Sample records for autoimmune connective tissue

  1. Therapy of Autoimmune Connective Tissue Diseases

    Microsoft Academic Search

    Timothy M. Wright; Dana P. Ascherman

    \\u000a The autoimmune diseases can be divided into two basic categories: organ specific and systemic. Organ specific autoimmune disease can affect virtually any tissue of the body and is associated most often with evidence\\u000a of both T and B cell autoimmune responses directed against the cells of the affected organ. Examples of organ specific autoimmune\\u000a disease include multiple sclerosis, Type I

  2. Renal involvement in autoimmune connective tissue diseases

    PubMed Central

    2013-01-01

    Connective tissue diseases (CTDs) are a heterogeneous group of disorders that share certain clinical presentations and a disturbed immunoregulation, leading to autoantibody production. Subclinical or overt renal manifestations are frequently observed and complicate the clinical course of CTDs. Alterations of kidney function in Sjögren syndrome, systemic scleroderma (SSc), auto-immune myopathies (dermatomyositis and polymyositis), systemic lupus erythematosus (SLE), antiphospholipid syndrome nephropathy (APSN) as well as rheumatoid arthritis (RA) are frequently present and physicians should be aware of that. In SLE, renal prognosis significantly improved based on specific classification and treatment strategies adjusted to kidney biopsy findings. Patients with scleroderma renal crisis (SRC), which is usually characterized by severe hypertension, progressive decline of renal function and thrombotic microangiopathy, show a significant benefit of early angiotensin-converting-enzyme (ACE) inhibitor use in particular and strict blood pressure control in general. Treatment of the underlying autoimmune disorder or discontinuation of specific therapeutic agents improves kidney function in most patients with Sjögren syndrome, auto-immune myopathies, APSN and RA. In this review we focus on impairment of renal function in relation to underlying disease or adverse drug effects and implications on treatment decisions. PMID:23557013

  3. Hair disorders associated with autoimmune connective tissue diseases.

    PubMed

    Cassano, N; Amerio, P; D'Ovidio, R; Vena, G A

    2014-10-01

    Hair disorders are frequently observed in various systemic diseases, including autoimmune connective tissue diseases (CTDs), with predilection of lupus erythematosus (LE), followed by dermatomyositis (DM) and scleroderma. Hair disorders in CTDs may manifest as various clinical patterns, such as telogen hair loss, diffuse thinning or fragility of hair, and scarring alopecia. Less common hair disorders include anagen effluvium, alopecia areata, and trichomegaly. Some drugs used to treat CTDs may cause hair loss in a drug-related manner or hyperthrichosis. In the assessment of common hair loss patterns, such as telogen effluvium, the possible association with CTDs must be borne in mind and should not be overlooked. Alopecia appears to be a significant sign in the course of LE and especially systemic LE. In DM, the involvement of the scalp is common, and is often characterized by a diffuse, violaceous, scaly, non-scarring and symptomatic hair loss. Linear scleroderma en coup de sabre is an uncommon localized form of morphea with involvement of the paramedian forehead and frontal scalp, where it is associated with cicatricial alopecia. The most important variant of scarring alopecia in the context of CTDs is that associated with discoid lupus erythematosus (DLE). In the diagnostic work-up of DLE-related cicatrical alopecia, histopathological and immunopathological studies are useful, and a relevant role has been attributed to dermatoscopy (trichoscopy) over the last years. Hair loss has been reported in several other CTDs, including mixed and undifferentiated CTDs, and primary Sjögren's syndrome, although it is likely to be underestimated in such diseases. PMID:24975949

  4. Treatment of dermatologic connective tissue disease and autoimmune blistering disorders in pregnancy.

    PubMed

    Braunstein, Inbal; Werth, Victoria

    2013-01-01

    Autoimmune skin disease occurs in pregnancy, and treatment is often required to control both maternal disease and fetal outcomes. Here we present the available safety data in pregnancy and lactation for medications used to treat autoimmune skin diseases, including cutaneous lupus erythematosus, dermatomyositis, morphea and systemic sclerosis, pemphigus vulgaris, pemphigus foliaceus, and pemphigoid gestationis. A PubMed search of the English-language literature using keywords, "pregnancy" "rheumatic disease," and "connective tissue disease" was performed. Relevant articles found in the search and references were included. Reasonable evidence supports the careful and cautious use of topical steroids, topical calcineurin inhibitors, systemic corticosteroids, hydroxychloroquine, and azathioprine in pregnancy. Case reports or clinical experience suggest intravenous immunoglobulin, dapsone, phototherapy, rituximab, and plasmapheresis may be safe. Several treatment options exist for autoimmune skin disease in pregnancy and lactation, and should be considered when treating these patients. PMID:23914893

  5. Connective Tissue Disorders

    MedlinePLUS

    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 ...

  6. Connective Tissue Ulcers

    PubMed Central

    Dabiri, Ganary; Falanga, Vincent

    2013-01-01

    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. PMID:23756459

  7. The Role of Dendritic Cells in Tissue-Specific Autoimmunity

    PubMed Central

    Langridge, William

    2014-01-01

    In this review, we explore the role of dendritic cell subsets in the development of tissue-specific autoimmune diseases. From the increasing list of dendritic cell subclasses, it is becoming clear that we are only at the beginning of understanding the role of these antigen presenting cells in mediating autoimmunity. Emerging research areas for the study of dendritic cell involvement in the onset and inhibition of tissue-specific autoimmunity are presented. Further, we compare tissue specific to systemic autoimmunity to demonstrate how development of dendritic cell-based therapies may be broadly applicable to both classes of autoimmunity. Continued development of these research areas will lead us closer to clinical assessment of novel immunosuppressive therapy for the reversal and prevention of tissue-specific autoimmunity. Through description of dendritic cell functions in the modulation of tissue-specific autoimmunity, we hope to stimulate a greater appreciation and understanding of the role dendritic cells play in the development and treatment of autoimmunity. PMID:24877157

  8. Cutaneous mucinosis in mixed connective tissue disease.

    PubMed

    Favarato, Maria Helena Sampaio; Miranda, Sofia Silveira de Castro; Caleiro, Maria Teresa Correia; Assad, Ana Paula Luppino; Halpern, Ilana; Fuller, Ricardo

    2013-01-01

    Cutaneous mucinosis is a group of conditions involving an accumulation of mucin or glycosaminoglycan in the skin and its annexes. It is described in some connective tissue diseases but never in association with mixed connective tissue disease. This report concerns two cases of cutaneous mucinosis in patients with mixed connective tissue disease in remission; one patient presented the papular form, and the other reticular erythematous mucinosis. These are the first cases of mucinosis described in mixed connective tissue disease. Both cases had skin lesions with no other clinical or laboratorial manifestations, with clinical response to azathioprine in one, and to an association of chloroquine and prednisone in the other. PMID:24068142

  9. Cutaneous mucinosis in mixed connective tissue disease*

    PubMed Central

    Favarato, Maria Helena Sampaio; Assad, Ana Paula Luppino; Miranda, Sofia Silveira de Castro; Halpern, Ilana; Caleiro, Maria Teresa Correia; Fuller, Ricardo

    2013-01-01

    Cutaneous mucinosis is a group of conditions involving an accumulation of mucin or glycosaminoglycan in the skin and its annexes. It is described in some connective tissue diseases but never in association with mixed connective tissue disease. This report concerns two cases of cutaneous mucinosis in patients with mixed connective tissue disease in remission; one patient presented the papular form, and the other reticular erythematous mucinosis. These are the first cases of mucinosis described in mixed connective tissue disease. Both cases had skin lesions with no other clinical or laboratorial manifestations, with clinical response to azathioprine in one, and to an association of chloroquine and prednisone in the other. PMID:24068142

  10. Rheumatic fever, autoimmunity, and molecular mimicry: the streptococcal connection.

    PubMed

    Cunningham, Madeleine W

    2014-01-01

    The group A streptococcus, Streptococcus pyogenes, and its link to autoimmune sequelae, has acquired a new level of understanding. Studies support the hypothesis that molecular mimicry between the group A streptococcus and heart or brain are important in directing immune responses in rheumatic fever. Rheumatic carditis, Sydenham chorea and a new group of behavioral disorders called pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections are reviewed with consideration of autoantibody and T cell responses and the role of molecular mimicry between the heart, brain and group A streptococcus as well as how immune responses contribute to pathogenic mechanisms in disease. In rheumatic carditis, studies have investigated human monoclonal autoantibodies and T cell clones for their crossreactivity and their mechanisms leading to valve damage in rheumatic heart disease. Although studies of human and animal sera from group A streptococcal diseases or immunization models have been crucial in providing clues to molecular mimicry and its role in the pathogenesis of rheumatic fever, study of human monoclonal autoantibodies have provided important insights into how antibodies against the valve may activate the valve endothelium and lead to T cell infiltration. Passive transfer of anti-streptococcal T cell lines in a rat model of rheumatic carditis illustrates effects of CD4+ T cells on the valve. Although Sydenham chorea has been known as the neurological manifestation of rheumatic fever for decades, the combination of autoimmunity and behavior is a relatively new concept linking brain, behavior and neuropsychiatric disorders with streptococcal infections. In Sydenham chorea, human mAbs and their expression in transgenic mice have linked autoimmunity to central dopamine pathways as well as dopamine receptors and dopaminergic neurons in basal ganglia. Taken together, the studies reviewed provide a basis for understanding streptococcal sequelae and how immune responses against group A streptococci influence autoimmunity and inflammatory responses in the heart and brain. PMID:24892819

  11. Action of hyperoxia on connective tissue

    NASA Technical Reports Server (NTRS)

    Shimkevich, L. L.

    1973-01-01

    A general morphological, electron microscopic and cytochemical study of subcutaneous connective tissue of white rats while keeping them under conditions of increased partial pressure of oxygen was conducted. A short term action of pure oxygen at 1 ata caused activation of metabolism in the connective tissue cells without disturbance of ultrastructures. Noticeable pathological changes arose after twelve hours, later they advanced and appeared as destruction of cellular organelles, as suppression of cellular metabolism, and partially as a reduction in the activity of the oxidative enzymes. Destructive changes of collagenic fibers were noticed. Data are also presented on the structure and cytochemistry of connective tissue under other conditions of hyperoxia.

  12. Heritable Disorders of Connective Tissue

    MedlinePLUS

    ... made up of dozens of proteins, including collagens, proteoglycans, and glycoproteins. The combination of these proteins can ... gene defects in mice and humans (Apert syndrome) proteoglycans, a group of proteins that maintain tissue stiffness ...

  13. Mechanisms of tissue injury in autoimmune liver diseases.

    PubMed

    Liaskou, Evaggelia; Hirschfield, Gideon M; Gershwin, M Eric

    2014-09-01

    Autoimmune diseases affecting the liver are mainly represented by autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC). The characteristic morphologic patterns of injury are a chronic hepatitis pattern of damage in AIH, destruction of small intrahepatic bile ducts in PBC and periductal fibrosis and inflammation involving larger bile ducts in PSC. The factors responsible for initiation and perpetuation of the injury in all the three autoimmune liver diseases are not understood completely but are likely to be environmental triggers on the background of genetic variation in immune regulation. In this review, we summarise the current understanding of the mechanisms underlying the breakdown of self-tolerance in autoimmune liver diseases. PMID:25082647

  14. What Are Heritable Disorders of Connective Tissue?

    MedlinePLUS

    ... Heritable Disorders of the Connective Tissue Q&A full-text version, please contact NIAMS using the contact information above. To view the complete text or to order online, visit ... NIAMS Site NIH… Turning Discovery Into Health ® Home | ...

  15. Pulmonary hypertension associated with connective tissue disease.

    PubMed

    Fagan, Karen A; Badesch, David B

    2002-01-01

    Pulmonary arterial hypertension is a life threatening complication of several connective tissue diseases including scleroderma (both diffuse and limited scleroderma, or the CREST syndrome--calcinosis cutis, Raynaud's phenomenon, esophageal dysfunction, sclerodactyly, and telangectasia), systemic lupus erythomatosis (SLE), mixed connective tissue disease (MCTD), and less commonly, rheumatoid arthritis (RA) and dermatomyositis/polymyositis. This report reviews the occurrence of this complication, potential etiologies, clinical presentation, and treatment options. PMID:12525998

  16. Evidence of Connective Tissue Involvement in Acupuncture

    Microsoft Academic Search

    Helene M. Langevin; David L. Churchill; Junru Wu; Gary J. Badger; Jason A. Yandow; James R. Fox; Martin H. Krag

    2002-01-01

    ABSTRACT Acupuncture needle manipulation gives rise to “needle grasp,” a biomechanical phenomenon characterized by an,increase in the force necessary to pull the needle out of the tissue (pullout force). This study investigates the hypothesis that winding of connective tissue, rather than muscle contraction, is the mechanism responsible for needle grasp. We performed 1) measurements of pullout ,force in humans with

  17. Autoimmune hepatitis

    MedlinePLUS

    Autoimmune hepatitis is inflammation of the liver that occurs when immune cells mistake the liver's normal cells ... This form of hepatitis is an autoimmune disease . The body's immune ... body tissue and harmful, outside substances. The result is an ...

  18. Update on Management of Connective Tissue Panniculitides

    PubMed Central

    Braunstein, Inbal; Werth, Victoria P.

    2012-01-01

    In connective tissue diseases panniculitis can be the sole manifestation or occur along with the underlying disease process. The best described forms of connective tissue panniculitis are lupus erythematosus panniculitis (LEP) and lupus profundus, panniculitis associated with dermatomyositis, and morphea and scleroderma associated panniculitis. These processes cause significant morbidity, such as deep atrophic scars, cosmetic disfigurement and psychiatric sequelae. Due to the location of the inflammation in the subcutaneous adipose layer, topical therapies may not penetrate enough to be effective, and systemic agents are required. Despite the large number of reported cases and therapies, recommendations for treatment are based largely on case series and expert opinion due to a lack of controlled therapeutic trials. All treatments are off-label in the United States. The lack of validated clinical outcome measures makes systematic and controlled studies difficult. Nonetheless further investigation into the most effective therapies for these conditions are needed. PMID:22741936

  19. Pulmonary hypertension complicating connective tissue disease.

    PubMed

    Lynch, Joseph P; Belperio, John A; Saggar, Rajeev; Fishbein, Michael C; Saggar, Rajan

    2013-10-01

    Pulmonary hypertension (PH) may complicate connective tissue disease (CTD), particularly systemic sclerosis (SSc, scleroderma), and markedly increases mortality. More than 70% of cases of PH complicating CTD occur in SSc, which is the major focus of this article. Pulmonary complications (i.e., interstitial lung disease [ILD] and PH) are the leading causes of scleroderma-related deaths. "Isolated" PH (i.e., without ILD) complicates SSc in 7.5 to 20% of cases; secondary PH may also occur in patients with SSc-associated ILD. Several clinical markers and specific autoantibody profiles have been associated with PH in SSc. The role of PH-specific therapy is controversial, as prognosis and responsiveness to therapy are worse in SSc-associated PH compared with idiopathic pulmonary arterial hypertension. We discuss medical therapies for CTD-associated PH and the role of lung transplantation for patients failing medical therapy. PMID:24037627

  20. The arthritis of mixed connective tissue disease.

    PubMed Central

    Bennett, R M; O'Connell, D J

    1978-01-01

    Twenty patients with mixed connective tissue disease were followed for 5 years. Arthritis occurred in all 20 patients, being the presenting complaint in 11 patients. The joints most frequently involved were the proximal interphalangeal (PIP), metacarpophalangeal (MCP), wrists, metatarsophalangeal (MTP), and knee; the distribution tended to be symmetrical, mimicking early rheumatoid arthritis. Joint deformities occurred in 6 patients, but apart from 1 patient with arthritis mutilans, significant functional impairment was not encountered. Radiologically small punched out bone erosions, asymmetrically distributed, were the most characteristic finding; other notable changes were aseptic necrosis, tuft erosions, and periarticular calcification. Joint effusions were non-inflammatory, the cellular content was predominantly lymphocytic and the C3 level was normal. Most cases were controlled with non-steroidal anti-inflammatory agents and invariably responded to prednisone less than or equal to 7.5 mg/day. Images PMID:718271

  1. Fibroblast involvement in soft connective tissue calcification

    PubMed Central

    Ronchetti, Ivonne; Boraldi, Federica; Annovi, Giulia; Cianciulli, Paolo; Quaglino, Daniela

    2013-01-01

    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 pseudoxanthoma elasticum (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 fibers 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. PMID:23467434

  2. Drug induction in connective tissue diseases.

    PubMed

    Verdelli, A; Antiga, E; Bonciolini, V; Bonciani, D; Volpi, W; Caproni, M

    2014-10-01

    Connective tissue diseases (CTDs) are defined as a group of acquired disorders resulting from persistent immuno-mediated inflammation. Several classes of drugs seem to be capable of inducing or exacerbating CTDs. A drug-induced (DI) syndrome is defined as a condition temporally related to continuous drug exposure, which resolves upon drug discontinuation. Among CTDs, lupus erythematosus is the most widely known and investigated DI syndrome. However, in recent years, the association between the onset of other CTDs, such as dermatomyositis (DM) and morphea/systemic sclerosis (SSc) has increased in patients with preceding exposure to particular substances. Herein, we conducted a review of published case reports including DM and morphea/SSc, evaluating the real causality among drugs and these syndromes. PMID:24975950

  3. Chondroitin sulphate inhibits connective tissue mast cells

    PubMed Central

    Theoharides, T C; Patra, P; Boucher, W; Letourneau, R; Kempuraj, D; Chiang, G; Jeudy, S; Hesse, Leah; Athanasiou, A

    2000-01-01

    Mast cells derive from the bone marrow and are responsible for the development of allergic and possibly inflammatory reactions. Mast cells are stimulated by immunoglobulin E (IgE) and specific antigen, but also by a number of neuropeptides such as neurotensin (NT), somatostatin or substance P (SP), to secrete numerous pro-inflammatory molecules that include histamine, cytokines and proteolytic enzymes.Chondroitin sulphate, a major constituent of connective tissues and of mast cell secretory granules, had a dose-dependent inhibitory effect on rat peritoneal mast cell release of histamine induced by the mast cell secretagogue compound 48/80 (48/80). This inhibition was stronger than that of the clinically available mast cell ‘stabilizer' disodium cromoglycate (cromolyn). Inhibition by chondroitin sulphate increased with the length of preincubation and persisted after the drug was washed off, while the effect of cromolyn was limited by rapid tachyphylaxis.Immunologic stimulation of histamine secretion from rat connective tissue mast cells (CTMC) was also inhibited, but this effect was weaker in umbilical cord-derived human mast cells and was absent in rat basophilic leukemia (RBL) cells which are considered homologous to mucosal mast cells (MMC). Oligo- and monosaccharides were not as effective as the polysaccharides.Inhibition, documented by light and electron microscopy, involved a decrease of intracellular calcium ion levels shown by confocal microscopy and image analysis. Autoradiography at the ultrastructural level showed that chondroitin sulphate was mostly associated with plasma and perigranular membranes.Chondroitin sulphate appears to be a potent mast cell inhibitor of allergic and nonimmune stimulation with potential clinical implications. PMID:11082109

  4. Questions and Answers on Autoimmunity and Autoimmune Diseases

    MedlinePLUS

    ... dermatomyositis. What are some of the treatments for autoimmune diseases? Of first importance in treating any autoimmune ... being researched. What is the family connection in autoimmune diseases? The ability to develop an autoimmune disease ...

