, the mean root coverage was found to be 84.84% ± 16.81% and 84.0% ± 15.19% in SCTG Group and GTRC Group, respectively. The mean keratinized gingival width increase was 1.50 ± 0.70 mm and 2.30 ± 0.67 mm in the SCTG and GTRC group, respectively, which was not statistically significant. Conclusion: It may be concluded that resorbable collagen membrane can be a reliable alternative to autogenous connective tissue graft in the treatment of gingival recession.

  9. Unique gene expression and MR T2 relaxometry patterns define chronic murine dextran sodium sulphate colitis as a model for connective tissue changes in human Crohn's disease.

    Directory of Open Access Journals (Sweden)

    Christine Breynaert

    Full Text Available INTRODUCTION: Chronically relapsing inflammation, tissue remodeling and fibrosis are hallmarks of inflammatory bowel diseases. The aim of this study was to investigate changes in connective tissue in a chronic murine model resulting from repeated cycles of dextran sodium sulphate (DSS ingestion, to mimic the relapsing nature of the human disease. MATERIALS AND METHODS: C57BL/6 mice were exposed to DSS in drinking water for 1 week, followed by a recovery phase of 2 weeks. This cycle of exposure was repeated for up to 3 times (9 weeks in total. Colonic inflammation, fibrosis, extracellular matrix proteins and colonic gene expression were studied. In vivo MRI T 2 relaxometry was studied as a potential non-invasive imaging tool to evaluate bowel wall inflammation and fibrosis. RESULTS: Repeated cycles of DSS resulted in a relapsing and remitting disease course, which induced a chronic segmental, transmural colitis after 2 and 3 cycles of DSS with clear induction of fibrosis and remodeling of the muscular layer. Tenascin expression mirrored its expression in Crohn's colitis. Microarray data identified a gene expression profile different in chronic colitis from that in acute colitis. Additional recovery was associated with upregulation of unique genes, in particular keratins, pointing to activation of molecular pathways for healing and repair. In vivo MRI T2 relaxometry of the colon showed a clear shift towards higher T2 values in the acute stage and a gradual regression of T2 values with increasing cycles of DSS. CONCLUSIONS: Repeated cycles of DSS exposure induce fibrosis and connective tissue changes with typical features, as occurring in Crohn's disease. Colonic gene expression analysis revealed unique expression profiles in chronic colitis compared to acute colitis and after additional recovery, pointing to potential new targets to intervene with the induction of fibrosis. In vivo T2 relaxometry is a promising non-invasive assessment of

  10. Yap controls stem/progenitor cell proliferation in the mouse postnatal epidermis.

    Science.gov (United States)

    Beverdam, Annemiek; Claxton, Christina; Zhang, Xiaomeng; James, Gregory; Harvey, Kieran F; Key, Brian

    2013-06-01

    Tissue renewal is an ongoing process in the epithelium of the skin. We have begun to examine the genetic mechanisms that control stem/progenitor cell activation in the postnatal epidermis. The conserved Hippo pathway regulates stem cell turnover in arthropods through to vertebrates. Here we show that its downstream effector, yes-associated protein (YAP), is active in the stem/progenitor cells of the postnatal epidermis. Overexpression of a C-terminally truncated YAP mutant in the basal epidermis of transgenic mice caused marked expansion of epidermal stem/progenitor cell populations. Our data suggest that the C-terminus of YAP controls the balance between stem/progenitor cell proliferation and differentiation in the postnatal interfollicular epidermis. We conclude that YAP functions as a molecular switch of stem/progenitor cell activation in the epidermis. Moreover, our results highlight YAP as a possible therapeutic target for diseases such as skin cancer, psoriasis, and epidermolysis bullosa.

  11. Novel muscle and connective tissue design enables high extensibility and controls engulfment volume in lunge-feeding rorqual whales.

    Science.gov (United States)

    Shadwick, Robert E; Goldbogen, Jeremy A; Potvin, Jean; Pyenson, Nicholas D; Vogl, A Wayne

    2013-07-15

    Muscle serves a wide variety of mechanical functions during animal feeding and locomotion, but the performance of this tissue is limited by how far it can be extended. In rorqual whales, feeding and locomotion are integrated in a dynamic process called lunge feeding, where an enormous volume of prey-laden water is engulfed into a capacious ventral oropharyngeal cavity that is bounded superficially by skeletal muscle and ventral groove blubber (VGB). The great expansion of the cavity wall presents a mechanical challenge for the physiological limits of skeletal muscle, yet its role is considered fundamental in controlling the flux of water into the mouth. Our analyses of the functional properties and mechanical behaviour of VGB muscles revealed a crimped microstructure in an unstrained, non-feeding state that is arranged in parallel with dense and straight elastin fibres. This allows the muscles to accommodate large tissue deformations of the VGB yet still operate within the known strain limits of vertebrate skeletal muscle. VGB transverse strains in routine-feeding rorquals were substantially less than those observed in dead ones, where decomposition gas stretched the VGB to its elastic limit, evidence supporting the idea that eccentric muscle contraction modulates the rate of expansion and ultimate size of the ventral cavity during engulfment.

  12. Comparative evaluation of platelet-rich fibrin with connective tissue grafts in the treatment of miller's Class I gingival recessions

    Directory of Open Access Journals (Sweden)

    Sonam Mufti

    2017-01-01

    Full Text Available Background: One of the most common aesthetic problem encountered in the field of periodontology is gingival recession, which is, perceived by the patients as increase in length of teeth. The treatment of buccal gingival recession is a common requirement due to aesthetic concern or root sensitivity. This study was planned to evaluate the efficacy of PRF membrane compared to that of CTG in Miller's class I gingival recessions. Materials and Methods: 32 sites with Miller's Class I gingival recessions, out of which 16 sites received PRF (test and 16 sites received CTG (control. Each patient had undergone an initial periodontal treatment, including oral hygiene instructions, plaque control, and scaling and root planing, followed by re-evaluation. All clinical recordings; recession height, recession width, clinical attachment level, height of keratinized tissue, thickness of keratinized tissue, healing index and pain perception, were performed immediately before surgery (baseline and after 6 months interval following periodontal surgery. Results: In the test group, significant improvement was seen in terms CAL, REC-HT, REC-WD, HKT and TKT from baseline to 6 months. In the control group, only significant improvement seen was in REC-HT and TKT from baseline to 6 months. Comparison of both Healing Index and VAS score was done and it showed no significant difference between test and the control group except VAS at 1 week. Conclusion: Though CTG is a gold standard procedure, PRF can be used as an alternative procedure by keeping patient's comfort and recognition in mind.

  13. The prognostic value of nailfold capillary changes for the development of connective tissue disease in children and adolescents with primary raynaud phenomenon: a follow-up study of 250 patients.

    Science.gov (United States)

    Pavlov-Dolijanović, Slavica; Damjanov, Nemanja; Ostojić, Predrag; Susić, Gordana; Stojanović, Roksanda; Gacić, Dragica; Grdinić, Aleksandra

    2006-01-01

    To assess the prognostic value of capillaroscopy findings for the development of connective tissue disease in children and adolescents with Raynaud phenomenon, we followed up a group of 250 (mean age 15 years) for 1 to 6 years after the first capillaroscopy was performed. Every 6 months they were screened for signs and symptoms of connective tissue disease. Analysis was performed on capillary changes registered 6 months before the development of connective tissue disease. Capillary changes were classified into three types: normal, nonspecific, and sclerodermatous. At the end of the follow-up period, 191 (76%) subjects had primary Raynaud phenomenon, 27 (10.8%) were diagnosed as having undifferentiated connective tissue disease, and 32 (12.8%) fulfilled the criteria for a diagnosis of a specific connective tissue disease. Systemic lupus erythematosus was found in nine (3.6%) patients, rheumatoid arthritis in 10 (4%) patients (six of them with juvenile onset rheumatoid arthritis), and scleroderma spectrum disorders in 13 (5.2%). The mean time for the evolution of Raynaud phenomenon into undifferentiated connective tissue disease or a form of the disease was 2 years. Most of the subjects with primary Raynaud phenomenon (173/191, 91%), undifferentiated connective tissue disease (22/27, 81%), juvenile onset rheumatoid arthritis/rheumatoid arthritis (7/10, 70%), and systemic lupus erythematosus (6/9, 67%) had normal capillary findings. Nonspecific capillary changes occurred in 3 of 10 (30%) patients with rheumatoid arthritis, 2 of 9 (22%) with systemic lupus erythematosus, 4 of 27 (15%) with undifferentiated connective tissue disease, and 18 of 191 (9%) with primary Raynaud phenomenon. Of all the subjects, only 10 (4%) showed sclerodermatous disease type capillary changes 6 months before the expression of a particular disease: eight (62%) of these developed scleroderma spectrum disorders, one expressed systemic lupus erythematosus, and one had undifferentiated connective

  14. Characteristics of meniscus progenitor cells migrated from injured meniscus.

    Science.gov (United States)

    Seol, Dongrim; Zhou, Cheng; Brouillette, Marc J; Song, Ino; Yu, Yin; Choe, Hyeong Hun; Lehman, Abigail D; Jang, Kee W; Fredericks, Douglas C; Laughlin, Barbara J; Martin, James A

    2017-09-01

    Serious meniscus injuries seldom heal and increase the risk for knee osteoarthritis; thus, there is a need to develop new reparative therapies. In that regard, stimulating tissue regeneration by autologous stem/progenitor cells has emerged as a promising new strategy. We showed previously that migratory chondrogenic progenitor cells (CPCs) were recruited to injured cartilage, where they showed a capability in situ tissue repair. Here, we tested the hypothesis that the meniscus contains a similar population of regenerative cells. Explant studies revealed that migrating cells were mainly confined to the red zone in normal menisci: However, these cells were capable of repopulating defects made in the white zone. In vivo, migrating cell numbers increased dramatically in damaged meniscus. Relative to non-migrating meniscus cells, migrating cells were more clonogenic, overexpressed progenitor cell markers, and included a larger side population. Gene expression profiling showed that the migrating population was more similar to CPCs than other meniscus cells. Finally, migrating cells equaled CPCs in chondrogenic potential, indicating a capacity for repair of the cartilaginous white zone of the meniscus. These findings demonstrate that, much as in articular cartilage, injuries to the meniscus mobilize an intrinsic progenitor cell population with strong reparative potential. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1966-1972, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  15. David valve-sparing aortic root replacement: equivalent mid-term outcome for different valve types with or without connective tissue disorder.

    Science.gov (United States)

    Kvitting, John-Peder Escobar; Kari, Fabian A; Fischbein, Michael P; Liang, David H; Beraud, Anne-Sophie; Stephens, Elizabeth H; Mitchell, R Scott; Miller, D Craig

    2013-01-01

    Although implicitly accepted by many that the durability of valve-sparing aortic root replacement in patients with bicuspid aortic valve disease and connective tissue disorders will be inferior, this hypothesis has not been rigorously investigated. From 1993 to 2009, 233 patients (27% bicuspid aortic valve, 40% Marfan syndrome) underwent Tirone David valve-sparing aortic root replacement. Follow-up averaged 4.7 ± 3.3 years (1102 patient-years). Freedom from adverse outcomes was determined using log-rank calculations. Survival at 5 and 10 years was 98.7% ± 0.7% and 93.5% ± 5.1%, respectively. Freedom from reoperation (all causes) on the aortic root was 92.2% ± 3.6% at 10 years; 3 reoperations were aortic valve replacement owing to structural valve deterioration. Freedom from structural valve deterioration at 10 years was 96.1% ± 2.1%. No significant differences were found in survival (P = .805, P = .793, respectively), reoperation (P = .179, P = .973, respectively), structural valve deterioration (P = .639, P = .982, respectively), or any other functional or clinical endpoints when patients were stratified by valve type (tricuspid aortic valve vs bicuspid aortic valve) or associated connective tissue disorder. At the latest echocardiographic follow-up (95% complete), 202 patients (94.8%) had none or trace aortic regurgitation, 10 (4.7%) mild, 0 had moderate to severe, and 1 (0.5%) had severe aortic regurgitation. Freedom from greater than 2+ aortic regurgitation at 10 years was 95.3% ± 2.5%. Six patients sustained acute type B aortic dissection (freedom at 10 years, 90.4% ± 5.0%). Tirone David reimplantation valve-sparing aortic root replacement in carefully selected young patients was associated with excellent clinical and echocardiographic outcome in patients with either a tricuspid aortic valve or bicuspid aortic valve. No demonstrable adverse influence was found for Marfan syndrome or connective tissue disorder on durability, clinical outcome

  16. Bobby Sox homology regulates odontoblast differentiation of human dental pulp stem cells/progenitors

    Science.gov (United States)

    2014-01-01

    Background Transcription factors have been implicated in regulating the differentiation of odontoblasts from dental pulp stem cells/progenitors (DPSCs/progenitors), but their regulatory network is not completely understood. Result New transcription factors that control the odontoblast differentiation of human DPSCs/progenitors were analyzed using a microarray. The result revealed bobby sox homolog (BBX) to be expressed most strongly during odontoblast differentiation. Validation using RT-PCR also revealed the strong expression of BBX during the odontoblast differentiation of DPSCs/progenitors. BBX expression was also detected in adult molar odontoblasts and other tissues, including the heart, kidney, testis, and bone marrow. To understand the role of BBX in odontoblast differentiation, BBX variant 1 and 2 cDNA were cloned and overexpressed in DPSCs/progenitors. The results showed that the overexpression of BBX cDNA in DPSCs/progenitors induced substantial mineralization and expression of the odontoblast marker genes, such as ALP, OPN, BSP, DMP1, and DSPP. The knockdown of BBX using shRNA, however, did not affect mineralization, but the expression of ALP and DSPP was decreased substantially. Meanwhile overexpression or knockdown of BBX did not modulate proliferation of DPSCs/progenitors. Conclusion Our results suggest that BBX plays an important role during the odontoblast differentiation of human DPSCs/progenitors. PMID:24885382

  17. In vivo tissue engineering of musculoskeletal tissues.

    Science.gov (United States)

    McCullen, Seth D; Chow, Andre G Y; Stevens, Molly M

    2011-10-01

    Tissue engineering of musculoskeletal tissues often involves the in vitro manipulation and culture of progenitor cells, growth factors and biomaterial scaffolds. Though in vitro tissue engineering has greatly increased our understanding of cellular behavior and cell-material interactions, this methodology is often unable to recreate tissue with the hierarchical organization and vascularization found within native tissues. Accordingly, investigators have focused on alternative in vivo tissue engineering strategies, whereby the traditional triad (cells, growth factors, scaffolds) or a combination thereof are directly implanted at the damaged tissue site or within ectopic sites capable of supporting neo-tissue formation. In vivo tissue engineering may offer a preferential route for regeneration of musculoskeletal and other tissues with distinct advantages over in vitro methods based on the specific location of endogenous cultivation, recruitment of autologous cells, and patient-specific regenerated tissues. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Soft Tissue and Marginal Bone Adaptation on Platform-Switched Implants with a Morse Cone Connection: A Histomorphometric Study in Dogs.

    Science.gov (United States)

    Bolle, Caroline; Gustin, Marie-Paule; Fau, Didier; Boivin, Georges; Exbrayat, Patrick; Grosgogeat, Brigitte

    2016-01-01

    The purpose of this study was to investigate peri-implant tissue adaptation on platform-switched implants with a Morse cone-type connection, after 3 and 12 weeks of healing in dogs. Ten weeks after mandibular premolar extractions, eight beagle dogs received three implants each. At each biopsy interval, four animals were sacrificed and biopsies were processed for histologic analysis. The height of the peri-implant mucosa was 2.32 mm and 2.88 mm, respectively, whereas the bone level in relation to the implant platform was -0.39 mm and -0.67 mm, respectively, after 3 and 12 weeks of healing. Within the limits of the present study, platform-switched implants exhibited reduced values of biologic width and marginal bone loss when compared with previous data.

