WorldWideScience

Sample records for basophils connective tissue

  1. Undifferentiated Connective Tissue Disease

    Science.gov (United States)

    ... Home Conditions Undifferentiated Connective Tissue Disease (UCTD) Undifferentiated Connective Tissue Disease (UCTD) Make an Appointment Find a Doctor ... L. Goldstein, MD, MMSc (February 01, 2016) Undifferentiated connective tissue disease (UCTD) is a systemic autoimmune disease. This ...

  2. Connective Tissue Disorders

    Science.gov (United States)

    Connective tissue is the material inside your body that supports many of its parts. It is the "cellular ... their work. Cartilage and fat are examples of connective tissue. There are over 200 disorders that impact connective ...

  3. Connective Tissue Naevus

    Directory of Open Access Journals (Sweden)

    Bhat Ramesh M

    1999-01-01

    Full Text Available A young adult female patient of connective tissue naevus presented with papules and indurated plaques on both les and left arm. Histopathology showed increased amount of collagen in the dermis. Osteopoikilosis was absent.

  4. Connective Tissue Disorder

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008349 A clinical analysis of 32 patients with diffuse alveolar hemorrhage in diffuse connective tissue diseases. CHEN Guangxing(陈光星), et al. Dept Rheumatol, PUMC & CAMS Beijing 100730. Chin J Intern Med 2008;47(5):362-365.Objective To provide clues to diagnosis and treatment for diffuse alveolar hemorrhage(DAH)in patients with diffuse connective tissue diseases(CTD).Method To analyze restropectively the data of clinical features,

  5. [Connective tissue and inflammation].

    Science.gov (United States)

    Jakab, Lajos

    2014-03-23

    The author summarizes the structure of the connective tissues, the increasing motion of the constituents, which determine the role in establishing the structure and function of that. The structure and function of the connective tissue are related to each other in the resting as well as inflammatory states. It is emphasized that cellular events in the connective tissue are part of the defence of the organism, the localisation of the damage and, if possible, the maintenance of restitutio ad integrum. The organism responds to damage with inflammation, the non specific immune response, as well as specific, adaptive immunity. These processes are located in the connective tissue. Sterile and pathogenic inflammation are relatively similar processes, but inevitable differences are present, too. Sialic acids and glycoproteins containing sialic acids have important roles, and the role of Siglecs is also highlighted. Also, similarities and differences in damages caused by pathogens and sterile agents are briefly summarized. In addition, the roles of adhesion molecules linked to each other, and the whole event of inflammatory processes are presented. When considering practical consequences it is stressed that the structure (building up) of the organism and the defending function of inflammation both have fundamental importance. Inflammation has a crucial role in maintaining the integrity and the unimpaired somato-psychological state of the organism. Thus, inflammation serves as a tool of organism identical with the natural immune response, inseparably connected with the specific, adaptive immune response. The main events of the inflammatory processes take place in the connective tissue.

  6. 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....... 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...... 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...

  7. Heritable Disorders of Connective Tissue

    Science.gov (United States)

    ... Connective Tissue Find a Clinical Trial Journal Articles Connective Tissue August 2016 Questions and Answers about Heritable Disorders of Connective Tissue This publication contains general information about heritable (genetic) ...

  8. 18.CONNECTIVE TISSUE DISORDER

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930734 Measurement of serum soluble interleukin—2 receptor in connective tissue diseases.CAI Houronget al.Dept Intern Med,Affili Gulou Hosp,Med School,Nanjing Univ,Nanjing,210008,ShanghaiJ Immunol 1993;13(4):216—218December 1993 Vol 10 No 4

  9. Connective tissue ulcers.

    Science.gov (United States)

    Dabiri, Ganary; Falanga, Vincent

    2013-11-01

    Connective tissue disorders (CTD), which are often also termed collagen vascular diseases, include a number of related inflammatory conditions. Some of these diseases include rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis (scleroderma), localized scleroderma (morphea variants localized to the skin), Sjogren's syndrome, dermatomyositis, polymyositis, and mixed connective tissue disease. In addition to the systemic manifestations of these diseases, there are a number of cutaneous features that make these conditions recognizable on physical exam. Lower extremity ulcers and digital ulcers are an infrequent but disabling complication of long-standing connective tissue disease. The exact frequency with which these ulcers occur is not known, and the cause of the ulcerations is often multifactorial. Moreover, a challenging component of CTD ulcerations is that there are still no established guidelines for their diagnosis and treatment. The morbidity associated with these ulcerations and their underlying conditions is very substantial. Indeed, these less common but intractable ulcers represent a major medical and economic problem for patients, physicians and nurses, and even well organized multidisciplinary wound healing centers.

  10. Genetic analysis of basophil function in vivo

    OpenAIRE

    Sullivan, Brandon M.; Liang, Hong-Erh; Bando, Jennifer K.; Wu, Davina; Cheng, Laurence E.; McKerrow, James K.; Allen, Christopher D.C.; Locksley, Richard M.

    2011-01-01

    Contributions by basophils to allergic and helminth immunity remain incompletely defined. Using sensitive IL-4 reporter alleles, we demonstrate that basophil IL-4 production occurs by a CD4+ T cell-dependent process restricted to affected peripheral tissues. We genetically marked and specifically deleted basophils and demonstrate that basophils do not mediate TH2 priming in vivo. Two-photon imaging confirmed that basophils do not interact with antigen-specific T cells in lymph nodes, but can ...

  11. [Muscles and connective tissue: histology].

    Science.gov (United States)

    Delage, J-P

    2012-10-01

    Here, we give some comments about the DVD movies "Muscle Attitudes" from Endovivo productions, the movies up lighting some loss in the attention given to studies on the connective tissue, and especially them into muscles. The main characteristics of the different components in the intra-muscular connective tissue (perimysium, endomysium, epimysium) are shown here with special references to their ordered architecture and special references to their spatial distributions. This connective tissue is abundant into the muscles and is in continuity with the muscles in vicinity, with their tendons and their sheath, sticking the whole on skin. This connective tissue has also very abundant connections on the muscles fibres. It is then assumed that the connective tissue sticks every organs or cells of the locomotion system. Considering the elastic properties of the collagen fibres which are the most abundant component of connective tissue, it is possible to up light a panel of connective tissue associated functions such as the transmission of muscle contractions or the regulation of protein and energetic muscles metabolism.

  12. [Connective tissue diseases in adolescents].

    Science.gov (United States)

    Peitz, J; Tantcheva-Poór, I

    2016-04-01

    In this article we provide a brief review of systemic lupus erythematosus, juvenile dermatomyositis, systemic scleroderma, and mixed connective tissue disease in adolescents. As skin manifestations often belong to the presenting symptoms and may have a significant impact on the quality of life, dermatologists play an important role in the management of patients with connective tissue diseases. Early diagnosis and therapy onset are crucial for the patients' long-term outcome.

  13. Pleura: In connective tissue diseases

    Directory of Open Access Journals (Sweden)

    Kaushik Saha

    2016-01-01

    Full Text Available Connective tissue diseases (CTDs (or collagen vascular diseases represent a heterogeneous group of immunologically mediated disorders that affects many organs of the body including pleura. Frequency, presentation, and prognosis of pleural involvement depend on the underlying CTD. Connective tissue disorders may be heritable such as Marfan syndrome, Ehlers-Danlos syndrome, and osteogenesis imperfecta; and autoimmune such as systemic lupus erythematosus (SLE, rheumatoid arthritis (RA, systemic sclerosis, mixed connective tissue disease (MCTD, Sjögren's syndrome (SS, dermatomyositis (DM, and polymyositis (PM. The subject of this review is to describe the variety of pleural disorders observed in the most frequent types of CTD: SLE, RA, scleroderma, SS, DM, PM, and MCTD.

  14. Genetic analysis of basophil function in vivo.

    Science.gov (United States)

    Sullivan, Brandon M; Liang, Hong-Erh; Bando, Jennifer K; Wu, Davina; Cheng, Laurence E; McKerrow, James K; Allen, Christopher D C; Locksley, Richard M

    2011-06-01

    Contributions by basophils to allergic and helminth immunity remain incompletely defined. Using sensitive interleukin 4 (Il4) reporter alleles, we demonstrate here that basophil IL-4 production occurs by a CD4(+) T cell-dependent process restricted to the peripheral tissues affected. We genetically marked and achieved specific deletion of basophils and found that basophils did not mediate T helper type 2 (T(H)2) priming in vivo. Two-photon imaging confirmed that basophils did not interact with antigen-specific T cells in lymph nodes but engaged in prolonged serial interactions with T cells in lung tissues. Although targeted deletion of IL-4 and IL-13 in either CD4(+) T cells or basophils had a minimal effect on worm clearance, deletion from both lineages demonstrated a nonredundant role for basophil cytokines in primary helminth immunity.

  15. Adipokines in connective tissue diseases.

    Science.gov (United States)

    Sawicka, Karolina; Krasowska, Dorota

    2016-01-01

    Adipokines, pleiotropic molecules produced by white adipose tissue (WAT) have attracted the attention of scientists since 1994. The role of adipokines in metabolic syndrome is known and fixed. Adipokines exerting a variety of metabolic activities have contributed to the ethiopathogenesis and the consequences of metabolic syndrome. Furthermore, adipokines are involved in the regulation of inflammatory processes and autoimmunity in the light of pathogenesis of connective tissue diseases. Given some evidence for the influence of adipokines in metabolic syndrome, there may be a link between CVDs and rheumatic diseases. This review provides an overview of the literature focusing on the role of adipokines in rheumatic diseases by putting special emphasis on the potential role of leptin, resistin, adiponectin, chemerin, visfatin and novel adipokines in connective tissue diseases.

  16. Autoimmune connective tissue disease: scleroderma.

    Science.gov (United States)

    Wilson, Helen; Vincent, Rachel

    Scleroderma is an umbrella term for a spectrum of rare and complex autoimmune connective tissue diseases, the cause and pathogenesis of which is only partially defined. Scleroderma can be divided into two main subgroups--systemic and localized--but the hallmark of both is skin fibrosis. As yet no drug has been found to be effective in reversing the disease process, however early intervention has been shown to give maximum benefit. Due to the chronic nature of the condition a multidisciplinary approach is essential and the nurse's input from an early stage is vital in supporting the patient to manage both their medical treatment and their activities of daily living.

  17. Hematopoietic stem cell origin of connective tissues.

    Science.gov (United States)

    Ogawa, Makio; Larue, Amanda C; Watson, Patricia M; Watson, Dennis K

    2010-07-01

    Connective tissue consists of "connective tissue proper," which is further divided into loose and dense (fibrous) connective tissues and "specialized connective tissues." Specialized connective tissues consist of blood, adipose tissue, cartilage, and bone. In both loose and dense connective tissues, the principal cellular element is fibroblasts. It has been generally believed that all cellular elements of connective tissue, including fibroblasts, adipocytes, chondrocytes, and bone cells, are generated solely by mesenchymal stem cells. Recently, a number of studies, including those from our laboratory based on transplantation of single hematopoietic stem cells, strongly suggested a hematopoietic stem cell origin of these adult mesenchymal tissues. This review summarizes the experimental evidence for this new paradigm and discusses its translational implications.

  18. 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.

  19. [Gastroenterologic aspects of connective tissue diseases].

    Science.gov (United States)

    Altomonte, L; Zoli, A; Alessi, F; Ghirlanda, G; Greco, A V; Magarò, M

    1985-07-14

    The connective tissue disorders are a protean group of acquired diseases which have in common widespread immunologic and inflammatory alterations of connective tissue. The acquired connective tissue diseases generally include the following clinical entities: rheumatoid arthritis, systemic lupus erythematosus, polymyositis, polyarteritis nodosa, scleroderma, mixed connective tissue disease, Sjögren's and Behcet's sindromes. These entities have certain features in common which include sinovitis, pleuritis, myocarditis, endocarditis, pericarditis, peritonitis, vasculitis, myositis, changes in skin, alteration of connective tissue and nephritis. Gastrointestinal and hepatic involvement in connective tissue disorders are not the most important features, nevertheless appear almost regularly. Anorexia, nausea, vomiting, abdominal pain, malabsorption may affect patients suffering by rheumatoid arthritis, systemic lupus erythematosus and other collagenophaties. In some cases mesenteric vasculitis may cause intestinal ischemia which may result in bowel infarction, mucosal ulceration, hemorrhage, perforation. After an extensive review of the existing literature the Authors make an accurate evaluation of gastrointestinal and hepatic alterations in connective tissue diseases.

  20. [Connective tissue and prolapse genesis].

    Science.gov (United States)

    Tremollieres, F

    2010-06-01

    The pathophysiology of pelvic floor disorders still remains not well understood. Increasing age as well as vaginal multiparity are the main commonly accepted factors. The hypothesis of a defect of connective tissues of the pelvic floor with aging due to collagen deficiency and/or elastic fiber degradation is often highlighted. The issue of a potential protective role of HRT is also discussed although the recent results from the WHI would suggest a negative impact of HRT on urinary incontinence, especially when HRT is initiated in elderly women, far from the menopause. Nevertheless, environmental factors cannot explain the full pathogenesis of pelvic organ prolapse (POP) and the contribution of genetic factors to the development of pelvic floor disorders is widely recognized. Support for a genetic influence on POP derives from reports suggesting that heritability is a strong contributing factor and a familial history of POP is considered as a classical risk factor. However, the characterization of the underlying molecular mechanisms remains limited, since POP may be considered the end result of a multifactorial process leading to destruction of vaginal wall connective tissue. Experimental studies in mice with null mutations in the genes encoding different putative factors involved in elastic fibers remodeling and homeostasis are crucial in the understanding of the pathogenesis of POP. Mice with null mutation in the gene encoding lysyl oxidase-like 1 (LOXL1) or fibulin-5, demonstrate signs of elastinopathy including the development of a POP in the postpartum. Likewise, homeobox genes such as HOXA11, which are essential in the embryonic development of the urogenital tract might also be involved in the pathogenesis of POP. The better understanding of the underlying determinants of pelvic floor disorders with a special focus on genetic factors may offer new therapeutic strategies, in addition to or replacement of surgical procedures.

  1. Basophils and skin disorders.

    Science.gov (United States)

    Borriello, Francesco; Granata, Francescopaolo; Marone, Gianni

    2014-05-01

    Since their discovery in 1879, basophils have been viewed as circulating blood granulocytes with limited immune function. New research tools for their functional analysis in vivo have revealed previously unrecognized roles for basophils in several skin disorders. Human basophils infiltrate different skin lesions and have been implicated in the pathogenesis of diseases ranging from chronic idiopathic urticaria to systemic lupus erythematosus. In mouse models, basophils participate in IgE-mediated chronic allergic inflammation of the skin and have a protective role in tick infestation. In this review, we discuss critical advances in our understanding of basophil biology and their roles in the pathophysiology of skin disorders.

  2. Newly appreciated roles for basophils in allergy and protective immunity.

    Science.gov (United States)

    Karasuyama, H; Obata, K; Wada, T; Tsujimura, Y; Mukai, K

    2011-09-01

    Basophils are evolutionarily conserved in many animal species, in spite of the fact that they account for basophils have an indispensable and nonredundant role in vivo, even though they show some phenotypic similarity with tissue-resident mast cells. However, their functional significance remained uncertain long after Paul Ehrlich discovered them as blood-circulating cells with basophilic granules more than 130 years ago. The study of basophils has been far behind that of mast cells, owing to the rarity of basophils and the paucity of tools for their detection and functional analysis. Recent development of novel analytical tools, including basophil-depleting antibodies and genetically engineered mice deficient only in basophils, has greatly advanced basophil research and illuminated previously unrecognized roles of basophils. We now appreciate that basophils and mast cells play distinct roles in immune responses. Basophils have crucial roles in the development of acute and chronic allergic responses, the protective immunity against ecto- and endoparasites, and the regulation of acquired immunity, including the augmentation of humoral memory responses and the initiation of Th2 responses. Thus, basophils are no longer the neglected minority and are key players in the immune system.

  3. Radiotherapy of hypertrophic connective tissue

    Energy Technology Data Exchange (ETDEWEB)

    Haase, W.

    1982-10-11

    Peyronie's disease, Dupuytren's contractures and keloids produce similar pathologic-anatomic alterations of hypertrophic tissue. Different therapeutic modalities are presented in detail. The radiation therapy is one of the most effective treatments. Radiation technique, dose and fractionation are discussed. The results of the different modalities are reviewed.

  4. Silicone breast implants and connective tissue disease

    DEFF Research Database (Denmark)

    Lipworth, Loren; Holmich, Lisbet R; McLaughlin, Joseph K

    2011-01-01

    The association of silicone breast implants with connective tissue diseases (CTDs), including systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, and fibromyalgia, as well as a hypothesized new "atypical" disease, which does not meet established diagnostic criteria for any known...

  5. Microgravity Stress: Bone and Connective Tissue.

    Science.gov (United States)

    Bloomfield, Susan A; Martinez, Daniel A; Boudreaux, Ramon D; Mantri, Anita V

    2016-03-15

    The major alterations in bone and the dense connective tissues in humans and animals exposed to microgravity illustrate the dependency of these tissues' function on normal gravitational loading. Whether these alterations depend solely on the reduced mechanical loading of zero g or are compounded by fluid shifts, altered tissue blood flow, radiation exposure, and altered nutritional status is not yet well defined. Changes in the dense connective tissues and intervertebral disks are generally smaller in magnitude but occur more rapidly than those in mineralized bone with transitions to 0 g and during recovery once back to the loading provided by 1 g conditions. However, joint injuries are projected to occur much more often than the more catastrophic bone fracture during exploration class missions, so protecting the integrity of both tissues is important. This review focuses on the research performed over the last 20 years in humans and animals exposed to actual spaceflight, as well as on knowledge gained from pertinent ground-based models such as bed rest in humans and hindlimb unloading in rodents. Significant progress has been made in our understanding of the mechanisms for alterations in bone and connective tissues with exposure to microgravity, but intriguing questions remain to be solved, particularly with reference to biomedical risks associated with prolonged exploration missions.

  6. Regulation of the Il4 gene is independently controlled by proximal and distal 3' enhancers in mast cells and basophils.

    Science.gov (United States)

    Yagi, Ryouji; Tanaka, Shinya; Motomura, Yasutaka; Kubo, Masato

    2007-12-01

    Mast cells and basophils are known to be a critical interleukin 4 (IL-4) source for establishing Th2 protective responses to parasitic infections. Chromatin structure and histone modification patterns in the Il13/Il4 locus of mast cells were similar to those of IL-4-producing type 2 helper T cells. However, using a transgenic approach, we found that Il4 gene expression was distinctly regulated by individual cis regulatory elements in cell types of different lineages. The distal 3' element contained conserved noncoding sequence 2 (CNS-2), which was a common enhancer for memory phenotype T cells, NKT cells, mast cells, and basophils. Targeted deletion of CNS-2 compromised production of IL-4 and several Th2 cytokines in connective-tissue-type and immature-type mast cells but not in basophils. Interestingly, the proximal 3' element containing DNase I-hypersensitive site 4 (HS4), which controls Il4 gene silencing in T-lineage cells, exhibited selective enhancer activity in basophils. These results indicate that CNS-2 is an essential enhancer for Il4 gene transcription in mast cell but not in basophils. The transcription of the Il4 gene in mast cells and basophils is independently regulated by CNS-2 and HS4 elements that may be critical for lineage-specific Il4 gene regulation in these cell types.

  7. [Pulmonary involvement in connective tissue disease].

    Science.gov (United States)

    Bartosiewicz, Małgorzata

    2016-01-01

    The connective tissue diseases are a variable group of autoimmune mediated disorders characterized by multiorgan damage. Pulmonary complications are common, usually occur after the onset of joint symptoms, but can also be initially presenting complaint. The respiratory system may be involved in all its component: airways, vessels, parenchyma, pleura and respiratory muscles. Lung involvement is an increasing cause of morbidity and mortality in the connective tissue diseases. Clinical course is highly variable - can range from mild to rapidly progressive, some processes are reversible, while others are irreversible. Thus, the identification of reversible disease , and separately progressive disease, are important clinical issues. The frequency, clinical presentation, prognosis and responce to therapy are different, depending on the pattern of involvement as well as on specyfic diagnostic method used to identify it. High- resolution computed tompography plays an important role in identifying patients with respiratory involvement. Pulmonary function tests are a sensitive tool detecting interstitial lung disease. In this article, pulmonary lung involvement accompanying most frequently apperaing connective tissue diseases - rheumatoid arthritis, systemic sclerosis, lupus erythematosus, polymyositis/dermatomyositis, Sjögrens syndrome and mixed connective tissue disaese are reviewed.

  8. Stretching Impacts Inflammation Resolution in Connective Tissue.

    Science.gov (United States)

    Berrueta, Lisbeth; Muskaj, Igla; Olenich, Sara; Butler, Taylor; Badger, Gary J; Colas, Romain A; Spite, Matthew; Serhan, Charles N; Langevin, Helene M

    2016-07-01

    Acute inflammation is accompanied from its outset by the release of specialized pro-resolving mediators (SPMs), including resolvins, that orchestrate the resolution of local inflammation. We showed earlier that, in rats with subcutaneous inflammation of the back induced by carrageenan, stretching for 10 min twice daily reduced inflammation and improved pain, 2 weeks after carrageenan injection. In this study, we hypothesized that stretching of connective tissue activates local pro-resolving mechanisms within the tissue in the acute phase of inflammation. In rats injected with carrageenan and randomized to stretch versus no stretch for 48 h, stretching reduced inflammatory lesion thickness and neutrophil count, and increased resolvin (RvD1) concentrations within lesions. Furthermore, subcutaneous resolvin injection mimicked the effect of stretching. In ex vivo experiments, stretching of connective tissue reduced the migration of neutrophils and increased tissue RvD1 concentration. These results demonstrate a direct mechanical impact of stretching on inflammation-regulation mechanisms within connective tissue.

  9. 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.

  10. Nevos de tejido conectivo Connective tissue nevi

    Directory of Open Access Journals (Sweden)

    RE Achenbach

    Full Text Available Comunicamos dos casos de nevo del tejido conectivo, el primero con patrón histológico mixto y el segundo con predominio de alteraciones en las fibras elásticas. No se constataron síndromes ni patología sistémica asociada. Un caso presentó disposición linear y un nevo acrómico asociado.Two cases of connective tissue nevi are reported, one of them with a mixed histopatologic pattern and one with elastin fibers diminished. None of the patients had systemic involvement or associated syndromes. The mixed connective tissue nevi type showed a linear distribution and has associated an acromic nevi.

  11. Klinefelter syndrome and acute basophilic leukaemia--case report.

    Science.gov (United States)

    Ljubić, Nives; Lang, Nada; Skelin, Ika Kardum; Lasan, Ruzica; Dominis, Mara; Perković, Leila; Zupanić-Krmek, Dubraka; Grgurević-Batinica, Anita

    2010-06-01

    Patients with 47, XXY karyotype (Klinefelter syndrome) appear to have increased risk of developing cancer, especially male breast cancer, germ cell tumours and non Hodgkin lymphomas, but rarely acute myeloid leukaemia. We report a patient with acute basophilic leukaemia with 47, XXY karyotype in both the tumour and constitutional cells. Acute basophilic leukaemia is very rare disease comprising less than 1% of all acute myeloid leukaemias. Morphological characteristic of leukaemic blast cells is moderately basophilic cytoplasm containing a variable number of coarse basophilic granules. The most characteristic cytochemical reaction is metachromatic positivity with toluidine blue. Blast are myeloperoxidase negative. Also leukemic blasts express myeloid and monocyte markers. There is no consistent chromosomal abnormality identified in this leukaemia. This is the first reported case of acute basophilic leukaemia in patient with Klinefelter syndrome. In this article the medical history of the patient is given and the possible connection between Klinefelter syndrome and acute myeloid leukaemia is discussed.

  12. 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.

  13. Soft Tissue Engineering with Micronized-Gingival Connective Tissues.

    Science.gov (United States)

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

    2017-02-24

    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. This article is protected by copyright. All rights reserved.

  14. MIXED CONNECTIVE TISSUE DISORDER WITH PREGNANCY

    Directory of Open Access Journals (Sweden)

    Narmadha

    2015-12-01

    Full Text Available Mixed connective tissue disease (MCTD is a term involving the features of lupus systemic sclerosis, polymyositis, rheumatoid arthritis and high titre of anti ribonucleoprotein (RNP antibodies, exact etiology is not known. It is characterized by microvascular damage, immune system activation leading to inflammation and excessive deposition of collagen in the skin, lungs, heart, gastrointestinal tract and kidneys. The females are being more affected especially after childbirth attributed to the hypothesis of microchimerism, the pathogenesis being a two way migration of fetal cells through the placenta. It cannot be cured completely but treatment with corticosteroids is helpful. ACE inhibitors are useful in renal involvement and hypertension. We had a case of mixed connective tissue disorder in a patient aged 28 years with 12 weeks of gestation for medical termination of pregnancy (MTP and permanent sterilization. The complications are preeclampsia, preterm labor, fetal growth restriction, eclampsia, thrombocytopenia and infections like pneumonia, sepsis like syndrome and the maternal mortality rate is 325/100000. This is a unique case of MCTD wherein we had limited cutaneous disease like CREST-calcinosis, Raynaud’s phenomenon, esophageal involvement, sclerodactyly and telangiectasia of a lesser degree. So early diagnosis and timely intervention is advocated to prevent complications

  15. Connective tissue metabolism in chikungunya patients

    Directory of Open Access Journals (Sweden)

    Vemula Sarojamma

    2008-02-01

    Full Text Available Abstract Background Chikungunya (CHIK fever is a viral disease transmitted to humans by the bite of Chikungunya virus (CHIK virus infected Aedes mosquitoes. CHIK virus is a member of the Alphavirus genus of the family Togaviridae. Previous reports have indicated that infection with CHIK virus produces an acute arthritis in human hosts by large area of necrosis and collagenosis or fibrosis. Results We carried out the present study to determine the effect of chikungunya on the collagen and connective tissue metabolism in 75 chikungunya-affected people. First, we screened for mucopolysaccharides in urine by Cetyl Trimethyl Ammonium Bromide (CTAB test. Appearance of heavy precipitate indicates the presence of higher levels of mucopolysaccharides and later quantified by DMB dye method. The urinary mucopolysaccharide in CHIK patients was 342 ± 45 mg/l compared to healthy controls (45 ± 5.6 mg/l. The collagen building blocks, proline and hydroxyproline were also measured in CHIK patients and observed higher excretion compared to healthy controls. Urinary excretions hydroxyproline was greater than the proline levels. Conclusion These results indicate that CHIK virus infection affects and damage the cartilage and connective metabolism and releases the degraded products from the tissue and responsible for increasing the levels of proline, hydroxyproline and mucopolysaccharides in CHIK affected patients.

  16. [Marfan syndrome and related connective tissue disorders].

    Science.gov (United States)

    Steindl, Katharina

    2013-11-27

    Marfan syndrome is an autosomal dominantly inherited connective tissue disorder with a prevalence of approximately 1:5000 people. Typical manifestations affect the cardiovascular system, eyes, skeleton, lungs, skin and dura mater. Most patients have a so-called marfanoid habitus with tall stature, long and narrow limbs, a long and narrow head shape and other skeletal abnormalities. Of particular medical importance are the possible complications such as severe scoliosis or pectus excavatum, spontaneous pneumothorax, retinal detachment, or an acute glaucoma evoked by lens luxation. However, the most dangerous complication is acute dissection of the ascending aorta, which is usually the result of a slowly progressive aortic dilatation. With the introduction of therapies the average life expectancy of previously just 32 years could be raised to above 60 years.

  17. 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.

  18. FIBROBLAST INVOLVEMENT IN SOFT CONNECTIVE TISSUE CALCIFICATION

    Directory of Open Access Journals (Sweden)

    Ivonne eRonchetti

    2013-03-01

    Full Text Available Soft connective tissue calcification is not a passive process, but the consequence of metabolic changes of local mesenchymal cells that, depending on both genetic and environmental factors, alter the balance between pro- and anti-calcifying pathways. While the role of smooth muscle cells and pericytes in ectopic calcifications has been widely investigated, the involvement of fibroblasts is still elusive. Fibroblasts isolated from the dermis of PXE patients and of patients exhibiting PXE-like clinical and histopathological findings offer an attractive model to investigate the mechanisms leading to the precipitation of mineral deposits within elastic fibres and to explore the influence of the genetic background and of the extracellular environment on fibroblast-associated calcifications, thus improving the knowledge on the role of mesenchymal cells on pathologic mineralization.

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

    Directory of Open Access Journals (Sweden)

    Dustin Baldridge

    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.

  20. 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.

  1. [Autoimmune connective tissue diseases and vaccination].

    Science.gov (United States)

    Więsik-Szewczyk, Ewa; Jahnz-Różyk, Karina

    2015-12-31

    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 sensitive 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. Connective tissue diseases mimicking multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Maryam Moghaddassi-Jahromi

    2011-11-01

    Full Text Available Background: Connective tissue diseases (CTD can involve nervous system. Diagnosis and differentiation from multiple sclerosis (MS can be difficult especially when the disease presented by symptoms and signs related to demyelinating process. The aim of this article is to review the variant forms of central nervous system involvement in CTD especially useful points for differentiation from demyelinating disorders. Materials and Method: We used the relevant articles in PUBMED, Scopus and other databases especially published in recent ten years. Results: Systemic lupus erythematosus (SLE, antiphospholipid syndrome (APS, Behcet’s disease (BD, Sjogren's syndrome (SS, and some vasculitides can involve nervous system. Patients may be present by demyelination areas in the white matter of the brain and spinal cord, which are difficult to differentiate from MS and other demyelinating processes, such as transverse myelitis and optic neuritis. On the other hand, autoantibodies such as antinuclear antibodies (ANA and antiphospholipid antibodies (aPL can also occur in MS. Treatment and prognosis of these diseases are quite different. In demyelinating diseases the diagnosis is established on the basis of clinical presentation, magnetic resonance imaging (MRI, cerebrospinal fluid (CSF examination, visual evoked potentials (VEP and autoantibody investigation.Conclusion: In many patients, distinction between different etiologies of demyelination can be made by considering clinical and paraclinical data, but in some cases, accurate diagnosis can only be made after long-term follow-up

  3. 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.

  4. Pectus excavatum and heritable disorders of the connective tissue.

    Science.gov (United States)

    Tocchioni, Francesca; Ghionzoli, Marco; Messineo, Antonio; Romagnoli, Paolo

    2013-09-24

    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.

  5. Basophil stimulation and signaling pathways.

    Science.gov (United States)

    Knol, Edward F; Gibbs, Bernhard F

    2014-01-01

    Despite growing use of flow cytometry to analyze the functional characteristics of primary basophils the intracellular signaling cascades that control their ability to elaborate various inflammatory mediators and cytokines remain comparatively obscure. Additionally, some studies require the analysis of pro-allergic and inflammatory mediators, such as histamine, LTC4, and various basophil-derived cytokines (e.g., IL-4 and IL-13). Elucidation of intracellular signaling proteins by Western blotting, cytosolic free calcium concentration by spectrofluorophotometry, and detection of mediator releases, as well as analysis of gene expressions by RT-PCR, generally require relatively large numbers of purified basophils. In selected assays, flow cytometry can enable the analysis of relatively low cell numbers and purity for the expression of intracellular signaling proteins or measurement of cytosolic free calcium concentrations by basophil-specific gating strategies. Unfortunately, many aspects of signal transduction relevant to human basophils cannot be readily extrapolated from the use of basophil or mast cell lines. This chapter therefore focuses on how to employ primary human basophils for studying mediator releases and signaling characteristics.

  6. 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

  7. Imaging of connective tissue diseases of the head and neck.

    Science.gov (United States)

    Abdel Razek, Ahmed Abdel Khalek

    2016-06-01

    We review the imaging appearance of connective tissue diseases of the head and neck. Bilateral sialadenitis and dacryoadenitis are seen in Sjögren's syndrome; ankylosis of the temporo-mandibular joint with sclerosis of the crico-arytenoid joint are reported in rheumatoid arthritis and lupus panniculitis with atypical infection are reported in patients with systemic lupus erythematosus. Relapsing polychondritis shows subglottic stenosis, prominent ear and saddle nose; progressive systemic sclerosis shows osteolysis of the mandible, fibrosis of the masseter muscle with calcinosis of the subcutaneous tissue and dermatomyositis/polymyositis shows condylar erosions and autoimmune thyroiditis. Vascular thrombosis is reported in antiphospholipid antibodies syndrome; cervical lymphadenopathy is seen in adult-onset Still's disease, and neuropathy with thyroiditis reported in mixed connective tissue disorder. Imaging is important to detect associated malignancy with connective tissue disorders. Correlation of the imaging findings with demographic data and clinical findings are important for the diagnosis of connective tissue disorders.

  8. Biomarkers of connective tissue disease in patients with intracranial aneurysms.

    Science.gov (United States)

    Yurt, Alaattin; Vardar, Enver; Selçuki, Mehmet; Ertürk, Ali Riza; Ozbek, Gülriz; Atçi, Burak

    2010-09-01

    Connective tissue defects may play a significant role in the development of intracranial aneurysms (IAs). Multiorgan connective tissue disorders may, therefore, indicate a risk of IA development. We investigated biomarkers of connective tissue disease in patients with IAs. A series of 62 patients with IAs was studied by physical examination, echocardiography, ultrasound examination of the kidneys and abdomen, and microscopic examination of skin tissue (temporal area) and superficial temporal artery taken at operation. Patients with IAs had a higher incidence of biomarkers of systemic connective tissue disease than controls and identification of these markers may be important for screening for IAs. Microscopic investigation of biopsies of the skin and superficial temporal artery from patients and their relatives may become valuable for clinical diagnosis, identification of people at risk and basic studies of the pathogenesis of this vascular disease.

  9. Development and characterization of a monoclonal antibody specific for human basophils and the identification of a unique secretory product of basophil activation.

    Science.gov (United States)

    McEuen, A R; Buckley, M G; Compton, S J; Walls, A F

    1999-01-01

    Despite increasing evidence that basophils can infiltrate into inflamed tissues during allergic reactions, determination of the extent of infiltration and elucidation of their role in allergic disease has been frustrated by the lack of reliable means for detecting this cell type in tissues. In the present study, we report on a new monoclonal antibody specific for basophils and on the initial characterization of the antigen it recognizes. Basophils were isolated from peripheral blood by Percoll density gradient centrifugation and a positive-selection immunomagnetic procedure and injected into mice to produce monoclonal antibodies. A hybridoma clone, designated BB1, secreted antibody of the IgG2a isotype; this antibody bound selectively to basophils on immunocytochemistry but did not react with any other cell type or tissue structure, although it did stain a proportion of cells from the basophilic cell line KU812F. In sections of mixed populations of peripheral blood cells, similar numbers of cells stained with Alcian blue dye and BB1 over a wide range of basophil purity. BB1 antibody was effective in identifying basophils in sections of mixed cells or in tissues after fixation with ethanol, Carnoy's solution, or formalin. Staining of basophils with BB1 gave a granular appearance, although flow cytometry indicated that some antigen was also present on the surface of the cell. Activation of these cells with anti-IgE antibody or with the calcium ionophore A23187 provoked release of the antigen in parallel with that of histamine. BB1 antibody did not, by itself, stimulate histamine release. The molecular mass of the antigen was determined on Hedrick-Smith gels to be 124+/-11 kd. This new monoclonal antibody will be a valuable experimental tool in future studies, allowing the reliable detection of basophils in tissues of patients with allergic and chronic inflammatory disease; in addition, the antigen it identifies has potential as a unique marker of basophil activation.

  10. Imaging of Pulmonary Manifestations of Connective Tissue Diseases.

    Science.gov (United States)

    Ahuja, Jitesh; Arora, Deepika; Kanne, Jeffrey P; Henry, Travis S; Godwin, J David

    2016-11-01

    Connective tissue diseases (CTDs) are a heterogeneous group of conditions characterized by circulating autoantibodies and autoimmune-mediated organ damage. Common CTDs with lung manifestations are rheumatoid arthritis, scleroderma or systemic sclerosis, Sjögren syndrome, polymyositis/dermatomyositis, systemic lupus erythematosis, mixed connective tissue disease, and undifferentiated connective tissue disease. The most common histopathologic patterns of CTD-related interstitial lung disease are nonspecific interstitial pneumonia, usual interstitial pneumonia, organizing pneumonia, and lymphoid interstitial pneumonia. Drug treatment of CTDs can cause complications, including opportunistic infection.

  11. 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.

  12. Connective tissue markers of rheumatoid arthritis

    DEFF Research Database (Denmark)

    Møller, H J

    1998-01-01

    biochemical research is devoted to characterizing molecules which are of diagnostic and prognostic value, as well as molecules which are indicators of the degree of joint cartilage and bone destruction. The present survey summarizes current knowledge concerning possible tissue-specific marker molecules of RA....

  13. [CT imaging features of pulmonary involvement in connective tissue disorders].

    Science.gov (United States)

    Brillet, P Y; Mama, N; Nunes, H; Uzunhan, Y; Abbad, S; Brauner, M W

    2009-11-01

    Connective tissue disorders correspond to a heterogeneous group of inflammatory diseases characterized by abnormal immune system activity leading to connective tissue alterations in multiple parts of the body. In adults, connective tissue disorders include rheumatoid arthritis, progressive systemic sclerosis, Sjögren syndrome, systemic lupus erythematosus, dermatomyositis and polymyositis, ankylosing spondylitis, and mixed connective tissue disease. Broncho-pulmonary involvement may be variable with involvement of all anatomical components of the lung. Involvement of other intrathoracic structures (pleura, respiratory muscles, heart, rib cage) is frequent. The most specific manifestations include interstitial lung diseases and pulmonary hypertension. During follow-up, progressive respiratory diseases may occur due to the treatment, infections, pulmonary embolism or neoplasms.

  14. Infiltration of hypertrophic esophageal smooth muscle by mast cells and basophils.

    Science.gov (United States)

    Tung, H N; Schulze-Delrieu, K; Shirazi, S

    1993-01-01

    Partial obstruction leads to chronic distension and muscular hypertrophy of the opossum esophagus. The smooth muscle cells of the circular muscle layer enlarge, become pleomorphic and are surrounded by an amorphous ground substance in the extracellular space. Here we describe the histological and ultrastructural features of a peculiar cellular infiltrate in the hypertrophic smooth muscle. The infiltrate consisted uniquely of mast cells and basophils. In per unit area, the number of mast cells increased from 0.9 +/- 0.1 cells in controls to 3.7 +/- 0.2 in hypertrophic smooth muscle; the corresponding numbers for basophils were 2.5 +/- 0.2 and 7.2 +/- 0.3 cells. Cells were seen primarily in the septal spaces of the circular muscle layer and at the interface of the circular and longitudinal muscle layer. The cytoplasm of basophils is normally packed with round and oval granules. The granules stain metachromatically and with varying intensity on Wright-Giemsa stains. On transmission electronmicroscopy, granules display a membrane and a great diversity in the structure of their luminal contents. In hypertrophic muscle, most granules were discharging their contents into the cytoplasm or extracellular space. The membranes of adjacent empty granules then fused to form a chain of vacuoles. Similar changes occurred also in the mast cells which differed from the basophil by their lack of nuclear lobulation and by the greater homogeneity of their cytoplasmic granules. It is possible that these inflammatory cells are involved in the reconstruction of the smooth muscle and its connective tissue which occur during esophageal distension and hypertrophy.

  15. FIBROBLAST CYTOSKELETAL REMODELING CONTRIBUTES TO CONNECTIVE TISSUE TENSION

    Science.gov (United States)

    Langevin, Helene M.; Bouffard, Nicole A.; Fox, James R.; Palmer, Bradley M.; Wu, Junru; Iatridis, James C.; Barnes, William D.; Badger, Gary J.; Howe, Alan K.

    2011-01-01

    The viscoelastic behavior of connective tissue is generally attributed to the material properties of the extracellular matrix rather than cellular activity. We have previously shown that fibroblasts within areolar connective tissue exhibit dynamic cytoskeletal remodeling within minutes in response to tissue stretch ex vivo and in vivo. Here, we tested the hypothesis that fibroblasts, through this cytoskeletal remodeling, actively contribute to the viscoelastic behavior of the whole tissue. We measured significantly increased tissue tension when cellular function was broadly inhibited by sodium azide and when cytoskeletal dynamics were compromised by disrupting microtubules (with colchicine) or actomyosin contractility (via Rho kinase inhibition). These treatments led to a decrease in cell body cross-sectional area and cell field perimeter (obtained by joining the end of all of a fibroblast’s processes). Suppressing lamellipodia formation by inhibiting Rac-1 decreased cell body cross-sectional area but did not affect cell field perimeter or tissue tension. Thus, by changing shape, fibroblasts can dynamically modulate the viscoelastic behavior of areolar connective tissue through Rho-dependent cytoskeletal mechanisms. These results have broad implications for our understanding of the dynamic interplay of forces between fibroblasts and their surrounding matrix, as well as for the neural, vascular and immune cell populations residing within connective tissue. PMID:20945345

  16. Fibroblast cytoskeletal remodeling contributes to connective tissue tension.

    Science.gov (United States)

    Langevin, Helene M; Bouffard, Nicole A; Fox, James R; Palmer, Bradley M; Wu, Junru; Iatridis, James C; Barnes, William D; Badger, Gary J; Howe, Alan K

    2011-05-01

    The visco-elastic behavior of connective tissue is generally attributed to the material properties of the extracellular matrix rather than cellular activity. We have previously shown that fibroblasts within areolar connective tissue exhibit dynamic cytoskeletal remodeling within minutes in response to tissue stretch ex vivo and in vivo. Here, we tested the hypothesis that fibroblasts, through this cytoskeletal remodeling, actively contribute to the visco-elastic behavior of the whole tissue. We measured significantly increased tissue tension when cellular function was broadly inhibited by sodium azide and when cytoskeletal dynamics were compromised by disrupting microtubules (with colchicine) or actomyosin contractility (via Rho kinase inhibition). These treatments led to a decrease in cell body cross-sectional area and cell field perimeter (obtained by joining the end of all of a fibroblast's processes). Suppressing lamellipodia formation by inhibiting Rac-1 decreased cell body cross-sectional area but did not affect cell field perimeter or tissue tension. Thus, by changing shape, fibroblasts can dynamically modulate the visco-elastic behavior of areolar connective tissue through Rho-dependent cytoskeletal mechanisms. These results have broad implications for our understanding of the dynamic interplay of forces between fibroblasts and their surrounding matrix, as well as for the neural, vascular, and immune cell populations residing within connective tissue.

  17. Hypericin-mediated selective photomodification of connective tissues

    Science.gov (United States)

    Hovhannisyan, V.; Hovhannisyan, A.; Ghukasyan, V.; Guo, H. W.; Chen, Y. F.; Dong, C. Y.

    2014-12-01

    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.

  18. 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.

  19. Basic Components of Connective Tissues and Extracellular Matrix

    DEFF Research Database (Denmark)

    Halper, Jaroslava; Kjær, Michael

    2014-01-01

    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...... 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......, elastic fibers and other components of extracellular matrix and participate in formation of elastic fibers. Tenascins are ECM polymorphic glycoproteins found in many connective tissues in the body. Their expression is regulated by mechanical stress both during development and in adulthood. Tenascins...

  20. 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.

  1. Root coverage using epithelial embossed connective tissue graft

    Directory of Open Access Journals (Sweden)

    T Ramakrishnan

    2011-01-01

    Full Text Available In periodontal practice, root coverage after marginal soft tissue recession requires daily clinical decisions. Numerous longitudinal human studies have been presented to support the efficacy and predictability of different mucogingival surgical techniques for root coverage. Over the years, root coverage procedure using the subepithelial connective tissue graft with variations has emerged as the favorite surgical technique. In the case presented in this report, subepithelial connective tissue graft with embossed epithelium was used to cover Miller′s class II gingival recession in the upper right canine. The design is such that embossed epithelium exactly fits the recession site and the connective tissue portion is tucked below the gingival margin of the recipient site. In this technique, coronal advancement of flap is not needed. Wider zone of attached gingiva at the recipient site was achieved by this technique.

  2. Invited review: mesenchymal progenitor cells in intramuscular connective tissue development.

    Science.gov (United States)

    Miao, Z G; Zhang, L P; Fu, X; Yang, Q Y; Zhu, M J; Dodson, M V; Du, M

    2016-01-01

    The abundance and cross-linking of intramuscular connective tissue contributes to the background toughness of meat, and is thus undesirable. Connective tissue is mainly synthesized by intramuscular fibroblasts. Myocytes, adipocytes and fibroblasts are derived from a common pool of progenitor cells during the early embryonic development. It appears that multipotent mesenchymal stem cells first diverge into either myogenic or non-myogenic lineages; non-myogenic mesenchymal progenitors then develop into the stromal-vascular fraction of skeletal muscle wherein adipocytes, fibroblasts and derived mesenchymal progenitors reside. Because non-myogenic mesenchymal progenitors mainly undergo adipogenic or fibrogenic differentiation during muscle development, strengthening progenitor proliferation enhances the potential for both intramuscular adipogenesis and fibrogenesis, leading to the elevation of both marbling and connective tissue content in the resulting meat product. Furthermore, given the bipotent developmental potential of progenitor cells, enhancing their conversion to adipogenesis reduces fibrogenesis, which likely results in the overall improvement of marbling (more intramuscular adipocytes) and tenderness (less connective tissue) of meat. Fibrogenesis is mainly regulated by the transforming growth factor (TGF) β signaling pathway and its regulatory cascade. In addition, extracellular matrix, a part of the intramuscular connective tissue, provides a niche environment for regulating myogenic differentiation of satellite cells and muscle growth. Despite rapid progress, many questions remain in the role of extracellular matrix on muscle development, and factors determining the early differentiation of myogenic, adipogenic and fibrogenic cells, which warrant further studies.

  3. 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 

  4. 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

    Chondroitin sulphate proteoglycans are widespread connective tissue components and chemical analysis of cartilage and other proteoglycans has demonstrated molecular speciation involving the degree and position of sulphation of the carbohydrate chains. This may, in turn, affect the properties...... 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...... and dermatan sulphate. These provide novel opportunities to study the in vivo distribution of chondroitin sulphate proteoglycans. We demonstrate that chondroitin sulphates exhibit remarkable connective tissue specificity and furthermore provide evidence that some proteoglycans may predominantly carry only one...

  5. [Connective tissue: big unifying element of the organism].

    Science.gov (United States)

    Kapandji, A-I

    2012-10-01

    The anatomical unity of the organism is realized by the connective tissue, which assumes five functions: the filling of the spaces between organs; the connexion between these organs; the driving of the vascular and nervous pedicles to these organs; the stocking of nutritive reserves in fat pads; an aesthetic role with hollows and bumps erasing. The space filling is done with jointed polyedric volumes, which are constituted, according to the theories of J.-C. Guimberteau, with microvacuoles, filled with under pressure fundamental substance. This is a status of preconstraint resulting in a form memory. So, the connective tissue under constraint get back its initial status after this constraint is over, according to the laws of a new science, the tensegrity. The explorations of the connective tissue with a 25× magnifying micro endoscopes are showing micro fibrillar structures, evoluting under constraint. Its arrangement, that seems chaotic, is in fractal disposition, in reality, and follows the "universal parcimony law" established by Williams of Ockham. The structure of the connective tissue can be integrated in a holistic conception of the organism. Many characteristics of this tissue have still to be discovered.

  6. 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

  7. 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.

  8. 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.

  9. Systemic connective tissue features in women with fibromuscular dysplasia.

    Science.gov (United States)

    O'Connor, Sarah; Kim, Esther Sh; Brinza, Ellen; Moran, Rocio; Fendrikova-Mahlay, Natalia; Wolski, Kathy; Gornik, Heather L

    2015-10-01

    Fibromuscular dysplasia (FMD) is a non-atherosclerotic disease associated with hypertension, headache, dissection, stroke, and aneurysm. The etiology is unknown but hypothesized to involve genetic and environmental components. Previous studies suggest a possible overlap of FMD with other connective tissue diseases that present with dissections and aneurysms. The aim of this study was to investigate the prevalence of connective tissue physical features in FMD. A total of 142 FMD patients were consecutively enrolled at a single referral center (97.9% female, 92.1% of whom had multifocal FMD). Data are reported for 139 female patients. Moderately severe myopia (29.1%), high palate (33.1%), dental crowding (29.7%), and early-onset arthritis (15.6%) were prevalent features. Classic connective features such as hypertelorism, cleft palate, and hypermobility were uncommon. The frequency of systemic connective tissue features was compared between FMD patients with a high vascular risk profile (having had ⩾1 dissection and/or ⩾2 aneurysms) and those with a standard vascular risk profile. A history of spontaneous pneumothorax (5.9% high risk vs 0% standard risk) and atrophic scarring (17.6% high risk vs 6.8% standard risk) were significantly more prevalent in the high risk group, pconnective tissue features such as high palate and pneumothorax were more prominent among FMD patients with a high vascular risk profile.

  10. PDGFRα plays a crucial role in connective tissue remodeling.

    Science.gov (United States)

    Horikawa, Shinjiro; Ishii, Yoko; Hamashima, Takeru; Yamamoto, Seiji; Mori, Hisashi; Fujimori, Toshihiko; Shen, Jie; Inoue, Ran; Nishizono, Hirofumi; Itoh, Hiroshi; Majima, Masataka; Abraham, David; Miyawaki, Toshio; Sasahara, Masakiyo

    2015-12-07

    Platelet derived growth factor (PDGF) plays a pivotal role in the remodeling of connective tissues. Emerging data indicate the distinctive role of PDGF receptor-α (PDGFRα) in this process. In the present study, the Pdgfra gene was systemically inactivated in adult mouse (α-KO mouse), and the role of PDGFRα was examined in the subcutaneously implanted sponge matrices. PDGFRα expressed in the fibroblasts of Pdgfra-preserving control mice (Flox mice), was significantly reduced in the sponges in α-KO mice. Neovascularized areas were largely suppressed in the α-KO mice than in the Flox mice, whereas the other parameters related to the blood vessels and endothelial cells were similar. The deposition of collagen and fibronectin and the expression of collagen 1a1 and 3a1 genes were significantly reduced in α-KO mice. There was a significantly decrease in the number and dividing fibroblasts in the α-KO mice, and those of macrophages were similar between the two genotypes. Hepatocyte growth factor (Hgf) gene expression was suppressed in Pdgfra-inactivated fibroblasts and connective tissue. The findings implicate the role of PDGFRα-dependent ECM and HGF production in fibroblasts that promotes the remodeling of connective tissue and suggest that PDGFRα may be a relevant target to regulate connective tissue remodeling.

  11. 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.

  12. Force Transmission between Synergistic Skeletal Muscles through Connective Tissue Linkages

    Directory of Open Access Journals (Sweden)

    Huub Maas

    2010-01-01

    Full Text Available The classic view of skeletal muscle is that force is generated within its muscle fibers and then directly transmitted in-series, usually via tendon, onto the skeleton. In contrast, recent results suggest that muscles are mechanically connected to surrounding structures and cannot be considered as independent actuators. This article will review experiments on mechanical interactions between muscles mediated by such epimuscular myofascial force transmission in physiological and pathological muscle conditions. In a reduced preparation, involving supraphysiological muscle conditions, it is shown that connective tissues surrounding muscles are capable of transmitting substantial force. In more physiologically relevant conditions of intact muscles, however, it appears that the role of this myofascial pathway is small. In addition, it is hypothesized that connective tissues can serve as a safety net for traumatic events in muscle or tendon. Future studies are needed to investigate the importance of intermuscular force transmission during movement in health and disease.

  13. The STAT5-GATA2 pathway is critical in basophil and mast cell differentiation and maintenance.

    Science.gov (United States)

    Li, Yapeng; Qi, Xiaopeng; Liu, Bing; Huang, Hua

    2015-05-01

    Transcription factor GATA binding protein 2 (GATA2) plays critical roles in hematopoietic stem cell survival and proliferation, granulocyte-monocyte progenitor differentiation, and basophil and mast cell differentiation. However, precise roles of GATA2 in basophil and mast cell differentiation and maintenance have not been delineated. We have identified GATA2 as an essential transcription factor in differentiation of newly identified common basophil and mast cell progenitors into basophils and mast cells. We observed Gata2 haploinsufficiency for mast cell differentiation, but not for basophil differentiation. We examined the precise role of GATA2 in maintaining the expression of a wide range of genes that are important for performing basophil or mast cell functions. The effects of GATA2 on gene expression were broadly based. We demonstrated that GATA2 was required for maintaining Fcer1a mRNA and FcεRIα protein expression on both basophils and mast cells, as well as for maintaining Kit mRNA and c-Kit protein expression on mast cells. GATA2 was required for histamine synthesis and was also critical for Il4 mRNA expression in basophils and Il13 mRNA expression in mast cells. We demonstrate a STAT5-GATA2 connection, showing that the STAT5 transcription factor directly bound to the promoter and an intronic region of the Gata2 gene. Overexpression of the Gata2 gene was sufficient to direct basophil and mast cell differentiation in the absence of the Stat5 gene. Our study reveals that the STAT5-GATA2 pathway is critical for basophil and mast cell differentiation and maintenance.

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

    DEFF Research Database (Denmark)

    Mackey, Abigail Louise; Kjaer, Michael

    2016-01-01

    the adaptation throughout this process of both the connective tissue structures surrounding the myofibres, and the fibroblasts, the cells responsible for synthesising this connective tissue. However, the few studies investigating muscle connective tissue remodelling demonstrate a strong response that appears...... 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...

  15. Role of PTPα in the destruction of periodontal connective tissues.

    Science.gov (United States)

    Rajshankar, Dhaarmini; Sima, Corneliu; Wang, Qin; Goldberg, Stephanie R; Kazembe, Mwayi; Wang, Yongqiang; Glogauer, Michael; Downey, Gregory P; McCulloch, Christopher A

    2013-01-01

    IL-1β contributes to connective tissue destruction in part by up-regulating stromelysin-1 (MMP-3), which in fibroblasts is a focal adhesion-dependent process. Protein tyrosine phosphatase-α (PTPα) is enriched in and regulates the formation of focal adhesions, but the role of PTPα in connective tissue destruction is not defined. We first examined destruction of periodontal connective tissues in adult PTPα(+/+) and PTPα(-/-) mice subjected to ligature-induced periodontitis, which increases the levels of multiple cytokines, including IL-1β. Three weeks after ligation, maxillae were processed for morphometry, micro-computed tomography and histomorphometry. Compared with unligated controls, there was ∼1.5-3 times greater bone loss as well as 3-fold reduction of the thickness of the gingival lamina propria and 20-fold reduction of the amount of collagen fibers in WT than PTPα(-/-) mice. Immunohistochemical staining of periodontal tissue showed elevated expression of MMP-3 at ligated sites. Second, to examine mechanisms by which PTPα may regulate matrix degradation, human MMP arrays were used to screen conditioned media from human gingival fibroblasts treated with vehicle, IL-1β or TNFα. Although MMP-3 was upregulated by both cytokines, only IL-1β stimulated ERK activation in human gingival fibroblasts plated on fibronectin. TIRF microscopy and immunoblotting analyses of cells depleted of PTPα activity with the use of various mutated constructs or with siRNA or PTPα(KO) and matched wild type fibroblasts were plated on fibronectin to enable focal adhesion formation and stimulated with IL-1β. These data showed that the catalytic and adaptor functions of PTPα were required for IL-1β-induced focal adhesion formation, ERK activation and MMP-3 release. We conclude that inflammation-induced connective tissue degradation involving fibroblasts requires functionally active PTPα and in part is mediated by IL-1β signaling through focal adhesions.

  16. Role of PTPα in the destruction of periodontal connective tissues.

    Directory of Open Access Journals (Sweden)

    Dhaarmini Rajshankar

    Full Text Available IL-1β contributes to connective tissue destruction in part by up-regulating stromelysin-1 (MMP-3, which in fibroblasts is a focal adhesion-dependent process. Protein tyrosine phosphatase-α (PTPα is enriched in and regulates the formation of focal adhesions, but the role of PTPα in connective tissue destruction is not defined. We first examined destruction of periodontal connective tissues in adult PTPα(+/+ and PTPα(-/- mice subjected to ligature-induced periodontitis, which increases the levels of multiple cytokines, including IL-1β. Three weeks after ligation, maxillae were processed for morphometry, micro-computed tomography and histomorphometry. Compared with unligated controls, there was ∼1.5-3 times greater bone loss as well as 3-fold reduction of the thickness of the gingival lamina propria and 20-fold reduction of the amount of collagen fibers in WT than PTPα(-/- mice. Immunohistochemical staining of periodontal tissue showed elevated expression of MMP-3 at ligated sites. Second, to examine mechanisms by which PTPα may regulate matrix degradation, human MMP arrays were used to screen conditioned media from human gingival fibroblasts treated with vehicle, IL-1β or TNFα. Although MMP-3 was upregulated by both cytokines, only IL-1β stimulated ERK activation in human gingival fibroblasts plated on fibronectin. TIRF microscopy and immunoblotting analyses of cells depleted of PTPα activity with the use of various mutated constructs or with siRNA or PTPα(KO and matched wild type fibroblasts were plated on fibronectin to enable focal adhesion formation and stimulated with IL-1β. These data showed that the catalytic and adaptor functions of PTPα were required for IL-1β-induced focal adhesion formation, ERK activation and MMP-3 release. We conclude that inflammation-induced connective tissue degradation involving fibroblasts requires functionally active PTPα and in part is mediated by IL-1β signaling through focal adhesions.