  5. Relationship of acupuncture points and meridians to connective tissue planes

    Microsoft Academic Search

    Helene M. Langevin; Jason A. Yandow

    2002-01-01

    Acupuncture meridians traditionally are believed to constitute channels connecting the surface of the body to internal organs. We hypothesize that the network of acupuncture points and meridians can be viewed as a representation of the network formed by interstitial connective tissue. This hypothesis is supported by ultrasound images showing connective tissue cleavage planes at acupuncture points in normal human subjects.

  6. Connective Tissue Disorders and Smooth Muscle Disorders in Cardiology

    Microsoft Academic Search

    K. van Engelen; B. J. M. Mulder

    \\u000a The hereditary disorders of connective tissue encompass a spectrum of clinically and genetically heterogeneous conditions caused by genetic defects in structural connective\\u000a tissue proteins, such as collagen, fibrillin, and elastin. Clinical manifestations of these disorders are variable, and include\\u000a musculoskeletal, skin, ocular, cardiovascular, and other visceral pathologies. Substantial overlap in clinical features between\\u000a different disorders of connective tissue is present.

  7. Autoimmune Diabetes Is Suppressed by Treatment with Recombinant Human Tissue Kallikrein-1

    PubMed Central

    Maneva-Radicheva, Lilia; Amatya, Christina; Parker, Camille; Ellefson, Jacob; Radichev, Ilian; Raghavan, Arvind; Charles, Matthew L.; Williams, Mark S.; Robbins, Mark S.; Savinov, Alexei Y.

    2014-01-01

    The kallikrein-kinin system (KKS) comprises a cascade of proteolytic enzymes and biogenic peptides that regulate several physiological processes. Over-expression of tissue kallikrein-1 and modulation of the KKS shows beneficial effects on insulin sensitivity and other parameters relevant to type 2 diabetes mellitus. However, much less is known about the role of kallikreins, in particular tissue kallikrein-1, in type 1 diabetes mellitus (T1D). We report that chronic administration of recombinant human tissue kallikrein-1 protein (DM199) to non-obese diabetic mice delayed the onset of T1D, attenuated the degree of insulitis, and improved pancreatic beta cell mass in a dose- and treatment frequency-dependent manner. Suppression of the autoimmune reaction against pancreatic beta cells was evidenced by a reduction in the relative numbers of infiltrating cytotoxic lymphocytes and an increase in the relative numbers of regulatory T cells in the pancreas and pancreatic lymph nodes. These effects may be due in part to a DM199 treatment-dependent increase in active TGF-beta1. Treatment with DM199 also resulted in elevated C-peptide levels, elevated glucagon like peptide-1 levels and a reduction in dipeptidyl peptidase-4 activity. Overall, the data suggest that DM199 may have a beneficial effect on T1D by attenuating the autoimmune reaction and improving beta cell health. PMID:25259810

  8. Myofibroblasts and mechano-regulation of connective tissue remodelling

    Microsoft Academic Search

    Giulio Gabbiani; Boris Hinz; Christine Chaponnier; Robert A. Brown; James J. Tomasek

    2002-01-01

    During the past 20 years, it has become generally accepted that the modulation of fibroblastic cells towards the myofibroblastic phenotype, with acquisition of specialized contractile features, is essential for connective-tissue remodelling during normal and pathological wound healing. Yet the myofibroblast still remains one of the most enigmatic of cells, not least owing to its transient appearance in association with connective-tissue

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

    PubMed

    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 43weeks; 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?g/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 previously estimated which could explain why absolute silicon deficiency is difficult to achieve but, when it is achieved in young growing animals, it results in stunted growth and abnormal development of bone and other connective tissues. PMID:25687224

  10. Association of anti-phospholipid antibodies with connective tissue diseases

    PubMed Central

    Rai, Reena; Swetha, T.

    2015-01-01

    Background: The antiphospholipid antibodies (APLA) are directed against phospholipids and their binding proteins and are frequently found in association with connective tissue disorders. Systemic lupus erythematoses (SLE) with APLA may cause a diagnostic dilemma as there are several manifestations like haemolytic anemia, thrombocytopenia, neurologic manifestations, leg ulcerations, serositis proteinuria which overlap in both these conditions. We conducted a study to find out the association of antiphospholipid antibodies with connective tissue diseases and compared the clinical and laboratory parameters between antiphoshpolipid antibody positive and antiphoshpolipid antibody negative group. Materials and Methods: This study was carried out in 102 patients diagnosed with connective tissue diseases. APLA testing was done at baseline and for those positive, the test was repeated after 12 weeks. Results: 14.7 % of patients with connective tissue diseases tissue had positive antiphoshpolipid antibodies. Positive antiphoshpolipid antibody was detected in 73.3% of patients with SLE group, 13.3% of patients with mixed connective tissue disease (MCTD) and 13.3% of patients with systemic sclerosis. APLA positivity was seen in SLE patients with leg ulcers (87.2%), neurologic manifestation (72.7%), hemolytic anemia (62.3%), thrombocytopenia (72.7%), serositis (27.8%) and proteinuria(19.6%). Conclusions: Antiphoshpolipid antibodies should be tested in all patients with connective tissue disease.

  11. Real-time tissue elastography in the diagnosis of autoimmune pancreatitis.

    PubMed

    Dietrich, C F; Hirche, T O; Ott, M; Ignee, A

    2009-08-01

    Endoscopic ultrasound (EUS) elastography distinguishes tissues on the basis of their specific consistency. The preoperative diagnosis of autoimmune pancreatitis (AIP) is of the utmost importance in order to avoid surgery. The aim of this prospective evaluation of five patients was to investigate the role of this new technique in the characterization of mass lesions caused by AIP, with histology as the gold standard. All five patients with AIP presented with a characteristic stiff elastographic pattern not only of the mass lesion but also of the surrounding pancreatic parenchyma, which was not found in 17 patients with ductal adenocarcinoma and 10 healthy subjects. EUS elastography of the pancreas shows a typical and unique finding with homogenous stiffness of the whole organ, and this distinguishes AIP from the circumscribed mass lesion in ductal adenocarcinoma. PMID:19618344

  12. Detection of Connective Tissue Disorders from 4D Aortic MR

    E-print Network

    of connective tissue disorders leading to aortic aneurysms and dissections. Automated and accurate segmentation bindevćvs- sygdomme, som fřrer til aortic aneurysms og dissections. En automatisk og prćcis metode til

  13. Interpretation of autoantibody positivity in interstitial lung disease and lung-dominant connective tissue disease*

    PubMed Central

    Pereira, Daniel Antunes Silva; Kawassaki, Alexandre de Melo; Baldi, Bruno Guedes

    2013-01-01

    The initial evaluation of patients with interstitial lung disease (ILD) primarily involves a comprehensive, active search for the cause. Autoantibody assays, which can suggest the presence of a rheumatic disease, are routinely performed at various referral centers. When interstitial lung involvement is the condition that allows the definitive diagnosis of connective tissue disease and the classical criteria are met, there is little debate. However, there is still debate regarding the significance, relevance, specificity, and pathophysiological role of autoimmunity in patients with predominant pulmonary involvement and only mild symptoms or formes frustes of connective tissue disease. The purpose of this article was to review the current knowledge of autoantibody positivity and to discuss its possible interpretations in patients with ILD and without clear etiologic associations, as well as to enhance the understanding of the natural history of an allegedly new disease and to describe the possible prognostic implications. We also discuss the proposition of a new term to be used in the classification of ILDs: lung-dominant connective tissue disease. PMID:24473767

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

    PubMed Central

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

    2015-01-01

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

  15. Hypericin-mediated selective photomodification of connective tissues

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

    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. PMID:22884219

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

    PubMed Central

    Ahn, Andrew C; Wu, Junru; Badger, Gary J; Hammerschlag, Richard; Langevin, Helene M

    2005-01-01

    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 ?Amps) 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 ?) compared with control segments (75.0 ± 5.9 ?) (p = 0.0003). At the Spleen location, mean impedance for meridian (67.8 ± 6.8 ?) and control segments (68.5 ± 7.5 ?) were not significantly different (p = 0.70). Conclusion Tissue impedance was on average lower along the Pericardium meridian, but not along the Spleen meridian, compared with their respective controls. Ultrasound imaging of meridian and control segments suggested that contact of the needle with connective tissue may explain the decrease in electrical impedance noted at the Pericardium meridian. Further studies are needed to determine whether tissue impedance is lower in (1) connective tissue in general compared with muscle and (2) meridian-associated vs. non meridian-associated connective tissue. PMID:15882468

  18. Connective Tissue Disease-Associated Interstitial Lung Disease: A Focused Review.

    PubMed

    Solomon, Joshua J; Fischer, Aryeh

    2013-12-25

    The connective tissue diseases (CTDs) are a group of systemic disorders characterized by autoimmunity and autoimmune-mediated organ damage. The lung is a frequent target and all components of the respiratory system are at risk. Interstitial lung disease (ILD) represents a broad group of diffuse parenchymal lung injury patterns characterized by varying degrees of inflammation and fibrosis, is a common manifestation of CTD particularly common in systemic sclerosis, polymyositis/dermatomyositis, and rheumatoid arthritis, and is a leading cause of significant morbidity and mortality. The lung injury patterns of CTD-associated ILD (CTD-ILD) mirror those of idiopathic interstitial pneumonia and may arise at any time during the course of the CTD or may be the first manifestation of CTD. Patients with CTD that present with respiratory failure often present significant diagnostic dilemmas. Thorough and comprehensive assessments to exclude respiratory *infection, acute interstitial pneumonia, medication toxicity, pulmonary embolism, cardiac dysfunction, and diffuse alveolar hemorrhage are the fundamental components for the evaluation of such patients. Furthermore, patients with CTD are also at risk of acute exacerbations of underlying ILD. Acute exacerbations are manifested by subacute respiratory deterioration with worsening hypoxemia in the setting of new radiographic abnormalities. The prognosis of patients with CTD having respiratory failure is often quite poor, highlighting the need for prompt and thorough clinical assessments to determine the underlying etiology and implementation of appropriate therapeutic strategies. PMID:24371251

  19. Metalloproteinase inhibitors and the prevention of connective tissue breakdown

    Microsoft Academic Search

    T. E. Cawston

    1996-01-01

    The primary agents responsible for cartilage and bone destruction in joint diseases are active proteinases degrading collagen and proteoglycan. All four main classes of proteolytic enzymes are involved in either the normal turnover of connective tissue or its pathological destruction. These proteinases are made by different cells found within the joints. Both extracellular and intracellular pathways exist, and individual enzymes

  20. Connective Tissue Growth Factor: What's in a Name?

    Microsoft Academic Search

    Essam El-Din A. Moussad; David R. Brigstock

    2000-01-01

    Connective tissue growth factor (CTGF) is a member of the recently described CCN gene family which contains CTGF itself, cyr61, nov, elm1, Cop1, and WISP-3. CTGF is transcriptionally activated by several factors although its stimulation by transforming growth factor ? (TGF-?) has attracted considerable attention. CTGF acts to promote fibroblast proliferation, migration, adhesion, and extracellular matrix formation, and its overproduction

  1. Electron Microscopy: Attachment Sites between Connective Tissue Cells

    Microsoft Academic Search

    Russell Ross; Theodore K. Greenlee Jr.

    1966-01-01

    Regions of attachment have been observed between connective tissue cells from four different structures: fibroblasts in embryonic and fetal tendons, fibroblasts in fetal ligamentum nuchae, odontoblasts, and osteoblasts. Morphologically these sites appear to be focal and to consist of an approximation of the plasma membranes of adjacent cells to within approximately 200 angstrom. In the region of approximation both the

  2. Absorption of Hydrocortisone Acetate in Human Connective Tissue Using Phonophoresis

    PubMed Central

    Gurney, A. Burke; Wascher, Daniel; Schenck, Robert; Tennison, Alexandria; Jaramillo, Bettina

    2011-01-01

    Background: Therapeutic ultrasound to drive medication (phonophoresis) has been a mainstay in physical therapy. The most common drug used in phonophoresis is hydrocortisone acetate (HA). A number of studies have been done examining phonophoresis in the delivery of HA through the skin to underlying tissues; however, a study has never been done examining the absorption of HA using phonophoresis on human connective tissue. Hypothesis: Phonophoresis will facilitate the transmission of HA in human connective tissue. Study Design: Randomized controlled study. Methods: Twenty-one patients undergoing anterior cruciate ligament reconstruction surgery were randomly assigned to either a sham or true phonophoresis treatment group. The latter group received 6 minutes of 10% HA ultrasound at a point consistent with the gastrocnemius slip of the semitendinosis tendon (treatment site). The sham group received 6 minutes of 10% HA ultrasound to the same area, but the ultrasound was not turned on. The slip and a sample of the distal attachment of the tendon (control) were removed. Samples were analyzed for HA levels. Results: Although the mean and median levels of HA found at the treatment site were greater than those of the control site (means, 34.1 vs 22.9 parts per billion; medians, 7 vs 0 parts per billion), the levels of HA found at the treatment site were not significantly greater than those at the control site (P = 0.15). There were no statistically significant differences between the true and sham phonophoresis groups in HA levels (P = 0.80) nor in age, sex, or skin thickness. Conclusion: Phonophoresis does not appear to facilitate the absorption of HA in connective tissue when compared with simple absorption (sham). Clinical Relevance: Phonophoresis does not appear to enhance the transmission of HA in human connective tissue; therefore, use of phonophoresis should be reconsidered in inflammatory conditions. PMID:23016027

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

    NASA Technical Reports Server (NTRS)

    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.

  4. Role of Connective Tissue Growth Factor in Cardiac Fibrosis

    Microsoft Academic Search

    Daiji Kawanami; Saptarsi M. Haldar; Mukesh K. Jain

    \\u000a Cardiac fibrosis is an important pathogenic feature of the remodeling process that occurs in heart failure and myocardial\\u000a infarction. This process is triggered by a number of signaling pathways that result in excessive production and deposition\\u000a of extracellular matrix (ECM). Connective Tissue Growth factor (CTGF, CCN2), a member of CCN (Cyr61, Ctgf, Nov) family, is a multifunctional protein that is

  5. Neurologic manifestations of inherited disorders of connective tissue.

    PubMed

    Debette, Stéphanie; Germain, Dominique P

    2014-01-01

    Inherited disorders of connective tissue are single gene disorders affecting structure or function of the connective tissue. Neurological manifestations are classic and potentially severe complications of many such disorders. The most common neurological manifestations are cerebrovascular. Ischemic stroke is a classic complication of vascular Ehlers-Danlos syndrome (type IV), homocystinuria, and arterial tortuosity syndrome, and may occasionally be seen in Marfan syndrome and pseudoxanthoma elasticum with distinct underlying mechanisms for each disease. Vascular Ehlers-Danlos syndrome can also lead to cervical artery dissection (with or without ischemic stroke), carotid-cavernous fistula, intracranial dissections and aneurysms potentially causing subarachnoid or intracerebral hemorrhage, and arterial rupture. Other neurological manifestations include nerve root compression and intracranial hypotension due to dural ectasia in Marfan and Loeys-Dietz syndrome, spinal cord compression in osteogenesis imperfecta, and mucopolysaccharidosis type I and VI, carpal tunnel syndrome in mucopolysaccharidosis type I, II, and VI. Impaired mental development can be observed in homocystinuria, mucopolysaccharidosis type II, and the severe form of mucopolysaccharidosis type I. For the neurologist, being aware of these complications and of the diagnostic criteria for inherited connective tissue disorders is important since neurological complications can be the first manifestation of the disease and because caution may be warranted for the management of these patients. PMID:24365320

  6. Stimulation of Fibroblast Cell Growth, Matrix Production, and Granulation Tissue Formation by Connective Tissue Growth Factor

    Microsoft Academic Search

    Ken Frazier; Shawn Williams; Devashish Kothapalli; Helene Klapper; Gary R. Grotendorst

    1996-01-01

    Connective tissue growth factor (CTGF) is a 36- to 38-kDa peptide that is selectively induced by transforming growth factor-? (TGF-?) in fibroblastic cell types. We compared the biologic activities of CTGF with TGF-? on fibroblasts in culture and in animal models of fibroplasia. CTGF was active as a mitogen in monolayer cultures of normal rat kidney fibroblasts. CTGF did not

  7. Hair follicle nevi and accessory tragi: variable quantity of adipose tissue in connective tissue framework.

    PubMed

    Ban, M; Kamiya, H; Yamada, T; Kitajima, Y

    1997-01-01

    Controversy exists about the histologic differences between hair follicle nevi and accessory tragi. We examined 10 congenital lesions histologically, possible diagnoses of which were hair follicle nevi or accessory tragi. Two specimens out of the 10 had tiny, mature hair follicles surrounded by thick fibrous root sheaths, a few fat cells, and no cartilage. The subcutaneous fat cells of their bases were segmented by a connective tissue framework. They had histologic features of hair follicle nevi. One specimen had cartilage and abundant fat cells with a connective tissue framework in the nodule, as well as a conglomeration of numerous well-differentiated hair follicles. It possessed both elements of a hair follicle nevus and an accessory tragus. Seven specimens had abundant subcutaneous fat and showed a prominent connective tissue framework. These were typical accessory tragi. The present study suggests that the number of fat cells in the nodule or papule differs between these two conditions. All the lesions studied revealed a connective tissue framework in the subcutaneous fat. Histologic features of both hair follicle nevi and accessory tragi can coexist in a single lesion. Hair follicle nevi may represent incomplete accessory tragi with scant fat cells. PMID:9436838

  8. Coverage of gingival recession using tunnel connective tissue graft technique

    PubMed Central

    Khuller, Nitin

    2009-01-01

    The recession of gingiva is increasingly becoming a more prominent condition in the oral health of many patients and should be treated at its earliest detection. The multi-factorial etiology, decision modality, and current trends followed in treatment of gingival recession are discussed in this presentation. The correction of class I and II gingival recessions are presented as a means of minimizing surgical trauma and achieving predictable aesthetic results. In this case report, I present an alternative technique in treating gingival recession- the tunnel connective tissue graft. PMID:20407659

  9. Connective tissue photodamage in the hairless mouse is partially reversible

    SciTech Connect

    Kligman, L.H.