  19. The state of «the pituitary gland - thyroid gland system» in the young men with undifferentiated dysplasia of the connective tissue

    Directory of Open Access Journals (Sweden)

    P. A. Yurchenko

    2013-01-01

    Full Text Available To investigate the state of «the pituitary gland-thyroid gland system» in the patients with undifferentiated dysplasia of the connective tissue (UDCT 83 young men of the call up age (18.2±0.4 y.o. were examined. The control group consisted of 26 practically healthy young men of the same age (18.5±0.2 y.o.. Autoimmune thyroiditis (AIT was diagnosed in 32.5 % of the men with UDCT. The rate of the internal (visceral phenotypical signs of UDCT in this group was significantly higher than in the men with UDCT but without thyroid problems.

  20. Eggshell membrane: A possible new natural therapeutic for joint and connective tissue disorders. Results from two open-label human clinical studies

    Directory of Open Access Journals (Sweden)

    Kevin J Ruff

    2009-05-01

    Full Text Available Kevin J Ruff1, Dale P DeVore2, Michael D Leu3, Mark A Robinson41ESM Technologies, LLC, Carthage, MO, USA; 2Membrell, LLC, Carthage, MO, USA; 3Private Practice, Jenks, OK, USA; 4Robinson Family Health Center, Carthage, MO, USABackground: Natural Eggshell Membrane (NEM® is a novel dietary supplement that contains naturally occurring glycosaminoglycans and proteins essential for maintaining healthy joint and connective tissues. Two single center, open-label human clinical studies were conducted to evaluate the efficacy and safety of NEM® as a treatment for pain and inflexibility associated with joint and connective tissue disorders. Methods: Eleven (single-arm trial and 28 (double-arm trial patients received oral NEM® 500 mg once daily for four weeks. The primary outcome measure was to evaluate the change in general pain associated with the treatment joints/areas (both studies. In the single-arm trial, range of motion (ROM and related ROM-associated pain was also evaluated. The primary treatment response endpoints were at seven and 30 days. Both clinical assessments were performed on the intent-to-treat (ITT population within each study.Results: Single-arm trial: Supplementation with NEM® produced a significant treatment response at seven days for flexibility (27.8% increase; P = 0.038 and at 30 days for general pain (72.5% reduction; P = 0.007, flexibility (43.7% increase; P = 0.006, and ROM-associated pain (75.9% reduction; P = 0.021. Double-arm trial: Supplementation with NEM® produced a significant treatment response for pain at seven days for both treatment arms (X: 18.4% reduction; P = 0.021. Y: 31.3% reduction; P = 0.014. There was no clinically meaningful difference between treatment arms at seven days, so the Y arm crossed over to the X formulation for the remainder of the study. The significant treatment response continued through 30 days for pain (30.2% reduction; P = 0.0001. There were no adverse events reported during either

  1. Plasma connective tissue growth factor is an independent predictor of end-stage renal disease and mortality in type 1 diabetic nephropathy

    DEFF Research Database (Denmark)

    Nguyen, Tri Q; Tarnow, Lise; Jorsal, Anders

    2008-01-01

    OBJECTIVE: We evaluated the predictive value of baseline plasma connective tissue growth factor (CTGF) in a prospective study of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: Subjects were 198 type 1 diabetic patients with established diabetic nephropathy and 188 type 1 diabetic.......1-1.7]). In contrast, in normoalbuminuric patients, plasma CTGF did not correlate with clinical parameters and did not predict outcome. CONCLUSIONS: Plasma CTGF contributes significantly to prediction of ESRD and mortality in patients with type 1 diabetic nephropathy....... patients with persistent normoalbuminuria. Follow-up time was 12.8 years. Prediction of end-stage renal disease (ESRD) and mortality by plasma CTGF was analyzed in conjunction with conventional risk factors. RESULTS: Plasma CTGF was higher in patients with nephropathy than in patients with normoalbuminuria...

  2. Relationship between meat toughness and properties of connective tissue from cows and young bulls heat treated at low temperatures for prolonged times

    DEFF Research Database (Denmark)

    Christensen, Line; Ertbjerg, Per; Løje, Hanne

    2013-01-01

    The aim of the current study was to elucidate whether cows and young bulls require different combinations of heating temperature and heating time to reduce toughness of the meat. The combined effect of heating temperature and time on toughness of semitendinosus muscle from the two categories...... of beef was investigated and the relationship to properties of connective tissue was examined. Measurements of toughness, collagen solubility, cathepsin activity and protein denaturation of beef semitendinosus heated at temperatures between 53. °C and 63. °C for up to 19 1/2. h were conducted. The results...... revealed that slightly higher temperatures and prolonged heating times were required to reduce toughness of semitendinosus from cows to the same level as in young bulls. Reduced toughness of semitendinosus as a result of low temperature for prolonged time is suggested to result from weakening...

  3. Two novel distinct COL1A2 mutations highlight the complexity of genotype-phenotype correlations in osteogenesis imperfecta and related connective tissue disorders.

    Science.gov (United States)

    Reuter, Miriam S; Schwabe, Georg C; Ehlers, Christian; Marschall, Christoph; Reis, André; Thiel, Christian; Graul-Neumann, Luitgard

    2013-12-01

    Osteogenesis imperfecta is a heritable connective tissue disorder characterized by variable symptoms including predisposition to fractures. Despite the identification of numerous mutations, a reliable genotype-phenotype correlation has remained notoriously difficult. We now describe two patients with osteogenesis imperfecta and novel, so far undescribed mutations in the COL1A2 gene, further highlighting this complexity. A 3-year-old patient presented with features reminiscent of a connective tissue disorder, with joint hypermobility, Wormian bones, streaky lucencies in the long bones and relative macrocephaly. The patient carried a heterozygous c.1316G > A (p.Gly439Asp) mutation in the COL1A2 gene located in a triple-helix region, in which glycine substitutions have been assumed to cause perinatal lethal OI (Sillence type II). A second family with type I osteogenesis imperfecta carried a heterozygous nonsense mutation c.4060C > T (p.Gln1354X) within the last exon of COL1A2. Whereas other heterozygous nonsense mutations in COL1A2 do not lead to a phenotype, in this case the mRNA is presumed to escape nonsense-mediated decay. Therefore the predicted COL1A2 propeptide lacks the last 13 C-terminal amino acids, suggesting that the OI phenotype results from decelerated assembly and overmodification of the collagen triple helix. The presented COL1A2 mutations exemplify the complexity of COL1A2 genotype-phenotype correlation in genetic counselling in OI. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  4. Efficacy and safety of alendronate for the treatment of osteoporosis in diffuse connective tissue diseases in children: a prospective multicenter study.

    Science.gov (United States)

    Bianchi, M L; Cimaz, R; Bardare, M; Zulian, F; Lepore, L; Boncompagni, A; Galbiati, E; Corona, F; Luisetto, G; Giuntini, D; Picco, P; Brandi, M L; Falcini, F

    2000-09-01

    Osteopenia/osteoporosis is being increasingly reported as a complication of many chronic diseases, even in children. In this preliminary study, we evaluated the effect of an oral bisphosphonate (alendronate) on bone mass in children with diffuse connective tissue diseases. Thirty-eight children with low bone mass were treated with alendronate for 1 year; 38 children who had the same primary disorders as the study patients but in a less severe form served as untreated control patients. We were also able to evaluate changes in bone mass (before and after alendronate) in 16 of the treated patients whose bone mineral density (BMD) had been routinely measured before the present study was initiated. BMD increased by a mean +/- SD of 14.9 +/- 9.8% (P < 0.002 versus baseline) in the treated patients (reaching the normal range in 13 patients), while the BMD was 2.6 +/- 5% (not significant versus baseline) in the control group (15 had a decrease). Most interestingly, there was a large increase in BMD (15.3 +/-9.9%) after alendronate therapy in the 16 children who had their BMD followed up in the year before the study, during which time they had shown little increase in BMD (1.03 +/- 6.3%), and often a decrease. Considering their condition, increases in the height of all patients was satisfactory. No new fractures were observed after alendronate therapy was initiated. Bisphosphonates can be considered essential components of the treatment of secondary osteoporosis, not only in adults, but also in pediatric patients. Alendronate has a positive effect on secondary osteopenia/osteoporosis in children with connective tissue diseases.

  5. Expression of transcription factors Slug in the lens epithelial cells undergoing epithelial-mesenchymal transition induced by connective tissue growth factor

    Directory of Open Access Journals (Sweden)

    Ying-Na Wang

    2015-10-01

    Full Text Available AIM:To investigate the expression of transcription factors Slug in human lens epithelial cells (HLECs undergoing epithelial-mesenchymal transition (EMT induced by connective tissue growth factor (CTGF.METHODS: HLECs were treated with CTGF of different concentrations (20, 50 and 100 ng/mL or without CTGF (control for 24h. The morphological changes of HLECs were analysed by microscopy. The expression and cellular localization of Slug was evaluated by immumo-fluorescence. Expressions of Slug, E-cadherin and alpha smooth muscle actin (α-SMA were further determined by Western blot analysis. RESULTS: HLECs showed spidle fibrolasts-like characteristics and loosely connected each other after CTGF treatment. The immuno-fluorescence staining indicated that Slug was localized in the nuclei and its expression was induced by CTGF. The relative expressions of Slug protein were 1.64±0.11, 1.96 ±0.03, 3.12 ±0.10, and 4.08±0.14, respectively, in response to control group and treatment with CTGF of 20, 50 and 100 ng/mL (F=443.86, PCONCLUSION: Transcription factor Slug may be involved in EMT of HLECs induced by CTGF in vitro.

  6. Expression of transcription factors Slug in the lens epithelial cells undergoing epithelial-mesenchymal transition induced by connective tissue growth factor.

    Science.gov (United States)

    Wang, Ying-Na; Qin, Li; Li, Jing-Ming; Chen, Li; Pei, Cheng

    2015-01-01

    To investigate the expression of transcription factors Slug in human lens epithelial cells (HLECs) undergoing epithelial-mesenchymal transition (EMT) induced by connective tissue growth factor (CTGF). HLECs were treated with CTGF of different concentrations (20, 50 and 100 ng/mL) or without CTGF (control) for 24h. The morphological changes of HLECs were analysed by microscopy. The expression and cellular localization of Slug was evaluated by immumo-fluorescence. Expressions of Slug, E-cadherin and alpha smooth muscle actin (α-SMA) were further determined by Western blot analysis. HLECs showed spidle fibrolasts-like characteristics and loosely connected each other after CTGF treatment. The immuno-fluorescence staining indicated that Slug was localized in the nuclei and its expression was induced by CTGF. The relative expressions of Slug protein were 1.64±0.11, 1.96 ±0.03, 3.12 ±0.10, and 4.08±0.14, respectively, in response to control group and treatment with CTGF of 20, 50 and 100 ng/mL (F=443.86, PSlug protein levels were correlated well with up-expression of α-SMA (0.78±0.05, 0.85±0.06, 2.17±0.15, 2.86±0.10; F=449.85, PSlug may be involved in EMT of HLECs induced by CTGF in vitro.

  7. The rehabilitation of facial involvement in systemic sclerosis: efficacy of the combination of connective tissue massage, Kabat's technique and kinesitherapy: a randomized controlled trial.

    Science.gov (United States)

    Maddali-Bongi, S; Landi, G; Galluccio, F; Del Rosso, A; Miniati, I; Conforti, M L; Casale, R; Matucci-Cerinic, M

    2011-07-01

    In Systemic Sclerosis (SSc), face involvement causes functional loss as well as aesthetic changes and loss of the self-image. The aim of the work is to evaluate the efficacy of a rehabilitation program based on the combination of Kabat's technique, connective massage and kinesitherapy specifically conceived for the face of SSc patients. Forty SSc patients were enrolled: 20 patients (interventional group) were treated for 9 weeks (twice a week, 1 h per session) with a combined connective tissue massage, Kabat's technique, kinesitherapy and home exercise program, and 20 patients (control group) were assigned only home exercise program. All patients were assessed at baseline (T0), at the end of the treatment (T1) and after 9 weeks of follow-up (T2). They were evaluated with SF-36, HAQ, modified Rodnan skin score, mouth opening in centimeters and Mouth Handicap in Systemic Sclerosis (MHISS) scale. At T1, both groups improved in mouth opening (P massage, Kabat's technique, kinesitherapy and home-based exercises is more effective than a home exercise program alone in the rehabilitative treatment of SSc facial involvement.

  8. Ultrastructural and biochemical observations on proteoglycans and collagen in the mutable connective tissue of the feather star Antedon bifida (Echinodermata, Crinoidea).

    Science.gov (United States)

    Erlinger, R; Welsch, U; Scott, J E

    1993-01-01

    Mutable connective tissue, unique to echinoderms, changes its mechanical behaviour within seconds of nervous stimulation. The molecular mechanism of this phenomenon is not understood. In this study proteoglycans and collagen of the brachial ligaments connecting neighbouring ossicles of the arms of the feather star Antedon bifida have been investigated by biochemistry, light and electron microscopy and the critical electrolyte concentration (CEC) technique using the dye Cupromeronic Blue (CB). The ligaments consist mainly of parallel cross-striated collagen fibrils, 82 +/- 12 nm in diameter, with a characteristic banding pattern and a D-period of 52.8 +/- 3.2 nm. Some fibrils were disaggregated into bundles of 10-11 nm protofibrils, lying between the normal fibrils. Proteoglycans occur at the surface of the fibrils with 2 binding sites (each with a different CEC) per D-period and also inside the fibrils. The surface proteoglycans are more highly sulphated (i.e. their CECs are > 1.3 M) than the intrafibrillar proteoglycans (CEC < 0.9 M). The glycosaminoglycans consist of a highly sulphated chondroitin sulphate, possibly with fucose residues. The results are consistent with the theory that disaggregation of the fibrils into protofibrils and reaggregation might be a mechanism of mutability, without excluding the possibility that fibrils may slide alongside each other during movements in the viscous phase of the ligament. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 PMID:8270464

  9. Cardiac Progenitor Cell Extraction from Human Auricles

    KAUST Repository

    Di Nardo, Paolo

    2017-02-22

    For many years, myocardial tissue has been considered terminally differentiated and, thus, incapable of regenerating. Recent studies have shown, instead, that cardiomyocytes, at least in part, are slowly substituted by new cells originating by precursor cells mostly embedded into the heart apex and in the atria. We have shown that an elective region of progenitor cell embedding is represented by the auricles, non-contractile atria appendages that can be easily sampled without harming the patient. The protocol here reported describes how from auricles a population of multipotent, cardiogenic cells can be isolated, cultured, and differentiated. Further studies are needed to fully exploit this cell population, but, sampling auricles, it could be possible to treat cardiac patients using their own cells circumventing rejection or organ shortage limitations.

  10. Progenitor cell populations in the periodontal ligament of mice

    International Nuclear Information System (INIS)

    McCulloch, C.A.