  17. 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.

  18. The diagnosis and classification of undifferentiated connective tissue diseases.

    Science.gov (United States)

    Mosca, Marta; Tani, Chiara; Vagnani, Sabrina; Carli, Linda; Bombardieri, Stefano

    2014-01-01

    The term undifferentiated connective tissue disease (UCTD) refers to unclassifiable systemic autoimmune diseases which share clinical and serological manifestations with definite connective tissue diseases (CTDs) but not fulfilling any of the existing classification criteria. In this review we will go through the more recent evidence on UCTD and we will discuss in what extent the availability of new criteria for the CTDs could interfere with the "UCTD concept". The development of criteria able to identify early phases of defined CTD, may help in the differentiation of stable UCTD form their early stages and may offer a valuable guide to the treating physician to set up appropriate follow up schedules as well as therapeutic protocols. This simplified subset of CTD could offer a model to study clinic pathological correlations as well as the role of possible environmental factors in the development of autoimmunity.

  19. 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.

  20. Connective tissue manipulation: a review of theory and clinical evidence.

    Science.gov (United States)

    Holey, Liz A; Dixon, John

    2014-01-01

    Connective tissue manipulation or connective tissue massage (bindegewebsmassage) is a manual reflex therapy in that it is applied with the therapist's hands which are in contact with the patient's skin. The assessment of the patient and the clinical decision-making that directs treatment is based on a theoretical model that assumes a reflex effect on the autonomic nervous system which is induced by manipulating the fascial layers within and beneath the skin to stimulate cutaneo-visceral reflexes. This paper reviews the literature and current research findings to establish the theoretical framework for CTM and the evidence for its clinical effects. The rationale for the principles of treatment are discussed and the evidence for the clinical effectiveness assessed through an analytical review of the clinical research.

  1. Pediatric rehabilitation. 5. Joint and connective tissue diseases.

    Science.gov (United States)

    Dykstra, D D; Badell, A; Binder, H; Easton, J K; Matthews, D J; Molnar, G E; Noll, S F; Perrin, J C

    1989-05-01

    This self-directed learning module presents pertinent information about rehabilitation management of specific joint and connective tissue diseases affecting children. This section highlights juvenile rheumatoid arthritis, Lyme disease, rheumatic fever, hemophilia, dermatomyositis, polymyositis, systemic lupus erythematosus, and other forms of arthritis. It is a section of the chapter of pediatric rehabilitation for the Self-Directed Medical Knowledge Program Study Guide for practitioners and trainees in physical medicine and rehabilitation.

  2. Mucinous Naevus: A Rare Variant of Connective Tissue Naevus

    Directory of Open Access Journals (Sweden)

    Bhavna Nayal

    2013-04-01

    Full Text Available Mucinous naevus is a form of primary cutaneous mucinosis and connective tissue neavus characterized by deposition of dermal type of mucin in the dermis. Clinically, these lesions may present as papulonodules or plaques and are treated by simple surgical excision. This case is being reported because of the unusual location and rarity of this lesion. [J Interdiscipl Histopathol 2013; 1(2.000: 89-92

  3. Psoriasis and connective tissue diseases: What about Sjogren syndrome?

    Directory of Open Access Journals (Sweden)

    Zohra Aydi

    2015-07-01

    Full Text Available Psoriasis (Ps is an autoimmune chronic skin disease with a high prevalence in the general population. Connective tissue diseases (CTD are also autoimmune disorders of unknown cause with highly variable clinical expression. The combination of CTD and psoriasis is uncommon and has rarely been described. We report two cases of CTD associated with psoriasis: a case of systemic lupus erythematosus (SLE and a case of Sjogren syndrome (SSs.

  4. Undifferentiated connective tissue diseases-related hepatic injury

    Institute of Scientific and Technical Information of China (English)

    Ying Zhang; Fu-Kui Zhang; Xiao-Ning Wu; Tai-Ling Wang; Ji-Dong Jia; Bao-En Wang

    2008-01-01

    Hepatic injury is rarely associated with undifferentiated connective tissue diseases (UCTD).We report,here,a case of a middle-aged woman with UCTD-related hepatic injury,including its case history,clinical manifestations,laboratory findings,treatment and its short-term effect.The patient was admitted to the hospital with symptoms of fatigue,anorexia,low-grade fever and skin rashes.She had a past history of left knee joint replacement.Laboratory tests showed elevated levels of serum transaminase,IgG and globulin,accelerated erythrocyte sedimentation rate,eosinophilia and a high titer of antinuclear antibodies (1:320).Imaging studies showed interstitial pneumonitis and hydropericardium.Liver biopsy showed the features which were consistent with those of connective tissue diseases-related polyangitis.After treatment with a low-dose of oral prednisone,both symptoms and laboratory findings were significantly improved.UCTD-related hepatic injury should be considered in the differential diagnosis of connective tissue diseases with abnormal liver function tests.Lowdose prednisone may effectively improve both symptoms and laboratory tests.

  5. FOXO1 expression in keratinocytes promotes connective tissue healing

    Science.gov (United States)

    Zhang, Chenying; Lim, Jason; Liu, Jian; Ponugoti, Bhaskar; Alsadun, Sarah; Tian, Chen; Vafa, Rameen; Graves, Dana T.

    2017-01-01

    Wound healing is complex and highly orchestrated. It is well appreciated that leukocytes, particularly macrophages, are essential for inducing the formation of new connective tissue, which requires the generation of signals that stimulate mesenchymal stem cells (MSC), myofibroblasts and fibroblasts. A key role for keratinocytes in this complex process has yet to be established. To this end, we investigated possible involvement of keratinocytes in connective tissue healing. By lineage-specific deletion of the forkhead box-O 1 (FOXO1) transcription factor, we demonstrate for the first time that keratinocytes regulate proliferation of fibroblasts and MSCs, formation of myofibroblasts and production of collagen matrix in wound healing. This stimulation is mediated by a FOXO1 induced TGFβ1/CTGF axis. The results provide direct evidence that epithelial cells play a key role in stimulating connective tissue healing through a FOXO1-dependent mechanism. Thus, FOXO1 and keratinocytes may be an important therapeutic target where healing is deficient or compromised by a fibrotic outcome. PMID:28220813

  6. Pauci-Immune Crescentic Glomerulonephritis in Connective Tissue Disease

    Directory of Open Access Journals (Sweden)

    Supraja Yeturi

    2016-01-01

    Full Text Available Pauci-immune crescentic glomerulonephritis is commonly seen in ANCA-associated vasculitis but it is rarely seen during the course of other connective tissue diseases like lupus or Sjogren’s syndrome or MCTD. We report 3 cases of pauci-immune crescentic glomerulonephritis in patients with connective tissue disease other than vasculitis. We reviewed literature and made summary of previously reported cases of this rare entity. Clinical and laboratory features of these patients varied widely, but most of patients have met criteria for lupus. In this small population of patients there is no correlation with ANCAs. Most of the patients were treated with aggressive immunosuppression and did well if they were treated early in the course of their disease. One of our patients required renal transplant, but she presented late in the course of her disease, as evidenced by chronicity on her renal biopsy. Whether these patients are overlap of vasculitis and other connective tissue diseases or to be considered as a separate entity is yet to be described. Clinicians must be aware of these presentations because initial presentation can be severe.

  7. Automated Detection of Connective Tissue by Tissue Counter Analysis and Classification and Regression Trees

    Directory of Open Access Journals (Sweden)

    Josef Smolle

    2001-01-01

    Full Text Available Objective: To evaluate the feasibility of the CART (Classification and Regression Tree procedure for the recognition of microscopic structures in tissue counter analysis. Methods: Digital microscopic images of H&E stained slides of normal human skin and of primary malignant melanoma were overlayed with regularly distributed square measuring masks (elements and grey value, texture and colour features within each mask were recorded. In the learning set, elements were interactively labeled as representing either connective tissue of the reticular dermis, other tissue components or background. Subsequently, CART models were based on these data sets. Results: Implementation of the CART classification rules into the image analysis program showed that in an independent test set 94.1% of elements classified as connective tissue of the reticular dermis were correctly labeled. Automated measurements of the total amount of tissue and of the amount of connective tissue within a slide showed high reproducibility (r=0.97 and r=0.94, respectively; p < 0.001. Conclusions: CART procedure in tissue counter analysis yields simple and reproducible classification rules for tissue elements.

  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. Comparison of connective tissue graft and guided tissue regeneration in covering root surfaces

    OpenAIRE

    LotfazarM.; Faghihi Sh.

    2002-01-01

    There are many researches evaluation different methods for covering the root surface. In the most of these studies, type I and II of Miller treatment had been searched. The purpose of this study was a comparison between connective tissue graft (CTG) and guided tissue regeneration (GTR) with a collagen membrane in the treatment of gingival recession defects (Miller class III). Six patients, each contributing a pair of Miller class III buccal gingival recessions, were treated. The clinical meas...

  10. Mechanisms of lamellar collagen formation in connective tissues.

    Science.gov (United States)

    Ghazanfari, Samaneh; Khademhosseini, Ali; Smit, Theodoor H

    2016-08-01

    The objective of tissue engineering is to regenerate functional tissues. Engineering functional tissues requires an understanding of the mechanisms that guide the formation and evolution of structure in the extracellular matrix (ECM). In particular, the three-dimensional (3D) collagen fiber arrangement is important as it is the key structural determinant that provides mechanical integrity and biological function. In this review, we survey the current knowledge on collagen organization mechanisms that can be applied to create well-structured functional lamellar tissues and in particular intervertebral disc and cornea. Thus far, the mechanisms behind the formation of cross-aligned collagen fibers in the lamellar structures is not fully understood. We start with cell-induced collagen alignment and strain-stabilization behavior mechanisms which can explain a single anisotropically aligned collagen fiber layer. These mechanisms may explain why there is anisotropy in a single layer in the first place. However, they cannot explain why a consecutive collagen layer is laid down with an alternating alignment. Therefore, we explored another mechanism, called liquid crystal phasing. While dense concentrations of collagen show such behavior, there is little evidence that the conditions for liquid crystal phasing are actually met in vivo. Instead, lysyl aldehyde-derived collagen cross-links have been found essential for correct lamellar matrix deposition. Furthermore, we suggest that supra-cellular (tissue-level) shear stress may be instrumental in the alignment of collagen fibers. Understanding the potential mechanisms behind the lamellar collagen structure in connective tissues will lead to further improvement of the regeneration strategies of functional complex lamellar tissues.

  11. Cysteine protease antigens cleave CD123, the α subunit of murine IL-3 receptor, on basophils and suppress IL-3-mediated basophil expansion

    Energy Technology Data Exchange (ETDEWEB)

    Nishikado, Hideto [Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo (Japan); Fujimura, Tsutomu; Taka, Hikari; Mineki, Reiko [Laboratory of Proteomics and Biomolecular Science, BioMedical Research Center, Juntendo University Graduate School of Medicine, Tokyo (Japan); Ogawa, Hideoki; Okumura, Ko [Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo (Japan); Takai, Toshiro, E-mail: t-takai@juntendo.ac.jp [Atopy (Allergy) Research Center, Juntendo University Graduate School of Medicine, Tokyo (Japan)

    2015-05-01

    Th2 type immune responses are essential for protective immunity against parasites and play crucial roles in allergic disorders. Helminth parasites secrete a variety of proteases for their infectious cycles including for host entry, tissue migration, and suppression of host immune effector cell function. Furthermore, a number of pathogen-derived antigens, as well as allergens such as papain, belong to the family of cysteine proteases. Although the link between protease activity and Th2 type immunity is well documented, the mechanisms by which proteases regulate host immune responses are largely unknown. Here, we demonstrate that the cysteine proteases papain and bromelain selectively cleave the α subunit of the IL-3 receptor (IL-3Rα/CD123) on the surface of murine basophils. The decrease in CD123 expression on the cell surface, and the degradation of the extracellular domain of recombinant CD123 were dependent on the protease activity of papain and bromelain. Pre-treatment of murine basophils with papain resulted in inhibition of IL-3-IL-3R signaling and suppressed IL-3- but not thymic stromal lymphopoietin-induced expansion of basophils in vitro. Our unexpected findings illuminate a novel mechanism for the regulation of basophil functions by protease antigens. Because IL-3 plays pivotal roles in the activation and proliferation of basophils and in protective immunity against helminth parasites, pathogen-derived proteases might contribute to the pathogenesis of infections by regulating IL-3-mediated functions in basophils. - Highlights: • We identified the murine IL3R as a novel target of papain-family cysteine proteases. • Papain-family cysteine proteases cleaved IL3Rα/CD123 on murine basophils. • Papain suppressed IL3- but not TSLP-induced expansion of murine basophils. • The inactivation of IL3R might be a strategy for pathogens to suppress host immunity.

  12. 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.

  13. Interstitial lung disease in the connective tissue diseases.

    Science.gov (United States)

    Antin-Ozerkis, Danielle; Rubinowitz, Ami; Evans, Janine; Homer, Robert J; Matthay, Richard A

    2012-03-01

    The connective tissue diseases (CTDs) are inflammatory, immune-mediated disorders in which interstitial lung disease (ILD) is common and clinically important. Interstitial lung disease may be the first manifestation of a CTD in a previously healthy patient. CTD-associated ILD frequently presents with the gradual onset of cough and dyspnea, although rarely may present with fulminant respiratory failure. Infection and drug reaction should always be ruled out. A diagnosis of idiopathic ILD should never be made without a careful search for subtle evidence of underlying CTD. Treatment of CTD-ILD typically includes corticosteroids and immunosuppressive agents.

  14. [Ultrasonography in chronic inflammatory rheumatic and connective tissue disorders].

    Science.gov (United States)

    Mérot, O; Le Goff, B

    2014-08-01

    Musculoskeletal ultrasonography is now widely used by almost all rheumatologists thanks to an improvement in the quality of ultrasound unit and probe and to the systematic teaching of this imaging technique to the rheumatology fellows. Applications have broadened from the study of degenerative and mechanical diseases to inflammatory rheumatic diseases. Ultrasound is more sensitive than clinical examination. Power Doppler allows the direct visualisation of inflammation within the tissues. Finally, it is a prognostic tool helping the physician in the management of the disease. This review will focus on the value and applications of ultrasonography in the 2 most frequent rheumatic diseases: rheumatoid arthritis and spondyloarthritis. We will also give some recent data on the usefulness of this imaging technique in the study of musculoskeletal manifestations associated with connective tissue disease.

  15. Affine kinematics in planar fibrous connective tissues: an experimental investigation.

    Science.gov (United States)

    Jayyosi, C; Affagard, J-S; Ducourthial, G; Bonod-Bidaud, C; Lynch, B; Bancelin, S; Ruggiero, F; Schanne-Klein, M-C; Allain, J-M; Bruyère-Garnier, K; Coret, M

    2017-03-29

    The affine transformation hypothesis is usually adopted in order to link the tissue scale with the fibers scale in structural constitutive models of fibrous tissues. Thanks to the recent advances in imaging techniques, such as multiphoton microscopy, the microstructural behavior and kinematics of fibrous tissues can now be monitored at different stretching within the same sample. Therefore, the validity of the affine hypothesis can be investigated. In this paper, the fiber reorientation predicted by the affine assumption is compared to experimental data obtained during mechanical tests on skin and liver capsule coupled with microstructural imaging using multiphoton microscopy. The values of local strains and the collagen fibers orientation measured at increasing loading levels are used to compute a theoretical estimation of the affine reorientation of collagen fibers. The experimentally measured reorientation of collagen fibers during loading could not be successfully reproduced with this simple affine model. It suggests that other phenomena occur in the stretching process of planar fibrous connective tissues, which should be included in structural constitutive modeling approaches.

  16. Basophil-activation tests in hymenoptera allergy

    NARCIS (Netherlands)

    Dubois, Anthony E. J.; van der Heide, Sicco

    2007-01-01

    The measurement of basophil-activation markers may be useful in detecting IgIE-mediated sensitization but the relevance for application of the basophil-activation test in prediction of clinical reactivity in Hymenoptera allergy is very limited. For this reason, this test currently has no established

  17. Pulmonary hypertension in connective tissue diseases: an update.

    Science.gov (United States)

    Aithala, Ramya; Alex, Anoop G; Danda, Debashish

    2017-02-16

    Pulmonary hypertension (PH) is a relatively commoner complication of systemic sclerosis (SSc) with estimated prevalence ranging between 8% and 12% as compared to much lower figures in other connective tissue diseases (CTD). It is a major cause of morbidity and mortality in CTDs. PH is classified into five major groups. CTD-associated PH belongs to group 1 PH, also known as pulmonary arterial hypertension (PAH). Around 30% of scleroderma-related deaths are due to PAH. Underlying pathogenesis is related to pulmonary vasculopathy involving small vessels. The Evidence-based Detection of Pulmonary Arterial Hypertension in Systemic sclerosis (DETECT) algorithm outperforms the current European Society of Cardiology/European Respiratory Society guidelines as a screening tool in SSc-PAH; it can, therefore, suggest when to refer a patient for right heart catheterization. CTD-PAH patients constitute at least 20% of patients included in all major trials of PH-specific therapy and the results are comparable to those of idiopathic PAH. The role of anticoagulation in CTD-PAH is associated with a high risk-benefit ratio with the caveat of its potential role in those with severe disease. There appears to be no role of immunosuppression in scleroderma-PAH; however, immunosuppressive agents, namely the combination of glucocorticoids and pulse cyclophosphamide / possibly mycophenolate, may result in clinical improvement in a subset of patients with systemic lupus erythematosus and mixed connective tissue disease-related PAH.

  18. 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

  19. 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

  20. Mutual interaction of Basophils and T cells in chronic inflammatory diseases

    Directory of Open Access Journals (Sweden)

    Marika eSarfati

    2015-08-01

    Full Text Available Basophils are, together with mast cells, typical innate effector cells of allergen-induced IgE-dependent allergic diseases. Both cell types express the high affinity receptor for IgE (FcεR1, release histamine, inflammatory mediators and cytokines following FcεR1 cross-linking. Basophils are rare granulocytes in blood, lymphoid and non-lymphoid tissues and the difficulties to detect and isolate these cells has hampered the study of their biology and the understanding of their possible role in pathology. Furthermore, the existence of other FcεR1-expressing cells, including professional Ag-presenting dendritic cells, generated some controversy regarding the ability of basophils to express MHC Class II molecules, present Ag and drive naïve T cell differentiation into Th2 cells. The focus of this review is to present the recent advances on the interactions between basophils and peripheral blood and tissue memory Th1, Th2 and Th17 cells, as well as their potential role in IgE-independent non allergic chronic inflammatory disorders, including human inflammatory bowel diseases. Basophils interactions with the innate players of IgE-dependent allergic inflammation, particularly innate lymphoid cells, will also be considered. The previously unrecognized function for basophils in skewing adaptive immune responses opens novel perspectives for the understanding of their contribution to the pathogenesis of inflammatory diseases.

  1. [Age changes of the connective tissue structures of human penis].

    Science.gov (United States)

    Klimachev, V V; Neĭmark, A I; Gerval'd, V Ia; Bobrov, I P; Avdalian, A M; Muzalevskaia, N I; Gerval'd, I V; Aliev, R T; Cherdantseva, T M

    2011-01-01

    This investigation was aimed at the study of age changes of penis connective tissue structures. Tissue fragments of penis were obtained from 20 cadavers of men at the age of 20-38 years in group I, and from 20 cadavers of men at the age of 41-59 years in group II. The criteria for the exclusion of material from the research were arterial hypertension, diabetes mellitus, atherosclerosis of internal iliac arteries, Peyronie's disease, and anomalies of genital organ development. It was shown that in the cavernous body of penis, aging was associated with the increased amount and thickening of collagen and argyrophilic fibers, decreased content and thinning of elastic fibers, and the reduced amount of smooth muscle cells (SMC). The average area of fibroblast and SMC nucleolus was not different in both groups studied. The average area of endotheliocyte nucleolus was equal to 1.9+/-0.9 microm2 in group II, being lower than that one in group I, in which this index was equal to 2.1+/-0.9 microm2. No differences in the content of type III and IV collagen were found between the study groups. Age-associated decrease in the average area of endothelial cell nucleolus in the cavernous bodies may reflect the reduction of the activity of these cells and may indicate the development of endothelial dysfunction, which is one of the most important steps in the morphogenesis of age-related male erectile dysfunction.

  2. Muscle and tendon connective tissue adaptation to unloading, exercise and NSAID.

    Science.gov (United States)

    Dideriksen, Kasper

    2014-04-01

    The extracellular matrix network of skeletal muscle and tendon connective tissue is primarily composed of collagen and connects the muscle contractile protein to the bones in the human body. The mechanical properties of the connective tissue are important for the effectiveness of which the muscle force is transformed into movement. Periods of unloading and exercise affect the synthesis rate of connective tissue collagen protein, whereas only sparse information exits regarding collagen protein degradation. It is likely, though, that changes in both collagen protein synthesis and degradation are required for remodeling of the connective tissue internal structure that ultimately results in altered mechanical properties of the connective tissue. Both unloading and exercise lead to increased production of growth factors and inflammatory mediators that are involved in connective tissue remodeling. Despite the fact that non-steroidal anti-inflammatory drugs seem to inhibit the healing process of connective tissue and the stimulating effect of exercise on connective tissue protein synthesis, these drugs are often consumed in relation to connective tissue injury and soreness. However, the potential effect of non-steroidal anti-inflammatory drugs on connective tissue needs further investigation.

  3. [Oral rehabilitation with metalloceramic restorations in patients with non-differentiated systemic connective tissue dysplasia].

    Science.gov (United States)

    Stafeev, A A

    2015-01-01

    False formation of connective tissues have a great influence on structure and function of organs and tissues of the human body. In prosthodontics, the changes in connective tissues greatly occur during clinical stages of preparing metal ceramic dentures. The algorithm of treatment patients with connective tissue dysplasia during metal ceramic dentures was developed and introduced into practical dentistry based on studying the morphology and functionality of dentition and clinical experience.

  4. Human cord blood derived immature basophils show dual characteristics, expressing both basophil and eosinophil associated proteins

    OpenAIRE

    Jeanette Grundström; Jenny M Reimer; Sofia E Magnusson; Gunnar Nilsson; Sara Wernersson; Lars Hellman

    2012-01-01

    Basophils are blood cells of low abundance associated with allergy, inflammation and parasite infections. To study the transcriptome of mature circulating basophils cells were purified from buffy coats by density gradient centrifugations and two-step magnetic cell sorting. However, after extensive analysis the cells were found to be transcriptionally inactive and almost completely lack functional mRNA. In order to obtain transcriptionally active immature basophils for analysis of their transc...

  5. Non-myogenic Contribution to Muscle Development and Homeostasis: The Role of Connective Tissues.

    Science.gov (United States)

    Nassari, Sonya; Duprez, Delphine; Fournier-Thibault, Claire

    2017-01-01

    Skeletal muscles belong to the musculoskeletal system, which is composed of bone, tendon, ligament and irregular connective tissue, and closely associated with motor nerves and blood vessels. The intrinsic molecular signals regulating myogenesis have been extensively investigated. However, muscle development, homeostasis and regeneration require interactions with surrounding tissues and the cellular and molecular aspects of this dialogue have not been completely elucidated. During development and adult life, myogenic cells are closely associated with the different types of connective tissue. Connective tissues are defined as specialized (bone and cartilage), dense regular (tendon and ligament) and dense irregular connective tissue. The role of connective tissue in muscle morphogenesis has been investigated, thanks to the identification of transcription factors that characterize the different types of connective tissues. Here, we review the development of the various connective tissues in the context of the musculoskeletal system and highlight their important role in delivering information necessary for correct muscle morphogenesis, from the early step of myoblast differentiation to the late stage of muscle maturation. Interactions between muscle and connective tissue are also critical in the adult during muscle regeneration, as impairment of the regenerative potential after injury or in neuromuscular diseases results in the progressive replacement of the muscle mass by fibrotic tissue. We conclude that bi-directional communication between muscle and connective tissue is critical for a correct assembly of the musculoskeletal system during development as well as to maintain its homeostasis in the adult.

  6. Dynamic adaptation of tendon and muscle connective tissue to mechanical loading

    DEFF Research Database (Denmark)

    Mackey, Abigail; Heinemeier, Katja Maria; Koskinen, Satu Osmi Anneli

    2008-01-01

    The connective tissue of tendon and skeletal muscle is a crucial structure for force transmission. A dynamic adaptive capacity of these tissues in healthy individuals is evident from reports of altered gene expression and protein levels of the fibrillar and network-forming collagens, when subjected...... in this article provide strong evidence for the highly adaptable nature of connective tissue in muscle and tendon....

  7. Connective Tissue Growth Factor Expression in Human Bronchial Epithelial Cells

    Institute of Scientific and Technical Information of China (English)

    Amrita DOSANJH

    2006-01-01

    Connective tissue growth factor (CTGF) is a cysteine-rich protein that promotes extracellular matrix deposition. CTGF is selectively induced by transforming growth factor β and des-Arg kallidin in lung fibroblasts and increases steady-state mRNA levels of α type I collagen, 5α-integrin and fibronectin in fibroblasts. Bronchial epithelial cells have been proposed to functionally interact with lung fibroblasts. We therefore investigated if bronchial epithelial cells are able to synthesize CTGF. Human bronchial epithelial cells were grown to subconfluence in standard growth media. Proliferating cells grown in small airway growth media were harvested following starvation for up to 24 h. Expression of CTGF transcripts was measured by PCR. Immunocytochemistry was also completed using a commercially available antibody.The cells expressed readily detectable CTGF transcripts. Starvation of these cells resulted in a quantitative decline of CTGF transcripts. Direct sequencing of the PCR product identified human CTGF. Immunocytochemistry confirmed intracellular CTGF in the cells and none in negative control cells. We conclude that bronchial epithelial cells could be a novel source of CTGF. Bronchial epithelial cell-derived CTGF could thus directly influence the deposition of collagen in certain fibrotic lung diseases.

  8. 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.

  9. Idiopathic interstitial pneumonias with connective tissue diseases features: A review.

    Science.gov (United States)

    Cottin, Vincent

    2016-02-01

    A systematic approach is recommended to search for clinical and biological features of connective tissue disease (CTD) in any patient with interstitial lung disease (ILD). In the diagnostic approach to ILD, a diagnosis of CTD should be considered particularly in women and subjects younger than 50 years, and in those with an imaging and/or pathological pattern of non-specific interstitial pneumonia. However, the diagnosis of CTD may be difficult when ILD is the presenting or the dominant manifestation of CTD. A proportion of patients with ILD present symptoms that belong to the spectrum of CTD and/or biological autoimmune features, but do not fulfil diagnostic criteria for a given CTD. Some imaging and histopathological patterns may also suggest the presence of an underlying CTD. Although studies published to date used heterogeneous definitions and terminology for this condition, evidence is accumulating that even limited CTD features are relevant regarding symptoms, imaging features, pathological pattern and possibly evolution to overt CTD, whereas the impact on prognosis needs confirmation. Conversely, autoantibodies alone do not seem to impact the prognosis or management in patients with otherwise typical idiopathic pulmonary fibrosis and no extra-pulmonary manifestation. A collective international multidisciplinary effort has proposed a uniform definition and criteria for 'interstitial pneumonia with autoimmune features', a condition characterized by limited CTD features occurring in the setting of ILD, with the aim of fostering future clinical studies. Referral of ILD patients suspect to have CTD to a rheumatologist and possibly multidisciplinary discussion may contribute to a better management.

  10. 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.

  11. Breast implant rupture and connective tissue disease: a review of the literature

    DEFF Research Database (Denmark)

    Hölmich, Lisbet Rosenkrantz; Lipworth, Loren; McLaughlin, Joseph K

    2007-01-01

    Large-scale epidemiologic studies to date have not found any credible association between silicone breast implants and either well-defined connective tissue diseases or undefined or atypical connective tissue diseases. It has been hypothesized that implant rupture could prompt an immunologic...... reaction giving rise to autoimmune or related diseases. In this article, the authors review the available literature on implant ruptures and connective tissue disease....

  12. 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...... in skin. Using antibodies specific for chondroitin-4-sulfated proteoglycan, their presence was demonstrated in dermal connective tissue and connective tissue surrounding nerve and muscle sheaths. However, chondroitin-4-sulfated proteoglycan was completely absent in the epidermis of skin and areas...... surrounding invaginating hair follicles. These immunological procedures are currently being used to complement conventional biochemical analyses of proteoglycans found in different connective tissue matrices....

  13. Comparison of connective tissue graft and guided tissue regeneration in covering root surfaces

    Directory of Open Access Journals (Sweden)

    LotfazarM.

    2002-08-01

    Full Text Available There are many researches evaluation different methods for covering the root surface. In the most of these studies, type I and II of Miller treatment had been searched. The purpose of this study was a comparison between connective tissue graft (CTG and guided tissue regeneration (GTR with a collagen membrane in the treatment of gingival recession defects (Miller class III. Six patients, each contributing a pair of Miller class III buccal gingival recessions, were treated. The clinical measurements were obtained at baseline and 1,2,4,6,12,18 months after surgery. Statistical analysis were performed using paired t-test between periods (baseline versus 6 months and baseline versus 18 months within each treatment group and also between treatment groups before treatment and 6, 12 and 18 months after the treatment. The treatments were compared by a triple analysis of variance along the time (treatment, patient, time. Both CTG and GTR with a bioabsorbable membrane demonstrated significant clinical and esthetic improvement for gingival recession coverage. The CTG and GTR procedures had mean root coverage of 55% and 47.5% respectively, in the end of study. The CTG group was statistically better than GTR for recession depth, recession width and keratinized tissue width. Also, passing the time (18 months as a distinct factor of treatment procedures was effective in increasing of clinical attachment level and keratinized tissue width.

  14. Human basophils express interleukin-4 receptors

    Energy Technology Data Exchange (ETDEWEB)

    Valent, P.; Besemer, J.; Kishi, K.; Di Padova, F.; Geissler, K.; Lechner, K.; Bettelheim, P. (Univ. of Vienna (Austria))

    1990-11-01

    Interleukin-4 (IL-4), a multipotential lymphokine reputed to play an important role in the regulation of immune responses, interacts with a variety of hemopoietic target cells through specific cell surface membrane receptors. The present study was designed to investigate whether human basophils express IL-4 binding sites. For this purpose, basophils were enriched to homogeneity (93% and 98% purity, respectively) from the peripheral blood of two chronic granulocytic leukemia (CGL) donors using a cocktail of monoclonal antibodies (MoAbs) and complement. Purified basophils bound 125I-radiolabeled recombinant human (rh) IL-4 in a specific manner. Quantitative binding studies and Scatchard plot analysis revealed the presence of a single class of high affinity IL-4 binding sites (280 +/- 40 sites per cell in donor 1 and 640 +/- 45 sites per cell in donor 2) with an apparent dissociation constant, kd, of 7.12 x 10(-11) +/- 2.29 x 10(-11) and 9.55 +/- 3.5 x 10(-11) mol/L, respectively. KU812-F, a human basophil precursor cell line, was found to express a single class of 810 to 1,500 high affinity IL-4 binding sites with a kd of 2.63 to 5.54 x 10(-10) mol/L. No change in the numbers or binding constants of IL-4 receptors was found after exposure of KU812-F cells to rhIL-3 (a potent activator of basophils) for 60 minutes. No effect of rhIL-4 on 3H-thymidine uptake, release or synthesis of histamine, or expression of basophil differentiation antigens (Bsp-1, CD11b, CD25, CD40, CD54) on primary human CGL basophils or KU812-F cells was observed.

  15. Viscoelastic properties of bovine orbital connective tissue and fat: constitutive models.

    Science.gov (United States)

    Yoo, Lawrence; Gupta, Vijay; Lee, Choongyeop; Kavehpore, Pirouz; Demer, Joseph L

    2011-12-01

    Reported mechanical properties of orbital connective tissue and fat have been too sparse to model strain-stress relationships underlying biomechanical interactions in strabismus. We performed rheological tests to develop a multi-mode upper convected Maxwell (UCM) model of these tissues under shear loading. From 20 fresh bovine orbits, 30 samples of connective tissue were taken from rectus pulley regions and 30 samples of fatty tissues from the posterior orbit. Additional samples were defatted to determine connective tissue weight proportion, which was verified histologically. Mechanical testing in shear employed a triborheometer to perform: strain sweeps at 0.5-2.0 Hz; shear stress relaxation with 1% strain; viscometry at 0.01-0.5 s(-1) strain rate; and shear oscillation at 1% strain. Average connective tissue weight proportion was 98% for predominantly connective tissue and 76% for fatty tissue. Connective tissue specimens reached a long-term relaxation modulus of 668 Pa after 1,500 s, while corresponding values for fatty tissue specimens were 290 Pa and 1,100 s. Shear stress magnitude for connective tissue exceeded that of fatty tissue by five-fold. Based on these data, we developed a multi-mode UCM model with variable viscosities and time constants, and a damped hyperelastic response that accurately described measured properties of both connective and fatty tissues. Model parameters differed significantly between the two tissues. Viscoelastic properties of predominantly connective orbital tissues under shear loading differ markedly from properties of orbital fat, but both are accurately reflected using UCM models. These viscoelastic models will facilitate realistic global modeling of EOM behavior in binocular alignment and strabismus.

  16. 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

  17. Fibrillin degradation by matrix metalloproteinases: implications for connective tissue remodelling.

    Science.gov (United States)

    Ashworth, J L; Murphy, G; Rock, M J; Sherratt, M J; Shapiro, S D; Shuttleworth, C A; Kielty, C M

    1999-05-15

    Fibrillin is the principal structural component of the 10-12 nm diameter elastic microfibrils of the extracellular matrix. We have previously shown that both fibrillin molecules and assembled microfibrils are susceptible to degradation by serine proteases. In this study, we have investigated the potential catabolic effects of six matrix metalloproteinases (MMP-2, MMP-3, MMP-9, MMP-12, MMP-13 and MMP-14) on fibrillin molecules and on intact fibrillin-rich microfibrils isolated from ciliary zonules. Using newly synthesized recombinant fibrillin molecules, major cleavage sites within fibrillin-1 were identified. In particular, the six different MMPs generated a major degradation product of approximately 45 kDa from the N-terminal region of the molecule, whereas treatment of truncated, unprocessed and furin-processed C-termini also generated large degradation products. Introduction of a single ectopia lentis-causing amino acid substitution (E2447K; one-letter symbols for amino acids) in a calcium-binding epidermal growth factor-like domain, predicted to disrupt calcium binding, markedly altered the pattern of C-terminal fibrillin-1 degradation. However, the fragmentation pattern of a mutant fibrillin-1 with a comparable E-->K substitution in an upstream calcium-binding epidermal growth factor-like domain was indistinguishable from wild-type molecules. Ultrastructural examination highlighted that fibrillin-rich microfibrils isolated from ciliary zonules were grossly disrupted by MMPs. This is the first demonstration that fibrillin molecules and fibrillin-rich microfibrils are degraded by MMPs and that certain amino acid substitutions change the fragmentation patterns. These studies have important implications for physiological and pathological fibrillin catabolism and for loss of connective tissue elasticity in ageing and disease.

  18. [Peculiarities of the action of hyaluronidase of different origin to the connective tissue].

    Science.gov (United States)

    Habriyev, R U; Kamayev, N O; Danilova, T I; Kakhoyan, E G

    2016-01-01

    The lecture is devoted to consideration of mechanism of therapeutic action of the enzyme hyaluronidase in hyperplastic connective tissue. Drugs based on hyaluronidase increase bioavailability of other drugs used in adjuvant therapy; they significantly increase effectiveness of treatment, and also provide targeted synthesis of hyaluronic acid, ths regulating the regeneration process of connective tissue.

  19. Connective tissue growth factor induces extracellular matrix in asthmatic airway smooth muscle

    NARCIS (Netherlands)

    Johnson, Peter R A; Burgess, Janette K; Ge, Qi; Poniris, Maree; Boustany, Sarah; Twigg, Stephen M; Black, Judith L

    2006-01-01

    Transforming growth factor (TGF)-beta and connective tissue growth factor may be implicated in extracellular matrix protein deposition in asthma. We have recently reported that TGF-beta increased connective tissue growth factor expression in airway smooth muscle cells isolated from patients with ast

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

    DEFF Research Database (Denmark)

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

    microtomography provides high resolution, the thin structures of the connective tissues are difficult to segment. This is mainly due to partial object voxels, image noise and artifacts. The segmentation of connective tissue is important for quantitative analysis purposes. Factors such as the surface area......, 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...... the a priori probability of neighborhood dependencies, and the field can either be isotropic or anisotropic. For the segmentation of connective tissue, the local information of the structure orientation and coherence is extracted to steer the smoothing (anisotropy) of the final segmentation. The results show...

  1. [The effect of the biopolymer chondroitin sulfate on reparative regeneration of connective tissue].

    Science.gov (United States)

    Belova, S V; Norkin, I A; Puchinyan, D M

    2015-01-01

    The research objective is a study of an intra-articular method of introduction of the preparation "mukosat" for stimulation of reparative regeneration of connective tissue of knee joints in rabbits with an experimental arthritis. It is ascertained that intra-articular maintenance of chondroitin sulfate (the preparation "mukosat") acts as a stimulus for reparative regeneration of connective tissue thus showing up positive changes in the status of connective tissue elements of joints: decrease in glycosaminoglycan content in blood serum and normalization of the composition of glycosaminoglycan carbohydrate component. It probably depends on stimulation of biosynthesis of autologous normal glycosaminoglycans in tissues of animal knee joints.

  2. 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.

  3. Enhancement of basophil apoptosis by olopatadine and theophylline.

    Science.gov (United States)

    Kawakami, Ayako; Suzukawa, Maho; Koketsu, Rikiya; Komiya, Akiko; Ohta, Ken; Yamamoto, Kazuhiko; Yamaguchi, Masao

    2008-01-01

    Regulation of basophil survival is an important aspect in the pathogenesis of allergic inflammation associated with local accumulation of basophils. However, pharmacologic modulation of basophil survival is largely unknown except for the apoptosis-enhancing effect of glucocorticoids. We tested the effects of two anti-allergic and anti-asthmatic drugs, olopatadine and theophylline, on basophil survival. Basophils were highly purified from normal human peripheral blood. Apoptosis was analyzed by flow cytometry using annexin V staining or another staining method that detected alterations in the mitochondrial transmembrane potential. In addition to the conventional method using annexin V, basophil apoptosis was successfully established by analysis of the mitochondrial transmembrane potential. Olopatadine decreased the number of live basophils, and they induced apoptosis of basophils during culture. The decline in live basophils was induced by olopatadine even when low doses of IL-3 were included in the culture medium. Theophylline also affected basophil apoptosis and induced a decrease in the number of live basophils. Basophil apoptosis was enhanced by both olopatadine and theophylline. This effect may partly explain the pharmacologic basis of why these drugs are effective on allergic diseases.

  4. Measuring histamine and cytokine release from basophils and mast cells

    DEFF Research Database (Denmark)

    Jensen, Bettina M; Falkencrone, Sidsel; Skov, Per S

    2014-01-01

    Basophils and mast cells are known for their capability to release both preformed and newly synthesized inflammatory mediators. In this chapter we describe how to stimulate and detect histamine released from basophils in whole blood, purified basophils, in vitro cultured mast cells, and in situ...

  5. Spontaneous and cytokine induced basophil adhesion evaluated by microtiter assay

    DEFF Research Database (Denmark)

    Quan, Sha; Poulsen, Lars K; Reimert, Claus Michael;

    2002-01-01

    We have developed a microtiter assay for evaluating basophil spontaneous adhesion to extracellular matrix (ECM) proteins exemplified by fibronectin and cytokine induced basophil adhesion to bovine serum albumin (BSA). The percentage of basophils adhering to either ECM or BSA was quantified...

  6. 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

    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...

  7. Diagnostic tests based on human basophils

    DEFF Research Database (Denmark)

    Kleine-Tebbe, Jörg; Erdmann, Stephan; Knol, Edward F;

    2006-01-01

    -maximal responses, termed 'intrinsic sensitivity'. These variables give rise to shifts in the dose-response curves which, in a diagnostic setting where only a single antigen concentration is employed, may produce false-negative data. Thus, in order to meaningfully utilize the current basophil activation tests...

  8. Connective tissue and bacterial deposits on rubber dam sheet and ePTFE barrier membranes in guided periodontal tissue regeneration.

    Science.gov (United States)

    Apinhasmit, Wandee; Swasdison, Somporn; Tamsailom, Suphot; Suppipat, Nophadol

    2002-01-01

    The aim of this study was to compare the connective tissue and bacterial deposits on rubber dam sheets and expanded polytetrafluoroethylene membranes used as barrier membranes in guided tissue regeneration for periodontal treatment. Twenty patients having intrabony defects and/or furcation defects were surgically treated by guided tissue regeneration employing either rubber dam sheets (10 patients) or expanded polytetrafluoroethylene membranes (10 patients) as barrier membranes. Four to six weeks after the first operation, membranes were retrieved from the lesion sites and processed for scanning electron microscopy. The lesion-facing surfaces of membranes were examined for the presence of connective tissue and bacterial deposits. The differences between the numbers of fields and the distributions of connective tissue and bacteria on both types of membranes were analysed by the Chi-square test at the level of 0.05 significance. The results showed a lot of fibroblasts with their secreted extracellular matrices, known as components of the connective tissue on rubber dam sheets and expanded polytetrafluoroethylene membranes. There was no significant difference in the total number of connective tissue on both types of membranes (P = 0.456). Many bacterial forms including cocci, bacilli, filaments and spirochetes with the interbacterial matrices were identified. The total number of bacteria on rubber dam sheets was statistically less than that on expanded polytetrafluoroethylene membranes (P tissue on both types of membranes suggests that the healing process under both types of membranes was also comparable. Therefore, the rubber dam sheet might be used as a barrier membrane in guided tissue regeneration.

  9. Stretching of the back improves gait, mechanical sensitivity and connective tissue inflammation in a rodent model.

    Science.gov (United States)

    Corey, Sarah M; Vizzard, Margaret A; Bouffard, Nicole A; Badger, Gary J; Langevin, Helene M

    2012-01-01

    The role played by nonspecialized connective tissues in chronic non-specific low back pain is not well understood. In a recent ultrasound study, human subjects with chronic low back pain had altered connective tissue structure compared to human subjects without low back pain, suggesting the presence of inflammation and/or fibrosis in the low back pain subjects. Mechanical input in the form of static tissue stretch has been shown in vitro and in vivo to have anti-inflammatory and anti-fibrotic effects. To better understand the pathophysiology of lumbar nonspecialized connective tissue as well as potential mechanisms underlying therapeutic effects of tissue stretch, we developed a carrageenan-induced inflammation model in the low back of a rodent. Induction of inflammation in the lumbar connective tissues resulted in altered gait, increased mechanical sensitivity of the tissues of the low back, and local macrophage infiltration. Mechanical input was then applied to this model as in vivo tissue stretch for 10 minutes twice a day for 12 days. In vivo tissue stretch mitigated the inflammation-induced changes leading to restored stride length and intrastep distance, decreased mechanical sensitivity of the back and reduced macrophage expression in the nonspecialized connective tissues of the low back. This study highlights the need for further investigation into the contribution of connective tissue to low back pain and the need for a better understanding of how interventions involving mechanical stretch could provide maximal therapeutic benefit. This tissue stretch research is relevant to body-based treatments such as yoga or massage, and to some stretch techniques used with physical therapy.

  10. Stretching of the back improves gait, mechanical sensitivity and connective tissue inflammation in a rodent model.

    Directory of Open Access Journals (Sweden)

    Sarah M Corey

    Full Text Available The role played by nonspecialized connective tissues in chronic non-specific low back pain is not well understood. In a recent ultrasound study, human subjects with chronic low back pain had altered connective tissue structure compared to human subjects without low back pain, suggesting the presence of inflammation and/or fibrosis in the low back pain subjects. Mechanical input in the form of static tissue stretch has been shown in vitro and in vivo to have anti-inflammatory and anti-fibrotic effects. To better understand the pathophysiology of lumbar nonspecialized connective tissue as well as potential mechanisms underlying therapeutic effects of tissue stretch, we developed a carrageenan-induced inflammation model in the low back of a rodent. Induction of inflammation in the lumbar connective tissues resulted in altered gait, increased mechanical sensitivity of the tissues of the low back, and local macrophage infiltration. Mechanical input was then applied to this model as in vivo tissue stretch for 10 minutes twice a day for 12 days. In vivo tissue stretch mitigated the inflammation-induced changes leading to restored stride length and intrastep distance, decreased mechanical sensitivity of the back and reduced macrophage expression in the nonspecialized connective tissues of the low back. This study highlights the need for further investigation into the contribution of connective tissue to low back pain and the need for a better understanding of how interventions involving mechanical stretch could provide maximal therapeutic benefit. This tissue stretch research is relevant to body-based treatments such as yoga or massage, and to some stretch techniques used with physical therapy.

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

    Science.gov (United States)

    Esfahanian, Vahid; Golestaneh, Hedayatollah; Moghaddas, Omid; Ghafari, Mohammad Reza

    2014-01-01

    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 effectiveness 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 patients 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 gingival 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 reduction: 3.1±0.6 (Pconnective 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.

  12. Human cord blood derived immature basophils show dual characteristics, expressing both basophil and eosinophil associated proteins.

    Directory of Open Access Journals (Sweden)

    Jeanette Grundström

    Full Text Available Basophils are blood cells of low abundance associated with allergy, inflammation and parasite infections. To study the transcriptome of mature circulating basophils cells were purified from buffy coats by density gradient centrifugations and two-step magnetic cell sorting. However, after extensive analysis the cells were found to be transcriptionally inactive and almost completely lack functional mRNA. In order to obtain transcriptionally active immature basophils for analysis of their transcriptome, umbilical cord blood cells were therefore cultured in the presence of interleukin (IL-3 for 9 days and basophils were enriched by removing non-basophils using magnetic cell sorting. The majority of purified cells demonstrated typical metachromatic staining with Alcian blue dye (95% and expression of surface markers FcεRI and CD203c, indicating a pure population of cells with basophil-like phenotype. mRNA was extracted from these cells and used to construct a cDNA library with approximately 600 000 independent clones. This library served as tool to determine the mRNA frequencies for a number of hematopoietic marker proteins. It was shown that these cells express basophil/mast cell-specific transcripts, i.e. β-tryptase, serglycin and FcεRI α-chain, to a relatively low degree. In contrast, the library contained a high number of several eosinophil-associated transcripts such as: major basic protein (MBP, charcot leyden crystal (CLC, eosinophil cationic protein (ECP, eosinophil derived neurotoxin (EDN and eosinophil peroxidase (EPO. Out of these transcripts, MBP and EPO were the most frequently observed, representing 8% and 3.2% of the total mRNA pool, respectively. Moreover, in a proteome analysis of cultured basophils we identified MBP and EPO as the two most prominent protein bands, suggesting a good correlation between protein and mRNA analyses of these cells. The mixed phenotype observed for these cells strengthens the conclusion that

  13. Human cord blood derived immature basophils show dual characteristics, expressing both basophil and eosinophil associated proteins.

    Science.gov (United States)

    Grundström, Jeanette; Reimer, Jenny M; Magnusson, Sofia E; Nilsson, Gunnar; Wernersson, Sara; Hellman, Lars

    2012-01-01

    Basophils are blood cells of low abundance associated with allergy, inflammation and parasite infections. To study the transcriptome of mature circulating basophils cells were purified from buffy coats by density gradient centrifugations and two-step magnetic cell sorting. However, after extensive analysis the cells were found to be transcriptionally inactive and almost completely lack functional mRNA. In order to obtain transcriptionally active immature basophils for analysis of their transcriptome, umbilical cord blood cells were therefore cultured in the presence of interleukin (IL)-3 for 9 days and basophils were enriched by removing non-basophils using magnetic cell sorting. The majority of purified cells demonstrated typical metachromatic staining with Alcian blue dye (95%) and expression of surface markers FcεRI and CD203c, indicating a pure population of cells with basophil-like phenotype. mRNA was extracted from these cells and used to construct a cDNA library with approximately 600 000 independent clones. This library served as tool to determine the mRNA frequencies for a number of hematopoietic marker proteins. It was shown that these cells express basophil/mast cell-specific transcripts, i.e. β-tryptase, serglycin and FcεRI α-chain, to a relatively low degree. In contrast, the library contained a high number of several eosinophil-associated transcripts such as: major basic protein (MBP), charcot leyden crystal (CLC), eosinophil cationic protein (ECP), eosinophil derived neurotoxin (EDN) and eosinophil peroxidase (EPO). Out of these transcripts, MBP and EPO were the most frequently observed, representing 8% and 3.2% of the total mRNA pool, respectively. Moreover, in a proteome analysis of cultured basophils we identified MBP and EPO as the two most prominent protein bands, suggesting a good correlation between protein and mRNA analyses of these cells. The mixed phenotype observed for these cells strengthens the conclusion that eosinophils and

  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

    Life-long regular endurance exercise is known to counteract the deterioration of cardiovascular and metabolic function and overall mortality. Yet it remains unknown if life-long regular endurance exercise can influence the connective tissue accumulation of advanced glycation endproducts (AGEs...... 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. Treatment of gingival recession in two surgical stages: Free gingival graft and connective tissue grafting.

    Science.gov (United States)

    Henriques, Paulo Sergio Gomes; Nunes, Marcelo Pereira; Pelegrine, Andre Antonio

    2011-01-01

    This report describes a clinical case of severe Miller Class II gingival recession treated by two stages of surgery that combined a free gingival graft and connective tissue grafting. First, a free gingival graft (FGG) was performed to obtain an adequate keratinized tissue level. Three months later, a connective tissue graft (CTG) was performed to obtain root coverage. The results indicated that the FGG allows for a gain in the keratinized tissue level and the CTG allows for root coverage with decreased recession level after 16 months. Therefore, for this type of specific gingival recession, the combination of FGG and CTG can be used.

  16. Effects of microgravity on rat bone, cartlage and connective tissues

    Science.gov (United States)

    Doty, S.

    1990-01-01

    The response to hypogravity by the skeletal system was originally thought to be the result of a reduction in weight bearing. Thus a reduced rate of new bone formation in the weight-bearing bones was accepted, when found, as an obvious result of hypogravity. However, data on non-weight-bearing tissues have begun to show that other physiological changes can be expected to occur to animals during spaceflight. This overview of the Cosmos 1887 data discusses these results as they pertain to individual bones or tissues because the response seems to depend on the architecture and metabolism of each tissue under study. Various effects were seen in different tissues from the rats flown on Cosmos 1887. The femur showed a reduced bone mineral content but only in the central region of the diaphysis. This same region in the tibia showed changes in the vascularity of bone as well as some osteocytic cell death. The humerus demonstrated reduced morphometric characteristics plus a decrease in mechanical stiffness. Bone mineral crystals did not mature normally as a result of flight, suggesting a defect in the matrix mineralization process. Note that these changes relate directly to the matrix portion of the bone or some function of bone which slowly responds to changes in the environment. However, most cellular functions of bone are rapid responders. The stimulation of osteoblast precursor cells, the osteoblast function in collagen synthesis, a change in the proliferation rate of cells in the epiphyseal growth plate, the synthesis and secretion of osteocalcin, and the movement of water into or out of tissues, are all processes which respond to environmental change. These rapidly responding events produced results from Cosmos 1887 which were frequently quite different from previous space flight data.

  17. Extraction of Ku antigen and anti-Ku antibody assay in various autoimmune connective tissue diseases

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To extract Ku antigen and to detect anti-Ku antibody in connective tissue diseases (CTDs). Methods: Ku antigen was prepared from rabbit thymus acetone powder. Anti-Ku antibodies were tested in 50 normal controls and 438 patients

  18. 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......-wave peak) and at 45\\$\\backslash\\$% of the R-R interval were used to evaluate the performance of our method. The automated 3D segmentation result produced accurate aortic surfaces covering the aorta. The CAD method distinguished between normal and connective tissue disorder subjects with a classification...

  19. Aortic tear and dissection related to connective tissues abnormalities resembling Marfan syndrome in a Great Dane.

    Science.gov (United States)

    Lenz, Jennifer A; Bach, Jonathan F; Bell, Cynthia M; Stepien, Rebecca L

    2015-06-01

    Aortic tears and acute aortic dissection are rarely reported in dogs. This report describes a case of aortic dissection and probable sinus of Valsalva rupture in a young Great Dane with associated histopathologic findings suggestive of a connective tissue abnormality.

  20. 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...... on the ovaries, and collected from the saline solution, containing surplus medulla tissue, following dissection of the ovarian cortical tissue for cryopreservation. The immature oocytes were cultured for 48 h in an Embryoscope™ Time-lapse System or in culture dishes overlaid with liquid paraffin using commercial...

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    INTRODUCTION: In 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....... CONCLUSIONS: The later appearance of a stimulating effect of WPH on the IMCT FSR after strenuous muscle contractions lends support to its ability to promote recovery of the muscle connective tissue matrix after exercise. Muscle Nerve 55: 128-130, 2017....

  2. Focal dermal hypoplasia: ultrastructural abnormalities of the connective tissue.

    Science.gov (United States)

    del Carmen Boente, María; Asial, Raúl A; Winik, Beatriz C

    2007-02-01

    We followed over 10 years three girls with focal dermal hypoplasia syndrome. The histopathological changes demonstrated at the optical level an hypoplastic dermis with thin and scarce collagen bundles and a marked diminution of elastic fibers. Mature adipose tissue was found scattered within the papillary and reticular dermis. No alterations in the basal membrane were observed by immunocytochemical or ultrastructural techniques. Ultrastructurally, in the skin-affected areas, loosely arranged collagen bundles composed of few fibrils were seen scattered in the extracellular matrix. Scarce elastic fibers of normal morphology were also observed. Fibroblasts were smaller, oval-shaped, and diminished in number with a poorly developed cytoplasm. In these fibroblasts, the most conspicuous feature was a remarkable and irregular thickening of the nuclear fibrous lamina. Taking into account that a common link between all laminopaties may be a failure of stem cells to regenerate mesenchymal tissue, this failure would induce the dermal hypoplasia observed in our patients presenting Goltz syndrome.

  3. Connective tissue spectrum abnormalities associated with spontaneous cerebrospinal fluid leaks: a prospective study.

    Science.gov (United States)

    Reinstein, Eyal; Pariani, Mitchel; Bannykh, Serguei; Rimoin, David L; Schievink, Wouter I

    2013-04-01

    We aimed to assess the frequency of connective tissue abnormalities among patients with cerebrospinal fluid (CSF) leaks in a prospective study using a large cohort of patients. We enrolled a consecutive group of 50 patients, referred for consultation because of CSF leak. All patients have been carefully examined for the presence of connective tissue abnormalities, and based on findings, patients underwent genetic testing. Ancillary diagnostic studies included echocardiography, eye exam, and histopathological examinations of skin and dura biopsies in selected patients. We identified nine patients with heritable connective tissue disorders, including Marfan syndrome, Ehlers-Danlos syndrome and other unclassified forms. In seven patients, spontaneous CSF leak was the first noted manifestation of the genetic disorder. We conclude that spontaneous CSF leaks are associated with a spectrum of connective tissue abnormalities and may be the first noted clinical presentation of the genetic disorder. We propose that there is a clinical basis for considering spontaneous CSF leak as a clinical manifestation of heritable connective tissue disorders, and we suggest that patients with CSF leaks should be screened for connective tissue and vascular abnormalities.

  4. Identification of tumor cells infiltrating into connective tissue in esophageal cancer by multiphoton microscopy

    Science.gov (United States)

    Xu, Jian; Jiang, Liwei; Kang, Deyong; Wu, Xuejing; Xu, Meifang; Zhuo, Shuangmu; Zhu, Xiaoqin; Lin, Jiangbo; Chen, Jianxin

    2016-10-01

    Esophageal cancer is one of the most common malignancies of the gastrointestinal cancers and carries poorer prognosis than other gastrointestinal cancers. In general practice, the depth of tumor infiltration in esophageal wall is crucial to establishing appropriate treatment plan which is established by detecting the tumor infiltration depth. Connective tissue is one of the main structures that form the esophageal wall. So, identification of tumor cells infiltrating into connective tissue is helping for detecting the tumor infiltration depth. Our aim is to evaluate whether multiphoton microscopy (MPM) can be used to detect tumor cells infiltrating into connective tissue in the esophageal cancer. MPM is well-suited for real-time detecting morphologic and cellular changes in fresh tissues since many endogenous fluorophores of fresh tissues are excited through two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). In this work, microstructure of tumor cells and connective tissue are first studied. Then, morphological changes of collagen fibers after the infiltration of tumor cells are shown. These results show that MPM has the ability to detect tumor cells infiltrating into connective tissue in the esophageal cancer. In the future, MPM may be a promising imaging technique for detecting tumor cells in esophageal cancer.