    1987-03-01

    Photodamaged connective tissue in animal and human skin is characterized by excessive accumulations of elastic fibers, loss of mature collagen, concomitant overproduction of new collagen, and greatly increased levels of glycosaminoglycans. Formerly considered irreversible changes, we recently showed in hairless mice, post irradiation, that a band of normal connective tissue was laid down subepidermally. The present studies focused on 2 aspects of this repair: whether repair would occur if animals were protected by sunscreens after dermal damage was induced and irradiation continued; whether retinoic acid could enhance the repair process. To examine the first aspect, albino hairless mice were irradiated with Westinghouse FS 20 sunlamps thrice weekly for 30 weeks. Sunscreens of high sun-protection factors were applied after 10 and 20 weeks. Not only was further damage prevented, but the damage incurred before sunscreen application was repaired. This appeared as subepidermal reconstruction zones containing normal, mature collagen and a network of fine elastic fibers. The second aspect was examined by applying 0.05% retinoic acid, topically, to animals preirradiated for 10 weeks. In contrast to controls treated with vehicle, the reconstruction zone was significantly wider in retinoic acid-treated mice. The enhanced repair was dose-related.

  10. Connective tissue disease-associated pulmonary arterial hypertension

    PubMed Central

    Howard, Luke S.

    2015-01-01

    Although rare in its idiopathic form, pulmonary arterial hypertension (PAH) is not uncommon in association with various associated medical conditions, most notably connective tissue disease (CTD). In particular, it develops in approximately 10% of patients with systemic sclerosis and so these patients are increasingly screened to enable early detection. The response of patients with systemic sclerosis to PAH-specific therapy appears to be worse than in other forms of PAH. Survival in systemic sclerosis-associated PAH is inferior to that observed in idiopathic PAH. Potential reasons for this include differences in age, the nature of the underlying pulmonary vasculopathy and the ability of the right ventricle to cope with increased afterload between patients with systemic sclerosis-associated PAH and idiopathic PAH, while coexisting cardiac and pulmonary disease is common in systemic sclerosis-associated PAH. Other forms of connective tissue-associated PAH have been less well studied, however PAH associated with systemic lupus erythematosus (SLE) has a better prognosis than systemic sclerosis-associated PAH and likely responds to immunosuppression. PMID:25705389

  11. Autoimmune Inner Ear Disease (AIED)

    MedlinePLUS

    ... VEDA” to receive a 15% discount. Autoimmune Inner Ear Disease What is autoimmunity? How is it connected ... reaction. The immune system can attack just the ear, attack the ear and some other body part ...

  12. Immune response against ocular tissues after immunization with optic nerve antigens in a model of autoimmune glaucoma

    PubMed Central

    Reinehr, Sabrina; Kuehn, Sandra; Laspas, Panagiotis; Gramlich, Oliver W.; Kuehn, Mathias; Tischoff, Iris; von Pein, Harald D.; Dick, H. Burkhard; Grus, Franz H.

    2013-01-01

    Purpose In recent years, numerous studies have investigated the involvement of immunological mechanisms in glaucoma. Until now, it has not been determined whether the altered antibody pattern detected in patients is harmful to retinal ganglion cells (RGCs) or triggers disease formation in any way. In a model of experimental autoimmune glaucoma, RGC loss can be induced through immunization with certain ocular antigens. In the current study, the time course of the levels of autoreactivity against ocular tissues after immunization was examined. Methods Intraocular pressure was measured regularly. Ten weeks after immunization with an optic nerve homogenate antigen (ONA), the number of RGCs was determined. Immunoglobulin G levels in aqueous humor were measured via enzyme-linked immunosorbent assay at the same time point. Serum from different time points was used to analyze the possible occurrence of autoreactive antibodies against the retina or optic nerve in this autoimmune glaucoma model. Additionally, optic nerve and brain sections were evaluated for possible pathological findings. Results Intraocular pressure stayed within the normal range throughout this study. A continuous increase of autoreactive antibodies against the optic nerve and retina sections was observed. At 4, 6, and 10 weeks, antibody reactivity was significantly higher in ONA animals (p<0.01). Aqueous humor immunoglobulin G levels were also significantly higher in the ONA group (p=0.006). Ten weeks after immunization, significantly fewer RGCs were noted in the ONA group (p=0.00003). The optic nerves from ONA animals exhibited damaged axons. No pathological findings appeared in any brain sections. Conclusions Our findings suggest that these modified antibodies play a substantial role in mechanisms leading to RGC death. The slow dissolution of RGCs observed in animals with autoimmune glaucoma is comparable to the slow progressive RGC loss in glaucoma patients, thus making this a useful model to develop neuroprotective therapies in the future. PMID:23946635

  13. Erythropoietin-derived nonerythropoietic peptide ameliorates experimental autoimmune neuritis by inflammation suppression and tissue protection.

    PubMed

    Liu, Yuqi; Luo, Bangwei; Han, Fuyu; Li, Xiaoming; Xiong, Jian; Jiang, Man; Yang, Xioafeng; Wu, Yuzhang; Zhang, Zhiren

    2014-01-01

    Experimental autoimmune neuritis (EAN) is an autoantigen-specific T-cell-mediated disease model for human demyelinating inflammatory disease of the peripheral nervous system. Erythropoietin (EPO) has been known to promote EAN recovery but its haematopoiesis stimulating effects may limit its clinic application. Here we investigated the effects and potential mechanisms of an EPO-derived nonerythropoietic peptide, ARA 290, in EAN. Exogenous ARA 290 intervention greatly improved EAN recovery, improved nerve regeneration and remyelination, and suppressed nerve inflammation. Furthermore, haematopoiesis was not induced by ARA 290 during EAN treatment. ARA 290 intervention suppressed lymphocyte proliferation and altered helper T cell differentiation by inducing increase of Foxp3+/CD4+ regulatory T cells and IL-4+/CD4+ Th2 cells and decrease of IFN-?+/CD4+ Th1 cells in EAN. In addition, ARA 290 inhibited inflammatory macrophage activation and promoted its phagocytic activity. In vitro, ARA 290 was shown to promote Schwann cell proliferation and inhibit its inflammatory activation. In summary, our data demonstrated that ARA 290 could effectively suppress EAN by attenuating inflammation and exerting direct cell protection, indicating that ARA 290 could be a potent candidate for treatment of autoimmune neuropathies. PMID:24603865

  14. Lipodermatosclerosis in patients with diffuse connective tissue diseases.

    PubMed

    Dias Gonzalez, Fernanda; Pedreira Magalhăes, Fernanda; Pontes Vilas Boas Freitas, Alice; Castro Lima Filho, Humberto; Santiago, Mittermayer B

    2006-07-01

    Lipodermatosclerosis (LDS) is a clinical condition characterized by the appearance of hardened, painful, and hyperchromic plaques on the legs. We describe three patients with diffuse connective tissue diseases (DCTD) who developed this clinical condition. The first one was a systemic lupus erythematosus patient with secondary antiphospholipid syndrome; the second patient had a superposition of DCTD (rheumatoid arthritis, Sjögren's syndrome, morphea); and the last one had been diagnosed with CREST 10 years earlier but had more recently developed primary biliary cirrhosis. Although its etiopathogenesis is unknown, LDS has been frequently seen in association with venous insufficiency. Its recognition by professionals who deal with DCTD is very relevant since it is characterized by thickening of the skin, similar to scleroderma. Its identification can avoid the inadvertent use of medications such as penicillamine and immunosuppressants, which have potentially serious side effects. PMID:16762781

  15. Meta-analysis reveals an association of PTPN22 C1858T with autoimmune diseases, which depends on the localization of the affected tissue.

    PubMed

    Zheng, J; Ibrahim, S; Petersen, F; Yu, X

    2012-12-01

    Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a strong susceptibility gene shared by many autoimmune diseases. The aim of this study was to explore the mechanisms underlying this relationship. We performed a comprehensive analysis of the association between PTPN22 polymorphism C1858T and autoimmune diseases. The results showed a remarkable pattern; PTPN22 C1858T was strongly associated with type I diabetes, rheumatoid arthritis, immune thrombocytopenia, generalized vitiligo with concomitant autoimmune diseases, idiopathic inflammatory myopathies, Graves' disease, juvenile idiopathic arthritis, myasthenia gravis, systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody-associated vasculitis and Addison's disease. By contrast, PTPN22 C1858T showed a negligible association with systemic sclerosis, celiac disease, multiple sclerosis, psoriasis, ankylosing spondylitis, pemphigus vulgaris, ulcerative colitis, primary sclerosing cholangitis, primary biliary cirrhosis, Crohn's disease and acute anterior uveitis. Further analysis revealed a clear distinction between the two groups of diseases with regard to their targeted tissues: most autoimmune diseases showing an insignificant association with PTPN22 C1858T manifest in skin, the gastrointestinal tract or in immune privileged sites. These results showed that the association of PTPN22 polymorphism with autoimmune diseases depends on the localization of the affected tissue, suggesting a role of targeted organ variation in the disease manifestations. PMID:23076337

  16. Vascularized interpositional periosteal connective tissue flap: A modern approach to augment soft tissue

    PubMed Central

    Agarwal, Chitra; Deora, Savita; Abraham, Dennis; Gaba, Rohini; Kumar, Baron Tarun; Kudva, Praveen

    2015-01-01

    Context: Nowadays esthetics plays an important role in dentistry along with function of the prosthesis. Various soft tissue augmentation procedures are available to correct the ridge defects in the anterior region. The newer technique, vascularized interpositional periosteal connective tissue (VIP-CT) flap has been introduced, which has the potential to augment predictable amount of tissue and has many benefits when compared to other techniques. Aim: The study was designed to determine the efficacy of the VIP-CT flap in augmenting the ridge defect. Materials and Methods: Ten patients with Class III (Seibert's) ridge defects were treated with VIP-CT flap technique before fabricating fixed partial denture. Height and width of the ridge defects were measured before and after the procedure. Subsequent follow-up was done every 3 months for 1-year. Statistical Analysis Used: Paired t-test was performed to detect the significance of the procedure. Results: The surgical site healed uneventfully. The predictable amount of soft tissue augmentation had been achieved with the procedure. The increase in height and width of the ridge was statistically highly significant. Conclusion: The VIP-CT flap technique was effective in augmenting the soft tissue in esthetic area that remained stable over a long period.

  17. A Fluid Mechanics Model of Tissue Fluid Flow in Limb Connective Tissue—A Mechanism of Acupuncture Signal Transmission

    Microsoft Academic Search

    Di ZHANG; Wei YAO; Guang-hong DING; Jing YANG; Wolfgang SCHWARZ; Shanghai FEI Lun; Fang LIU; Xue-yong SHEN; Li-xing LAO

    2009-01-01

    This article explores the mechanisms of acupuncture meridians by determining characteristics of the tissue fluid flow in the connective tissue along meridians. Based on deep dissection of acupoints on the upper and lower limbs of the human body and micro and macro observation and measurement, a mathematical model of the flow of tissue fluid in interosseous membranes is constructed. It

  18. A Novel Esthetic Approach using Connective Tissue Graft for Soft Tissue Defect Following Surgical Excision of Gingival Fibrolipoma.

    PubMed

    Balasundaram, Aruna; Parthasarathy, Harinath; Kumar, Praveenkrishna; Gajendran, Priyalochana; Appukuttan, Devapriya

    2014-11-01

    The aim of the present case report is to evaluate the adjunctive use of a connective tissue graft to overcome soft tissue defects following excision of a gingival fibrolipoma in the aesthetic region. Connective tissue graft has been well documented for treating defects of esthetic concern. However, the literature does not contain many reports on the esthetic clinical outcome following the use of connective tissue graft secondary to excision of soft tissue tumours. A 28-year-old male patient reported with a complaint of a recurrent growth in relation to his lower front tooth region. The lesion which was provisionally diagnosed as fibroma was treated with a complete surgical excision, following which a modified coronally advanced flap and connective tissue graft was adopted to overcome the soft tissue defect. The excised growth was diagnosed histologically as fibrolipoma. One year follow up showed no recurrence of the lesion and good esthetics.The adjunctive use of the connective tissue graft and modified coronally advanced flap predictably yields optimal soft tissue fill and excellent esthetics. Hence, routine use of this procedure may be recommended for surgical excision of soft tissue growths in esthetically sensitive areas. PMID:25584336

  19. A Novel Esthetic Approach using Connective Tissue Graft for Soft Tissue Defect Following Surgical Excision of Gingival Fibrolipoma

    PubMed Central

    Parthasarathy, Harinath; Kumar, Praveenkrishna; Gajendran, Priyalochana; Appukuttan, Devapriya

    2014-01-01

    The aim of the present case report is to evaluate the adjunctive use of a connective tissue graft to overcome soft tissue defects following excision of a gingival fibrolipoma in the aesthetic region. Connective tissue graft has been well documented for treating defects of esthetic concern. However, the literature does not contain many reports on the esthetic clinical outcome following the use of connective tissue graft secondary to excision of soft tissue tumours. A 28-year-old male patient reported with a complaint of a recurrent growth in relation to his lower front tooth region. The lesion which was provisionally diagnosed as fibroma was treated with a complete surgical excision, following which a modified coronally advanced flap and connective tissue graft was adopted to overcome the soft tissue defect. The excised growth was diagnosed histologically as fibrolipoma. One year follow up showed no recurrence of the lesion and good esthetics.The adjunctive use of the connective tissue graft and modified coronally advanced flap predictably yields optimal soft tissue fill and excellent esthetics. Hence, routine use of this procedure may be recommended for surgical excision of soft tissue growths in esthetically sensitive areas. PMID:25584336

  20. Polymer-tethered epidermal growth factor as an inductive biomaterial surface for connective tissue progenitors

    E-print Network

    Fan, Vivian H. (Vivian Hanbing)

    2006-01-01

    Connective tissue progenitors (CTP) can act as a pluripotent source of reparative cells during injury and therefore have great potential in regenerative medicine and tissue engineering. However, the response of CTP to most ...

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

    PubMed

    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. PMID:21207094

  2. Connective tissue growth factor is a substrate of ADAM28

    SciTech Connect

    Mochizuki, Satsuki; Tanaka, Rena; Shimoda, Masayuki; Onuma, Junko [Department of Pathology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-0016 (Japan)] [Department of Pathology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-0016 (Japan); Fujii, Yutaka [Department of Molecular Biology and Chemistry, University of Fukui Faculty of Medical Sciences, 23-3, Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193 (Japan)] [Department of Molecular Biology and Chemistry, University of Fukui Faculty of Medical Sciences, 23-3, Matsuokashimoaizuki, Eiheiji-cho, Yoshida-gun, Fukui 910-1193 (Japan); Jinno, Hiromitsu [Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-0016 (Japan)] [Department of Surgery, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-0016 (Japan); Okada, Yasunori, E-mail: okada@sc.itc.keio.ac.jp [Department of Pathology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-0016 (Japan)] [Department of Pathology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-0016 (Japan)

    2010-11-26

    Research highlights: {yields} The hyper-variable region in the cysteine-rich domain of ADAM28 binds to C-terminal domain of CTGF. {yields} ADAM28 cleaves CTGF alone and CTGF in the CTGF/VEGF{sub 165} complex. {yields} CTGF digestion by ADAM28 releases biologically active VEGF{sub 165} from the complex. {yields} ADAM28, CTGF and VEGF{sub 165} are commonly co-expressed by carcinoma cells in human breast carcinoma tissues. {yields} These suggest that ADAM28 promotes VEGF{sub 165}-induced angiogenesis in the breast carcinomas by selective CTGF digestion in the CTGF/VEGF{sub 165} complex. -- Abstract: ADAM28, a member of the ADAM (a disintegrin and metalloproteinase) gene family, is over-expressed by carcinoma cells and the expression correlates with carcinoma cell proliferation and progression in human lung and breast carcinomas. However, information about substrates of ADAM28 is limited. We screened interacting molecules of ADAM28 in human lung cDNA library by yeast two-hybrid system and identified connective tissue growth factor (CTGF). Binding of CTGF to proADAM28 was demonstrated by yeast two-hybrid assay and protein binding assay. ADAM28 cleaved CTGF in dose- and time-dependent manners at the Ala{sup 181}-Tyr{sup 182} and Asp{sup 191}-Pro{sup 192} bonds in the hinge region of the molecule. ADAM28 selectively digested CTGF in the complex of CTGF and vascular endothelial growth factor{sub 165} (VEGF{sub 165}), releasing biologically active VEGF{sub 165} from the complex. RT-PCR and immunohistochemical analyses demonstrated that ADAM28, CTGF and VEGF are commonly co-expressed in the breast carcinoma tissues. These data provide the first evidence that CTGF is a novel substrate of ADAM28 and suggest that ADAM28 may promote VEGF{sub 165}-induced angiogenesis in the breast carcinomas by the CTGF digestion in the CTGF/VEGF{sub 165} complex.