    1985-01-01

    Stem cells in a variety of renewal tissues exhibit a slow rate of cell proliferation. The periodontal ligament of mouse molars was examined for the presence of slowly cycling progenitor cells to provide evidence for the existence of stem cells in this tissue. A pulse injection of 3 H-thymidine was administered and mice were sacrificed between 1 hour and 14 days after injection. Analysis of radioautographs using percentage of labeled cells and grain counts demonstrated that a population of label-retaining cells within 10 micron of blood vessels traversed the cell cycle more slowly than proliferating cells located greater than 10 micron from blood vessels. These data suggest that there is a slowly dividing population of progenitor cells in paravascular sites in mouse molar periodontal ligament which may be stem cells

  11. Probing the mystery of Chinese medicine meridian channels with special emphasis on the connective tissue interstitial fluid system, mechanotransduction, cells durotaxis and mast cell degranulation

    Directory of Open Access Journals (Sweden)

    Fung Peter

    2009-05-01

    Full Text Available Abstract This article hypothesizes that the Chinese medicine meridian system is a special channel network comprising of skin with abundant nerves and nociceptive receptors of various types, and deeper connective tissues inside the body with the flowing interstitial fluid system. These meridian channels provide efficient migratory tracks mainly due to durotaxis (also including chemotaxis for mast cells, fibroblasts and other cells to migrate and carry out a number of physiological functions. Acupuncture acting on meridian channel causes cytoskeletal remodeling through mechanotransduction, leading to regulation of gene expression and the subsequent production of related proteins. Also, stimulation on cell surface can trigger Ca2+ activities, resulting in a cascade of intra- and inter-cellular signaling. Moreover, nerve endings in the meridian channels interact with mast cells and induce the degranulation of these cells, leading to the release of many specific biomolecules needed for homeostasis, immune surveillance, wound healing and tissue repair. Acupoint along a meridian channel is a functional site to trigger the above functions with specificity and high efficiency.

  12. In-vivo nonlinear optical microscopy (NLOM) of epithelial-connective tissue interface (ECTI) reveals quantitative measures of neoplasia in hamster oral mucosa.

    Science.gov (United States)

    Pal, Rahul; Yang, Jinping; Ortiz, Daniel; Qiu, Suimin; Resto, Vicente; McCammon, Susan; Vargas, Gracie

    2015-01-01

    The epithelial-connective tissue interface (ECTI) plays an integral role in epithelial neoplasia, including oral squamous cell carcinoma (OSCC). This interface undergoes significant alterations due to hyperproliferating epithelium that supports the transformation of normal epithelium to precancers and cancer. We present a method based on nonlinear optical microscopy to directly assess the ECTI and quantify dysplastic alterations using a hamster model for oral carcinogenesis. Neoplastic and non-neoplastic normal mucosa were imaged in-vivo by both multiphoton autofluorescence microscopy (MPAM) and second harmonic generation microscopy (SHGM) to obtain cross-sectional reconstructions of the oral epithelium and lamina propria. Imaged sites were biopsied and processed for histopathological grading and measurement of ECTI parameters. An ECTI shape parameter was calculated based on deviation from the linear geometry (ΔLinearity) seen in normal mucosa was measured using MPAM-SHGM and histology. The ECTI was readily visible in MPAM-SHGM and quantitative shape analysis showed ECTI deformation in dysplasia but not in normal mucosa. ΔLinearity was significantly (p epithelial thickness was seen with increasing grade of dysplasia. MPAM-SHGM provides new noninvasive ways for direct characterization of ECTI which may be used in preclinical studies to investigate the role of this interface in early transformation. Further development of the method may also lead to new diagnostic approaches to differentiate non-neoplastic tissue from precancers and neoplasia, possibly with other cellular and layer based indicators of abnormality.

  13. Evaluation of the Effects of BioCell Collagen, a Novel Cartilage Extract, on Connective Tissue Support and Functional Recovery From Exercise.

    Science.gov (United States)

    Lopez, Hector L; Ziegenfuss, Tim N; Park, Joosang

    2015-06-01

    Little is known about the effect of nutritional supplementation on metabolic optimization for enhancing adaptation and recovery of the connective tissue elements that support musculoskeletal function. The study aimed to determine the potential effect of supplementation with a novel, hydrolyzed chicken sternal cartilage extract-called BioCell Collagen-on biomarkers and functional indices of recovery from intense exercise. The research team designed a randomized, double-blind, placebo-controlled pilot study. The study was conducted at the Center for Applied Health Sciences in Stow, OH, USA. Participants were 8 healthy, recreationally active individuals, with a mean age of 29.3 y. Participants ingested either 3 g of a novel, hydrolyzed chicken sternal cartilage extract called BioCell Collagen ("supplement") or 3 g of a placebo daily for 6 wk prior to challenge with an upper-body, muscle-damaging resistance exercise (UBC) on day 43 and a rechallenge on day 46 to assess functional recovery. Primary endpoints were levels of 3 blood biomarkers-creatine kinase (CK), lactate dehydrogenase (LDH), and C-reactive protein (CRP)- and scores on a clinical pain scale and a perceived recovery scale (PRS). The extract attenuated the post-UBC increase in serum markers for muscle tissue damage: CK, LDH, and CRP. For the intervention group vs the placebo group, the mean changes were as follows: (1) an increase in CK of 20 U/L vs 4726 U/L, respectively; (2) a decrease in LDH of 3.5 U/L vs an increase of 82.9 U/L, respectively; and (3) an increase in CRP of 0.07 mg/L vs an increase of 0.7 mg/L, respectively. The performance decrement in bench press repetitions to failure was 57.9% on day 43 and 57.8% on day 46 for the intervention group vs 72.2% on day 43 and 65% on day 46 for the placebo group. The overall trend for the performance decrement, together with the results for the PRS, suggested that a more robust muscular recovery and adaptive response occurred with use of the extract. The

  14. Low-level laser therapy as an adjunct to connective tissue graft procedure in the treatment of gingival recession defects: A systematic review and meta-analysis.

    Science.gov (United States)

    Akram, Zohaib; Vohra, Fahim; Javed, Fawad

    2018-03-26

    The aim of this study was to systematically evaluate the effectiveness of low level laser therapy (LLLT) as an adjunct to connective tissue graft (CTG) procedure for the treatment of gingival recession (GR). The addressed PICO question was; "In patients with Miller Class I or II recession defects (Population), what is the effect of LLLT as adjunct to CTG (Intervention) in comparison to CTG alone (Comparison) on gingival recession depth (Outcome)" Electronic databases were searched up to December 2017. Primary outcomes included gingival recession depth (GRD), whereas secondary outcomes were width of keratinized tissue (WKT) and relative clinical attachment level gain (RCAL). The weighted mean differences (WMD) of outcomes and 95% confidence intervals (CI) for each variable were calculated using random effect model. Four randomized clinical studies were included. Two studies showed significantly greater improvements with LLLT whereas, 2 studies showed comparable outcomes between LLLT and CTG group. Considering the effects of adjunctive LLLT as compared to CTG, a high degree of heterogeneity for GRD (Q value = 9.40, P = .02, I 2 =68.11%) and WKT ((Q value = 16.04, P = .001, I 2 =81.31%) was noticed among both the groups. Meta-analysis showed a statistically significant GRD (WMD= -0.61, 95% CI= -1.23 to 0.004, P = .05) for LLLT + CTG treatment versus CTG alone only. LLLT improves clinical and patient-centered outcomes of CTG procedures for the treatment of GR remains debatable. However, due to the small number of included studies and high heterogeneity in the laser parameters, precautions must be exercised when interpreting the results of the present systematic review. Gingival recessions in dentistry are of major esthetic concern. Minimal gingival recessions can be treated by flap operations, but the predictability and stability of the outcomes is debatable. In the present review, low level laser therapy (LLLT) adjunct to connective tissue

  15. Date Palm (Phoenix dactylifera) Fruits as a Potential Cardioprotective Agent: The Role of Circulating Progenitor Cells

    Science.gov (United States)

    Alhaider, Ibrahim A.; Mohamed, Maged E.; Ahmed, K. K. M.; Kumar, Arun H. S.

    2017-01-01

    Context: Date palms, along with their fruits’ dietary consumption, possess enormous medicinal and pharmacological activities manifested in their usage in a variety of ailments in the various traditional systems of medicine. In recent years, the identification of progenitor cells in the adult organ systems has opened an altogether new approach to therapeutics, due to the ability of these cells to repair the damaged cells/tissues. Hence, the concept of developing therapeutics, which can mobilize endogenous progenitor cells, following tissue injury, to enhance tissue repair process is clinically relevant. Objectives: The present study investigates the potential of date of palm fruit extracts in repairing tissue injury following myocardial infarction (MI) potentially by mobilizing circulating progenitor cells. Methods: Extracts of four different varieties of date palm fruits common in Saudi Arabia eastern provision were scrutinized for their total flavonoid, total phenolic, in vitro antioxidant capacity, as well as their effects on two different rodent MI models. Results: High concentrations of phenolic and flavonoid compounds were observed in date palm fruit extracts, which contributed to the promising antioxidant activities of these extracts and the observed high protective effect against various induced in vivo MI. The extracts showed ability to build up reserves and to mobilize circulating progenitor cells from bone marrow and peripheral circulation to the site of myocardial infraction. Conclusion: Date palm fruit extracts have the potential to mobilize endogenous circulating progenitor cells, which can promote tissue repair following ischemic injury. PMID:28928656

  16. Date Palm (Phoenix dactylifera) Fruits as a Potential Cardioprotective Agent: The Role of Circulating Progenitor Cells.

    Science.gov (United States)

    Alhaider, Ibrahim A; Mohamed, Maged E; Ahmed, K K M; Kumar, Arun H S

    2017-01-01

    Context: Date palms, along with their fruits' dietary consumption, possess enormous medicinal and pharmacological activities manifested in their usage in a variety of ailments in the various traditional systems of medicine. In recent years, the identification of progenitor cells in the adult organ systems has opened an altogether new approach to therapeutics, due to the ability of these cells to repair the damaged cells/tissues. Hence, the concept of developing therapeutics, which can mobilize endogenous progenitor cells, following tissue injury, to enhance tissue repair process is clinically relevant. Objectives: The present study investigates the potential of date of palm fruit extracts in repairing tissue injury following myocardial infarction (MI) potentially by mobilizing circulating progenitor cells. Methods: Extracts of four different varieties of date palm fruits common in Saudi Arabia eastern provision were scrutinized for their total flavonoid, total phenolic, in vitro antioxidant capacity, as well as their effects on two different rodent MI models. Results: High concentrations of phenolic and flavonoid compounds were observed in date palm fruit extracts, which contributed to the promising antioxidant activities of these extracts and the observed high protective effect against various induced in vivo MI. The extracts showed ability to build up reserves and to mobilize circulating progenitor cells from bone marrow and peripheral circulation to the site of myocardial infraction. Conclusion: Date palm fruit extracts have the potential to mobilize endogenous circulating progenitor cells, which can promote tissue repair following ischemic injury.

  17. Microtubules CLASP to Adherens Junctions in epidermal progenitor cells

    DEFF Research Database (Denmark)

    Shahbazi, Marta N; Perez-Moreno, Mirna

    2014-01-01

    Cadherin-mediated cell adhesion at Adherens Junctions (AJs) and its dynamic connections with the microtubule (MT) cytoskeleton are important regulators of cellular architecture. However, the functional relevance of these interactions and the molecular players involved in different cellular contexts...... and cellular compartments are still not completely understood. Here, we comment on our recent findings showing that the MT plus-end binding protein CLASP2 interacts with the AJ component p120-catenin (p120) specifically in progenitor epidermal cells. Absence of either protein leads to alterations in MT...... dynamics and AJ functionality. These findings represent a novel mechanism of MT targeting to AJs that may be relevant for the maintenance of proper epidermal progenitor cell homeostasis. We also discuss the potential implication of other MT binding proteins previously associated to AJs in the wider context...

  18. The direct identification of core-collapse supernova progenitors.

    Science.gov (United States)

    Van Dyk, Schuyler D

    2017-10-28

    To place core-collapse supernovae (SNe) in context with the evolution of massive stars, it is necessary to determine their stellar origins. I describe the direct identification of SN progenitors in existing pre-explosion images, particularly those obtained through serendipitous imaging of nearby galaxies by the Hubble Space Telescope I comment on specific cases representing the various core-collapse SN types. Establishing the astrometric coincidence of a SN with its putative progenitor is relatively straightforward. One merely needs a comparably high-resolution image of the SN itself and its stellar environment to perform this matching. The interpretation of these results, though, is far more complicated and fraught with larger uncertainties, including assumptions of the distance to and the extinction of the SN, as well as the metallicity of the SN environment. Furthermore, existing theoretical stellar evolutionary tracks exhibit significant variations one from the next. Nonetheless, it appears fairly certain that Type II-P (plateau) SNe arise from massive stars in the red supergiant phase. Many of the known cases are associated with subluminous Type II-P events. The progenitors of Type II-L (linear) SNe are less established. Among the stripped-envelope SNe, there are now a number of examples of cool, but not red, supergiants (presumably in binaries) as Type IIb progenitors. We appear now finally to have an identified progenitor of a Type Ib SN, but no known example yet for a Type Ic. The connection has been made between some Type IIn SNe and progenitor stars in a luminous blue variable phase, but that link is still thin, based on direct identifications. Finally, I also describe the need to revisit the SN site, long after the SN has faded, to confirm the progenitor identification through the star's disappearance and potentially to detect a putative binary companion that may have survived the explosion.This article is part of the themed issue 'Bridging the gap: from

  19. Transcriptional pathways in cPGI2-induced adipocyte progenitor activation for browning

    Directory of Open Access Journals (Sweden)

    Irem eBayindir

    2015-08-01

    Full Text Available De novo formation of beige/brite adipocytes from progenitor cells contributes to the thermogenic adaptation of adipose tissue and holds great potential for the therapeutic remodeling of fat as a treatment for obesity. Despite the recent identification of several factors regulating browning of white fat, there is a lack of physiological cell models for the mechanistic investigation of progenitor-mediated beige/brite differentiation. We have previously revealed prostacyclin (PGI2 as one of the few known endogenous extracellular mediators promoting de novo beige/brite formation by relaying beta-adrenergic stimulation to the progenitor level. Here we present a cell model based on murine primary progenitor cells defined by markers previously shown to be relevant for in vivo browning, including a simplified isolation procedure. We demonstrate the specific and broad induction of thermogenic gene expression by PGI2 signaling in the absence of lineage conversion, and reveal the previously unidentified nuclear relocalization of the Ucp1 gene locus in association with transcriptional activation. By profiling the time course of the progenitor response we show that PGI2 signaling promoted progenitor cell activation through cell cycle and adhesion pathways prior to metabolic maturation towards an oxidative cell phenotype. Our results highlight the importance of core progenitor activation pathways for the recruitment of thermogenic cells and provide a resource for further mechanistic investigation.

  20. Enamel matrix proteins (Emdogain) in combination with coronally advanced flap or subepithelial connective tissue graft in the treatment of shallow gingival recessions.

    Science.gov (United States)

    Berlucchi, Ignazio; Francetti, Luca; Del Fabbro, Massimo; Testori, Tiziano; Weinstein, Roberto L

    2002-12-01

    This article describes two different surgical techniques of root coverage using Emdogain and shows preliminary results on 26 shallow recessions in 14 patients. For the treatment of 13 recessions, Emdogain was used in combination with a coronally advanced flap (CAF+EMD group). In the other 13 recessions, Emdogain and the flap were used in combination with a subepithelial connective tissue graft (CAF+CTG+EMD group). For the CAF+EMD group, the root coverage at 6 months was 93.97%, with an attachment gain of 3.2 mm; for the CAF+CTG+EMD group, the root coverage was 93.59%, with an attachment gain of 3.4 mm (no statistically significant difference between groups). When complete root coverage was not achieved, the residual recession was 1 mm in four cases and 2 mm in one case. Keratinized gingiva was increased for both groups, but more for the CAF+CTG+EMD group (1.38 mm versus 0.69 mm; statistically significant difference). Clinical attachment level decreased significantly in both groups, from 4.46 to 1.23 mm in the CAF+EMD group, and from 4.62 to 1.23 mm in the CAF+CTG+EMD group. Preliminary results show that Emdogain, in combination with CAF or CAF+CTG for the treatment of Miller Class I or II gingival recessions, displays good clinical results, with percentage of root coverage comparable or superior to other techniques. Further experimental studies on the dynamics of wound healing are needed to prove that EMD is really responsible for improving the percentage of regenerated versus repaired tissues with respect to other techniques.