  5. Mueller matrix approach for probing multifractality in the underlying anisotropic connective tissue

    Science.gov (United States)

    Das, Nandan Kumar; Dey, Rajib; Ghosh, Nirmalya

    2016-09-01

    Spatial variation of refractive index (RI) in connective tissues exhibits multifractality, which encodes useful morphological and ultrastructural information about the disease. We present a spectral Mueller matrix (MM)-based approach in combination with multifractal detrended fluctuation analysis (MFDFA) to exclusively pick out the signature of the underlying connective tissue multifractality through the superficial epithelium layer. The method is based on inverse analysis on selected spectral scattering MM elements encoding the birefringence information on the anisotropic connective tissue. The light scattering spectra corresponding to the birefringence carrying MM elements are then subjected to the Born approximation-based Fourier domain preprocessing to extract ultrastructural RI fluctuations of anisotropic tissue. The extracted RI fluctuations are subsequently analyzed via MFDFA to yield the multifractal tissue parameters. The approach was experimentally validated on a simple tissue model comprising of TiO2 as scatterers of the superficial isotropic layer and rat tail collagen as an underlying anisotropic layer. Finally, the method enabled probing of precancer-related subtle alterations in underlying connective tissue ultrastructural multifractality from intact tissues.

  6. A survey of clearing techniques for 3D imaging of tissues with special reference to connective tissue.

    Science.gov (United States)

    Azaripour, Adriano; Lagerweij, Tonny; Scharfbillig, Christina; Jadczak, Anna Elisabeth; Willershausen, Brita; Van Noorden, Cornelis J F

    2016-08-01

    For 3-dimensional (3D) imaging of a tissue, 3 methodological steps are essential and their successful application depends on specific characteristics of the type of tissue. The steps are 1° clearing of the opaque tissue to render it transparent for microscopy, 2° fluorescence labeling of the tissues and 3° 3D imaging. In the past decades, new methodologies were introduced for the clearing steps with their specific advantages and disadvantages. Most clearing techniques have been applied to the central nervous system and other organs that contain relatively low amounts of connective tissue including extracellular matrix. However, tissues that contain large amounts of extracellular matrix such as dermis in skin or gingiva are difficult to clear. The present survey lists methodologies that are available for clearing of tissues for 3D imaging. We report here that the BABB method using a mixture of benzyl alcohol and benzyl benzoate and iDISCO using dibenzylether (DBE) are the most successful methods for clearing connective tissue-rich gingiva and dermis of skin for 3D histochemistry and imaging of fluorescence using light-sheet microscopy.

  7. Basophil competence during hookworm (Necator americanus) infection.

    Science.gov (United States)

    Pritchard, David I; Hooi, Doreen S W; Brown, Alan; Bockarie, Moses J; Caddick, Rebecca; Quinnell, Rupert J

    2007-11-01

    A popular hypothesis to explain parasite survival in the presence of a pronounced T helper 2 phenotype in helminth-parasitized populations has been Fc epsilonRI blockade by parasite-induced polyclonal IgE. To begin to test the hypothesis that Fc epsilonRI-bearing cells would be refractory to activation in parasitized populations, we investigated basophil function in 43 individuals from a hookworm endemic area. Study individuals had high levels of total IgE and eosinophilia and a mean hookworm burden of 2,257 epg. Basophils from all members of this parasitized population were shown to release histamine to a number of agonists, including anti IgE and a hookworm allergen, calreticulin. These data would indicate that Fc epsilonRI blockade at the level of the basophil did not occur in this parasitized population despite the presence of possible immunologic blocking agents. This would suggest that this effector arm of the T helper 2 phenotype remains operative in infected populations.

  8. Perimuscular connective tissue contains more and larger lymphatic vessels than the shallower layers in human gallbladders

    Institute of Scientific and Technical Information of China (English)

    Masayuki Nagahashi; Yoshio Shirai; Toshifumi Wakai; Jun Sakata; Yoichi Ajioka; Katsuyoshi Hatakeyama

    2007-01-01

    AIM: To clarify whether perimuscular connective tissue contains more lymphatic vessels than the shallower layers in human gallbladders.METHODS: Lymphatic vessels were stained immunohistochemically with monoclonal antibody D2-40,which is a specific marker of lymphatic endothelium, in representative sections of 12 normal human gallbladders obtained at the time of resection for colorectal carcinoma liver metastases. In individual gallbladder specimens,nine high-power (× 200) fields with the highest lymphatic vessel density (LVD), termed "hot spots", were identified for each layer (mucosa, muscle layer, and perimuscular connective tissue). In individual hot spots,the LVD and relative lymphatic vessel area (LVA) were measured microscopically using a computer-aided image analysis system. The mean LVD and LVA values for the nine hot spots in each layer were used for statistical analyses.RESULTS: In the mucosa, muscle layer, and perimuscular connective tissue, the LVD was 16.1 ± 9.2,35.4 ± 15.7, and 65.5 ± 12.2, respectively, and the LVA was 0.4 ± 0.4, 2.1 ± 1.1, and 9.4 ± 2.6, respectively.Thus, both the LVD and LVA differed significantly (P <0.001 and P < 0.001, respectively; Kruskal-Wallis test)among the individual layers of the wall of the gallbladder,with the highest LVD and LVA values in the perimuscular connective tissue. Most (98 of 108) of the hot spots within the perimuscular connective tissue were located within 500 μm of the lower border of the muscle layer.CONCLUSION: The perimuscular connective tissue contains more and larger lymphatic vessels than the shallower layers in the human gallbladder. This observation partly explains why the incidence of lymph node metastasis is high in T2 (tumor invading the perimuscular connective tissue) or more advanced gallbladder carcinoma.

  9. 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.

  10. Adherence of human basophils to cultured umbilical vein endothelial cells.

    OpenAIRE

    1988-01-01

    The mechanism by which circulating human basophils adhere to vascular endothelium and migrate to sites of allergic reactions is unknown. Agents have been identified which stimulate the adherence of purified basophils to cultured human umbilical vein vascular endothelial cells (HuVEC). Treatment of HuVEC with interleukin 1, tumor necrosis factor (TNF), bacterial endotoxin, and 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in time and dose-dependent increases of adhesiveness for basophils...

  11. Should Endovascular Therapy Be Considered for Patients With Connective Tissue Disorder?

    Science.gov (United States)

    Gagné-Loranger, Maude; Voisine, Pierre; Dagenais, François

    2016-01-01

    Because of early diagnosis, strict imaging follow-up, and advances in medical and surgical management, life expectancy of Marfan patients has dramatically improved since the 1970s. Although disease of the root and ascending aorta are more frequent in patients with connective tissue disorders, a subset of patients present with diffuse disease that might involve any portion of the thoracoabdominal aorta. Thoracic endovascular aortic repair (TEVAR) has gained widespread acceptance for the treatment of different pathologies of the descending aorta. In contrast, TEVAR in patients with connective tissue disorders is associated with a high risk of early and mid-term complications and reinterventions. Currently, a consensus of experts recommend that an open approach should be reserved for use in acceptable risk candidates with connective tissue disorders. TEVAR should be considered solely in patients in a complex repeat surgical setting or in patients judged to have prohibitive open surgical risk. Finally, as a bridge to a definite open repair, TEVAR might be life-saving in patients with connective tissue disorders who present with exsanguination or severe malperfusion. Future developments in stent-graft technology might decrease stent-graft-related complications in patients with connective tissue disorders, although securing a device with radial force in a fragile aorta in the long-term will be challenging.

  12. 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.

  13. Effect of MELT method on thoracolumbar connective tissue: The full study.

    Science.gov (United States)

    Sanjana, Faria; Chaudhry, Hans; Findley, Thomas

    2017-01-01

    Altered connective tissue structure has been identified in adults with chronic low back pain (LBP). A self-care treatment for managing LBP is the MELT method. The MELT method is a hands-off, self-treatment that is said to alleviate chronic pain, release tension and restore mobility, utilizing specialized soft treatments balls, soft body roller and techniques mimicking manual therapy. The objective of this study was to determine whether thickness of thoracolumbar connective tissue and biomechanical and viscoelastic properties of myofascial tissue in the low back region change in subjects with chronic LBP as a result of MELT. This study was designed using a quasi experimental pre-post- design that analyzed data from subjects who performed MELT. Using ultrasound imaging and an algorithm developed in MATLAB, thickness of thoracolumbar connective tissue was analyzed in 22 subjects. A hand-held digital palpation device, called the MyotonPRO, was used to assess biomechanical properties such as stiffness, elasticity, tone and mechanical stress relaxation time of the thoracolumbar myofascial tissue. A forward bending test assessing flexibility and pain scale was added to see if MELT affected subjects with chronic LBP. A significant decrease in connective tissue thickness and pain was observed in participants. Significant increase in flexibility was also recorded.

  14. [Klinefelter's syndrome associated with mixed connective tissue disease (Sharp's syndrome) and thrombophilia with postthrombotic syndrome].

    Science.gov (United States)

    Kasten, Robert; Pfirrmann, Gudrun; Voigtländer, Volker

    2005-08-01

    A 43-year-old male with eunuchoid body proportions and a history of deep venous thromboses in the right leg presented with recurrent ulcers in the right perimalleolar region for 6 years. Karyotyping revealed a 47 XXY Klinefelter's syndrome, while serologic testing showed protein S deficiency, hyperhomocysteinemia and positive lupus anticoagulant. He also had mixed connective tissue disease (Sharp's syndrome) with acrosclerosis, proximal finger edema, Raynaud's phenomenon, and high titers of ANA and U1-RNP-antibodies, as well as osteoporosis. There is evidence that patients with Klinefelter's syndrome are prone to develop connective tissue diseases and thrombophilia as a result of low androgen levels. Substitution of testosterone in Klinefelter's syndrome can have a favorable therapeutic effect on the associated connective tissue disease, thrombophilia and osteoporosis.

  15. The connective tissue phenotype of glaucomatous cupping in the monkey eye - Clinical and research implications.

    Science.gov (United States)

    Yang, Hongli; Reynaud, Juan; Lockwood, Howard; Williams, Galen; Hardin, Christy; Reyes, Luke; Stowell, Cheri; Gardiner, Stuart K; Burgoyne, Claude F

    2017-03-12

    In a series of previous publications we have proposed a framework for conceptualizing the optic nerve head (ONH) as a biomechanical structure. That framework proposes important roles for intraocular pressure (IOP), IOP-related stress and strain, cerebrospinal fluid pressure (CSFp), systemic and ocular determinants of blood flow, inflammation, auto-immunity, genetics, and other non-IOP related risk factors in the physiology of ONH aging and the pathophysiology of glaucomatous damage to the ONH. The present report summarizes 20 years of technique development and study results pertinent to the characterization of ONH connective tissue deformation and remodeling in the unilateral monkey experimental glaucoma (EG) model. In it we propose that the defining pathophysiology of a glaucomatous optic neuropathy involves deformation, remodeling, and mechanical failure of the ONH connective tissues. We view this as an active process, driven by astrocyte, microglial, fibroblast and oligodendrocyte mechanobiology. These cells, and the connective tissue phenomena they propagate, have primary and secondary effects on retinal ganglion cell (RGC) axon, laminar beam and retrolaminar capillary homeostasis that may initially be "protective" but eventually lead to RGC axonal injury, repair and/or cell death. The primary goal of this report is to summarize our 3D histomorphometric and optical coherence tomography (OCT)-based evidence for the early onset and progression of ONH connective tissue deformation and remodeling in monkey EG. A second goal is to explain the importance of including ONH connective tissue processes in characterizing the phenotype of a glaucomatous optic neuropathy in all species. A third goal is to summarize our current efforts to move from ONH morphology to the cell biology of connective tissue remodeling and axonal insult early in the disease. A final goal is to facilitate the translation of our findings and ideas into neuroprotective interventions that target

  16. Mechanical tension as a driver of connective tissue growth in vitro.

    Science.gov (United States)

    Wilson, Cameron J; Pearcy, Mark J; Epari, Devakara R

    2014-07-01

    We propose the progressive mechanical expansion of cell-derived tissue analogues as a novel, growth-based approach to in vitro tissue engineering. The prevailing approach to producing tissue in vitro is to culture cells in an exogenous "scaffold" that provides a basic structure and mechanical support. This necessarily pre-defines the final size of the implantable material, and specific signals must be provided to stimulate appropriate cell growth, differentiation and matrix formation. In contrast, surgical skin expansion, driven by increments of stretch, produces increasing quantities of tissue without trauma or inflammation. This suggests that connective tissue cells have the innate ability to produce growth in response to elevated tension. We posit that this capacity is maintained in vitro, and that order-of-magnitude growth may be similarly attained in self-assembling cultures of cells and their own extracellular matrix. The hypothesis that growth of connective tissue analogues can be induced by mechanical expansion in vitro may be divided into three components: (1) tension stimulates cell proliferation and extracellular matrix synthesis; (2) the corresponding volume increase will relax the tension imparted by a fixed displacement; (3) the repeated application of static stretch will produce sustained growth and a tissue structure adapted to the tensile loading. Connective tissues exist in a state of residual tension, which is actively maintained by resident cells such as fibroblasts. Studies in vitro and in vivo have demonstrated that cellular survival, reproduction, and matrix synthesis and degradation are regulated by the mechanical environment. Order-of-magnitude increases in both bone and skin volume have been achieved clinically through staged expansion protocols, demonstrating that tension-driven growth can be sustained over prolonged periods. Furthermore, cell-derived tissue analogues have demonstrated mechanically advantageous structural adaptation in

  17. GATA-1 regulates the generation and function of basophils.

    Science.gov (United States)

    Nei, Yuichiro; Obata-Ninomiya, Kazushige; Tsutsui, Hidemitsu; Ishiwata, Kenji; Miyasaka, Masayuki; Matsumoto, Kenji; Nakae, Susumu; Kanuka, Hirotaka; Inase, Naohiko; Karasuyama, Hajime

    2013-11-12

    Developmental processes of hematopoietic cells are orchestrated by transcriptional networks. GATA-1, the founding member of the GATA family of transcription factors, has been demonstrated to play crucial roles in the differentiation of erythroid cells, magakaryocytes, eosinophils, and mast cells. However, the role of GATA-1 in basophils remains elusive. Here we show that basophils abundantly express Gata1 mRNAs, and that siRNA-mediated knockdown of Gata1 resulted in impaired production of IL-4 by basophils in response to the stimulation with IgE plus antigens. ΔdblGATA mice that carry the mutated Gata1 promoter and are widely used for functional analysis of eosinophils owing to their selective loss of eosinophils showed a decreased number of basophils with reduced expression of Gata1 mRNAs. The number of basophil progenitors in bone marrow was reduced in these mice, and the generation of basophils from their bone marrow cells in culture with IL-3 or thymic stromal lymphopoietin was impaired. ΔdblGATA basophils responded poorly ex vivo to stimulation with IgE plus antigens compared with wild-type basophils as assessed by degranulation and production of IL-4 and IL-6. Moreover, ΔdblGATA mice showed impaired responses in basophil-mediated protective immunity against intestinal helminth infection. Thus, ΔdblGATA mice showed numerical and functional aberrancy in basophils in addition to the known deficiency of eosinophils. Our findings demonstrate that GATA-1 plays a key role in the generation and function of basophils and underscore the need for careful distinction of the cell lineage responsible for each phenotype observed in ΔdblGATA mice.

  18. Association of cervical artery dissection with connective tissue abnormalities in skin and arteries.

    Science.gov (United States)

    Brandt, T; Morcher, M; Hausser, I

    2005-01-01

    Spontaneous cervical artery dissections (sCAD) often occur in otherwise healthy individuals without known risk factors for stroke and frequently develop spontaneously without relevant trauma. An underlying arteriopathy leading to a so-called 'weakness of the vessel wall' and predisposing certain individuals to dissection has often been postulated. Therefore, the morphology of connective tissue, a main component of vessel wall and environment, was investigated in carotids and skin. While the overall morphology of dermal connective tissue is normal, about half of patients with sCAD show mild ultrastructural connective tissue alterations. These ultrastructural morphological aberrations can be designated either as 'Ehlers-Danlos syndrome (EDS) III-like', resembling mild findings in patients with the hypermobility type of EDS (EDS III); or coined 'EDS IV-like' with collagen fibers containing fibrils with highly variable diameters resembling mild findings in vascular EDS; or the abnormalities are restricted to the elastic fibers (with fragmentation and minicalcifications) without significant alterations in the morphology of the collagen fibrils. These findings had some similarity with the morphology found in heterozygous carriers of pseudoxanthoma elasticum. A grading scale according to the severity of the findings has been introduced. Similar connective tissue abnormalities were detected in some first-degree relatives of patients with sCAD showing hereditary at least in a subgroup. They can serve as a phenotypic marker for further genetic studies in patients with sCAD and large families to possibly identify the underlying basic molecular defect(s). Very few of patients (connective tissue abnormalities have clinical manifestations of skin, joint, or skeletal abnormalities of a defined heritable connective tissue disorder. In specimens of arterial walls of carotid, aortic, and renal arteries of patients with sCAD, pronounced systemic, histopathological, and

  19. The connective tissue of the adductor canal--a morphological study in fetal and adult specimens.

    Science.gov (United States)

    de Oliveira, Flavia; de Vasconcellos Fontes, Ricardo Bragança; da Silva Baptista, Josemberg; Mayer, William Paganini; de Campos Boldrini, Silvia; Liberti, Edson Aparecido

    2009-03-01

    The adductor canal is a conical or pyramid-shaped pathway that contains the femoral vessels, saphenous nerve and a varying amount of fibrous tissue. It is involved in adductor canal syndrome, a claudication syndrome involving young individuals. Our objective was to study modifications induced by aging on the connective tissue and to correlate them to the proposed pathophysiological mechanism. The bilateral adductor canals and femoral vessels of four adult and five fetal specimens were removed en bloc and analyzed. Sections 12 microm thick were obtained and the connective tissue studied with Sirius Red, Verhoeff, Weigert and Azo stains. Scanning electron microscopy (SEM) photomicrographs of the surfaces of each adductor canal were also analyzed. Findings were homogeneous inside each group. The connective tissue of the canal was continuous with the outer layer of the vessels in both groups. The pattern of concentric, thick collagen type I bundles in fetal specimens was replaced by a diffuse network of compact collagen bundles with several transversal fibers and an impressive content of collagen III fibers. Elastic fibers in adults were not concentrated in the thick bundles but dispersed in line with the transversal fiber system. A dynamic compression mechanism with or without an evident constricting fibrous band has been proposed previously for adductor canal syndrome, possibly involving the connective tissue inside the canal. The vessels may not slide freely during movement. These age-related modifications in normal individuals may represent necessary conditions for this syndrome to develop.

  20. Sensory innervation of the nonspecialized connective tissues in the low back of the rat.

    Science.gov (United States)

    Corey, Sarah M; Vizzard, Margaret A; Badger, Gary J; Langevin, Helene M

    2011-01-01

    Chronic musculoskeletal pain, including low back pain, is a worldwide debilitating condition; however, the mechanisms that underlie its development remain poorly understood. Pathological neuroplastic changes in the sensory innervation of connective tissue may contribute to the development of nonspecific chronic low back pain. Progress in understanding such potentially important abnormalities is hampered by limited knowledge of connective tissue's normal sensory innervation. The goal of this study was to evaluate and quantify the sensory nerve fibers terminating within the nonspecialized connective tissues in the low back of the rat. With 3-dimensional reconstructions of thick (30-80 μm) tissue sections we have for the first time conclusively identified sensory nerve fiber terminations within the collagen matrix of connective tissue in the low back. Using dye labeling techniques with Fast Blue, presumptive dorsal root ganglia cells that innervate the low back were identified. Of the Fast Blue-labeled cells, 60-88% also expressed calcitonin gene-related peptide (CGRP) immunoreactivity. Based on the immunolabeling with CGRP and the approximate size of these nerve fibers (≤2 μm) we hypothesize that they are Aδ or C fibers and thus may play a role in the development of chronic pain.

  1. Live Imaging of Axolotl Digit Regeneration Reveals Spatiotemporal Choreography of Diverse Connective Tissue Progenitor Pools.

    Science.gov (United States)

    Currie, Joshua D; Kawaguchi, Akane; Traspas, Ricardo Moreno; Schuez, Maritta; Chara, Osvaldo; Tanaka, Elly M

    2016-11-21

    Connective tissues-skeleton, dermis, pericytes, fascia-are a key cell source for regenerating the patterned skeleton during axolotl appendage regeneration. This complexity has made it difficult to identify the cells that regenerate skeletal tissue. Inability to identify these cells has impeded a mechanistic understanding of blastema formation. By tracing cells during digit tip regeneration using brainbow transgenic axolotls, we show that cells from each connective tissue compartment have distinct spatial and temporal profiles of proliferation, migration, and differentiation. Chondrocytes proliferate but do not migrate into the regenerate. In contrast, pericytes proliferate, then migrate into the blastema and give rise solely to pericytes. Periskeletal cells and fibroblasts contribute the bulk of digit blastema cells and acquire diverse fates according to successive waves of migration that choreograph their proximal-distal and tissue contributions. We further show that platelet-derived growth factor signaling is a potent inducer of fibroblast migration, which is required to form the blastema.

  2. Esthetic Root Coverage with Double Papillary Subepithelial Connective Tissue Graft: A Case Report

    Directory of Open Access Journals (Sweden)

    Ramesh Babu Mutthineni

    2014-01-01

    Full Text Available Patients today have become excessively concerned about esthetics. These esthetic concerns of patients have become an integral part of periodontal practice. Gingival recession is an esthetic problem that can be successfully treated by means of several mucogingival surgical approaches, any of which can be used, provided that the biologic conditions for accomplishing root coverage are satisfied with no loss of soft and hard tissue height interdentally. There are currently different techniques for root coverage which include pedicle grafts, free gingival grafts, connective tissue grafts, and guided tissue regeneration (GTR. This paper reports a case in which a new double papillary connective tissue graft technique has been used in the treatment of gingival recession.

  3. [Biological Role of Oligomerny Matriksny of Protein of the Cartilage in Exchange Processes Connecting Tissue].

    Science.gov (United States)

    Belova, Yu S

    2015-01-01

    In the review the literary data on studying of biological role of a oligomerny matriksny of protein of the cartilage in exchange processes connecting tissue at people and animals are provided, and also results of own researches on definition of a oligomerny matriksny of protein of the cartilage as a modern marker of a metabolism of an articulate cartilage at children from undifferentiated displaziy conjunctive tissue are briefly described.

  4. A New Variant of Connective Tissue Nevus with Elastorrhexis and Predilection for the Upper Chest.

    Science.gov (United States)

    Chu, Derek H; Goldbach, Hayley; Wanat, Karolyn A; Rubin, Adam I; Yan, Albert C; Treat, James R

    2015-01-01

    Localized changes in cutaneous elastic tissue often manifest with flesh-colored, hypopigmented, or yellow papules, plaques, and nodules. We present five children with clinically similar cobblestone plaques composed of multiple hypopigmented, nonfollicular, pinpoint papules located unilaterally over the upper chest. All lesions first appeared at birth or during early infancy. No associated extracutaneous abnormalities have been identified. Histopathology was remarkable for many, thick elastic fibers with elastorrhexis. We believe that these cases represent a distinct and unique variant of connective tissue nevi.

  5. Dynamic morphometric characterization of local connective tissue network structure in humans using ultrasound

    Directory of Open Access Journals (Sweden)

    Konofagou Elisa E

    2007-06-01

    Full Text Available Abstract Background In humans, connective tissue forms a complex, interconnected network throughout the body that may have mechanosensory, regulatory and signaling functions. Understanding these potentially important phenomena requires non-invasive measurements of collagen network structure that can be performed in live animals or humans. The goal of this study was to show that ultrasound can be used to quantify dynamic changes in local connective tissue structure in vivo. We first performed combined ultrasound and histology examinations of the same tissue in two subjects undergoing surgery: in one subject, we examined the relationship of ultrasound to histological images in three dimensions; in the other, we examined the effect of a localized tissue perturbation using a previously developed robotic acupuncture needling technique. In ten additional non-surgical subjects, we quantified changes in tissue spatial organization over time during needle rotation vs. no rotation using ultrasound and semi-variogram analyses. Results 3-D renditions of ultrasound images showed longitudinal echogenic sheets that matched with collagenous sheets seen in histological preparations. Rank correlations between serial 2-D ultrasound and corresponding histology images resulted in high positive correlations for semi-variogram ranges computed parallel (r = 0.79, p Conclusion The combination of ultrasound and semi-variogram analyses allows quantitative assessment of dynamic changes in the structure of human connective tissue in vivo.

  6. Pros and Cons of Clinical Basophil Testing (BAT)

    NARCIS (Netherlands)

    Hoffmann, Hans Jürgen; Knol, Edward F; Ferrer, Martha; Mayorga, Lina; Sabato, Vito; Santos, Alexandra F; Eberlein, Bernadette; Nopp, Anna; MacGlashan, Donald

    2016-01-01

    PURPOSE OF REVIEW: We review basophil testing by flow cytometry with an emphasis on advantages and disadvantages. RECENT FINDINGS: There are many tools available to assess the presence and severity of allergic diseases in patients. For 50 years, peripheral blood basophils have been used as tools to

  7. Basophil leucocyte response in leprosy with lepromin-A

    Directory of Open Access Journals (Sweden)

    Okhandiar R

    1993-01-01

    Full Text Available Study of ′Basophil Leucocyte Response′ in two polar groups of leprosy patients (tuberculoid and lepromatous was undertaken employing Lepromin-A (Armadillo by the method of Open Window Technique of Rebuck. Significant infiltration of Basophils at the test side is demonstrated both at 48 hours and at 72 hours in lepromatous leprosy as compared to the control groups i.e., in placebo and tuberculin positive healthy volunteers as well as against tuberculoid leprosy group (p value being less than 0.05 and 0.001. The basophils also go into degeneration and degranulation at 72 hours. . The role of basophils in the different types of allergic reactions is discussed in context of above finding. The possible effect of high infiltration of basophils in lepromatous leprosy with its subsequent release of histamine and other factors by degranulation, and its possible role in immuno-regulation through specialised suppressor cells is postulated in the light of available data.

  8. Muscle connective tissue content of endurance-trained and inactive individuals

    DEFF Research Database (Denmark)

    Mackey, Abigail; Donnelly, A E; Roper, H P

    2005-01-01

    Although it is known that exercise exerts a positive regulatory effect on collagen synthesis, the effects of endurance training on muscle endomysial connective tissue in man are not so well documented. To investigate this, a single muscle biopsy was collected from two groups of volunteers...

  9. 结缔组织病与发热%Connective tissue disease and fever

    Institute of Scientific and Technical Information of China (English)

    左晓霞

    2009-01-01

    @@ 弥漫性结缔组织病习惯上简称为结缔组织病(connective tissue disease,CTD),是指一类可能与遗传、环境因素相关,主要累及皮肤、关节、肌肉、血管等结缔组织的疾病.

  10. Connective tissue integrity is lost in vitamin B-6-deficient chicks

    Science.gov (United States)

    Masse, P. G.; Yamauchi, M.; Mahuren, J. D.; Coburn, S. P.; Muniz, O. E.; Howell, D. S.

    1995-01-01

    The objective of the present investigation was to characterize further the connective tissue disorder produced by pyridoxine (vitamin B-6) deficiency, as previously evidenced by electron microscopy. Following the second post-natal week, fast growing male chicks were deprived of pyridoxine for a 1-mo period. Six weeks post-natally, blood concentrations in the experimental deficiency group had declined to deficiency levels as registered by low concentrations of pyridoxal phosphate (coenzyme form) in erythrocytes, but did not reach levels associated with neurological symptoms. Light microscopic study showed abnormalities in the extracellular matrix of the connective tissues. Collagen cross-links and the aldehyde contents were not significantly lower in cartilage and tendon collagens of vitamin B-6-deficient animals than in age-matched controls; also, their proteoglycan degrading protease and collagenase activities measured in articular cartilages were not greater. Thus, proteolysis was an unlikely alternative mechanism to account for the loss of connective tissue integrity. These results point to the need for further investigation into adhesive properties of collagen associated proteoglycans or other proteins in vitamin B-6-deficient connective tissue.

  11. Elastin Cables Define the Axial Connective Tissue System in the Murine Lung.

    Science.gov (United States)

    Wagner, Willi; Bennett, Robert D; Ackermann, Maximilian; Ysasi, Alexandra B; Belle, Janeil; Valenzuela, Cristian D; Pabst, Andreas; Tsuda, Akira; Konerding, Moritz A; Mentzer, Steven J

    2015-11-01

    The axial connective tissue system is a fiber continuum of the lung that maintains alveolar surface area during changes in lung volume. Although the molecular anatomy of the axial system remains undefined, the fiber continuum of the lung is central to contemporary models of lung micromechanics and alveolar regeneration. To provide a detailed molecular structure of the axial connective tissue system, we examined the extracellular matrix of murine lungs. The lungs were decellularized using a 24 hr detergent treatment protocol. Systematic evaluation of the decellularized lungs demonstrated no residual cellular debris; morphometry demonstrated a mean 39 ± 7% reduction in lung dimensions. Scanning electron microscopy (SEM) demonstrated an intact structural hierarchy within the decellularized lung. Light, fluorescence, and SEM of precision-cut lung slices demonstrated that alveolar duct structure was defined by a cable line element encased in basement membrane. The cable line element arose in the distal airways, passed through septal tips and inserted into neighboring blood vessels and visceral pleura. The ropelike appearance, collagenase resistance and anti-elastin immunostaining indicated that the cable was an elastin macromolecule. Our results indicate that the helical line element of the axial connective tissue system is composed of an elastin cable that not only defines the structure of the alveolar duct, but also integrates the axial connective tissue system into visceral pleura and peripheral blood vessels.

  12. 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 decrease

  13. Renal proximal tubular dysfunction is a major determinant of urinary connective tissue growth factor excretion.

    NARCIS (Netherlands)

    Gerritsen, K.G.; Peters, H.P.E.; Nguyen, T.Q.; Koeners, M.P.; Wetzels, J.F.M.; Joles, J.A.; Christensen, E.I.; Verroust, P.J.; Li, D.; Oliver, N.; Xu, L.; Kok, R.J.; Goldschmeding, R.

    2010-01-01

    Connective tissue growth factor (CTGF) plays a key role in renal fibrosis. Urinary CTGF is elevated in various renal diseases and may have biomarker potential. However, it is unknown which processes contribute to elevated urinary CTGF levels. Thus far, urinary CTGF was considered to reflect renal ex

  14. Structure of the rat subcutaneous connective tissue in relation to its sliding mechanism.

    Science.gov (United States)

    Kawamata, Seiichi; Ozawa, Junya; Hashimoto, Masakazu; Kurose, Tomoyuki; Shinohara, Harumichi

    2003-08-01

    Mammalian skin can extensively slide over most parts of the body. To study the mechanism of this mobility of the skin, the structure of the subcutaneous connective tissue was examined by light microscopy. The subcutaneous connective tissue was observed to be composed of multiple layers of thin collagen sheets containing elastic fibers. These piled-up collagen sheets were loosely interconnected with each other, while the outer and inner sheets were respectively anchored to the dermis and epimysium by elastic fibers. Collagen fibers in each sheet were variable in diameter and oriented in different directions to form a thin, loose meshwork under conditions without mechanical stretching. When a weak shear force was loaded between the skin and the underlying abdominal muscles, each collagen sheet slid considerably, resulting in a stretching of the elastic fibers which anchor these sheets. When a further shear force was loaded, collagen fibers in each sheet seemed to align in a more parallel manner to the direction of the tension. With the reduction or removal of the force, the arrangement of collagen fibers in each sheet was reversed and the collagen sheets returned to their original shapes and positions, probably with the stabilizing effect of elastic fibers. Blood vessels and nerves in the subcutaneous connective tissue ran in tortuous routes in planes parallel to the unloaded skin, which seemed very adaptable for the movement of collagen sheets. These findings indicate that the subcutaneous connective tissue is extensively mobile due to the presence of multilayered collagen sheets which are maintained by elastic fibers.

  15. Sonographic Measurements of Subsynovial Connective Tissue Thickness in Patients With Carpal Tunnel Syndrome

    NARCIS (Netherlands)

    van Doesburg, Margriet H. M.; van der Molen, Aebele Mink; Henderson, Jacqueline; Cha, Stephen S.; An, Kai Nan; Amadio, Peter C.

    2012-01-01

    Objectives-A major pathologic finding in patients with idiopathic carpal tunnel syndrome is noninflammatory fibrosis and thickening of the subsynovial connective tissue. The objective of this study was to determine the ability of sonography to depict this thickening by comparing subsynovial connecti

  16. Pharmacokinetics of connective tissue growth factor : implications for its use as biomarker

    NARCIS (Netherlands)

    Gerritsen, K.G.F.

    2012-01-01

    Fibrosis represents the common final pathway of many chronic diseases including inflammatory, ischemic and metabolic disorders. There is great need for non-invasive biomarkers that reflect activity of the fibrogenic process and can help predict progression. Connective tissue growth factor (CTGF) see

  17. 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

    2005-01-01

    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 t

  18. Effect of GFR on plasma N-terminal connective tissue growth factor (CTGF) concentrations.

    NARCIS (Netherlands)

    Gerritsen, K.G.; Abrahams, A.C.; Peters, H.P.E.; Nguyen, T.Q.; Koeners, M.P.; Hoedt, C.H. den; Dendooven, A.; Dorpel, M.A. van den; Blankestijn, P.J.; Wetzels, J.F.M.; Joles, J.A.; Goldschmeding, R.; Kok, R.J.

    2012-01-01

    BACKGROUND: Connective tissue growth factor (CTGF) has a key role in the pathogenesis of renal and cardiac fibrosis. Its amino-terminal fragment (N-CTGF), the predominant form of CTGF detected in plasma, has a molecular weight in the middle molecular range (18 kDa). However, it is unknown whether N-

  19. Expression of Connective Tissue Growth Factor in Male Breast Cancer : Clinicopathologic Correlations and Prognostic Value

    NARCIS (Netherlands)

    Lacle, Miangela M.; van Diest, Paul J.; Goldschmeding, Roel; van der Wall, Elsken; Nguyen, Tri Q.

    2015-01-01

    Connective tissue growth factor (CTGF/CCN2) is a member of the CCN family of secreted proteins that are believed to play an important role in the development of neoplasia. In particular, CTGF has been reported to play an important role in mammary tumorigenesis and to have prognostic value in female

  20. 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.

  1. Morphometric Analysis of Nonsclerosed Glomeruli Size and Connective Tissue Content during the Aging Process

    Directory of Open Access Journals (Sweden)

    Vesna R. Stojanović

    2012-01-01

    Full Text Available Number of sclerotic glomeruli increases during the aging process. Consequently, majority of remained nonsclerosed glomeruli become hypertrophic and some of them sclerotic, too. The aim of this study was to quantify the size and connective tissue content of nonsclerosed glomeruli and to evaluate the percentage of hypertrophic ones in examined human cases during the aging. Material was right kidney's tissue of 30 cadavers obtained during routine autopsies. Cadavers were without previously diagnosed kidney disease, diabetes, hypertension, or any other systemic disease. Tissue specimens were routinely prepared for histological and morphometric analysis. Images of the histological slices were analyzed and captured under 400x magnification with digital camera. Further they were morphometrically and statistically analyzed with ImageJ and NCSS-PASS software. Multiple and linear regression of obtained morphometric parameters showed significant increase of glomerular connective tissue area and percentage. Cluster analysis showed the presence of two types of glomeruli. Second type was characterized with significantly larger size, connective tissue content, and significantly lower cellularity, in relation to the first type. Such glomeruli might be considered as hypertrophic. First type of glomeruli was predominant in younger cases, while second type of glomeruli was predominant in cases older than 55 years.

  2. Expanding the clinical and genetic heterogeneity of hereditary disorders of connective tissue.

    Science.gov (United States)

    Alazami, Anas M; Al-Qattan, Sarah M; Faqeih, Eissa; Alhashem, Amal; Alshammari, Muneera; Alzahrani, Fatema; Al-Dosari, Mohammed S; Patel, Nisha; Alsagheir, Afaf; Binabbas, Bassam; Alzaidan, Hamad; Alsiddiky, Abdulmonem; Alharbi, Nasser; Alfadhel, Majid; Kentab, Amal; Daza, Riza M; Kircher, Martin; Shendure, Jay; Hashem, Mais; Alshahrani, Saif; Rahbeeni, Zuhair; Khalifa, Ola; Shaheen, Ranad; Alkuraya, Fowzan S

    2016-05-01

    Ehlers-Danlos syndrome (EDS) describes a group of clinical entities in which the connective tissue, primarily that of the skin, joint and vessels, is abnormal, although the resulting clinical manifestations can vary widely between the different historical subtypes. Many cases of hereditary disorders of connective tissue that do not seem to fit these historical subtypes exist. The aim of this study is to describe a large series of patients with inherited connective tissue disorders evaluated by our clinical genetics service and for whom a likely causal variant was identified. In addition to clinical phenotyping, patients underwent various genetic tests including molecular karyotyping, candidate gene analysis, autozygome analysis, and whole-exome and whole-genome sequencing as appropriate. We describe a cohort of 69 individuals representing 40 families, all referred because of suspicion of an inherited connective tissue disorder by their primary physician. Molecular lesions included variants in the previously published disease genes B3GALT6, GORAB, ZNF469, B3GAT3, ALDH18A1, FKBP14, PYCR1, CHST14 and SPARC with interesting variations on the published clinical phenotypes. We also describe the first recessive EDS-like condition to be caused by a recessive COL1A1 variant. In addition, exome capture in a familial case identified a homozygous truncating variant in a novel and compelling candidate gene, AEBP1. Finally, we also describe a distinct novel clinical syndrome of cutis laxa and marked facial features and propose ATP6V1E1 and ATP6V0D2 (two subunits of vacuolar ATPase) as likely candidate genes based on whole-genome and whole-exome sequencing of the two families with this new clinical entity. Our study expands the clinical spectrum of hereditary disorders of connective tissue and adds three novel candidate genes including two that are associated with a highly distinct syndrome.

  3. Tensile properties, collagen content, and crosslinks in connective tissues of the immature knee joint.

    Directory of Open Access Journals (Sweden)

    Sriram V Eleswarapu

    Full Text Available BACKGROUND: The major connective tissues of the knee joint act in concert during locomotion to provide joint stability, smooth articulation, shock absorption, and distribution of mechanical stresses. These functions are largely conferred by the intrinsic material properties of the tissues, which are in turn determined by biochemical composition. A thorough understanding of the structure-function relationships of the connective tissues of the knee joint is needed to provide design parameters for efforts in tissue engineering. METHODOLOGY/PRINCIPAL FINDINGS: The objective of this study was to perform a comprehensive characterization of the tensile properties, collagen content, and pyridinoline crosslink abundance of condylar cartilage, patellar cartilage, medial and lateral menisci, cranial and caudal cruciate ligaments (analogous to anterior and posterior cruciate ligaments in humans, respectively, medial and lateral collateral ligaments, and patellar ligament from immature bovine calves. Tensile stiffness and strength were greatest in the menisci and patellar ligament, and lowest in the hyaline cartilages and cruciate ligaments; these tensile results reflected trends in collagen content. Pyridinoline crosslinks were found in every tissue despite the relative immaturity of the joints, and significant differences were observed among tissues. Notably, for the cruciate ligaments and patellar ligament, crosslink density appeared more important in determining tensile stiffness than collagen content. CONCLUSIONS/SIGNIFICANCE: To our knowledge, this study is the first to examine tensile properties, collagen content, and pyridinoline crosslink abundance in a direct head-to-head comparison among all of the major connective tissues of the knee. This is also the first study to report results for pyridinoline crosslink density that suggest its preferential role over collagen in determining tensile stiffness for certain tissues.

  4. 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.

  5. Subepithelial connective tissue graft for root coverage: clinical case reports and histologic evaluation.

    Science.gov (United States)

    Roman, Alexandra; Câmpian, R; Domşa, I; Soancă, Andrada; Gocan, H

    2010-01-01

    If the clinical goal of the periodontal plastic surgery is the complete root coverage of gingival recessions, then the microscopically goal standard is to obtain a true periodontal regeneration. Only the histological examination can reveal cellular events unrolled into the grafted tissue-root surface interface and the nature of the clinically observed attachment. To our knowledge, there are no studies that obtained the biopsies of grafted tissues from humans, in vivo, and so, the aim of the present study was to develop such a method, using a bone marrow biopsy needle. Two patients with gingival recessions were treated with coronally advanced flap and subepithelial connective tissue graft, and the clinical and histological results were observed. Complete root coverage was obtained for both cases. Clinically, the grafted tissues seemed to be attached to the root surfaces. The histological findings revealed dense grafted tissues, providing long-term stability of the area. No ligament or bone, characteristic for periodontal regeneration were observed. However, no sign of healing characterized by a long junctional epithelium was observed either. This indicated that the healing that occurred in our cases was a long connective tissue attachment, which has been shown to be stable over time. However, even if the method we proposed is not invasive, it is very difficult to convince the patient to accept a biopsy elevation once the exposed root surface was covered.

  6. Mast cells and basophils in cutaneous immune responses.

    Science.gov (United States)

    Otsuka, A; Kabashima, K

    2015-02-01

    Mast cells and basophils share some functions in common and are generally associated with T helper 2 (Th2) immune responses, but taking basophils as surrogate cells for mast cell research or vice versa for several decades is problematic. Thus far, their in vitro functions have been well studied, but their in vivo functions remained poorly understood. New research tools for their functional analysis in vivo have revealed previously unrecognized roles for mast cells and basophils in several skin disorders. Newly developed mast cell-deficient mice provided evidence that mast cells initiate contact hypersensitivity via activating dendritic cells. In addition, studies using basophil-deficient mice have revealed that basophils were responsible for cutaneous Th2 skewing to haptens and peptide antigens but not to protein antigens. Moreover, human basophils infiltrate different skin lesions and have been implicated in the pathogenesis of skin diseases ranging from atopic dermatitis to autoimmune diseases. In this review, we will discuss the recent advances related to mast cells and basophils in human and murine cutaneous immune responses.

  7. Aberrations of dermal connective tissue in patients with cervical artery dissection (sCAD).

    Science.gov (United States)

    Uhlig, Phillip; Bruckner, Peter; Dittrich, Ralf; Ringelstein, E Bernd; Kuhlenbäumer, Gregor; Hansen, Uwe

    2008-03-01

    Spontaneous cervical artery dissection (sCAD) is a common cause of stroke in patients below 55 years of age. Hereditary connective tissue disorders, including Ehlers-Danlos syndrome type IV, have been associated with sCAD and suprastructural abnormalities of both collagen fibrils and elastic fibers have been found by transmission electron microscopy in the dermis of about 50% of sCAD patients. Here, we investigated dermal connective tissue abnormalities using a novel method. Transmission and immunogold electron microscopy were used to study mechanically generated fragments of dermal matrix suprastructures, in particular collagen fibrils. Analysis of dermal tissue of sCAD patients revealed structurally abnormal collagen fibrils with irregularly contoured surfaces and increased diameters, often associated with a faint or absent banding pattern. Interestingly, only a small number of fibrils displayed short abnormal sections along the length of the fibril. Collagens I and III were present in normal as well as abnormal sections of the fibrils.However, immunogold labeling for the two proteins was strongly increased in abnormal sections.A systematic blinded investigation of skin biopsies of 31 sCAD patients and 17 controls revealed abnormal collagen fibrils in 7 sCAD patients but none of the controls. We conclude that approximately 20% of sCAD patients show collagen fibril alterations, establishing a promising basis for further investigation of connective tissue aberrations in skin biopsies of sCAD patients.

  8. Basophilic deposits on the cupula: preliminary findings describing the problems involved in studies regarding the incidence of basophilic deposits on the cupula.

    Science.gov (United States)

    Naganuma, H; Kohut, R I; Ryu, J H; Tokumasu, K; Okamoto, M; Fujino, A; Hoshino, I; Arai, M

    1996-01-01

    In this study, the possibility of whether basophilic deposits adhered to the cupulas in the semicircular canals was investigated histologically. Results indicated that basophilic deposits were present in all three cupulas of the semicircular canals. The overall incidence of basophilic deposits in the superior, lateral and posterior semicircular canal cupulas was 26%, 41% and 37%, respectively. The incidence of basophilic deposits bound to the cupulas increased with age. The possible origin of these basophilic deposits on the cupulas and the increased incidence of basophilic deposits with increasing age are discussed.

  9. Clinical evaluation of subepithelial connective tissue graft and guided tissue regeneration for treatment of Miller's class 1 gingival recession: comparative, split mouth, six months study

    OpenAIRE

    Trivedi, Sakshee R.; Bhavsar, Neeta V.; Dulani, Kirti; Trivedi, Rahul

    2014-01-01

    Objectives: The present study aims to clinically compare and evaluate subepithelial connective tissue graft and the GTR based root coverage in treatment of Miller’s Class I gingival recession. Study Design: 30 patients with at least one pair of Miller’s Class I gingival recession were treated either with Subepithelial connective tissue graft (Group A) or Guided tissue regeneration (Group B). Clinical parameters monitored included recession RD, width of keratinized gingiva (KG), probing depth ...

  10. Comparing dynamic connective tissue in echinoderms and sponges: morphological and mechanical aspects and environmental sensitivity.

    Science.gov (United States)

    Sugni, Michela; Fassini, Dario; Barbaglio, Alice; Biressi, Anna; Di Benedetto, Cristiano; Tricarico, Serena; Bonasoro, Francesco; Wilkie, Iain C; Candia Carnevali, Maria Daniela

    2014-02-01

    Echinoderms and sponges share a unique feature that helps them face predators and other environmental pressures. They both possess collagenous tissues with adaptable viscoelastic properties. In terms of morphology these structures are typical connective tissues containing collagen fibrils, fibroblast- and fibroclast-like cells, as well as unusual components such as, in echinoderms, neurosecretory-like cells that receive motor innervation. The mechanisms underpinning the adaptability of these tissues are not completely understood. Biomechanical changes can lead to an abrupt increase in stiffness (increasing protection against predation) or to the detachment of body parts (in response to a predator or to adverse environmental conditions) that are regenerated. Apart from these advantages, the responsiveness of echinoderm and sponge collagenous tissues to ionic composition and temperature makes them potentially vulnerable to global environmental changes.

  11. 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.

  12. Signaling transduction pathways involved in basophil adhesion and histamine release

    DEFF Research Database (Denmark)

    Sha, Quan; Poulsen, Lars K.; Gerwien, Jens

    2006-01-01

    Little is known about basophil with respect to the different signaling transduction pathways involved in spontaneous, cytokine or anti-IgE induced adhesion and how this compares to IgE-dependent and IgE-independent mediator secretion. The purpose of the present study was to investigate the roles ...... of beta1 and beta2 integrins in basophil adhesion as well as hosphatidylinositol 3-kinase (PI3K), src-kinases and extracellular signal regulated kinase (ERK) 1/2 in basophil adhesion and histamine release (HR)....

  13. Signaling transduction pathways involved in basophil adhesion and histamine release

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Background Little is known about basophil with respect to the different signaling transduction pathways involved in spontaneous, cytokine or anti-IgE induced adhesion and how this compares to IgE-dependent and IgE-independent mediator secretion. The purpose of the present study was to investigate the roles of β1 andβ2 integrins in basophil adhesion as well as hosphatidylinositol 3-kinase (PI3K), src-kinases and extracellular signal regulated kinase (ERK)1/2 in basophil adhesion and histamine release (HR). Methods Basophils (purity of 10%-50%) were preincubated with anti-CD29 or anti-CD18 blocking antibodies before used for adhesion study. Basophils were preincubated with the pharmacological inhibitors wortmannin, PP1, PD98059 before used for adhesion and HR study. Cell adherence to bovine serum albumin (BSA) or fibronectin (Fn) was monitored using cell associated histamine as a basophil marker and the histamine was measured by the glass fiber assay.Results Basophil spontaneous adhesion to Fn was inhibited by anti-CD29. Interleukin (IL)-3, granulocyte/macrophage colony stimulating factor (GM-CSF) induced adhesion to BSA was inhibited by anti-CD18. Wortmannin at 1 μmol/L and PP1 at 20 μmol/L strongly interfered with, whereas PD98059 at 50 μmol/L weakly inhibited basophil spontaneous adhesion to Fn. One μmol/L wortmannin strongly inhibited IL-3, IL-5, GM-CSF and anti-IgE induced adhesion to BSA. PP1 at 20 μmol/L partly inhibited anti-IgE induced adhesion. Fifty μmol/L PD98059 marginally inhibited IL-5, weakly inhibited anti-IgE, partly inhibited GM-CSF induced adhesion. Wortmannin, PP1 and PD98059 inhibited anti-IgE (1:100 or 1:1000) induced basophil HR in a dose dependent manner. They inhibited calcium ionophore A23187 (10 μmol/L, 5 μmol/L) induced basophil HR in a dose dependent manner, but to different extend with PP1 being the most efficient.Conclusions Basophil spontaneous adhesion to Fn is mediated by β1-integrins whereas cytokine induced adhesion

  14. Diurnal variation of connective tissue metabolites in early and long-standing rheumatoid arthritis and in healthy individuals

    DEFF Research Database (Denmark)

    Lottenburger, T; Junker, P; Hørslev-Petersen, K

    2011-01-01

    To study the circadian variability of circulating connective tissue metabolites in patients with very early (VERA) and long-standing rheumatoid arthritis (LRA) and in healthy control individuals.......To study the circadian variability of circulating connective tissue metabolites in patients with very early (VERA) and long-standing rheumatoid arthritis (LRA) and in healthy control individuals....

  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. De novo engineering of reticular connective tissue in vivo by silk fibroin nonwoven materials.

    Science.gov (United States)

    Dal Pra, Ilaria; Freddi, Giuliano; Minic, Jasminka; Chiarini, Anna; Armato, Ubaldo

    2005-05-01

    Biologically tolerated biomaterials are the focus of intense research. In this work, we examined the biocompatibility of three-dimensional (3D) nonwovens of sericin-deprived, Bombyx mori silk fibroin (SF) in beta-sheet form implanted into the subcutaneous tissue of C57BL6 mice, using sham-operated mice as controls. Both groups of mice similarly healed with no residual problem. Macroarray analysis showed that an early (day 3) transient expression of macrophage migration inhibitory factor (MIF) mRNA, but not of the mRNAs encoding for 22 additional proinflammatory cytokines, occurred solely at SF-grafted places, where no remarkable infiltration of macrophages or lymphocytes subsequently happened. Even an enduring moderate increase in total cytokeratins without epidermal hyperkeratosis and a transient (days 10-15) upsurge of vimentin occurred exclusively at SF-grafted sites, whose content of collagen type-I, after a delayed (day 15) rise, ultimately fell considerably under that proper of sham-operated places. By day 180, the interstices amid and surfaces of the SF chords, which had not been appreciably biodegraded, were crammed with a newly produced tissue histologically akin to a vascularized reticular connective tissue, while some macrophages but no lymphocytic infiltrates or fibrous capsules occurred in the adjoining tissues. Therefore, SF nonwovens may be excellent candidates for clinical applications since they both enjoy a long-lasting biocompatibility, inducing a quite mild foreign body response, but no fibrosis, and efficiently guide reticular connective tissue engineering.

  17. Application of exogenous enzymes to beef muscle of high and low-connective tissue.

    Science.gov (United States)

    Sullivan, G A; Calkins, C R

    2010-08-01

    Exogenous enzymes tenderize meat through proteolysis. Triceps brachii and Supraspinatus were randomly assigned to the seven enzyme treatments, papain, ficin, bromelain, homogenized fresh ginger, Bacillus subtilis protease, and two Aspergillus oryzae proteases or control to determine the extent of tenderization (Warner-Bratzler shear and sensory evaluation) and mode of action (myofibrillar or collagen degradation). Sensory evaluation showed improvement (P<0.0009) for tenderness and connective tissue component and all except ginger had a lower shear force than the control (P<0.003). Ginger produced more off-flavor than all other treatments (P<0.0001). Only papain increased soluble collagen (P<0.0001). Control samples were only significantly less than ficin for water soluble (P=0.0002) and A. oryzae concentrate for salt soluble proteins (P=0.0148). All enzyme treatments can increase tenderness via myofibrillar and collagenous protein degradation with no difference among high and low-connective tissue muscles.

  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. 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.

  1. 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.

  2. Nail changes in connective tissue diseases: a study of 39 cases

    OpenAIRE

    Elmansour, Imane; Chiheb, Soumia; Benchikhi, Hakima

    2014-01-01

    The objective is to identify nail unit changes associated with connective tissue diseases (CTD) and evaluate their frequency. We carried a prospective study between March 2012 and March2013 in our department. All patients with CTD were included. A clinical examination of the fingernails was done by the same dermatologist. Nail features were noted and classified and photos taken. Thirty nine patients were enrolled including: 16 systemic sclerosis, 14 lupus erythematosus (SLE), 8 dermatomyositi...

  3. Connective Tissue Growth Factor (CTGF) as a Regulator of Lactogenic Differentiation

    Science.gov (United States)

    2009-06-09

    and connective tissue growth factor at different stages of diabetic nephropathy and their interdependent roles in mesangial response to diabetic ...pituitary gland, such as growth hormone (GH), also play roles in ductal morphogenesis during puberty. In ovariectomized mice, treatment with estrogen...restores the TEB formation that had been lost (52), while the treatment with growth hormone rescues the TEB formation in hypophysectomized mice (136

  4. Cellular and molecular responses of periodontal connective tissue cells to Actinobacillus actinomycetemcomitans cytolethal distending toxin

    OpenAIRE

    2004-01-01

    Actinobacillus actinomycetemcomitans is present in elevated proportions and numbers in dental bacterial biofilms of patients with localized aggressive periodontitis. This variant of periodontal disease, occurring in adolescents and young adults, is characterized by rapid and severe destruction of the connective tissues and bone supporting the teeth, eventually culminating in tooth loss. The cytolethal distending toxin (Cdt) is a newly discovered bacterial protein toxin, uniquely present in A....

  5. The expression of CD123 can decrease with basophil activation: implications for the gating strategy of the basophil activation test

    OpenAIRE

    Santos, Alexandra F.; Bécares, Natalia; Stephens, Alick; Turcanu, Victor; Lack, Gideon

    2016-01-01

    Background Basophil activation test (BAT) reproduces IgE-mediated allergic reactions in vitro and has been used as a diagnostic test. Different markers can be used to identify basophils in whole blood and have implications for the outcome of the test. We aimed to assess changes in the expression of CD123 and HLA-DR following basophil activation and to select the best gating strategy for BAT using these markers. Methods BAT was performed in whole blood from 116 children. Peanut extract, anti-I...

  6. From detecting astrocyte connectivity to uncovering drug effects in living tissues

    CERN Document Server

    Pires, Marcelo; Vaz, Sandra; Sebastião, Ana; Lind, Pedro G

    2013-01-01

    We introduce a simple procedure of multivariate signal analysis to uncover the connectivity structure among cells composing a living tissue and describe how to apply it for extracting insight on the effect of drugs in the tissue. The procedure is based in the covariance matrix of time resolved activity signals. By determining the time-lag that maximizes covariance one derives the weight of the corresponding connection between cells. Introducing simple constraints, it is possible to conclude if pairs of cells are connected or not and in which direction. After testing the method against synthetic data we apply it to study propagation of $Ca^{2+}$ waves in astrocytes, with the aim of uncovering the cell connectivity structure. Our method shows to be particularly suited for this type of networking signal propagation where signals are pulse-like and have short time-delays, and is shown to be superior to standard methods, namely a multivariate Granger algorithm. Finally, based the statistical analysis of the connec...

  7. Mechano-sensing and mechano-reaction of soft connective tissue cells

    Science.gov (United States)

    Lambert, Ch. A.; Nusgens, B. V.; Lapière, Ch. M.

    One main function of the connective tissues is to provide cells with a mechanically resistant attachment support required for survival, division and differentiation. All cells contain membrane-anchored attachment proteins able to recognize specific chemical motifs in the extracellular macromolecules forming the supporting scaffold, made of various types of collagen, adhesive glycoproteins, elastin, proteoglycans, etc... These cell-matrix interactions are mainly mediated by re ceptors of the integrins family, heterodimeric molecules made of an extracellular domain connected through a transmembrane sequence to an intracytoplasmic tail. Upon recognition of the extracellular ligand, the clustering and activation of the integrins result in the recruitment of a complex of proteins and formation of the focal adhesion plaque, containing both cytoskeletal and catalytic signaling molecules. Activation results in polymerization of actin and formation of stress fibers. These structures establish a physical link between the extracellular matrix components and the cytoskeleton through the integrins providing a continuous path acting as a mechanotransducer. This connection is used by the cells to perform their mechanical functions as adhesion, migration and traction. In vitro experimental models using fibroblasts in a collagen gel demonstrate that cells are in mechanical equilibrium with their support which regulates their replicative and biosynthetic phenotype. The present review discusses the molecular structures operating in the transmission of the mechanical messages from the support to the connective tissue cells, and their effect on the cellular machinery. We present arguments for investigating these mechanisms in understanding the perception of reduced gravity and the resulting reaction leading to microgravity induced pathologies.

  8. Different types of connective tissue alterations associated with cervical artery dissections.

    Science.gov (United States)

    Hausser, Ingrid; Müller, Uta; Engelter, Stefan; Lyrer, Philippe; Pezzini, Alessandro; Padovani, Alessandro; Moormann, Birgit; Busse, Otto; Weber, Ralf; Brandt, Tobias; Grond-Ginsbach, Caspar

    2004-06-01

    This study describes the technical handling and the diagnostic evaluation of skin biopsies in order to standardize the assessment of the delicate morphologic abnormalities that are found in patients with spontaneous cervical artery dissections (sCAD). Skin biopsies from 126 patients with sCAD and from 29 healthy relatives were analyzed. The morphology of the connective tissue was normal in 54 patients with sCAD (43%) and aberrant in 72 patients with sCAD (57%). These latter patients were classified into three groups: in 43 patients, we repeatedly observed composite collagen fibrils and elastic fibers with fragmentation and minicalcifications. In 13 further patients, the dermis was significantly thinner than in healthy subjects. The collagen fibers contained fibrils with highly variable diameters. In a third group of 16 sCAD patients, the abnormalities were restricted to the elastic fibers (with fragmentation and minicalcifications) without significant alterations in the morphology of the collagen fibrils. The finding of different morphologic classes of aberrations among patients suggests that the connective tissue defects are genetically heterogeneous. The segregation of the connective tissue phenotype in three families suggested an autosomal dominant pattern of inheritance.