  3. Inhibition of rheumatoid arthritis by blocking connective tissue growth factor

    PubMed Central

    Nozawa, Kazuhisa; Fujishiro, Maki; Takasaki, Yoshinari; Sekigawa, Iwao

    2014-01-01

    The pathogenesis of rheumatoid arthritis (RA) remains to be completely elucidated so far; however, it is known that proinflammatory cytokines play a pivotal role in the induction of RA. Tumor necrosis factor (TNF-?), in particular, is considered to play a central role in bone destruction by mediating the abnormal activation of osteoclasts or the production of proteolytic enzymes through direct or indirect mechanisms. The use of TNF-? blocking agents has a significant impact on RA therapy. Anti-TNF-? blocking agents such as infliximab are very effective for treatment of RA, especially for the prevention of articular destruction. We have previously shown that several proteins exhibited extensive changes in their expression after amelioration of RA with infliximab treatment. Among the proteins, connective tissue growth factor (CTGF) has a significant role for the development of RA. Herein, we review the function of CTGF in the pathogenesis of RA and discuss the possibility of a novel treatment for RA. We propose that CTGF is a potentially novel effector molecule in the pathogenesis of RA. Blocking the CTGF pathways by biological agents may have great beneficial effect in patients with RA. PMID:25405094

  4. Inhibition of rheumatoid arthritis by blocking connective tissue growth factor.

    PubMed

    Nozawa, Kazuhisa; Fujishiro, Maki; Takasaki, Yoshinari; Sekigawa, Iwao

    2014-11-18

    The pathogenesis of rheumatoid arthritis (RA) remains to be completely elucidated so far; however, it is known that proinflammatory cytokines play a pivotal role in the induction of RA. Tumor necrosis factor (TNF-?), in particular, is considered to play a central role in bone destruction by mediating the abnormal activation of osteoclasts or the production of proteolytic enzymes through direct or indirect mechanisms. The use of TNF-? blocking agents has a significant impact on RA therapy. Anti-TNF-? blocking agents such as infliximab are very effective for treatment of RA, especially for the prevention of articular destruction. We have previously shown that several proteins exhibited extensive changes in their expression after amelioration of RA with infliximab treatment. Among the proteins, connective tissue growth factor (CTGF) has a significant role for the development of RA. Herein, we review the function of CTGF in the pathogenesis of RA and discuss the possibility of a novel treatment for RA. We propose that CTGF is a potentially novel effector molecule in the pathogenesis of RA. Blocking the CTGF pathways by biological agents may have great beneficial effect in patients with RA. PMID:25405094

  5. Aging of connective tissues: experimental facts and theoretical considerations.

    PubMed

    Labat-Robert, J; Robert, L

    2014-01-01

    In this chapter, we describe in detail the age-dependent modifications of connective tissues, separately for their cellular and extracellular compartments. Cell aging was studied by the in vitro method established by Hayflick as well as by ex vivo explant cultures, and results with both methods are discussed. Follows then the description of age changes of macromolecular components of extracellular matrix as well as the decline with age of receptor-mediated cell-matrix interactions. These interactions mediated by several types of receptors, as integrins, the elastin receptor and others, play a crucial role for the definition and regulation of the differentiated cell phenotype. Age-related modifications of both matrix components and receptors are discussed in order to explain the mechanisms of the age-dependent modulations of cell-matrix interactions. Finally, we discuss the relations between age changes of matrix components and the onset of age-related diseases, especially cardiovascular pathologies mostly involved in age-dependence of functions and limitation of longevity. PMID:24862017

  6. Connective tissue growth factor induces cardiac hypertrophy through Akt signaling

    SciTech Connect

    Hayata, Nozomi; Fujio, Yasushi; Yamamoto, Yasuhiro; Iwakura, Tomohiko; Obana, Masanori; Takai, Mika; Mohri, Tomomi; Nonen, Shinpei; Maeda, Makiko [Department of Clinical Pharmacology and Pharmacogenomics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan); Azuma, Junichi [Department of Clinical Pharmacology and Pharmacogenomics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871 (Japan)], E-mail: azuma@phs.osaka-u.ac.jp

    2008-05-30

    In the process of cardiac remodeling, connective tissue growth factor (CTGF/CCN2) is secreted from cardiac myocytes. Though CTGF is well known to promote fibroblast proliferation, its pathophysiological effects in cardiac myocytes remain to be elucidated. In this study, we examined the biological effects of CTGF in rat neonatal cardiomyocytes. Cardiac myocytes stimulated with full length CTGF and its C-terminal region peptide showed the increase in cell surface area. Similar to hypertrophic ligands for G-protein coupled receptors, such as endothelin-1, CTGF activated amino acid uptake; however, CTGF-induced hypertrophy is not associated with the increased expression of skeletal actin or BNP, analyzed by Northern-blotting. CTGF treatment activated ERK1/2, p38 MAPK, JNK and Akt. The inhibition of Akt by transducing dominant-negative Akt abrogated CTGF-mediated increase in cell size, while the inhibition of MAP kinases did not affect the cardiac hypertrophy. These findings indicate that CTGF is a novel hypertrophic factor in cardiac myocytes.

  7. Congenital complete heart block and maternal connective tissue disease.

    PubMed

    Jayaprasad, N; Johnson, Francis; Venugopal, K

    2006-09-20

    Congenital complete heart block can be isolated or can occur in association with other structural heart diseases. Isolated congenital complete heart block (CCHB) is due to transplacental transfer of autoantibodies from mothers with connective tissue disease. Congenital heart block is usually complete, but incomplete blocks, sinus bradycardia and QTc prolongation are also reported. Anti SS A and Anti SS B antibodies transferred from mothers have inflammatory and arrhythmogenic effects in the fetal conduction system. Cardiac manifestations reported include dilated cardiomyopathy, endocardial fibroelastosis and mitral insufficiency. Low ventricular rate, QT prolongation and arrhythmias on monitoring are high risk features. CCHB has a mortality of 30%, and 60% of infants require pacemaker therapy. Fetal echocardiography is useful in early diagnosis. Prophylactic steroid therapy is controversial. Beta adrenergic agonists were tried in mothers with fetuses having congenital heart block to increase fetal heart rate. Early pacemaker therapy is indicated in patients with symptomatic bradycardia and ventricular dysfunction. The indications for pacing in congenital heart block continue to evolve with advances in techniques and most of these children will ultimately require permanent pacemakers by adulthood. PMID:16815568

  8. Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells

    PubMed Central

    2011-01-01

    Prolonged life expectancy, life style and environmental changes have caused a changing disease pattern in developed countries towards an increase of degenerative and autoimmune diseases. Stem cells have become a promising tool for their treatment by promoting tissue repair and protection from immune-attack associated damage. Patient-derived autologous stem cells present a safe option for this treatment since these will not induce immune rejection and thus multiple treatments are possible without any risk for allogenic sensitization, which may arise from allogenic stem cell transplantations. Here we report the outcome of treatments with culture expanded human adipose-derived mesenchymal stem cells (hAdMSCs) of 10 patients with autoimmune associated tissue damage and exhausted therapeutic options, including autoimmune hearing loss, multiple sclerosis, polymyotitis, atopic dermatitis and rheumatoid arthritis. For treatment, we developed a standardized culture-expansion protocol for hAdMSCs from minimal amounts of fat tissue, providing sufficient number of cells for repetitive injections. High expansion efficiencies were routinely achieved from autoimmune patients and from elderly donors without measurable loss in safety profile, genetic stability, vitality and differentiation potency, migration and homing characteristics. Although the conclusions that can be drawn from the compassionate use treatments in terms of therapeutic efficacy are only preliminary, the data provide convincing evidence for safety and therapeutic properties of systemically administered AdMSC in human patients with no other treatment options. The authors believe that ex-vivo-expanded autologous AdMSCs provide a promising alternative for treating autoimmune diseases. Further clinical studies are needed that take into account the results obtained from case studies as those presented here. PMID:22017805

  9. Autoimmune Polyglandular Syndrome Type 1

    Microsoft Academic Search

    Pärt Peterson

    Autoimmune polyglandular syndrome type 1 (APS1) is a monogenic autoimmune disease with organ-specific autoimmune destruction\\u000a of several endocrine tissues. Most common disorders of the syndrome are chronic mucocutaneous candidiasis, hypoparathyoidism\\u000a and Addison’s disease but the clinical spectrum may vary. The disease is caused by the mutations in autoimmune regulator (AIRE)\\u000a gene. More than 50 mutations have been described, which are

  10. Understanding Autoimmune Diseases

    MedlinePLUS

    ... Autoimmune Diseases Progress and Promise Key Words The Immune System Your immune system is the network of cells and tissues throughout ... having two parts: the acquired and the innate immune systems. The acquired (or adaptive) immune system develops as ...

  11. Connective Tissue Growth Factor as a Mediator of Intraocular Fibrosis

    PubMed Central

    He, Shikun; Chen, Youxin; Khankan, Rima; Barron, Ernesto; Burton, Richard; Zhu, DanHong; Ryan, Stephen J.; Oliver, Noelynn; Hinton, David R

    2008-01-01

    Purpose To investigate the role of connective tissue growth factor (CTGF) in the pathogenesis of proliferative vitreoretinopathy (PVR). Methods Expression of CTGF was evaluated immunohistochemically in human PVR membranes, while the accumulation of CTGF in the vitreous was evaluated by ELISA. The effects of CTGF on type I collagen mRNA and protein expression in RPE were assayed by real time PCR and ELISA, while migration was assayed with a Boyden chamber assay. Experimental PVR was induced in rabbits using vitreous injection of RPE cells plus rhCTGF; injection of RPE cells plus platelet derived growth factor with or without rhCTGF; or by injection of RPE cells infected with an adenoviral vector expressing CTGF. Results CTGF was highly expressed in human PVR membranes and partially co-localized with cytokeratin-positive RPE cells. Treatment of RPE with rhCTGF stimulated migration with a peak response at 50ng/ml (P<0.05), and increased expression of type I collagen (P<0.05). There was a prominent accumulation of N-terminal half of CTGF in the vitreous of patients with PVR. Intravitreal injection of rhCTGF alone did not produce PVR, while such injections into rabbits with mild, nonfibrotic PVR promoted the development of dense, fibrotic epiretinal membranes. Similarly, intravitreal injection of RPE cells infected with adenoviral vectors overexpressing CTGF induced fibrotic PVR. Experimental PVR was associated with increased CTGF mRNA in PVR membranes and accumulation of CTGF half fragments in vitreous. Conclusion Our results identify CTGF as a major mediator of retinal fibrosis and potentially an effective therapeutic target for PVR. PMID:18450591

  12. An excess of dietary iodine accelerates the development of a thyroid-associated lymphoid tissue in autoimmune prone BB rats.

    PubMed

    Mooij, P; de Wit, H J; Drexhage, H A

    1993-11-01

    Previous studies have shown that dietary iodine enhances the severity and incidence of focal thyroiditis in autoimmune BB rats and OS chickens. However, which lymphoid cells are involved in the development of the iodine-induced focal thyroiditis and what the consequences are for the anticolloid antibody production have not been studied in detail. We therefore performed a study in which 3-week-old female BB rats were kept on either an enriched iodine diet (EID; iodine intake, 100 micrograms iodine/day) or a normal iodine diet (NID; iodine intake, 7 micrograms iodine/day) for a period of 18 weeks. The development of the focal thyroiditis was immunohistologically studied. Immunohistological data were compared to the thyroid hormone status and anti-colloid antibody production. Our data confirm that a high dietary iodine intake results in an accelerated development of the focal lymphoid cell infiltrates in the thyroid of the BB rat. After 12-18 weeks of an EID 50% of the BB rats developed these infiltrates. Our data additionally show that: (a) the process starts with increases in the number of infiltrating MHC class II-positive dendritic cells and a clustering of these cells with T cells, B cells, and some macrophages and (b) the focal infiltrates are highly organized and consist of central B cell follicle-like structures surrounded by rims and areas of T cells. The architecture of the focal thyroiditis is hence very similar to mucosa-associated lymphoid tissue and secondary lymphoid organs (spleen and lymph node). Only minor signs of thyrocyte destruction were observed. We therefore consider the term "thyroiditis" as inappropriate and prefer the term "thyroid-associated lymphoid tissue." Since the thyroiditis component was small, it is also not surprising that the BB rats on the EID remained euthyroid. The presence of the thyroid-associated lymphoid tissue in the BB rats was positively correlated to the presence of anti-colloid antibody in the serum of the BB rats. We speculate that the dietary iodine might have direct effects on cells of the immune system or on cells forming the microenvironment of lymphoid tissue (reticulum cells). A role for highly iodinated thyroglobulin in the accelerated development of thyroid-associated lymphoid tissue is also possible. PMID:8403556

  13. Stretching of the Back Improves Gait, Mechanical Sensitivity and Connective Tissue Inflammation in a Rodent Model

    Microsoft Academic Search

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

    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

  14. The Arrangement and Function of Octopus Arm Musculature and Connective Tissue

    E-print Network

    Kier, William M.

    The Arrangement and Function of Octopus Arm Musculature and Connective Tissue William M. Kier-3280 ABSTRACT The morphology of the musculature and connective tissues of the arms of Octopus bimaculoides-hydrostat; muscle; octopus; skeletal support The eight arms of octopuses are capable of a re- markable diversity

  15. Expression of Connective Tissue Growth Factor in Intra-Abdominal Adhesions

    Microsoft Academic Search

    Klaus Thaler; Judith A. Mack; Rong Hua Zhao; Mariana Berho; Gary R. Grotendorst; Matthew R. Duncan; Shawn Williams; Julianne R. Miranda; Steven D. Wexner; Susan R. Abramson

    2002-01-01

    PURPOSE: Connective tissue growth factor stimulates fibroblast proliferation and extracellular matrix deposition in many fibrotic disorders. The aim of our study was to determine the expression pattern of connective tissue growth factor in postoperative intra-abdominal adhesions. METHODS: Adhesions were created in 46 Sprague-Dawley rats by complete dissection and resuturing of a peritoneal patch 2 cm in diameter, lateral from the

  16. Carpal tunnel syndrome as a herald of autoimmune rheumatic disorders.

    PubMed Central

    Pal, B

    1997-01-01

    In six patients aged 59-71 years carpal tunnel syndrome, seemingly idiopathic, was followed by connective tissue disorders, in most cases autoimmune in nature. Patients with idiopathic carpal tunnel syndrome may therefore require long-term follow-up, if inflammatory rheumatic conditions are not to be missed. PMID:9155757

  17. Connective Tissue Growth Factor Gene Expression in Tissue Sections From Localized Scleroderma, Keloid, and Other Fibrotic Skin Disorders

    Microsoft Academic Search

    Atsuyuki Igarashi; Kiyoko Nashiro; Kanako Kikuchi; Shinichi Sato; Hironobu Ihn; Manabu Fujimoto; Gary R. Grotendorst; Kazuhiko Takehara

    1996-01-01

    Connective tissue growth factor (CTGF) is a novel peptide that exhibits platelet-derived growth factor- like activities and is produced by skin fibroblasts after activation with transforming growth factor-?. Coordinate expression of transforming growth factor-? followed by CTGF during wound repair suggests a cascade process for control of tissue regeneration. We recently reported a significant correlation between CTGF mRNA expression and

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

    NASA Technical Reports Server (NTRS)

    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.

  19. Biochemical Composition of the Connective Tissue in Keloids and Analysis of Collagen Metabolism in Keloid Fibroblast Cultures

    Microsoft Academic Search

    R. Patrick Abergel; Damon Pizzurro; Cheryl A. Meeker; Gary Lask; Louis Y. Matsuoka; Ronald R. Minor; Mon-Li Chu; Jouni Uitto

    1985-01-01

    Keloids are histologically characterized by an abundance of the extracellular matrix of connective tissue. In the present study, we examined the connective tissue composition of keloids, and analyzed the details of collagen metabolism utilizing fibroblast cultures established from keloid tissue. Quantitative connective tissue analyses indicated that collagen was the predominant extracellular matrix component in keloids. The ratio of genetically distinct

  20. Pregnancy, postpartum autoimmune thyroiditis, and autoimmune hypophysitis: intimate relationships

    PubMed Central

    Landek-Salgado, Melissa A.; Gutenberg, Angelika; Lupi, Isabella; Kimura, Hiroaki; Mariotti, Stefano; Rose, Noel R.; Caturegli, Patrizio

    2009-01-01

    Autoimmune diseases comprise a group of about 85 heterogeneous conditions that can affect virtually any organ and tissue in the body. Many autoimmune diseases change significantly during pregnancy: some ameliorate, some worsen, and others are unaffected. Two autoimmune diseases present prominently in relation to pregnancy: postpartum autoimmune thyroiditis and autoimmune hypophysitis. This article will review the current state of knowledge of the immunological changes that occur during normal pregnancy, and will explore the striking temporal association with pregnancy observed in thyroiditis and hypophysitis. PMID:19539059

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

    PubMed

    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. PMID:22238664

  2. Metals and kidney autoimmunity.

    PubMed Central

    Bigazzi, P E

    1999-01-01

    The causes of autoimmune responses leading to human kidney pathology remain unknown. However, environmental agents such as microorganisms and/or xenobiotics are good candidates for that role. Metals, either present in the environment or administered for therapeutic reasons, are prototypical xenobiotics that cause decreases or enhancements of immune responses. In particular, exposure to gold and mercury may result in autoimmune responses to various self-antigens as well as autoimmune disease of the kidney and other tissues. Gold compounds, currently used in the treatment of patients with progressive polyarticular rheumatoid arthritis, can cause a nephrotic syndrome. Similarly, an immune-mediated membranous nephropathy frequently occurred when drugs containing mercury were commonly used. Recent epidemiologic studies have shown that occupational exposure to mercury does not usually result in autoimmunity. However, mercury induces antinuclear antibodies, sclerodermalike disease, lichen planus, or membranous nephropathy in some individuals. Laboratory investigations have confirmed that the administration of gold or mercury to experimental animals leads to autoimmune disease quite similar to that observed in human subjects exposed to these metals. In addition, studies of inbred mice and rats have revealed that a few strains are susceptible to the autoimmune effects of gold and mercury, whereas the majority of inbred strains are resistant. These findings have emphasized the importance of genetic (immunogenetic and pharmacogenetic) factors in the induction of metal-associated autoimmunity. (italic)In vitro(/italic) and (italic)in vivo(/italic) research of autoimmune disease caused by mercury and gold has already yielded valuable information and answered a number of important questions. At the same time it has raised new issues about possible immunostimulatory or immunosuppressive mechanisms of xenobiotic activity. Thus it is evident that investigations of metal-induced renal autoimmunity have the potential to produce new knowledge with relevance to autoimmune disease caused by xenobiotics in general as well as to idiopathic autoimmunity. PMID:10502542

  3. [Development of retroperitoneal connective tissue and its neural apparatus in the prenatal period of human ontogenesis].

    PubMed

    Ma?boroda, Iu N; Mokin, Iu N; Monastyrski?, Ia G; Pervushin, V Iu

    1982-02-01

    Dynamic parallelism of development in neural and fat tissue-fascial formations of the kidneys and pancreas have been studied in the human prenatal ontogenesis. At various stages of embryogenesis, there are certain correlative connections between formation and differentiation of the renal connective tissue structures, that of the pancreas and the development of their intramural apparatus. The greatest concentration of the neural elements is noted in fat tissue at the level of the posterior surface of the pancreatic head, as well as in the facial-fat tissue formations of the inferior pole and the hilus renalis. PMID:7082183

  4. Connective tissue disorders and cardiovascular complications: the indomitable role of transforming growth factor-beta signaling.