  1. PET imaging of adoptive progenitor cell therapies

    International Nuclear Information System (INIS)

    Gelovani, Juri G.

    2008-01-01

    The overall objective of this application is to develop novel technologies for non-invasive imaging of adoptive stem cell-based therapies with positron emission tomography (PET) that would be applicable to human patients. To achieve this objective, stem cells will be genetically labeled with a PET-reporter gene and repetitively imaged to assess their distribution, migration, differentiation, and persistence using a radiolabeled reporter probe. This new imaging technology will be tested in adoptive progenitor cell-based therapy models in animals, including: delivery pro-apoptotic genes to tumors, and T-cell reconstitution for immunostimulatory therapy during allogeneic bone marrow progenitor cell transplantation. Technical and Scientific Merits. Non-invasive whole body imaging would significantly aid in the development and clinical implementation of various adoptive progenitor cell-based therapies by providing the means for non-invasive monitoring of the fate of injected progenitor cells over a long period of observation. The proposed imaging approaches could help to address several questions related to stem cell migration and homing, their long-term viability, and their subsequent differentiation. The ability to image these processes non-invasively in 3D and repetitively over a long period of time is very important and will help the development and clinical application of various strategies to control and direct stem cell migration and differentiation. Approach to accomplish the work. Stem cells will be genetically with a reporter gene which will allow for repetitive non-invasive 'tracking' of the migration and localization of genetically labeled stem cells and their progeny. This is a radically new approach that is being developed for future human applications and should allow for a long term (many years) repetitive imaging of the fate of tissues that develop from the transplanted stem cells. Why the approach is appropriate. The novel approach to stem cell imaging

  2. PET imaging of adoptive progenitor cell therapies.

    Energy Technology Data Exchange (ETDEWEB)

    Gelovani, Juri G.

    2008-05-13

    Objectives. The overall objective of this application is to develop novel technologies for non-invasive imaging of adoptive stem cell-based therapies with positron emission tomography (PET) that would be applicable to human patients. To achieve this objective, stem cells will be genetically labeled with a PET-reporter gene and repetitively imaged to assess their distribution, migration, differentiation, and persistence using a radiolabeled reporter probe. This new imaging technology will be tested in adoptive progenitor cell-based therapy models in animals, including: delivery pro-apoptotic genes to tumors, and T-cell reconstitution for immunostimulatory therapy during allogeneic bone marrow progenitor cell transplantation. Technical and Scientific Merits. Non-invasive whole body imaging would significantly aid in the development and clinical implementation of various adoptive progenitor cell-based therapies by providing the means for non-invasive monitoring of the fate of injected progenitor cells over a long period of observation. The proposed imaging approaches could help to address several questions related to stem cell migration and homing, their long-term viability, and their subsequent differentiation. The ability to image these processes non-invasively in 3D and repetitively over a long period of time is very important and will help the development and clinical application of various strategies to control and direct stem cell migration and differentiation. Approach to accomplish the work. Stem cells will be genetically with a reporter gene which will allow for repetitive non-invasive “tracking” of the migration and localization of genetically labeled stem cells and their progeny. This is a radically new approach that is being developed for future human applications and should allow for a long term (many years) repetitive imaging of the fate of tissues that develop from the transplanted stem cells. Why the approach is appropriate. The novel approach to

  3. Mechanosensory organ regeneration in zebrafish depends on a population of multipotent progenitor cells kept latent by Schwann cells.

    Science.gov (United States)

    Sánchez, Mario; Ceci, Maria Laura; Gutiérrez, Daniela; Anguita-Salinas, Consuelo; Allende, Miguel L

    2016-04-07

    Regenerating damaged tissue is a complex process, requiring progenitor cells that must be stimulated to undergo proliferation, differentiation and, often, migratory behaviors and morphological changes. Multiple cell types, both resident within the damaged tissue and recruited to the lesion site, have been shown to participate. However, the cellular and molecular mechanisms involved in the activation of progenitor cell proliferation and differentiation after injury, and their regulation by different cells types, are not fully understood. The zebrafish lateral line is a suitable system to study regeneration because most of its components are fully restored after damage. The posterior lateral line (PLL) is a mechanosensory system that develops embryonically and is initially composed of seven to eight neuromasts distributed along the trunk and tail, connected by a continuous stripe of interneuromastic cells (INCs). The INCs remain in a quiescent state owing to the presence of underlying Schwann cells. They become activated during development to form intercalary neuromasts. However, no studies have described if INCs can participate in a regenerative event, for example, after the total loss of a neuromast. We used electroablation in transgenic larvae expressing fluorescent proteins in PLL components to completely ablate single neuromasts in larvae and adult fish. This injury results in discontinuity of the INCs, Schwann cells, and the PLL nerve. In vivo imaging showed that the INCs fill the gap left after the injury and can regenerate a new neuromast in the injury zone. Further, a single INC is able to divide and form all cell types in a regenerated neuromast and, during this process, it transiently expresses the sox2 gene, a neural progenitor cell marker. We demonstrate a critical role for Schwann cells as negative regulators of INC proliferation and neuromast regeneration, and that this inhibitory property is completely dependent on active ErbB signaling. The potential

  4. Isolation and characterization of progenitor-like cells from human renal proximal tubules.

    Science.gov (United States)

    Lindgren, David; Boström, Anna-Karin; Nilsson, Kristina; Hansson, Jennifer; Sjölund, Jonas; Möller, Christina; Jirström, Karin; Nilsson, Elise; Landberg, Göran; Axelson, Håkan; Johansson, Martin E

    2011-02-01

    The tubules of the kidney display a remarkable capacity for self-renewal on damage. Whether this regeneration is mediated by dedifferentiating surviving cells or, as recently suggested, by stem cells has not been unequivocally settled. Herein, we demonstrate that aldehyde dehydrogenase (ALDH) activity may be used for isolation of cells with progenitor characteristics from adult human renal cortical tissue. Gene expression profiling of the isolated ALDH(high) and ALDH(low) cell fractions followed by immunohistochemical interrogation of renal tissues enabled us to delineate a tentative progenitor cell population scattered through the proximal tubules (PTs). These cells expressed CD24 and CD133, previously described markers for renal progenitors of Bowman's capsule. Furthermore, we show that the PT cells, and the glomerular progenitors, are positive for KRT7, KRT19, BCL2, and vimentin. In addition, tubular epithelium regenerating on acute tubular necrosis displayed long stretches of CD133(+)/VIM(+) cells, further substantiating that these cells may represent a progenitor cell population. Furthermore, a potential association of these progenitor cells with papillary renal cell carcinoma was discovered. Taken together, our data demonstrate the presence of a previously unappreciated subset of the PT cells that may be endowed with a more robust phenotype, allowing increased resistance to acute renal injury, enabling rapid repopulation of the tubules. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  5. In-vivo nonlinear optical microscopy (NLOM of epithelial-connective tissue interface (ECTI reveals quantitative measures of neoplasia in hamster oral mucosa.

    Directory of Open Access Journals (Sweden)

    Rahul Pal

    Full Text Available The epithelial-connective tissue interface (ECTI plays an integral role in epithelial neoplasia, including oral squamous cell carcinoma (OSCC. This interface undergoes significant alterations due to hyperproliferating epithelium that supports the transformation of normal epithelium to precancers and cancer. We present a method based on nonlinear optical microscopy to directly assess the ECTI and quantify dysplastic alterations using a hamster model for oral carcinogenesis. Neoplastic and non-neoplastic normal mucosa were imaged in-vivo by both multiphoton autofluorescence microscopy (MPAM and second harmonic generation microscopy (SHGM to obtain cross-sectional reconstructions of the oral epithelium and lamina propria. Imaged sites were biopsied and processed for histopathological grading and measurement of ECTI parameters. An ECTI shape parameter was calculated based on deviation from the linear geometry (ΔLinearity seen in normal mucosa was measured using MPAM-SHGM and histology. The ECTI was readily visible in MPAM-SHGM and quantitative shape analysis showed ECTI deformation in dysplasia but not in normal mucosa. ΔLinearity was significantly (p < 0.01 higher in dysplasia (0.41±0.24 than normal (0.11±0.04 as measured in MPAM-SHGM and results were confirmed in histology which showed similar trends in ΔLinearity. Increase in ΔLinearity was also statistically significant for different grades of dysplasia. In-vivo ΔLinearity measurement alone from microscopy discriminated dysplasia from normal tissue with 87.9% sensitivity and 97.6% specificity, while calculations from histology provided 96.4% sensitivity and 85.7% specificity. Among other quantifiable architectural changes, a progressive statistically significant increase in epithelial thickness was seen with increasing grade of dysplasia. MPAM-SHGM provides new noninvasive ways for direct characterization of ECTI which may be used in preclinical studies to investigate the role of this

  6. A Case of Subacute Cutaneous Lupus Erythematosus in a Patient with Mixed Connective Tissue Disease: Successful Treatment with Plasmapheresis and Rituximab

    Directory of Open Access Journals (Sweden)

    M. Fantò

    2013-01-01

    Full Text Available A 30-year-old woman affected by Mixed Connective Tissue Disease with scleroderma spectrum developed a facial eruption, a clinical and histological characteristic of subacute cutaneous lupus erythematosus (SCLE. Speckled anti-nuclear antibodies, high-titer anti-ribonucleoprotein1, anti-Sm, anti-Cardiolipin (aCL IgG/IgM, and anti-Ro/SSA antibodies were positive. SCLE was resistant to Azathioprine, Hydroxychloroquine, and Methotrexate while Mycophenolate Mofetil was suspended due to side effects. Subsequently, the patient was treated with three cycles of therapeutic plasma exchange (TPE followed, one month after the last TPE, by the anti-CD20 antibody Rituximab (RTX (375 mg/m2 weekly for 4 weeks. Eight and 16 months later the patient received other two TPE and RTX cycles, respectively. This therapeutic approach has allowed to obtain a complete skin healing persistent even after 8-month follow-up. Moreover, mitigation of Raynaud's phenomenon, resolution of alopecia, and a decline of aCL IgG/IgM and anti-Ro/SSA antibodies were observed.

  7. Role of Autoantibodies in the Diagnosis of Connective-Tissue Disease ILD (CTD-ILD and Interstitial Pneumonia with Autoimmune Features (IPAF

    Directory of Open Access Journals (Sweden)

    Adelle S. Jee

    2017-05-01

    Full Text Available The diagnosis of interstitial lung disease (ILD requires meticulous evaluation for an underlying connective tissue disease (CTD, with major implications for prognosis and management. CTD associated ILD (CTD-ILD occurs most commonly in the context of an established CTD, but can be the first and/or only manifestation of an occult CTD or occur in patients who have features suggestive of an autoimmune process, but not meeting diagnostic criteria for a defined CTD—recently defined as “interstitial pneumonia with autoimmune features” (IPAF. The detection of specific autoantibodies serves a critical role in the diagnosis of CTD-ILD, but there remains a lack of data to guide clinical practice including which autoantibodies should be tested on initial assessment and when or in whom serial testing should be performed. The implications of detecting autoantibodies in patients with IPAF on disease behaviour and management remain unknown. The evaluation of CTD-ILD is challenging due to the heterogeneity of presentations and types of CTD and ILD that may be encountered, and thus it is imperative that immunologic tests are interpreted in conjunction with a detailed rheumatologic history and examination and multidisciplinary collaboration between respiratory physicians, rheumatologists, immunologists, radiologists and pathologists.

  8. Effect of a Connective Tissue Graft in Combination With a Single Flap Approach in the Regenerative Treatment of Intraosseous Defects [Formula: see text].

    Science.gov (United States)

    Trombelli, Leonardo; Simonelli, Anna; Minenna, Luigi; Rasperini, Giulio; Farina, Roberto

    2017-04-01

    In the attempt to limit the post-surgery increase in buccal gingival recession (bREC), effect of a connective tissue graft (CTG) when combined with a buccal single flap approach (SFA) in the regenerative treatment of intraosseous defects is evaluated. Data related to 30 patients with an intraosseous defect treated with a buccal SFA with (SFA+CTG group; n = 15) or without (SFA group; n = 15) placement of a CTG and regenerative treatment were retrospectively derived at three clinical centers. bREC and probing parameters were assessed at presurgery and 6 months post-surgery. In addition to a significant attachment gain and probing depth reduction, adjunctive use of a CTG to a buccal SFA in the regenerative treatment of periodontal intraosseous defects associated with a buccal bone dehiscence resulted in a limited post-surgery bREC, a lower prevalence of defects with a clinically detectable apical displacement of the gingival margin, and an increase in gingival width and thickness. Adjunctive use of a CTG in the regenerative treatment of intraosseous defects associated with buccal bone dehiscence accessed by buccal SFA may support the stability of the gingival profile.

  9. Use of Leeds-Keio connective tissue prosthesis (L-K CTP) for reconstruction of deficient extensor mechanism with total knee replacement.

    Science.gov (United States)

    Sherief, Tamer I; Naguib, Ashraf M; Sefton, Graham K

    2005-08-01

    This study was carried out in order to assess the results of reconstruction of a deficient extensor mechanism in the presence of a total knee replacement (TKR) using the Leeds-Keio Connective Tissue Prosthesis (L-K CTP). The L-K CTP is available as flat tapes constructed from polyester in an open weave structure. It was used to reinforce and reconstruct the extensor mechanism, which was deficient in three patients who had undergone total knee replacement or were about to undergo total knee replacement. Two cases had extensor mechanism deficiency as a complication following total knee replacement while the third case had extensor mechanism deficiency at the time of the primary knee replacement. The average follow-up was 2 years (range of follow up was 12 to 48 months). All three cases showed good results with no extension lag and good range of movement at follow up. The use of L-K CTP for reconstruction of the knee extensor mechanism offers a good option for the management of the uncommon but difficult problem of extensor mechanism deficiency in patients with a total knee replacement.

  10. The risk of cancer in patients with connective tissue diseases but without dermatomyositis or polymyositis: A multicenter cohort study conducted over 15 years in China.

    Science.gov (United States)

    Xu, Wei; Guo, Huan; Liu, Zhi; Chen, Chen; Lei, Cong-Cong

    2016-09-01

    To investigate the relative risk of cancer in Chinese patients with connective tissue diseases (CTD) associated with and without dermatomyositis or polymyositis. A retrospective, multicenter cohort study investigated 32,380 CTD patients (2334 diagnosed with dermatomyositis or polymyositis) without a history of malignancies treated from January 1, 1997, to December 31, 2011. Standardized incidence ratios (SIR) of cancers determined the incidence of malignancies during follow-up. The data was compared with the cancer morbidity of the general population from the Chinese Cancer Registry Annual Report of National Central Cancer Registry. A total of 113 patients (348.98 per 100,000) developed cancer during follow-up, 75 (249.62 per 100,000) were patients with CTD without dermatomyositis or polymyositis. The risk of cancer among patients with CTD was increased (SIR=1.45, 95% confidence interval [CI] 1.22-1.71), and this risk increased with age (60 years SIR=2.34 (95%CI 0.93-2.77]) and the time of follow-up (dermatomyositis or polymyositis was not affected (SIR=0.93, 95%CI 0.75-1.16), regardless of gender, age, or follow-up. The cancer risk for patients with CTD without dermatomyositis or polymyositis was not increased or decreased, but it was increased when patients with dermatomyositis or polymyositis were included. Copyright © 2016 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

  11. Relationships between values of antibodies to several connective tissue disease autoantigens and pulmonary function in a Japanese general population: the Takahata study.