  9. Summers' technique modification for sinus floor elevation using a connective tissue graft. A case report.

    Science.gov (United States)

    Pontes, Fernando Salimon Ribeiro Ana Emília Farias; Zuza, Elizangela Partata; de Toledo, Benedicto Egbert Corrêa

    2010-01-01

    The sinus floor elevation technique with Summers' osteotome is simpler and less invasive than access through the lateral wall of the sinus; however, it is susceptible to a higher level of sinusal membrane rupture. The objective of the present study was to display a modification of the osteotomy technique by connective tissue interposition in order to weaken the impact of sinus cortical fracture, and therefore prevent perforations in the sinusal membrane. A case is reported in which a patient presented with an absent tooth #4 for osseointegrated implant rehabilitation. Maxillary sinus elevation was required to perform the procedure. Initially, the flap was raised and the receptor site was prepared with a sequence of burs, without disrupting cortical bone. In order to weaken the fracture impact with the osteotome, a connective tissue graft was interposed to allow access to the sinus. Clinically, a satisfactory primary locking was obtained with torque greater than 50 Ncm. Through radiographic evaluation, good bone filling was observed immediately after surgery, with maxillary sinus wall elevation without membrane rupture. Two years after the initial procedure, a 5.3 mm increase in bone extension formed in contact with implant distal surface was observed. Thus, the osteotomy technique modification with connective tissue interposition was successful, both clinically and radiographically, showing an image suggesting long-term osseous formation.

  10. [Clinical and serologic course of patients with mixed connective tissue disease].

    Science.gov (United States)

    López-Longo, F J; Fernández, J; Monteagudo, I; Rodríguez-Mahou, M; Sánchez-Atrio, A I; Pérez, T; Escalona, M; González, C M; Lapointe, N; Carreño, L

    1994-09-01

    The so called mixed connective tissue disease (MCTD), continues to be a controversial entity, while some authors considered it a good characterized disease, others think that is an undifferentiated connective tissue disease. OBJECTIVE. To analyse the clinical and serological evolution of a group of patients diagnosed of MCTD, with particular consideration to the meaning of anti-nRNP and anti-Sm antibodies. METHOD. We have studied 20 patients diagnosed of MCTD and 112 with systemic lupus erythematosus (SLE). Anti-nRNP and anti-Sm antibodies were detected through counter immunoelectrophoresis, immunoblotting and ELISA. RESULTS. After an average time of evolution of 10 years, 70% (14/20) of the patients diagnosed of MCTD fulfill criteria for SLE (6 cases), scleroderma (6 cases) or polymyositis (2 cases). Anti-nRNP response is persistent, directed mainly against the 70 Kd and A-nRNP polypeptides and qualitatively higher in MCTD in SLE (absorbencies 2.64 vs 1.25. The immunoblotting test detected anti-Sm antibodies in 5 patients (25%) and ELISA test in 14 (70%). CONCLUSIONS. Clinical and serological evolution suggest that MCTD is an undifferentiated connective tissue disease. Anti-nRNP antibodies are characteristic, although anti-Sm antibodies can be detected with ELISA regardless whether on not patients fulfill SLE criteria.

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

    Science.gov (United States)

    Navarro-Gonzálvez, José Antonio; Rodríguez-Lozano, Beatriz

    2017-01-01

    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. PMID:28210273

  12. 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.

  13. Transient inhibition of connective tissue infiltration and collagen deposition into porous poly(lactic-co-glycolic acid) discs.

    Science.gov (United States)

    Love, Ryan J; Jones, Kim S

    2013-12-01

    Connective tissue rapidly proliferates on and around biomaterials implanted in vivo, which impairs the function of the engineered tissues, biosensors, and devices. Glucocorticoids can be utilized to suppress tissue ingrowth, but can only be used for a limited time because they nonselectively arrest cell proliferation in the local environment. The present study examined use of a prolyl-4-hydroxylase inhibitor, 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (1,4-DPCA), to suppress connective tissue ingrowth in porous PLGA discs implanted in the peritoneal cavity for 28 days. The prolyl-4-hydroxylase inhibitor was found to be effective at inhibiting collagen deposition within and on the outer surface of the disc, and also limited connective tissue ingrowth, but not to the extent of glucocorticoid inhibition. Finally, it was discovered that 1,4-DPCA suppressed Scavenger Receptor A expression on a macrophage-like cell culture, which may account for the drug's ability to limit connective tissue ingrowth in vivo.

  14. Repair of dense connective tissues via biomaterial-mediated matrix reprogramming of the wound interface.

    Science.gov (United States)

    Qu, Feini; Pintauro, Michael P; Haughan, Joanne E; Henning, Elizabeth A; Esterhai, John L; Schaer, Thomas P; Mauck, Robert L; Fisher, Matthew B

    2015-01-01

    Repair of dense connective tissues in adults is limited by their intrinsic hypocellularity and is exacerbated by a dense extracellular matrix (ECM) that impedes cellular migration to and local proliferation at the wound site. Conversely, healing in fetal tissues occurs due in part to an environment conducive to cell mobility and division. Here, we investigated whether the application of a degradative enzyme, collagenase, could reprogram the adult wound margin to a more fetal-like state, and thus abrogate the biophysical impediments that hinder migration and proliferation. We tested this concept using the knee meniscus, a commonly injured structure for which few regenerative approaches exist. To focus delivery and degradation to the wound interface, we developed a system in which collagenase was stored inside poly(ethylene oxide) (PEO) electrospun nanofibers and released upon hydration. Through a series of in vitro and in vivo studies, our findings show that partial digestion of the wound interface improves repair by creating a more compliant and porous microenvironment that expedites cell migration to and/or proliferation at the wound margin. This innovative approach of targeted manipulation of the wound interface, focused on removing the naturally occurring barriers to adult tissue repair, may find widespread application in the treatment of injuries to a variety of dense connective tissues.

  15. High elastic modulus nanoparticles: a novel tool for subfailure connective tissue matrix damage.

    Science.gov (United States)

    Empson, Yvonne M; Ekwueme, Emmanuel C; Hong, Jung K; Paynter, Danielle M; Kwansa, Albert L; Brown, Chalmers; Pekkanen, Allison M; Roman, Maren; Rylander, Nichole M; Brolinson, Gunnar P; Freeman, Joseph W

    2014-09-01

    Subfailure matrix injuries such as sprains and strains account for a considerable portion of ligament and tendon pathologies. In addition to the lack of a robust biological healing response, these types of injuries are often characterized by seriously diminished matrix biomechanics. Recent work has shown nanosized particles, such as nanocarbons and nanocellulose, to be effective in modulating cell and biological matrix responses for biomedical applications. In this article, we investigate the feasibility and effect of using high stiffness nanostructures of varying size and shape as nanofillers to mechanically reinforce damaged soft tissue matrices. To this end, nanoparticles (NPs) were characterized using atomic force microscopy and dynamic light scattering techniques. Next, we used a uniaxial tensile injury model to test connective tissue (porcine skin and tendon) biomechanical response to NP injections. After injection into damaged skin and tendon specimens, the NPs, more notably nanocarbons in skin, led to an increase in elastic moduli and yield strength. Furthermore, rat primary patella tendon fibroblast cell activity evaluated using the metabolic water soluble tetrazolium salt assay showed no cytotoxicity of the NPs studied, instead after 21 days nanocellulose-treated tenocytes exhibited significantly higher cell activity when compared with nontreated control tenocytes. Dispersion of nanocarbons injected by solution into tendon tissue was investigated through histologic studies, revealing effective dispersion and infiltration in the treated region. Such results suggest that these high modulus NPs could be used as a tool for damaged connective tissue repair.

  16. Alveolar Ridge Contouring with Free Connective Tissue Graft at Implant Placement: A 5-Year Consecutive Clinical Study.

    Science.gov (United States)

    Hanser, Thomas; Khoury, Fouad

    2016-01-01

    This study evaluated volume stability after alveolar ridge contouring with free connective tissue grafts at implant placement in single-tooth gaps. A total of 52 single-tooth gaps with labial volume deficiencies in the maxilla (incisors, canines, and premolars) were consecutively treated with implants and concomitant free palatal connective tissue grafts in 46 patients between 2006 and 2009. Implants had to be covered with at least 2 mm peri-implant local bone after insertion. At implant placement, a free connective tissue graft from the palate was fixed inside a labial split-thickness flap to form an existing concave buccal alveolar ridge contour due to tissue volume deficiency into a convex shape. Standardized volumetric measurements of the labial alveolar contour using a template were evaluated before connective tissue grafting and at 2 weeks, 1 year, and 5 years after implantprosthetic incorporation. Tissue volume had increased significantly (P tissue contour of the implant before connective tissue grafting to baseline (2 weeks after implant-prosthetic incorporation). Statistically, 50% of the reference points (P > .05) kept their volume from baseline to 1 year after prosthetic incorporation and from baseline to 5 years after prosthetic incorporation, respectively, whereas reference points located within the area of the implant sulcus showed a significant (P connective tissue grafting appears to be an appropriate long-term means to contour preexisting buccal alveolar volume deficiencies in single implants.

  17. Improving prosthetic prognosis by connective tissue ridge augmentation of alveolar ridge

    Directory of Open Access Journals (Sweden)

    Mishra Niraj

    2010-01-01

    Full Text Available The contour of edentulous ridge should be carefully evaluated before a fixed partial denture is undertaken. The ideal ridge height and width allows placement of a natural looking pontic which facilitates maintenance of plaque-free environment. The localized alveolar ridge defect refers to the volumetric deficit of the limited extent of bone and soft tissue within the alveolar process. Such type of ridge defects can be corrected by surgical ridge augmentation that can be accomplished by the addition of either soft or hard tissues. This article describes a procedure of surgical connective tissue augmentation of a localized deficient alveolar ridge in the maxilla, followed by fixed partial denture, enhancing the esthetics, function and health.

  18. Improving prosthetic prognosis by connective tissue ridge augmentation of alveolar ridge.

    Science.gov (United States)

    Mishra, Niraj; Singh, Balendra P; Rao, Jitendra; Rastogi, Pavitra

    2010-01-01

    The contour of edentulous ridge should be carefully evaluated before a fixed partial denture is undertaken. The ideal ridge height and width allows placement of a natural looking pontic which facilitates maintenance of plaque-free environment. The localized alveolar ridge defect refers to the volumetric deficit of the limited extent of bone and soft tissue within the alveolar process. Such type of ridge defects can be corrected by surgical ridge augmentation that can be accomplished by the addition of either soft or hard tissues. This article describes a procedure of surgical connective tissue augmentation of a localized deficient alveolar ridge in the maxilla, followed by fixed partial denture, enhancing the esthetics, function and health.

  19. [Human basophil degranulation test. Results of a modified technic (I)].

    Science.gov (United States)

    Román Pérez, F; Berlanga Cortés, J A; Urquiă, M; Guerra Pasadas, F; Peña Martínez, J

    1986-01-01

    The degranulation of human basophils towards antigenic substances, to which they must be previously sensitized as a result of the antigen-antibody union at the membrane level, is a phenomenon that has an important application complementing diagnosis of diseases mediated by the Gell and Coombs classification of Type I Hypersensitivity, on which the principle of Human Basophils Degranulation Test (HBDT) was based. An essential requirement is to be able to collect an adequate quantity of basophils, as well as the visualization by means of a technique of convenient stain. In this work, we show a modified HBDT technique for basophil granulocytes staining. A total of 33 HBDT was carried out on patients sensitive to grass pollen and/or Olea europea pollen and/or D. pteronyssinus, and as controls, HBDT was done on healthy individuals with negative clinical history. Basophil enrichemnt from the circulating blood sample was done by means of centrifugation in Percoll density gradients of 1072, 1076, 1080 and 1082, and we obtained a higher number of basophils with a density of 1080 at 400 Xg for 30 minutes. The cellular bottom was resuspended in 600 microliters of PBS. We employed lyophilized antigenic extracts from grass pollen, Olea europea and D. pteronyssinus, employing weight/volume concentration of 10(-4), 10(-5), 10(-6) and 10(-7). The optimum dilutions were 10(-5) for grass pollen and D. pteronyssinus.

  20. The effect of connective tissue material uncertainties on knee joint mechanics under isolated loading conditions.

    Science.gov (United States)

    Dhaher, Yasin Y; Kwon, Tae-Hyun; Barry, Megan

    2010-12-01

    Although variability in connective tissue parameters is widely reported and recognized, systematic examination of the effect of such parametric uncertainties on predictions derived from a full anatomical joint model is lacking. As such, a sensitivity analysis was performed to consider the behavior of a three-dimensional, non-linear, finite element knee model with connective tissue material parameters that varied within a given interval. The model included the coupled mechanics of the tibio-femoral and patello-femoral degrees of freedom. Seven primary connective tissues modeled as non-linear continua, articular cartilages described by a linear elastic model, and menisci modeled as transverse isotropic elastic materials were included. In this study, a multi-factorial global sensitivity analysis is proposed, which can detect the contribution of influential material parameters while maintaining the potential effect of parametric interactions. To illustrate the effect of material uncertainties on model predictions, exemplar loading conditions reported in a number of isolated experimental paradigms were used. Our findings illustrated that the inclusion of material uncertainties in a coupled tibio-femoral and patello-femoral model reveals biomechanical interactions that otherwise would remain unknown. For example, our analysis revealed that the effect of anterior cruciate ligament parameter variations on the patello-femoral kinematic and kinetic response sensitivities was significantly larger, over a range of flexion angles, when compared to variations associated with material parameters of tissues intrinsic to the patello-femoral joint. We argue that the systematic sensitivity framework presented herein will help identify key material uncertainties that merit further research and provide insight on those uncertainties that may not be as relative to a given response.

  1. A connective tissue component of a myocardium: a new stage of studying of an old problem.

    Directory of Open Access Journals (Sweden)

    Gorbunov A.A.

    2007-01-01

    Full Text Available Majority of the myocardial cells belongs to its connective tissue component, which is built up of endomysial, perimysial and epimysial streaks. Cellular population exhibit remarkable polymorphism – among them are different types of fibroblasts, including myofibroblasts and fibroclasts, mast cells, macrophages, lymphoid cells. All of them product biologically active substances and serve as local regulators. Every cardiomyocyte connected merely to one fibroblast by the dense and nexus type of contacts, which allow mechanical and chemical interactions between these cells. Cardiomyocytes and connective tissue cells surrounded by the intercellular matrix, which consists fibrous and amorphous components. Collagen and elastic fibers make a framework for cardiac myocytes, which has a sophisticated spatial arrangement. Amorphous substance is a polyanionic buffer environment that provides trophic and regulatory processes in the myocardium. Intercellular matrix undergo permanent turnover, synthesis of the fiber proteins comes together with its degradation. Hitherto, myocardium is a multicomponent system that has a sophisticated mechanisms of regulation for the quantitative and qualitative composition of its elements.

  2. Apoptosis of gingival connective tissue cells in diabetic individuals with chronic periodontitis

    Directory of Open Access Journals (Sweden)

    Farin Kiani Yazdy

    2013-05-01

    Full Text Available   Background and Aims: Apoptosis or programmed cell death plays an important role in the pathogenesis of many diseases. Previous studies suggest that apoptosis is involved in the pathogenesis of periodontal disease, on the other hand it is also suggested that diabetes mellitus enhances apoptosis of connective tissue cells. Thus, we measured expression of proteins which are relevant to apoptosis in the gingival tissue of diabetic patients with chronic periodontitis in comparison to non diabetic individuals.   Materials and Methods: 25 patients with diabetes and chronic periodontitis and 16 non diabetic controls were included in this study. 4 weeks after scaling and root planning and oral hygiene instructions, periodontal surgery was done and gingival tissues obtained during surgery, were sent to lab to investigate expression of Fas, P53, Bcl-2 and Survivin using real-time PCR technique. Data were analyzed using Mann-Whitney and Chi-squared.   Results: Pro-apoptotic proteins (Fas, P53 were significantly (P<0.05 higher in gingival tissues of diabetics (9.5×10-6, 2.4×10-6, respectively in comparison to non diabetics (9.4×10-7, 5.6×10-7, whereas the difference in expression of anti-apoptotic proteins (Bcl-2, Survivin between 2 groups was not significant (9.7×10-8, 3.5×10-7 in comparison to 1.4×10-7, 3.1×10-7, respectively( P =0.91, P =0.29 respectively.   Conclusion: Apoptosis was increased in gingival connective tissue of diabetic patients with chronic periodontitis in comparison to non diabetic ones. Therefore , intervention in expression or function of pro-apoptotic proteins (Fas, P53 could be a new goal in the treatment of periodontal disease of diabetic patients.

  3. Molecular regulation of CCN2 in the intervertebral disc: lessons learned from other connective tissues.

    Science.gov (United States)

    Tran, Cassie M; Shapiro, Irving M; Risbud, Makarand V

    2013-08-08

    Connective tissue growth factor (CCN2/CTGF) plays an important role in extracellular matrix synthesis, especially in skeletal tissues such as cartilage, bone, and the intervertebral disc. As a result there is a growing interest in examining the function and regulation of this important molecule in the disc. This review discusses the regulation of CCN2 by TGF-β and hypoxia, two critical determinants that characterize the disc microenvironment, and discusses known functions of CCN2 in the disc. The almost ubiquitous regulation of CCN2 by TGF-β, including that seen in the disc, emphasizes the importance of the TGF-β-CCN2 relationship, especially in terms of extracellular matrix synthesis. Likewise, the unique cross-talk between CCN2 and HIF-1 in the disc highlights the tissue and niche specific mode of regulation. Taken together the current literature supports an anabolic role for CCN2 in the disc and its involvement in the maintenance of tissue homeostasis during both health and disease. Further studies of CCN2 in this tissue may reveal valuable targets for the biological therapy of disc degeneration.

  4. Resorption of elastic fibers in monkey gingival connective tissue: ultrastructural and immunocytochemical evidence.

    Science.gov (United States)

    Sawada, Takashi

    2011-04-01

    Little is known about the remodeling of elastic fibers in gingival connective tissue. In this study, elastic fibers in the lamina propria of monkey gingiva were examined by transmission electron microscopy and immunocytochemistry. Some elastic fibers were localized at invagination on the surface of the narrow processes of fibroblasts distributed among dense assemblies of collagen fibrils, and also within coated pits, which were pinching off as coated vesicles. At a higher magnification, the coated vesicles contained filamentous structures, as well as pentagonal structures similar those previously reported in elastic fibers. Immunoelectron microscopy demonstrated positive staining for fibrillin, one of the main components of microfibril, localized either in the coated pits or vesicles. These observations indicate that at least some elastic fibers were resorbed by fibroblasts, and that, in spite of the general belief that little remodeling of elastic fibers occurs under normal conditions, resorption of elastic fibers does occur in monkey gingival connective tissue. The functional significance of this is not yet clear, but it may be involved in facilitating the delicate and efficient adaptation of tissue to physical requirements during mastication.

  5. The other mechanism of muscular referred pain: the "connective tissue" theory.

    Science.gov (United States)

    Han, Dong-Gyun

    2009-09-01

    Muscular referred pain, that is, pain perceived in a somatic area other than the site of the noxious stimulation, takes place on a specific place to each muscle in constant and predictable pattern. The central hyperexcitability theory focused on spinal cord, the most proper theory at present, can explain well the segmental pattern of referred pain showing delayed onset. But it is hard to explain the non segmental pattern of referred pain areas of superficial-seated or limb girdle and limb muscles. Referred pain areas of limb girdle and limb muscles appear on the skin above a belt of synergistic muscles beyond the segmental areas. In the case of forearm and calf muscles, referred pain shows up on the palm and sole, the point of force application to the outer object. This finding reflects biomechanical relationship between muscle and its referred pain area. From the phylogenetic perspective, aquatic vertebrated animals (e.g. fish) use myoseptum surrounding myomere, connected to skin to keep tensile strength with it for effective swimming. Likewise, in terrestrial vertebrated animals, there are skin parts weakly interconnected with muscles, though the tensile property of nearly all the skin devolutes except the points of action with the outside. These points are dynamic maximal skin tension areas connected with muscles through superficial fascia, in other words, referred pain areas. Referred pain of deep-seated or truncal muscles appears on the trunk segmentally via spinal cord (the central hyperexcitability theory), but superficial-seated or limb girdle and limb muscles elicit referred pain on dynamic maximal skin tension area through connective tissue (the "connective tissue" theory).

  6. Diagnosis of clavulanic acid allergy using basophil activation and leukotriene release by basophils.

    Science.gov (United States)

    Longo, N; Gamboa, P M; Gastaminza, G; Audícana, M T; Antepara, I; Jaúregui, I; Sanz, M L

    2008-01-01

    Clavulanic acid is a potent inhibitor of B-lactamase that is increasingly prescribed in association with amoxicillin. We report 2 cases of patients who experienced pruritus, wheals, and angioedema after oral intake of amoxicillin/clavulanic acid. Routine skin tests for B-lactam antibiotics and specific immunoglobulin (Ig) E were negative in both patients. Analysis of CD63 expression by the basophil activation test (BAT) using flow cytometry and of sulphidoleukotriene (sLT) release by basophils using the cellular allergen stimulation test (CAST) revealed significant positive responses with amoxicillin/clavulanic acid and with clavulanic acid, and negative responses with amoxicillin and other beta-lactam antibiotics. In addition, cultured CD3+CD4+ cells showed a significant increase in the expression of CD69, CD25, and HLA-DR in the presence of clavulanic acid. Both patients tolerated therapeutic doses of amoxicillin. BAT and CAST are useful ex vivo procedures for the detection of specific IgE-mediated allergy to clavulanic acid, especially for patients with negative skin test results.

  7. Connective tissue fibroblast properties are position-dependent during mouse digit tip regeneration.

    Science.gov (United States)

    Wu, Yuanyuan; Wang, Karen; Karapetyan, Adrine; Fernando, Warnakulusuriya Akash; Simkin, Jennifer; Han, Manjong; Rugg, Elizabeth L; Muneoka, Ken

    2013-01-01

    A key factor that contributes to the regenerative ability of regeneration-competent animals such as the salamander is their use of innate positional cues that guide the regeneration process. The limbs of mammals has severe regenerative limitations, however the distal most portion of the terminal phalange is regeneration competent. This regenerative ability of the adult mouse digit is level dependent: amputation through the distal half of the terminal phalanx (P3) leads to successful regeneration, whereas amputation through a more proximal location, e.g. the subterminal phalangeal element (P2), fails to regenerate. Do the connective tissue cells of the mammalian digit play a role similar to that of the salamander limb in controlling the regenerative response? To begin to address this question, we isolated and cultured cells of the connective tissue surrounding the phalangeal bones of regeneration competent (P3) and incompetent (P2) levels. Despite their close proximity and localization, these cells show very distinctive profiles when characterized in vitro and in vivo. In vitro studies comparing their proliferation and position-specific interactions reveal that cells isolated from the P3 and P2 are both capable of organizing and differentiating epithelial progenitors, but with different outcomes. The difference in interactions are further characterized with three-dimension cultures, in which P3 regenerative cells are shown to lack a contractile response that is seen in other fibroblast cultures, including the P2 cultures. In in vivo engraftment studies, the difference between these two cell lines is made more apparent. While both P2 and P3 cells participated in the regeneration of the terminal phalanx, their survival and proliferative indices were distinct, thus suggesting a key difference in their ability to interact within a regeneration permissive environment. These studies are the first to demonstrate distinct positional characteristics of connective tissue

  8. Connective tissue fibroblast properties are position-dependent during mouse digit tip regeneration.

    Directory of Open Access Journals (Sweden)

    Yuanyuan Wu

    Full Text Available A key factor that contributes to the regenerative ability of regeneration-competent animals such as the salamander is their use of innate positional cues that guide the regeneration process. The limbs of mammals has severe regenerative limitations, however the distal most portion of the terminal phalange is regeneration competent. This regenerative ability of the adult mouse digit is level dependent: amputation through the distal half of the terminal phalanx (P3 leads to successful regeneration, whereas amputation through a more proximal location, e.g. the subterminal phalangeal element (P2, fails to regenerate. Do the connective tissue cells of the mammalian digit play a role similar to that of the salamander limb in controlling the regenerative response? To begin to address this question, we isolated and cultured cells of the connective tissue surrounding the phalangeal bones of regeneration competent (P3 and incompetent (P2 levels. Despite their close proximity and localization, these cells show very distinctive profiles when characterized in vitro and in vivo. In vitro studies comparing their proliferation and position-specific interactions reveal that cells isolated from the P3 and P2 are both capable of organizing and differentiating epithelial progenitors, but with different outcomes. The difference in interactions are further characterized with three-dimension cultures, in which P3 regenerative cells are shown to lack a contractile response that is seen in other fibroblast cultures, including the P2 cultures. In in vivo engraftment studies, the difference between these two cell lines is made more apparent. While both P2 and P3 cells participated in the regeneration of the terminal phalanx, their survival and proliferative indices were distinct, thus suggesting a key difference in their ability to interact within a regeneration permissive environment. These studies are the first to demonstrate distinct positional characteristics of

  9. Antinuclear antibodies in scleroderma, mixed connective tissue disease and "primary" Raynaud's phenomenon.

    Science.gov (United States)

    Cruz, M; Mejia, G; Lavalle, C; Cortes, J J; Reyes, P A

    1988-03-01

    The diversity of antibodies in patients with scleroderma, mixed connective tissue disease or "primary" Raynaud's phenomenon could be used as a laboratory aid in the clinical diagnosis. In serum samples of 75 patients we screened for antinuclear antibodies (HEp 2 cells), anti DNA, soluble nucleoprotein and extractable nuclear antigens (Sm, rRNP, U1-nRNP, SSA/Ro, SSB/La and Scl-70). Distinctive antinuclear antibodies pattern was identified in each group of patients. This immunologic profile is valuable for clinical diagnosis and the preferential association of certain autoantibodies with some diseases and not with others, suggest an antigen-driven stimulus for its production.

  10. [Syndromes of peripheral nervous system lesions and mechanisms of their formation in disorders of connective tissue].

    Science.gov (United States)

    Spirin, N N; Bulanova, V A; Pizova, N V; Shilkina, N P

    2005-01-01

    Systemic rheumatoid diseases are often concomitant with the development of central and peripheral systems pathologies. Presented are the results revealing high frequency of peripheral nervous system lesions (lupus erythematosus and systemic scleroderma), which characterized by polyneuropathy and tunnel syndromes. Based on the results of literature and own studies, pathological mechanisms of peripheral nervous system lesions in diffusion disorders of connective tissue were singled out as follows: ischemic, immunological and metabolic. Taking these mechanisms into account will permit to conduct pathogenetically valid therapy and to improve its results.

  11. Peripheral nervous system lesion syndromes and the mechanisms of their formation in connective tissue diseases.

    Science.gov (United States)

    Spirin, N N; Bulanova, V A; Pizova, N V; Shilkina, N P

    2007-01-01

    Systemic rheumatological diseases are often accompanied by the development of central and peripheral nervous system pathology. Data providing evidence of the high incidence of peripheral nervous system lesions in systemic lupus erythematosus and systemic scleroderma are presented. These diseases in particular are characterized by polyneuropathies and tunnel syndromes. Our own observations, along with published data, revealed the following major pathogenetic mechanisms of peripheral nervous system lesions in diffuse connective tissue diseases - ischemic, immunological, and metabolic. Consideration of these mechanisms will lead to pathogenetically based treatment and improved therapeutic outcomes.

  12. Protein L. A bacterial Ig-binding protein that activates human basophils and mast cells.

    Science.gov (United States)

    Patella, V; Casolaro, V; Björck, L; Marone, G

    1990-11-01

    Peptostreptococcus magnus strain 312 (10(6) to 10(8)/ml), which synthesizes a protein capable of binding to kappa L chains of human Ig (protein L), stimulated the release of histamine from human basophils in vitro. P. magnus strain 644, which does not synthesize protein L, did not induce histamine secretion. Soluble protein L (3 x 10(-2) to 3 micrograms/ml) induced histamine release from human basophils. The characteristics of the release reaction were similar to those of rabbit IgG anti-Fc fragment of human IgE (anti-IgE): it was Ca2(+)- and temperature-dependent, optimal release occurring at 37 degrees C in the presence of 1.0 mM extracellular Ca2+. There was an excellent correlation (r = 0.82; p less than 0.001) between the maximal percent histamine release induced by protein L and that induced by anti-IgE, as well as between protein L and protein A from Staphylococcus aureus (r = 0.52; p less than 0.01). Preincubation of basophils with either protein L or anti-IgE resulted in complete cross-desensitization to a subsequent challenge with the heterologous stimulus. IgE purified from myeloma patients PS and PP (lambda-chains) blocked anti-IgE-induced histamine release but failed to block the histamine releasing activity of protein L. In contrast, IgE purified from myeloma patient ADZ (kappa-chains) blocked both anti-IgE- and protein L-induced releases, whereas human polyclonal IgG selectively blocked protein L-induced secretion. Protein L acted as a complete secretagogue, i.e., it activated basophils to release sulfidopeptide leukotriene C4 as well as histamine. Protein L (10(-1) to 3 micrograms/ml) also induced the release of preformed (histamine) and de novo synthesized mediators (leukotriene C4 and/or PGD2) from mast cells isolated from lung parenchyma and skin tissues. Intradermal injections of protein L (0.01 to 10 micrograms/ml) in nonallergic subjects caused a dose-dependent wheal-and-flare reaction. Protein L activates human basophils and mast cells in

  13. Mutation of fibulin-1 causes a novel syndrome involving the central nervous system and connective tissues.

    Science.gov (United States)

    Bohlega, Saeed; Al-Ajlan, Huda; Al-Saif, Amr

    2014-05-01

    Fibulin-1 is an extracellular matrix protein that has an important role in the structure of elastic fibers and basement membranes of various tissues. Using homozygosity mapping and exome sequencing, we discovered a missense mutation, p.(Cys397Phe), in fibulin-1 in three patients from a consanguineous family presented with a novel syndrome of syndactyly, undescended testes, delayed motor milestones, mental retardation and signs of brain atrophy. The mutation discovered segregated with the phenotype and was not found in 374 population-matched alleles. The affected cysteine is highly conserved across vertebrates and its mutation is predicted to abolish a disulfide bond that defines the tertiary structure of fibulin-1. Our findings emphasize the crucial role fibulin-1 has in development of the central nervous system and various connective tissues.

  14. Targeted ablation of the abcc6 gene results in ectopic mineralization of connective tissues.

    Science.gov (United States)

    Klement, John F; Matsuzaki, Yasushi; Jiang, Qiu-Jie; Terlizzi, Joseph; Choi, Hae Young; Fujimoto, Norihiro; Li, Kehua; Pulkkinen, Leena; Birk, David E; Sundberg, John P; Uitto, Jouni

    2005-09-01

    Pseudoxanthoma elasticum (PXE), characterized by connective tissue mineralization of the skin, eyes, and cardiovascular system, is caused by mutations in the ABCC6 gene. ABCC6 encodes multidrug resistance-associated protein 6 (MRP6), which is expressed primarily in the liver and kidneys. Mechanisms producing ectopic mineralization as a result of these mutations remain unclear. To elucidate this complex disease, a transgenic mouse was generated by targeted ablation of the mouse Abcc6 gene. Abcc6 null mice were negative for Mrp6 expression in the liver, and complete necropsies revealed profound mineralization of several tissues, including skin, arterial blood vessels, and retina, while heterozygous animals were indistinguishable from the wild-type mice. Particularly striking was the mineralization of vibrissae, as confirmed by von Kossa and alizarin red stains. Electron microscopy revealed mineralization affecting both elastic structures and collagen fibers. Mineralization of vibrissae was noted as early as 5 weeks of age and was progressive with age in Abcc6(-/-) mice but was not observed in Abcc6(+/-) or Abcc6(+/+) mice up to 2 years of age. A total body computerized tomography scan of Abcc6(-/-) mice revealed mineralization in skin and subcutaneous tissue as well as in the kidneys. These data demonstrate aberrant mineralization of soft tissues in PXE-affected organs, and, consequently, these mice recapitulate features of this complex disease.

  15. Relationship between the level of interleukin-9 expression in serum of connective tissue disease patients with interstitial lung disease

    Institute of Scientific and Technical Information of China (English)

    欧阳涵

    2013-01-01

    Objective To investigate the level of interleukin (IL) -9 in patients with connective tissue disease (CTD) and connective tissue disease with interstitial lung disease (CTD-ILD) ,and explore the role of IL-9 in the pathogenesis of CTD and CTD-ILD.Methods Sixty-one hospitalized untreated CTD patients were recruited and 20healthy volunteers were enrolled as healthy controls.Patients in the CTD group included 19 systemic sclerosis (SSc) patients,15 rheumatoid arthritis (RA) patients,

  16. 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

  17. 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.

  18. Laterally positioned flap associated with subepithelial connective tissue graft for coverage of isolated gingival recession

    Directory of Open Access Journals (Sweden)

    Thiago Marchi Martins

    2011-10-01

    Full Text Available Introduction: The coverage of denuded roots represents one of the challenges of periodontal treatment. Among the several techniques for this purpose is the laterally positioned flap, which has undergone some modifications since its first reports and is currently combined with other techniques such as subepithelial connective tissue graft. Objective: To report a case of a 41-year-old female patient who presented Miller class I gingival recession at labial surface of tooth #43. Case report: The main symptom of the patient was dentin hypersensitivity. Clinical and radiographic exams were performed and gingival inflammation due to the presence of bacterial plaque was diagnosed as the main cause of root recession. After basic periodontal treatment, surgery for root coverage was performed. Since the area adjacent to the recession showed a good amount of attached gingiva and no interproximal bone loss, the surgical technique of choice was a laterally positioned flap associated with a subepithelial connective tissue graft. Conclusion: Postoperative assessment showed complete root coverage, an increased keratinized gingival band, absence of dentin hypersensitivity, and an excellent esthetic outcome.

  19. 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.

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

    Science.gov (United States)

    Jeong, Seri; Yang, Heeyoung; Hwang, Hyunyong

    2017-01-01

    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.

  1. Connective tissue, Ehlers-Danlos syndrome(s), and head and cervical pain.

    Science.gov (United States)

    Castori, Marco; Morlino, Silvia; Ghibellini, Giulia; Celletti, Claudia; Camerota, Filippo; Grammatico, Paola

    2015-03-01

    Ehlers-Danlos syndrome (EDS) is an umbrella term for a growing group of hereditary disorders of the connective tissue mainly manifesting with generalized joint hypermobility, skin hyperextensibility, and vascular and internal organ fragility. In contrast with other well known heritable connective tissue disorders with severe cardiovascular involvement (e.g., Marfan syndrome), most EDS patients share a nearly normal life span, but are severely limited by disabling features, such as pain, fatigue and headache. In this work, pertinent literature is reviewed with focus on prevalence, features and possible pathogenic mechanisms of headache in EDSs. Gathered data are fragmented and generally have a low level of evidence. Headache is reported in no less than 1/3 of the patients. Migraine results the most common type in the hypermobility type of EDS. Other possibly related headache disorders include tension-type headache, new daily persistent headache, headache attributed to spontaneous cerebrospinal fluid leakage, headache secondary to Chiari malformation, cervicogenic headache and neck-tongue syndrome, whose association still lacks of reliable prevalence studies. The underlying pathogenesis seems complex and variably associated with cardiovascular dysautonomia, cervical spine and temporomandibular joint instability/dysfunction, meningeal fragility, poor sleep quality, pain-killer drugs overuse and central sensitization. Particular attention is posed on a presumed subclinical cervical spine dysfunction. Standard treatment is always symptomatic and usually unsuccessful. Assessment and management procedures are discussed in order to put some basis for ameliorating the actual patients' needs and nurturing future research.

  2. 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.

  3. 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.

  4. Extracellular matrix and cell surface as determinants of connective tissue differentiation.

    Science.gov (United States)

    Solursh, M

    1989-09-01

    This paper reviews in vitro studies, largely from the author's laboratory, concerning the conditions that are permissive for the differentiation of limb bud mesenchymal cells into chondrocytes. In high-density cell culture, even in a defined medium, the same normal sequence of events that is found in vivo in developing cartilage is also observed. This system can be used to study heritable disorders in model systems such as in mutant mouse embryos. In addition, single mesenchymal cells can differentiate into hypertrophic chondrocytes in hydrated collagen gel or agarose cultures. A rounded cell shape promotes chondrogenesis, while a flattened cell shape promotes fibroblast differentiation. The actin cytoskeleton is shown to play a central role in regulating connective tissue cell differentiation. By use of such cell culture manipulations, it is now possible to grow large numbers of fibroblastic cells from human biopsy material for storage and to carry out experimental studies after re-expression of chondrogenesis in gel cultures. It is suggested that cytoskeletal-extracellular matrix interactions play a fundamental role in connective tissue differentiation. Matrix receptors might be developmentally regulated and modify epithelial effects on mesenchymal cells. In this way mesenchymal cells differentiate in a highly organized manner in spatial and temporal terms.

  5. Mechanical properties of human autologous tubular connective tissues (human biotubes) obtained from patients undergoing peritoneal dialysis.

    Science.gov (United States)

    Nakayama, Yasuhide; Kaneko, Yoshiyuki; Takewa, Yoshiaki; Okumura, Noriko

    2016-10-01

    Completely autologous in vivo tissue-engineered connective tissue tubes (Biotubes) have promise as arterial vascular grafts in animal implantation studies. In this clinical study of patients undergoing peritoneal dialysis (PD) (n = 11; age: 39-83 years), we evaluated human Biotubes' (h-Biotubes) mechanical properties to determine whether Biotubes with feasibility as vascular grafts could be formed in human bodies. We extracted PD catheters, embedded for 4-47 months, and obtained tubular connective tissues as h-Biotubes (internal diameter: 5 mm) from around the catheter' silicone tubular parts. h-Biotubes were composed mainly of collagen with smooth luminal surfaces. The average wall thickness was 278 ± 178 μm. No relationship was founded between the tubes' mechanical properties and patients' ages or PD catheter embedding periods statistically. However, the elastic modulus (2459 ± 970 kPa) and tensile strength (623 ± 314 g) of h-Biotubes were more than twice as great as those from animal Biotubes, formed from the same PD catheters by embedding in the beagle subcutaneous pouches for 1 month, or beagle arteries. The burst strength (6338 ± 1106 mmHg) of h-Biotubes was almost the same as that of the beagle thoracic or abdominal aorta. h-Biotubes could be formed in humans over a 4-month embedding period, and they satisfied the mechanical requirements for application as vascular grafts. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1431-1437, 2016.

  6. Basophil degranulation induced by oral poison ivy antigen.

    Science.gov (United States)

    Shelley, W B; Resnik, S S

    1965-08-01

    Seven subjects shown by patch test to be sensitive to poison ivy oleoresin were challenged with graded oral doses of ivy extract. In each instance the circulating basophil leukocytes showed significant degranulation within one hour of challenge. This finding was interpreted as evidence of the presence of immediate-type circulating antibody to ivy antigen in these subjects. No drop in the absolute basophil count was noted, but with higher oral doses the degranulation persisted for several days. Thirteen control subjects showed no change in the basophil morphology or count, indicating that the resin at these levels was not toxic to this cell. All but one of the sensitive subjects showed objective patch test evidence of hyposensitization following the intensive three-week course of oral poison ivy antigen.

  7. The peri-esophageal connective tissue layers and related compartments: visualization by histology and magnetic resonance imaging.

    Science.gov (United States)

    Weijs, T J; Goense, L; van Rossum, P S N; Meijer, G J; van Lier, A L H M W; Wessels, F J; Braat, M N G; Lips, I M; Ruurda, J P; Cuesta, M A; van Hillegersberg, R; Bleys, R L A W

    2017-02-01

    An organized layer of connective tissue coursing from aorta to esophagus was recently discovered in the mediastinum. The relations with other peri-esophageal fascias have not been described and it is unclear whether this layer can be visualized by non-invasive imaging. This study aimed to provide a comprehensive description of the peri-esophageal fascias and determine whether the connective tissue layer between aorta and esophagus can be visualized by magnetic resonance imaging (MRI). First, T2-weighted MRI scanning of the thoracic region of a human cadaver was performed, followed by histological examination of transverse sections of the peri-esophageal tissue between the thyroid gland and the diaphragm. Secondly, pretreatment motion-triggered MRI scans were prospectively obtained from 34 patients with esophageal cancer and independently assessed by two radiologists for the presence and location of the connective tissue layer coursing from aorta to esophagus. A layer of connective tissue coursing from the anterior aspect of the descending aorta to the left lateral aspect of the esophagus, with a thin extension coursing to the right pleural reflection, was visualized ex vivo in the cadaver on MR images, macroscopic tissue sections, and after histologic staining, as well as on in vivo MR images. The layer connecting esophagus and aorta was named 'aorto-esophageal ligament' and the layer connecting aorta to the right pleural reflection 'aorto-pleural ligament'. These connective tissue layers divides the posterior mediastinum in an anterior compartment containing the esophagus, (carinal) lymph nodes and vagus nerve, and a posterior compartment, containing the azygos vein, thoracic duct and occasionally lymph nodes. The anterior compartment was named 'peri-esophageal compartment' and the posterior compartment 'para-aortic compartment'. The connective tissue layers superior to the aortic arch and at the diaphragm corresponded with the currently available anatomic

  8. Connective tissue growth factor promoter activity in normal and wounded skin

    Directory of Open Access Journals (Sweden)

    Kapoor Mohit

    2008-10-01

    Full Text Available Abstract In skin, connective tissue growth factor (CTGF/CCN2 is induced during tissue repair. However, what the exact cell types are that express CTGF in normal and wounded skin remain controversial. In this report, we use transgenic knock-in mice in which the Pacific jellyfish Aequorea victoria enhanced green fluorescent protein (E-GFP gene has been inserted between the endogenous CTGF promoter and gene. Unwounded (day 0 and wounded (days 3 and 7 skin was examined for GFP to detect cells in which the CTGF promoter was active, α-smooth muscle actin (α-SMA to detect myofibroblasts, and NG2 expression to detect pericytes. In unwounded mice, CTGF expression was absent in epidermis and was present in a few cells in the dermis. Upon wounding, CTGF expression was induced in the dermis. Double immunolabeling revealed that CTGF-expressing cells also expressed α-SMA, indicating the CTGF was expressed in myofibroblasts. A subset (~30% of myofibroblasts were also NG2 positive, indicating that pericytes significantly contributed to the number of myofibroblasts in the wound. Pericytes also expressed CTGF. Collectively, these results indicate that CTGF expression in skin correlates with myofibroblast induction, and that CTGF-expressing pericytes are significant contributors to myofibroblast activity during cutaneous tissue repair.

  9. Identification and quantification of basophils in the airways of asthmatics following segmental allergen challenge.

    Science.gov (United States)

    Dijkstra, Dorothea; Hennig, Christian; Hansen, Gesine; Biller, Heike; Krug, Norbert; Hohlfeld, Jens M

    2014-07-01

    During asthma attacks, allergens activate sensitized basophils in the lung, thereby aggravating symptoms. Due to the paucity of basophils in bronchial lavage fluid and the lack of specific basophil detection and quantification methods, basophil-directed research in these samples was hampered in the past. This study aimed to establish and validate a flow cytometry-based basophil detection and quantification method for human basophils from bronchoalveolar lavage (BAL) and blood as a prerequisite for a better understanding of their pathogenic contribution and subtyping of asthma phenotypes. BAL and blood leukocytes from seasonal asthmatics were analyzed by flow cytometry. Chipcytometry, a highly sensitive single-cell analysis method, was used to validate the staining panel for basophils. Cell differentials of May-Grünwald-Giemsa-stained cytospins were used to compare basophil percentages. BAL basophils are identifiable as CD123(+) HLA-DR(-) CD3(-) CD14(-) CD19(-) CD20(-) CD56(-) cells in flow cytometrical analysis. Their identity was validated by Chipcytometry. CD203c was highly expressed by BAL basophils, whereas it was expressed at variable levels on blood basophils. The two quantification methods correlated, although more basophils were detected by flow cytometry. Furthermore, the increase in basophil percentages in the lung correlated with the decrease in the basophil percentages in the blood after allergen challenge. We here validated a reliable basophil quantification method, which is independent of the cell's activation and degranulation state. The results obtained with this method indicate that basophils are directly recruited from the blood circulation to the airway lumen.

  10. Orientation de la réponse immune par les basophiles

    OpenAIRE

    Galeotti, C.; Stephen-Victor, E.; Sharma, M; Kaveri, S.V.; Bayry, J.

    2016-01-01

    International audience; Basophils are infrequent granulocytes which are important for Th2 responses, protection against helminthic parasites and the pathogenesis of allergy and other inflammatory conditions. Recent reports suggest that in mice basophils function as antigen-presenting cells for mediation of Th2 responses. However, human basophils lack features of antigen-presenting cells.; Les basophiles sont de rares granulocytes et ont un rôle important dans les réponses Th2, dans la protect...

  11. Upregulated expression of substance P in basophils of the patients with chronic spontaneous urticaria: induction of histamine release and basophil accumulation by substance P.

    Science.gov (United States)

    Zheng, Wenjiao; Wang, Junling; Zhu, Wei; Xu, Chiyan; He, Shaoheng

    2016-06-01

    Human basophils have been implicated in the pathogenesis of chronic spontaneous urticaria (CSU), and substance P (SP) is a possible candidate as histamine-releasing factor in some patients with CSU. However, little is known of relationship between basophils and SP in CSU. In the present study, we investigated expression of SP and NK1R on basophils from patients with CSU, and influence of SP on basophil functions by using flow cytometry analysis, basophil challenge, and mouse sensitization model techniques. The results showed that plasma SP level and basophil numbers in CSU patients were higher than that in HC subject. The percentages of SP+ and NK1R+ basophils were markedly elevated in CSU blood in comparison with HC blood. Once added, SP induced up to 41.2 % net histamine release from basophils of CSU patients, which was comparable with that provoked by anti-IgE, and fMLP. It appeared that SP induced dramatic increase in blood basophil numbers of mice following peritoneal injection. Ovalbumin (OVA)-sensitized mice had much more SP+ and NK1R+ basophils in blood than non-sensitized mice. In conclusion, the elevated plasma concentration of SP, upregulated expression of SP and NK1R on basophils, and the ability of SP in induction of basophil degranulation and accumulation indicate strongly that SP is most likely a potent proinflammatory mediator, which contributes greatly to the pathogenesis of CSU through basophils. Inhibitors of SP and blockers of NK1R are likely useful agents for treatment of CSU.

  12. Cyclo-oxygenase-2 mediated prostaglandin release regulates blood flow in connective tissue during mechanical loading in humans

    DEFF Research Database (Denmark)

    Langberg, H; Boushel, Robert Christopher; Skovgaard, D

    2003-01-01

    Mechanical loading is known to increase connective tissue blood flow of human tendons and to cause local release of vasodilatory substances. The present study investigated the importance of prostaglandins (PG) formed by cyclo-oxygenase isoforms (COX-1 and 2) for the exercise-related increase...... in blood flow in connective tissue. Healthy individuals (n = 24, age: 23-31 years) underwent 30 min of intermittent, isometric, plantarflexion with both calf muscles either without (n = 6, Control, C) or with blockade of PG formation, either COX-2 specific (n = 10, Celecoxib 2 x 100 mg day-1 for 3 days.......2 +/- 2.0)(P tissue prostaglandin plays an important role for blood flow in peritendinous connective tissue during physical loading in vivo....

  13. Estimating the incidence of connective tissue diseases and vasculitides in a defined population in Northern Savo area in 2010.

    Science.gov (United States)

    Elfving, P; Marjoniemi, O; Niinisalo, H; Kononoff, A; Arstila, L; Savolainen, E; Rutanen, J; Kaipiainen-Seppänen, O

    2016-07-01

    Objective of the study was to evaluate the annual incidence and distribution of autoimmune connective tissue diseases and vasculitides during 2010. All units practicing rheumatology in the Northern Savo area, Finland, participated in the study by collecting data on newly diagnosed adult patients with autoimmune connective tissue disease or vasculitis over 1-year period. Seventy-two cases with autoimmune connective tissue disease were identified. The annual incidence rates were as follows: systemic lupus erythematosus 3.4/100,000 (95 % CI 1.4-7.0), idiopathic inflammatory myopathies 1.9 (0.5-5.0), systemic sclerosis 4.4 (2.0-8.3), mixed connective tissue disease 1.0 (0.1-3.5), Sjögren's syndrome 10.7 (6.7-16.1) and undifferentiated connective tissue disease 13.6 (9.0-19.6). The annual incidence rates among vasculitis category were as follows: antineutrophil cytoplasmic antibody-associated vasculitis 1.5/100,000 (95 % CI 0.3-4.3), central nervous system vasculitis 0.5 (0-2.7) and Henoch-Schönlein purpura 1.5 (0.3-4.3). The annual incidence of giant cell arteritis in the age group of 50 years or older was 7.5/100,000 (95 % CI 3.2-14.8). The longest delay from symptom onset to diagnosis occurred in systemic sclerosis. The incidences of autoimmune connective tissue diseases and vasculitides were comparable with those in published literature. The present study showed female predominance in all connective tissue diseases, excluding idiopathic inflammatory muscle diseases and mean age at onset of disease around 50 years of age. Despite improved diagnostic tools, diagnostic delay is long especially among patients with systemic sclerosis.

  14. Update on undifferentiated connective tissue diseases%未分化结缔组织病的研究进展

    Institute of Scientific and Technical Information of China (English)

    程喜平; 曾凡钦; 许德清

    2011-01-01

    Undifferentiated connective tissue diseases are an actually existing clinical disease state of unknown origin. They clinically resemble autoimmune diseases with the presence of a kind of autoantibody, which does not meet the diagnostic criteria for any defined connective tissue disease. Evolution is the most prominent feature of undifferentiated connective tissue diseases, of which, 30% could evolve into connective tissue diseases, 70% remain in the initial state. The severity of connective tissue diseases evolving from undifferentiated connective tissue diseases tends to be mild with low-grade major organ injury. Clinical manifestations and evolution process reveal that undifferentiated connective tissue diseases are an important member in the spectrum of autoimmune diseases.%未分化结缔组织病是临床实际存在的一种疾病状态,目前发病机制尚不清楚。未分化结缔组织病的临床特征为具有自身免疫病的症状和体征,只有一种自身抗体阳性,不符合任何结缔组织病的诊断标准。演变是未分化结缔组织病疾病过程中最为突出的特点,30%可演变为结缔组织病,70%维持未分化结缔组织病的状态。经未分化结缔组织病演变而来的结缔组织病,病情相对轻微,重要器官损害较少。疾病特点和演变结果提示,未分化结缔组织病是自身免疫性疾病疾病谱中重要一员。

  15. 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

  16. 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.

  17. Evaluation of Basophil Infiltration into the Skin Lesions of Tick Bites

    Directory of Open Access Journals (Sweden)

    Kyoko Nakahigashi

    2013-02-01

    Full Text Available Recently, it has been described that basophils play an essential role in antibody-mediated acquired immunity against ticks in mice. However, it is still unknown whether basophil infiltration has any significance in the infestation with ticks in humans. In this report, we have evaluated the infiltration of basophils into human skin lesions of tick bites.

  18. Effects of connective tissue growth factor and collagen type Ⅰ scleroderma

    Institute of Scientific and Technical Information of China (English)

    Xiaoning Yan; Jie Feng; Bingjun Shi

    2007-01-01

    Objective: To investigate the effects of connective tissue growth factor(CTGF) and collagen type Ⅰ(COL-I) on the pathogenesis of scleroderma and explore the relationship between the level of COL-I and CTGF. Methods: 12 mice model of scleroderma was established by the injection of Bleomycin. The level of CTGF and COL-I were detected by immunohistochemical method. The relationship was analyzed between CTGF and COL-I level. As control group, 12 healthy mice were selected. Results: The levels of CTGF and COL-I in sclerotic models were higher than in normal controls (P < 0.05). It was found that there was a correlation between the level of CTGF and COL-I. Conclusion: CTGF and COL-I played an important role in the hardening process of the skin lesions of the mice model, which may be involved in the pathogenesis of scleroderma.

  19. Connective tissue growthfactor induces transforma-tion of renal fibroblasts into myofibroblasts

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Connective tissue growth factor (CTGF) is thought to be a specific mediator of TGF-β profibrogenic effect, but the role of CTGF in the transformation of renal fibroblasts to myofibroblasts, which are the most important host cells in the renal chronic fibrosis, is still unknown.Aimed at observing the biological effect of CTGF, we set up a cell line overexpressing CTGF, and analyzed the amount of myofibroblast and the level of extracellular matrix Collagen Ⅲ mRNA in cultured cells. Our results show that CTGF can directly induce myofibroblasts formation, and increase the level of Collagen Ⅲ mRNA. This suggests that CTGF may be a novel pharmacotherapeutical target protein for the interference with renal fibrosis, thus providing useful theoretic possibility for clinical prevention of chronic progression of kidney disease.``

  20. The beneficial effect of plasmapheresis in mixed connective tissue disease with coexisting antiphospholipid syndrome.

    Science.gov (United States)

    Szodoray, P; Hajas, A; Toth, L; Szakall, S; Nakken, B; Soltesz, P; Bodolay, E

    2014-09-01

    The authors report a rare case of a female patient with mixed connective tissue disease (MCTD) with coexisting antiphospholipid syndrome (APS). Five years after the diagnosis of MCTD high concentrations of anticardiolipin (anti-CL) and anti-β2-glycoprotein (anti-β2GPI) autoantibodies were present in the patient's serum without thrombotic events. Epstein-Barr virus (EBV) reactivation provoked APS, with the clinical manifestations of livedo reticularis, digital gangrene and leg ulcers. Skin biopsy from the necrotic area showed multiple fibrin microthrombi in the superficial vessels. Corticosteroid pulse therapy, and plasma exchange in combination with synchronized cyclophosphamide was administered, which led to improvement of the digital gangrenes, while no new lesions developed. The number of CD27high plasma cells decreased, and the previous high levels of autoantibodies also normalized in the peripheral blood. In the case of MCTD with coexisting APS combination therapy, including plasmapheresis has beneficial effects.

  1. Cyclical cell stretching of skin-derived fibroblasts downregulates connective tissue growth factor (CTGF) production.

    Science.gov (United States)

    Kanazawa, Yuichiro; Nomura, Jun; Yoshimoto, Shinya; Suzuki, Toshikazu; Kita, Kazuko; Suzuki, Nobuo; Ichinose, Masaharu

    2009-01-01

    Delayed healing of skin wounds can be caused by wound instability, whereas appropriate massage or exercise prevents sclerosis and scar contracture. However, the mechanism by which wound healing is related to mechanical stress has not been fully elucidated. The present study aimed to identify whether mechanical stretching of fibroblasts reduces their production of extracellular matrix. We transferred skin fibroblasts into collagen-coated elastic silicone chambers, cultured them on a stretching apparatus, and used RT-PCR to examine the effects of mechanical stretching on the expression levels of 17 genes related to extracellular matrix production and growth factor secretion. We found that connective tissue growth factor (CTGF) was downregulated after 24 hr of cell stretching. Specifically, the CTGF mRNA and protein levels were 50% and 48% of the control levels, respectively. These findings suggest that cyclic stretching of fibroblasts contributes to anti-fibrotic processes by reducing CTGF production.

  2. [Viscoelastic properties of isolated papillary muscle: contributions of connective tissue skeleton and intracellular matrix].

    Science.gov (United States)

    Protsenko, Iu L; Kobelev, A V; Lukin, O N; Balakin, A A; Smoliuk, L T

    2009-07-01

    Peculiarities of viscoelastic behavior of rabbit papillary muscle in passive state are studied by transversal versus longitudinal deformation curves, stress-strain and hysteresis curves, and stress relaxation curves under ramp stretching. The papillary muscle was chosen because of mostly longitudinal orientation of fibers and its elongated shape, which both make it as an appropriate model for uniaxial tests. The problem of evaluation of connective tissue protein structures and intracellular matrix contribution into the properties under consideration is solved by using the maceration method to remove intracellular structures. The different contribution of intracellular and extracellular protein features into total properties of a papillary muscle leads to nonlinearity of myocardial viscoelastic properties, such as the increase of differential elastic module and relaxation time with deformation.

  3. Nonspecific interstitial pneumonia overlaps organizing pneumonia in lung-dominant connective tissue disease.

    Science.gov (United States)

    Li, Xue-Ren; Peng, Shou-Chun; Wei, Lu-Qing

    2015-01-01

    Here, we reported two cases of nonspecific interstitial pneumonia overlap organizing pneumonia (NSIP/OP) with lung-dominant connective tissue disease (LD-ILD). The first case is a patient with hands of chapped skin, right-sided pleuritic chest discomfort, weakness, positive ANA and antibodies to Ro/SS-A (+++) and Ro-52 (++). In the second case, there were Reynaud's disease, and nucleolus-ANA increased (1:800). Chest high resolution CT scan in both cases showed ground-glass opacifications, predominantly in basal and subpleural region and the pathologic manifestation were correlated with NSIP/OP, which were previously discovered in Sjogren syndrome, PM/DM and other rheumatic diseases. The two cases of NSIP/OP with LD-CTD we reported expand disease spectrum of NSIP/OP pathological types in ILD. However, it is necessary to process large-scale studies.