    PubMed

    Wheeler, Jason B; Ikonomidis, John S; Jones, Jeffrey A

    2014-01-01

    Marfan Syndrome (MFS) and Loeys-Dietz Syndrome (LDS) represent heritable connective tissue disorders that cosegregate with a similar pattern of cardiovascular defects (thoracic aortic aneurysm, mitral valve prolapse/regurgitation, and aortic root dilatation with regurgitation). This pattern of cardiovascular defects appears to be expressed along a spectrum of severity in many heritable connective tissue disorders and raises suspicion of a relationship between the normal development of connective tissues and the cardiovascular system. Given the evidence of increased transforming growth factor-beta (TGF-?) signaling in MFS and LDS, this signaling pathway may represent the common link in this relationship. To further explore this hypothetical link, this chapter will review the TGF-? signaling pathway, heritable connective tissue syndromes related to TGF-? receptor (TGFBR) mutations, and discuss the pathogenic contribution of TGF-? to these syndromes with a primary focus on the cardiovascular system. PMID:24443024

  5. Fas and Fas ligand expressed on cells of the immune system, not on the target tissue, control induction of experimental autoimmune uveitis.

    PubMed

    Wahlsten, J L; Gitchell, H L; Chan, C C; Wiggert, B; Caspi, R R

    2000-11-15

    The Fas-Fas ligand (FasL) interaction is important for maintaining lymphocyte homeostasis by signaling for activation-induced cell death. Mice homozygous for the lpr or gld mutations do not express functional Fas or FasL, respectively, and spontaneously develop progressive autoimmune symptoms. Recent studies implicated expression of FasL on immunologically privileged tissues in protection from immune-mediated damage. Conversely, tissue expression of Fas may facilitate damage. We evaluated the susceptibility of lpr and gld mice to induction of experimental autoimmune uveitis (EAU), a T cell-mediated autoimmune disease induced with retinal Ags, which targets the neural retina. gld as well as lpr mice immunized with a retinal Ag developed disease of lower incidence and severity than wild-type controls. Delayed hypersensitivity responses were not significantly different among immunized gld, lpr, or wild-type mice, although in vitro Ag-specific lymphocyte responses of the mutant mice were lower. To evaluate whether the diminished ability of gld and lpr mice to develop EAU was due to a defect at the level of the tissue or the immune system, radiation bone marrow chimeras constructed between wild-type and mutant mice were immunized to induce EAU. Mutant recipients of wild-type bone marrow, but not wild-type recipients of mutant bone marrow, developed normal disease scores. These results indicate that normal expression of Fas and of FasL on cells of the immune system is important for EAU expression. Unexpectedly, neither lack of Fas nor lack of FasL on the ocular tissues affected expression of EAU. PMID:11067900

  6. Stimulation of connective tissue cell growth by substance P and substance K

    Microsoft Academic Search

    Jan Nilsson; Anne M. von Euler; Carl-Johan Dalsgaard

    1985-01-01

    Connective tissue cells proliferate actively when cultured in the presence of serum. Platelet-derived growth factor (PDGF), a basic protein of relative molecular mass ~30,000, has been identified as the major serum mitogen for these cells1; its main physiological\\/pathophysiological role may be to initiate wound healing in connection with tissue injury. However, growth of cultured cells is also influenced by several

  7. Isolated trigeminal sensory neuropathy: early manifestation of mixed connective tissue disease.

    PubMed

    Searles, R P; Mladinich, E K; Messner, R P

    1978-12-01

    A young woman with mixed connective tissue disease (MCTD) had an isolated trigeminal sensory neuropathy as an early manifestation of the disease. Raynaud phenomenon occurred almost synchronously with the onset of trigeminal neuropathy and was followed by myositis, diffuse hand swelling, synovitis, and increased ribonucleoprotein antibody. Mixed connective tissue disease has overlapping features of systemic lupus erythematosus, scleroderma, and polymyositis, and is differentiated from them by high-titer antibody to ribonucleoprotein. PMID:215941

  8. Interstitial lung disease in connective tissue diseases: evolving concepts of pathogenesis and management

    Microsoft Academic Search

    Flavia V Castelino; John Varga

    2010-01-01

    Interstitial lung disease (ILD) is a challenging clinical entity associated with multiple connective tissue diseases, and is a significant cause of morbidity and mortality. Effective therapies for connective tissue disease-associated interstitial lung disease (CTD-ILD) are still lacking. Multidisciplinary clinics dedicated to the early diagnosis and improved management of patients with CTD-ILD are now being established. There is rapid progress in

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

    NASA Technical Reports Server (NTRS)

    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.

  10. NEWS AND COMMENTARY Autoimmunity

    E-print Network

    Cai, Long

    susceptibility to autoimmunity include increased immune priming or reduced resistance to inflamma- tion. Enhanced levels of immune priming could occur through altered barrier perme- ability allowing increased leukocyte traffic through the tissue, or by increased sponta- neous apoptosis in the tissue seeding the draining

  11. Midterm results of the modified Senning operation for cavopulmonary connection with autologous tissue

    Microsoft Academic Search

    A. Benatar; R. Tanke; M. Roef; E. J. Meyboom; H. J. C. M. Van de Wal

    1995-01-01

    The aim of this study was to determine the results and mid-term outcome of a modified Senning technique using autologous tissue for total cavopulmonary connection. The study involved 31 children, 8 with tricuspid atresia and 23 with complex congenital heart disease. In this operation, a flap of autologous atrial free wall tissue was used to tunnel inferior vena caval blood

  12. Significant Correlation Between Connective Tissue Growth Factor Gene Expression and Skin Sclerosis in Tissue Sections from Patients with Systemic Sclerosis

    Microsoft Academic Search

    Atsuyuki Igarashi; Kiyoko Nashiro; Kanako Kikuchi; Shinichi Sato; Hironobu Ihn; Gary R. Grotendorst; Kazuhiko Takehara

    1995-01-01

    The role of some growth factors and cytokines in the pathogenesis of systemic sclerosis (SSc) has been suggested. In particular, the contribution of transforming growth factor ? in the progression of skin sclerosis is suspected. Connective tissue growth factor (CTGF) was originally identified in human umbilical vein endothelial cells, and a recent study has revealed that human skin fibroblasts produce

  13. Connective tissue growth factor: A new and important player in the pathogenesis of fibrosis

    Microsoft Academic Search

    Andrew Leask; Alan Holmes; David J. Abraham

    2002-01-01

    Connective tissue fibrosis is the final common pathogenic process for almost all forms of chronic tissue injury. Whether caused\\u000a by vascular dysfunction, inflammation, metabolic injury, trauma, or environmental agents, once initiated the fibrogenic process\\u000a results in the progressive replacement of the normal tissue architecture with fibrotic lesions that eventually lead to organ\\u000a compromise and failure. Fibrosis can be considered as

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

    PubMed Central

    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 (?=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 (P<0.0001); 2.5±1.0 mm (P<0.0001), CAL gain: 2.3±0.9 (P<0.0001); 2.2±1.0 mm (P<0.0001), bone fill: 2.2±0.7 mm (P<0.0001); 2.2±0.7 mm (P<0.0001), respectively. No significant differences in the position of free gingival margin were observed during 6 months compared to baseline in both groups. Conclusion. Combinations of periosteal connective tissue graft + ABBM and non-periosteal connective tissue graft + ABBM were similarly effective in treating intrabony defects without any favor for any group. Connective tissue and perio-steum can be equally effective in regeneration of intrabony defects. PMID:25587379

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

    PubMed

    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 (?=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 (P<0.0001); 2.5±1.0 mm (P<0.0001), CAL gain: 2.3±0.9 (P<0.0001); 2.2±1.0 mm (P<0.0001), bone fill: 2.2±0.7 mm (P<0.0001); 2.2±0.7 mm (P<0.0001), respectively. No significant differences in the position of free gingival margin were observed during 6 months compared to baseline in both groups. Conclusion. Combinations of periosteal connective tissue graft + ABBM and non-periosteal connective tissue graft + ABBM were similarly effective in treating intrabony defects without any favor for any group. Connective tissue and perio-steum can be equally effective in regeneration of intrabony defects. PMID:25587379

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

    NASA Astrophysics Data System (ADS)

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

    2002-01-01

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

  17. Phototherapy, Photodynamic therapy and Photophoresis in the Treatment of Connective-Tissue Diseases: A Review.

    PubMed

    Gordon Spratt, E A; Gorcey, L V; Soter, N A; Brauer, J A

    2014-11-15

    Connective-tissue disorders, which include lupus erythematosus, morphea/scleroderma, and dermatomyositis, are characterized by cutaneous manifestations that are sometimes resistant to conventional therapy. Light treatments, which include phototherapy, photodynamic therapy, and photopheresis, are routinely utilized in the treatment of dermatologic conditions and may provide unique mechanisms of action in the treatment of these connective-tissue disorders. The objective of this study is to conduct a review of the literature that describes the use of phototherapy, photodynamic therapy and photopheresis in the treatment of lupus erythematosus, morphea/scleroderma, and dermatomyositis. A MEDLINE search was conducted to find articles that discussed treatment of connective-tissue diseases with light therapies and greater than 30 publications that discussed light therapy for these diseases were identified. These ranged in design from case reports to randomized, prospective trials. Study outcomes and details were summarized and presented within each connective-tissue disease by light therapy modality, which include phototherapy, photodynamic therapy and photopheresis. Although there is a known association between photosensitivity and connective-tissue diseases, light therapies, when used appropriately, may be legitimate therapeutic options for recalcitrant cutaneous manifestations in lupus erythematosus, morphea/scleroderma, and dermatomyositis. This article is protected by copyright. All rights reserved. PMID:25400115

  18. The calcium-phosphate balance, modulation of thyroid autoimmune processes and other adverse effects connected with thyroid arterial embolization.

    PubMed

    Kaminski, Grzegorz; Jaroszuk, Andrzej; Zybek, Ariadna; Brzozowski, Krzysztof; Piasecki, Piotr; Ziecina, Piotr; Ruchala, Marek

    2014-06-01

    In search of new treatment options for thyroid diseases, when conventional procedures are ineffective, contraindicated or associated with serious side effects, safety of thyroid arteries embolization in the treatment of particular thyroid diseases was evaluated. The study included eight subjects with retrosternal toxic goiter, six patients affected by Graves' disease, five cases of retrosternal non-toxic goiter, two subjects with post-amiodarone hyperthyroidism, and one patient with severe thyroid-related orbitopathy, who underwent selective embolization of thyroid arteries. The study assessed and compared calcium-phosphate balance, modulation of thyroid autoimmunity and the presence of different side effects in patients who underwent the procedure. In addition, the serum concentrations of thyroid hormones, anti-thyroid autoantibodies and thyroid volume have been measured. Five of all enrolled subjects (22.7 %) experienced transient, not clinically relevant hypocalcaemia with no need for calcium supplementation. There were no significant changes in serum calcium levels in patients after embolization of both inferior thyroid arteries. The transient side effects associated with the treatment were neck pain and a slight increase in body temperature. Noted high concentration of free thyroid hormones immediately after the procedure was not accompanied by worsening of symptoms or signs of thyrotoxicosis. In patients with Graves' disease, a significant decrease in thyrotropin receptor antibodies level was observed. Thyroid arterial embolization does not disturb permanently calcium-phosphate balance, modulates positively thyroid autoimmune processes and is associated with no serious post-procedure side effects. Hence, it may be considered as a safe and effective treatment modality for selected thyroid disorders. PMID:24146411

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

    PubMed

    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 response to applied loading. Together, these data suggest that a program of incremental stretch constitutes an appealing way to replicate tissue growth in cell culture, by harnessing the constituent cells' innate mechanical responsiveness. In addition to offering a platform to study the growth and structural adaptation of connective tissues, tension-driven growth presents a novel approach to in vitro tissue engineering. Because the supporting structure is secreted and organised by the cells themselves, growth is not restricted by a "scaffold" of fixed size. This also minimises potential adverse reactions to exogenous materials upon implantation. Most importantly, we posit that the growth induced by progressive stretch will allow substantial volumes of connective tissue to be produced from relatively small initial cell numbers. PMID:24755458

  20. Epithelial and Connective Tissue Cell CTGF/CCN2 expression in Gingival Fibrosis

    PubMed Central

    Kantarci, Alpdogan; Black, Samuel A.; Xydas, Cristina E.; Murawel, Peggy; Uchida, Yuushi; Yucekal-Tuncer, Berrak; Atilla, Gul; Emingil, Gulnur; Uzel, Mehmet Ilhan; Lee, Alan; Firatli, Erhan; Sheff, Michael; Hasturk, Hatice; Van Dyke, Thomas E.; Trackman, Philip C.

    2006-01-01

    Gingival overgrowth and fibrosis is a side effect of certain medications and occurs in non-drug induced forms either as inherited (human gingival fibromatosis) or idiopathic gingival overgrowth. The most fibrotic drug-induced lesions develop in response to therapy with phenytoin, the least fibrotic lesions are caused by cyclosporin A, and intermediate fibrosis occurs in nifedipine-induced gingival overgrowth. Connective tissue growth factor (CTGF/CCN2) expression is positively related to the degree of fibrosis in these tissues. In the present study, the hypothesis was investigated that CTGF/CCN2 is expressed in human gingival fibromatosis tissues and contributes to this form of non-drug-induced gingival overgrowth. Histopathology/immunohistochemistry studies show that human gingival fibromatosis lesions are highly fibrotic, similar to phenytoin-induced lesions. Connective tissue CTGF/CCN2 levels were equivalent to the expression in phenytoin-induced gingival overgrowth. The additional novel observation was made that CTGF/CCN2 is highly expressed in the epithelium of fibrotic gingival tissues. This finding was confirmed by in situ hybridization. Real time PCR analyses of RNA extracted from control and drug-induced gingival overgrowth tissues for CTGF/CCN2 were fully consistent with these findings. Finally, normal primary gingival epithelial cell cultures were analyzed for the basal and TGF-?1 or lysophosphatidic acid stimulated CTGF/CCN2 expression at the protein and RNA levels. Data indicate that fibrotic human gingival tissues express CTGF/CCN2 in both the epithelium and connective tissues and cultured gingival epithelial cells express CTGF/CCN2, and lysophosphatidic acid further stimulates CTGF/CCN2 expression. These findings suggest that interactions between epithelial and connective tissues could contribute to gingival fibrosis. PMID:16841303

  1. Resistance of the target islet tissue to autoimmune destruction contributes to genetic susceptibility in Type 1 diabetes

    PubMed Central

    Hill, Natasha J; Stotland, Aleksandr; Solomon, Michelle; Secrest, Patrick; Getzoff, Elizabeth; Sarvetnick, Nora

    2007-01-01

    Type 1 diabetes occurs when self-reactive T lymphocytes destroy the insulin-producing islet ? cells of the pancreas. The defects causing this disease have often been assumed to occur exclusively in the immune system. We present evidence that genetic variation at the Idd9 diabetes susceptibility locus determines the resilience of the targets of autoimmunity, the islets, to destruction. Susceptible islets exhibit hyper-responsiveness to inflammatory cytokines resulting in enhanced cell death and increased expression of the death receptor Fas. Fas upregulation in ? cells is mediated by TNFR2, and colocalization of TNFR2 with the adaptor TRAF2 in NOD ? cells is altered. TNFR2 lies within the candidate Idd9 interval and the diabetes-associated variant contains a mutation adjacent to the TRAF2 binding site. A component of diabetes susceptibility may therefore be determined by the target of the autoimmune response, and protective TNFR2 signaling in islets inhibit early cytokine-induced damage required for the development of destructive autoimmunity. This article was reviewed by Matthiasvon Herrath, HaraldVon Boehmer, and Ciriaco Piccirillo (nominated by Ethan Shevach). PMID:17254331

  2. Cell density signal protein suitable for treatment of connective tissue injuries and defects

    DOEpatents

    Schwarz, Richard I. (Oakland, CA)

    2002-08-13

    Identification, isolation and partial sequencing of a cell density protein produced by fibroblastic cells. The cell density signal protein comprising a 14 amino acid peptide or a fragment, variant, mutant or analog thereof, the deduced cDNA sequence from the 14 amino acid peptide, a recombinant protein, protein and peptide-specific antibodies, and the use of the peptide and peptide-specific antibodies as therapeutic agents for regulation of cell differentiation and proliferation. A method for treatment and repair of connective tissue and tendon injuries, collagen deficiency, and connective tissue defects.

  3. Hereditary Connective Tissue Diseases in Young Adult Stroke: A Comprehensive Synthesis

    PubMed Central

    Vanakker, Olivier M.; Hemelsoet, Dimitri; De Paepe, Anne

    2011-01-01

    Though the genetic background of ischaemic and haemorrhagic stroke is often polygenetic or multifactorial, it can in some cases result from a monogenic disease, particularly in young adults. Besides arteriopathies and metabolic disorders, several connective tissue diseases can present with stroke. While some of these diseases have been recognized for decades as causes of stroke, such as the vascular Ehlers-Danlos syndrome, others only recently came to attention as being involved in stroke pathogenesis, such as those related to Type IV collagen. This paper discusses each of these connective tissue disorders and their relation with stroke briefly, emphasizing the main clinical features which can lead to their diagnosis. PMID:21331163

  4. Tetramers reveal IL-17-secreting CD4+ T cells that are specific for U1-70 in lupus and mixed connective tissue disease.