    Directory of Open Access Journals (Sweden)

    Hiroshi Nakano

    Full Text Available BACKGROUND: Accumulating evidence suggests the involvement of an autoimmune mechanism in the pathogenesis of respiratory dysfunction. The aim of this study was to investigate the relationship between pulmonary function and serum antibodies to several connective tissue disease autoantigens (ACTDA levels, which has not been investigated in a general population. METHODS: Blood sampling and spirometry were performed for subjects (n = 3,257 aged ≥40 years who participated in a community-based annual health check in Takahata, Japan, from 2004 to 2006. ACTDA was measured by enzyme immunoassay, and subjects with ACTDA values ≥20 were defined as positive. RESULTS: In males, there were significant inverse relationships between logarithmically transformed ACTDA values and spirometric parameters, including % predicted values for forced expiratory volume in 1 s (FEV1 and maximal midexpiratory flow (MMF as well as FEV1/forced vital capacity (FVC. Multiple linear regression analysis revealed that except for the relationship between ACTDA and FEV1/FVC, these relationships were still significant after adjustment for Brinkman index (a measure of inhaled cigarette consumption. The prevalence of positive ACTDA was greater in male never-smokers with mixed ventilation disorders and relatively severe airflow obstruction (% predicted FEV1 below the median value. CONCLUSIONS: Autoimmunity may be involved in the mechanism of impaired pulmonary function in the general population.

  12. Reconciling healthcare professional and patient perspectives in the development of disease activity and response criteria in connective tissue disease-related interstitial lung diseases.

    Science.gov (United States)

    Saketkoo, Lesley Ann; Mittoo, Shikha; Frankel, Sid; LeSage, Daphne; Sarver, Catherine; Phillips, Kristine; Strand, Vibeke; Matteson, Eric L

    2014-04-01

    Interstitial lung diseases (ILD), including those related to connective tissue disease (CTD), and idiopathic pulmonary fibrosis (IPF) carry high morbidity and mortality. Great efforts are under way to develop and investigate meaningful treatments in the context of clinical trials. However, efforts have been challenged by a lack of validated outcome measures and by inconsistent use of measures in clinical trials. Lack of consensus has fragmented effective use of strategies in CTD-ILD and IPF, with a history of resultant difficulties in obtaining agency approval of treatment interventions. Until recently, the patient perspective to determine domains and outcome measures in CTD-ILD and IPF had never been applied. Efforts described here demonstrate unequivocally the value and influence of patient involvement on core set development. Regarding CTD-ILD, this is the first OMERACT working group to directly address a manifestation/comorbidity of a rheumatic disease (ILD) as well as a disease not considered rheumatic (IPF). The OMERACT 11 proceedings of the CTD-ILD Working Group describe the forward and lateral process to include both the medical and patient perspectives in the urgently needed identification of a core set of preliminary domains and outcome measures in CTD-ILD and IPF.

  13. Membranous glomerulonephritis in a patient with anti-u1 ribonucleoprotein (RNP antibody-positive mixed connective tissue disease: A case report

    Directory of Open Access Journals (Sweden)

    Naoya Toriu

    2018-03-01

    Full Text Available We report a 33-year-old Japanese man diagnosed with mixed connective tissue disease (MCTD who developed nephrotic proteinuria. Both speckled antinuclear antibody (ANA and anti-U1 ribonucleoprotein (RNP antibody were positive, but anti-double-stranded DNA (dsDNA antibody and anti-Smith (Sm antibody were negative, while complement levels were normal. Renal biopsy revealed membranous glomerulonephritis (MGN with diffuse thickening of the glomerular basement membrane (GBM plus spike and bubble formation. Immunofluorescence demonstrated granular deposits of IgG and C3 along the GBM. Analysis of IgG subclasses showed predominant deposition of IgG1 and IgG4, unlike typical lupus nephritis in which there is predominant deposition of IgG1, IgG2, IgG3, and C1q. Electron microscopy identified numerous large electron-dense deposits (EDD of various types in the subepithelial region of the GBM, but there were no EDD localized in the mesangium or subendothelium. Based on these findings, MGN was considered to be closely related to MCTD in this patient.

  14. 2-Year Assessment of Tissue Biostimulation With Low-Level Laser on the Outcomes of Connective Tissue Graft in the Treatment of Single Gingival Recession: A Randomized Clinical Trial.

    Science.gov (United States)

    Santamaria, Mauro Pedrine; Fernandes-Dias, Stephanie Botti; Araújo, Cassia Fernandes; Lucas da Silva Neves, Felipe; Mathias, Ingrid Fernandes; Rebelato Bechara Andere, Naira Maria; Neves Jardini, Maria Aparecida

    2017-04-01

    Periodontal wound healing has been accelerated by different low-level laser therapy (LLLT) protocols. However, just a few studies have evaluated use of this therapy adjunctive to periodontal plastic surgery procedures. The present study shows 2-year results of a connective tissue graft (CTG) associated with LLLT in the treatment of gingival recession (GR) defects. Forty patients presenting Miller Class I and II GRs were previously treated by CTG (control group; n = 20) or CTG + LLLT (test group; n = 20). A diode laser (aluminum-gallium-arsenide, 660 nm) was applied to test sites immediately after surgery and every other day for 14 days (total of eight applications). After a follow-up of 2 years, clinical and esthetic evaluations were performed in 36 patients. Mean percentage of root coverage was 93.43% for the test group and 92.32% for the control group (P = 0.55). Complete root coverage was 79% (n = 15) for the test group and 76% (n = 13) for the control group (n = 13) (P = 0.80). Both groups showed esthetics maintenance after 2 years. Within the limitations of this study, results indicate that LLLT showed no additional benefit in the long term when associated with a CTG in the treatment of Miller Class I and II GRs.

  15. The Potential of Combination Therapeutics for More Complete Repair of Volumetric Muscle Loss Injuries: The Role of Exogenous Growth Factors and/or Progenitor Cells in Implantable Skeletal Muscle Tissue Engineering Technologies.

    Science.gov (United States)

    Passipieri, Juliana A; Christ, George J

    2016-01-01

    Despite the robust regenerative capacity of skeletal muscle, there are a variety of congenital and acquired conditions in which the volume of skeletal muscle loss results in major permanent functional and cosmetic deficits. These latter injuries are referred to as volumetric muscle loss (VML) injuries or VML-like conditions, and they are characterized by the simultaneous absence of multiple tissue components (i.e., nerves, vessels, muscles, satellite cells, and matrix). There are currently no effective treatment options. Regenerative medicine/tissue engineering technologies hold great potential for repair of these otherwise irrecoverable VML injuries. In this regard, three-dimensional scaffolds have been used to deliver sustained amounts of growth factors into a variety of injury models, to modulate host cell recruitment and extracellular matrix remodeling. However, this is a nascent field of research, and more complete functional improvements require more precise control of the spatiotemporal distribution of critical growth factors over a physiologically relevant range. This is especially true for VML injuries where incorporation of a cellular component into the scaffolds might provide not only a source of new tissue formation but also additional signals for host cell migration, recruitment, and survival. To this end, we review the major features of muscle repair and regeneration for largely recoverable injuries, and then discuss recent cell- and/or growth factor-based approaches to repair the more profound and irreversible VML and VML-like injuries. The underlying supposition is that more rationale incorporation of exogenous growth factors and/or cellular components will be required to optimize the regenerative capacity of implantable therapeutics for VML repair. © 2016 S. Karger AG, Basel.

  16. Cardiac involvement in undifferentiated connective tissue disease at risk for systemic sclerosis (otherwise referred to as very early-early systemic sclerosis): a TDI study.

    Science.gov (United States)

    D'Alto, Michele; Riccardi, Antonella; Argiento, Paola; Di Stefano, Ilaria; Romeo, Emanuele; Iacono, Agostino Mattera; D'Andrea, Antonello; Fasano, Serena; Sanduzzi, Alessandro; Bocchino, Marialuisa; Docimo, Ludovico; Tolone, Salvatore; Russo, Maria Giovanna; Valentini, Gabriele

    2017-10-09

    Undifferentiated connective tissue disease at risk for systemic sclerosis (UCTD-risk-SSc), otherwise referred to as very early-early SSc, is a condition characterized by Raynaud's phenomenon with serum SSc marker autoantibodies and/or typical capillaroscopic findings and unsatisfying classification criteria for the disease. The aim of the present study was to assess the prevalence of right (RV) or left ventricular (LV) systolic and/or diastolic dysfunction by standard echocardiography and tissue Doppler imaging (TDI). Thirty patients with UCTD-risk-SSc (28 female, mean age 47 ± 13 years, range 21-70) and 30 age- and sex-matched controls underwent cardiac assessment by standard echocardiography and TDI. UCTD-risk-SSc patients and controls did not show any difference at standard echocardiography. Despite results falling within the respective normal ranges, TDI pointed out a mild impairment of LV and RV diastolic (E m 15 ± 4 vs. 19 ± 5, p = 0.0004; E/E m 6.1 ± 1.7 vs. 4.8 ± 1.2, p = 0.001; E t 14 ± 3 vs. 16 ± 2, p = 0.02; E t /A t 0.9 ± 0.4 vs. 1.3 ± 0.3, p = 0.002; E/E t 3.5 ± 1.2 vs. 4.2 ± 0.9, p = 0.02) and systolic function (S m 13 ± 3 vs. 15 ± 2 cm/s, p risk-SSc patients as compared to controls. Notably, a statistically significant difference also emerged in the prevalence of TDI detected E'/A' t , (71% of UCTD-risk-SSc patients vs. 19% of controls; p risk-SSc patients show a previously unrecognized, mild biventricular systolic and diastolic dysfunction as compared to controls. The pathophysiologic meaning as well the predictive value of developing overt SSc await to be elucidated.

  17. Characterization of a resident population of adventitial macrophage progenitor cells in postnatal vasculature.

    Science.gov (United States)

    Psaltis, Peter J; Puranik, Amrutesh S; Spoon, Daniel B; Chue, Colin D; Hoffman, Scott J; Witt, Tyra A; Delacroix, Sinny; Kleppe, Laurel S; Mueske, Cheryl S; Pan, Shuchong; Gulati, Rajiv; Simari, Robert D

    2014-07-18

    Macrophages regulate blood vessel structure and function in health and disease. The origins of tissue macrophages are diverse, with evidence for local production and circulatory renewal. We identified a vascular adventitial population containing macrophage progenitor cells and investigated their origins and fate. Single-cell disaggregates from adult C57BL/6 mice were prepared from different tissues and tested for their capacity to form hematopoietic colony-forming units. Aorta showed a unique predilection for generating macrophage colony-forming units. Aortic macrophage colony-forming unit progenitors coexpressed stem cell antigen-1 and CD45 and were adventitially located, where they were the predominant source of proliferating cells in the aortic wall. Aortic Sca-1(+)CD45(+) cells were transcriptionally and phenotypically distinct from neighboring cells lacking stem cell antigen-1 or CD45 and contained a proliferative (Ki67(+)) Lin(-)c-Kit(+)CD135(-)CD115(+)CX3CR1(+)Ly6C(+)CD11b(-) subpopulation, consistent with the immunophenotypic profile of macrophage progenitors. Adoptive transfer studies revealed that Sca-1(+)CD45(+) adventitial macrophage progenitor cells were not replenished via the circulation from bone marrow or spleen, nor was their prevalence diminished by depletion of monocytes or macrophages by liposomal clodronate treatment or genetic deficiency of macrophage colony-stimulating factor. Rather adventitial macrophage progenitor cells were upregulated in hyperlipidemic ApoE(-/-) and LDL-R(-/-) mice, with adventitial transfer experiments demonstrating their durable contribution to macrophage progeny particularly in the adventitia, and to a lesser extent the atheroma, of atherosclerotic carotid arteries. The discovery and characterization of resident vascular adventitial macrophage progenitor cells provides new insight into adventitial biology and its participation in atherosclerosis and provokes consideration of the broader existence of local macrophage

  18. Wnt5a regulates dental follicle stem/progenitor cells of the periodontium.

    Science.gov (United States)

    Xiang, Lusai; Chen, Mo; He, Ling; Cai, Bin; Du, Yu; Zhang, Xinchun; Zhou, Chen; Wang, Chenglin; Mao, Jeremy J; Ling, Junqi

    2014-12-15

    Dental follicle gives rise to one or several tissues of the periodontium including the periodontal ligament, cementum and/or alveolar bone. Whether Wnt5a is expressed in the postnatal periodontium or regulates dental follicle stem/progenitor cells is unknown. Dental follicle stem/progenitor cells were isolated from postnatal day 1 (p1) to p11 from rat mandibular first molars. Immunolocalization mapped Wnt5a expression in the alveolar bone, periodontal ligament, and the developing ameloblast and odontoblast layers. Mononucleated and adherent cells were isolated from p7 dental follicle. Wnt5a was overexpressed in dental follicle stem/progenitor cells to study their proliferation, osteogenic differentiation and migration behavior, with subpopulations of native dental follicle stem/progenitor cells as controls, using real-time PCR (Taqman), Lenti-viral transfection, Western blotting and immunofluorescence. Wnt5a was expressed consistently in p1 to p11 rat peridontium. Native, p7 dental follicle stem/progenitor cells had modest ability to mineralize in the tested 14 days. Even in chemically defined osteogenesis medium, dental follicle stem/progenitor cells only showed modest mineralization. Upon addition of 300 ng/mL Wnt5a protein in osteogenesis medium, dental follicle stem/progenitor cells displayed mineralization that was still unremarkable. Chemically induced or Wnt5a-induced mineralization of dental follicle cells only occurred sparsely. Combination of Wnt5a with 100 ng/mL BMP2 finally prompted dental follicle stem/progenitor cells to produce robust mineralization with elevated expression of Runx2, alkaline phosphatase, collagen 1α1 and osteocalcin. Thus, native dental follicle stem/progenitor cells or some of their fractions may be somewhat modest in mineralization. Strikingly, Wnt5a protein significantly augmented RANKL ligand, suggesting putative regulatory roles of dental follicle stem/progenitor cells for the monocyte/osteoclast lineage and potential

  19. Local amino acid sequence patterns dominate the heterogeneous phenotype for the collagen connective tissue disease Osteogenesis Imperfecta resulting from Gly mutations.