  4. Substance P and Chronic Pain in Patients with Chronic Inflammation of Connective Tissue.

    Directory of Open Access Journals (Sweden)

    Barbara Lisowska

    Full Text Available Evidence suggests that substance P (SP is involved in chronic joint inflammation, such as the pathogenesis of rheumatoid arthritis and osteoarthritis. The goal of the research was to evaluate the correlation between chronic pain and changes in the SP level in patients with chronic inflammation of the connective tissue.Patients with osteoarthritis and rheumatoid arthritis were enrolled in this study. The relationship between chronic pain intensity and the serum SP concentration was evaluated in these groups of patients with osteoarthritis and rheumatoid arthritis.The results showed a positive correlation between the serum SP concentrations and chronic pain intensity.1. The SP serum concentration was significantly different between the groups of patients with OA and RA. 2. There was a positive correlation between the serum SP concentration and chronic pain intensity in OA and RA patients.

  5. 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.

  6. Pulmonary nocardiosis in patients with connective tissue disease: A report of two cases.

    Science.gov (United States)

    Hagiwara, Shinya; Tsuboi, Hiroto; Hagiya, Chihiro; Yokosawa, Masahiro; Hirota, Tomoya; Ebe, Hiroshi; Takahashi, Hiroyuki; Ogishima, Hiroshi; Asashima, Hiromitsu; Kondo, Yuya; Umeda, Naoto; Suzuki, Takeshi; Hitomi, Shigemi; Matsumoto, Isao; Sumida, Takayuki

    2014-02-01

    Reported here are 2 patients with connective tissue disease who developed pulmonary nocardiosis. Case 1 involved a 73-year-old man with malignant rheumatoid arthritis treated with prednisolone 25 mg/day. Chest X-rays revealed a pulmonary cavity and bronchoscopy detected Nocardia species. The patient was successfully treated with trimethoprim/sulfamethoxazole. Case 2 involved a 41-year-old woman with systemic lupus erythematosus. The patient received remission induction therapy with 50 mg/day of prednisolone and tacrolimus. Six weeks later, a chest CT scan revealed a pulmonary cavity; bronchoscopy resulted in a diagnosis of pulmonary nocardiosis. The patient had difficulty tolerating trimethoprim/sulfamethoxazole, so she was switched to and successfully treated with imipenem/cilastatin and amikacin.

  7. 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.

  8. 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.

  9. Efficacy and safety of liposomal amphotericin B for deep mycosis in patients with connective tissue disease.

    Science.gov (United States)

    Kotani, Takuya; Takeuchi, Tohru; Makino, Shigeki; Hata, Kenichiro; Yoshida, Shuzo; Nagai, Koji; Wakura, Daisuke; Isoda, Kentaro; Hanafusa, Toshiaki

    2013-08-01

    The efficacy and safety of liposomal amphotericin B (L-AMB) in the treatment of invasive fungal infections (IFIs) were retrospectively evaluated for patients with connective tissue diseases (CTDs) during treatment with immunosuppressive therapy. Subjects were 13 patients with CTDs complicated by IFI, on the basis of clinical symptoms, imaging findings, and microbiological and histological examinations. All patients were treated with L-AMB. Efficacy and safety were evaluated before and after administration of L-AMB. Underlying diseases were systemic lupus erythematosus for 4 patients, rheumatoid arthritis for 3, microscopic polyangiitis for 2, adult-onset Still disease for 1, dermatomyositis for 1, and mixed connective tissue disease for 1. Eight patients were resistant to other antifungal drugs. Prednisolone was given to 11 patients and the median dose was 10 mg/day. Immunosuppressants were used for 8 patients. The median duration of administration of L-AMB was 8.5 days (range 4-38 days). In proven and probable diagnosis patients (n = 5), the treatment was effective for 3 patients and ineffective for 2 (efficacy rate 60 %). Serum 1,3-β-D-glucan antigenemia (BG) levels decreased after treatment in the 2 patients who were positive for BG. Serum Aspergillus galactomannan antigen levels decreased in 3 of 4 patients with Aspergillus infection. No patient died of IFI. Regarding potential adverse reactions, there were no significant changes in serum creatinine and potassium levels. L-AMB is effective and well-tolerated for treatment of IFI in patients with CTDs.

  10. Contribution of Underlying Connective Tissue Cells to Taste Buds in Mouse Tongue and Soft Palate.

    Science.gov (United States)

    Boggs, Kristin; Venkatesan, Nandakumar; Mederacke, Ingmar; Komatsu, Yoshihiro; Stice, Steve; Schwabe, Robert F; Mistretta, Charlotte M; Mishina, Yuji; Liu, Hong-Xiang

    2016-01-01

    Taste buds, the sensory organs for taste, have been described as arising solely from the surrounding epithelium, which is in distinction from other sensory receptors that are known to originate from neural precursors, i.e., neural ectoderm that includes neural crest (NC). Our previous study suggested a potential contribution of NC derived cells to early immature fungiform taste buds in late embryonic (E18.5) and young postnatal (P1-10) mice. In the present study we demonstrated the contribution of the underlying connective tissue (CT) to mature taste buds in mouse tongue and soft palate. Three independent mouse models were used for fate mapping of NC and NC derived connective tissue cells: (1) P0-Cre/R26-tdTomato (RFP) to label NC, NC derived Schwann cells and derivatives; (2) Dermo1-Cre/RFP to label mesenchymal cells and derivatives; and (3) Vimentin-CreER/mGFP to label Vimentin-expressing CT cells and derivatives upon tamoxifen treatment. Both P0-Cre/RFP and Dermo1-Cre/RFP labeled cells were abundant in mature taste buds in lingual taste papillae and soft palate, but not in the surrounding epithelial cells. Concurrently, labeled cells were extensively distributed in the underlying CT. RFP signals were seen in the majority of taste buds and all three types (I, II, III) of differentiated taste bud cells, with the neuronal-like type III cells labeled at a greater proportion. Further, Vimentin-CreER labeled cells were found in the taste buds of 3-month-old mice whereas Vimentin immunoreactivity was only seen in the CT. Taken together, our data demonstrate a previously unrecognized origin of taste bud cells from the underlying CT, a conceptually new finding in our knowledge of taste bud cell derivation, i.e., from both the surrounding epithelium and the underlying CT that is primarily derived from NC.

  11. Contribution of Underlying Connective Tissue Cells to Taste Buds in Mouse Tongue and Soft Palate.

    Directory of Open Access Journals (Sweden)

    Kristin Boggs

    Full Text Available Taste buds, the sensory organs for taste, have been described as arising solely from the surrounding epithelium, which is in distinction from other sensory receptors that are known to originate from neural precursors, i.e., neural ectoderm that includes neural crest (NC. Our previous study suggested a potential contribution of NC derived cells to early immature fungiform taste buds in late embryonic (E18.5 and young postnatal (P1-10 mice. In the present study we demonstrated the contribution of the underlying connective tissue (CT to mature taste buds in mouse tongue and soft palate. Three independent mouse models were used for fate mapping of NC and NC derived connective tissue cells: (1 P0-Cre/R26-tdTomato (RFP to label NC, NC derived Schwann cells and derivatives; (2 Dermo1-Cre/RFP to label mesenchymal cells and derivatives; and (3 Vimentin-CreER/mGFP to label Vimentin-expressing CT cells and derivatives upon tamoxifen treatment. Both P0-Cre/RFP and Dermo1-Cre/RFP labeled cells were abundant in mature taste buds in lingual taste papillae and soft palate, but not in the surrounding epithelial cells. Concurrently, labeled cells were extensively distributed in the underlying CT. RFP signals were seen in the majority of taste buds and all three types (I, II, III of differentiated taste bud cells, with the neuronal-like type III cells labeled at a greater proportion. Further, Vimentin-CreER labeled cells were found in the taste buds of 3-month-old mice whereas Vimentin immunoreactivity was only seen in the CT. Taken together, our data demonstrate a previously unrecognized origin of taste bud cells from the underlying CT, a conceptually new finding in our knowledge of taste bud cell derivation, i.e., from both the surrounding epithelium and the underlying CT that is primarily derived from NC.

  12. Epithelial-connective tissue cross-talk is essential for regeneration of intestinal epithelium.

    Science.gov (United States)

    Ishizuya-Oka, Atsuko

    2005-02-01

    Epithelial cells of the gastrointestine undergo a rapid cell-renewal and originate from stem cells throughout the life of the organisms. Previous studies have provided a solid body of evidence to show that the epithelial cell-renewal is under the strict control of cell-cell and cell-extracellular matrix (ECM) interactions between the epithelium and the connective tissue. Especially, the microenvironment around the stem cells called "niche" is thought to play important roles in this control, and its disruption leads to diseases or disorders such as cancer in the human gastrointestine. Although understanding how the niche affects the stem cells is clinically important, its mechanisms still remain mostly unknown at the molecular level, possibly due to difficulties in the identification of the stem cells in the gastrointestine. Recent progress in cell and molecular biology is gradually beginning to shed light on some of the key signaling pathways in the cell-renewal of the intestinal epithelium, such as Wnt/T-cell factor (TCF)/beta-catenin, Notch, Sonic hedgehog (Shh)/bone morphogenetic protein (BMP) signaling pathways, which are also involved in embryonic organogenesis and/or adult carcinogenesis. At present, only fragmentary information is available on their precise functions in the intestine. Nevertheless, there is a growing body of evidence that such signaling pathways have conservative functions in the intestine throughout terrestrial vertebrates, suggesting the usefulness of experimental animals to clarify molecular mechanisms regulating epithelial cell-renewal. In this article, I review some recent findings in this field, with particular focus on our studies using the Xenopus laevis intestine, where the stem cells form the mammalian-type intestinal epithelium under the control of connective tissue during metamorphosis. This Xenopus experimental system will certainly serve as a useful model for the study of the intestinal niche, whose clarification is urgently

  13. 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.

  14. 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.

  15. 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.

  16. [Lower limb varicose veins as a manifestation of undifferentiated connective tissue dysplasia].

    Science.gov (United States)

    Potapov, M P; Potapov, P P; Staver, E V; Mazepina, L S

    2016-01-01

    Analysed herein are the data of 737 patients (a total of 745 lower limbs) suffering from lower-limb varicose veins (LLVV) and subjected to treatment at the Surgical Department consisting of crossectomy, truncal and tributary phlebectomy, dissection of perforant veins exclusively in the basin of the great saphenous vein. Relapses during five-year follow up occurred in 13.8% (102/745) of cases. Based on clinical signs and laboratory findings we studied the effect of the factor of undifferentiated connective tissue dysplasia (UDCTD) on the development of lower-limb varicosity. We carried out comparative analysis in the groups with relapsing LLVV (n=43), without relapses (n=39) and control group comprising volunteers not suffering from LLVV (n=37). The median of blood serum total oxiprolin concentration in LLVV patients both with and without relapses was elevated and amounted to 18.4 (IR 14.9-19.65) and 14.3 (IR 13.1-16.5) versus 8.35 (5.75-9.75) μmol/l, respectively. The mode of the clinical parameter of UDCTD degree in accordance with the rating scale of Smolnova T.Yu. (2003) in the group of patients with LLVV relapses turned out to be higher (Mo=19) than in the group of patients without relapses (Mo=10, p=0.003). The lowest score was in the control group. In patients having immediate relatives with LLVV the level of blood serum total oxiprolin and clinical scores of LLVV turned out to be statistically significantly higher. Hence, based on the obtained during the study clinical and laboratory findings it may be supposed that undifferentiated connective tissue dysplasia plays an important part in the development of both lower limb varicosity and relapses thereof.

  17. Laminar structure of the heart: ventricular myocyte arrangement and connective tissue architecture in the dog.

    Science.gov (United States)

    LeGrice, I J; Smaill, B H; Chai, L Z; Edgar, S G; Gavin, J B; Hunter, P J

    1995-08-01

    We have studied the three-dimensional arrangement of ventricular muscle cells and the associated extracellular connective tissue matrix in dog hearts. Four hearts were potassium-arrested, excised, and perfusion-fixed at zero transmural pressure. Full-thickness segments were cut from the right and left ventricular walls at a series of precisely located sites. Morphology was visualized macroscopically and with scanning electron microscopy in 1) transmural planes of section and 2) planes tangential to the epicardial surface. The appearance of all specimens was consistent with an ordered laminar arrangement of myocytes with extensive cleavage planes between muscle layers. These planes ran radially from endocardium toward epicardium in transmural section and coincided with the local muscle fiber orientation in tangential section. Stereological techniques were used to quantify aspects of this organization. There was no consistent variation in the cellular organization of muscle layers (48.4 +/- 20.4 microns thick and 4 +/- 2 myocytes across) transmurally or in different ventricular regions (23 sites in 6 segments), but there was significant transmural variation in the coupling between adjacent layers. The number of branches between layers decreased twofold from subepicardium to midwall, whereas the length distribution of perimysial collagen fibers connecting muscle layers was greatest in the midwall. We conclude that ventricular myocardium is not a uniformly branching continuum but a laminar hierarchy in which it is possible to identify three axes of material symmetry at any point.

  18. Is Sub-Epithelial Connective Tissue Graft Really a Gold Standard for the Treatment of Gingival Recession Defects?

    Directory of Open Access Journals (Sweden)

    Ajay Mahajan

    2011-04-01

    Full Text Available Gingival recession defects are one of the most common peri-odontal problems. In the past few decades there have been several attempts to treat the gingival recession defects. Among all the treatment options the sub-epithelial connective tis-sue graft is still the most widely used. The sub-epithelial connective tissue graft is considered to produce high percentage of root coverage and therefore considered to be the gold standard technique for the treatment of gingival reces-sion defects. Despite many research papers favoring the use of sub-epithelial connective tissue graft, recent data suggests no major difference in terms of percent root coverage when various other techniques for the treatment of gingival recession defects are compared with each other. In the light of present clinical evidence the criteria to determine whether sub-epithelial connective tissue graft technique should be considered a gold standard or not for be treatment of gingival recession must be re-evaluated. This article highlights some inherent drawbacks associated with sub-epithelial connective tissue graft and emphasizes the need to consider other available techniques for the treatment of gingival recession defects.

  19. Activin A-Smad Signaling Mediates Connective Tissue Growth Factor Synthesis in Liver Progenitor Cells.

    Science.gov (United States)

    Ding, Ze-Yang; Jin, Guan-Nan; Wang, Wei; Sun, Yi-Min; Chen, Wei-Xun; Chen, Lin; Liang, Hui-Fang; Datta, Pran K; Zhang, Ming-Zhi; Zhang, Bixiang; Chen, Xiao-Ping

    2016-03-22

    Liver progenitor cells (LPCs) are activated in chronic liver damage and may contribute to liver fibrosis. Our previous investigation reported that LPCs produced connective tissue growth factor (CTGF/CCN2), an inducer of liver fibrosis, yet the regulatory mechanism of the production of CTGF/CCN2 in LPCs remains elusive. In this study, we report that Activin A is an inducer of CTGF/CCN2 in LPCs. Here we show that expression of both Activin A and CTGF/CCN2 were upregulated in the cirrhotic liver, and the expression of Activin A positively correlates with that of CTGF/CCN2 in liver tissues. We go on to show that Activin A induced de novo synthesis of CTGF/CCN2 in LPC cell lines LE/6 and WB-F344. Furthermore, Activin A contributed to autonomous production of CTGF/CCN2 in liver progenitor cells (LPCs) via activation of the Smad signaling pathway. Smad2, 3 and 4 were all required for this induction. Collectively, these results provide evidence for the fibrotic role of LPCs in the liver and suggest that the Activin A-Smad-CTGF/CCN2 signaling in LPCs may be a therapeutic target of liver fibrosis.

  20. Substrate-protecting antiproteolytic agents for the prevention of pathological degradation of connective tissues. A review.

    Science.gov (United States)

    Robert, A-M

    2012-02-01

    Connective tissues play an important role in the physiological functions of the organism. The integrity of the macromolecular components of these tissues, also called extracellular matrix, is necessary for their functional efficiency. A number of proteinases present in the organism, and the activity of which increases with age and with several pathologies, specifically degrade the components of the extracellular matrix. For a long time, tentatives for the protection of the matrix-components against degradation were made with low molecular weight inhibitors, not very efficient in vivo and not devoid of inconveniencies. We initiated a different approach for the preservation of the macromolecules of the extracellular matrix against proteolytic degradation with substances which exert an intense antiproteolytic activity not only in vitro, but also in vivo. The particularity of these substances is the fact that they do not act on the enzymes, but combine with the macromolecules. This is the type of combination of substances with the macromolecules of the matrix that prevents their degradation by the proteinases. Because of this affinity of such antiproteolytic agents not for the enzymes but for the substrates, we called them "substrate protectors" (Robert et al., 1979). The aim of the present review is to summarise the essential of our experiments which led to the description of substrate protectors.

  1. Connective tissue growth factor is required for skeletal development and postnatal skeletal homeostasis in male mice.

    Science.gov (United States)

    Canalis, Ernesto; Zanotti, Stefano; Beamer, Wesley G; Economides, Aris N; Smerdel-Ramoya, Anna

    2010-08-01

    Connective tissue growth factor (CTGF), a member of the cysteine-rich 61 (Cyr 61), CTGF, nephroblastoma overexpressed (NOV) (CCN) family of proteins, is synthesized by osteoblasts, and its overexpression inhibits osteoblastogenesis and causes osteopenia. The global inactivation of Ctgf leads to defective endochondral bone formation and perinatal lethality; therefore, the consequences of Ctgf inactivation on the postnatal skeleton are not known. To study the function of CTGF, we generated Ctgf(+/LacZ) heterozygous null mice and tissue-specific null Ctgf mice by mating Ctgf conditional mice, where Ctgf is flanked by lox sequences with mice expressing the Cre recombinase under the control of the paired-related homeobox gene 1 (Prx1) enhancer (Prx1-Cre) or the osteocalcin promoter (Oc-Cre). Ctgf(+/LacZ) heterozygous mice exhibited transient osteopenia at 1 month of age secondary to decreased trabecular number. A similar osteopenic phenotype was observed in 1-month-old Ctgf conditional null male mice generated with Prx1-Cre, suggesting that the decreased trabecular number was secondary to impaired endochondral bone formation. In contrast, when the conditional deletion of Ctgf was achieved by Oc-Cre, an osteopenic phenotype was observed only in 6-month-old male mice. Osteoblast and osteoclast number, bone formation, and eroded surface were not affected in Ctgf heterozygous or conditional null mice. In conclusion, CTGF is necessary for normal skeletal development but to a lesser extent for postnatal skeletal homeostasis.

  2. [Normal connective tissue in penis and its changes in patients with erectile dysfunction and Peyronie's disease].

    Science.gov (United States)

    Neĭmark, A I; Klimachev, V V; Gerval'd, V Ia; Bobrov, I P; Avdalian, A M; Muzalevskaia, N I; Gerval'd, I V; Aliev, R T; Kazymov, M A

    2009-01-01

    The aim of this study was to examine the connective tissue of penis in normal individuals and in patients with erectile dysfunction (ED) and Peyronie's disease (PD) using computer methods of image analysis. Penis tissues were obtained from 20 males aged 20-40 years who died in accidents, penis biopsies were taken from 23 patients with ED and 9 patients with PD (average age: 51 +/- 11.5 years). In both groups of patients, the volumetric fraction of collagen fibers in the tunica albuginea and corpora cavernosa was increased, while that one of elastic fibers was decreased. At the same time, the changes of elastic fibers were noted: the fibers become thinner and formed "rods". The reduction of the amplitude and the wavelength in the collagen fibers of the tunica albuginea in patients with ED and the presence of fibrous plaques in corpora cavernosa in in patients with PD were registered. The methods of computer image analysis may improve the morphologic diagnosis of ED and PD.

  3. Conditional overexpression of connective tissue growth factor disrupts postnatal lung development.

    Science.gov (United States)

    Wu, Shu; Platteau, Astrid; Chen, Shaoyi; McNamara, George; Whitsett, Jeffrey; Bancalari, Eduardo

    2010-05-01

    Connective tissue growth factor (CTGF) is a member of an emerging family of immediate-early gene products that coordinates complex biological processes during development, differentiation, and tissue repair. Overexpression of CTGF is associated with mechanical ventilation with high tidal volume and oxygen exposure in newborn lungs. However, the role of CTGF in postnatal lung development and remodeling is not well understood. In the present study, a double-transgenic mouse model was generated with doxycycline-inducible overexpression of CTGF in respiratory epithelial cells. Overexpression of CTGF from Postnatal Days 1-14 resulted in thicker alveolar septa and decreased secondary septal formation. This is correlated with increased myofibroblast differentiation and disorganized elastic fiber deposition in alveolar septa. Overexpression of CTGF also decreased alveolar capillary network formation. There were increased alpha-smooth muscle actin expression and collagen deposition, and dramatic thickening in the peribronchial/peribronchiolar and perivascular regions in the double-transgenic lungs. Furthermore, overexpression of CTGF increased integrin-linked kinase expression, activated its downstream signaling target, Akt, as well as increased mRNA expression of fibronectin. These data demonstrate that overexpression of CTGF disrupts alveologenesis and capillary formation, and induces fibrosis during the critical period of alveolar development. These histologic changes are similar to those observed in lungs of infants with bronchopulmonary dysplasia.

  4. [Reparative regeneration of connective tissue structures of mammals under antioxidant therapy conditions].

    Science.gov (United States)

    Belova, S V; Norkin, I A; Puchin'ian, D M

    2015-01-01

    The influence of administration of the antioxidant complexes consisting of nonenzymatic antioxidants (alpha-tocopherol acetate preparation) and enzymatic antioxidants (ceruloplasmin) has been studied in rabbits with experimental arthritis. The introduction of alpha-tocopherol acetate (at a daily dose of 4 mg) improved metabolic processes in the organism (decreased in the rate of erythrocyte precipitation, total leukocytes and their stub and segmental forms; increased in erythrocyte count; reduced the glycosaminoglycan content as determined from uronic acid and hexose level; decreased ceruloplasmin activity and malonic dialdehyde level ion blood serum, all at p < 0.05), thus favoring reduction in the total activity of the inflammatory process as judged from hematological and biochemical data. Intra-articular introduction of ceruloplasmin (1.5 mg/kg, once per week) positively influenced the state of joint structures in damaged knee joints of the animals: decreased the activity of ceruloplasmin (from 5.28 ± 0.06 to 3.94 ± 0.01 AU), and malonic dialdehyde level (0.18 ± 0.02 to 0.08 ± 0.01 μM) in the articular fluid (all at p < 0.05). These effects are probably related to the elimination of inefficiency of the antioxidant system in the synovial medium, thus preventing inflammatory destruction of articular tissues, hindering the development of pannus, and assisting the activation of reparative regeneration of connective tissue structures.

  5. 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.

  6. Connective tissue growth factor is overexpressed in muscles of human muscular dystrophy.

    Science.gov (United States)

    Sun, Guilian; Haginoya, Kazuhiro; Wu, Yanling; Chiba, Yoko; Nakanishi, Tohru; Onuma, Akira; Sato, Yuko; Takigawa, Masaharu; Iinuma, Kazuie; Tsuchiya, Shigeru

    2008-04-15

    The detailed process of how dystrophic muscles are replaced by fibrotic tissues is unknown. In the present study, the immunolocalization and mRNA expression of connective tissue growth factor (CTGF) in muscles from normal and dystrophic human muscles were examined with the goal of elucidating the pathophysiological function of CTGF in muscular dystrophy. Biopsies of frozen muscle from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy, congenital muscular dystrophy, spinal muscular atrophy, congenital myopathy were analyzed using anti-CTGF polyclonal antibody. Reverse transcription-polymerase chain reaction (RT-PCR) was also performed to evaluate the expression of CTGF mRNA in dystrophic muscles. In normal muscle, neuromuscular junctions and vessels were CTGF-immunopositive, which suggests a physiological role for CTGF in these sites. In dystrophic muscle, CTGF immunoreactivity was localized to muscle fiber basal lamina, regenerating fibers, and the interstitium. Triple immunolabeling revealed that activated fibroblasts were immunopositive for CTGF and transforming growth factor-beta1 (TGF-beta1). RT-PCR analysis revealed increased levels of CTGF mRNA in the muscles of DMD patients. Co-localization of TGF-beta1 and CTGF in activated fibroblasts suggests that CTGF expression is regulated by TGF-beta1 through a paracrine/autocrine mechanism. In conclusion, TGF-beta1-CTGF pathway may play a role in the fibrosis that is commonly observed in muscular dystrophy.

  7. Luteolin, a flavonoid, inhibits AP-1 activation by basophils.

    Science.gov (United States)

    Hirano, Toru; Higa, Shinji; Arimitsu, Junsuke; Naka, Tetsuji; Ogata, Atsushi; Shima, Yoshihito; Fujimoto, Minoru; Yamadori, Tomoki; Ohkawara, Tomoharu; Kuwabara, Yusuke; Kawai, Mari; Matsuda, Hisashi; Yoshikawa, Masayuki; Maezaki, Naoyoshi; Tanaka, Tetsuaki; Kawase, Ichiro; Tanaka, Toshio

    2006-02-03

    Flavonoids including luteolin, apigenin, and fisetin are inhibitors of IL-4 synthesis and CD40 ligand expression by basophils. This study was done to search for compounds with greater inhibitory activity of IL-4 expression and to clarify the molecular mechanisms through which flavonoids inhibit their expression. Of the 37 flavonoids and related compounds examined, ayanin, luteolin, and apigenin were the strongest inhibitors of IL-4 production by purified basophils in response to anti-IgE antibody plus IL-3. Luteolin did not suppress Syk or Lyn phosphorylation in basophils, nor did suppress p54/46 SAPK/JNK, p38 MAPK, and p44/42 MAPK activation by a basophilic cell line, KU812 cells, stimulated with A23187 and PMA. However, luteolin did inhibit phosphorylation of c-Jun and DNA binding activity of AP-1 in nuclear lysates from stimulated KU812 cells. These results provide a fundamental structure of flavonoids for IL-4 inhibition and demonstrate a novel action of flavonoids that suppresses the activation of AP-1.

  8. Spontaneous and cytokine induced basophil adhesion evaluated by microtiter assay

    DEFF Research Database (Denmark)

    Quan, Sha; Poulsen, Lars K; Reimert, Claus Michael

    2002-01-01

    by the histamine content of the adhering basophils. The spontaneous adhesion to fibronectin was higher than to laminin and collagen type I. Both spontaneous adhesion to fibronectin and interleukin-3 (IL-3), interleukin-5 (IL-5), granulocyte/macrophage colony stimulating factor (GM-CSF) induced adhesion to BSA...

  9. Importance of basophil activation testing in insect venom allergy

    Directory of Open Access Journals (Sweden)

    Kosnik Mitja

    2009-12-01

    Full Text Available Abstract Background Venom immunotherapy (VIT is the only effective treatment for prevention of serious allergic reactions to bee and wasp stings in sensitized individuals. However, there are still many questions and controversies regarding immunotherapy, like selection of the appropriate allergen, safety and long term efficacy. Methods Literature review was performed to address the role of basophil activation test (BAT in diagnosis of venom allergy. Results In patients with positive skin tests or specific IgE to both honeybee and wasp venom, IgE inhibition test can identify sensitizing allergen only in around 15% and basophil activation test increases the identification rate to around one third of double positive patients. BAT is also diagnostic in majority of patients with systemic reactions after insect stings and no detectable IgE. High basophil sensitivity to allergen is associated with a risk of side effects during VIT. Persistence of high basophil sensitivity also predicts a treatment failure of VIT. Conclusion BAT is a useful tool for better selection of allergen for immunotherapy, for identification of patients prone to side effects and patients who might be treatment failures. However, long term studies are needed to evaluate the accuracy of the test.

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

    OpenAIRE

    Haghighati F; Akbari S

    2006-01-01

    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...

  11. Connective tissue growth factor is overexpressed in human hepatocellular carcinoma and promotes cell invasion and growth

    Institute of Scientific and Technical Information of China (English)

    Ming Xiu; Ya-Hui Liu; David R Brigstock; Fang-Hui He; Rui-Juan Zhang; Run-Ping Gao

    2012-01-01

    AIM:To determine the expression characteristics of connective tissue growth factor (CTGF/CCN2) in human hepatocellular carcinoma (HCC) in histology and to elucidate the roles of CCN2 on hepatoma cell cycle progression and metastasis in vitro.METHODS:Liver samples from 36 patients (who underwent hepatic resection for the first HCC between 2006 and 2011) and 6 normal individuals were examined for transforming growth factor β1 (TGF-β1) or CCN2 mRNA by in situ hybridization.Computer image analysis was performed to measure integrated optimal density of CCN2 mRNA-positive cells in carcinoma foci and the surrounding stroma.Fibroblast-specific protein-1 (FSP-1) and E-cadherin were examined to evaluate the process of epithelial to mesenchymal transition,α-smooth muscle actin and FSP-1 were detected to identify hepatic stellate cells,and CD34 was measured to evaluate the extent of vascularization in liver tissues by immunohistochemical staining.CCN2 was assessed for its stimulation of HepG2 cell migration and invasion using commercial kits while flow cytometry was used to determine CCN2 effects on HepG2 cell-cycle.RESULTS:In situ hybridization analysis showed that TGF-β1 mRNA was mainly detected in connective tissues and vasculature around carcinoma foci.In comparison to normal controls,CCN2 mRNA was enhanced 1.9-fold in carcinoma foci (12.36 ± 6.08 vs 6.42 ± 2.35)or 9.4-fold in the surrounding stroma (60.27 ± 28.71 vs 6.42 ± 2.35),with concomitant expression of CCN2 and TGF-β1 mRNA in those areas.Epithelial-mesenchymal transition phenotype related with CCN2 was detected in 12/36 (33.3%) of HCC liver samples at the edges between carcinoma foci and vasculature.Incubation of HepG2 cells with CCN2 (100 ng/mL) resulted in more of the cells transitioning into S phase (23.85 ± 2.35vs 10.94 ± 0.23),and induced a significant migratory (4.0-fold) and invasive (5.7-fold) effect.TGF-β1-induced cell invasion was abrogated by a neutralizing CCN2 antibody showing that CCN2

  12. Clinical significance of connective tissue growth factor in hepatitis B virus-induced hepatic fibrosis

    Institute of Scientific and Technical Information of China (English)

    Rong-Li Piao; David R Brigstock; Jie Zhu; Man-Li Zhang; Run-Ping Gao

    2012-01-01

    AIM:To determine the utility of connective tissue growth factor (CCN2/CTGF) for assessing hepatic fibrosis in hepatitis B virus (HBV)-induced chronic liver diseases (CLD-B).METHODS:Enzyme-linked immunosorbent assay was used to measure CCN2 in sera from 107 patients with chronic hepatitis B (CHB) and 39 patients with HBVinduced active liver cirrhosis and 30 healthy individuals.Liver samples from 31 patients with CHB,8 patients with HBV-induced liver cirrhosis and 8 HBV carriers with normal liver histology were examined for transforming growth factor β-1 (TGF-β1) or CCN2 mRNA levels by in situ hybridization,and computer image analysis was performed to measure integrated optimal density (IOD) of CCN2 mRNA-positive cells in liver tissues.Histological inflammation grading and fibrosis staging were evaluated by H and E staining and Van Gieson's method.RESULTS:Serum CCN2 concentrations were,respectively,4.0-or 4.9-fold higher in patients with CHB or active liver cirrhosis as compared to healthy individuals (P < 0.01).There was good consistency between the levels of CCN2 in sera and CCN2 mRNA expression in liver tissues (r =0.87,P < 0.01).The levels of CCN2 in sera were increased with the enhancement of histological fibrosis staging in patients with CLD-B (r =0.85,P < 0.01).Serum CCN2 was a reliable marker for the assessment of liver fibrosis,with areas under the receiver operating characteristic (ROC) curves (AUC) of 0.94 or 0.85 for,respectively,distinguishing normal liver controls from patients with F1 stage liver fibrosis or discriminating between mild and significant fibrosis.CONCLUSION:Detection of serum CCN2 in patients with CLD-B may have clinical significance for assessment of severity of hepatic fibrosis.

  13. Bacterial flagellin induces IL-6 expression in human basophils.

    Science.gov (United States)

    Jeon, Jun Ho; Ahn, Ki Bum; Kim, Sun Kyung; Im, Jintaek; Yun, Cheol-Heui; Han, Seung Hyun

    2015-05-01

    Binding of allergen to IgE on basophils positively affects allergic inflammation by releasing inflammatory mediators. Recently, basophils were shown to express pattern-recognition receptors, such as toll-like receptors (TLRs), for recognizing microbe-associated molecular patterns (MAMPs) that are independent of allergen-IgE binding. In this study, we investigated whether MAMP alone can induce IL-6 production in a human basophil cell line, KU812. Stimulation with flagellin in the absence of allergen-IgE association induced IL-6 expression in KU812 cells, while stimulation with lipoteichoic acid, peptidoglycan, or poly I:C did not under the same condition. Flagellin-induced IL-6 expression was also observed in human primary basophils. Flow cytometric analysis showed that KU812 cells expressed flagellin-recognizing TLR5 both on the cell surface and in the cytoplasm while TLR2 and TLR3 were observed only in the cytoplasm. We further demonstrated that although flagellin augmented the phosphorylation of mitogen-activated protein kinases including p38 kinase, ERK, and JNK, flagellin-induced IL-6 production was attenuated by inhibitors for p38 kinase and ERK, but not by JNK inhibitors. In addition, flagellin enhanced phosphorylation of signaling molecules including CREB, PKCδ, and AKT. The inhibitors for PKA and PKC also showed inhibitory effects. Interestingly, flagellin-induced IL-6 production was further enhanced by pretreatment with inhibitors for PI3K, implying that PI3K negatively affects the flagellin-induced IL-6 production. Furthermore, DNA binding activities of NF-κB, AP-1, and CREB, which play pivotal roles in the induction of IL-6 gene expression, were increased by flagellin. These results suggest that flagellin alone is sufficient to induce IL-6 gene expression via TLR5 signaling pathways in human basophils.

  14. Basophil-derived IL-6 regulates TH17 cell differentiation and CD4 T cell immunity

    Science.gov (United States)

    Yuk, Chae Min; Park, Hyeung Ju; Kwon, Bo-In; Lah, Sang Joon; Chang, Jun; Kim, Ji-Young; Lee, Kyung-Mi; Park, Su-Hyung; Hong, Seokchan; Lee, Seung-Hyo

    2017-01-01

    Basophils are rare, circulating granulocytes proposed to be involved in T helper (TH) type 2 immunity, mainly through secretion of interleukin (IL)-4. In addition to IL-4, basophils produce IL-6 and tumor necrosis factor (TNF)-α in response to immunoglobulin E (IgE) crosslinking. Differentiation of TH17 cells requires IL-6 and transforming growth factor (TGF)-β, but whether basophils play a significant role in TH17 induction is unknown. Here we show a role for basophils in TH17 cell development by using in vitro T cell differentiation and in vivo TH17-mediated inflammation models. Bone marrow derived-basophils (BMBs) and splenic basophils produce significant amounts of IL-6 as well as IL-4 following stimulation with IgE crosslink or cholera toxin (CT). In addition, through IL-6 secretion, BMBs cooperate with dendritic cells to promote TH17 cell differentiation. In the TH17 lung inflammation model, basophils are recruited to the inflamed lungs following CT challenge, and TH17 responses are significantly reduced in the absence of basophils or IL-6. Furthermore, reconstitution with wild-type, but not IL-6-deficient, basophils restored CT-mediated lung inflammation. Lastly, basophil-deficient mice showed reduced phenotypes of TH17-dependent experimental autoimmune encephalomyelitis. Therefore, our results indicate that basophils are an important inducer of TH17 cell differentiation, which is dependent on IL-6 secretion. PMID:28134325

  15. Hierarchical mechanics of connective tissues: integrating insights from nano to macroscopic studies.

    Science.gov (United States)

    Gohl, Kheng Lim; Listrat, Anne; Béchet, Daniel

    2014-10-01

    As the key component of the musculoskeletal system, the extracellular matrix of soft connective tissues such as ligaments and tendons is a biological example of fibre-reinforced composite but with a complex hierarchical architecture. To establish a comprehensive structure-function relationship at the respective levels (i.e., from molecule to tissue) of the hierarchical architecture is challenging and requires a multidisciplinary approach, involving the integration of findings from the fields of molecular biology, biochemistry, structural biology, materials science and biophysics. Accordingly, in recent years, some of these fields, namely structural biology, materials science and biophysics, have made significant progress in the microscale and nanoscale studies of extracellular matrix using new tools, such as microelectromechanical systems, optical tweezers and atomic force microscopy, complemented by new techniques in simultaneous imaging and mechanical testing and computer modelling. The intent of this paper is to review the key findings on the mechanical response of extracellular matrix at the respective levels of the hierarchical architecture. The main focus is on the structure and function--the findings are compared across the different levels to provide insights that support the goal of establishing a comprehensive structure-function relationship of extracellular matrix. For this purpose, the review is divided into two parts. The first part explores the features of key structural units of extracellular matrix, namely tropocollagen molecule (the lowest level), microfibril, collagen fibril, collagen fibre and fascicle. The second part examines the mechanics of the structural units at the respective levels. Finally a framework for extracellular matrix mechanics is proposed to support the goal to establish a comprehensive structure-function relationship. The framework describes the integration of the mechanisms of reinforcement by the structural units at the

  16. 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

    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...... bioavailability of IGF-I in OC. In conclusion, synthetic female sex hormones administered as OC had an inhibiting effect on collagen synthesis in tendon, bone, and muscle connective tissue, which may be related to a lower bioavailability of IGF-I....

  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. An IL-1 cytokine member, IL-33, induces human basophil activation via its ST2 receptor.

    Science.gov (United States)

    Suzukawa, Maho; Iikura, Motoyasu; Koketsu, Rikiya; Nagase, Hiroyuki; Tamura, Chise; Komiya, Akiko; Nakae, Susumu; Matsushima, Kouji; Ohta, Ken; Yamamoto, Kazuhiko; Yamaguchi, Masao

    2008-11-01

    Basophils are thought to play pivotal roles in allergic inflammation through rapid release of chemical mediators in addition to sustained production of Th2 cytokines, including IL-4. A newly identified cytokine, IL-33, has been recognized as one of the key cytokines enhancing Th2-balanced immune regulation through its receptor, ST2. The present study was conducted to elucidate whether IL-33 acts directly on, and affects the functions of, human basophils. Real-time PCR analysis showed that basophils express transcripts for ST2. The expression levels were significantly higher compared with eosinophils and neutrophils, and treatment with IL-33 significantly up-regulated basophil ST2 mRNA expression. Expressions of IL-4 and IL-13 mRNA were also up-regulated by IL-33, and there was also enhanced secretion of IL-4 protein. IL-33 increased the surface levels of basophil CD11b expression and enhanced basophil adhesiveness. Although IL-33 failed to directly induce degranulation or attract basophils, it exerted priming effects on basophils. It enhanced degranulation in response to IgE-crosslinking stimulus and also enhanced basophil migration toward eotaxin without changing surface CCR3. Also, IL-33 synergistically enhanced IL-4 production and CD11b expression by IL-3-stimulated basophils. Neutralization using Ab specific for ST2 significantly diminished the enhancing effects of IL-33 on both basophil CD11b expression and migration toward eotaxin, indicating that IL-33 signals via ST2 expressed on basophils. This study revealed that IL-33 potently regulates migration and activation of human basophils. IL-33 may be a key cytokine in the pathogenesis of Th2-dominant inflammation by acting not only on lymphocytes but also on effector cells such as basophils.

  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. Passive muscle stiffness may be influenced by active contractility of intramuscular connective tissue.

    Science.gov (United States)

    Schleip, Robert; Naylor, Ian L; Ursu, Daniel; Melzer, Werner; Zorn, Adjo; Wilke, Hans-Joachim; Lehmann-Horn, Frank; Klingler, Werner

    2006-01-01

    The article introduces the hypothesis that intramuscular connective tissue, in particular the fascial layer known as the perimysium, may be capable of active contraction and consequently influence passive muscle stiffness, especially in tonic muscles. Passive muscle stiffness is also referred to as passive elasticity, passive muscular compliance, passive extensibility, resting tension, or passive muscle tone. Evidence for the hypothesis is based on five indications: (1) tonic muscles contain more perimysium and are therefore stiffer than phasic muscles; (2) the specific collagen arrangement of the perimysium is designed to fit a load-bearing function; (3) morphological considerations as well as histological observations in our laboratory suggest that the perimysium is characterized by a high density of myofibroblasts, a class of fibroblasts with smooth muscle-like contractile kinetics; (4) in vitro contraction tests with fascia have demonstrated that fascia, due to the presence of myofibroblasts, is able to actively contract, and that the resulting contraction forces may be strong enough to influence musculoskeletal dynamics; (5) the pronounced increase of the perimysium in muscle immobilization and in the surgical treatment of distraction osteogenesis indicates that perimysial stiffness adapts to mechanical stimulation and hence influences passive muscle stiffness. In conclusion, the perimysium seems capable of response to mechanostimulation with a myofibroblast facilitated active tissue contraction, thereby adapting passive muscle stiffness to increased tensional demands, especially in tonic musculature. If verified, this new concept may lead to novel pharmaceutical or mechanical approaches to complement existing treatments of pathologies which are accompanied by an increase or decrease of passive muscle stiffness (e.g., muscle fibroses such as torticollis, peri-partum pelvic pain due to pelvic instability, and many others). Methods for testing this new concept

  1. Alteration of Connective Tissue Growth Factor (CTGF) Expression in Orbital Fibroblasts from Patients with Graves' Ophthalmopathy.

    Science.gov (United States)

    Tsai, Chieh-Chih; Wu, Shi-Bei; Chang, Pei-Chen; Wei, Yau-Huei

    2015-01-01

    Graves' ophthalmopathy (GO) is a disfiguring and sometimes blinding disease, which is characterized by inflammation and swelling of orbital tissues, with fibrosis and adipogenesis being predominant features. The aim of this study is to investigate whether the expression levels of fibrosis-related genes, especially that of connective tissue growth factor (CTGF), are altered in orbital fibroblasts of patients with GO. The role of oxidative stress in the regulation of CTGF expression in GO orbital fibroblasts is also examined. By a SYBR Green-based real time quantitative PCR (RT-QPCR), we demonstrated that the mRNA expression levels of fibronectin, apolipoprotein J, and CTGF in cultured orbital fibroblasts from patients with GO were significantly higher than those of age-matched normal controls (p = 0.007, 0.037, and 0.002, respectively). In addition, the protein expression levels of fibronectin, apolipoprotein J, and CTGF analyzed by Western blot were also significantly higher in GO orbital fibroblasts (p = 0.046, 0.032, and 0.008, respectively) as compared with the control. Furthermore, after treatment of orbital fibroblasts with a sub-lethal dose of hydrogen peroxide (200 μM H2O2), we found that the H2O2-induced increase of CTGF expression was more pronounced in the GO orbital fibroblasts as compared with those in normal controls (20% vs. 7%, p = 0.007). Importantly, pre-incubation with antioxidants including N-acetylcysteine (NAC) and vitamin C, respectively, resulted in significant attenuation of the induction of CTGF in GO orbital fibroblasts in response to H2O2 (p = 0.004 and 0.015, respectively). Taken together, we suggest that oxidative stress plays a role in the alteration of the expression of CTGF in GO orbital fibroblasts that may contribute to the pathogenesis and progression of GO. Antioxidants may be used in combination with the therapeutic agents for effective treatment of GO.

  2. Intramuscular Connective Tissue Differences in Spastic and Control Muscle: A Mechanical and Histological Study

    Science.gov (United States)

    de Bruin, Marije; Smeulders, Mark J.; Kreulen, Michiel; Huijing, Peter A.; Jaspers, Richard T

    2014-01-01

    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. PMID:24977410

  3. 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.

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

    Science.gov (United States)

    de Bruin, Marije; Smeulders, Mark J; Kreulen, Michiel; Huijing, Peter A; Jaspers, Richard T

    2014-01-01

    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.

  5. Development of oral and extra-oral endosseous craniofacial implants by using a mesh structure for connective tissue attachment.

    Science.gov (United States)

    Mita, Atsushi; Yagihara, Atsushi; Wang, Wei; Takakuda, Kazuo

    2014-03-19

    Connective tissue attachment to a mesh structure incorporated on the surface of oral implants and extra-oral endosseous craniofacial implants (EOECI) was investigated. Two types of implants were prepared: TI and TI-Mesh. TI was composed of an upper and a lower component, both comprised of a titanium cylinder, which could be connected using a titanium screw. The composition of the TIMesh was similar, but the lower cylinder had a lateral groove that was covered with a titanium mesh. In animal experiments performed using rat calvaria, the lower component was first implanted and was left submerged for 3 weeks, then the upper component was mounted percutaneously. After an additional 2 weeks, each implant and the surrounding tissues were harvested and evaluated. Histological observations revealed collagen fibers originating from surrounding hypodermal tissues anchored to the mesh structures of the TI-Mesh whereas no such collagen fibers were observed around TI. Significantly greater values of the attachment strength, the thickness of the dermal tissue, the thickness of hypodermal tissue, and the attachment lengths were observed in TI-Mesh than those of TI. Thus connective tissue attachment with collagen fibers anchored to the mesh was achieved by incorporating mesh structures into the percutaneously placed implants.

  6. 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.

  7. 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.

  8. Lung involvement in connective tissue diseases: a comprehensive review and a focus on rheumatoid arthritis.

    Science.gov (United States)

    Marigliano, Benedetta; Soriano, Alessandra; Margiotta, Domenico; Vadacca, Marta; Afeltra, Antonella

    2013-09-01

    The lungs are frequently involved in Connective Tissue Diseases (CTDs). Interstitial lung disease (ILD) is one of the most common pleuropulmonary manifestations that affects prognosis significantly. In practice, rheumatologists and other physicians tend to underestimate the impact of CTD-ILDs and diagnose respiratory impairment when it has reached an irreversible fibrotic stage. Early investigation, through clinical evidence, imaging and - in certain cases - lung biopsy, is therefore warranted in order to detect a possible ILD at a reversible initial inflammatory stage. In this review, we focus on lung injury during CTDs, with particular attention to ILDs, and examine their prevalence, clinical manifestations and histological patterns, as well as therapeutic approaches and known complications till date. Although several therapeutic agents have been approved, the best treatment is still not certain and additional trials are required, which demand more knowledge of pulmonary involvement in CTDs. Our central aim is therefore to document the impact that lung damage has on CTDs. We will mainly focus on Rheumatoid Arthritis (RA), which - unlike other rheumatic disorders - resembles Idiopathic Pulmonary Fibrosis (IPF) in numerous aspects.

  9. Molecular mechanisms for uremic toxin-induced oxidative tissue damage via a cardiovascular-renal connection.

    Science.gov (United States)

    Watanabe, Hiroshi

    2013-01-01

    Chronic kidney disease (CKD), marked by a progressive loss in renal function, is a leading cause of hemodialysis initiation and cardiovascular disease (CVD). There are currently 13.3 million patients with CKD and 300 thousand patients are currently undergoing hemodialysis in Japan. Therefore, preventing the initiation of dialysis and reducing the risk of cardiovascular death are high-priority issues from the viewpoint of public health and economic implications. Understanding the molecular mechanism responsible for the progression of CKD and cardiovascular damage regarding crosstalk between the kidney and cardiovascular system is an important issue in controlling the pathogenesis of CKD-CVD. However, the mechanisms involved in CKD-CVD are not well understood. This hinders the development of new treatment strategies. We have been investigating the role of protein bound uremic toxins, that are difficult to remove by hemodialysis, on the onset and progression of CKD and CVD. The relationship between their redox properties and the pathogenesis of CKD-CVD was examined. In this review, we focus on two sulfate conjugated uremic toxins, namely, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), and summarize recent studies that provide new insights on the molecular mechanisms responsible for uremic toxin-induced oxidative tissue damage via a cardiovascular-renal connection.

  10. Role of Connective Tissue Growth Factor in Extracellular Matrix Degradation in Renal Tubular Epithelial Cells

    Institute of Scientific and Technical Information of China (English)

    ZHANG Chun; ZHU Zhonghua; LIU Jianshe; YANG Xiao; FU Ling; DENG Anguo

    2007-01-01

    In order to investigate the effects of connective tissue growth factor (CTGF) antisense oligodeoxynucleotide (ODN) on plasminogen activator inhibitor-1 (PAI-1) expression in renal tubular cells induced by transforming growth factor β1 (TGF-β1) and to explore the role of CTGF in the degradation of renal extracellular matrix (ECM), a human proximal tubular epithelial cell line (HKC) was cultured in vitro. Cationic lipid-mediated CTGF antisense ODN was transfected into HKC. After HKC were stimulated with TGF-β1 (5 μg/L), the mRNA level of PAI-1 was detected by RT-PCR. Intracellular PAI-1 protein synthesis was assessed by flow cytometry. The secreted PAI-1 in the media was determined by Western blot. The results showed that TGF-β1 could induce tubular CTGF and PAI-1 mRNA expression. The PAI-1 mRNA expression induced by TGF-β1 was significantly inhibited by CTGF antisense ODN. CTGF antisense ODN also inhibited intracellular PAI-1 protein synthesis and lowered the levels of PAI-1 protein secreted into the media. It was concluded that CTGF might play a crucial role in the degradation of excessive ECM during tubulointerstitial fibrosis, and blocking the biological effect of CTGF may be a novel way in preventing renal fibrosis.

  11. Nail changes in connective tissue diseases: a study of 39 cases.

    Science.gov (United States)

    Elmansour, Imane; Chiheb, Soumia; Benchikhi, Hakima

    2014-01-01

    The objective is to identify nail unit changes associated with connective tissue diseases (CTD) and evaluate their frequency. We carried a prospective study between March 2012 and March2013 in our department. All patients with CTD were included. A clinical examination of the fingernails was done by the same dermatologist. Nail features were noted and classified and photos taken. Thirty nine patients were enrolled including: 16 systemic sclerosis, 14 lupus erythematosus (SLE), 8 dermatomyositis (DM), 1 primary Sjorgen's syndrome. The mean age was 40 years old. The mean duration of the disease was 6 years. Nail unit changes were present in 27 patients (69%). The abnormalities observed were Longitidunal ridging in 11 patients, Peri ungueal erythema in 10 patients, Peri-ungual telangiectasia in 11 patients, Ragged cuticle in 10 patients fingertips scars in 9 patients, Increase of longitudinal curvature and beaking of the nail in 4 patients, Increase in transverse curvature in 4 patients, dyschromia of the proximal nail fold in 3 patients, Subungual hyperkeratosis in 3 patients, onycholysis in 2 patients, splinter haemorrhages in 3 patients, nail plate pigmentation in 2 patients, pseudoclubbing in 1 patient, macrolunula in 1 patients, Red lunulae in one patient, bluish-black discoloration of the nail plate in one patient. The proximal nailfold was found to be most sites affected.

  12. Connective tissue growth factor as a novel therapeutic target in high grade serous ovarian cancer

    Science.gov (United States)

    Moran-Jones, Kim; Gloss, Brian S.; Murali, Rajmohan; Chang, David K.; Colvin, Emily K.; Jones, Marc D.; Yuen, Samuel; Howell, Viive M.; Brown, Laura M.; Wong, Carol W.; Spong, Suzanne M.; Scarlett, Christopher J.; Hacker, Neville F.; Ghosh, Sue; Mok, Samuel C.; Birrer, Michael J.; Samimi, Goli

    2015-01-01

    Ovarian cancer is the most common cause of death among women with gynecologic cancer. We examined molecular profiles of fibroblasts from normal ovary and high-grade serous ovarian tumors to identify novel therapeutic targets involved in tumor progression. We identified 2,300 genes that are significantly differentially expressed in tumor-associated fibroblasts. Fibroblast expression of one of these genes, connective tissue growth factor (CTGF), was confirmed by immunohistochemistry. CTGF protein expression in ovarian tumor fibroblasts significantly correlated with gene expression levels. CTGF is a secreted component of the tumor microenvironment and is being pursued as a therapeutic target in pancreatic cancer. We examined its effect in in vitro and ex vivo ovarian cancer models, and examined associations between CTGF expression and clinico-pathologic characteristics in patients. CTGF promotes migration and peritoneal adhesion of ovarian cancer cells. These effects are abrogated by FG-3019, a human monoclonal antibody against CTGF, currently under clinical investigation as a therapeutic agent. Immunohistochemical analyses of high-grade serous ovarian tumors reveal that the highest level of tumor stromal CTGF expression was correlated with the poorest prognosis. Our findings identify CTGF as a promoter of peritoneal adhesion, likely to mediate metastasis, and a potential therapeutic target in high-grade serous ovarian cancer. These results warrant further studies into the therapeutic efficacy of FG-3019 in high-grade serous ovarian cancer. PMID:26575166

  13. Benefit of adjunctive tacrolimus in connective tissue disease-interstitial lung disease.

    Science.gov (United States)

    Witt, Leah J; Demchuk, Carley; Curran, James J; Strek, Mary E

    2016-02-01

    We evaluated the safety and effectiveness of adjunctive tacrolimus therapy with conventional immunosuppression in patients with severe connective tissue disease-related interstitial lung disease (CTD-ILD). We included patients from our interstitial lung disease (ILD) registry with CTD-ILD, in whom tacrolimus was added to corticosteroids and an additional immunosuppressive agent. Demographic data, clinical features, lung function, radiographic images, and pathologic findings were reviewed. Effectiveness was assessed by comparing pulmonary function tests (PFTs) closest to tacrolimus initiation to PFTs approximately 6-12 months later. Corticosteroid dose at these time points was also evaluated. We report adverse events attributed to tacrolimus. Seventeen patients with CTD-ILD were included in adverse event analysis; twelve were included in efficacy analysis. Length of tacrolimus therapy ranged from 6 to 110 months (mean 38.8 months ± 31.4). The mean improvement in percent predicted total lung capacity was 7.5% ± 11.7 (p = 0.02). Forced vital capacity mean improvement was 7.4% ± 12.5 (p = 0.06). The average decrease in corticosteroid dose at follow-up was 20.3 mg ± 25.2 (p = 0.02) with complete discontinuation in six patients. No patients experienced a life-threatening adverse event attributed to tacrolimus. Tacrolimus can be effective and is well tolerated as an adjunctive therapy and allows tapering of corticosteroids.

  14. Undifferentiated connective tissue disease-associated interstitial lung disease: changes in lung function.

    Science.gov (United States)

    Kinder, Brent W; Shariat, Cyrus; Collard, Harold R; Koth, Laura L; Wolters, Paul J; Golden, Jeffrey A; Panos, Ralph J; King, Talmadge E

    2010-04-01

    Undifferentiated connective tissue disease (UCTD) is a distinct clinical entity that may be accompanied by interstitial lung disease (ILD). The natural history of UCTD-ILD is unknown. We hypothesized that patients with UCTD-ILD would be more likely to have improvement in lung function than those with idiopathic pulmonary fibrosis (IPF) during longitudinal follow-up. We identified subjects enrolled in the UCSF ILD cohort study with a diagnosis of IPF or UCTD. The primary outcome compared the presence or absence of a > or = 5% increase in percent predicted forced vital capacity (FVC) in IPF and UCTD. Regression models were used to account for potential confounding variables. Ninety subjects were identified; 59 subjects (30 IPF, 29 UCTD) had longitudinal pulmonary function data for inclusion in the analysis. After accounting for baseline pulmonary function tests, treatment, and duration between studies, UCTD was associated with substantial improvement in FVC (odds ratio = 8.23, 95% confidence interval, 1.27-53.2; p = 0.03) during follow-up (median, 8 months) compared with IPF. Patients with UCTD-ILD are more likely to have improved pulmonary function during follow-up than those with IPF. These findings demonstrate the clinical importance of identifying UCTD in patients presenting with an "idiopathic" interstitial pneumonia.

  15. Nail changes in connective tissue diseases: a study of 39 cases

    Science.gov (United States)

    Elmansour, Imane; Chiheb, Soumia; Benchikhi, Hakima

    2014-01-01

    The objective is to identify nail unit changes associated with connective tissue diseases (CTD) and evaluate their frequency. We carried a prospective study between March 2012 and March2013 in our department. All patients with CTD were included. A clinical examination of the fingernails was done by the same dermatologist. Nail features were noted and classified and photos taken. Thirty nine patients were enrolled including: 16 systemic sclerosis, 14 lupus erythematosus (SLE), 8 dermatomyositis (DM), 1 primary Sjorgen's syndrome. The mean age was 40 years old. The mean duration of the disease was 6 years. Nail unit changes were present in 27 patients (69%). The abnormalities observed were Longitidunal ridging in 11 patients, Peri ungueal erythema in 10 patients, Peri-ungual telangiectasia in 11 patients, Ragged cuticle in 10 patients fingertips scars in 9 patients, Increase of longitudinal curvature and beaking of the nail in 4 patients, Increase in transverse curvature in 4 patients, dyschromia of the proximal nail fold in 3 patients, Subungual hyperkeratosis in 3 patients, onycholysis in 2 patients, splinter haemorrhages in 3 patients, nail plate pigmentation in 2 patients, pseudoclubbing in 1 patient, macrolunula in 1 patients, Red lunulae in one patient, bluish- black discoloration of the nail plate in one patient. The proximal nailfold was found to be most sites affected. PMID:25419288

  16. Connective Tissue Growth Factor Is Required for Normal Follicle Development and Ovulation

    Science.gov (United States)

    Nagashima, Takashi; Kim, Jaeyeon; Li, Qinglei; Lydon, John P.; DeMayo, Francesco J.; Lyons, Karen M.