    PubMed

    Kattah, Nicole H; Newell, Evan W; Jarrell, Justin Ansel; Chu, Alvina D; Xie, Jianming; Kattah, Michael G; Goldberger, Ofir; Ye, Jessica; Chakravarty, Eliza F; Davis, Mark M; Utz, Paul J

    2015-03-10

    Antigen-specific CD4(+) T cells are implicated in the autoimmune disease systemic lupus erythematosus (SLE), but little is known about the peptide antigens that they recognize and their precise function in disease. We generated a series of MHC class II tetramers of I-E(k)-containing peptides from the spliceosomal protein U1-70 that specifically stain distinct CD4(+) T-cell populations in MRL/lpr mice. The T-cell populations recognize an epitope differing only by the presence or absence of a single phosphate residue at position serine(140). The frequency of CD4(+) T cells specific for U1-70(131-150):I-E(k) (without phosphorylation) correlates with disease severity and anti-U1-70 autoantibody production. These T cells also express ROR?t and produce IL-17A. Furthermore, the U1-70-specific CD4(+) T cells that produce IL-17A are detected in a subset of patients with SLE and are significantly increased in patients with mixed connective tissue disease. These studies provide tools for studying antigen-specific CD4(+) T cells in lupus, and demonstrate an antigen-specific source of IL-17A in autoimmune disease. PMID:25713364

  5. The application of quantitative cytochemistry to the study of diseases of the connective tissues.

    PubMed

    Henderson, B

    1983-01-01

    The connective tissues are a complex organisation of tissues, cells and intercellular materials spread throughout the body and are subject to a large number of diseases. Such complexity makes the study of the metabolism of the connective tissues in health and more particularly in disease states difficult if one uses conventional biochemical methodology. Fortunately the techniques of quantitative cytochemistry, as developed in recent years, have made it possible to study the metabolism of even such complex and refractory connective tissues as bone. Using properly validated assays of enzyme activity in unfixed sections from various tissues a number of the diseases of the connective tissues have been studied. For example the synovia from patients with rheumatoid arthritis and related conditions have been studied using these techniques and marked alterations in the metabolism of the synovial lining cell population of this tissue have been demonstrated. These alterations in metabolism are believed to be related to the destruction of cartilage and bone found in such diseases. Investigations of the metabolism of the chondrocytes of articular cartilage in a strain of mice which spontaneously develops osteoarthritis has revealed a lack of certain key enzymes of carbohydrate metabolism in precisely those areas where degradation of the matrix of articular cartilage begins suggesting a causal relationship between these events. These same techniques have been used to study the cellular kinetics and metabolism of the dermis and epidermis in the disfiguring disease, psoriasis. The metabolism of healing bone fractures, the diagnosis and treatment of the mucopolysaccharidoses and the metabolic effects of currently used anti-inflammatory and anti-rheumatic drugs have also been examined. Perhaps the most exciting aspect of these studies has been the development and use of the technique of the cytochemical bioassay (CBA) to study hormonally mediated diseases of the connective tissues. Such studies have recently shed new light on the molecular lesion in pseudohypoparathyroidism. Though still in their relative infancy the studies described in this review show the potential inherent in the use of quantitative cytochemistry for the study of diseases of the connective tissues. PMID:6419282

  6. Roles of ?? T Cells in the Pathogenesis of Autoimmune Diseases

    PubMed Central

    Su, Dinglei; Shen, Minning; Li, Xia; Sun, Lingyun

    2013-01-01

    ? ? T cells are a minor population of T cells that express the TCR ?? chains, mainly distributed in the mucosal and epithelial tissue and accounting for less than 5% of the total T cells in the peripheral blood. By bridging innate and adaptive immunity, ?? T cells play important roles in the anti-infection, antitumor, and autoimmune responses. Previous research on ?? T cells was primarily concentrated on infectious diseases and tumors, whereas their functions in autoimmune diseases attracted much attention. In this paper, we summarized the various functions of ?? T cells in two prototypical autoimmune connective tissue diseases, that is, SLE and RA, elaborating on their antigen-presenting capacity, secretion of proinflammatory cytokines, immunomodulatory effects, and auxiliary function for B cells, which contribute to overproduction of proinflammatory cytokines and pathogenic autoantibodies, ultimately leading to the onset of these autoimmune diseases. Elucidation of the roles of ?? T cells in autoimmune diseases is not only conducive to in-depth understanding of the pathogenesis of these diseases, but also beneficial in providing theoretical support for the development of ?? T-cell-targeted therapy. PMID:23533458

  7. Control of connective tissue metabolism by lasers: recent developments and future prospects

    Microsoft Academic Search

    R. P. Abergel; C. A. Meeker; T. S. Lam; R. M. Dwyer; M. A. Lesavoy; J. Uitto

    1984-01-01

    Various laser modalities are currently in extensive use in dermatology and plastic surgery, particularly for treatment of vascular and pigmented lesions. A relatively new area of laser utilization involves the possible biologic effects of the lasers. In this overview, recent studies are summarized which indicate that lasers at specific wavelengths and energy densities modulate the connective tissue metabolism by skin

  8. Clinical outcome and changes in connective tissue metabolism after intravaginal slingplasty in stress incontinent women

    Microsoft Academic Search

    C. Falconer; G. Ekman-Ordeberg; A. Malmström; U. Ulmsten

    1996-01-01

    The intravaginal slingplasty procedure (IVS) was carried out on 75 patients with genuine stress urinary incontinence. The main aims of the operation are to create an artificial pubourethral ligament and to tighten the suburethral vaginal wall. An important ingredient in the supportive structures of the genitourinary region is fibrous connective tissue, consisting mainly of collagen. To analyse thi component biopsies

  9. Tetracyclines Inhibit Connective Tissue Breakdown by Multiple Non-Antimicrobial Mechanisms

    Microsoft Academic Search

    L. M. Golub; H.-M. Lee; M. E. Ryan; W. V. Giannobile; J. Payne; T. Sorsa

    1998-01-01

    A seminal experiment involving a germ-free rat model of connective tissue breakdown (followed soon thereafter by a series of in vitro studies) identified an unexpected non-antimicrobial property of tetracyclines (TCs). This ability of TCs to inhibit matrix metalloproteinases (MMPs) such as collagenase was found to reflect multiple direct and indirect mechanisms of action, and to be therapeutically useful in a

  10. Is Chronic Fatigue Syndrome a Connective Tissue Disorder? A Cross-Sectional Study in Adolescents

    Microsoft Academic Search

    E. M. van de Putte; C. S. P. M. Uiterwaal; M. L. Bots; W. Kuis; J. L. L. Kimpen; R. H. H. Engelbert

    2005-01-01

    Objectives. To investigate whether con- stitutional laxity of the connective tissues is more fre- quently present in adolescents with chronic fatigue syn- drome (CFS) than in healthy controls. Increased joint hypermobility in patients with CFS has been previously described, as has lower blood pressure in fatigued indi- viduals, which raises the question of whether constitu- tional laxity is a possible

  11. Endothelial cell markers reflecting endothelial cell dysfunction in patients with mixed connective tissue disease

    Microsoft Academic Search

    Pal Soltesz; Daniel Bereczki; Peter Szodoray; Maria T Magyar; Henrietta Der; Istvan Csipo; Agota Hajas; Gyorgy Paragh; Gyula Szegedi

    2010-01-01

    INTRODUCTION: The aim of the present study was to investigate the association between cardiovascular risk factors and endothelial dysfunction in patients with mixed connective tissue disease (MCTD) and to determine which biomarkers are associated with atherosclerotic complications, such as cardiovascular disease. METHODS: Fifty MCTD patients and 38 healthy age-matched and sex-matched controls were enrolled in this study. In order to

  12. Changes in clinical practice with the unravelling of diseases: Connective-tissue disorders

    Microsoft Academic Search

    J. Spranger; Gregor Mendel; Circle Greenwood

    2001-01-01

    Unravelling of diseases is achieved in steps by sequentially describing their phenotype, natural course, aetiology and pathogenesis. Through succinct clinical observation, conglomerates of heterogeneous connective-tissue disorders, such as various forms of disproportionate dwarfism, have been split into well-defined entities. They have often been confirmed by biochemical and molecular analysis. On the other hand, seemingly disparate disorders have been shown to

  13. Periostin Regulates Collagen Fibrillogenesis and the Biomechanical Properties of Connective Tissues

    PubMed Central

    Norris, Russell A.; Damon, Brook; Mironov, Vladimir; Kasyanov, Vladimir; Ramamurthi, Anand; Moreno-Rodriguez, Ricardo; Trusk, Thomas; Potts, Jay D.; Goodwin, Richard L.; Davis, Jeff; Hoffman, Stanley; Wen, Xuejun; Sugi, Yukiko; Kern, Christine B.; Mjaatvedt, Corey H.; Turner, Debi K.; Oka, Toru; Conway, Simon J.; Molkentin, Jeffery D.; Forgacs, Gabor; Markwald, Roger R.

    2012-01-01

    Periostin is predominantly expressed in collagen-rich fibrous connective tissues that are subjected to constant mechanical stresses including: heart valves, tendons, perichondrium, cornea, and the periodontal ligament (PDL). Based on these data we hypothesize that periostin can regulate collagen I fibrillogenesis and thereby affect the biomechanical properties of connective tissues. Immunoprecipitation and immunogold transmission electron microscopy experiments demonstrate that periostin is capable of directly interacting with collagen I. To analyze the potential role of periostin in collagen I fibrillogenesis, gene targeted mice were generated. Transmission electron microscopy and morphometric analyses demonstrated reduced collagen fibril diameters in skin dermis of periostin knockout mice, an indication of aberrant collagen I fibrillogenesis. In addition, differential scanning calorimetry (DSC) demonstrated a lower collagen denaturing temperature in periostin knockout mice, reflecting a reduced level of collagen cross-linking. Functional biomechanical properties of periostin null skin specimens and atrioventricular (AV) valve explant experiments provided direct evidence of the role that periostin plays in regulating the viscoelastic properties of connective tissues. Collectively, these data demonstrate for the first time that periostin can regulate collagen I fibrillogenesis and thereby serves as an important mediator of the biomechanical properties of fibrous connective tissues. PMID:17226767

  14. Adenoviral Gene Transfer of Connective Tissue Growth Factor in the Lung Induces Transient Fibrosis

    Microsoft Academic Search

    Philippe Bonniaud; Peter J. Margetts; Martin Kolb; Thomas Haberberger; Margaret Kelly; Jennifer Robertson; Jack Gauldie

    2003-01-01

    Connective tissue growth factor (CTGF) is felt to be one of the key profibrotic factors and is a downstream effector molecule mediating the action of transforming growth factor (TGF)-1, a cytokine known to induce severe and progressive fibrosis. However, the in vivo fibro- genic effect of isolated CTGF expression is not well described. We used adenoviral gene transfer to transiently

  15. Ontogenetic Changes in Fibrous Connective Tissue Organization in the Oval Squid, Sepioteuthis

    E-print Network

    Kier, William M.

    Ontogenetic Changes in Fibrous Connective Tissue Organization in the Oval Squid, Sepioteuthis lessoniana, the oval squid. Outer tunic fiber angle (the angle of a tunic collagen fiber relative to the long axis of the squid) decreased from 33.5° in newly hatched animals to 17.7° in the largest animals

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

    NASA Technical Reports Server (NTRS)

    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.

  17. Periostin regulates collagen fibrillogenesis and the biomechanical properties of connective tissues.

    PubMed

    Norris, Russell A; Damon, Brook; Mironov, Vladimir; Kasyanov, Vladimir; Ramamurthi, Anand; Moreno-Rodriguez, Ricardo; Trusk, Thomas; Potts, Jay D; Goodwin, Richard L; Davis, Jeff; Hoffman, Stanley; Wen, Xuejun; Sugi, Yukiko; Kern, Christine B; Mjaatvedt, Corey H; Turner, Debi K; Oka, Toru; Conway, Simon J; Molkentin, Jeffery D; Forgacs, Gabor; Markwald, Roger R

    2007-06-01

    Periostin is predominantly expressed in collagen-rich fibrous connective tissues that are subjected to constant mechanical stresses including: heart valves, tendons, perichondrium, cornea, and the periodontal ligament (PDL). Based on these data we hypothesize that periostin can regulate collagen I fibrillogenesis and thereby affect the biomechanical properties of connective tissues. Immunoprecipitation and immunogold transmission electron microscopy experiments demonstrate that periostin is capable of directly interacting with collagen I. To analyze the potential role of periostin in collagen I fibrillogenesis, gene targeted mice were generated. Transmission electron microscopy and morphometric analyses demonstrated reduced collagen fibril diameters in skin dermis of periostin knockout mice, an indication of aberrant collagen I fibrillogenesis. In addition, differential scanning calorimetry (DSC) demonstrated a lower collagen denaturing temperature in periostin knockout mice, reflecting a reduced level of collagen cross-linking. Functional biomechanical properties of periostin null skin specimens and atrioventricular (AV) valve explant experiments provided direct evidence of the role that periostin plays in regulating the viscoelastic properties of connective tissues. Collectively, these data demonstrate for the first time that periostin can regulate collagen I fibrillogenesis and thereby serves as an important mediator of the biomechanical properties of fibrous connective tissues. PMID:17226767

  18. Microstructure alterations in beef intramuscular connective tissue caused by hydrodynamic pressure processing

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Scanning electron microscopy (SEM) was utilized to evaluate microstructural changes in intramuscular connective tissue of beef semimembranosus muscle subjected to hydrodynamic pressure processing (HDP). Samples were HDP treated in a plastic container (HDP-PC) or a steel commercial unit (HDP-CU). C...

  19. Morphometric analysis of nonsclerosed Glomeruli size and connective tissue content during the aging process.

    PubMed

    Stojanovi?, Vesna R; Jovanovi?, Ivan D; Ugrenovi?, Sladjana Z; Vasovi?, Ljiljana P; Živkovi?, Vladimir S; Joci?, Miodrag V; Kundali?, Braca K; Pavlovi?, Miljana N

    2012-01-01

    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. PMID:22654637

  20. A novel composition for in vitro and in vivo regeneration of skin and connective tissues.

    PubMed

    Gennero, Luisa; De Siena, Rocco; Denysenko, Tetyana; Roos, Maria Augusta; Calisti, Gian Franco; Martano, Manuela; Fiobellot, Simona; Panzone, Michele; Reguzzi, Stefano; Gabetti, Luisa; Vercelli, Andrea; Cavallo, Giovanni; Ricci, Elia; Pescarmona, Gian Piero

    2011-06-01

    The particular combination of polydeoxyribonucleotides, l-carnitine, calcium ions, proteolytic enzyme and other ingredients acts in a synergetic way in the regeneration of skin and connective tissues. This new formulation of active principles was tested in vitro as a cell and tissue culture medium and in vivo for various preparations in support of tissue regeneration. In vitro, the new blend allowed the maintenance of skin biopsies for more than 1 year in eutrophic conditions. Immunocytochemical analyses of fibroblasts isolated from these biopsies confirmed a significant increase of the epidermal and connective wound-healing markers such as collagen type I, collagen type IV, cytokeratin 1 (CK1), CK5, CK10 and CK14 versus controls. To examine the effects of the new compound in vivo, we studied impaired wound healing in genetically diabetic db/db mice. At day 18, diabetic mice treated with the new composition showed 100% closure of wounds and faster healing than mice treated with the other solutions. This complex of vital continuity factors or life-keeping factors could be used as a tissue-preserving solution or a cosmetic/drug/medical device to accelerate wound healing in the treatment of patients with deficient wound repair to promote the regeneration of cutaneous and connective tissues (injuries-wound, dermatitis) and prevent the recurrent relapses. PMID:21491468

  1. Characterization of the autoimmune response against the nerve tissue S100? in patients with type 1 diabetes.

    PubMed

    Gómez-Tourińo, I; Simón-Vázquez, R; Alonso-Lorenzo, J; Arif, S; Calvińo-Sampedro, C; González-Fernández, Á; Pena-González, E; Rodríguez, J; Vińuela-Roldán, J; Verdaguer, J; Cordero, O J; Peakman, M; Varela-Calvino, R

    2015-05-01

    Type 1 diabetes results from destruction of insulin-producing beta cells in pancreatic islets and is characterized by islet cell autoimmunity. Autoreactivity against non-beta cell-specific antigens has also been reported, including targeting of the calcium-binding protein S100?. In preclinical models, reactivity of this type is a key component of the early development of insulitis. To examine the nature of this response in type 1 diabetes, we identified naturally processed and presented peptide epitopes derived from S100?, determined their affinity for the human leucocyte antigen (HLA)-DRB1*04:01 molecule and studied T cell responses in patients, together with healthy donors. We found that S100? reactivity, characterized by interferon (IFN)-? secretion, is a characteristic of type 1 diabetes of varying duration. Our results confirm S100? as a target of the cellular autoimmune response in type 1 diabetes with the identification of new peptide epitopes targeted during the development of the disease, and support the preclinical findings that autoreactivity against non-beta cell-specific autoantigens may have a role in type 1 diabetes pathogenesis. PMID:25516468

  2. [Autoimmune thyroid disease and associated diseases].