    Science.gov (United States)

    Xiao, Jianxi; Yang, Zhangfu; Sun, Xiuxia; Addabbo, Rayna; Baum, Jean

    2015-10-01

    Osteogenesis Imperfecta (OI), a hereditary connective tissue disease in collagen that arises from a single Gly → X mutation in the collagen chain, varies widely in phenotype from perinatal lethal to mild. It is unclear why there is such a large variation in the severity of the disease considering the repeating (Gly-X-Y)n sequence and the uniform rod-like structure of collagen. We systematically evaluate the effect of local (Gly-X-Y)n sequence around the mutation site on OI phenotype using integrated bio-statistical approaches, including odds ratio analysis and decision tree modeling. We show that different Gly → X mutations have different local sequence patterns that are correlated with lethal and nonlethal phenotypes providing a mechanism for understanding the sensitivity of local context in defining lethal and non-lethal OI. A number of important trends about which factors are related to OI phenotypes are revealed by the bio-statistical analyses; most striking is the complementary relationship between the placement of Pro residues and small residues and their correlation to OI phenotype. When Pro is present or small flexible residues are absent nearby a mutation site, the OI case tends to be lethal; when Pro is present or small flexible residues are absent further away from the mutation site, the OI case tends to be nonlethal. The analysis also reveals the dominant role of local sequence around mutation sites in the Major Ligand Binding Regions that are primarily responsible for collagen binding to its receptors and shows that non-lethal mutations are highly predicted by local sequence considerations alone whereas lethal mutations are not as easily predicted and may be a result of more complex interactions. Understanding the sequence determinants of OI mutations will enhance genetic counseling and help establish which steps in the collagen hierarchy to target for drug therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Isolated congenital heart block in undifferentiated connective tissue disease and in primary Sjögren’s syndrome: a clinical study of 81 pregnancies in 41 patients

    Directory of Open Access Journals (Sweden)

    S. Todesco

    2011-09-01

    Full Text Available Objective: To study the incidence and the features of congenital heart block (CHB in patients with undifferentiated connective tissue disease (UCTD and primary Sjögren’s syndrome (pSS. Methods: We studied 81 pregnancies of 41 women attending the Outpatients’ Clinic of the Rheumatology Unit of University Hospital of Padova from July 1989 to March 2004. Twenty five of these (61% were affected with UCTD and 16 (39% with pSS. Serologic inclusion criteria was anti-Ro/La positivity, assessed by counterimmunoelectrophoresis and ELISA. Results: CHB was found in 2 out of the 46 (4,3% pregnancies followed by our Staff and in 2 out of the 35 (5,7% included in the retrospective part of the study. In 3 cases CHB was a 3rd degree block, causing pregnancy termination in 2. The only 2nd degree block was identified in one patient at the 22nd week of gestation and treated with dexamethasone and plasma-exchange. All of the women were positive to 52 kd and 60 kd Ro autoantibodies. CHB mothers had higher titer antibodies to 52 kd Ro protein than did the mothers with healthy infants (P = 0,026. Electrocardiographic abnormalities at birth were found in 3 out of 29 asymptomatic infants. One presented sinus bradycardia, the second abnormalities of ventricular repolarization, both regressed spontaneously, while the third ventricular extrasystoles which continue even now at 5 months. Conclusion: These results showed that in UCTD and pSS there is a higher incidence of CHB than that reported in Systemic Lupus Erythematosus. Electrocardiographic screening in all infants born to mothers with anti-Ro/La antibodies would seem an important measure to identify those with irreversible heart conduction abnormalities.

  1. The first Russian experience with the endothelin 1 receptor inhibitor traclir used in patients with pulmonary hypertension associated with systemic connective tissue diseases

    Directory of Open Access Journals (Sweden)

    Aleksandr Vitalyevich Volkov

    2011-01-01

    Full Text Available Objective: to study the efficacy and safety of the endothelin 1 receptor inhibitor traclir in patients with pulmonary hypertension (PH asso ciated with systemic connective tissue diseases. Subjects and methods. The study included 4 patients: 3 with scleroderma systematica and 1 with exanthematous lupus erythematosus. The diagnosis of PH was established on the basis of right heart catheterization data and after exclusion of all its other causes of HP. In addition to hemodynamic evaluation, the female patients underwent echocardiography (EchoCG, lung function tests, 6-minute walk test, and blood biochemical study (determination of uric acid levels. Traclir was given in a dose of 62.5 mg twice in the first 4 weeks of the study and then in a dose of 125 mg twice for the subsequent 12 weeks. Every 4 weeks, the levels of transaminases were monitored and a pregnancy test was carried out in patients of fertile age. Results. After 16-week intake of the drug, all the female patients were found to have obvious positive changes as a longer 6-min walk test distance and two female patients had improvement in the functional class of PH. Estimation of hemodynamic parameters suggested a posi tive effect in all the female patients, as confirmed primarily by an increase in cardiac index and a reduction in pulmonary vascular resist ance. According to EchoCG data, there was a substantial increase in tricuspid annular plane systolic excursion; other parameters had no informative value. During traclir therapy, there was also an increase in lung diffusion capacity and a reduction in uric acid levels. There were no adverse events throughout the trial. Conclusion. Thus, the experience with traclir used in patients with PH associated with systemic autoimmune diseases suggests its high effi cacy and safety.

  2. Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor OGR1 in human airway smooth muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Matsuzaki, Shinichi [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Ishizuka, Tamotsu, E-mail: tamotsui@showa.gunma-u.ac.jp [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Yamada, Hidenori; Kamide, Yosuke; Hisada, Takeshi; Ichimonji, Isao; Aoki, Haruka; Yatomi, Masakiyo [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Komachi, Mayumi [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan); Tsurumaki, Hiroaki; Ono, Akihiro; Koga, Yasuhiko [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Dobashi, Kunio [Gunma University Graduate School of Health Sciences, Maebashi 371-8511 (Japan); Mogi, Chihiro; Sato, Koichi; Tomura, Hideaki [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan); Mori, Masatomo [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Okajima, Fumikazu [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan)

    2011-10-07

    Highlights: {yields} The involvement of extracellular acidification in airway remodeling was investigated. {yields} Extracellular acidification alone induced CTGF production in human ASMCs. {yields} Extracellular acidification enhanced TGF-{beta}-induced CTGF production in human ASMCs. {yields} Proton-sensing receptor OGR1 was involved in acidic pH-stimulated CTGF production. {yields} OGR1 may play an important role in airway remodeling in asthma. -- Abstract: Asthma is characterized by airway inflammation, hyper-responsiveness and remodeling. Extracellular acidification is known to be associated with severe asthma; however, the role of extracellular acidification in airway remodeling remains elusive. In the present study, the effects of acidification on the expression of connective tissue growth factor (CTGF), a critical factor involved in the formation of extracellular matrix proteins and hence airway remodeling, were examined in human airway smooth muscle cells (ASMCs). Acidic pH alone induced a substantial production of CTGF, and enhanced transforming growth factor (TGF)-{beta}-induced CTGF mRNA and protein expression. The extracellular acidic pH-induced effects were inhibited by knockdown of a proton-sensing ovarian cancer G-protein-coupled receptor (OGR1) with its specific small interfering RNA and by addition of the G{sub q/11} protein-specific inhibitor, YM-254890, or the inositol-1,4,5-trisphosphate (IP{sub 3}) receptor antagonist, 2-APB. In conclusion, extracellular acidification induces CTGF production through the OGR1/G{sub q/11} protein and inositol-1,4,5-trisphosphate-induced Ca{sup 2+} mobilization in human ASMCs.

  3. Tissue-protective activity of selenomethionine and D-panthetine in B16 melanoma-bearing mice under doxorubicin treatment is not connected with their ROS scavenging potential.

    Science.gov (United States)

    Panchuk, Rostyslav R; Skorokhyd, Nadia R; Kozak, Yuliya S; Lehka, Liliya V; Moiseenok, Andrey G; Stoika, Rostyslav S

    2017-04-14

    To evaluate molecular mechanisms of tissue-protective effects of antioxidants selenomethionine (SeMet) and D-pantethine (D-Pt) applied in combination with doxorubicin (Dx) in B16 melanoma-bearing-mice. Impact of the chemotherapy scheme on a survival of tumor-bearing animals, general nephro- and hepatotoxicity, blood cell profile in vivo, and ROS content in B16 melanoma cells in vitro was compared with the action of Dx applied alone. Nephrotoxicity of the drugs was evaluated by measuring creatinine indicator assay, hepatotoxicity was studied by measuring the activity of ALT/AST enzymes, and myelotoxicity was assessed by light microscopic analysis of blood smears. Changes in ROS content in B16 melanoma cells under Dx, SeMet, and D-Pt action in vitro were measured by incubation with fluorescent dyes dihydrodichlorofluoresceindiacetate (DCFDA, H2O2-specific) and dihydroethidium (DHE, O2--specific), and further analysis at FL1 (DCFDA) or FL2 channels (DHE) of FACScan flow cytometer. The impact of aforementioned compounds on functional status of mitochondria was measured by Rhodamine 123 assay and further analysis at FL1 channel of FACScan flow cytometer. Selenomethionine (1200 µg/kg) and D-pantethine (500 mg/kg) in combination with Dx (10 mg/kg) significantly reduced tumor-induced neutrophilia, lymphocytopenia, and leukocytosis in comparison to Dx treatment alone. Moreover, SeMet and D-Pt decreased several side effects of Dx, namely an elevated creatinine level in blood and monocytosis, thus normalizing health conditions of B16 melanoma-bearing animals. Our results showed that antioxidants selenomethionine and D-pantethine possess significant nephroprotective and myeloprotective activity toward Dx action on murine B16 melanoma in vivo, but fail to boost a survival of B16 melanoma-bearing animals. The observed cytoprotective effects of studied antioxidants are not directly connected with their ROS scavenging.

  4. Cervical and scapulothoracic stabilization exercises with and without connective tissue massage for chronic mechanical neck pain: A prospective, randomised controlled trial.

    Science.gov (United States)

    Celenay, Seyda Toprak; Kaya, Derya Ozer; Akbayrak, Turkan

    2016-02-01

    This study was planned to assess and compare the effectiveness of cervical and scapulothoracic stabilization exercise treatment with and without connective tissue massage (CTM) on pain, anxiety, and the quality of life in patients with chronic mechanical neck pain (MNP). Sixty patients with chronic MNP (18-65 years) were recruited and randomly allocated into stabilization exercise with (Group 1, n = 30) and without the CTM (Group 2, n = 30). The program was carried out for 12 sessions, 3 days/week in 4 weeks. Pain intensity with Visual Analog Scale, pressure pain threshold with digital algometer (JTech Medical Industries, ZEVEX Company), level of anxiety with Spielberger State Trait Anxiety Inventory, and quality of life with Short Form-36 were evaluated before and after the treatment. After the program, pain intensity and the level of anxiety decrease, physical health increase in Group 1 and 2 were found (p < 0.05). Pressure pain threshold and mental health increase were detected in only Group 1 (p < 0.05). The intergroup comparison showed that significant difference in pain intensity at night, pressure pain threshold, state anxiety and mental health were seen in favor of Group 1 (p < 0.05). The study suggested that stabilization exercises with and without the CTM might be a useful treatment for patients with chronic MNP. However, stabilization exercises with CTM might be superior in improving pain intensity at night, pressure pain threshold, state anxiety and mental health compared to stabilization exercise alone. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Oxygen-enhanced MRI for patients with connective tissue diseases: Comparison with thin-section CT of capability for pulmonary functional and disease severity assessment

    Energy Technology Data Exchange (ETDEWEB)

    Ohno, Yoshiharu, E-mail: yosirad@kobe-u.ac.jp [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Nishio, Mizuho [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Koyama, Hisanobu [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Yoshikawa, Takeshi; Matsumoto, Sumiaki [Advanced Biomedical Imaging Research Center, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Division of Functional and Diagnostic Imaging Research, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Seki, Shinichiro [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Tsubakimoto, Maho [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan); Department of Radiology, Graduate School of Medical Science, University of the Ryukyus, Nakagami-Gun, Okinawa (Japan); Sugimura, Kazuro [Division of Radiology, Department of Radiology, Kobe University Graduate School of Medicine, Kobe, Hyogo (Japan)

    2014-02-15

    Purpose: To prospectively and directly compare oxygen-enhanced (O{sub 2}-enhanced) MRI with thin-section CT for pulmonary functional loss and disease severity assessment in connective tissue disease (CTD) patients with interstitial lung disease (ILD). Materials and methods: Thin-section CT, O{sub 2}-enhanced MRI, pulmonary function test and serum KL-6 were administered to 36 CTD patients with ILD (23 men, 13 women; mean age: 63.9 years) and nine CTD patients without ILD (six men, and three women; mean age: 62.0 years). A relative-enhancement ratio (RER) map was generated from O{sub 2}-enhanced MRI and mean relative enhancement ratio (MRER) for each subject was calculated from all ROI measurements. CT-assessed disease severity was evaluated with a visual scoring system from each of the thin-section CT data. MRER and CT-assessed disease severities of CTD patients with and without ILD were then statistically compared. To assess capability for pulmonary functional loss and disease severity assessment in CTD patients, correlations of MRER and CT-assessed disease severity with pulmonary functional parameters and serum KL-6 in all subjects were statistically determined. Results: MRER and CT-assessed disease severity showed significant differences between CTD patients with (MRER: 0.15 ± 0.08, CT-assessed disease severity: 13.0 ± 7.4%) and without ILD (MRER: 0.25 ± 0.06, p = 0.0011; CT-assessed disease severity: 1.6 ± 1.6%, p < 0.0001). MRER and CT-assessed disease severity correlated significantly with pulmonary functional parameters and serum KL-6 in all subjects (0.61 ≤ r ≤ 0.79, p < 0.05). Conclusion: O{sub 2}-enhanced MRI was found to be as useful as thin-section CT for pulmonary functional loss and disease severity assessment of CTD patients with ILD.

  6. Presence of Antiphospholipid Antibodies as a Risk Factor for Thrombotic Events in Patients with Connective Tissue Diseases and Idiopathic Thrombocytopenic Purpura.

    Science.gov (United States)

    Habe, Koji; Wada, Hideo; Matsumoto, Takeshi; Ohishi, Kohshi; Ikejiri, Makoto; Matsubara, Kimiko; Morioka, Tatsuhiko; Kamimoto, Yuki; Ikeda, Tomoaki; Katayama, Naoyuki; Mizutani, Hitoshi

    2016-01-01

    Antiphospholipid syndrome (APS) is a well-known complication of habitual abortion and/or thrombosis and is frequently associated with autoimmune diseases. We retrospectively investigated the relationships between the presence of antiphospholipid antibodies (aPLs) and the incidence of thrombotic events (THEs) in 147 patients with various connective tissue diseases (CTD) suspected of having APS and 86 patients with idiopathic thrombocytopenic purpura (ITP). THEs were observed in 41 patients, including 14 cases of venous thrombosis, 21 cases of arterial thrombosis and eight cases of complications of pregnancy. The prevalence of THE was significantly high in the systemic lupus erythematosus (SLE) patients compared with the other CTD patients and ITP patients. The frequency of lupus anticoagulant (LA), anticardiolipin antibodies (aCL)-β2-glycoprotein (GPI) complex IgG and aPL was significantly high in the SLE patients compared with the ITP patients. Subsequently, the rate of development of THE was significantly high in the patients with aPLs. In particular, the incidence of THE was significantly high in the SLE or ITP patients with LA, aCL-β2GPI IgG or aPL. The optimal cut-off values for LA, aCL IgG and aCL-β2GPI complex IgG for the risk of THEs were higher in the SLE patients in comparison to the values obtained when using the kit provided by the manufacturer. Although aPLs is frequently associated with SLE and is a causative factor for thrombosis, the optimal cut-off value for aPL for predicting the occurrence of THEs varies among different underlying diseases.

  7. Comparison of enamel matrix derivative (Emdogain) and subepithelial connective tissue graft for root coverage in patients with multiple gingival recession defects: A randomized controlled clinical study.

    Science.gov (United States)

    Alexiou, Angeliki; Vouros, Ioannis; Menexes, Georgios; Konstantinidis, Antonis

    2017-01-01

    The purpose of the present study was to compare the clinical efficiency of enamel matrix derivative (EMD) placed under a coronally advanced flap (CAF; test group), to a connective tissue graft (CTG) placed under a CAF (control group), in patients with multiple recession defects. Twelve patients with multiple Miller's Class I or II gingival recessions in contralateral quadrants of the maxilla were selected. The primary outcome variable was the change in depth of the buccal recession (REC), at 6 months (T6) after surgery. The secondary outcome parameters included the clinical attachment level (CAL), the probing pocket depth (PPD), and the width of keratinized gingiva (WKT) apical to the recession. Recession defects were randomly divided to the test or control group by using a computer-generated randomization list. Data were analyzed within the frame of Mixed Linear Models with the ANOVA method. There were no statistically significantly differences observed between test and control groups in regards with the depth of buccal recession with a mean REC of 1.82 mm (CTG) and 1.72 mm (EMD) respectively. Similarly the mean PPD value was 1.3 mm for both groups at T6, while the respective value for CAL was 1.7 mm (EMD) and 1.8 mm (CTG). Statistically significant differences were observed only for the WKT, which were 3.0 mm and 3.6 mm for the test and control groups respectively (P < .001) at T6. The use of EMD in conjunction with a CAF resulted in similar results as compared to the CTG plus CAF.