    2011-01-01

    Connective tissue growth factor (CTGF) is a cysteine-rich protein the synthesis and secretion of which are hypothesized to be selectively regulated by activins and other members of the TGF-β superfamily. To investigate the in vivo roles of CTGF in female reproduction, we generated Ctgf ovarian and uterine conditional knockout (cKO) mice. Ctgf cKO mice exhibit severe subfertility and multiple reproductive defects including disrupted follicle development, decreased ovulation rates, increased numbers of corpus luteum, and smaller but functionally normal uterine horns. Steroidogenesis is disrupted in the Ctgf cKO mice, leading to increased levels of serum progesterone. We show that disrupted follicle development is accompanied by a significant increase in granulosa cell apoptosis. Moreover, despite normal cumulus expansion, Ctgf cKO mice exhibit a significant decrease in oocytes ovulated, likely due to impaired ovulatory process. During analyses of mRNA expression, we discovered that Ctgf cKO granulosa cells show gene expression changes similar to our previously reported granulosa cell-specific knockouts of activin and Smad4, the common TGF-β family intracellular signaling protein. We also discovered a significant down-regulation of Adamts1, a progesterone-regulated gene that is critical for the remodeling of extracellular matrix surrounding granulosa cells of preovulatory follicles. These findings demonstrate that CTGF is a downstream mediator in TGF-β and progesterone signaling cascades and is necessary for normal follicle development and ovulation. PMID:21868453

  17. Interstitial lung disease in connective tissue disease--mechanisms and management.

    Science.gov (United States)

    Wells, Athol U; Denton, Christopher P

    2014-12-01

    Pulmonary complications are an important extra-articular feature of autoimmune rheumatic diseases and a major cause of mortality. The underlying pathogenesis probably involves multiple cellular compartments, including the epithelium, lung fibroblasts, and the innate and adaptive immune system. Heterogeneity in the extent and progression of lung fibrosis probably reflects differences in underlying pathogenic mechanisms. Growing understanding of the key pathogenic drivers of lung fibrosis might lead to the development of more effective targeted therapies to replicate the treatment advances in other aspects of these diseases. Interstitial lung disease (ILD) in connective tissue disease (CTD) is characterized using the classification of the idiopathic interstitial pneumonias. Systemic sclerosis is most frequently associated with ILD and, in most of these patients, ILD manifests as a histological pattern of nonspecific interstitial pneumonia. Conversely, in rheumatoid arthritis, the pattern of ILD is most often usual interstitial pneumonia. The key goals of clinical assessment of patients with both ILD and CTD are the detection of ILD and prognostic evaluation to determine which patients should be treated. Data from treatment trials in systemic sclerosis support the use of immunosuppressive therapy, with the treatment benefit largely relating to the prevention of progression of lung disease.

  18. Regulation and role of connective tissue growth factor in AngII-induced myocardial fibrosis.

    Science.gov (United States)

    Rosin, Nicole L; Falkenham, Alec; Sopel, Mryanda J; Lee, Timothy D G; Légaré, Jean-Francois

    2013-03-01

    Exposure of rodents to angiotensin II (AngII) is a common model of fibrosis. We have previously shown that cellular infiltration of bone marrow-derived progenitor cells (fibrocytes) occurs before deposition of extracellular matrix and is associated with the production of connective tissue growth factor (CTGF). In the present study, we characterized the role of CTGF in promoting fibrocyte accumulation and regulation after AngII exposure. In animals exposed to AngII using osmotic minipumps (2.0 μg/kg per min), myocardial CTGF mRNA peaked at 6 hours (21-fold; P fibrocyte migration (1 day) into the myocardium or ECM deposition (3 days). CTGF protein expression was evident by day 3 of AngII exposure and seemed to be localized to resident cells. Isolated cardiomyocytes and microvascular endothelial cells responded to AngII with increased CTGF production (2.1-fold and 2.8-fold, respectively; P fibrocytes suggested a role in fibrocyte proliferation (twofold; P fibrocytes or TGF-β mRNA up-regulation. In addition, CTGF contributes to fibrocyte proliferation in the myocardium and enhances fibrocyte differentiation into a myofibroblast phenotype responsible for ECM deposition.

  19. The Effect of Connective Tissue Growth Factor on Human Renal Tubular Epithelial Cell Transdifferentiation

    Institute of Scientific and Technical Information of China (English)

    张春; 朱忠华; 邓安国

    2004-01-01

    To investigate the role of connective tissue growth factor (CTGF) in transdifferentiation of human renal tubular epithelial cell (HKC), in vitro cultured HKC cells were divided into 3 groups: negtive control, low dose CTGF-treated group (rh CTGF, 2.5 ng/ml) and high dose CTGF-treated (rhCTGF, 5.0 ng/ml). Then the expression of α-smooth muscle actin (α-SMA) were assessed by indirect immuno-fluorescence, and the percentage of α-SMA positive cells were assessed by flow cytometry. RT-PCR were also performed to examine the mRNA level of α-SMA. Upon the stimulation of different concentrations of rhCTGF, the expression of α-SMA were markedly stronger than that in negative controls. The percentages of α-SMA positive cells were significantly higher in the stimulated groups than that of negative controls (38.9 %, 65.5 % vs 2.4 %, P<0.01) . α-SMA mRNA levels were also up-regulated by the stimulation of rhCTGF (P<0.01). These results suggest that CTGF can promote the transdifferentiation of human renal tubular epithelial cells towards myofibroblast (Myo-F).

  20. U1-RNP and TLR receptors in the pathogenesis of mixed connective tissue diseasePart I. The U1-RNP complex and its biological significance in the pathogenesis of mixed connective tissue disease.

    Science.gov (United States)

    Paradowska-Gorycka, Agnieszka

    2015-01-01

    Mixed connective tissue disease (MCTD) is a rare autoimmune syndrome, signified by complex interactions between disease-related phenomena, including inflammation, proliferative vascular arteriopathy, thrombotic events and humoral autoimmune processes. It is still controversial whether MCTD is a distinct clinical entity among systemic connective tissue diseases, although several authors consider that it is distinct and underline characteristic, distinct clinical, serological and immunogenetic features. The putative target of autoimmunity in MCTD is U1-RNP, which is a complex of U1-RNA and small nuclear RNP. Both the U1-RNA component and the specific proteins, particularly U1-70K, engage immune cells and their receptors in a complex network of interactions that ultimately lead to autoimmunity, inflammation, and tissue injury. U1-RNA is capable of inducing manifestations consistent with TLR activation. Stimulation of innate immunity by native RNA molecules with a double-stranded secondary structure may help explain the high prevalence of autoimmunity to RNA binding proteins.

  1. HEMOBILIA DUE TO VASCULITIS OF THE GALL-BLADDER IN A PATIENT WITH MIXED CONNECTIVE-TISSUE DISEASE

    NARCIS (Netherlands)

    KUIPERS, EJ; VANLEEUWEN, MA; NIKKELS, PGJ; JAGER, J; VANRIJSWIJK, MH

    1991-01-01

    A 30-year-old woman with mixed connective tissue disease presented with acute abdominal pain and signs of blood loss. At cholecystectomy she appeared to have lost a considerable amount of blood into the biliary tract due to bleeding of the gall bladder. Microscopic examination showed vasculitis of t

  2. Diagnosis of Connective Tissue Disorders based on Independent Component Analysis of Aortic Shape and Motion from 4D MR Images

    DEFF Research Database (Denmark)

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

    2006-01-01

    Independent component analysis (ICA) is employed for com\\$\\backslash\\$-puter-aided diagnosis (CAD) allowing objective identification of subjects with connective tissue disorder from 4D aortic MR images. Stationary independent components assist in the disease detection, which is the first...

  3. Injection of marinade with actinidin increases tenderness of porcine M. biceps femoris and affects myofibrils and connective tissue

    DEFF Research Database (Denmark)

    Christensen, M.; Torngren, M. A.; Gunvig, A.

    2009-01-01

    BACKGROUND: Marination of beef muscles with brine solutions containing proteolytic enzymes from fruit extracts has been shown to tenderize meat. However, the effect of marination with actinidin on tenderness of pork muscles has not been investigated. Tenderness and eating quality of porcine M. bi...... indicate that actinidin tenderizes pork M. biceps femoris by affecting both the myofibrils and connective tissue....

  4. 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

    2014-01-01

    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 discrete 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.

  5. 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.

  6. Elevated Urinary Connective Tissue Growth Factor in Diabetic Nephropathy Is Caused by Local Production and Tubular Dysfunction

    NARCIS (Netherlands)

    Gerritsen, Karin G. F.; Leeuwis, JanWillem; Koeners, Maarten P.; Bakker, Stephan J. L.; van Oeveren, Willem; Aten, Jan; Tarnow, Lise; Rossing, Peter; Wetzels, Jack F. M.; Joles, Jaap A.; Kok, Robbert Jan; Goldschmeding, Roel; Nguyen, Tri Q.

    2015-01-01

    Connective tissue growth factor (CTGF; CCN2) plays a role in the development of diabetic nephropathy (DN). Urinary CTGF (uCTGF) is elevated in DN patients and has been proposed as a biomarker for disease progression, but it is unknown which pathophysiological factors contribute to elevated uCTGF. We

  7. [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.

  8. 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.

  9. Comparative electron microscopy of basophils and mast cells, in vivo and in vitro.

    Science.gov (United States)

    Eguchi, M

    1991-01-01

    We compared the fine structure and electron microscopic cytochemical findings of basophils and mast cells from humans, guinea pigs, rabbits, mice and rats. The particulate structure was the most frequently observed and most typical structure of human and rabbit basophil granules and of guinea pig mast cell granules. The most prominent feature of guinea pig basophils and murine mast cells was that the fine structure of the granules was homogeneous. The fine structure of the granules in guinea pig basophils resembled that in murine mast cells, while the fine structure of the granules of guinea pig mast cells resembled those in human and rabbit mast cells. In mouse mast cells in culture, the majority of the granules contained small vesicles, which were also observed in human basophils in culture and in mouse basophils in vivo. The degrees of cytochemical reactivity of acid mucopolysaccharides among the species were different. Peroxidase activity was positive in most basophils and in human mast cells. Among mammals, the granules of basophils and mast cells present heterogeneous fine structure. It is of interest that the basophil granules of some species resemble the mast cell granules rather than the basophil granules of other species.

  10. Role of human mast cells and basophils in bronchial asthma.

    Science.gov (United States)

    Marone, Gianni; Triggiani, Massimo; Genovese, Arturo; De Paulis, Amato

    2005-01-01

    Mast cells and basophils are the only cells expressing the tetrameric (alphabetagamma2) structure of the high affinity receptor for IgE (FcepsilonRI) and synthesizing histamine in humans. Human FcepsilonRI+ cells are conventionally considered primary effector cells of bronchial asthma. There is now compelling evidence that these cells differ immunologically, biochemically, and pharmacologically, which suggests that they might play distinct roles in the appearance and fluctuation of the asthma phenotype. Recent data have revealed the complexity of the involvement of human mast cells and basophils in asthma and have shed light on the control of recruitment and activation of these cells in different lung compartments. Preliminary evidence suggests that these cells might not always be detrimental in asthma but, under some circumstances, they might exert a protective effect by modulating certain aspects of innate and acquired immunity and allergic inflammation.

  11. Isolation and characterization of connective tissue progenitor cells derived from human fracture-induced hemarthrosis in vitro.

    Science.gov (United States)

    Lee, Sang Yang; Miwa, Masahiko; Sakai, Yoshitada; Kuroda, Ryosuke; Oe, Keisuke; Niikura, Takahiro; Matsumoto, Tomoyuki; Fujioka, Hiroyuki; Doita, Minoru; Kurosaka, Masahiro

    2008-02-01

    In our search for alternative sources of connective tissue progenitor cells that can be obtained with minimal invasion, we studied human intraarticular fracture-induced hemarthrosis of the knee and attempted to isolate connective tissue progenitors from the hemarthrosis. Hemarthrosis was aspirated from the knee joints of 13 patients suffering from intraarticular osteochondral fractures of the knee. Mononuclear cells were isolated from the aspirated hemarthrosis by density gradient separation, and cultured. We were able to obtain fibroblastic adherent cells from the mononuclear cell fractions. Flow cytometry analysis after in vitro expansion on tissue culture plastic revealed that the fibroblastic cells were positive for CD29, CD44, CD105, and CD166, and negative for CD14, CD34, CD45, and CD133. These cells could differentiate in vitro into osteogenic, chondrogenic, and adipogenic cells in the presence of lineage-specific induction factors. These results demonstrate that human intraarticular fracture-induced knee hemarthrosis contains connective tissue progenitor cells with morphologic features, immunophenotypic markers, and differentiation potential that are similar to bone marrow stromal cells. This suggests that hemarthrosis, which is easy to harvest without unnecessary invasion to the patient, has possible future clinical applications such as in tissue-engineered therapies for severe osteochondral defects, posttraumatic osteoarthritis, and delayed fracture unions or nonunions.

  12. The mechanically adaptive connective tissue of echinoderms: its potential for bio-innovation in applied technology and ecology.

    Science.gov (United States)

    Barbaglio, A; Tricarico, S; Ribeiro, A; Ribeiro, C; Sugni, M; Di Benedetto, C; Wilkie, I; Barbosa, M; Bonasoro, F; Candia Carnevali, M D

    2012-05-01

    Echinoderms possess unique connective tissues, called mutable collagenous tissues (MCTs), which undergo nervously mediated, drastic and reversible or irreversible changes in their mechanical properties. Connective tissue mutability influences all aspects of echinoderm biology and is a key-factor in the ecological success of the phylum. Due to their sensitivity to endogenous or exogenous agents, MCTs may be targets for a number of common pollutants, with potentially drastic effects on vital functions. Besides its ecological relevance, MCT represents a topic with relevance to several applied fields. A promising research route looks at MCTs as a source of inspiration for the development of novel biomaterials. This contribution presents a review of MCT biology, which incorporates recent ultrastructural, biomolecular and biochemical analyses carried out in a biotechnological context.

  13. 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

  14. 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

  15. A bioreactor test system to mimic the biological and mechanical environment of oral soft tissues and to evaluate substitutes for connective tissue grafts.

    Science.gov (United States)

    Mathes, Stephanie H; Wohlwend, Lorenz; Uebersax, Lorenz; von Mentlen, Roger; Thoma, Daniel S; Jung, Ronald E; Görlach, Christoph; Graf-Hausner, Ursula

    2010-12-15

    Gingival cells of the oral connective tissue are exposed to complex mechanical forces during mastication, speech, tooth movement and orthodontic treatments. Especially during wound healing following surgical procedures, internal and external forces may occur, creating pressure upon the newly formed tissue. This clinical situation has to be considered when developing biomaterials to augment soft tissue in the oral cavity. In order to pre-evaluate a collagen sponge intended to serve as a substitute for autogenous connective tissue grafts (CTGs), a dynamic bioreactor system was developed. Pressure and shear forces can be applied in this bioreactor in addition to a constant medium perfusion to cell-material constructs. Three-dimensional volume changes and stiffness of the matrices were analyzed. In addition, cell responses such as cell vitality and extracellular matrix (ECM) production were investigated. The number of metabolic active cells constantly increased under fully dynamic culture conditions. The sponges remained elastic even after mechanical forces were applied for 14 days. Analysis of collagen type I and fibronectin revealed a statistically significant accumulation of these ECM molecules (P tissue remodeling processes, was observed under dynamic conditions only. The results indicate that the tested in vitro cell culture system was able to mimic both the biological and mechanical environments of the clinical situation in a healing wound.

  16. 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 .

  17. Molecular evolution of connective tissue growth factor in Cyprinidae (Teleostei: Cypriniformes)

    Institute of Scientific and Technical Information of China (English)

    Xianghui Kong; Xuzhen Wang; Xiaoni Gan; Junbing Li; Shunping He

    2008-01-01

    Connective tissue growth factor (CTGF) plays an important role in regulation ofcell growth, differentiation, apoptosis and individual development in animals. The study of sequences variation and molecular evolution of CTGF gene across various species of the cyprinid could be helpful for understanding of speciation and gene divergence in this kind of fish. In this study, 19 novel sequences of CTGF gene were obtained from the representative species of the family Cyprinidae using PCR amplification, cloning and sequencing. Phylogenetic relationships of Cyprinidae were reconstructed by neighbor-joining (N J), maximum parsimony (MP), maximum likelihood (ML) and Bayesian method. Oryzias latipes from the family Cyprinodontidae was assigned to be the outgroup taxon. Leuciscini and Barbini were clustered into the monophyletic lineages, respectively, with the high nodal supports. The estimation of the ratio of non-synonymous to synonymous substitution (dN/dS) for the various branches indicated that there stood the different evolution rates between the Leuciscini and the Barbini. With the ratio of dN/dS of the Leuciscini being lower than that of the Barbini, species within the Barbini were demonstrated to be subjected to the relatively less selection pressure and under the relaxable evolution background. A 6 bp indel (insertion/deletion) was found at the 5' end of CTGF gene of Cyprinidae, and this 6 bp deletion only appeared in the Leuciscini, which is a typical characteristic of the Leuciscini and provides evidence for the monophylogeny of the Leuciscini. For the amino acid sequences of CTGF protein, the most variations and indels were distributed in the signal region and IGFBP region of this protein, implying that these variations were correlated with the regulation of the CTGF gene expression and protein activity.

  18. Human recombinant RNASET2-induced inflammatory response and connective tissue remodeling in the medicinal leech.

    Science.gov (United States)

    Baranzini, Nicolò; Pedrini, Edoardo; Girardello, Rossana; Tettamanti, Gianluca; de Eguileor, Magda; Taramelli, Roberto; Acquati, Francesco; Grimaldi, Annalisa

    2017-01-09

    In recent years, several studies have demonstrated that the RNASET2 gene is involved in the control of tumorigenicity in ovarian cancer cells. Furthermore, a role in establishing a functional cross-talk between cancer cells and the surrounding tumor microenvironment has been unveiled for this gene, based on its ability to act as an inducer of the innate immune response. Although several studies have reported on the molecular features of RNASET2, the details on the mechanisms by which this evolutionarily conserved ribonuclease regulates the immune system are still poorly defined. In the effort to clarify this aspect, we report here the effect of recombinant human RNASET2 injection and its role in regulating the innate immune response after bacterial challenge in an invertebrate model, the medicinal leech. We found that recombinant RNASET2 injection induces fibroplasias, connective tissue remodeling and the recruitment of numerous infiltrating cells expressing the specific macrophage markers CD68 and HmAIF1. The RNASET2-mediated chemotactic activity for macrophages has been further confirmed by using a consolidated experimental approach based on injection of the Matrigel biomatrice (MG) supplemented with recombinant RNASET2 in the leech body wall. One week after injection, a large number of CD68(+) and HmAIF-1(+) macrophages massively infiltrated MG sponges. Finally, in leeches challenged with lipopolysaccharides (LPS) or with the environmental bacteria pathogen Micrococcus nishinomiyaensis, numerous macrophages migrating to the site of inoculation expressed high levels of endogenous RNASET2. Taken together, these results suggest that RNASET2 is likely involved in the initial phase of the inflammatory response in leeches.

  19. A patient with ascending aortic dilatation, similar to phenotypes of connective tissue disorders.

    Science.gov (United States)

    Onrat, S T; Emmiler, M; Sivaci, Y; Söylemez, Z; Ozgöz, A; Imirzalioğlu, N

    2009-04-14

    We report on the clinical and molecular findings of a patient who presented alopecia, epicanthus, micrognathia, retrognathia, high arched palate, hypertelorism, Chiari type I malformation, mixed-type hearing loss but with normal heartbeat Q-T interval, malformed earlobes, down-slanted palpebral fissures, downturned corners of the mouth, syndactyly, atopic eczema, and seizures. The patient was a male adult, 23 years old, with short stature (153 cm) and low weight (50.5 kg), due to severe aortic insufficiency and dilatation of the ascending aorta. Conventional cytogenetic screening did not show any chromosomal gains or losses. Molecular genetic screening was conducted for gene mutations involved in various syndromes; the mutations found included [beta-fibrinogen -455 G>A wt/wt (wt/mut), PAI-1 4G/5G (4G/4G), HPA1 a/b (a/a), MTHFR C677T wt/wt (wt/mut), ACE I/D (I/I), and Apo E E3/E4]. Many clinical and molecular genetics findings overlapped with other conditions associated with arterial tortuosity and arterial aneurysms, including the Marfan, Ehler-Danlos, Shprintzen-Goldberg, and Loeys-Dietz syndromes. Although a diagnosis of Shprintzen-Goldberg syndrome was based on clinical findings and radiographic findings indicate other syndromes, aortic root dilatation seems to be a new symptom, similar to phenotypes of connective tissue disorders. The unique grouping of clinical manifestations in this patient and the molecular genetics findings lead us to suggest that this case could be an example of a previously unrecognized syndrome.

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

    Science.gov (United States)

    Iudici, Michele; Irace, Rosaria; Riccardi, Antonella; Cuomo, Giovanna; Vettori, Serena; Valentini, Gabriele

    2017-01-01

    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 (pRaynaud’s phenomenon Fibromyalgia is one of the major contributors of physical QoL, whereas no factor influencing mental component has been identified. An improvement in QoL can be observed in less than half of patients over a 2-year follow-up. Larger studies are needed to identify factors influencing QoL and to define the role of pharmacological treatments. PMID:28203114

  1. Comparison of different test systems for simultaneous autoantibody detection in connective tissue diseases.

    Science.gov (United States)

    Eissfeller, Petra; Sticherling, Michael; Scholz, Dietmar; Hennig, Kirsten; Lüttich, Tanja; Motz, Manfred; Kromminga, Arno

    2005-06-01

    The serological diagnosis of connective tissue diseases (CTDs) is based on the analysis of circulating autoantibodies to cytoplasmic and nuclear proteins (extractable nuclear antigens [ENAs]). The determination of autoantibody specificities supports the clinical diagnosis of the type of CTD and also often the prognosis of the disease. The former indirect immunofluorescence (IIF) technique still provides a useful screening method that currently is supplemented by a range of different techniques allowing the exact determination of single autoantibody specificities. These ENA profiling techniques include ELISA, immunoblotting, line-blot assays, and flow cytometric bead-based multiplex assays. The novel line immunoassay (LIA) from Mikrogen has been introduced in a recent study as a suitable technique for the simultaneous detection of autoantibodies in a routine clinical laboratory, providing comparable results as ELISA and ELiA (both from Pharmacia Diagnostics) (see Damoiseaux et al., this volume). In this study, LIAs from three different manufacturers were performed in 30 serum samples from patients with dermatological manifestations and 27 samples from SLE patients with renal involvement. The line assays from Mikrogen (recomLine ANA/ENA), Innogenetics (Inno-Lia ANA Update), and Imtec (ANA-LIA) were compared for antigen composition, handling, and statistical analysis including sensitivity and concordance. Autoantibody frequencies detected by the Mikrogen, Innogenetics, and Imtec line assays were 14.0%, 19.3%, and 15.8% for RNP; 14.0%, 22.8%, and 14.0% for Sm; 26.3%, 31.6%, and 40.3% for SSA; 3.5%, 12.3%, and 14.0% for SSB; and 3.5%, 14.0%, and 10.5% for histones. Our studies show that the line assay format is an easy-to-use, sensitive, and specific method for ENA antibody detection in human sera.

  2. [The clinical immunology laboratory in diagnosis and monitoring of systemic lupus erythematosus and connective tissue diseases].

    Science.gov (United States)

    Sinico, R A; Radice, A

    2005-01-01

    The laboratory and particularly clinical immunology laboratories have an essential role in diagnosing and monitoring systemic lupus erythematosus (SLE), as well as other connective tissue diseases. The role of the clinical immunology laboratory in these diseases is to confirm or exclude diagnosis, to monitor disease activity, and to identify subgroup of patients. To obtain the best results in terms of diagnostic performance and clinical usefulness, the following recommendations should be fulfilled: anti-nuclear antibodies (ANA) determination by indirect immunofluorescence on Hep-2 cells is an effective screening assay in patients with clinical features of SLE. A negative ANA test makes the diagnosis of SLE unlikely. Anti-dsDNA antibodies are highly specific for SLE and are associated with renal involvement. The method of choice for anti-dsDNA is the Farr assay; however, the necessity of using radioactive materials reduces its applicability. As an alternative, immunofluorescence on Crithidia Luciliae can be used in the diagnostic phase due to its high specificity. The detection of antibodies to extractable nuclear antigens (ENA) and to phospholipids (lupus anticoagulant and anti-cardiolipin antibodies) is useful in identifying subgroups of patients at risk for some clinical manifestations. Anti-dsDNA measurement with a quantitative assay (the Farr assay or ELISA) is currently the best method to monitor disease activity along with complement levels. New assays (anti-C1q and anti-nucleosome antibodies) have been recently proposed for the diagnosis (anti-nucleosome) and monitoring of SLE patients (anti-C1q and anti-nucleosome antibodies), with promising results.

  3. Brachial Neuritis With Phrenic Nerve Involvement in a Patient With a Possible Connective Tissue Disease

    Directory of Open Access Journals (Sweden)

    Meera Subash BS

    2014-05-01

    Full Text Available Background. Brachial neuritis (BN is a rare inflammatory condition of peripheral nerves, usually involving the cervicobrachial plexus. These patients present with sudden onset of shoulder and arm pain that evolves into muscle weakness and atrophy.. Case Report. A 33-year-old woman presented with a 1-month history of diffuse pain in her thorax. She had no trauma or inciting incident prior to the onset of this pain and was initially treated for muscle spasms. The patient was seen in the emergency room multiple times and was treated with several courses of antibiotics for pneumonia on the basis of clinical symptoms and abnormal x-rays. The pleuritic chest pain persisted for at least 4 months, and the patient was eventually admitted for worsening pain and dyspnea. On physical examination, crackles were heard at both lung bases, and chest inspection revealed increased expansion in the upper thorax but poor expansion of the lower thorax and mild paradoxical respiration. “Sniff” test revealed no motion of the left hemidiaphragm and reduced motion on the right hemidiaphragm. Her computed tomography scan revealed bilateral atelectasis, more severe at the left base. She reported no symptoms involving her joints or skin or abdomen. Her presentation and clinical course are best explained by BN with a bilateral diaphragmatic weakness. However, she had a positive ANA, RF, anti-RNP antibody, and anti SS-A. Conclusion. Patients with BN can present with diffuse thoracic pain, pleuritic chest pain, and diaphragmatic weakness. Our patient may represent a case of connective tissue disease presenting with brachial plexus neuritis.

  4. Susceptibility to glaucoma damage related to age and connective tissue mutations in mice.

    Science.gov (United States)

    Steinhart, Matthew R; Cone-Kimball, Elizabeth; Nguyen, Cathy; Nguyen, Thao D; Pease, Mary E; Chakravarti, Shukti; Oglesby, Ericka N; Quigley, Harry A

    2014-02-01

    The purpose of this research was to study the effects of age and genetic alterations in key connective tissue proteins on susceptibility to experimental glaucoma in mice. We used mice haploinsufficient in the elastin gene (EH) and mice without both alleles of the fibromodulin gene (FM KO) and their wild type (WT) littermates of B6 and CD1 strains, respectively. FM KO mice were tested at two ages: 2 months and 12 months. Intraocular pressure (IOP) was measured by Tonolab tonometer, axial lengths and widths measured by digital caliper post-enucleation, and chronic glaucoma damage was measured using a bead injection model and optic nerve axon counts. IOP in EH mice was not significantly different from WT, but FM KO were slightly lower than their controls (p = 0.04). Loss of retinal ganglion cell (RGC) axons was somewhat, but not significantly greater in young EH and younger or older FM KO strains than in age-matched controls (p = 0.48, 0.34, 0.20, respectively, multivariable regression adjusting for IOP exposure). Older CD1 mice lost significantly more RGC axons than younger CD1 (p = 0.01, multivariable regression). The CD1 mouse strain showed age-dependence of experimental glaucoma damage to RGC in the opposite, and more expected, direction than in B6 mice in which older mice are more resistant to damage. Genetic alteration in two genes that are constituents of sclera, fibromodulin and elastin do not significantly affect RGC loss.

  5. [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)

  6. 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.

  7. Rapamycin regulates connective tissue growth factor expression of lung epithelial cells via phosphoinositide 3-kinase.

    Science.gov (United States)

    Xu, Xuefeng; Wan, Xuan; Geng, Jing; Li, Fei; Yang, Ting; Dai, Huaping

    2013-09-01

    The pathogenesis of idiopathic pulmonary fibrosis (IPF) remains largely unknown. It is believed that IPF is mainly driven by activated alveolar epithelial cells that have a compromised migration capacity, and that also produce substances (such as connective tissue growth factor, CTGF) that contribute to fibroblast activation and matrix protein accumulation. Because the mechanisms regulating these processes are unclear, the aim of this study was to determine the role of rapamycin in regulating epithelial cell migration and CTGF expression. Transformed epithelial cell line A549 and normal human pulmonary alveolar or bronchial epithelial cells were cultured in regular medium or medium containing rapamycin. Real time reverse transcriptase polymerase chain reaction was employed to determine CTGF mRNA expression. Western blotting and an enzyme-linked immunosorbent assay were used for detecting CTGF protein. Wound healing and migration assays were used to determine the cell migration potential. Transforming growth factor (TGF)-β type I receptor (TβRI) inhibitor, SB431542 and phosphoinositide 3-kinase (PI3K) inhibitor, LY294002 were used to determine rapamycin's mechanism of action. It was found that treatment of A549 and normal human alveolar or bronchial epithelial cells with rapamycin significantly promoted basal or TGF-β1 induced CTGF expression. LY294002, not SB431542 attenuated the promotional effect of rapamycin on CTGF expression. Cell mobility was not affected by rapamycin in wound healing and migration assays. These data suggest rapamycin has a profibrotic effect in vitro and underscore the potential of combined therapeutic approach with PI3K and mammalian target of rapamycin inhibitors for the treatment of animal or human lung fibrosis.

  8. 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.

  9. Expression of connective tissue growth factor in male breast cancer: clinicopathologic correlations and prognostic value.

    Directory of Open Access Journals (Sweden)

    Miangela M Lacle

    Full Text Available Connective tissue growth factor (CTGF/CCN2 is a member of the CCN family of secreted proteins that are believed to play an important role in the development of neoplasia. In particular, CTGF has been reported to play an important role in mammary tumorigenesis and to have prognostic value in female breast cancer (FBC. The aim of the present study was to investigate clinicopathologic correlations and prognostic value of CTGF in male breast cancer (MBC and to compare these findings with FBC. For this, we studied CTGF protein expression by immunohistochemistry in 109 MBC cases and 75 FBC cases. In MBC, stromal CTGF expression was seen in the majority of the cases 78% (85/109 with high expression in 31/109 cases (28.4%, but expression in tumor cells was only seen in 9.2% (10/109 of cases. High stromal CTGF expression correlated with high grade and high proliferation index (>15% assessed by MIB-1 immunohistochemical staining. CTGF expression in tumor epithelial cells did not correlate with any of the clinicopathologic features. In FBC, stromal CTGF expression positively correlated with mitotic count and tumor CTGF expression was associated with triple negative status of the tumor (p = 0.002. Neither stromal nor tumor epithelial cell CTGF expression had prognostic value in MBC and FBC. In conclusion, stromal CTGF expression was seen in a high percentage of MBC and was correlated with high grade and high proliferation index. In view of the important role of the microenvironment in cancer progression, this might suggest that stromal CTGF could be an interesting target for novel therapies and molecular imaging. However, the lack of association with prognosis warrants caution. The potential role of CTGF as a therapeutic target for triple negative FBC deserves to be further studied.

  10. Connective tissue growth factor hammerhead ribozyme attenuates human hepatic stellate cell function

    Institute of Scientific and Technical Information of China (English)

    Run-Ping Gao; David R Brigstock

    2009-01-01

    AIM: To determine the effect of hammerhead ribozyme targeting connective tissue growth factor (CCN2) on human hepatic stellate cell (HSC) function. METHODS: CCN2 hammerhead ribozyme cDNA plus two self-cleaving sequences were inserted into pTriEx2 to produce pTriCCN2-Rz. Each vector was individually transfected into cultured LX-2 human HSCs, which were then stimulated by addition of transforming growth factor (TGF)-b1 to the culture medium. Semiquantitative RT-PCR was used to determine mRNA levels for CCN2 or collagen Ⅰ, while protein levels of each molecule in cell lysates and conditioned medium were measured by ELISA. Cell-cycle progression of the transfected cells was assessed by flow cytometry. RESULTS: In pTriEx2-transfected LX-2 cells, TGF-β1 treatment caused an increase in the mRNA level for CCN2 or collagen Ⅰ, and an increase in produced and secreted CCN2 or extracellular collagen Ⅰ protein levels. pTriCCN2-Rz-transfected LX-2 cells showed decreased basal CCN2 or collagen mRNA levels, as well as produced and secreted CCN2 or collagen Ⅰ protein. Furthermore, the TGF-b1-induced increase in mRNA or protein for CCN2 or collagen Ⅰ was inhibited partially in pTriCCN2-Rz-transfected LX-2 cells. Inhibition of CCN2 using hammerhead ribozyme cDNA resulted in fewer of the cells transitioning into S phase. CONCLUSION: Endogenous CCN2 is a mediator of basal or TGF-b1-induced collagen Ⅰ production in human HSCs and regulates entry of the cells into Sphase.

  11. Root coverage stability of the subepithelial connective tissue graft and guided tissue regeneration: A 30-month follow-up clinical trial

    OpenAIRE

    Rosetti, Elizabeth P. [UNESP; Marcantonio Júnior, Elcio [UNESP; Zuza, Elizangela P. [UNESP; Marcantonio, Rosemary Adriana Chierici [UNESP

    2013-01-01

    Objectives: The aim of this study was to compare the long-term clinical effects produced by subepithelial connective tissue graft (SCTG) and guided tissue regeneration combined with demineralized freeze-dried bone allograft (GTR-DFDBA) in the treatment of gingival recessions in a 30-month follow-up clinical trial. Methods: Twenty-four defects were treated in 12 patients who presented canine or pre-molar Miller class I and/or II bilateral gingival recessions. GTR-DFDBA and SCTG treatments were...

  12. Histamine content and secretion in basophils and mast cells.

    Science.gov (United States)

    Dvorak, A M

    1998-01-01

    Biochemical determinations of the histamine content and secretion from basophils and mast cells have been available for some time, and much of the complex anatomy of these cellular populations and their release reactions has been documented using the electron microscope. The ultrastructural analyses led to the description of vesicular transport between secretory granules and the plasma membrane as a mechanism for secretion from basophils and mast cells--a process termed piecemeal degranulation. Proof of concepts incorporated in a general degranulation model put forth in 1975 (DVORAK, H.F. and DVORAK, A.M.) requires high magnification imaging of a granule constituent in trafficking vesicles in the process of a stimulated release reaction in which the constituent release is monitored biochemically. Development and application of a new enzyme-affinity method to detect histamine at high magnifications in well-preserved ultrastructural samples have provided the necessary means to establish proof that appropriate secretagogues can stimulate the vesicular transport of histamine in basophils and mast cells during release reactions monitored biochemically. The background information necessary to the understanding of this result is presented here, as well as the development and verification of the diamine oxidase-gold method to image histamine in human mast cell granules as the test system. Also presented are applications using this technology to examine histamine stores and secretion in vitro, in vivo, and ex vivo in human basophils and mast cells and in mouse mast cells. Specifically examined are histamine stores developing in maturing mast cells induced to develop de novo from cultured human cord blood cells, secretagogue-stimulated release and recovery of histamine stores from isolated, purified human lung mast cells ex vivo, cytokine-stimulated degranulation of human skin mast cells and their histamine stores in vivo, piecemeal degranulation of human gut mast cells and

  13. Palatal Augmentation Technique: A Predictable Method to Increase the Palatal Connective Tissue at Donor Sites- A Consecutive Case Series.

    Science.gov (United States)

    Carnio, João; Koutouzis, Theofilos

    2015-01-01

    The palatal masticatory mucosa between the canine and first molar is the main source of connective tissue graft (CTG) for use in periodontal plastic surgery. The purpose of this study was to evaluate the palatal augmentation technique (PAT) to increase the palatal connective tissue donor area using a collagen sponge inserted between the palatal flap and bone. The 26 patients enrolled in this study were referred for root coverage and ridge augmentation procedures. All patients lacked adequate donor palatal tissue thickness. The PAT uses a full-thickness flap and insertion of a sterile lyophilized bovine collagen sponge between the flap and bone. The palatal thickness was clinically assessed before and after collagen sponge insertion. A manual probe was inserted in the mucosal surface perpendicular to the long axis of each tooth approximately 6 mm from the gingival margin. Probing depth (PD) and recession (REC) were also recorded. Treatment with PAT resulted in a statistically significant increase in the palatal thickness. The overall mean increase was from 2.03 mm before surgery to 3.57 mm after surgery, with no major alterations in PD and REC. Healing proceeded uneventfully and occurred by primary intention. PAT appeared to be a predictable procedure to create connective tissue donor graft in deficient areas and had uneventful postoperative healing.

  14. Dynamic culture induces a cell type-dependent response impacting on the thickness of engineered connective tissues.

    Science.gov (United States)

    Fortier, Guillaume Marceau; Gauvin, Robert; Proulx, Maryse; Vallée, Maud; Fradette, Julie

    2013-04-01

    Mesenchymal cells are central to connective tissue homeostasis and are widely used for tissue-engineering applications. Dermal fibroblasts and adipose-derived stromal cells (ASCs) allow successful tissue reconstruction by the self-assembly approach of tissue engineering. This method leads to the production of multilayered tissues, devoid of exogenous biomaterials, that can be used as stromal compartments for skin or vesical reconstruction. These tissues are formed by combining cell sheets, generated through cell stimulation with ascorbic acid, which favours the cell-derived production/organization of matrix components. Since media motion can impact on cell behaviour, we investigated the effect of dynamic culture on mesenchymal cells during tissue reconstruction, using the self-assembly method. Tissues produced using ASCs in the presence of a wave-like movement were nearly twice thicker than under standard conditions, while no difference was observed for tissues produced from dermal fibroblasts. The increased matrix deposition was not correlated with an increased proliferation of ASCs, or by higher transcript levels of fibronectin or collagens I and III. A 30% increase of type V collagen mRNA was observed. Interestingly, tissues engineered from dermal fibroblasts featured a four-fold higher level of MMP-1 transcripts under dynamic conditions. Mechanical properties were similar for tissues reconstructed using dynamic or static conditions. Finally, cell sheets produced using ASCs under dynamic conditions could readily be manipulated, resulting in a 2 week reduction of the production time (from 5 to 3 weeks). Our results describe a distinctive property of ASCs' response to media motion, indicating that their culture under dynamic conditions leads to optimized tissue engineering.

  15. 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.

  16. 89 Is Basophil Specific Response to Hymenoptera Venom Related to T Regulatory Cells?

    OpenAIRE

    Kucera, Petr; Hulikova, Katarina; Cvackova, Milada; Planska, Daniela; Riegerova, Kamila

    2012-01-01

    Background The exact mechanism of systemic hypersensitivity to venom is not exactly understood. It is suggested T cells with regulatory potential can downregulate other T cell subsets and effector cells, ex. mast cell or basophils. We focused on relationship of specific basophil reactivity in relationship to proportion of regulatory T cells. Methods Forty-five patients with history of systemic symptoms of allergy to Hymenoptera venom were included. Basophil reactivity before the treatment and...

  17. Development of a microarray-based method to detect exposure of human basophils to IL-3.

    Science.gov (United States)

    MacGlashan, Donald

    2012-11-30

    Human basophils are an accessible participant of the human allergic reaction. There is natural variation in various functional endpoints and in signaling molecule expression but there has been only a limited effort to place this information in the context of mRNA expression profiles. The goal of these studies was to develop gene transcript profiles associated with IL-3 exposure for use in probing basophil phenotypes. Highly purified human basophils were cultured under several conditions and the cells subsequently analyzed by microarray analysis of gene transcript expression. Basophils were cultured with or without IL-3 for 24 h and the expression profile, relative to pre-culture, analyzed for transcripts that act in a reciprocal fashion depending on the condition. A 51-gene transcript set was identified that was composed of 34 transcripts that increased with IL-3 and decreased without IL-3 and a further 17 transcripts that did the reverse. This set of transcripts was validated on two microarray chips. The changes induced by IL-3 were stable in time, with 3 day cultures generating a signature concordant with 1 day cultures. The inverted nature of the response to ±IL-3 suggested that the normal circulating basophil is balanced between a state of high and low IL-3 exposure and thus is very sensitive to changes in IL-3. For example, the basophil could detect the early generation of IL-3 that follows IgE-mediated stimulation of basophils. When this signature tool was applied to freshly isolated basophils, it was observed that the signature was similar for the same subjects' basophil sampled weeks apart. It was also shown that the 51-gene transcript was insensitive to the method of preparing purified basophils. Finally, these studies provided an estimate for the normal in vivo exposure of circulating basophils to IL-3 or IL-3-like functionality. These studies identified an IL-3 signature to probe changes in basophils occurring in vivo.

  18. Short-, Intermediate-, and Long-Term Changes in Basophil Reactivity Induced by Venom Immunotherapy

    OpenAIRE

    Rodríguez Trabado, Ana; Cámara Hijón, Carmen; Ramos Cantariño, Alfonso; Romero-Chala, Silvia; García-Trujillo, José Antonio; Fernández Pereira, Luis Miguel

    2016-01-01

    Purpose The basophil activation test (BAT) has been used to monitor venom immunotherapy (VIT) due to its high specificity. A previous study has reported a good correlation between a significant decrease in basophil activation during 5 years of VIT and clinical protection assessed by sting challenge. The following prospective study was performed to examine changes in basophil reactivity over a complete VIT period of 5 years. Methods BAT in a dose-response curve was studied prospectively in 10 ...

  19. Downregulation of connective tissue growth factor inhibits the growth and invasion of gastric cancer cells and attenuates peritoneal dissemination

    Directory of Open Access Journals (Sweden)

    Zhang Hong-Yan

    2011-09-01

    Full Text Available Abstract Background Connective tissue growth factor (CTGF has been shown to be implicated in tumor development and progression. However, the role of CTGF in gastric cancer remains largely unknown. Results In this study, we showed that CTGF was highly expressed in gastric cancer tissues compared with matched normal gastric tissues. The CTGF expression in tumor tissue was associated with histologic grade, lymph node metastasis and peritoneal dissemination (P 1 expression. Moreover, knockdown of CTGF expression also markedly reduced the migration and invasion of gastric cancer cells and decreased the expression of matrix metalloproteinase (MMP-2 and MMP-9. Animal studies revealed that nude mice injected with the CTGF knockdown stable cell lines featured a smaller number of peritoneal seeding nodules than the control cell lines. Conclusions These data suggest that CTGF plays an important role in cell growth and invasion in human gastric cancer and it appears to be a potential prognostic marker for patients with gastric cancer.

  20. Contribution of basophils to cutaneous immune reactions and Th2-mediated allergic responses

    Directory of Open Access Journals (Sweden)

    Atsushi eOtsuka

    2015-08-01

    Full Text Available Basophils are potent effector cells of innate immunity and also play a role in T helper 2 (Th2-mediated allergic responses. But, although their in vitro functions are well studied, their in vivo functions remain largely unknown. However, several mouse models of basophil depletion have recently been developed and used to investigate basophil functions. For example, in a croton oil-induced model of irritant contact dermatitis in conditionally basophil-depleted transgenic mice, we found that basophils rapidly infiltrate inflamed skin and subsequently induce infiltration of eosinophils. We also showed that basophils induce Th2 skewing upon epicutaneous sensitization with various haptens and peptide antigens. Intriguingly, basophils also promoted Th2 polarization upon protein antigen exposure in the presence of dendritic cells (DCs. The dermal DC subset associated with Th2 skewing was recently identified as CD301b+ DC. Such studies with basophil-deficient mouse models have significantly improved our understanding of the mechanisms involved in human immune-related diseases. In this review, we will focus on the relative contribution of basophils and DCs to Th2-mediated allergic responses.

  1. 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...... is a major route of tissue clearance for these components. The lymph/serum ratio of PICP was 1.0 in conscious pigs, indicating a direct release into the circulation. Total protein in lymph decreased (p less than 0.04) during surgery/anesthesia, whereas no changes were observed in serum. Pigs can be used...

  2. The role of tumor cell-derived connective tissue growth factor (CTGF/CCN2) in pancreatic tumor growth

    DEFF Research Database (Denmark)

    Bennewith, Kevin L; Huang, Xin; Ham, Christine M

    2009-01-01

    Pancreatic cancer is highly aggressive and refractory to existing therapies. Connective tissue growth factor (CTGF/CCN2) is a fibrosis-related gene that is thought to play a role in pancreatic tumor progression. However, CCN2 can be expressed in a variety of cell types, and the contribution of CCN2...... adenocarcinomas. Furthermore, we found increased CCN2 staining in clinical pancreatic tumor tissue relative to stromal cells surrounding the tumor, supporting our assertion that tumor cell-derived CCN2 is important for pancreatic tumor growth. Taken together, these data improve our understanding of the mechanisms...

  3. Frequency of autoantibodies and connective tissue diseases in Chinese patients with optic neuritis.

    Directory of Open Access Journals (Sweden)

    Hongyang Li

    Full Text Available BACKGROUND: Optic neuritis (ON is often associated with other clinical or serological markers of connective tissue diseases (CTDs. To date, the effects of autoantibodies on ON are not clear. PURPOSE: To assess the prevalence, clinical patterns, and short outcomes of autoantibodies and Sjögren's syndrome (SS involvement in Chinese ON patients and evaluate the relationship between ON, including their subtypes, and autoantibodies. METHODS: A total of 190 ON patients were divided into recurrent ON (RON, bilateral ON (BON, and isolated monocular ON (ION. Demographic, clinical, and serum autoantibodies data were compared between them with and without SS involvement. Serum was drawn for antinuclear antibody (ANA, extractable nuclear antigen antibodies (SSA/SSB, rheumatoid factor (RF, anticardiolipin antibodies (ACA, and anti-double-stranded DNA antibody (A-ds DNA, anticardiolipin antibody (ACLs, anti-β2-glycoprotein I (β2-GPI and Aquaporin-4 antibodies (AQP4-Ab. Spectral-domain optical coherence tomography (SD-OCT was used to evaluate the atrophy of the optic nerve. RESULTS: 68 patients (35.79% had abnormal autoantibodies, 26(13.68% patients met diagnostic criteria for CTDs, including 15(7.89% patients meeting the criteria for SS. Antibodies including SSA/SSB 23 (30.26% (p1 and p 2<0.001 and AQP4-Ab10 (13.16% (p1 = 0.044, p2 = 0.01 were significantly different in patients in the RON group when compared with those in the BON (P1 = RON VS ION and ION (p2 = RON VS ION groups. SS was more common in RON patients (p1 = 0.04, p2 = 0.028. There was no significant difference between SSA/SSB positive and negative patients in disease characteristics or severity. Similar results were obtained when SS was diagnosed in SSA/SSB positive patients. CONCLUSION: RON and BON were more likely associated with abnormal autoantibodies; furthermore, AQP4 antibody, SSA/SSB and SS were more common in the RON patients. AQP4 antibody determination is

  4. Injury and regeneration of intramuscular connective tissue subjected to various regimes of distraction

    Institute of Scientific and Technical Information of China (English)

    ZHAO Li; XU Song-jie; SUN Xiao-tang

    2008-01-01

    To investigate the effect on intramuscular connective tissue and passive range of joint motion by the stress produced in limb lengthening. Methods:An animal model of limb lengthening was established in the tibia of rabbits. Distraction was initiated at a rate of 1 mm/d and 2 mm/d in two steps respectively,and both proceeded until 10%and 20% of the tibia length was achieved. Muscle samples were harvested at the time when distraction ended and at the 4th week of consolidation after the distraction. Scanning electron microscope was applied to observe the morphological changes of the perimysium. The goniometer,which we made for this study,was used to measure the passive range of joint motion.Results:The collagen fibers were partitioned in bundles, crimped and interconnected closely and orderly.In the regime of 1 mm/d distraction with 10% lengthening,no apparent changes of the collagen fiber and passive range of joint motion was demonstrated. When tibia was increased to 20%,the crimped fibers showed a tendency of being straightened while the passive range of joint motion was reduced. The findings remained the same at the 4th week of consolidation. In the regime of 2 mm/d distraction with 10% lengthening,the crimped structure of the collagen fibers in the perimysium disappeared and the fibers were almost straightened. Additionally,the interconnection of the collagen fibers became loosened and interstice was presented among the fibers. At the 4th week of consolidation,the restoration to the original crimped structure was not completed. When the lengthening ratio was increased to 20%,the collagen fibers were straightened completely. This condition remained unchanged throughout all 4 weeks. The passive range of joint motion was reduced dramatically in the regime of 2 mm/d distraction.Conclusion:The ultrastructure of perimysium and the passive range of joint motion in the regime of 1 mm/d lengthening shows the condition closest to the normal ones. The regime of 2 mm

  5. Optimum scratch assay condition to evaluate connective tissue growth factor expression for anti-scar therapy.

    Science.gov (United States)

    Moon, Heekyung; Yong, Hyeyoung; Lee, Ae-Ri Cho

    2012-02-01

    To evaluate a potential anti-scar therapy, we first need to have a reliable in vitro wound model to understand dermal fibroblast response upon cell injury and how cytokine levels are changed upon different wound heal phases. An in vitro wound model with different scratch assay conditions on primary human foreskin fibroblast monolayer cultures was prepared and cytokine levels and growth properties were evaluated with the aim of determining optimum injury conditions and observation time. Morphological characteristics of differently scratched fibroblasts from 0 to 36 h post injury (1 line, 2 lines and 3 lines) were investigated. The expression of connective tissue growth factor, CTGF, which is a key mediator in hyper-tropic scarring, and relative intensity of CTGF as a function of time were determined by western blot and gelatin Zymography. After injury (1 line), CTGF level was increased more than 2-fold within 1 h and continuously increased up to 3-fold at 6 h and was leveled down to reach normal value at 36 h, at which cell migration was complete. In more serious injury (2 lines), higher expression of CTGF was observed. The down regulation of CTGF expression after CTGF siRNA/lipofectamine transfection in control, 1 line and 2 lines scratch conditions were 40%, 75% and 55%, respectively. As a model anti-CTGF based therapy, CTGF siRNA with different ratios of linear polyethyleneimine (PEI) complexes (1:1, 1:5, 1:10, 1:20 and 1:30) were prepared and down-regulation efficacy of CTGF was evaluated with our optimized scratch assay, which is 1 line injury at 6 h post injury observation time. As the cationic linear PEI ratio increased, the down regulation efficacy was increased from 20% (1:20) to 55% (1:30). As CTGF level was increased to the highest at 6 h and leveled down afterwards, CTGF level at 6 h could provide the most sensitive response upon CTGF siRNA transfection. The scratch assay in the present study can be employed as a useful experimental tool to differentiate

  6. Role of connective tissue growth factor in experimental radiation nephropathy in rats

    Institute of Scientific and Technical Information of China (English)

    LIU Dian-ge; WANG Tie-min

    2008-01-01

    Background Connective tissue growth factor (CTGF) is a potent fibrogenic cytokine which has been associated with progressive glomerulosclerosis and tubulointerstitial fibrosis. We investigated the role of CTGF on the progression of a rat model of radiation nephropathy.Methods The model of radiation nephropathy in rats was established as follows: control group (n=-12), underwent only laparotomy; irradiated group (n=20), underwent a laparotomy, then the rats were subjected to a single dose 25 Gy X-ray to the kidneys. The rats were followed up one, three, six and nine months after renal exposure to radiation.Results Renal dysfunction was noted early in irradiated rats. Histological analysis showed focal glomerular sclerotic lesions at an early stage after irradiation. Radiation-induced glomerular and tubulointerstitial injudes were particularly severe the sixth month after irradiation as compared to the control group (P <0.01). By immunohistochemistry, increased expression of CTGF was noted in the irradiated kidneys, which began to increase from the first month after irradiation,and remained significantly higher at the sixth and ninth month after irradiation (P <0.01). Upon Westem blot analysis CTGF protein expression showed an increase in the radiation treated kidneys compared with the control rats. The expression of CTGF closely correlated with the progression of radiation nephropathy. The expression of α-smooth muscle actin, vimentin, type Ⅲ collagen and type Ⅳ collagen was also high in the irradiated kidney as compared to control rat kidneys (P <0.05), and was most severe at the sixth and ninth month after irradiation (P <0.01). By double immunostaining, CTGF expressing cells were found to be α-SMA-positive myofibroblasts and vimentin-positive tubular epithelial cells. Glomerular expression of CTGF closely correlated with the glomerular expression of α-SMA (r=0.628, P <0.01), vimentin (r=0.462, P <0.05) and accumulation of type Ⅳ collagen (r=0.584, P <0

  7. 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.

  8. [Chosen problems of mental functioning in patients with chronic systemic connective tissue diseases base on example of rheumatoid arthritis].

    Science.gov (United States)

    Nasiłowska-Barud, Alicja; Żuk, Mariola

    2015-01-01

    Disorders in mental functioning are indicated as the cause of all connective tissue diseases and also as their consequences. That is why psychologist's help may be very important for patients with rheumatoid arthritis. Psychological observations of patients with chronic systemic connective tissue diseases show a number of negative emotional states such as fear, anxiety, insecurity, depressed mood, depression, impatience, anger and a sense of loss These patients constantly experience pain of varying intensity and location. In many of them progressive disease leads to the advancement of mental crisis. Methods of psychological therapy must be focused on strenghtening mental resilience and helping in surviving mental crisis. Psychological therapy should concentrate on raising self-esteem, training interpersonal skills and teaching relaxation techniques to cope better with pain and suffering. Psychological therapy should support the patient in struggling with the problems caused by the disease and developing ways of adapting to life with the disease.

  9. Developmental delay and connective tissue disorder in four patients sharing a common microdeletion at 6q13-14.

    Science.gov (United States)

    Van Esch, Hilde; Rosser, Elisabeth M; Janssens, Sandra; Van Ingelghem, Ingrid; Loeys, Bart; Menten, Bjorn

    2010-10-01

    Interstitial deletions of the long arm of chromosome 6 are rare, and most reported cases represent large, cytogenetically detectable deletions. The implementation of array comparative genome hybridisation in the diagnostic work-up of patients presenting with congenital disorders, including developmental delay, has enabled identification of many patients with smaller chromosomal imbalances. In this report, the cases are presented of four patients with a de novo interstitial deletion of chromosome 6q13-14, resulting in a common microdeletion of 3.7 Mb. All presented with developmental delay, mild dysmorphism and signs of lax connective tissue. Interestingly, the common deleted region harbours 16 genes, of which COL12A1 is a good candidate for the connective tissue pathology.

  10. Coordination between catch connective tissue and muscles through nerves in the spine joint of the sea urchin Diadema setosum.

    Science.gov (United States)

    Motokawa, Tatsuo; Fuchigami, Yoshiro

    2015-03-01

    Echinoderms have catch connective tissues that change their stiffness as a result of nervous control. The coordination between catch connective tissue and muscles was studied in the spine joint of the sea urchin Diadema setosum. Spine joints are equipped with two kinds of effector: spine muscles and a kind of catch connective tissue, which is called the catch apparatus (CA). The former is responsible for spine movements and the latter for maintenance of spine posture. Diadema show a shadow reaction in which they wave spines when a shadow falls on them, which is a reflex involving the radial nerves. Dynamic mechanical tests were performed on the CA in a joint at which the muscles were severed so as not to interfere with the mechanical measurements. The joint was on a piece of the test that contained other spines and a radial nerve. Darkening of the preparation invoked softening of the CA and spine waving (the shadow reaction). Electrical stimulation of the radial nerve invoked a similar response. These responses were abolished after the nerve pathways from the radial nerve to spines had been cut. A touch applied to the CA stiffened it and the adjacent spines inclined toward the touched CA. A touch to the base of the adjacent spine softened the CA and the spines around the touched spine inclined towards it. The softening of the CA can be interpreted as a response that reduces the resistance of the ligaments to spine movements. Our results clearly show coordination between catch connective tissue and muscles through nerves.