    PubMed

    Lapcevi?, Mirjana

    2005-10-01

    Autoimmune thyroid disease (ATD) is a multifactorial, genetic disease. It is the sequelae of the impaired immunoregulation, tolerance and poor recognition of one's own proteins, oligopolysaccharides and polypeptides, due to development of somatic lymphocyte mutations. It is manifested by different clinical and morphological entities, inter-related by etiopathogenetic association, i.e., all of them are caused by disorder of immune system regulation. Chronic autoimmune thyroidism (Thyreoiditis lymphocytaria Hashimoto, HT), as well as immunogenic hyperthyroidism (Morbus Graves Basedow, MGB) are frequently associated with autoimmune diseases of other organs, such as: chronic insufficiency of salivary glands (Sy Sjögren), autoimmune hemolytic anemia, megalocytic pernicious anemia, thrombocytopenia, Rheumatoid arthritis, Diabetes mellitus (more often type 2, but also type 1), Morbus Addison, Coeliakia, and other autoimmune diseases such as systemic diseases of connecting tissue (Lupus erythematosus-SLE, Sclerodermia, Vasculitis superficialis). The incidence of autoimmune diseases has been at increase in all age groups of our population. The prevalence of organ-specific and organ-nonspecific antibodies increases with the age. Antigenicity of thyroid epithelial cell may be triggered by different chemical and biological agents (repeated viral infections), repeated stress, and in individuals with genetic propensity. Unrecognized ATD progressively leads to hypothyroidism with hyperlipidemia, blood vessel changes, osteoporosis, deformities, invalidity which substantially reduces the quality of life of patient and requires medical attention and expensive treatment on what account it is medically and socio-economically significant. Multiple diagnostic procedures contribute to faster recognition of this condition. The goal of the primary health care physician (given that preclinical phase of ATD and other associated diseases have different duration) and other specialists is to recognize ATD and, by early diagnosis and multidisciplinary treatment, to take secondary preventive measures of manifestation of above-mentioned associated autoimmune diseases, and in that way, to avoid the development of comorbidity and complications. It is particularly supported by medical doctrine based on evidence of application of corticosteroids, cytostatics, thyro-suppressive and substitution therapy, antilipemics, bisphosphonates and other drugs, significant for autoimmune diseases. PMID:16405263

  3. Autoimmune thyroid disorders.

    PubMed

    Antonelli, Alessandro; Ferrari, Silvia Martina; Corrado, Alda; Di Domenicantonio, Andrea; Fallahi, Poupak

    2015-02-01

    Autoimmune thyroid diseases (AITD) result from a dysregulation of the immune system leading to an immune attack on the thyroid. AITD are T cell-mediated organ-specific autoimmune disorders. The prevalence of AITD is estimated to be 5%; however, the prevalence of antithyroid antibodies may be even higher. The AITD comprise two main clinical presentations: Graves' disease (GD) and Hashimoto's thyroiditis (HT), both characterized by lymphocytic infiltration of the thyroid parenchyma. The clinical hallmarks of GD and HT are thyrotoxicosis and hypothyroidism, respectively. The mechanisms that trigger the autoimmune attack to the thyroid are still under investigation. Epidemiological data suggest an interaction among genetic susceptibility and environmental triggers as the key factor leading to the breakdown of tolerance and the development of disease. Recent studies have shown the importance of cytokines and chemokines in the pathogenesis of AT and GD. In thyroid tissue, recruited T helper 1 (Th1) lymphocytes may be responsible for enhanced IFN-? and TNF-? production, which in turn stimulates CXCL10 (the prototype of the IFN-?-inducible Th1 chemokines) secretion from the thyroid cells, therefore creating an amplification feedback loop, initiating and perpetuating the autoimmune process. Associations exist between AITD and other organ specific (polyglandular autoimmune syndromes), or systemic autoimmune disorders (Sjögren's syndrome, rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, cryoglobulinemia, sarcoidosis, psoriatic arthritis). Moreover, several studies have shown an association of AITD and papillary thyroid cancer. These data suggest that AITD patients should be accurately monitored for thyroid dysfunctions, the appearance of thyroid nodules, and other autoimmune disorders. PMID:25461470

  4. Fractal analysis of the structural complexity of the connective tissue in human carotid bodies

    PubMed Central

    Guidolin, Diego; Porzionato, Andrea; Tortorella, Cinzia; Macchi, Veronica; De Caro, Raffaele

    2014-01-01

    The carotid body (CB) may undergo different structural changes during perinatal development, aging, or in response to environmental stimuli. In the previous literature, morphometric approaches to evaluate these changes have considered quantitative first order parameters, such as volumes or densities, while changes in spatial disposition and/or complexity of structural components have not yet been considered. In the present study, different strategies for addressing morphological complexity of CB, apart from the overall amount of each tissue component, were evaluated and compared. In particular, we considered the spatial distribution of connective tissue in the carotid bodies of young control subjects, young opiate-related deaths and aged subjects, through analysis of dispersion (Morisita's index), gray level co-occurrence matrix (entropy, angular second moment, variance, correlation), and fractal analysis (fractal dimension, lacunarity). Opiate-related deaths and aged subjects showed a comparable increase in connective tissue with respect to young controls. However, the Morisita's index (p < 0.05), angular second moment (p < 0.05), fractal dimension (p < 0.01), and lacunarity (p < 0.01) permitted to identify significant differences in the disposition of the connective tissue between these two series. A receiver operating characteristic (ROC) curve was also calculated to evaluate the efficiency of each parameter. The fractal dimension and lacunarity, with areas under the ROC curve of 0.9651 (excellent accuracy) and 0.8835 (good accuracy), respectively, showed the highest discriminatory power. They evidenced higher level of structural complexity in the carotid bodies of opiate-related deaths than old controls, due to more complex branching of intralobular connective tissue. Further analyses will have to consider the suitability of these approaches to address other morphological features of the CB, such as different cell populations, vascularization, and innervation. PMID:25414672

  5. Comparative Clinical Evaluation of Subepithelial Connective Tissue Graft and Acellular Dermal Matrix Allograft for the Treatment of Gingival Recession

    Microsoft Academic Search

    F. Haghighati; M. Mousavi; N. Moslemi

    2006-01-01

    Statement of Problem: Various surgical procedures have been used to achieve root coverage and subepithelial connective tissue graft (SCTG) is identified as one of the most successful techniques. Recently, acellular dermal matrix allograft (ADMA) has been developed as a substitute for SCTG to avoid removing the palatal connective tissue. Purpose: The present study compared the clinical efficiency of ADMA and

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

    PubMed Central

    Li, Qiaoli; Uitto, Jouni

    2014-01-01

    Ectopic mineralization has been linked to several common clinical conditions with considerable morbidity and mortality. The mineralization processes, both metastatic and dystrophic, affect the skin and vascular connective tissues. There are several contributing metabolic and environmental factors that make uncovering of the precise pathomechanisms of these acquired disorders exceedingly difficult. Several relatively rare heritable disorders share phenotypic manifestations similar to those in common conditions, and, consequently, they serve as genetically controlled model systems to study the details of the mineralization process in peripheral tissues. This overview will highlight diseases with mineral deposition in the skin and vascular connective tissues, as exemplified by familial tumoral calcinosis, pseudoxanthoma elasticum, generalized arterial calcification of infancy, and arterial calcification due to CD73 deficiency. These diseases, and their corresponding mouse models, provide insight into the pathomechanisms of soft tissue mineralization and point to the existence of intricate mineralization/anti-mineralization networks in these tissues. This information is critical for understanding the pathomechanistic details of different mineralization disorders, and it has provided the perspective to develop pharmacological approaches to counteract the consequences of ectopic mineralization. PMID:23665350

  7. Autoimmune Retinopathies

    Microsoft Academic Search

    Jennifer K. Hall; Nicholas J. Volpe

    ? Autoimmune retinopathies should be included in the neuroophthalmic differential diagnosis for subacute vision loss with\\u000a minimal fundus changes. \\u000a \\u000a ? Particularly relevant are paraneoplastic retinopathies [cancer-associated retinopathy (CAR), melanoma-associated retinopathy\\u000a (MAR), bilateral diffuse uveal melanocytic proliferation (BDUMP)], autoimmune-related retinopathy and optic neuropathy (ARRON),\\u000a and the acute outer retinopathies with blind spot enlargement [acute idiopathic blind spot enlargement (AIBSE), multiple evanescent

  8. Autoimmune Autonomic Ganglionopathy

    MedlinePLUS

    ... Mediated Syncope (NMS) Familial Dysautonomia (FD) Learn More Autoimmune Autonomic Ganglionopathy What is autoimmune autonomic ganglionopathy (AAG)? Autoimmune autonomic ganglionopathy (AAG) is ...

  9. The suction mechanism as a factor in intrathoracic oedema, connective tissue or pleural effusion.

    PubMed

    Felekis, Vasilios A

    2002-10-01

    In pathological conditions, the negative intrapleural pressures (Ppl) may increase unequally. At some sites they may remain increased. We maintain that at these sites the increased pressures may lead to the production of oedema in the adjacent pleural walls and in adjacent pre-existing connective tissue, which may remain as oedema or may become connective tissue. Occasionally the increased negative Ppl may contribute to the production of pleural effusion. We term all these processes the suction mechanism (SM). This mechanism affords an interpretation of a series of images observed in chest X-rays. According to this view, lung shrinkage, narrowing of the pulmonary vessels and impairment of the lung function are not caused by the diffuse pleural fibrosis, but result from damage to the lung parenchyma. We also interpret the apical cap, the blunting of the costophrenic sulci, the broadening of the mediastinum and the retrosternal stripe in terms of the SM. PMID:12208189

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

    PubMed

    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. PMID:20416788

  11. Genetic Dissection of Marfan Syndrome and Related Connective Tissue Disorders: An Update 2012

    PubMed Central

    Hoffjan, S.

    2012-01-01

    Marfan syndrome (MFS) is an autosomal dominant disorder of the connective tissue characterized by early development of thoracic aortic aneurysms/dissections together with symptoms of the ocular and skeletal systems. While most patients/families with a classic phenotypic expression of MFS harbour mutations in the gene encoding fibrillin-1 (FBN1), genetic studies of the recent years revealed that the clinical features, as well as the mutated genes, show a high degree of overlap between MFS and other connective tissue diseases (e.g. Loeys-Dietz syndrome, Ehlers-Danlos syndrome, familial thoracic aneurysms and dissections and others). We summarize herein the current knowledge about the wide spectrum of differential diagnoses and their genetic background as well as novel therapeutic approaches in order to provide appropriate counselling and clinical follow-up for the patients. PMID:23326250

  12. The connective tissue response to Ti, NiCr and AgPd alloys.

    PubMed

    ?ukomska-Syma?ska, Monika; Brzezi?ski, Piotr M; Zieli?ski, Andrzej; Soko?owski, Jerzy

    2010-09-30

    The aim of the study was to compare the connective tissue response of Lewis rats to Ti, NiCr and AgPd alloys. It was found that implants were covered by collagen-rich, well vascularized capsules. Titanium was covered by the thinnest capsule (57 ± 20 ?m) and AgPd alloy was covered by the thickest capsule (239 ± 50 ?m). The PCNA+ cell prevalence in the capsules was lower for titanium than for AgPd and NiCr. Mast cells formed a gradient to a depth of 1200 ?m only for titanium implants. Cells with brown to black silver granules in the cytoplasm were observed close to AgPd implants. The results suggest that titanium implants induce a weaker connective tissue response than implants made from NiCr and AgPd alloys. PMID:21071336

  13. Connective tissue growth factor: a mediator of TGF-? action on fibroblasts

    Microsoft Academic Search

    Gary R. Grotendorst

    1997-01-01

    Connective tissue growth factor (CTGF) is a cysteine-rich mitogenic peptide that binds heparin and is secreted by fibroblasts after activation with transforming growth factor beta (TGF-?). CTGF is a member of a highly conserved family of peptides that include immediate early gene products cef10, cyr61, fisp12; a putative avian proto-oncogene, nov; and a drosophila gene, twisted gastrulation, tsg, that controls

  14. Indices of skeletal muscle damage and connective tissue breakdown following eccentric muscle contractions

    Microsoft Academic Search

    S. J. Brown; R. B. Child; S. H. Day; A. E. Donnelly

    1997-01-01

    Indirect indices of exercise-induced human skeletal muscle damage and connective tissue breakdown were studied following\\u000a a single bout of voluntary eccentric muscle contractions. Subjects (six female, two male), mean (SD) age 22 (2) years performed\\u000a a bout of 50 maximum voluntary eccentric contractions of the knee extensors of a single leg. The eccentric exercise protocol\\u000a induced muscle soreness (P?

  15. Nitric oxide down-regulates connective tissue growth factor in rat mesangial cells

    Microsoft Academic Search

    Annette Keil; Ingrid E Blom; Roel Goldschmeding; Harald D Rupprecht

    2002-01-01

    Nitric oxide down-regulates connective tissue growth factor in rat mesangial cells.BackgroundNitric oxide (NO) exerts complex regulatory actions on mesangial cell (MC) biology, such as inhibition of proliferation, adhesion or contractility and induction of apoptosis. In our previous studies the NO-donor S-nitroso-glutathione (GSNO) was found to be a potent inhibitor of MC growth. This effect was mediated at least in part

  16. Fucoidan a sulfated polysaccharide from brown algae is a potent modulator of connective tissue proteolysis

    Microsoft Academic Search

    Karim Senni; Farida Gueniche; Alexandrine Foucault-Bertaud; Sylvie Igondjo-Tchen; Florence Fioretti; Sylvia Colliec-Jouault; Patrick Durand; Jean Guezennec; Gaston Godeau; Didier Letourneur

    2006-01-01

    Fucoidans are sulfated fucosylated polymers from brown algae cell wall that exhibit some heparin\\/heparan sulfate properties. We previously demonstrated that these polysaccharides were able in vitro to stimulate dermal fibroblast proliferation and extracellular matrix deposition. Here, we investigated the action of a 16kDa fucoidan fraction on parameters involved in connective tissue breakdown. This fucoidan is able to inhibit gelatinase A

  17. Scanning electron microscope study of connective tissue in raw and cooked muscles

    E-print Network

    Percy, Mary Lou

    1976-01-01

    of cathepsins, other enzymes which could affect tenderness were released concomitantly. Tenderness could be affected by B-glucuronidase which hydrolyzes the glucose-galactose moieties that are present in collagen and the mucopolysaccharide protein complexes... ultrastructure and tensile properties of cathepsin and collagenase treated muscle fibers. J. Food Sci. 38:51. Field, R. A. , Pearson, A. N. and Schweigert, B. S. 1970. Labile collagen from epimysial and intramuscular connective tissue as related to Marner...

  18. Progressive Overgrowth of the Cerebriform Connective Tissue Nevus in Patients with Proteus Syndrome

    PubMed Central

    Beachkofsky, Thomas M.; Sapp, Julie C.; Biesecker, Leslie G.; Darling, Thomas N.

    2011-01-01

    Background Proteus syndrome is a rare overgrowth disorder that almost always affects the skin. Objective Our purpose was to evaluate progression of skin lesions in patients with Proteus syndrome. Methods Skin findings were documented in 36 patients with Proteus syndrome. Progression of skin lesions in 16 of these patients was assessed by comparing photographs obtained on repeat visits for an average total duration of 53 months. Results The skin lesion most characteristic of Proteus syndrome, the cerebriform connective tissue nevus showed progression in 13 children but not in 3 adults. The cerebriform connective tissue nevus progressed by expansion into previously uninvolved skin, increased thickness, and development of new lesions. Lipomas increased in size and/or number in 8/10 children with lipomas. In contrast, epidermal nevi and vascular malformations generally did not spread or increase in number. Limitations Only 3 adults with Proteus syndrome were evaluated longitudinally. Conclusion The cerebriform connective tissue nevus in Proteus syndrome grows throughout childhood but tends to remain stable in adulthood. PMID:20709429

  19. Quantitative nailfold capillaroscopy findings in a population with connective tissue disease and in normal healthy controls.

    PubMed Central

    Kabasakal, Y; Elvins, D M; Ring, E F; McHugh, N J

    1996-01-01

    OBJECTIVE: To describe and quantify the morphological characteristics of nailfold capillaries that distinguish different forms of connective tissue disease from healthy controls. METHODS: A CCD video microscope with fibreoptic illumination and PC based image processing was used to visualise nailfold capillaries and to quantify findings in 23 patients with systemic sclerosis (SSc), 22 patients with systemic lupus erythematosus (SLE), 21 patients with undifferentiated connective tissue disease (UCTD), and 38 healthy controls. RESULTS: Capillary density was reduced in SSc (5.2 (SD 1.3) capillaries/mm) compared with other patient groups and controls. The average number of enlarged capillaries/finger was high in all disease groups (5.5-6.6) compared with controls (2). However, giant capillaries were most frequent in SSc (43%) and were not present in controls. Mild and moderate avascular areas were present in all groups (35%-68%), but severe avascularity was most frequent in SSc (44%) compared with other patients (18%-19%) and controls (0%). The greatest frequency of extensive haemorrhage was in SSc (35%). CONCLUSIONS: There is a range of abnormal capillary findings in patients with connective tissue disease and healthy controls. However, certain abnormalities such as a reduced number of capillaries, severe avascularity, giant capillaries, and haemorrhage are most commonly associated with SSc. Videomicroscopy with image processing offers many technical advantages that can be exploited in further studies of nailfold capillaries. Images PMID:8774177

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

    NASA Astrophysics Data System (ADS)

    Lambert, Ch. A.; Nusgens, B. V.; Lapičre, 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.

  1. Rheumatic and autoimmune thyroid disorders: a causal or casual relationship?

    PubMed

    Bourji, Khalil; Gatto, Mariele; Cozzi, Franco; Doria, Andrea; Punzi, Leonardo

    2015-01-01

    A number of dysfunctions may affect the thyroid gland leading either to hyper- or hypothyroidism which are mediated by autoimmune mechanisms. Thyroid abnormalities may represent an isolated alteration or they may be the harbinger of forthcoming disorders as is the case of well-characterized polyendocrine syndromes. Also, they may precede or follow the appearance of rheumatic manifestations in patients affected with connective tissue diseases or rheumatoid arthritis. The mechanisms by which autoimmune thyroid disorders may be linked to systemic autoimmune diseases have not been fully unraveled yet, however alterations of common pathways are suggested by shared genetic variants affecting autoantigen presentation and regulation of the immune response. On the other hand, the higher prevalence of autoimmune thyroid disorders over rheumatic diseases compels the chance of a mere causal concomitancy in the same patient. The aim of our paper is to provide an overview of available data on thyroid involvement in different rheumatic diseases and to go over the main rheumatic manifestations in the context of autoimmune thyroid diseases. PMID:25315745

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

    PubMed

    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. PMID:24924347

  3. Connective tissue reaction of rats to a new zinc-oxide-eugenol endodontic sealer.

    PubMed

    Trichęs, Karen Melina; Júnior, Jacy Simi; Calixto, Joăo Batista; Machado, Ricardo; Rosa, Tiago Pereira; Silva, Emmanuel Joăo Nogueira Leal; Vansan, Luiz Pascoal

    2013-12-01

    The aim of this study was to evaluate the biocompatibility in rat subcutaneous connective tissue of a new zinc oxide endodontic sealer (Endomethasone N) compared to those provided by Endofill and Sealer 26. Polyethylene tubes containing the test materials were implanted into dorsal subcutaneous connective tissue of Wistar albino rats. After 7 and 42 days, the implants with the surrounding tissue were collected, fixed, and processed for histologic evaluation. Sections were evaluated for the presence of inflammatory cells (poly or monomorfonuclear), blood vessels, necrosis area, and thickness of fibrous capsule. Comparisons between groups and time-periods were performed with Kruskal-Wallis and Mann-Whitney U non-parametric tests for 5% significance level. No differences in the biocompatibility patterns among the materials for the 2 experimental periods were observed. Independently of the sealer, the tissue behavior showed a tendency to decrease the irritation effect over time. It can be concluded that all sealers are irritant, but its toxicity decreased with time. Endomethásone N showed biocompatible characteristics comparable with those provided by Endofill and Sealer 26. PMID:24123537

  4. Histological analysis of esophageal muscular layers from 27 autopsy cases with mixed connective tissue disease (MCTD).