  8. Chest Abnormalities in Juvenile-Onset Mixed Connective Tissue Disease: Assessment with High-Resolution Computed Tomography and Pulmonary Function Tests

    International Nuclear Information System (INIS)

    Aaloekken, T.M.; Mynarek, G.; Kolbenstvedt, A.; Lilleby, V.; Foerre, Oe.; Soeyseth, V.; Pripp, A.H.; Johansen, B.

    2009-01-01

    Background: Mixed connective tissue disease (MCTD) is associated with several chest manifestations. Only a few studies have focused on chest manifestations in juvenile-onset MCTD (jMCTD), and the true prevalence of pulmonary abnormalities on high-resolution computed tomography (HRCT) in these patients is unknown. Purpose: To investigate the occurrence of pulmonary abnormalities in jMCTD with particular reference to interstitial lung disease (ILD), and to evaluate a possible association between pulmonary findings and disease-related variables. Material and Methods: Twenty-four childhood-onset MCTD patients with median disease duration of 10.5 years (range 1-21 years) were investigated in a cross-sectional study by means of HRCT, pulmonary function tests (PFT), and clinical assessment. Results: Discrete ILD was identified in six patients (25%). Median extent of ILD was 2.0%, and all except one of the patients had very mild disease in which 5% or less of the parenchyma was affected. The CT features of fibrosis were mainly microcystic and fine intralobular. The most frequently abnormal PFT was carbon monoxide uptake from the lung, which was abnormal in 33% of the patients. PFT and disease duration were not significantly associated with HRCT findings of ILD. Conclusion: The prevalence of ILD in childhood-onset MCTD patients was lower than previously believed. In most of the patients with ILD, the findings were subtle and without clinical correlation. The results suggest a low extent of ILD in childhood-onset MCTD, even after long-term disease duration

  9. Oxygen-enhanced MRI for patients with connective tissue diseases: Comparison with thin-section CT of capability for pulmonary functional and disease severity assessment

    International Nuclear Information System (INIS)

    Ohno, Yoshiharu; Nishio, Mizuho; Koyama, Hisanobu; Yoshikawa, Takeshi; Matsumoto, Sumiaki; Seki, Shinichiro; Tsubakimoto, Maho; Sugimura, Kazuro

    2014-01-01

    Purpose: To prospectively and directly compare oxygen-enhanced (O 2 -enhanced) MRI with thin-section CT for pulmonary functional loss and disease severity assessment in connective tissue disease (CTD) patients with interstitial lung disease (ILD). Materials and methods: Thin-section CT, O 2 -enhanced MRI, pulmonary function test and serum KL-6 were administered to 36 CTD patients with ILD (23 men, 13 women; mean age: 63.9 years) and nine CTD patients without ILD (six men, and three women; mean age: 62.0 years). A relative-enhancement ratio (RER) map was generated from O 2 -enhanced MRI and mean relative enhancement ratio (MRER) for each subject was calculated from all ROI measurements. CT-assessed disease severity was evaluated with a visual scoring system from each of the thin-section CT data. MRER and CT-assessed disease severities of CTD patients with and without ILD were then statistically compared. To assess capability for pulmonary functional loss and disease severity assessment in CTD patients, correlations of MRER and CT-assessed disease severity with pulmonary functional parameters and serum KL-6 in all subjects were statistically determined. Results: MRER and CT-assessed disease severity showed significant differences between CTD patients with (MRER: 0.15 ± 0.08, CT-assessed disease severity: 13.0 ± 7.4%) and without ILD (MRER: 0.25 ± 0.06, p = 0.0011; CT-assessed disease severity: 1.6 ± 1.6%, p < 0.0001). MRER and CT-assessed disease severity correlated significantly with pulmonary functional parameters and serum KL-6 in all subjects (0.61 ≤ r ≤ 0.79, p < 0.05). Conclusion: O 2 -enhanced MRI was found to be as useful as thin-section CT for pulmonary functional loss and disease severity assessment of CTD patients with ILD

  10. Guided bone regeneration and abutment connection augment the buccal soft tissue contour: 3-year results of a prospective comparative clinical study.

    Science.gov (United States)

    Benic, Goran I; Ge, Yanjun; Gallucci, German O; Jung, Ronald E; Schneider, David; Hämmerle, Christoph H F

    2017-02-01

    To test whether implant placement with simultaneous guided bone regeneration (GBR) differs from implant placement without GBR regarding the change in marginal mucosal contour. In 28 patients, single implants were placed >4 months after tooth extraction. Eighteen implants were completely surrounded by native bone, and no bone augmentation was performed. At 10 implant sites, bone defects and thin bone plates were grafted with deproteinized bovine-derived bone mineral and covered with collagen membrane. Impressions were taken prior to implant placement (baseline), at 3 months before abutment connection, at 6 months immediately after crown insertion, at 1 year, and at 3 years. Models were optically scanned and 3D images were superimposed for the evaluation of mucosal contour changes at the mid-buccal aspect. The nonparametric Mann-Whitney U-test was applied to detect differences. From baseline to 6 months, horizontal contour change at the level 1 and 2 mm apical to the mucosal margin measured 0.65 ± 0.74 mm and 0.55 ± 0.56 mm at sites without GBR, and 1.92 ± 0.87 mm and 1.76 ± 0.70 mm at sites with GBR (P < 0.05). In the period from baseline to 1 year, the corresponding values amounted to 0.81 ± 0.67 mm and 0.60 ± 0.55 mm in the group without GBR, and to 1.81 ± 0.86 mm and 1.37 ± 0.62 mm in the group with GBR (P < 0.05). From baseline to 6 months, mucosal margin moved 0.16 ± 0.49 mm in the coronal direction in the group without GBR and 0.82 ± 0.65 mm in the group with GBR (P < 0.05). In the period from baseline to 1 year, vertical change of mucosal margin amounted to 0.64 ± 0.54 mm in the group without GBR and to 1.17 ± 0.53 mm in the GBR group (P < 0.05). From 1 to 3 years, the mucosal contours remained stable. Implant placement with simultaneous GBR resulted in more gain of buccal soft tissue contour in comparison with implant placement without GBR. Abutment connection increased the contour of the

  11. [Intervention of pyrrolidine dithiocarbamate on expressions of connective tissue growth factor, type I collagen, and type III collage in acute paraquat poisoned rats].

    Science.gov (United States)

    Huang, Min; Yang, Hui-fang; Zhang, Ping; Chang, Xiu-li; Zhou, Zhi-jun

    2013-01-01

    To observe the changes in the expression of connective tissue growth factor (CTGF), type I collagen (Col I), and type III collagen (Col III) among the rats with acute paraquat (PQ) poisoning and the intervention effect of pyrrolidine dithiocarbamate (PDTC) on their expression, and to investigate the mechanism of PQ-induced pulmonary fibrosis and the intervention effect of PDTC on the disease. Sprague-Dawley rats were randomly divided into control group (n = 6), PQ group (n = 36), and PQ + PDTC group (n = 36). The PQ group and PQ + PDTC group were given a single dose of saline-diluted PQ (80 mg/kg) by gavage; 2 h later, the PQ + PDTC group was intraperitoneally injected with a single dose of PDTC (100 mg/kg), and the PQ group was intraperitoneally injected with the same amount of saline. The control group was given saline (1 ml/kg) by gavage and was intraperitoneally injected with the same amount of saline 2h later. At 1, 3, 7, 14, 25, and 56 days after operation, the protein expression of CTGF was evaluated by Western blot; the mRNA expression of CTGF, Col I, and Col III was analyzed by real-time quantitative PCR; the content of hydroxyproline in lung tissue was measured, and the pathological changes of lung tissue of the poisoned rats were observed. The protein expression of CTGF in the PQ group increased as the time went on, slowly from the 3rd to the 14th day and rapidly from the 28th to the 56th day, significantly higher than that in the control group at each time point (P < 0.05 or P < 0.01). The mRNA expression of CTGF in the PQ group began to rise markedly on the 1st day, increased rapidly from the 3rd to the 14th day, and remained at a relatively high level from the 28th to the 56th day, significantly higher than that in the control group at each time point (P < 0.01). The mRNA expression of Col I in the PQ group changed little on the 1st and 3rd day, increased slightly on the 7th day, and increased greatly from the 14th to the 56th day, significantly

  12. GLIS1-3: emerging roles in reprogramming, stem and progenitor cell differentiation and maintenance.

    Science.gov (United States)

    Scoville, David W; Kang, Hong Soon; Jetten, Anton M

    2017-01-01

    Recent studies have provided evidence for a regulatory role of GLI-similar (GLIS) transcription factors in reprogramming, maintenance and differentiation of several stem and progenitor cell populations. GLIS1, in conjunction with several other reprogramming factors, was shown to markedly increase the efficiency of generating induced pluripotent stem cells (iPSC) from somatic cells. GLIS2 has been reported to contribute to the maintenance of the pluripotent state in hPSCs. In addition, GLIS2 has a function in regulating self-renewal of hematopoietic progenitors and megakaryocytic differentiation. GLIS3 plays a critical role during the development of several tissues. GLIS3 is able to promote reprogramming of human fibroblasts into retinal pigmented epithelial (RPE) cells. Moreover, GLIS3 is essential for spermatogonial stem cell renewal and spermatogonial progenitor cell differentiation. During pancreas development, GLIS3 protein is first detectable in bipotent pancreatic progenitors and pro-endocrine progenitors and plays a critical role in the generation of pancreatic beta cells. Here, we review the current status of the roles of GLIS proteins in the maintenance and differentiation of these different stem and progenitor cells.

  13. Human mammary progenitor cell fate decisions are products of interactions with combinatorial microenvironments

    Energy Technology Data Exchange (ETDEWEB)

    LaBarge, Mark A; Nelson, Celeste M; Villadsen, Rene; Fridriksdottir, Agla; Ruth, Jason R; Stampfer, Martha R; Petersen, Ole W; Bissell, Mina J

    2008-09-19

    In adult tissues, multi-potent progenitor cells are some of the most primitive members of the developmental hierarchies that maintain homeostasis. That progenitors and their more mature progeny share identical genomes, suggests that fate decisions are directed by interactions with extrinsic soluble factors, ECM, and other cells, as well as physical properties of the ECM. To understand regulation of fate decisions, therefore, would require a means of understanding carefully choreographed combinatorial interactions. Here we used microenvironment protein microarrays to functionally identify combinations of cell-extrinsic mammary gland proteins and ECM molecules that imposed specific cell fates on bipotent human mammary progenitor cells. Micropatterned cell culture surfaces were fabricated to distinguish between the instructive effects of cell-cell versus cell-ECM interactions, as well as constellations of signaling molecules; and these were used in conjunction with physiologically relevant 3 dimensional human breast cultures. Both immortalized and primary human breast progenitors were analyzed. We report on the functional ability of those proteins of the mammary gland that maintain quiescence, maintain the progenitor state, and guide progenitor differentiation towards myoepithelial and luminal lineages.

  14. Local Klotho enhances neuronal progenitor proliferation in the adult hippocampus.

    Science.gov (United States)

    Salech, Felipe; Varela-Nallar, Lorena; Arredondo, Sebastián B; Bustamante, Daniel B; Andaur, Gabriela A; Cisneros, Rodrigo; Ponce, Daniela P; Ayala, Patricia; Inestrosa, Nibaldo C; Valdés, José L; Behrens, María I; Couve, Andrés

    2017-12-30

    Klotho is an aging-related protein associated with hippocampal cognitive performance in mammals. Klotho regulates progenitor cell proliferation in non-neuronal tissues, but its role in adult hippocampal neurogenesis (AHN) has not been explored. Klotho expression in the adult mouse hippocampus was examined by immunofluorescence and PCR. AHN was evaluated in the hippocampus of klotho knock-out mice (KO), klotho KO/vitamin D-receptor mutant mice, and in a model of local klotho hippocampal knockdown. The recombinant Klotho effect on proliferation was measured in mouse-derived hippocampal neural progenitor cells. Hippocampal-dependent memory was assessed by a dry-land version of the Morris water maze. Klotho was expressed in the granular cell layer of the adult Dentate Gyrus. AHN was increased in klotho KO mice, but not in klotho KO/vitamin D-receptor mutant mice. Inversely, local downregulation of hippocampal Klotho diminished AHN. Recombinant Klotho increased the proliferation rate of neural progenitors. Downregulation of hippocampal Klotho correlated with a decreased performance in hippocampal dependent memory. These results suggest that Klotho directly participates in regulating AHN. Our observations indicate that Klotho promotes proliferation, AHN and hippocampal dependent cognition. Increased neurogenesis in klotho KO mice may be secondary to the activation of other pathways altered in the model, such as vitamin D. © The Author(s) 2017. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Glial progenitor cell-based treatment of the childhood leukodystrophies.

    Science.gov (United States)

    Osorio, M Joana; Goldman, Steven A

    2016-09-01

    The childhood leukodystrophies comprise a group of hereditary disorders characterized by the absence, malformation or destruction of myelin. These disorders share common clinical, radiological and pathological features, despite their diverse molecular and genetic etiologies. Oligodendrocytes and astrocytes are the major affected cell populations, and are either structurally impaired or metabolically compromised through cell-intrinsic pathology, or are the victims of mis-accumulated toxic byproducts of metabolic derangement. In either case, glial cell replacement using implanted tissue or pluripotent stem cell-derived human neural or glial progenitor cells may comprise a promising strategy for both structural remyelination and metabolic rescue. A broad variety of pediatric white matter disorders, including the primary hypomyelinating disorders, the lysosomal storage disorders, and the broader group of non-lysosomal metabolic leukodystrophies, may all be appropriate candidates for glial progenitor cell-based treatment. Nonetheless, a variety of specific challenges remain before this therapeutic strategy can be applied to children. These include timely diagnosis, before irreparable neuronal injury has ensued; understanding the natural history of the targeted disease; defining the optimal cell phenotype for each disorder; achieving safe and scalable cellular compositions; designing age-appropriate controlled clinical trials; and for autologous therapy of genetic disorders, achieving the safe genetic editing of pluripotent stem cells. Yet these challenges notwithstanding, the promise of glial progenitor cell-based treatment of the childhood myelin disorders offers hope to the many victims of this otherwise largely untreatable class of disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Periodontal Bioengineering: A Discourse in Surface Topographies, Progenitor Cells and Molecular Profiles

    Science.gov (United States)

    Dangaria, Smit J.

    2011-12-01

    Stem/progenitor cells are a population of cells capable of providing replacement cells for a given differentiated cell type. We have applied progenitor cell-based technologies to generate novel tissue-engineered implants that use biomimetic strategies with the ultimate goal of achieving full regeneration of lost periodontal tissues. Mesenchymal periodontal tissues such as cementum, alveolar bone (AB), and periodontal ligament (PDL) are neural crest-derived entities that emerge from the dental follicle (DF) at the onset of tooth root formation. Using a systems biology approach we have identified key differences between these periodontal progenitors on the basis of global gene expression profiles, gene cohort expression levels, and epigenetic modifications, in addition to differences in cellular morphologies. On an epigenetic level, DF progenitors featured high levels of the euchromatin marker H3K4me3, whereas PDL cells, AB osteoblasts, and cementoblasts contained high levels of the transcriptional repressor H3K9me3. Secondly, we have tested the influence of natural extracellular hydroxyapatite matrices on periodontal progenitor differentiation. Dimension and structure of extracellular matrix surfaces have powerful influences on cell shape, adhesion, and gene expression. Here we show that natural tooth root topographies induce integrin-mediated extracellular matrix signaling cascades in tandem with cell elongation and polarization to generate physiological periodontium-like tissues. In this study we replanted surface topography instructed periodontal ligament progenitors (PDLPs) into rat alveolar bone sockets for 8 and 16 weeks, resulting in complete attachment of tooth roots to the surrounding alveolar bone with a periodontal ligament fiber apparatus closely matching physiological controls along the entire root surface. Displacement studies and biochemical analyses confirmed that progenitor-based engineered periodontal tissues were similar to control teeth and

  17. Three-Dimensional Normal Human Neural Progenitor Tissue-Like Assemblies: A Model for Persistent Varicell-Zoster Virus Infection and Platform to Study Viral Infectivity and Oxidative Stress and Damage

    Science.gov (United States)

    Goodwin, T. J.; McCarthy, M.; Osterrieder, N.; Cohrs, R. J.; Kaufer, B. B.