  11. Surgical treatment of localized gingival recessions using coronally advanced flaps with or without subepithelial connective tissue graft

    Science.gov (United States)

    Bellver-Fernández, Ricardo; Martínez-Rodriguez, Ana-María; Gioia-Palavecino, Claudio; Caffesse, Raul-Guillermo

    2016-01-01

    Background A coronally advanced flap with subepithelial connective tissue graft is the gold standard surgical treatment of gingival recessions, since it offers a higher probability of achieving complete root coverage compared with other techniques. However, optimum short- and middle-term clinical results have also been obtained with coronally advanced flaps alone. The aim of the present study was to evaluate the results obtained by the surgical treatment of localized gingival recessions using coronally advanced flaps with or without subepithelial connective tissue graft. Material and Methods The reduction of recession height was assessed, together with the gain in gingival attachment apical to the recession, and total reduction of recession, in a comparative study of two techniques. Twenty-two gingival recessions were operated upon: 13 in the control group (coronally advanced flap) and 9 in the test group (coronally advanced flap associated to subepithelial connective tissue graft). Results After 18 months, the mean reduction of recession height was 2.2 ± 0.8 mm in the control group and 2.3 ± 0.7 mm in the test group, with a mean gain in gingival attachment of 1.3 ± 0.9 mm and 2.3 ± 1.3 mm, respectively. In percentage terms, the mean reduction of recession height was 84.6 ± 19.6% in the control group and 81.7 ± 17.8% in the test group, with a mean gain in gingival attachment of 20.5 ± 37.4% and 184.4 ± 135.5%, respectively. Conclusions Significant reduction of gingival recession was achieved with both techniques, though the mean gain in gingival attachment (in mm and as a %) was greater in test group. Key words:Gingival recession, coronally advanced flap, subepthelial connective tissue graft. PMID:26595836

  12. 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.

  13. 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.

  14. UVA/UVA1 phototherapy and PUVA photochemotherapy in connective tissue diseases and related disorders: a research based review

    Directory of Open Access Journals (Sweden)

    Breuckmann Frank

    2004-09-01

    Full Text Available Abstract Background Broad-band UVA, long-wave UVA1 and PUVA treatment have been described as an alternative/adjunct therapeutic option in a number of inflammatory and malignant skin diseases. Nevertheless, controlled studies investigating the efficacy of UVA irradiation in connective tissue diseases and related disorders are rare. Methods Searching the PubMed database the current article systematically reviews established and innovative therapeutic approaches of broad-band UVA irradiation, UVA1 phototherapy and PUVA photochemotherapy in a variety of different connective tissue disorders. Results Potential pathways include immunomodulation of inflammation, induction of collagenases and initiation of apoptosis. Even though holding the risk of carcinogenesis, photoaging or UV-induced exacerbation, UVA phototherapy seems to exhibit a tolerable risk/benefit ratio at least in systemic sclerosis, localized scleroderma, extragenital lichen sclerosus et atrophicus, sclerodermoid graft-versus-host disease, lupus erythematosus and a number of sclerotic rarities. Conclusions Based on the data retrieved from the literature, therapeutic UVA exposure seems to be effective in connective tissue diseases and related disorders. However, more controlled investigations are needed in order to establish a clear-cut catalogue of indications.

  15. [Rhythmic changes in morphometric parameters of fiber structure of myocardial connective scar tissue in rats].

    Science.gov (United States)

    Malyshev, I I

    1993-02-01

    The results of morphometrical and stereological analysis of cardiomyocytes and rats' cardiac scar conjunctive tissue are stated in this article. It was shown that during the myocardial construction, the collagen fibril tension occurs. When diastole ensues, they goes back to point of departure. The author supposes that such a rhythmical, synchronous with systole changes of scar conjunctive tissue collagen fibres indicates the conjunctive tissue scar participation in cardiac contractile activity.

  16. Clinical Comparison of Full and Partial Double Pedicle Flaps with Connective Tissue Grafts for Treatment of Gingival Recession

    Directory of Open Access Journals (Sweden)

    Ardeshir Ranjbari

    2016-09-01

    Full Text Available Statement of the Problem: Gingival recession has been considered as the most chal-lenging issue in the field of periodontal plastic surgery. Purpose: The purpose of this study was to evaluate the clinical efficacy of root cover-age procedures by using partial thickness double pedicle graft and compare it with full thickness double pedicle graft. Materials and Method: Eight patients, aged 15 to 58 years including 6 females and 2 males with 20 paired (mirror image defects with class I and II gingival recession were randomly assigned into two groups. Clinical parameters such as recession depth, recession width, clinical attachment level, probing depth, and width of keratinized tissue were measured at the baseline and 6 months post-surgery. A mucosal double papillary flap was elevated and the respective root was thoroughly planed. The con-nective tissue graft was harvested from the palate, and then adapted over the root. The pedicle flap was secured over the connective tissue graft and sutured. The surgical technique was similar in the control group except for the prepared double pedicle graft which was full thickness. Results: The mean root coverage was 88.14% (2.83 mm in the test group and 85.7% (2.75 mm in the control group. No statistical differences were found in the mean reduction of vertical recession, width of recession, or probing depth between the test and control groups. In both procedures, the width of keratinized tissue increased after three months and the difference between the two groups was not statistically signifi-cant in this respect. Conclusion: Connective tissue with partial and full thickness double pedicle grafts can be successfully used for treatment of marginal gingival recession.

  17. Direct microCT imaging of non-mineralized connective tissues at high resolution.

    Science.gov (United States)

    Naveh, Gili R S; Brumfeld, Vlad; Dean, Mason; Shahar, Ron; Weiner, Steve

    2014-01-01

    The 3D imaging of soft tissues in their native state is challenging, especially when high resolution is required. An X-ray-based microCT is, to date, the best choice for high resolution 3D imaging of soft tissues. However, since X-ray attenuation of soft tissues is very low, contrasting enhancement using different staining materials is needed. The staining procedure, which also usually involves tissue fixation, causes unwanted and to some extent unknown tissue alterations. Here, we demonstrate that a method that enables 3D imaging of soft tissues without fixing and staining using an X-ray-based bench-top microCT can be applied to a variety of different tissues. With the sample mounted in a custom-made loading device inside a humidity chamber, we obtained soft tissue contrast and generated 3D images of fresh, soft tissues with a resolution of 1 micron voxel size. We identified three critical conditions which make it possible to image soft tissues: humidified environment, mechanical stabilization of the sample and phase enhancement. We demonstrate the capability of the technique using different specimens: an intervertebral disc, the non-mineralized growth plate, stingray tessellated radials (calcified cartilage) and the collagenous network of the periodontal ligament. Since the scanned specimen is fresh an interesting advantage of this technique is the ability to scan a specimen under load and track the changes of the different structures. This method offers a unique opportunity for obtaining valuable insights into 3D structure-function relationships of soft tissues.

  18. Repair of full-thickness tendon injury using connective tissue progenitors efficiently derived from human embryonic stem cells and fetal tissues.

    Science.gov (United States)

    Cohen, Shahar; Leshansky, Lucy; Zussman, Eyal; Burman, Michael; Srouji, Samer; Livne, Erella; Abramov, Natalie; Itskovitz-Eldor, Joseph

    2010-10-01

    The use of stem cells for tissue engineering (TE) encourages scientists to design new platforms in the field of regenerative and reconstructive medicine. Human embryonic stem cells (hESC) have been proposed to be an important cell source for cell-based TE applications as well as an exciting tool for investigating the fundamentals of human development. Here, we describe the efficient derivation of connective tissue progenitors (CTPs) from hESC lines and fetal tissues. The CTPs were significantly expanded and induced to generate tendon tissues in vitro, with ultrastructural characteristics and biomechanical properties typical of mature tendons. We describe a simple method for engineering tendon grafts that can successfully repair injured Achilles tendons and restore the ankle joint extension movement in mice. We also show the CTP's ability to differentiate into bone, cartilage, and fat both in vitro and in vivo. This study offers evidence for the possibility of using stem cell-derived engineered grafts to replace missing tissues, and sets a basic platform for future cell-based TE applications in the fields of orthopedics and reconstructive surgery.

  19. 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.

  20. Protein Fv produced during vital hepatitis is a novel activator of human basophils and mast cells.

    Science.gov (United States)

    Patella, V; Bouvet, J P; Marone, G

    1993-11-15

    Protein Fv is found in the normal liver and is released in the stools of patients suffering from viral hepatitis. Protein Fv isolated from five patients stimulated the release of histamine and sulfidopeptide leukotriene C4 from purified and unpurified peripheral blood basophils. Protein Fv absorbed with protein A-Sepharose coated with polyclonal IgG did not induce histamine secretion, whereas removal of putative contaminating Ig did not modify the releasing activity. The characteristics of the release reaction were similar to those of rabbit IgG anti-Fc fragment of human IgE (anti-IgE). There was an excellent correlation (Spearman rank coefficient (rs) = 0.83; p ADZ) blocked both anti-IgE- and protein Fv-induced releases, whereas human polyclonal IgG and a monoclonal IgG purified from another myeloma patient (patient ZEG) selectively blocked protein Fv-induced secretion. Protein Fv also induced the release of preformed (histamine and tryptase) and de novo synthesized mediators (sulfidopeptide leukotriene C4 and/or PGD2) from mast cells purified from human lung parenchyma and skin tissues. There was a significant correlation between the maximal percent histamine release induced by protein Fv and anti-IgE from skin mast cells (rs = 0.63; p < 0.01). There was also an excellent correlation between histamine and tryptase release caused by protein Fv from both lung (rs = 0.80; p < 0.001) and skin mast cells (rs = 0.70; p < 0.01). Thus, we established that protein Fv acts as a novel activator of human basophils and mast cells presumably by interacting with the VH domain of the IgE.

  1. 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 ...

  2. Evaluation of Allergy Effector Cell Function: Suppression of Basophils in Chronic Helminth Infections

    Science.gov (United States)

    2011-01-01

    basophils are probably best known for their participation in the effector phase of immediate hypersensitivity reactions, some studies have suggested...had Schistosoma mansoni infections were then sensitized to Penicillin V. When mice in these groups were challenged with Pen V, body temperature was... hypersensitivity reactions, reduced basophil functionality could be one way helminth infection protects against allergic disease. 2. Determine the

  3. Increased level of basophil CD203c expression predicts severe chronic urticaria.

    Science.gov (United States)

    Ye, Young-Min; Yang, Eun-Mi; Yoo, Hye-Soo; Shin, Yoo-Seob; Kim, Seung-Hyun; Park, Hae-Sim

    2014-01-01

    Increased FcεR1α expression with upregulated CD203c expression on peripheral basophils is seen in patients with chronic urticaria (CU). However, there has been no published report on the association between CD203c expression level and clinical disease activity in CU patients. To investigate whether the increase of basophil activation is associated with the disease activity of CU, we measured basophil CD203c expression using a tricolor flow cytometric method in 82 CU patients and 21 normal controls. The relationship between the percentage of CD203c-expressing basophils and clinical parameters was analyzed. The mean basophil CD203c expression was significantly higher in CU patients than in healthy controls (57.5% vs 11.6%, P basophil CD203c expression in severe CU patients was significantly higher than in non-severe CU (66.5% ± 23.3% vs 54.0% ± 23.3%, P = 0.033). Multiple logistic regression analysis indicated that both ≥ 72% basophil CD203c expression and urticaria activity score (UAS)≥ 13 were significant predictors of severe CU (P = 0.005 and P = 0.032, respectively). These findings suggest that the quantification of basophil activation with CD203c at baseline may be used as a potential predictor of severe CU requiring another treatment option beyond antihistamines.

  4. Unusual cause of sudden cardiac death : Basophilic degeneration of coronary arteries

    NARCIS (Netherlands)

    Jessurun, GAJ; Tio, RA; Ribbert, LSM; Willemse, F; Boonstra, PW; Crijns, HJGM

    1996-01-01

    Basophilic or mucoid degeneration of the intima in the coronary arteries is an extremely rare cause of premature atherosclerosis. An unusual case of fatal basophilic degeneration of the coronary arteries 142 days after delivery is reported. (C) 1996 Wiley-Liss, Inc.

  5. Basophil activation test with food additives in chronic urticaria patients.

    Science.gov (United States)

    Kang, Min-Gyu; Song, Woo-Jung; Park, Han-Ki; Lim, Kyung-Hwan; Kim, Su-Jung; Lee, Suh-Young; Kim, Sae-Hoon; Cho, Sang-Heon; Min, Kyung-Up; Chang, Yoon-Seok

    2014-01-01

    The role of food additives in chronic urticaria (CU) is still under investigation. In this study, we aimed to explore the association between food additives and CU by using the basophil activation test (BAT). The BAT using 15 common food additives was performed for 15 patients with CU who had a history of recurrent urticarial aggravation following intake of various foods without a definite food-specific IgE. Of the 15 patients studied, two (13.3%) showed positive BAT results for one of the tested food additives. One patient responded to monosodium glutamate, showing 18.7% of CD203c-positive basophils. Another patient showed a positive BAT result to sodium benzoate. Both patients had clinical correlations with the agents, which were partly determined by elimination diets. The present study suggested that at least a small proportion of patients with CU had symptoms associated with food additives. The results may suggest the potential utility of the BAT to identity the role of food additives in CU.

  6. 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.

  7. U1-RNP and Toll-like receptors in the pathogenesis of mixed connective tissue diseasePart II. Endosomal TLRs and their biological significance in the pathogenesis of mixed connective tissue disease.

    Science.gov (United States)

    Paradowska-Gorycka, Agnieszka

    2015-01-01

    Mixed connective tissue disease (MCTD) is a chronic autoimmune immunopathological disease of unknown etiology, which is characterized by the presence of various clinical symptoms and the presence of autoantibodies against U1-RNP particles. The U1-RNP component engages immune cells and their receptors in a complex network of interactions that ultimately lead to autoimmunity, inflammation, and tissue injury. The anti-U1-RNP autoantibodies form an immune complex with self-RNA, present in MCTD serum, which can act as endosomal Toll-like receptor (TLR) ligands. Inhibition of TLRs by nucleic acids is a promising area of research for the development of novel therapeutic strategies against pathogenic infection, tumorigenesis and autoimmunity. In this review we summarize current knowledge of endogenous TLRs and discuss their biological significance in the pathogenesis of MCTD. In part I we described the structure, biological function and significance of the U1-RNP complex in MCTD.

  8. A thermomechanical framework for reconciling the effects of ultraviolet radiation exposure time and wavelength on connective tissue elasticity.

    Science.gov (United States)

    Goh, K L; Chen, S Y; Liao, K

    2014-10-01

    Augmentation of the mechanical properties of connective tissue using ultraviolet (UV) radiation-by targeting collagen cross-linking in the tissue at predetermined UV exposure time [Formula: see text] and wavelength [Formula: see text]-has been proposed as a therapeutic method for supporting the treatment for structural-related injuries and pathologies. However, the effects of [Formula: see text] and [Formula: see text] on the tissue elasticity, namely elastic modulus [Formula: see text] and modulus of resilience [Formula: see text], are not entirely clear. We present a thermomechanical framework to reconcile the [Formula: see text]- and [Formula: see text]-related effects on [Formula: see text] and [Formula: see text]. The framework addresses (1) an energy transfer model to describe the dependence of the absorbed UV photon energy, [Formula: see text], per unit mass of the tissue on [Formula: see text] and [Formula: see text], (2) an intervening thermodynamic shear-related parameter, [Formula: see text], to quantify the extent of UV-induced cross-linking in the tissue, (3) a threshold model for the [Formula: see text] versus [Formula: see text] relationship, characterized by   [Formula: see text]-the critical [Formula: see text] underpinning the association of [Formula: see text] with [Formula: see text]-and (4) the role of [Formula: see text] in the tissue elasticity. We hypothesized that [Formula: see text] regulates [Formula: see text] (UV-stiffening hypothesis) and [Formula: see text] (UV-resilience hypothesis). The framework was evaluated with the support from data derived from tensile testing on isolated ligament fascicles, treated with two levels of [Formula: see text] (365 and 254 nm) and three levels of [Formula: see text] (15, 30 and 60 min). Predictions from the energy transfer model corroborated the findings from a two-factor analysis of variance of the effects of [Formula: see text] and [Formula: see text] treatments. Student's t test revealed

  9. 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

  10. A rare case of mixed connective tissue disease presenting with central nervous system glioma, vasculitis and polymyositis

    Directory of Open Access Journals (Sweden)

    Rushabh Parikh

    2015-12-01

    Full Text Available Mixed connective tissue disease (MCTD was first recognized by Sharp and Colleagues in 1972 among a group of patients with overlapping clinical features of systemic lupus erythematosis (SLE, scleroderma and myositis, with the presence of distinctive antibodies against, what now is known to be U1-ribonucleoprotein (RNP. We report an unusual case of a 23-year old female with MCTD characterized by the coexistence of signs, symptoms and immunological features of 3 defined autoimmune diseases SLE, systemic sclerosis (SSc, polymyositis (PM and an unusual presence of central nervous system (CNS Glioma. [Int J Res Med Sci 2015; 3(12.000: 3917-3920

  11. Treatment of Vasodilator-resistant Mixed Connective Tissue Disease-associated Pulmonary Arterial Hypertension with Glucocorticoid and Cyclophosphamide.

    Science.gov (United States)

    Sugawara, Eri; Kato, Masaru; Hisada, Ryo; Oku, Kenji; Bohgaki, Toshiyuki; Horita, Tetsuya; Yasuda, Shinsuke; Atsumi, Tatsuya

    2017-01-01

    Pulmonary arterial hypertension (PAH) associated with systemic lupus erythematosus (SLE) or mixed connective tissue disease (MTCD), in contrast to other types of PAH, may respond to immunosuppressive therapy. Most PAH cases with an immunosuppressant response were in the early stages of the disease (WHO functional class III or less). The present case was a 34-year-old woman with MCTD-associated PAH (WHO functional class IV) who was resistant to a combination of three vasodilators. Afterwards, she was treated with glucocorticoid and cyclophosphamide. This case suggested the potential benefit of immunosuppressants in patients with severe MCTD-associated PAH.

  12. 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

  13. Subcutaneous Connective Tissue Reaction to a New Nano Zinc-Oxide Eugenol Sealer in Rat Model

    Science.gov (United States)

    Omidi, Salma; Javidi, Maryam; Zarei, Mina; Mushakhian, Siavash; Jafarian, Amirhossein

    2017-01-01

    Introduction: The aim of this animal study was to evaluate the histological response of the new nano zinc-oxide eugenol (NZOE) sealer in comparison with Pulp Canal Sealer (ZOE based) and AH-26 (epoxy resin sealer). Methods and Materials: A total of 27 Wistar rats were used. Four polyethylene tubes were implanted in the back of each rat (three tubes containing the test materials and an empty tube as a control). Then, 9 animals were sacrificed at each interval of 15, 30 and 60 days, and the implants were removed with the surrounding tissues.Samples were evaluated for the presence of inflammatory cell (mononuclear cell), vascular changes, fibrous tissue formation and present of giant cell. Comparisons between groups and time-periods were performed using the Kruskal-Wallis and Mann-Whitney U non-parametric tests. The level of significance was set at 0.05. Results: No significant difference was observed in tissue reactions and biocompatibility pattern of three sealers during 3 experimental periods (P<0.05). In all groups the tissue behavior showed tendency to decrease the irritation effect over time. Conclusion: The new nano zinc-oxide eugenol sealer has histocompatibility properties comparable to conventional commercial sealers. PMID:28179927

  14. Expression of connective tissue growth factor in asthmatic airway smooth muscle cells

    NARCIS (Netherlands)

    Burgess, Janette K; Johnson, Peter R A; Ge, Qi; Au, Wendy W; Poniris, Maree H; McParland, Brent E; King, Greg; Roth, Michael; Black, Judith L

    2003-01-01

    There is strong evidence to implicate transforming growth factor-beta in the remodeling that occurs in asthma, as levels are increased in bronchial lavage fluid and gene expression is increased in bronchial tissue. Transforming growth factor-beta is also known to increase the release of collagen fro

  15. 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.

  16. Circulating protein fragments of cartilage and connective tissue degradation are diagnostic and prognostic markers of rheumatoid arthritis and ankylosing spondylitis.

    Directory of Open Access Journals (Sweden)

    Anne C Bay-Jensen

    Full Text Available Inflammation driven connective tissue turnover is key in rheumatic diseases, such as ankylosing spondylitis (AS. Few biomarkers are available for measuring disease prognosis or the efficacy of interventions applied in these tissue-related conditions. Type II collagen is the primary structural protein of cartilage and type III collagen of connective tissues, and obvious targets for the collagenalytic, which increase during tissue inflammation. The objective of the study was to investigate the diagnostic and prognostic utility of cartilage, C2M, and synovial, C3M, turnover biomarkers in AS. Serum samples were retrieved from patients suffering from AS (n = 103, RA (n = 47 and healthy controls (n = 56. AS progressors were defined as having new vertebral syndesmophytes or more that 3 unit change in mSASSS over a two-year period. Type II collagen degradation markers in serum were measured by the C2M ELISA, and type III collagen degradation by the C3M ELISA. Logistic regression and dichotomized decision tree were used to analyze the prognostic value of the markers individually or in combination. Both C2M and C3M levels were significantly higher in RA patients than in healthy controls (p<0.0001. Diagnostic utility was analyzed by ROC and areas under the curve (AUCs were 72% and 89% for C2M and C3M, respectively. Both C2M and C3M, were significantly higher in serum samples from AS patient than from healthy controls (p<0.0001. The AUCs of C2M and C3M, respectively, were 70% and 81% for AS. A combination of C2M and C3M, dichotomized according to best cut-offs for individual markers, could correctly identify 80% of the progressors and 61% of the non-progressors. The present study is the first to show that specific biomarkers of cartilage and connective tissue degradation facilitate both diagnosis and prediction of progression of RA and AS.

  17. 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 ("fo

  18. The saddle connective tissue graft: a periodontal plastic surgery technique to obtain soft tissue coronal gain on immediate implants. A case report.

    Science.gov (United States)

    González, David; Cabello, Gustavo; Olmos, Gema; Niñoles, Carlos L

    2015-01-01

    Based on recent studies regarding the advantages of flapless immediate implants on the maintenance of the soft tissue architecture (especially at papillae level) in those situations where it is necessary to extract an anterior tooth, this case report describes a clinical procedure designed to replace a hopeless central incisor (2.1) showing root resorption adjacent to an implant-supported crown (1.1), whose gingival margin is 2 mm coronal regarding the hopeless tooth to be replaced. After the extraction of the hopeless tooth (2.1), a flapless immediate implant was placed. The implant-bone gap was then filled with bone substitute and a palatal connective tissue graft was placed ad modum saddle extending at buccal level from apical to the mucogingival line, sealing the socket and extending until 6 mm at palatal level ad modum saddle. This procedure allowed symmetry of the soft tissue margins between the two implants (1.1 and 2.1) to be obtained as well as the preservation of the inter-implant papillae (1.1).

  19. Use of subepithelial connective tissue graft as a biological barrier: a human clinical and histologic case report.

    Science.gov (United States)

    Santagata, Mario; Guariniello, Luigi; Prisco, Rosario V E; Tartaro, Gianpaolo; D'Amato, Salvatore

    2014-08-01

    The aim of the present study was to develop a method to study the healing process after gingival grafting and to observe the histologic results after use of the modified edentulous ridge expansion technique. A 47-year-old nonsmoking woman with a noncontributory past medical history affected by edentulism associated with a horizontal alveolar ridge defect was referred to the authors for surgical correction of the deficit to improve implant support and the final esthetics of an implant-borne prosthesis. At the 4-month follow-up visit, a biopsy was performed by a punch technique in the same sites of healing abutment connection. The tissue was elevated from the attached gingival. Clinically, the grafted tissues seemed to be attached to the bone surfaces. The histologic findings revealed dense grafted tissues, providing long-term stability to the area. No ligament or bone, characteristic for periodontal regeneration, were observed. The presence of thick attached keratinized tissue around implants may constitute a protective factor against marginal inflammation or trauma.

  20. 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.

  1. 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.

  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

    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...... of the connective tissue, caused partly by denaturation or conformational changes of the proteins and/or by solubilization of collagen. © 2012 Elsevier Ltd....

  3. 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.

  4. Determination of collagen fibril structure and orientation in connective tissues by X-ray diffraction

    Science.gov (United States)

    Wilkinson, S. J.; Hukins, D. W. L.

    1999-08-01

    Elastic scattering of X-rays can provide the following information on the fibrous protein collagen: its molecular structure, the axial arrangement of rod-like collagen molecules in a fibril, the lateral arrangement of molecules within a fibril, and the orientation of fibrils within a biological tissue. The first part of the paper reviews the principles involved in deducing this information. The second part describes a new computer program for measuring the equatorial intensity distribution, that provides information on the lateral arrangement of molecules within a fibril, and the angular distribution of the equatorial peaks that provides information on the orientation of fibrils. Orientation of fibrils within a tissue is quantified by the orientation distribution function, g( φ), which represents the probability of finding a fibril oriented between φ and φ+ δφ. The application of the program is illustrated by measurement of g( φ) for the collagen fibrils in demineralised cortical bone from cow tibia.

  5. Varying assay geometry to emulate connective tissue planes in an in vitro model of acupuncture needling

    OpenAIRE

    Julias, Margaret; Buettner, Helen M; Shreiber, David I.

    2010-01-01

    During traditional acupuncture, fine needles are inserted subcutaneously and rotated, which causes loose fascial tissue to wind around the needle. This coupling is stronger at acupuncture points, which tend to fall above intermuscular fascial planes, than control points, which lay above skeletal muscle. These different anatomical constraints may affect the mechanical coupling. Fascia at acupuncture points is bounded on two sides by skeletal muscle, but at control points is essentially unbound...

  6. Improving prosthetic prognosis by connective tissue ridge augmentation of alveolar ridge

    OpenAIRE

    2010-01-01

    The contour of edentulous ridge should be carefully evaluated before a fixed partial denture is undertaken. The ideal ridge height and width allows placement of a natural looking pontic which facilitates maintenance of plaque-free environment. The localized alveolar ridge defect refers to the volumetric deficit of the limited extent of bone and soft tissue within the alveolar process. Such type of ridge defects can be corrected by surgical ridge augmentation that can be accomplished by the ad...

  7. Mouse basophils reside in extracellular matrix-enriched bone marrow niches which control their motility.

    Science.gov (United States)

    Smaniotto, Salete; Schneider, Elke; Goudin, Nicolas; Bricard-Rignault, Rachel; Machavoine, François; Dardenne, Mireille; Dy, Michel; Savino, Wilson

    2013-01-01

    Basophils co-express FcεRIα and CD49b, the α-2 chain of integrin-type receptor VLA-2 (α2β1), which recognizes type-1 collagen as a major natural ligand. The physiological relevance of this integrin for interactions with extracellular bone marrow matrix remains unknown. Herein, we examined the expression of several receptors of this family by bone marrow-derived basophils sorted either ex-vivo or after culture with IL-3. Having established that both populations display CD49d, CD49e and CD49f (α-4, α-5 and α-6 integrins subunits, respectively), we addressed receptor functions by measuring migration, adhesion, proliferation and survival after interacting with matched natural ligands. Type I collagen, laminin and fibronectin promoted basophil migration/adhesion, the former being the most effective. None of these ligands affected basophil viability and expansion. Interactions between basophils and extracellular matrix are likely to play a role in situ, as supported by confocal 3D cell imaging of femoral bone marrow sections, which revealed basophils exclusively in type-1 collagen-enriched niches that contained likewise laminin and fibronectin. This is the first evidence for a structure/function relationship between basophils and extracellular matrix proteins inside the mouse bone marrow.

  8. Mouse basophils reside in extracellular matrix-enriched bone marrow niches which control their motility.

    Directory of Open Access Journals (Sweden)

    Salete Smaniotto

    Full Text Available Basophils co-express FcεRIα and CD49b, the α-2 chain of integrin-type receptor VLA-2 (α2β1, which recognizes type-1 collagen as a major natural ligand. The physiological relevance of this integrin for interactions with extracellular bone marrow matrix remains unknown. Herein, we examined the expression of several receptors of this family by bone marrow-derived basophils sorted either ex-vivo or after culture with IL-3. Having established that both populations display CD49d, CD49e and CD49f (α-4, α-5 and α-6 integrins subunits, respectively, we addressed receptor functions by measuring migration, adhesion, proliferation and survival after interacting with matched natural ligands. Type I collagen, laminin and fibronectin promoted basophil migration/adhesion, the former being the most effective. None of these ligands affected basophil viability and expansion. Interactions between basophils and extracellular matrix are likely to play a role in situ, as supported by confocal 3D cell imaging of femoral bone marrow sections, which revealed basophils exclusively in type-1 collagen-enriched niches that contained likewise laminin and fibronectin. This is the first evidence for a structure/function relationship between basophils and extracellular matrix proteins inside the mouse bone marrow.

  9. The basophil activation test by flow cytometry: recent developments in clinical studies, standardization and emerging perspectives

    Directory of Open Access Journals (Sweden)

    Debard Anne-Lise

    2005-06-01

    Full Text Available Abstract The diagnosis of immediate allergy is mainly based upon an evocative clinical history, positive skin tests (gold standard and, if available, detection of specific IgE. In some complicated cases, functional in vitro tests are necessary. The general concept of those tests is to mimic in vitro the contact between allergens and circulating basophils. The first approach to basophil functional responses was the histamine release test but this has remained controversial due to insufficient sensitivity and specificity. During recent years an increasing number of studies have demonstrated that flow cytometry is a reliable tool for monitoring basophil activation upon allergen challenge by detecting surface expression of degranulation/activation markers (CD63 or CD203c. This article reviews the recent improvements to the basophil activation test made possible by flow cytometry, focusing on the use of anti-CRTH2/DP2 antibodies for basophil recognition. On the basis of a new triple staining protocol, the basophil activation test has become a standardized tool for in vitro diagnosis of immediate allergy. It is also suitable for pharmacological studies on non-purified human basophils. Multicenter studies are now required for its clinical assessment in large patient populations and to define the cut-off values for clinical decision-making.

  10. The basophil activation test by flow cytometry: recent developments in clinical studies, standardization and emerging perspectives.

    Science.gov (United States)

    Boumiza, Radhia; Debard, Anne-Lise; Monneret, Guillaume

    2005-06-30

    The diagnosis of immediate allergy is mainly based upon an evocative clinical history, positive skin tests (gold standard) and, if available, detection of specific IgE. In some complicated cases, functional in vitro tests are necessary. The general concept of those tests is to mimic in vitro the contact between allergens and circulating basophils. The first approach to basophil functional responses was the histamine release test but this has remained controversial due to insufficient sensitivity and specificity. During recent years an increasing number of studies have demonstrated that flow cytometry is a reliable tool for monitoring basophil activation upon allergen challenge by detecting surface expression of degranulation/activation markers (CD63 or CD203c). This article reviews the recent improvements to the basophil activation test made possible by flow cytometry, focusing on the use of anti-CRTH2/DP2 antibodies for basophil recognition. On the basis of a new triple staining protocol, the basophil activation test has become a standardized tool for in vitro diagnosis of immediate allergy. It is also suitable for pharmacological studies on non-purified human basophils. Multicenter studies are now required for its clinical assessment in large patient populations and to define the cut-off values for clinical decision-making.

  11. 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.

  12. Probing multi-scale mechanical damage in connective tissues using X-ray diffraction.

    Science.gov (United States)

    Bianchi, Fabio; Hofmann, Felix; Smith, Andrew J; Thompson, Mark S

    2016-11-01

    The accumulation of microstructural collagen damage following repetitive loading is linked to painful and debilitating tendon injuries. As a hierarchical, semi-crystalline material, collagen mechanics can be studied using X-ray diffraction. The aim of the study was to describe multi-structural changes in tendon collagen following controlled plastic damage (5% permanent strain). We used small angle X-ray scattering (SAXS) to interrogate the spacing of collagen molecules within a fibril, and wide angle X-ray scattering (WAXS) to measure molecular strains under macroscopic loading. Simultaneous recordings of SAXS and WAXS patterns, together with whole-tissue strain in physiologically hydrated rat-tail tendons were made during increments of in situ tensile loading. Results showed that while tissue level modulus was unchanged, fibril modulus decreased significantly, and molecular modulus significantly increased. Further, analysis of higher order SAXS peaks suggested structural changes in the gap and overlap regions, possibly localising the damage to molecular cross-links. Our results provide new insight into the fundamental damage processes at work in collagenous tissues and point to new directions for their mitigation and repair.

  13. Diagnosis and treatment of mixed connective tissue disease%混合性结缔组织病的诊治

    Institute of Scientific and Technical Information of China (English)

    王文芳; 邓丹琪

    2013-01-01

    混合性结缔组织病发病并不少见,本病为临床上具有系统性红斑狼疮、系统性硬化症、多发性肌炎/皮肌炎及类风湿性关节炎等疾病混合表现,血清中有高滴度RNP抗体为特征.本文对混合性结缔组织病的发病机制、临床表现、诊断标准、治疗等予以介绍.%Mixed connective tissue disease is not a rare disease,which has mixed clinical features of systemic lupus erythema-tosus,systemic sclerosis,polymyositis/dermatomyositis and rheumatoid arthritis with high titer of U1RNP antibody in blood serum. In this paper,the pathogenesis,clinical manifestation,diagnosis and treatment of mixed connective tissue disease are reviewed.

  14. 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.

  15. A boy with developmental delay, malformations, and evidence of a connective tissue disorder: possibly a new type of cutis laxa.

    Science.gov (United States)

    Armstrong, Linlea; Jimenez, Carmencita; Hunter, Alasdair G W

    2003-05-15

    We report a 7.5-year-old boy with loose translucent skin, aortic dilatation, hyperextensible veins, recurrent respiratory problems, pectus excavatum, arthralgias, lax joints, mild epiphyseal dysplasia, and umbilical and inguinal hernias. He also has developmental delay, progressive bilateral sensorineural hearing loss, an unusual facial appearance, terminal digit hypoplasia with unusual radiographic changes in some of the phalanges, glandular hypospadias, shawl scrotum, and undescended testes. Biochemical investigations, including electrophoresis of Types 1 and 3 procollagens and collagens, and quantification of serum copper and ceruloplasmin, are normal. Relative to age-matched control patients the electron micrographs of the boy's dermis show elastin fibers to be decreased in number, and abnormal in appearance, with a low matrix to microfibril ratio. The organ distribution of abnormalities and the nature of the findings suggest a connective tissue disorder. We contrast and compare this boy's phenotype to those of the classic connective tissue disorders. We conclude that he has cutis laxa with features that distinguish him from previously described types of cutis laxa.

  16. Development and preclinical evaluation of acellular collagen scaffolding and autologous artificial connective tissue in the regeneration of oral mucosa wounds.

    Science.gov (United States)

    Espinosa, Lady; Sosnik, Alejandro; Fontanilla, Marta R

    2010-05-01

    This work assessed wound healing response in rabbit oral lesions grafted with autologous artificial connective tissue or acellular collagen scaffolds. Autologous artificial oral connective tissue (AACT) was produced using rabbit fibroblasts and collagen I scaffolds. Before implantation, AACT grafts were assayed to demonstrate the presence of fibroblasts and extracellular matrix components, as well as the expression of characteristic genes and secretion of chemokines, cytokines, and growth factors. AACT grafts were tested in the rabbits from which the fibroblasts were obtained, whereas acellular collagen type I scaffolds (CS) were evaluated in a separate group of rabbits. In both cases, contralateral wounds closed by secondary intention were used as controls. In a separate experiment, AACT-grafted wounds were directly compared with contralateral CS-grafted wounds in the same animals. Wound contraction and histological parameters were examined to evaluate closure differences between the treatments in the three animal experiments performed. Contraction of wounds grafted with AACT and CS was significantly lower than in their controls (p oral mucosa.

  17. The effect of stimuli on basophil-mediated atopic responses during asthmatic lying-in women and in newborns.

    Science.gov (United States)

    Yang, Ling; Guo, Yin-Shi; Jiang, Jin-Qi; Guo, Xue-Jun; Xu, Yi-Ping; Tian, Ye; Xiong, Ying; Han, Li

    2012-08-01

    Morbidity from allergic diseases is increasing. Basophils play a critical role in systemic anaphylaxis and chronic allergic inflammation. The prenatal environment must be regarded as a possible early risk factor for allergic diseases in children. Our objective was to determine if basophils harvested from neonates genetically predisposed to atopic disease had different levels of CD63 expression and IL-4 release properties in response to various stimuli (peptidoglycan, Dermatophagoides farinae, hyperosmotic mannitol). Blood samples were collected from 16 asthmatic and 18 healthy women and their newborns. Peripheral blood basophil histamine was measured using the human basophil degranulation test (HBDT), whereas activation was assessed by flow cytometric measurement of CD63 expression on the cord blood basophil surface. IL-4 levels were quantified by ELISA following allergen stimulation. The basophil degranulation index (DI) in granulocytes harvested from the peripheral blood of asthmatic women was assessed following stimulation with peptidoglycan (PGN), Dermatophagoides farinae (Df ) extract, or hyperosmotic mannitol. The DI was significantly higher in atopic women than in healthy controls. Upregulation of CD63 on the cord blood basophil surface was also detected in response to these stimuli. Basophils purified from the cord blood of neonates born to atopic mothers produced more IL-4 compared to basophils purified from the controls. These data suggested that various stimuli play a role in augmenting allergic reactions via modulation of activated basophil cytokine secretion. It may require new methods to stabilize the basophils in allergic diseases.

  18. Basophil sensitivity through CD63 or CD203c is a functional measure for specific immunotherapy

    Directory of Open Access Journals (Sweden)

    Dahl Ronald

    2010-02-01

    Full Text Available Abstract Background Subcutaneous Immunotherapy (SCIT modifies the allergic response and relieves allergic symptoms. SCIT is the only and a very effective treatment for insect venom allergy. We hypothesized that basophil sensitivity, measured through the basophil activation test, would decrease during SCIT up dosing. Expression of CD203c was compared to CD63 as marker for basophil activation, using a Bland Altman plot and ROC curves. Methods Patients (n = 18 starting subcutaneous SCIT for wasp allergy with an up dosing scheme of 7 to 11 weeks were enrolled. Heparinised blood samples were drawn at weeks 1-4, 7 and at the first maintenance visit. Basophils were stimulated at 7 log dilutions of V. vespula allergen for 15 min, and were stained with CD203c and CD63. Basophils were identified as CD203c+ leukocytes, and the proportion of CD63+ and CD203c+ cells were plotted against allergen concentration. A sigmoid curve was fitted to the points, and the allergen concentration at which half of the maximal activation was achieved, LC50, was calculated. In another series of experiments, LC50 calculated in whole blood (AP was subtracted from LC50 calculated with basophils suspended in plasma from a nonatopic donor (HS to determine the protective effect of soluble factors in blood of patients treated with SCIT. Results Heparin blood basophil activation was similar through CD63 and CD203c. Basophils were significantly more sensitized three weeks after initiation of SCIT compared to baseline (p Conclusion Basophil activation is a versatile and sensitive tool that measures changes in the humoral immune response to allergen during SCIT.

  19. Increased Level of Basophil CD203c Expression Predicts Severe Chronic Urticaria

    OpenAIRE

    Ye, Young-Min; Yang, Eun-Mi; Yoo, Hye-Soo; Shin, Yoo-Seob; Kim, Seung-Hyun; Park, Hae-Sim

    2013-01-01

    Increased FcεR1α expression with upregulated CD203c expression on peripheral basophils is seen in patients with chronic urticaria (CU). However, there has been no published report on the association between CD203c expression level and clinical disease activity in CU patients. To investigate whether the increase of basophil activation is associated with the disease activity of CU, we measured basophil CD203c expression using a tricolor flow cytometric method in 82 CU patients and 21 normal con...

  20. Difference in CD22 molecules in human B cells and basophils

    OpenAIRE

    Toba, Ken; Hanawa, Haruo; Fuse, Ichiro; Sakaue, Minori; Watanabe, Kenichi; Uesugi, Yumiko; Higuchi, Wataru; Takahashi, Wataru; Aizawa, Yoshifusa; 鳥羽, 健

    2002-01-01

    Objective. CD22 is believed to be restricted to normal and neoplastic B cells. Human basophils were found to express CD22 molecules. Among the antibodies against CD22, Leu14, which recognized the ligand binding domain reacted to basophils, and B3 and 4KB128, which recognized the amino terminus side and carboxy terminus side of the ligand binding epitope, respectively, did not. To clarify the difference of CD22 antigenicity in human B cells and basophils, we investigated RNA sequence and struc...

  1. Trisomy 19 and T(9;22 In a Patient with Acute Basophilic Leukemia

    Directory of Open Access Journals (Sweden)

    Alicia Rojas-Atencio

    2011-01-01

    Full Text Available We report a case of acute basophilic leukemia with two coexisting clonal abnormalities, t(9;22 and trisomy 19. The blast showed positive reaction with myeloperoxidase but negative reaction with chloroacetate esterase and acid phosphatase. Metachromatic features of the blast were observed with toluidine blue stain. Ultrastructure study showed the presence of azurophilic granules in basophils and blast mast cells. Conventional and molecular cytogenetic studies revealed, t(9;22 with BCR/ABL positive and trisomy 19 in all metaphase cells. To our knowledge, this paper here is the first to present acute basophilic leukemia with trisomy 19 and t(9;22.

  2. 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.

  3. Integrin-extracellular matrix interactions in connective tissue remodeling and osteoblast differentiation

    Science.gov (United States)

    Globus, R. K.; Moursi, A.; Zimmerman, D.; Lull, J.; Damsky, C.

    1995-01-01

    The differentiaton of bone cells is a complex multistep process. Bone is somewhat unusual in that it is very actively and continually remodeled in the adult and that maintenance of its mass in the mature organism is exquisitely sensitive to mechanical as well as chemical signals. Bone is also unique because it consists of a very large amount of extracellular matrix (ECM) that is mineralized. The integrin family of ECM receptors has been shown to play an important role in tissue morphogenesis in several systems. Our studies on the regulation of matrix remodeling enzymes by integrins in rabbit synovial fibroblasts show that two b1 integrin fibronectin (FN) receptor complexes (alpha 5 beta 1 and alpha 4 beta 1) cooperate in detecting subtle changes in the composition of the ECM. As a result of signal transduction by these integrins, the levels of mRNA and protein for several members of the metalloproteinase family are regulated in these cells. We have also used antibody and RGD peptide perturbation studies to determine the significance of cell/ECM interactions to normal osteogenesis. We found that interactions between the cell binding domain of FN and integrins are required for both normal morphogenesis and gene expression in cultured osteoblasts that differentiate to form bone-like tissue in culture. These data lead us to propose that beta 1 integrins play an important role in osteoblast differentiation as well as in bone remodeling.

  4. 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.

  5. 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.

  6. The enzyme profiles in the connective tissue attaching pin bones to the surrounding tissue is specific in farmed salmon (Salmo salar) and cod (Gadus morhua L.).

    Science.gov (United States)

    Vuong, Tram T; Rønning, Sissel B; Kolset, Svein O; Pedersen, Mona E

    2017-02-01

    Post mortem storage is a necessary process for removal of pin bones without destruction of fillets, thereby avoiding volume and economic loss. However, the enzymes involved in loosening pin bones during storage have not been studied to a great extent. In this study, the activities and localization of MMPs in the connective tissue (CT) of pin bones dissected from fillet of salmon and cod were investigated. Interestingly, the enzyme activity profile in these two species was different during post mortem storage of fish fillets. Adding MMP inhibitor (GM6001) and serine protease inhibitor (Pefabloc) revealed different effects in the two species, suggesting different regulations in salmon and cod. In situ zymography with the same inhibitors verified MMP and serine protease activity in CT close to pin bone at early post mortem (6 h) in salmon. However, MMP inhibition was not evident in cod in this area at that time point. Immunohistochemistry further revealed MMP9 and MMP13 were located more to the outer rim of CT, facing the pin bone and adipose tissue, while MMP7 was more randomly distributed within CT in salmon. In contrast, all these three MMPs were randomly distributed in CT in cod. In summary, our study reveals different MMP enzyme profiles in salmon and cod in the pin bone area, influenced by serine proteases, and suggests that MMPs and serine proteases must be taken in consideration when studying the conditions for early pin bone removal.

  7. Immunogenicity of influenza H1N1 vaccination in mixed connective tissue disease: effect of disease and therapy

    Directory of Open Access Journals (Sweden)

    Renata Miossi

    2013-01-01

    Full Text Available OBJECTIVE: To assess the potential acute effects regarding the immunogenicity and safety of non-adjuvanted influenza A H1N1/2009 vaccine in patients with mixed connective tissue disease and healthy controls. METHODS: Sixty-nine mixed connective tissue disease patients that were confirmed by Kasukawa's classification criteria and 69 age- and gender-matched controls participated in the study; the participants were vaccinated with the non-adjuvanted influenza A/California/7/2009 (H1N1 virus-like strain. The percentages of seroprotec-tion, seroconversion, geometric mean titer and factor increase in the geometric mean titer were calculated. The patients were clinically evaluated, and blood samples were collected pre- and 21 days post-vaccination to evaluate C-reactive protein, muscle enzymes and autoantibodies. Anti-H1N1 titers were determined using an influenza hemagglutination inhibition assay. ClinicalTrials.gov: NCT01151644. RESULTS: Before vaccination, no difference was observed regarding the seroprotection rates (p = 1.0 and geometric mean titer (p = 0.83 between the patients and controls. After vaccination, seroprotection (75.4% vs. 71%, (p = 0.7, seroconversion (68.1% vs. 65.2%, (p = 1.00 and factor increase in the geometric mean titer (10.0 vs. 8.0, p = 0.40 were similar in the two groups. Further evaluation of seroconversion in patients with and without current or previous history of muscle disease (p = 0.20, skin ulcers (p = 0.48, lupus-like cutaneous disease (p = 0.74, secondary Sjogren syndrome (p = 0.78, scleroderma-pattern in the nailfold capillaroscopy (p = 1.0, lymphopenia #1000/mm³ on two or more occasions (p = 1.0, hypergammaglobulinemia $1.6 g/d (p = 0.60, pulmonary hypertension (p = 1.0 and pulmonary fibrosis (p = 0.80 revealed comparable rates. Seroconversion rates were also similar in patients with and without immunosuppressants. Disease parameters, such as C-reactive protein (p = 0.94, aldolase (p = 0.73, creatine

  8. The Evolution of Human Basophil Biology from Neglect towards Understanding of Their Immune Functions

    Science.gov (United States)

    Steiner, Markus; Huber, Sara; Harrer, Andrea

    2016-01-01

    Being discovered long ago basophils have been neglected for more than a century. During the past decade evidence emerged that basophils share features of innate and adaptive immunity. Nowadays, basophils are best known for their striking effector role in the allergic reaction. They hence have been used for establishing new diagnostic tests and therapeutic approaches and for characterizing natural and recombinant allergens as well as hypoallergens, which display lower or diminished IgE-binding activity. However, it was a long way from discovery in 1879 until identification of their function in hypersensitivity reactions, including adverse drug reactions. Starting with a historical background, this review highlights the modern view on basophil biology. PMID:28078302

  9. Increasing time interval and decreasing allergen dose interval improves ex vivo desensitization of human blood basophils

    DEFF Research Database (Denmark)

    Witting Christensen, Sara K; Krohn, Inge Kortekaas; Thuraiaiyah, Jani;

    2016-01-01

    BACKGROUND: Desensitization is a method for inducing temporary tolerance to allergen. The mechanism underlying desensitization is yet to be established. METHODS: Basophil granulocytes in whole blood from grass pollen allergic subjects were desensitized ex vivo by sequential addition of increasing...... allergen concentrations. At each step basophil activation (CD193(+) CD63(+) ) was monitored with and without (background activation) allergen challenge at optimal concentration. The sequential desensitization protocol was compared to a single-dose desensitization protocols with threshold and subthreshold...... allergen concentrations. Incubation intervals and allergen concentrations were varied in order to optimise the protocol. RESULTS: Sequential desensitization effectively reduced basophil response. The single-dose subthreshold protocol and single-dose threshold protocols did not reduce basophil activation...

  10. Surface profiling of normally responding and nonreleasing basophils by flow cytometry

    DEFF Research Database (Denmark)

    Kistrup, Kasper; Poulsen, Lars Kærgaard; Jensen, Bettina Margrethe

    Background Human basophils are granulocytes with the capacity to play important roles in allergy for example by releasing histamine when activated by cross-linking of their high affinity IgE receptors (Fc¿RI). However, not all individuals have basophils responding with a histamine release after......c, C3aR, C5aR CCR3, FPR1, ST2, CRTH2 on anti-IgE respondsive and nonreleasing basophils by flow cytometry, thereby generating a surface profile of the two phenotypes. Methods Fresh buffy coat blood (histamine release and nonreleases were defined as having...... a maximum release basophils, defined as FceRIa+CD3-CD14-CD19-CD56-,were analysed for surface expression of relevant markers. All samples were compensated and analysed in logicle display. All gates...

  11. Aspirin Augments IgE-Mediated Histamine Release from Human Peripheral Basophils via Syk Kinase Activation

    Directory of Open Access Journals (Sweden)

    Hiroaki Matsuo

    2013-01-01

    Conclusions: Aspirin enhanced histamine release from basophils via increased Syk kinase activation, and that the augmentation of histamine release by NSAIDs or FAs may be one possible cause of worsening symptoms in patients with chronic urticaria and FDEIA.

  12. Expressions of cysteine-rich61, connective tissue growth factor and Nov genes in hepatocellular carcinoma and their clinical significance

    Institute of Scientific and Technical Information of China (English)

    Zhi-Jun Zeng; Lian-Yue Yang; Xiang Ding; Wei Wang

    2004-01-01

    AIM: To investigate the expression of cysteine-rich61 (Cyr61),connective tissue growth factor (CTGF) and nephroblastoma overexpressed gene (Nov) in hepatocellular carcinoma (HCC),and to evaluate the relationship between Cyr61, CTGF and Nov genes expression with invasion and metastasis of HCC.METHODS: Thirty-one HCC specimens were divided into small hepatocellular carcinoma (SHCC), nodular hepatocellular carcinoma (NHCC), solitary large hepatocellular carcinoma (SLHCC) according to their diameter and number of nodes. Reverse transcription polymerse chain reaction (RT-PCR) was used to detect the mRNA expression levels of Cyr61, CTGF and Nov genes in 31 resected specimens of hepatocellular carcinoma and para-cancerous normal liver tissues semi-quantitatively and the relation between their expression levels and clinical pathological parameters were compared.RESULTS: The expressions of Cyr61 and CTGF mRNA in carcinoma tissues were significantly higher than those in para-cancerous normal liver tissues (P<0.01). The expressions of Cyr61 and CTGF mRNA in HCC with venous invasion were higher than those in HCC without venous invasion. CTGF expression in HCC Edmondson's grade Ⅲ-Ⅳ was significantly higher than that in HCC Edmondson's grade Ⅰ-Ⅱ (P = 0.022). There was no obvious correlation between Nov mRNA and clinical-pathological features.Compared to NHCC, SLHCC had better cell differentiation,easier capsule formation, less microscopic venous invasion,milder liver cirrhosis. The expressions of Cyr61 and CTGF mRNA in NHCC were significantly higher than those in SLHCC and SHCC.CONCLUSION: Cyr61 and CTGF genes may play an important role in hepatocellular carcinogenesis and correlate with recurrence and metastasis of hepatocellular carcinoma.SLHCC has better biological behaviors than NHCC.

  13. Analysis of obstetric complications and uterine connective tissue in tenascin-X-deficient humans and mice.

    Science.gov (United States)

    Egging, David F; van Vlijmen-Willems, Ivonne; Choi, Jiwon; Peeters, Anita C T M; van Rens, Desiree; Veit, Guido; Koch, Manuel; Davis, Elaine C; Schalkwijk, Joost

    2008-06-01

    Tenascin-X (TNX) is a large, multi-domain, extracellular matrix glycoprotein. Complete deficiency of TNX in humans leads to a recessive form of Ehlers-Danlos syndrome (EDS), and TNX haploinsufficiency is a cause of hypermobility type EDS. EDS patients appear to have a higher risk of several complications during pregnancy, such as pelvic instability, premature rupture of membranes, and postpartum hemorrhage. Here, we present a study of genitourinary and obstetric complications in TNX-deficient women of reproductive age. We have found complications, such as uterus prolapses, that are in agreement with previous findings in other EDS types. In TNX knockout (KO) mice, we have observed mild pregnancy-related abnormalities. Morphological and immunohistological analysis of uterine tissues has not revealed obvious quantitative or spatial differences between TNX KO and wildtype mice with respect to collagen types I, III, V, and XII or elastic fibers. We conclude that TNX-deficient women are at risk of obstetric complications, but that TNX KO mice show only a mild phenotype. Furthermore, we show that TNX is involved in the stability of elastic fibers rather than in their initial deposition.

  14. [Ocular changes associated with connective tissue disorders: role of the elastic and collagen components].

    Science.gov (United States)

    Gimeno, M J; Bellón, J M; Buján, J

    2001-08-01

    Every day, the emerging fields of genomics and proteomics provide new information about both normal and pathological processes, among which, the extracellular matrix appears to play a significant role. Over the past decade, the classic fibrillar components of the matrix, collagen and elastin, have been the subject of extensive research leading to a wealth of information which is far form being fully interpreted. Although the basic composition and structure of the matrix components has been well established, today more than twenty five different varieties of collagen have been described, and elastic fibers are currently described as polymeric complexes, composed of at least 19 different proteins in their microfibrillar and amorphic portions. Mutations in three of the genes coding for some of the most abundant proteins in the elastic fibers give rise to a wide range of elastic tissue phenotypes, from skeletal or dermal anomalies to vascular or ocular defects. In this review, our aim was to gain insight into the fibrillar component of the extracellular matrix in an attempt to improve our understanding of certain ocular disorders.

  15. Clinical predictors of adverse course of nonspecific bacterial vulvovaginitis at girls born from mothers with dysplasia of connective tissue

    Directory of Open Access Journals (Sweden)

    Mozes V.G.

    2012-06-01

    Full Text Available Research objective: To define clinical predictors of adverse course of nonspecific bacterial vulvovaginitis (NBV at girls born from mothers with the undifferentiated forms of dysplasia of connective tissue (UFDCT. Materials: At 157 girls clinical research, bacteriological and bacterioscopy research of leucorrhoea from vagina has been conducted, NBV has been diagnosed at 111 girls. At all girls and at their mothers the immunity has been investigated; at all mothers of girls with NBV phenotypic reveals of UFDCT have been found out. Results: At girls with NBV born from mothers with UFDCT severe course of a disease has been marked; and at mothers with UFDCT and at their children with NBV disorders of humoral immunity have been revealed. Presence of more than 5 stigmas of dysembryogenesis with prevalence of thoracodiaphragmatic, articular, cosmetic syndromes and pathology of organs of vision at mothers of girls with NBV is possible to use as predictors of adverse course of the disease

  16. Immunity and early atherosclerosis in the course of systemic lupus erythematosus, mixed connective tissue disease and antiphospholipid syndrome.

    Science.gov (United States)

    Haładyj, Ewa; Paradowska-Gorycka, Agnieszka; Felis-Giemza, Anna; Olesińska, Marzena

    2016-01-01

    Atherosclerosis is a chronic inflammatory disease of the arteries associated with various risk factors that promote lipid abnormalities, development and progression of atherosclerotic lesions, plaque rupture, and vascular thrombosis. Atherosclerosis is accelerated in autoimmune diseases. Non-invasive investigations showed increased intima-media thickness (IMT), carotid plaque, and coronary artery calcifications in patients with antiphospholipid syndrome, systemic lupus erythematosus and mixed connective tissue disease compared to controls. The balance between the proinflammatory and anti-inflammatory cytokines allows the immune equilibrium to be maintained. In autoimmune diseases the prevalence of proinflammatory factors leads to premature atherosclerosis. This review presents complementary knowledge on innate and adaptive immunity, cytokines and the role of inflammasomes in progression of early atherosclerosis.

  17. Immunity and early atherosclerosis in the course of systemic lupus erythematosus, mixed connective tissue disease and antiphospholipid syndrome

    Science.gov (United States)

    Paradowska-Gorycka, Agnieszka; Felis-Giemza, Anna; Olesińska, Marzena

    2016-01-01

    Atherosclerosis is a chronic inflammatory disease of the arteries associated with various risk factors that promote lipid abnormalities, development and progression of atherosclerotic lesions, plaque rupture, and vascular thrombosis. Atherosclerosis is accelerated in autoimmune diseases. Non-invasive investigations showed increased intima-media thickness (IMT), carotid plaque, and coronary artery calcifications in patients with antiphospholipid syndrome, systemic lupus erythematosus and mixed connective tissue disease compared to controls. The balance between the proinflammatory and anti-inflammatory cytokines allows the immune equilibrium to be maintained. In autoimmune diseases the prevalence of proinflammatory factors leads to premature atherosclerosis. This review presents complementary knowledge on innate and adaptive immunity, cytokines and the role of inflammasomes in progression of early atherosclerosis. PMID:27826173

  18. CEREBRAL SINUS THROMBOSIS IN A CASE OF ANTI-PHOSPHOLIPID ANTIBODY SYNDROME WITHOUT ASSOCIATED CONNECTIVE TISSUE INVOLVEMENT

    Directory of Open Access Journals (Sweden)

    Biswarup

    2014-12-01

    Full Text Available : The association of antiphospholipid antibodies with vascular thrombotic episodes is well established. In absence of other connective tissue disease such an association is very rare & known as the primary antiphospholipid antibody syndrome. Cerebral venous sinus thrombosis is associated with hypercoaguable states and a number of immune-mediated conditions. However the report of cerebral venous sinus thrombosis with antiphospholipid antibodies alone is limited. Here a case presenting with painful bilateral ophthalmoplegia with bilateral optic disc edema (due to raised intra cranial tension showing positive lupus anticoagulant in serum and right central venous sinus (transverse and sigmoid thrombosis on MRI and MR venogram is reported which showed clinical improvement with anticoagulant therapy

  19. Phosphaturic mesenchymal tumor, mixed connective tissue variant, of the mandible: Report of a case and review of the literature

    Science.gov (United States)

    Woo, Victoria L.; Landesberg, Regina; Imel, Erik A.; Singer, Steven R.; Folpe, Andrew L.; Econs, Michael J.; Kim, Taeyun; Harik, Lara R.; Jacobs, Thomas P.