    2014-01-01

    The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpesvirus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex threedimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6].

  18. Three-Dimensional Normal Human Neutral Progenitor Tissue-Like Assemblies: A Model for Persistent Varicella-Zoster Virus Infection and Platform to Study Oxidate Stress and Damage in Multiple Hit Scenarios

    Science.gov (United States)

    Goodwin, Thomas J.; McCarthy, M.; Osterrieder, N.; Cohrs, R. J.; Kaufer, B. B.

    2014-01-01

    The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpes virus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex three-dimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6]. By combining the RFs of microgravity, radiation, and viral infection we will demonstrate that living in the space environment leads to significant physiological consequences for the peripheral and subsequently the central nervous system (PNS, CNS) associated with OSaD generation and consequentially endangers long-duration and exploration-class missions.

  19. A musculoskeletal model of low grade connective tissue inflammation in patients with thyroid associated ophthalmopathy (TAO: the WOMED concept of lateral tension and its general implications in disease

    Directory of Open Access Journals (Sweden)

    Moncayo Helga

    2007-02-01

    Full Text Available Abstract Background Low level connective tissue inflammation has been proposed to play a role in thyroid associated ophthalmopathy (TAO. The aim of this study was to investigate this postulate by a musculoskeletal approach together with biochemical parameters. Methods 13 patients with TAO and 16 controls were examined. Erythrocyte levels of Zn, Cu, Ca2+, Mg, and Fe were determined. The musculoskeletal evaluation included observational data on body posture with emphasis on the orbit-head region. The angular foot position in the frontal plane was quantified following gait observation. The axial orientation of the legs and feet was evaluated in an unloaded supine position. Functional propioceptive tests based on stretch stimuli were done by using foot inversion and foot rotation. Results Alterations in the control group included neck tilt in 3 cases, asymmetrical foot angle during gait in 2, and a reaction to foot inversion in 5 cases. TAO patients presented facial asymmetry with displaced eye fissure inclination (mean 9.1° as well as tilted head-on-neck position (mean 5.7°. A further asymmetry feature was external rotation of the legs and feet (mean 27°. Both foot inversion as well as foot rotation induced a condition of neuromuscular deficit. This condition could be regulated by gentle acupressure either on the lateral abdomen or the lateral ankle at the acupuncture points gall bladder 26 or bladder 62, respectively. In 5 patients, foot rotation produced a phenomenon of moving toes in the contra lateral foot. In addition foot rotation was accompanied by an audible tendon snapping. Lower erythrocyte Zn levels and altered correlations between Ca2+, Mg, and Fe were found in TAO. Conclusion This whole body observational study has revealed axial deviations and body asymmetry as well as the phenomenon of moving toes in TAO. The most common finding was an arch-like displacement of the body, i.e. eccentric position, with foot inversion and head tilt

  20. A promoter polymorphism -945C>G in the connective tissue growth factor in heart failure patients with mechanical circulatory support: a new marker for bridge to recovery?

    Science.gov (United States)

    Posch, Maximilian G; Schmidt, Gunther; Steinhoff, Laura; Perrot, Andreas; Drews, Thorsten; Dandel, Michael; Krabatsch, Thomas; Hetzer, Roland; Potapov, Evgenij V

    2015-01-01

    Mechanical circulatory support (MCS) creates improvement of cardiac function in a small portion of patients with idiopathic dilated cardiomyopathy (iDCM). Among other factors, cardiomyocyte hypertrophy seems to represent an important prerequisite for MCS-related cardiac recovery. We have previously shown that connective tissue growth factor (CTGF) leads to adaptive cardiomyocyte hypertrophy associated with a protective cardiac function in transgenic mice. To test whether a functional genetic variant in the CTGF promoter impacts MCS-related cardiac recovery, three groups of iDCM patients with and without cardiac recovery on MCS were genotyped. The CTGF promoter variant (c.-945C>G) was analysed in 314 patients with iDCM receiving medical treatment only (Group I). Forty-nine iDCM patients who were either weaned from MCS for more than 6 months (Group II; n=20) or bridged to cardiac transplantation (Group III: n=29) were also genotyped. Patients on MCS were followed up for at least 12 months. Clinical characteristics and outcome on MCS were correlated with the respective genotypes. The c.-945C>G allele frequencies in 314 iDCM patients (Group I) were similar to controls deposited in the HapMap database or those published in a recent study. There were no differences in allele prevalence between patients with mild to moderate iDCM (Group I) compared with patients with severe iDCM requiring MCS (Groups II and III). Intriguingly, 50% of patients who were weaned from MCS (Group II) were homozygous for the G allele compared with only 17.2% of patients included in Group III, which is a significant difference (P=0.03). Homozygosity of the promoter-activating G allele in the CTGF_c.-945C>G variant is overrepresented in patients with cardiac recovery on MCS when compared with iDCM patients without cardiac recovery. Further studies are needed to evaluate c.-945C>G as a genetic predictor for clinical outcome on MCS. © The Author 2014. Published by Oxford University Press on behalf

  1. Red supergiants as supernova progenitors.

    Science.gov (United States)

    Davies, Ben

    2017-10-28

    It is now well-established from pre-explosion imaging that red supergiants (RSGs) are the direct progenitors of Type-IIP supernovae. These images have been used to infer the physical properties of the exploding stars, yielding some surprising results. In particular, the differences between the observed and predicted mass spectrum has provided a challenge to our view of stellar evolutionary theory. However, turning what is typically a small number of pre-explosion photometric points into the physical quantities of stellar luminosity and mass requires a number of assumptions about the spectral appearance of RSGs, as well as their evolution in the last few years of life. Here I will review what we know about RSGs, with a few recent updates on how they look and how their appearance changes as they approach supernova.This article is part of the themed issue 'Bridging the gap: from massive stars to supernovae'. © 2017 The Author(s).

  2. DISAPPEARANCE OF THE PROGENITOR OF SUPERNOVA iPTF13bvn

    Energy Technology Data Exchange (ETDEWEB)

    Folatelli, Gastón; Bersten, Melina C. [Facultad de Ciencias Astronómicas y Geofísicas, Universidad Nacional de La Plata, Instituto de Astrofísica de La Plata (IALP), CONICET, Paseo del Bosque S/N, B1900FWA La Plata (Argentina); Van Dyk, Schuyler D. [IPAC/Caltech, Mailcode 100-22, Pasadena, CA 91125 (United States); Kuncarayakti, Hanindyo; Pignata, Giuliano; Hamuy, Mario [Millennium Institute of Astrophysics (MAS), Santiago (Chile); Maeda, Keiichi; Nomoto, Ken’ichi; Quimby, Robert M. [Kavli Institute for the Physics and Mathematics of the Universe (WPI), The University of Tokyo, Kashiwa, Chiba 277-8583 (Japan); Zheng, WeiKang; Filippenko, Alexei V.; Clubb, Kelsey I. [Department of Astronomy, University of California, Berkeley, CA 94720-3411 (United States); Smith, Nathan [Steward Observatory, University of Arizona, 933 N. Cherry Avenue, Tucson, AZ 85721 (United States); Elias-Rosa, Nancy [INAF-Osservatorio Astronomico di Padova, Vicolo dell’Osservatorio 5, I-35122 Padova (Italy); Foley, Ryan J. [Astronomy Department, University of Illinois at Urbana-Champaign, 1002 W. Green Street, Urbana, IL 61801 (United States); Miller, Adam A., E-mail: gaston.folatelli@ipmu.jp [Jet Propulsion Laboratory, 4800 Oak Grove Drive, MS 169-506, Pasadena, CA 91109 (United States)

    2016-07-10

    Supernova (SN) iPTF13bvn in NGC 5806 was the first Type Ib SN to have been tentatively associated with a progenitor in pre-explosion images. We performed deep ultraviolet (UV) and optical Hubble Space Telescope observations of the SN site ∼740 days after explosion. We detect an object in the optical bands that is fainter than the pre-explosion object. This dimming is likely not produced by dust absorption in the ejecta; thus, our finding confirms the connection of the progenitor candidate with the SN. The object in our data is likely dominated by the fading SN, implying that the pre-SN flux is mostly due to the progenitor. We compare our revised pre-SN photometry with previously proposed models. Although binary progenitors are favored, models need to be refined. In particular, to comply with our deep UV detection limit, any companion star must be less luminous than a late-O star or substantially obscured by newly formed dust. A definitive progenitor characterization will require further observations to disentangle the contribution of a much fainter SN and its environment.

  3. Lineage tracing of resident tendon progenitor cells during growth and natural healing.

    Directory of Open Access Journals (Sweden)

    Nathaniel A Dyment

    Full Text Available Unlike during embryogenesis, the identity of tissue resident progenitor cells that contribute to postnatal tendon growth and natural healing is poorly characterized. Therefore, we utilized 1 an inducible Cre driven by alpha smooth muscle actin (SMACreERT2, that identifies mesenchymal progenitors, 2 a constitutively active Cre driven by growth and differentiation factor 5 (GDF5Cre, a critical regulator of joint condensation, in combination with 3 an Ai9 Cre reporter to permanently label SMA9 and GDF5-9 populations and their progeny. In growing mice, SMA9+ cells were found in peritendinous structures and scleraxis-positive (ScxGFP+ cells within the tendon midsubstance and myotendinous junction. The progenitors within the tendon midsubstance were transiently labeled as they displayed a 4-fold expansion from day 2 to day 21 but reduced to baseline levels by day 70. SMA9+ cells were not found within tendon entheses or ligaments in the knee, suggesting a different origin. In contrast to the SMA9 population, GDF5-9+ cells extended from the bone through the enthesis and into a portion of the tendon midsubstance. GDF5-9+ cells were also found throughout the length of the ligaments, indicating a significant variation in the progenitors that contribute to tendons and ligaments. Following tendon injury, SMA9+ paratenon cells were the main contributors to the healing response. SMA9+ cells extended over the defect space at 1 week and differentiated into ScxGFP+ cells at 2 weeks, which coincided with increased collagen signal in the paratenon bridge. Thus, SMA9-labeled cells represent a unique progenitor source that contributes to the tendon midsubstance, paratenon, and myotendinous junction during growth and natural healing, while GDF5 progenitors contribute to tendon enthesis and ligament development. Understanding the mechanisms that regulate the expansion and differentiation of these progenitors may prove crucial to improving future repair strategies.

  4. Profibrotic potential of Prominin-1+ epithelial progenitor cells in pulmonary fibrosis

    Directory of Open Access Journals (Sweden)

    Lüscher Thomas F

    2011-09-01

    Full Text Available Abstract Background In idiopathic pulmonary fibrosis loss of alveolar epithelium induces inflammation of the pulmonary tissue followed by accumulation of pathogenic myofibroblasts leading eventually to respiratory failures. In animal models inflammatory and resident cells have been demonstrated to contribute to pulmonary fibrosis. Regenerative potential of pulmonary and extra-pulmonary stem and progenitor cells raised the hope for successful treatment option against pulmonary fibrosis. Herein, we addressed the contribution of lung microenvironment and prominin-1+ bone marrow-derived epithelial progenitor cells in the mouse model of bleomycin-induced experimental pulmonary fibrosis. Methods Prominin-1+ bone marrow-derived epithelial progenitors were expanded from adult mouse lungs and differentiated in vitro by cytokines and growth factors. Pulmonary fibrosis was induced in C57Bl/6 mice by intratracheal instillation of bleomycin. Prominin-1+ progenitors were administered intratracheally at different time points after bleomycin challenge. Green fluorescence protein-expressing cells were used for cell tracking. Cell phenotypes were characterized by immunohistochemistry, flow cytometry and quantitative reverse transcription-polymerase chain reaction. Results Prominin-1+ cells expanded from healthy lung represent common progenitors of alveolar type II epithelial cells, myofibroblasts, and macrophages. Administration of prominin-1+ cells 2 hours after bleomycin instillation protects from pulmonary fibrosis, and some of progenitors differentiate into alveolar type II epithelial cells. In contrast, prominin-1+ cells administered at day 7 or 14 lose their protective effects and differentiate into myofibroblasts and macrophages. Bleomycin challenge enhances accumulation of bone marrow-derived prominin-1+ cells within inflamed lung. In contrast to prominin-1+ cells from healthy lung, prominin-1+ precursors isolated from inflamed organ lack regenerative

  5. The isolation and in vitro expansion of hepatic Sca-1 progenitor cells

    International Nuclear Information System (INIS)

    Clayton, Elizabeth; Forbes, Stuart J.

    2009-01-01

    The intra-hepatic population of liver progenitor cells expands during liver injury when hepatocyte proliferation is inhibited. These cells can be purified by density gradient centrifugation and cultured. Separated by size only this population contains small cells of hematopoietic, epithelial and endothelial lineages and is thought to contain liver stem cells. The identity of liver stem cells remains unknown although there is some evidence that tissue Sca1 + CD45 - cells display progenitor cell characteristics. We identified both intra-hepatic and gall bladder Sca1 + cells following liver injury and expanded ex vivo Sca1 cells as part of heterogenous cell culture or as a purified population. We found significant difference between the proliferation of Sca-1 cells when plated on laminin or collagen I while proliferation of heterogenous population was not affected by the extracellular matrix indicating the necessity for culture of Sca1 + cells with laminin matrix or laminin producing cells in long term liver progenitor cell cultures.

  6. Distinct adipocyte progenitor cells are associated with regional phenotypes of perivascular aortic fat in mice

    Directory of Open Access Journals (Sweden)

    Khanh-Van Tran

    2018-03-01

    Full Text Available Objective: Perivascular adipose tissue depots around the aorta are regionally distinct and have specific functional properties. Thoracic aorta perivascular adipose tissue (tPVAT expresses higher levels of thermogenic genes and lower levels of inflammatory genes than abdominal aorta perivascular adipose tissue (aPVAT. It is not known whether this distinction is due to the in-vivo functional environment or to cell-autonomous traits that persist outside the in-vivo setting. In this study, we asked whether the progenitor cells in tPVAT and aPVAT have cell-autonomous traits that lead to formation of regionally distinct PVAT. Methods: We performed microarray analysis of thoracic and abdominal peri-aortic adipose tissues of C57Bl/6J mice to define gene expression profile of each depot. To derive adipocyte progenitor cells, C57Bl/6J mice were sacrificed and thoracic and abdominal aorta fragments were embedded in Matrigel and cultured under pro-angiogenic conditions. Adipogenesis was induced using the Ppar-γ agonist rosiglitazone, a thiazolidinedione (TZD. TZD-induced adipocyte populations were analyzed using immunofluorescence and qRT-PCR. Results: Microarray analysis showed that tPVAT expressed higher levels of transcription factors related brown adipose tissue development compared to aPVAT. Classic brown adipose tissue (BAT genes such as Ucp-1