    2009-01-01

    Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome that results in renal phosphate wasting with hypophosphatemia. In most cases, the underlying cause of TIO is a small mesenchymal neoplasm that is often difficult to detect, resulting in delayed diagnosis. One such neoplasm is the phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT), an unusual entity with unique morphologic and biochemical features. The majority of these tumors are found at appendicular sites with only rare cases reported in the jaws. We describe a PMTMCT involving the mandible in a patient with a protracted history of osteomalacia. A review of the current literature is provided with emphasis on the clinical and histologic features, etiopathogenesis, and management of PMTMCT in the setting of TIO. PMID:19828339

  20. The basophil activation test by flow cytometry: recent developments in clinical studies, standardization and emerging perspectives

    OpenAIRE

    Debard Anne-Lise; Boumiza Radhia; Monneret Guillaume

    2005-01-01

    Abstract The diagnosis of immediate allergy is mainly based upon an evocative clinical history, positive skin tests (gold standard) and, if available, detection of specific IgE. In some complicated cases, functional in vitro tests are necessary. The general concept of those tests is to mimic in vitro the contact between allergens and circulating basophils. The first approach to basophil functional responses was the histamine release test but this has remained controversial due to insufficient...

  1. β2-Adrenoceptor is involved in connective tissue remodeling in regenerating muscles by decreasing the activity of MMP-9.

    Science.gov (United States)

    Silva, Meiricris T; Nascimento, Tábata L; Pereira, Marcelo G; Siqueira, Adriane S; Brum, Patrícia C; Jaeger, Ruy G; Miyabara, Elen H

    2016-07-01

    We investigated the role of β2-adrenoceptors in the connective tissue remodeling of regenerating muscles from β2-adrenoceptor knockout (β2KO) mice. Tibialis anterior muscles from β2KO mice were cryolesioned and analyzed after 3, 10, and 21 days. Regenerating muscles from β2KO mice showed a significant increase in the area density of the connective tissue and in the amount of collagen at 10 days compared with wild-type (WT) mice. A greater increase occurred in the expression levels of collagen I, III, and IV in regenerating muscles from β2KO mice evaluated at 10 days compared with WT mice; this increase continued at 21 days, except for collagen III. Matrix metalloproteinase (MMP-2) activity increased to a similar extent in regenerating muscles from both β2KO and WT mice at 3 and 10 days. This was also the case for MMP-9 activity in regenerating muscles from both β2KO and WT mice at 3 days; however, at 10 days post-cryolesion, this activity returned to baseline levels only in WT mice. MMP-3 activity was unaltered in regenerating muscles at 10 days. mRNA levels of tumor necrosis factor-α increased in regenerating muscles from WT and β2KO mice at 3 days and, at 10 days post-cryolesion, returned to baseline only in WT mice. mRNA levels of interleukin-6 increased in muscles from WT mice at 3 days post-cryolesion and returned to baseline at 10 days post-cryolesion but were unchanged in β2KO mice. Our results suggest that the β2-adrenoceptor contributes to collagen remodeling during muscle regeneration by decreasing MMP-9 activity.

  2. 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.

  3. Kidney injury secondary to connective tissue disease%结缔组织疾病肾损害

    Institute of Scientific and Technical Information of China (English)

    王金泉; 季大玺

    2011-01-01

    结缔组织疾病常累及肾脏,其中继发于系统性红斑狼疮的狼疮性肾炎和继发于系统性小血管炎的血管炎性肾损害在临床上比较常见,且多数病情重、进展快,需要积极的诱导治疗和长期维持治疗.在这两方面,近年国内外研究均取得了明显的进展.文章介绍狼疮性肾炎和血管炎性肾损害的最新研究进展及南京军区南京总医院全军肾脏病研究所对这两类疾病治疗的体会.%Connective tissue diseases often involve the kidney. Among the connective tissue disease, lupus nephritis and systemic small-vessel vasculitis-mediated renal lesions are the most often seen in clinic. The condition of most patients with lupus nephritis and small-vessel vasculitis related renal lesions are serious and progress rapidly;they need intensive inducing immunosuppressive therapy and long-term maintenance therapy. Much progress has been made in this field in recent years. The recent researches about lupus nephritis and small-vessel vasculitis-related renal lesions are reviewed in this article. The experience on treatment of lupus nephritis and smallvessel vasculitis-related renal lesions in our institude is also introduced.

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

    Science.gov (United States)

    Hansen, M; Miller, B F; Holm, L; Doessing, S; Petersen, S G; Skovgaard, D; Frystyk, J; Flyvbjerg, A; Koskinen, S; Pingel, J; Kjaer, M; Langberg, H

    2009-04-01

    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, body composition, and exercise-training status were included. The two groups were either habitual users of oral contraceptives exposed to a high concentration of synthetic estradiol and progestogens (OC, n = 11), or non-OC-users tested in the follicular phase of the menstrual cycle characterized by low 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 and vastus lateralis in both legs. Simultaneously, microdialysis catheters were inserted in vastus lateralis and in front of the patellar tendon for measurement of insulin-like growth factor I (IGF-I) and its binding proteins. Serum NH(2)-terminal propeptide of type I collagen (PINP) and urine COOH-terminal telopeptides of type-I collagen (CTX-I) were measured as markers for bone synthesis and breakdown, respectively. Tendon FSR and PINP were lower in OC compared with control. An increase in muscle collagen FSR postexercise was only observed in control (P collagen synthesis in tendon, bone, and muscle connective tissue, which may be related to a lower bioavailability of IGF-I.

  5. Experiment K-7-29: Connective Tissue Studies. Part 1; Rat Skin, Normal and Repair

    Science.gov (United States)

    Vailas, A. C.; Grindeland, R.; Ashman, R.; Choy, V.; Durnova, G.; Graf, B.; Griffith, P.; Kaplansky, A. S.; Kolis, S.; Martinez, D.; Rao, J. S.; Rayford, A. R.; Reddy, B. R.; Sears, J.; Thielke, R.; Ulm, M.; Vanderby, R.

    1994-01-01

    The skin repair studies started to be problematic for the following reasons: (1) It was very difficult to locate the wound and many lesions were not of the same dimensions. A considerable amount of time was devoted to the identification of the wound using polarized light. We understand that this experiment was added on to the overall project. Marking of the wound site and standard dimensions should be recommended for the next flight experiment. (2) The tissue was frozen, therefore thawing and fixation caused problems with some of the immunocytochemical staining for obtaining better special resolution with light microscopy image processing. Despite these problems, we were unable to detect any significant qualitative differences for the following wound markers: (1) Collagen Type 3, (2) Hematotoxylin and Eosin, and (3) Macrophage Factor 13. All protein markers were isolated from rat sources and antibodies prepared and tested for cross reactivity with other molecules at the University of Wisconsin Hybridoma Facility. However, rat skin from the non lesioned site 'normal' showed interesting biochemical results. Skin was prepared for the following measurements: (1) DNA content, (2) Collagen content by hydroxyproline, and (3) uronic acid content and estimation of ground substance. The results indicated there was a non-significant increase (10%) in the DNA concentration of skin from flight animals. However, the data expressed as a ratio DNA/Collagen estimates the cell or nuclear density that supports a given quantity of collagen showed a dramatic increase in the flight group (33%). This means flight conditions may have slowed down collagen secretion and/or increased cell proliferation in adult rat skin. Further biochemical tests are being done to determine the crosslinking of elastin which will enhance the insight to assessing changes in skin turnover.

  6. Varying assay geometry to emulate connective tissue planes in an in vitro model of acupuncture needling.

    Science.gov (United States)

    Julias, Margaret; Buettner, Helen M; Shreiber, David I

    2011-02-01

    During traditional acupuncture, fine needles are inserted subcutaneously and rotated, which causes loose fascial tissue to wind around the needle. This coupling is stronger at acupuncture points, which tend to fall above intermuscular fascial planes, than control points, which lay above skeletal muscle. These different anatomical constraints may affect the mechanical coupling. Fascia at acupuncture points is bounded on two sides by skeletal muscle, but at control points is essentially unbounded. These differences were approximated in simple in vitro models. To emulate the narrower boundary within the intermuscular plane, type I collagen was cast in circular gels of different radii. To model the channel-like nature of these planes, collagen was cast in elliptical gels with major and minor axes matching the large and small circular gels, respectively, and in planar gels constrained on two sides. Acupuncture needles were inserted into the gels and rotated via a computer-controlled motor while capturing the evolution of fiber alignment under cross-polarization. Small circular gels aligned faster, but failed earlier than large circular gels. Rotation in elliptical and planar gels generated more alignment-per-revolution than circular gels. Planar gels were particularly resistant to failure. Fiber alignment in circular gels was isotropic, but was stronger in the direction of the minor axis in elliptical and planar gels. In fibroblast-populated gels, cells followed the alignment of the collagen fibers, and also became denser in regions of stronger alignment. These results suggest that the anatomy at acupuncture points provides unique boundaries that accentuate the mechanical response to needle manipulation.

  7. Responsiveness of basophil granulocytes of horses suffering from chronic obstructive pulmonary disease to various allergens.

    Science.gov (United States)

    Dirscherl, P; Grabner, A; Buschmann, H

    1993-10-01

    As basophils are the major effector cells of allergic reactions, confirmation of the allergic etiology of chronic obstructive pulmonary disease (COPD) was sought by the demonstration of a specific in vitro response of equine basophilic blood cells to some potential allergens (Aspergillus, Cladosporidium, Mucor, Penicillium, extracts of dust particles of hay and straw). The allergen induced degranulation of basophils and the histamine and protease release from basophils during incubation with the allergens were tested. By evaluating the results obtained from 14 COPD horses and eight controls it could be shown that the sensitivity of the basophils of affected horses was increased, particularly against the allergen extract of Mucor mucedo and Mucor spinosus. Further a greater percentage of COPD horses reacted positively with the Mucor allergen extract. The mitogenic stimulation of lymphocytes by PHA and by the allergen extracts used gave comparable results in affected and control horses. Thus the in vitro stimulation of basophils may be an easily to perform testing device for the identification of potential allergens involved in the pathogenesis of equine COPD.

  8. 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.

  9. 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

    2017-01-01

    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.

  10. A numerical algorithm for stress integration of a fiber-fiber kinetics model with Coulomb friction for connective tissue

    Science.gov (United States)

    Kojic, M.; Mijailovic, S.; Zdravkovic, N.

    Complex behaviour of connective tissue can be modeled by a fiber-fiber kinetics material model introduced in Mijailovic (1991), Mijailovic et al. (1993). The model is based on the hypothesis of sliding of elastic fibers with Coulomb and viscous friction. The main characteristics of the model were verified experimentally in Mijailovic (1991), and a numerical procedure for one-dimensional tension was developed considering sliding as a contact problem between bodies. In this paper we propose a new and general numerical procedure for calculation of the stress-strain law of the fiber-fiber kinetics model in case of Coulomb friction. Instead of using a contact algorithm (Mijailovic 1991), which is numerically inefficient and never enough reliable, here the history of sliding along the sliding length is traced numerically through a number of segments along the fiber. The algorithm is simple, efficient and reliable and provides solutions for arbitrary cyclic loading, including tension, shear, and tension and shear simultaneously, giving hysteresis loops typical for soft tissue response. The model is built in the finite element technique, providing the possibility of its application to general and real problems. Solved examples illustrate the main characteristics of the model and of the developed numerical method, as well as its applicability to practical problems. Accuracy of some results, for the simple case of uniaxial loading, is verified by comparison with analytical solutions.

  11. 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...... instead of dogs and sheep in studies on lymph. The effect of surgery/anesthesia must be taken into consideration....... general anesthesia. We measured the carboxyterminal propeptide of type I procollagen (PICP), the aminoterminal propeptide of type III procollagen (PIIINP) hyaluronan (HA) and total protein. During surgery/anesthesia lymph PICP (p less than 0.04), lymph PIIINP (p less than 0.03) and serum PIIINP (p less...... is a major route of tissue clearance for these components. The lymph/serum ratio of PICP was 1.0 in conscious pigs, indicating a direct release into the circulation. Total protein in lymph decreased (p less than 0.04) during surgery/anesthesia, whereas no changes were observed in serum. Pigs can be used...

  12. Immediate placement and provisionalization of maxillary anterior single implant with guided bone regeneration, connective tissue graft, and coronally positioned flap procedures.

    Science.gov (United States)

    Waki, Tomonori; Kan, Joseph Y K

    2016-01-01

    Immediate implant placement and provisionalization in the esthetic zone have been documented with success. The benefit of immediate implant placement and provisionalization is the preservation of papillary mucosa. However, in cases with osseous defects presenting on the facial bony plate, immediate implant placement procedures have resulted in facial gingival recession. Subepithelial connective tissue grafts for immediate implant placement and provisionalization procedures have been reported with a good esthetic outcome. Biotype conversion around implants with subepithelial connective tissue grafts have been advocated, and the resulting tissues appear to be more resistant to recession. The dimensions of peri-implant mucosa in a thick biotype were significantly greater than in a thin biotype. Connective tissue graft with coronally positioned flap procedures on natural teeth has also been documented with success. This article describes a technique combining immediate implant placement, provisionalization, guided bone regeneration (GBR), connective tissue graft, and a coronally positioned flap in order to achieve more stable peri-implant tissue in facial osseous defect situations.

  13. 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.

  14. Expression of connective tissue growth factor in tumor tissues is an independent predictor of poor prognosis in patients with gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Lu-Ying Liu; Yan-Chun Han; Shu-Hua Wu; Zeng-Hua Lv

    2008-01-01

    AIM: To examine the expression of connective tissue growth factor (CTGF), also known as CCN2, in gastric carcinoma (GC), and the correlation between the expression of CTGF, dinicopathologic features and clinical outcomes of patients with GC.METHODS: One hundred and twenty-two GC patients were included in the present study. All patients were followed up for at least 5 years. Proteins of CTGF were detected using the Powervision two-step immunostaining method.RESULTS: Of the specimens from 122 GC patients analyzed for CTGF expression, 58 (58/122, 47.5%) had a high CTGF expression in cytoplasm of gastric carcinoma cells and 64 (64/122, 52.5%) had a low CTGF expression. Patients with a high CTGF expression showed a higher incidence of lymph node metastasis than those with a low CTGF expression {P = 0.032). Patients with a high CTGF expression had significantly lower 5-year survival rate than those with a low CTGF expression (27.6% vs 46.9%, P = 0.0178), especially those staging I + H + m (35.7% vs 65.2%, P = 0.0027).CONCLUSION: GC patients with an elevated CTGF expression have more lymph node metastases and a shorter survival time. CTGF seems to be an independent prognostic factor for the successful differentiation of high-risk GC patients staging I + n + m. Over-expression of CTGF in human GC cells results in an increased aggressive ability.

  15. IgE-mediated 15-hydroxyeicosatetraenoic acid (15-HETE) generation by peripheral blood leukocytes: its association with basophil activation

    OpenAIRE

    Michalak, Anna; Lewandowska-Polak, Anna; Moskwa, Sylwia; Kowalski, Marek L; Grzegorczyk, Janina Ł.

    2015-01-01

    Introduction Allergen-induced basophil activation has been associated with the release of several mediators and with an increased expression of CD203c molecules on basophils. Aim To assess the influence of specific allergens on the generation of 15-hydroxyeicosatetraenoic (15-HETE) from peripheral blood leukocytes in relation to basophil activation, on the basis of CD203c molecule expression and histamine release. Material and methods The study included 15 patients with clinical symptoms of b...

  16. 关注结缔组织病相关问质性肺疾病%Focus on connective tissue disease-associated interstitial lung disease

    Institute of Scientific and Technical Information of China (English)

    孙耕耘

    2012-01-01

    @@ 结缔组织病(connective tissues disease,CTD)是风湿性疾病中的一大类,常累及全身多个系统,表现为慢性炎症性自身免疫病,当侵犯呼吸系统时,可出现间质性肺疾病(interstitial lung disease,ILD)、胸膜炎和肺动脉高压等,见表l.CTD与ILD同时存在时,常称为结缔组织病相关间质性肺疾病(connective tissues disease-interstitial lung disease,CTD-ILD).

  17. Basophil count, a marker for disease activity in systemic lupus erythematosus.

    Science.gov (United States)

    Liang, Peifen; Tang, Ying; Fu, Sha; Lv, Jun; Liu, Bo; Feng, Min; Li, Jinggao; Lai, Deyuan; Wan, Xia; Xu, Anping

    2015-05-01

    Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease, with frequent flares amid remissions. Basophils contribute to the immunopathogenesis of SLE. This retrospective clinical study evaluated blood basophil count as a potential marker of SLE activity. This study included 213 patients with SLE, 70 with non-SLE chronic kidney disease (CKD), and 100 healthy volunteers. SLE disease activity was scored using the SLE Disease Activity Index (SLEDAI). Baseline and post-immunosuppressant bioparameters were compared in patients with active SLE, with second samples taken at total SLEDAI ≤4. Blood basophil counts and other conventional biomarkers were compared among the groups. Among the 213 SLE patients (192 women, 21 men; mean age 33.0 ± 12.0 years), 149 had active disease. Basophil counts were significantly lower in patients with SLE than in patients with non-SLE CKD and healthy controls (0.009 ± 0.010 vs. 0.025 ± 0.015 vs. 0.022 ± 0.010 × 10(9)/L, p Basophil counts in SLE patients were significantly higher after than before immunosuppressive treatment (0.021 ± 0.017 vs. 0.008 ± 0.008 × 10(9)/L, p analysis showed that basophil counts were similar to conventional markers (leukocytes, platelets, and double-stranded (ds) DNA IgG) in differentiating active from inactive SLE. These findings indicate that blood basophil counts may be a useful biomarker in evaluating SLE activity.

  18. Evaluation of the correlation and reproducibility between histamine, IL-4, and IL-13 release from human basophils.

    OpenAIRE

    Nahid Eskandari; Reza Bastan; Maryam Ahmadi; Peachell, Peter T

    2014-01-01

    Human basophils play a key role in allergic diseases such as asthma and in a variety of immunological disorders. The generation of IL-4 and IL-13 can be induced from basophil by IgE-mediated and non-IgE-mediated mechanisms. Time and stimulus-dependent differences in the regulation of these cytokines could have relevance to their biological effects. The aim of the present study was activation of basophils in order to evaluate the extent of histamine, IL-4, and IL-13 generations. Basophil-enric...

  19. Connective tissue and its growth factor CTGF distinguish the morphometric and molecular remodeling of the bladder in a model of neurogenic bladder.

    Science.gov (United States)

    Altuntas, Cengiz Z; Daneshgari, Firouz; Izgi, Kenan; Bicer, Fuat; Ozer, Ahmet; Sakalar, Cagri; Grimberg, Kerry O; Sayin, Ismail; Tuohy, Vincent K

    2012-11-01

    We previously reported that mice with experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), develop profound urinary bladder dysfunction. Because neurogenic bladder in MS patients causes marked bladder remodeling, we next examined morphometric and molecular alterations of the bladder in EAE mice. EAE was created in female SJL/J mice by immunization with the p139-151 encephalitogenic peptide of myelin proteolipid protein in complete Freund's adjuvant, along with intraperitoneal injections of Bordetella pertussis toxin. Seventy days after immunization, mice were scored for the level of neurological impairment and then killed. Spinal cord sections were assessed for demyelination, inflammation, and T cell infiltration; the composition of the bladder tissue was measured quantitatively; and gene expression of markers of tissue remodeling and fibrosis was assessed. A significant increase in the bladder weight-to-body weight ratio was observed with increasing neurological impairment, and morphometric analysis showed marked bladder remodeling with increased luminal area and tissue hypertrophy. Despite increased amounts of all tissue components (urothelium, smooth muscle, and connective tissue), the ratio of connective tissue to muscle increased significantly in EAE mice compared with control mice. Marked increases in mRNA expression of collagen type I α(2), tropoelastin, transforming growth factor-β3, and connective tissue growth factor (CTGF) were observed in EAE mice, as were decreased levels of mRNAs for smooth muscle myosin heavy chain, nerve growth factors, and muscarinic and purinergic receptors. Our results suggest that bladder remodeling corresponding to EAE severity may be due to enhanced expression of CTGF and increased growth of connective tissue.

  20. 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.

  1. Plasma CCN2/connective tissue growth factor is associated with right ventricular dysfunction in patients with neuroendocrine tumors

    Directory of Open Access Journals (Sweden)

    Aakhus Svend

    2010-01-01

    Full Text Available Abstract Background Carcinoid heart disease, a known complication of neuroendocrine tumors, is characterized by right heart fibrotic lesions. Carcinoid heart disease has traditionally been defined by the degree of valvular involvement. Right ventricular (RV dysfunction due to mural involvement may also be a manifestation. Connective tissue growth factor (CCN2 is elevated in many fibrotic disorders. Its role in carcinoid heart disease is unknown. We sought to investigate the relationship between plasma CCN2 and valvular and mural involvement in carcinoid heart disease. Methods Echocardiography was performed in 69 patients with neuroendocrine tumors. RV function was assessed using tissue Doppler analysis of myocardial systolic strain. Plasma CCN2 was analyzed using an enzyme-linked immunosorbent assay. Mann-Whitney U, Kruskal-Wallis, Chi-squared and Fisher's exact tests were used to compare groups where appropriate. Linear regression was used to evaluate correlation. Results Mean strain was -21% ± 5. Thirty-three patients had reduced RV function (strain > -20%, mean -16% ± 3. Of these, 8 had no or minimal tricuspid and/or pulmonary regurgitation (TR/PR. Thirty-six patients had normal or mildly reduced RV function (strain ≤ -20%, mean -25% ± 3. There was a significant inverse correlation between RV function and plasma CCN2 levels (r = 0.47, p Conclusions Elevated plasma CCN2 levels are associated with RV dysfunction and valvular regurgitation in NET patients. CCN2 may play a role in neuroendocrine tumor-related cardiac fibrosis and may serve as a marker of its earliest stages.

  2. Sub-epithelial connective tissue graft for root coverage in nonsmokers and smokers: A pilot comparative clinical study

    Directory of Open Access Journals (Sweden)

    Chini Doraswamy Dwarakanath

    2016-01-01

    Full Text Available Background: Gingival recession is a common condition and is more prevalent in smokers. It is widely believed that root coverage procedures in smokers result in less desirable outcome compared to nonsmokers', and there are few controlled studies in literature to support this finding. Therefore, the purpose of this study was to evaluate and compare the outcome of root coverage with sub-epithelial connective tissue graft (SCTG in nonsmokers and smokers. Materials and Methods: A sample of twenty subjects, 10 nonsmokers and 10 smokers were selected each with at least 1 Miller's Class I or II recession on a single rooted tooth. Clinical measurements of probing depth, clinical attachment level (CAL, gingival recession total surface area (GRTSA, depth of recession (RD, width of recession (RW, and width of keratinized tissue were determined at baseline, 3, and 6 months after surgery. Results: The treatment of gingival recession with SCTG and coronally advanced flap showed a decrease in the GRTSA, RD, RW, and an increase in CAL and width of keratinized gingiva in both the groups. However, the intergroup comparison of the clinical parameters showed no statistical significance. About 6 out of 10 nonsmokers (60% and 3 smokers (30% showed complete root coverage. The mean percentage of root coverage of 71.2% in nonsmokers and 38% in smokers was observed. Conclusion: The results of the present study suggest that smoking may negatively influence gingival recession reduction and CAL gain. In addition, smokers may exhibit fewer chances of complete root coverage. Overall, nonsmokers showed better improvements in all the parameters compared to smokers at the end of 6 months.

  3. The Role of Tumor Cell-Derived Connective Tissue Growth Factor (CTGF/CCN2) in Pancreatic Tumor Growth

    Science.gov (United States)

    Bennewith, Kevin L.; Huang, Xin; Ham, Christine M.; Graves, Edward E.; Erler, Janine T.; Kambham, Neeraja; Feazell, Jonathan; Yang, George P.; Koong, Albert

    2009-01-01

    Pancreatic cancer is highly aggressive and refractory to existing therapies. Connective tissue growth factor (CTGF/CCN2) is a fibrosis-related gene that is thought to play a role in pancreatic tumor progression. However, CCN2 can be expressed in a variety of cell types, and the contribution of CCN2 derived from either tumor cells or stromal cells as it affects the growth of pancreatic tumors is unknown. Using genetic inhibition of CCN2, we have discovered that CCN2 derived from tumor cells is a critical regulator of pancreatic tumor growth. Pancreatic tumor cells derived from CCN2 shRNA-expressing clones showed dramatically reduced growth in soft agar and when implanted subcutaneously. We also observed a role for CCN2 in the growth of pancreatic tumors implanted orthotopically, with tumor volume measurements obtained by PET imaging. Mechanistically, CCN2 protects cells from hypoxia-mediated apoptosis, providing an in vivo selection for tumor cells that express high levels of CCN2. We found that CCN2 expression and secretion was increased in hypoxic pancreatic tumor cells in vitro, and we observed co-localization of CCN2 and hypoxia in pancreatic tumor xenografts and clinical pancreatic adenocarcinomas. Furthermore, we found increased CCN2 staining in clinical pancreatic tumor tissue relative to stromal cells surrounding the tumor, supporting our assertion that tumor cell-derived CCN2 is important for pancreatic tumor growth. Taken together, these data improve our understanding of the mechanisms responsible for pancreatic tumor growth and progression, and also indicate that CCN2 produced by tumor cells represents a viable therapeutic target for the treatment of pancreatic cancer. PMID:19179545

  4. 18.CONNECTIVE TISSUE DISORDERS

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930376 The renal involvement of primary vas-culitis:Clinical and pathological analysis of 5eases:ZHAO Minghui (赵明辉),et al.NephrolDept,1st Hosp,Beijing Med Univ,Beijing,100034.Chin J Intern Med 1993;32 (1):40—43.Primary vasculitis,including microscopic pol-yarteritis (MPA) and Wegener’s granulomatosis(WG),is one of the causes of glomeru-Ionephritis and renal failure.Recently antineu-trophil cytoplasmic autoantibody (ANCA) isconsidered to be a very important tool for the di-agnosis of MPA and WG.The management ofANCA was performed in 42 patients wtih vari-ant primary glomeruionephritis with crescentsformation or sclerotic glomerulonephritis,and 5of them showing positive,appeared as a patternof P-ANCA.Most of the patients were old

  5. CONNECTIVE TISSUE DISORDER

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    950396 HLA-DQA1 genes involved in the genetic sus- ceptibility to systemic lupus.erythematosus in ChineseHans.PAN Xinghua(潘星华),et al.Genetic Instit.Fu-dan Univ,Shanghai.200433.Chin J immunol 1995;11(1):19-21.We studied the genetic susceptibitility of HLA-DQA1 alleles to Systemic Lupus Erythematosus(SLE) in Chinese Hans from Shanghai and its nearbyfregions (52 cases) by digesting the locus specific PCR

  6. Connective Tissue Disorder

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008562 A clinical study of tuberculosis infection in systemic lupus erythematosus. ZHANG Lu(章璐),et al. Dept Rheumatol,China-Japan Friendship Hosp,Beijing 100029. Chin J Intern Med 2008;47(10):808-810. Objective To investigate the characteristics and related risk factors associated with tuberculosis(TB)in patients with

  7. Connective Tissue Disorder

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    2009470 Insulin resistance and serum resistin levels in patients with systemic lupus erythematosus.LIU Lunfei,et al.Dept Dermatol,2nd Affili Hosp,Zhejiang Univ,Sch Med,Hangzhou 310009. Chin J Hematol 2009;42(9):593-595.

  8. CONNECTIVE TISSUE DISORDER

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930171 Lupus erythematosus in pregnancy:aprospective study.CHEN Shunle(陈顺乐),etal.Dept Rheumatol,Renji Hosp,Shanghai,200001.Natl Med J China 1992;72(9):534-537.The maternal and fetal outcome in 20 patientswith lupus erythematosus in pregnancy wasstudied prospectively.The conditions of the pa-tients were:remission in 4 patients,inactive(controlled by 10 mg prednisone for at least 6

  9. CONNECTIVE TISSUE DISORDER

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970390 Effects of methylprednis0Ione (MPS) on in-duction of apoptosis and expression of interleukin-1 B-converting enzyme(ICE) in the kidneys of MRL/Iprmice. WANG Jianzhong(王建中), et al. Dept Nephrol,General Hosp, PI, A, Beijing, 100853. Chin J Intern Med1997; 36(2): 79-82.

  10. CONNECTIVE TISSUE DISORDER

    Institute of Scientific and Technical Information of China (English)

    1992-01-01

    920734 A study on anti-histone fraction an-tibodies in patients with rheumatic disease.JIANG Ming(蒋明), et al. Dept Med, PUMCHosp, Beijing, 100730. Chin J Intern Med 1992;31(5): 287-289. By using Western blot method, we studied theantihistone fraction antibodies in sera of patientswith rheumatic diseases. After analysed with

  11. Analysis of basophil activation by flow cytometry in pediatric house dust mite allergy.

    Science.gov (United States)

    González-Muñoz, Miguel; Villota, Julian; Moneo, Ignacio

    2008-06-01

    Detection of allergen-induced basophil activation by flow cytometry has been shown to be a useful tool for allergy diagnosis. The aim of this study was to assess the potential of this technique for the diagnosis of pediatric house dust mite allergy. Quantification of total and specific IgE and basophil activation test were performed to evaluate mite allergic (n = 24), atopic (n = 23), and non-allergic children (n = 9). Allergen-induced basophil activation was detected as a CD63-upregulation. Receiver operating characteristics (ROC) curve analysis was performed to calculate the optimal cut-off value of activated basophils discriminating mite allergic and non-allergic children. ROC curve analysis yielded a threshold value of 18% activated basophils when mite-sensitized and atopic children were studied [area under the curve (AUC) = 0.99, 95% confidence interval (CI) = 0.97-1.01, p Analysis of the data obtained with 1.6 microg/ml mite extract defined a cut-off value of 8% activated basophils (AUC = 0.96, 95% CI = 0.91-1.01; p basophils (AUC = 1.0) with 16 microg/ml allergen extract and a sensitivity and specificity of 100%. The same threshold and specificity values were obtained with 1.6 microg/ml extract (AUC = 97%, 95% CI = 0.92-1.02; p basophil activation tests and high specific IgE (>43 kU/l) values for Dermatophagoides pteronyssinus allergen. They also showed positive prick (wheal diameter >1.0 cm) and basophil activation (>87%) tests and high specific IgE (>100 kU/l) with shrimp allergen. Shrimp sensitization was demonstrated by high levels of Pen a 1-specific IgE (>100 kU/l). Cross-reactivity between mite and shrimp was confirmed by fluorescence enzyme immunoassay (FEIA-CAP) inhibition study in these two cases. This study demonstrated that the analysis of allergen-induced CD63 upregulation by flow cytometry is a reliable tool for diagnosis of mite allergy in pediatric patients, with sensitivity similar to routine diagnostic tests and a higher specificity

  12. The prefabricated scapula flap consists of syngeneic bone, connective tissue, and a self-assembled epithelial coating.

    Science.gov (United States)

    Kunstfeld, R; Petzelbauer, P; Wickenhauser, G; Schlenz, I; Korak, K; Vinzenz, K; Holle, J

    2001-12-01

    The reconstruction of maxillary defects is a challenge in plastic surgery. The so-called prefabricated scapula flap consists of syngeneic bone covered with syngeneic dermis and is used to reconstruct maxillary defects. After placing these flaps into the oral cavity, they are reepithelialized within a short time period, raising the question of the cellular origin of the "neomucosa." We therefore obtained sequential biopsy samples of the prefabricated flap and of the flap after being placed into the oral cavity and analyzed the keratin expression profile of epithelial cells. We expected that after placing the prefabricated flap into the oral cavity, keratinocytes from adnexal structures of the dermal component of the graft would migrate onto the surface and reepithelialize the flap. Unexpectedly, reepithelialization occurred earlier. The flap had acquired a mucosa-like epithelium at the interface between the Gore-Tex coating and the dermis while still being positioned within the scapular region. The keratin expression profile of this epithelium was very similar to that of mucosal epithelium. Thus, the prefabricated scapula flap not only consisted of bone covered with connective tissue, but was also covered with epithelial cells derived from adnexal structures of the dermal graft. This seems to be the reason for the rapid restoration of an intact mucosa and the excellent outcome achieved with this surgical technique.

  13. Connective tissue growth factor and β-catenin constitute an autocrine loop for activation in rat sarcomatoid mesothelioma.

    Science.gov (United States)

    Jiang, Li; Yamashita, Yoriko; Chew, Shan-Hwu; Akatsuka, Shinya; Ukai, Shun; Wang, Shenqi; Nagai, Hirotaka; Okazaki, Yasumasa; Takahashi, Takashi; Toyokuni, Shinya

    2014-08-01

    Due to the formerly widespread use of asbestos, malignant mesothelioma (MM) is increasingly frequent worldwide. MM is classified into epithelioid (EM), sarcomatoid (SM), and biphasic subtypes. SM is less common than EM but is recognized as the most aggressive type of MM, and these patients have a poor prognosis. To identify genes responsible for the aggressiveness of SM, we induced EM and SM in rats, using asbestos, and compared their transcriptomes. Based on the results, we focused on connective tissue growth factor (Ctgf), whose expression was significantly increased in SM compared with EM; EM itself exhibited an increased expression of Ctgf compared with normal mesothelium. Particularly in SM, Ctgf was a major regulator of MM proliferation and invasion through activation of the β-catenin-TCF-LEF signalling pathway, which is autocrine and formed a positive feedback loop via LRP6 as a receptor for secreted Ctgf. High Ctgf expression also played a role in the epithelial-mesenchymal transition in MM. Furthermore, Ctgf is a novel serum biomarker for both early diagnosis and determining the MM prognosis in rats. These data link Ctgf to SM through the LRP6-GSK3β-β-catenin-TCF-Ctgf autocrine axis and suggest Ctgf as a therapeutic target.

  14. 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.

  15. Selective, α2β1 integrin-dependent secretion of il-6 by connective tissue mast cells.

    Science.gov (United States)

    McCall-Culbreath, Karissa D; Li, Zhengzhi; Zhang, Zhonghua; Lu, Lucy X; Orear, Lynda; Zutter, Mary M

    2011-01-01

    Mast cells, critical mediators of inflammation and anaphylaxis, are poised as one of the first lines of defense against external assault. Mast cells release several classes of preformed and de novo synthesized mediators. Cross-linking of the high-affinity FcεRI results in degranulation and the release of preformed, proinflammatory mediators including histamine and serotonin. We previously demonstrated that mast cell activation by Listeria monocytogenes requires the α2β1 integrin for rapid IL-6 secretion both in vivo and in vitro. However, the mechanism of IL-6 release is unknown. Here, we demonstrate the Listeria- and α2β1 integrin-mediated mast cell release of preformed IL-6 without the concomitant release of histamine or β-hexosaminidase. α2β1 integrin-dependent mast cell activation and IL-6 release is calcium independent. In contrast, IgE cross-linking-mediated degranulation is calcium dependent and does not result in IL-6 release, demonstrating that distinct stimuli result in the release of specific mediator pools. These studies demonstrate that IL-6 is presynthesized and stored in connective tissue mast cells and can be released from mast cells in response to distinct, α2β1 integrin-dependent stimulation, providing the host with a specific innate immune response without stimulating an allergic reaction.

  16. Inhibition of collagen production in scleroderma fibroblast cultures by a connective tissue glycoprotein extracted from normal dermis

    Energy Technology Data Exchange (ETDEWEB)

    Maquart, F.X.; Bellon, G.; Cornillet-Stoupy, J.; Randoux, A.; Triller, R.; Kalis, B.; Borel, J.P.

    1985-08-01

    It was shown in a previous paper that a connective tissue glycoprotein (CTGP) extracted from normal rabbit dermis was able to inhibit total protein and collagen syntheses by normal dermis fibroblast cultures. In the present study, the effects of CTGP on scleroderma fibroblasts were investigated. (/sup 14/C)Proline incorporation into total proteins of the supernatant was not significantly different from that found in controls. By contrast, the amount of collagen, expressed as percentage of total secreted protein, was far higher in scleroderma cultures than in normal ones (14.4% +/- 6.0% vs 4.6% +/- 0.9%). Addition of CTGP to the medium induced a concentration-dependent inhibition of (/sup 14/C)proline incorporation into proteins from both control and scleroderma cells. In control cultures, no significant decrease of the percentage of collagen was observed, but over 60 micrograms/ml, both cytotoxic effects and inhibition of protein synthesis occurred. In scleroderma cultures, the inhibition was twice as effective on collagen as on noncollagen protein synthesis. The inhibition of collagen secretion was not related either to changes in collagen hydroxylation or to the intracellular catabolism of newly synthesized procollagen.

  17. Schwann cells but not olfactory ensheathing cells inhibit CNS myelination via the secretion of connective tissue growth factor.

    Science.gov (United States)

    Lamond, Rebecca; Barnett, Susan C

    2013-11-20

    Cell transplantation is a promising strategy to promote CNS repair and has been studied for several decades with a focus on glial cells. Promising candidates include Schwann cells (SCs) and olfactory ensheathing cells (OECs). Both cell types are thought to be neural crest derived and share many properties in common, although OECs appear to be a better candidate for transplantation by evoking less astrogliosis. Using CNS mixed myelinating rat cultures plated on to a monolayer of astrocytes, we demonstrated that SCs, but not OECs, secrete a heat labile factor(s) that inhibits oligodendrocyte myelination. Comparative qRT-PCR and ELISA showed that SCs expressed higher levels of mRNA and protein for connective tissue growth factor (CTGF) than OECs. Anti-CTGF reversed the SCM-mediated effects on myelination. Both SCM and CTGF inhibited the differentiation of purified rat oligodendrocyte precursor cells (OPCs). Furthermore, pretreatment of astrocyte monolayers with SCM inhibited CNS myelination and led to transcriptional changes in the astrocyte, corresponding to upregulation of bone morphogenic protein 4 mRNA and CTGF mRNA (inhibitors of OPC differentiation) and the downregulation of insulin-like growth factor 2 mRNA (promoter of OPC differentiation). CTGF pretreatment of astrocytes increased their expression of CTGF, suggesting that this inhibitory factor can be positively regulated in astrocytes. These data provide evidence for the advantages of using OECs, and not mature SCs, for transplant-mediated repair and provide more evidence that they are a distinct and unique glial cell type.

  18. Mechanically relevant consequences of the composite laminate-like design of the abdominal wall muscles and connective tissues.

    Science.gov (United States)

    Brown, Stephen H M

    2012-05-01

    Together, three abdominal wall muscles (external oblique, internal oblique and transversus abdominis) form a tightly bound muscular sheet that has been likened to a composite-laminate structure. Previous work has demonstrated the ability of force generated by these three muscles to be passed between one another through connective tissue linkages. Muscle fibres in each muscle are obliquely oriented with respect to its neighbouring muscles. It is proposed here is that this unique morphology of the abdominal wall muscles functions, through the application of constraining forces amongst the muscles, to increase force- and stiffness-generating capabilities. This paper presents a mathematical formulation of the stress-strain relationship for a transversely isotropic fibrous composite, and establishes a strengthening and stiffening effect when stress can be transferred between the fibrous layers. Application of empirical mechanical properties to this formulation demonstrates this effect for the abdominal wall muscles and, in greater proportion, for the anterior aponeurosis of the abdominal wall. This has implications for increasing the stiffness and passive load bearing ability of the abdominal wall muscles, and has the potential to modulate the whole muscle force-length and force-velocity relationships during contraction.

  19. Passive mechanical properties of rat abdominal wall muscles suggest an important role of the extracellular connective tissue matrix.

    Science.gov (United States)

    Brown, Stephen H M; Carr, John Austin; Ward, Samuel R; Lieber, Richard L

    2012-08-01

    Abdominal wall muscles have a unique morphology suggesting a complex role in generating and transferring force to the spinal column. Studying passive mechanical properties of these muscles may provide insights into their ability to transfer force among structures. Biopsies from rectus abdominis (RA), external oblique (EO), internal oblique (IO), and transverse abdominis (TrA) were harvested from male Sprague-Dawley rats, and single muscle fibers and fiber bundles (4-8 fibers ensheathed in their connective tissue matrix) were isolated and mechanically stretched in a passive state. Slack sarcomere lengths were measured and elastic moduli were calculated from stress-strain data. Titin molecular mass was also measured from single muscle fibers. No significant differences were found among the four abdominal wall muscles in terms of slack sarcomere length or elastic modulus. Interestingly, across all four muscles, slack sarcomere lengths were quite long in individual muscle fibers (>2.4 µm), and demonstrated a significantly longer slack length in comparison to fiber bundles (p muscle lengths. Titin molecular mass was significantly less in TrA compared to each of the other three muscles (p < 0.0009), but this difference did not correspond to hypothesized differences in stiffness.

  20. Cucurbitacin I Attenuates Cardiomyocyte Hypertrophy via Inhibition of Connective Tissue Growth Factor (CCN2 and TGF- β/Smads Signalings.

    Directory of Open Access Journals (Sweden)

    Moon Hee Jeong

    Full Text Available Cucurbitacin I is a naturally occurring triterpenoid derived from Cucurbitaceae family plants that exhibits a number of potentially useful pharmacological and biological activities. However, the therapeutic impact of cucurbitacin I on the heart has not heretofore been reported. To evaluate the functional role of cucurbitacin I in an in vitro model of cardiac hypertrophy, phenylephrine (PE-stimulated cardiomyocytes were treated with a sub-cytotoxic concentration of the compound, and the effects on cell size and mRNA expression levels of ANF and β-MHC were investigated. Consequently, PE-induced cell enlargement and upregulation of ANF and β-MHC were significantly suppressed by pretreatment of the cardiomyocytes with cucurbitacin I. Notably, cucurbitacin I also impaired connective tissue growth factor (CTGF and MAPK signaling, pro-hypertrophic factors, as well as TGF-β/Smad signaling, the important contributing factors to fibrosis. The protective impact of cucurbitacin I was significantly blunted in CTGF-silenced or TGF-β1-silenced hypertrophic cardiomyocytes, indicating that the compound exerts its beneficial actions through CTGF. Taken together, these findings signify that cucurbitacin I protects the heart against cardiac hypertrophy via inhibition of CTGF/MAPK, and TGF- β/Smad-facilitated events. Accordingly, the present study provides new insights into the defensive capacity of cucurbitacin I against cardiac hypertrophy, and further suggesting cucurbitacin I's utility as a novel therapeutic agent for the management of heart diseases.

  1. Antiproliferative factor regulates connective tissue growth factor (CTGF/CCN2) expression in T24 bladder carcinoma cells

    Science.gov (United States)

    Matika, Christina A.; Wasilewski, Melissa; Arnott, John A.; Planey, Sonia Lobo

    2012-01-01

    Antiproliferative factor (APF) is a sialoglycopeptide elevated in the urine of patients with interstitial cystitis (IC)—a chronic, painful bladder disease of unknown etiology. APF inhibits the proliferation of normal bladder epithelial and T24 bladder carcinoma cells in vitro by binding to cytoskeleton-associated protein 4 (CKAP4) and altering the transcription of genes involved in proliferation, cellular adhesion, and tumorigenesis; however, specific molecular mechanisms and effector genes that control APF's antiproliferative effects are unknown. In this study, we found that there was a 7.5-fold up-regulation of connective tissue growth factor (CTGF/CCN2) expression in T24 bladder carcinoma cells treated with APF. Western blot revealed a dose-dependent increase in CCN2 protein levels, with secretion into the culture medium after APF treatment. CCN2 overexpression enhanced APF's antiproliferative activity, whereas CCN2 knockdown diminished APF-induced p53 expression. Using a luciferase reporter construct, we found that APF treatment resulted in fivefold activation of the CCN2 proximal promoter and, of importance, that small interfering RNA–mediated knockdown of CKAP4 inhibited CCN2 upregulation. In addition, we demonstrate that CKAP4 translocates to the nucleus and binds to the CCN2 proximal promoter in an APF-dependent manner, providing evidence that CCN2 regulation by APF involves CKAP4 nuclear translocation and binding to the CCN2 promoter. PMID:22438586

  2. Is it necessary to perform connective tissue disorders laboratory tests when a patient experiences the first demyelinating attack?

    Directory of Open Access Journals (Sweden)

    Masoud Etemadifar

    2013-01-01

    Full Text Available Background: It may be difficult to differentiate between the first demyelinating attack and the neurological manifestations of connective tissue diseases. Materials and Methods: A total of 79 patients with optic neuritis were compared with 79 healthy controls. Their blood samples were tested for erythrocyte sedimentation rate (ESR, C-reactive protein (CRP, antiβ2-Glycoprotein I antibody (IgG, IgM, anticardiolipin antibody (IgM, IgG, lupus anticoagulant, anti-double strand DNA (anri-ds DNA, antinuclear antibody (ANA, anti-myeloperoxidae (p-ANCA, and anti-Proteinase 3 (C-ANCA. Results: In clinically isolated syndrome group β2-Glycoprotein (IgM and lupus anti-coagulant were positive in 1.3% of patients whereas ANA was positive in 1.3% and anti-β2-Glycoprotein I (IgM was positive in 2.5% of control group. No rheumatologic disease was found in objects with positive tests. Conclusion: This study shows no specific difference between two groups.

  3. Inhibition of connective tissue growth factor overexpression decreases growth of hepatocellular carcinoma cells in vitro and in vivo

    Institute of Scientific and Technical Information of China (English)

    JIA Xiao-qin; CHENG Hai-qing; LI Hong; ZHU Yan; LI Yu-hua; FENG Zhen-qing; ZHANG Jian-ping

    2011-01-01

    Background We have previously found that connective tissue growth factor (CTGF) is highly expressed in a rat model of liver cancer.Here,we examined expression of CTGFin human hepatocellular carcinoma (HCC) cells and its effect on cell growth.Methods Real-time PCR was used to observe expression of CTGF in human HCC cell lines HepG2,SMMC-7721,MHCC-97H and LO2.siRNA for the CTGFgene was designed,synthesized and cloned into a Plk0.1-GFP-SP6 vector to construct a lentivirus-mediated shRNA/CTGF.CTGF mRNA and protein expression in HepG2 cells treated by CTGF-specific shRNA was evaluated by real-time PCR and Western blotting.3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was utilized to evaluate the growth effect,and a colony formation assay was used for observing clonogenic growth.In vivo,tumor cell proliferation was evaluated in a nude mouse model of xenotransplantation.Statistical significance was determined by t test for comparison between two groups,or analysis of variance (ANOVA) for multiple groups.Results Immunohistochemical staining of CTGF was seen in 35 of 40 HCC samples (87.5%).CTGF was overexpressed 5-fold in 20 HCC tissues,compared with surrounding non-tumor liver tissue.CTGF mRNA level was 5-8-fold higher in HepG2,SMMC-7721 and MHCC-97H than in LO2 cells.This indicated that the inhibition rate of cell growth was 43% after knockdown of CTGF expression (P <0.05).Soft agar colony formation assay showed that siRNA mediated knockdown of CTGF inhibited colony formation in soft agar of HepG2 cells (P <0.05).The volume of tumors from CTGF-shRNA-expressing cells only accounted for 35% of the tumors from the scrambled control-infected HepG2 cells (P <0.05).Conclusions CTGF was overexpressed in human HCC cells and downregulation of CTGF inhibited HCC growth in vitro and in vivo.Knockdown of CTGF may be a potential therapeutic strategy for treatment of HCC.

  4. Impact of thermal processing and the Maillard reaction on the basophil activation of hazelnut allergic patients.

    Science.gov (United States)

    Cucu, Tatiana; De Meulenaer, Bruno; Bridts, Chris; Devreese, Bart; Ebo, Didier

    2012-05-01

    Food allergy, an abnormal immunological response due to sensitization to a food component, has become an important health problem, especially in industrialized countries. The aim of this study was to investigate the impact of thermal processing and glycation on the basophil activation by hazelnut proteins using a basophil activation test. Patients with systemic allergic reactions (SR; n=6) to hazelnut as well as patients with an isolated oral allergy syndrome (OAS; n=4) were investigated. Thermal processing of hazelnut proteins either in the presence or absence of wheat proteins did not result in major changes in the stimulatory activity of the basophils for patients with SR or OAS. For the patients with OAS, incubation of hazelnut proteins with glucose led to complete depletion of the stimulatory activity of the basophils. An increase in stimulatory activity of the basophils for two out of six patients with SR was observed. For the other four patients slight or complete abolition of the stimulatory activity was observed. These results indicate that some patients with SR to hazelnut are at risk when exposed to hazelnut proteins, even in processed foods.

  5. Growth factor of Connective tissue Disease in Department of Ophthalmology%结缔组织生长因子在眼科疾病中的研究

    Institute of Scientific and Technical Information of China (English)

    朱海英

    2015-01-01

    Through the study on the expression of connective tissue growth factor,analysis ofthe relationship between the structure and the eye of connective tissue growth factor,can provide a more effective method for the treatment of diseases in Department of ophthalmology.As a result of connective tissue growth factor in vivoshowed widespread expression,and with many ocular diseases are closely related.Therefore,blocking or inhibiting connective tissue growth factor plays an important role in the treatment of eye diseases.%本文通过研究结缔组织生长因子表达,分析眼部结构与结缔组织生长因子的关系,为眼科疾病的治疗提供更有效的治疗方法。由于结缔组织生长因子在体内广泛表达,且与许多眼部疾病均密切相关。因此,阻断或抑制结缔组织生长因子对于眼部疾病治疗具有重要作用。

  6. A nationwide study of connective tissue disease and other rheumatic conditions among Danish women with long-term cosmetic breast implantation

    DEFF Research Database (Denmark)

    Fryzek, Jon P; Holmich, Lisbet; McLaughlin, Joseph K

    2007-01-01

    PURPOSE: Numerous epidemiologic studies have demonstrated that breast implants are not associated with connective tissue diseases (CTDs). However, many CTDs are rare, and continued follow-up of women with breast implants is warranted. METHODS: We extended by 5 years the follow-up of our earlier...

  7. 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.

  8. Inhibition of Collagen Synthesis and Regulation of Cell Motility in Vascular Smooth Muscle Cells by Suppression of Connective Tissue growth Factor Expression Using RNA Interference

    Institute of Scientific and Technical Information of China (English)

    Xiao-Jing LIU; Huai-Qing CHEN

    2005-01-01

    @@ 1 Introduction Vascular smooth muscle cell (VSMC) hyperplasia plays an important role in both chronic and acute pathologies including atherosclerosis and restenosis. Recent studies have shown that connective tissue growth factor (CTGF) is a novel growth factor involved in the development and progression of atherosclerosis.

  9. 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, T.Q.; Tarnow, L.; Jorsal, A.

    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...

  10. Plasma connective tissue growth factor is an independent predictor of end-stage renal disease and mortality in type 1 diabetic nephropathy.

    NARCIS (Netherlands)

    Nguyen, T.Q.; Tarnow, L.; Jorsal, A.; Oliver, N.; Roestenberg, P.M.H.; Ito, Y.; Parving, H.H.; Rossing, P.; Nieuwenhoven, FA van; Goldschmeding, R.

    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 patien

  11. EFFECTS OF CISAPRIDE ON THE ESOPHAGEAL MOTOR FUNCTION OF PATIENTS WITH PROGRESSIVE SYSTEMIC-SCLEROSIS OR MIXED CONNECTIVE-TISSUE DISEASE

    NARCIS (Netherlands)

    LIMBURG, AJ; SMIT, AJ; KLEIBEUKER, JH

    1991-01-01

    In a double-blind crossover study lower esophageal sphincter pressure and distal esophageal motility were studied in 10 patients with progressive systemic sclerosis or mixed connective tissue disease, following a single intravenous dose of cisapride or placebo. The measurements were carried out unde

  12. Reconstruction of a hard connective tissue utilizing a pressed silk sheet and type-I collagen as the scaffold for fibroblasts.

    Science.gov (United States)

    Takezawa, Toshiaki; Ozaki, Katsuyuki; Takabayashi, Chiyuki

    2007-06-01

    A pressed silk sheet is a new biomaterial composed of a network of numerous cocoon filaments and having excellent mechanical strength and shape stability compared to a cotton-gauze sheet. To reconstruct a hard connective tissue using the silk sheet and type-I collagen as the scaffold for fibroblasts, three different three-dimensional floating culture systems were designed. "On sheet" system: fibroblasts were seeded on the silk sheet coated with collagen and the cell-attached sheet was cultured. "In gel" system: fibroblasts and the silk sheet were co-embedded in a collagen gel and the gel was cultured. "On vitrigel" system: fibroblasts were seeded on both sides of a collagen vitrigel involving the silk sheet and the vitrigel was cultured. The fibroblasts in all culture systems grew and formed disk-shaped connective tissue models involving the silk sheet by 14 days of culture. The "on sheet" and "on vitrigel" models retained a maximum elastic load of about 23 kgf and an ultimate tensile load of about 3.6 kgf, which were almost the same as for the individual silk sheet. However, the "in gel" system showed a low value for the tensile load. Cell damage following application of mechanical stress was lowest in the "on vitrigel" system. These data demonstrated the advantage of the "on vitrigel" system in reconstructing hard connective tissues. Such a novel culture method would contribute to a regenerative medicine for the failure of ligaments, tendons, and other connective tissues.

  13. [THE COMBINATION OF RECURRENT INTUSSUSCEPTION DUODENAL, ZENKER DIVERTICULUM, HIATAL HERNIA AND HASTROPTOSIS AS A MANIFESTATION OF NON-DIFFERENT DYSPLASIA OF CONNECTIVE TISSUE].

    Science.gov (United States)

    Pavlov, M V; Orlova, N V

    2015-01-01

    Presented rare clinical case: a combination of recurrent intussusception duodenal, diverticulum Zenker, hiatal hernia and hastroptosis as a manifestation of non-different dysplasia of connective tissue. Special interest is recurrent intussusception upper horizontal portion duodenal in the bulb, is not detected when esophagogastroduodenoscopy.

  14. Inhibition effect of small interfering RNA of connective tissue growth factor on the expression of vascular endothelial growth factor and connective tissue growth factor in cultured human peritoneal mesothelial cells

    Institute of Scientific and Technical Information of China (English)

    LIU Fu-you; FU Xiao; ZHU Jian-lian; XIAO Li; PENG You-ming; DUAN Shao-bin; LIU Hong; LIU Ying-hong; LING Gui-hui; YUAN Fang; CHEN Jun-xiang

    2007-01-01

    Background The peritoneum response to peritoneal dialysis can lead to fibrosis. The transforming growth factor β1(TGF-β1) plays a key role in regulating tissue repair and remodelling after injury. Connective tissue growth factor (CTGF),a downstream mediator of TGF-β1 inducing fibrosis, has been implicated in peritoneal fibrosis. Vascular endothelial growth factor (VEGF) plays a key role in angiogenesis that can hasten peritoneal fibrosis. In this study, we investigated the effect of small interfering RNA (siRNA) of CTGF by pRETRO-SUPER (PRS) retrovirus vector on the expression of CTGF and VEGF in human peritoneal mesothelial cells.Methods Retrovirus producing CTGF siRNA were constructed from the inverted oligonucleotides and transferred into packaging cell line PT67 with lipofectamine, and the virus supernatant was used to infect human peritoneal mesothelial cell (HPMC). The cells were divided into seven groups: low glucose DMEM, low glucose DMEM + TGF-β1 5 ng/ml, low glucose DMEM + TGF-β1 5 ng/ml + PRS-CTGF-siRNA1-4 and low glucose DMEM + TGF-β1 5 ng/ml + PRS. The expression of CTGF and VEGF were measured by semiquantitative RT-PCR and Western blot.Results Low levels of CTGF and VEGF were detected in confluent HPMCs. Following stimulation with TGF-β1, the levels of CTGF and VEGF were significantly upregulated (P<0.01). Introduction of PRS-CTGF-siRNA1-4 resulted in the significant reduction of CTGF mRNA and protein, and VEGF mRNA (P<0.01), especially in groups PRS-CTGF-siRNA1 and PRS-CTGF-siRNA4. The introduction of PRS void vector did not have these effects (P>0.05).Conclusions The expression of CTGF siRNA mediated by PRS retrovirus vector can effectively reduce the level of CTGF and VEGF induced by TGF-β1 in cultured HPMCs. This study may provide potential therapeutic strategies to prevent the peritoneal fibrosis.

  15. The connective tissue and glial framework in the optic nerve head of the normal human eye: light and scanning electron microscopic studies.

    Science.gov (United States)

    Oyama, Tokuhide; Abe, Haruki; Ushiki, Tatsuo

    2006-12-01

    The arrangement of connective tissue components (i.e., collagen, reticular, and elastic fibers) and glial elements in the optic nerve head of the human eye was investigated by the combined use of light microscopy and scanning electron microscopy (SEM). Light-microscopically, the optic nerve head could be subdivided into four parts from the different arrangements of the connective tissue framework: a surface nerve fiber layer, and prelaminar, laminar, and postlaminar regions. The surface nerve fiber layer only possessed connective tissue elements around blood vessels. In the prelaminar region, collagen fibrils, together with delicate elastic fibers, formed thin interrupted sheaths for accommodating small nerve bundles. Immunohistochemistry for the glial fibrillary acidic protein (GFAP) showed that GFAP-positive cells formed columnar structures (i.e., glial columns), with round cell bodies piled up