    PubMed

    Uzuki, Miwa; Kamataki, Akihisa; Watanabe, Mika; Sasaki, Nobuhito; Miura, Yasuhiro; Sawai, Takashi

    2011-06-15

    Esophageal symptoms in mixed connective tissue disease (MCTD) have been investigated radiologically. We investigated the esophageal lesions in MCTD histopathologically, and analyzed relationships between these lesions and autoantibodies extracted from the serum of MCTD patients. Esophageal tissues from 27 MCTD patients submitted to autopsy were examined. We compared histopathological features of the esophagus in different wall layers from the mucosa, submucosa, and muscular layer to the adventitia, and in the upper, middle, and lower portions of esophagus. The most striking change observed was severe atrophy and occasional loss of smooth muscle cells in the muscular layer, followed by fibrosis. These muscular changes were particularly prominent in the inner layer of the lower esophagus. Immunohistochemically, degenerated muscular tissues of the esophagus were positive for anti-IgG and anti-C3 antibodies, but not for anti-IgM antibodies. IgG fractions extracted from three MCTD patients were immunohistochemically used to examine whether some antibodies in MCTD patients showed reactivity for esophageal components. The IgG fractions isolated from MCTD patients reacted with smooth muscle from non-connective tissue disease cases, suggesting that some serum antibodies may trigger esophageal changes. These findings suggest that esophageal lesions associated with clinical dysphagia in MCTD may be related to autoantibodies. PMID:21620578

  5. Reaction of rat connective tissue to mineral trioxide aggregate and diaket

    PubMed Central

    2011-01-01

    Background The aim of this study was to compare the reaction of rat connective tissue to two root-end filling materials: white Mineral Trioxide Aggregate (WMTA) and Diaket. Methods Each of the materials was placed in dentine tubes and implanted subcutaneously in the dorsal connective tissue of 21 Wistar albino rats. Tissue biopsies were collected 7, 30, and 60 days after the implantation procedure. The specimens were processed and stained with hematoxylin and eosin and examined microscopically. After determining inflammatory cell numbers in sections from each specimen, inflammatory reaction scores were defined as follows: 0; no or few inflammatory cells (no reaction), 1; less than 25 cells (mild reaction), 2; 25 to 125 cells, (moderate reaction), and 3; 125 or more cells (severe reaction). Statistical analysis was performed using the Kruskal-Wallis and Mann-Whitney tests. Results There were statistically significant differences in the median inflammatory cell numbers throughout the three test periods, with the most severe degree of inflammation observed at the one-week period. Few cases of necrosis were observed with WMTA. Diaket exhibited the most severe degree of inflammation and necrosis. After 30 days, both materials provoked moderate inflammatory reaction. The eight-week period showed the least severe degree of inflammation in all groups. Conclusions It was concluded that WMTA exhibits a more favourable tissue response compared with Diaket which induced more severe inflammatory reaction than WMTA and the control. PMID:21569463

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

    PubMed

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

    2011-10-01

    This case series evaluated the facial gingival stability following single immediate tooth replacement in conjunction with subepithelial connective tissue graft (SCTG). Implant success rate and peri-implant tissue response were also reported. Ten patients (6 male, 4 female), with a mean age of 52.1 (range = 22.7 to 67.1) years, underwent immediate implant placement and provisionalization with SCTG and were evaluated clinically and radiographically at presurgery (T0), at the time of immediate tooth replacement and SCTG (T1), and 3 months (T2), 6 months (T3), and 12 months (T4) after surgery. Data were analyzed using the Friedman and Wilcoxon signed-ranks tests at the significance level of ? = .05. At 1 year, 9 of 10 implants remained osseointegrated with the overall mean marginal bone change of -0.31 mm and a mean facial gingival level change of -0.05 mm. The modified plaque index scores showed that patients were able to maintain a good level of hygiene throughout the study. The papilla index score indicated that at T4, more than 50% of the papilla fill was observed in 89% of all sites. When proper 3-dimensional implant position is achieved and bone graft is placed into the implant-socket gap, favorable success rate and peri-implant tissue response of platform switching implants can be achieved following immediate tooth replacement in conjunction with subepithelial connective tissue graft. PMID:20883114

  7. Beneficial Autoimmunity at Body Surfaces – Immune Surveillance and Rapid Type 2 Immunity Regulate Tissue Homeostasis and Cancer

    PubMed Central

    Dalessandri, Tim; Strid, Jessica

    2014-01-01

    Epithelial cells (ECs) line body surface tissues and provide a physicochemical barrier to the external environment. Frequent microbial and non-microbial challenges such as those imposed by mechanical disruption, injury or exposure to noxious environmental substances including chemicals, carcinogens, ultraviolet-irradiation, or toxins cause activation of ECs with release of cytokines and chemokines as well as alterations in the expression of cell-surface ligands. Such display of epithelial stress is rapidly sensed by tissue-resident immunocytes, which can directly interact with self-moieties on ECs and initiate both local and systemic immune responses. ECs are thus key drivers of immune surveillance at body surface tissues. However, ECs have a propensity to drive type 2 immunity (rather than type 1) upon non-invasive challenge or stress – a type of immunity whose regulation and function still remain enigmatic. Here, we review the induction and possible role of type 2 immunity in epithelial tissues and propose that rapid immune surveillance and type 2 immunity are key regulators of tissue homeostasis and carcinogenesis. PMID:25101088

  8. Real-time immune cell interactions in target tissue during autoimmune-induced damage and graft tolerance

    PubMed Central

    Miska, Jason; Abdulreda, Midhat H.; Devarajan, Priyadharshini; Lui, Jen Bon; Suzuki, Jun; Pileggi, Antonello; Berggren, Per-Olof

    2014-01-01

    Real-time imaging studies are reshaping immunological paradigms, but a visual framework is lacking for self-antigen-specific T cells at the effector phase in target tissues. To address this issue, we conducted intravital, longitudinal imaging analyses of cellular behavior in nonlymphoid target tissues to illustrate some key aspects of T cell biology. We used mouse models of T cell–mediated damage and protection of pancreatic islet grafts. Both CD4+ and CD8+ effector T (Teff) lymphocytes directly engaged target cells. Strikingly, juxtaposed ? cells lacking specific antigens were not subject to bystander destruction but grew substantially in days, likely by replication. In target tissue, Foxp3+ regulatory T (Treg) cells persistently contacted Teff cells with or without involvement of CD11c+ dendritic cells, an observation conciliating with the in vitro “trademark” of Treg function, contact-dependent suppression. This study illustrates tolerance induction by contact-based immune cell interaction in target tissues and highlights potentials of tissue regeneration under antigenic incognito in inflammatory settings. PMID:24567447

  9. Real-time immune cell interactions in target tissue during autoimmune-induced damage and graft tolerance.

    PubMed

    Miska, Jason; Abdulreda, Midhat H; Devarajan, Priyadharshini; Lui, Jen Bon; Suzuki, Jun; Pileggi, Antonello; Berggren, Per-Olof; Chen, Zhibin

    2014-03-10

    Real-time imaging studies are reshaping immunological paradigms, but a visual framework is lacking for self-antigen-specific T cells at the effector phase in target tissues. To address this issue, we conducted intravital, longitudinal imaging analyses of cellular behavior in nonlymphoid target tissues to illustrate some key aspects of T cell biology. We used mouse models of T cell-mediated damage and protection of pancreatic islet grafts. Both CD4(+) and CD8(+) effector T (Teff) lymphocytes directly engaged target cells. Strikingly, juxtaposed ? cells lacking specific antigens were not subject to bystander destruction but grew substantially in days, likely by replication. In target tissue, Foxp3(+) regulatory T (Treg) cells persistently contacted Teff cells with or without involvement of CD11c(+) dendritic cells, an observation conciliating with the in vitro "trademark" of Treg function, contact-dependent suppression. This study illustrates tolerance induction by contact-based immune cell interaction in target tissues and highlights potentials of tissue regeneration under antigenic incognito in inflammatory settings. PMID:24567447

  10. The autoimmune diseases

    SciTech Connect

    Rose, N.R.; Mackay, I.R.

    1985-01-01

    This book contains 25 chapters. Some of the chapter titles are: Genetic Predisposition to Autoimmune Diseases; Systemic Lupus Erythematosus; Autoimmune Aspects of Rheumatoid Arthritis; Immunology of Insulin-Dependent Diabetes; and Adrenal Autoimmunity and Autoimmune Polyglandular Syndromes.

  11. Autoimmune encephalopathies.

    PubMed

    Leypoldt, Frank; Armangue, Thaís; Dalmau, Josep

    2015-03-01

    Over the past 10 years, the continual discovery of novel forms of encephalitis associated with antibodies to cell-surface or synaptic proteins has changed the paradigms for diagnosing and treating disorders that were previously unknown or mischaracterized. We review here the process of discovery, the symptoms, and the target antigens of 11 autoimmune encephalitic disorders, grouped by syndromes and approached from a clinical perspective. Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis, several subtypes of limbic encephalitis, stiff-person spectrum disorders, and other autoimmune encephalitides that result in psychosis, seizures, or abnormal movements are described in detail. We include a novel encephalopathy with prominent sleep dysfunction that provides an intriguing link between chronic neurodegeneration and cell-surface autoimmunity (IgLON5). Some of the caveats of limited serum testing are outlined. In addition, we review the underlying cellular and synaptic mechanisms that for some disorders confirm the antibody pathogenicity. The multidisciplinary impact of autoimmune encephalitis has been expanded recently by the discovery that herpes simplex encephalitis is a robust trigger of synaptic autoimmunity, and that some patients may develop overlapping syndromes, including anti-NMDAR encephalitis and neuromyelitis optica or other demyelinating diseases. PMID:25315420

  12. A physiological role for connective tissue growth factor in early wound healing

    PubMed Central

    Alfaro, Maria P; Deskins, Desirae L; Wallus, Meredith; DasGupta, Jayasri; Davidson, Jeffrey M; Nanney, Lillian B; Guney, Michelle A; Gannon, Maureen; Young, Pampee P

    2013-01-01

    Mesenchymal stem cells (MSCs) that overexpress secreted frizzled-related protein 2 (sFRP2) exhibit an enhanced reparative phenotype. The secretomes of sFRP2-overexpressing MSCs and vector control-MSCs were compared through liquid chromatography tandem mass spectrometry. Proteomic profiling revealed that connective tissue growth factor (CTGF; CCN2) was overrepresented in the conditioned media of sFRP2-overexpressing MSCs and MSC-derived CTGF could thus be an important paracrine effector. Subcutaneously implanted, MSC-loaded polyvinyl alcohol (PVA) sponges and stented excisional wounds were used as wound models to study the dynamics of CTGF expression. Granulation tissue generated within the sponges and full-thickness skin wounds showed transient upregulation of CTGF expression by MSCs and fibroblasts, implying a role for this molecule in early tissue repair. Although collagen and COL1A2 mRNA were not increased when recombinant CTGF was administered to sponges during the early phase (day 1–6) of tissue repair, prolonged administration (>15 days) of exogenous CTGF into PVA sponges resulted in fibroblast proliferation and increased deposition of collagen within the experimental granulation tissue. In support of its physiological role, CTGF immunoinhibition during early repair (days 0–7) reduced the quantity, organizational quality and vascularity of experimental granulation tissue in the sponge model. However, CTGF haploinsufficiency was not enough to reduce collagen deposition in excisional wounds. Similar to acute murine wound models, CTGF was transiently present in the early phase of human acute burn wound healing. Together, these results further support a physiological role for CTGF in wound repair and demonstrate that when CTGF expression is confined to early tissue repair, it serves a pro-reparative role. These data also further illustrate the potential of MSC-derived paracrine modulators to enhance tissue repair. PMID:23212098

  13. Fourier Transform Infrared Imaging and Infrared Fiber Optic Probe Spectroscopy Identify Collagen Type in Connective Tissues

    PubMed Central

    Hanifi, Arash; McCarthy, Helen; Roberts, Sally; Pleshko, Nancy

    2013-01-01

    Hyaline cartilage and mechanically inferior fibrocartilage consisting of mixed collagen types are frequently found together in repairing articular cartilage. The present study seeks to develop methodology to identify collagen type and other tissue components using Fourier transform infrared (FTIR) spectral evaluation of matrix composition in combination with multivariate analyses. FTIR spectra of the primary molecular components of repair cartilage, types I and II collagen, and aggrecan, were used to develop multivariate spectral models for discrimination of the matrix components of the tissues of interest. Infrared imaging data were collected from bovine bone, tendon, normal cartilage, meniscus and human repair cartilage tissues, and composition predicted using partial least squares analyses. Histology and immunohistochemistry results were used as standards for validation. Infrared fiber optic probe spectral data were also obtained from meniscus (a tissue with mixed collagen types) to evaluate the potential of this method for identification of collagen type in a minimally-invasive clinical application. Concentration profiles of the tissue components obtained from multivariate analysis were in excellent agreement with histology and immunohistochemistry results. Bone and tendon showed a uniform distribution of predominantly type I collagen through the tissue. Normal cartilage showed a distribution of type II collagen and proteoglycan similar to the known composition, while in repair cartilage, the spectral distribution of both types I and II collagen were similar to that observed via immunohistochemistry. Using the probe, the outer and inner regions of the meniscus were shown to be primarily composed of type I and II collagen, respectively, in accordance with immunohistochemistry data. In summary, multivariate analysis of infrared spectra can indeed be used to differentiate collagen type I and type II, even in the presence of proteoglycan, in connective tissues, using both imaging and fiber optic methodology. This has great potential for clinical in situ applications for monitoring tissue repair. PMID:23717662

  14. The Effect of Connective Tissue Material Uncertainties on Knee Joint Mechanics under Isolated Loading Conditions

    PubMed Central

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

    2012-01-01

    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 patellofemoral degrees of freedom. Seven primary connective tissues modeled as nonlinear 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 were 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, as well as provide insight on those uncertainties that may not be as relative to a given response. PMID:20810114

  15. Tbx4 and Tbx5 acting in connective tissue are required for limb muscle and tendon patterning

    PubMed Central

    Hasson, Peleg; DeLaurier, April; Bennett, Michael; Grigorieva, Elena; Naiche, L. A.; Papaioannou, Virginia E.; Mohun, Timothy J.; Logan, Malcolm P.O.

    2010-01-01

    Summary Proper functioning of the musculo-skeletal system requires the precise integration of bones, muscles and tendons. Complex morphogenetic events ensure that these elements are linked together in the appropriate 3D configuration. It has been difficult, however, to tease apart the mechanisms that regulate tissue morphogenesis. We find that deletion of Tbx5 in forelimb (or Tbx4 in hindlimbs) specifically affects muscle and tendon patterning without disrupting skeletal development thus suggesting that distinct cues regulate these processes. We identify muscle connective tissue as the site of action of these transcription factors and show that N-Cadherin and ?-Catenin are key downstream effectors acting in muscle connective tissue regulating soft-tissue morphogenesis. In humans, TBX5 mutations lead to Holt-Oram syndrome, which is characterised by forelimb musculo-skeletal defects. Our results suggest that a focus on connective tissue is required to understand the aetiology of diseases affecting soft tissue formation. PMID:20152185

  16. Autoimmune Retinopathy

    PubMed Central

    Grange, Landon; Dalal, Monica; Nussenblatt, Robert B.; Sen, H. Nida

    2013-01-01

    Purpose To provide a detailed review of current clinical guidelines for the diagnosis, work-up and treatment of autoimmune retinopathy, and briefly preview possible future therapies. Design Perspective based on literature review and clinical expertise. Methods Interpretation of current literature, relying on the authors’ clinical experience. Results Autoimmune retinopathy is a rare immunologic disease characterized by the presence of circulating anti-retinal antibodies along with electroretinographic (ERG) and visual field abnormalities. Ophthalmic exam can be normal or show minimal findings. The diagnosis of autoimmune retinopathy is made difficult by diagnostic criteria which are both limited and non-standardized. Currently, the diagnosis is made based on the demonstration of serum antiretinal antibodies and the presence of clinical manifestations (including abnormal ERGs). The mere presence of these antibodies is not diagnostic. Lack of an accepted gold standard for antiretinal antibodies detection and poor inter-laboratory concordance makes the diagnosis challenging. There are anecdotal reports on immunosuppressive therapy in autoimmune retinopathy; however, the response to treatment is variable, with more favorable results achieved in paraneoplastic retinopathy, particularly cancer-associated retinopathy, with a combination of chemotherapy and immunosuppression. Whether an earlier attempt to treat non-paraneoplastic autoimmune retinopathy would be more beneficial is unknown. Early treatment attempts are limited by lack of sensitive and specific assays and definitive clinical criteria. Conclusions Little is known about the clinical course, prognosis and treatment of autoimmune retinopathy. Additional studies should examine the specificity and pathogenicity of antiretinal antibodies, screen for biomarkers, and should be conducted concurrently with studies seeking to identify appropriate treatment. PMID:24315290

  17. Multimodal and Multi-tissue Measures of Connectivity Revealed by Joint Independent Component Analysis

    PubMed Central

    Ling, Josef; Caprihan, Arvind; Calhoun, Vince D.; Jung, Rex E.; Heileman, Gregory L.

    2009-01-01

    The human brain functions as an efficient system where signals arising from gray matter are transported via white matter tracts to other regions of the brain to facilitate human behavior. However, with a few exceptions, functional and structural neuroimaging data are typically optimized to maximize the quantification of signals arising from a single source. For example, functional magnetic resonance imaging (FMRI) is typically used as an index of gray matter functioning whereas diffusion tensor imaging (DTI) is typically used to determine white matter properties. While it is likely that these signals arising from different tissue sources contain complementary information, the signal processing algorithms necessary for the fusion of neuroimaging data across imaging modalities are still in a nascent stage. In the current paper we present a data-driven method for combining measures of functional connectivity arising from gray matter sources (FMRI resting state data) with different measures of white matter connectivity (DTI). Specifically, a joint independent component analysis (J-ICA) was used to combine these measures of functional connectivity following intensive signal processing and feature extraction within each of the individual modalities. Our results indicate that one of the most predominantly used measures of functional connectivity (activity in the default mode network) is highly dependent on the integrity of white matter connections between the two hemispheres (corpus callosum) and within the cingulate bundles. Importantly, the discovery of this complex relationship of connectivity was entirely facilitated by the signal processing and fusion techniques presented herein and could not have been revealed through separate analyses of both data types as is typically performed in the majority of neuroimaging experiments. We conclude by discussing future applications of this technique to other areas of neuroimaging and examining potential limitations of the methods. PMID:19777078

  18. Use of growth factors and adhesive ligands to promote connective tissue progenitor colony formation from fresh marrow

    E-print Network

    Marcantonio, Nicholas A. (Nicholas Alexander)

    2008-01-01

    The current gold standard for bone graft material is autologous bone, which provides mechanical support, possesses factors that promote bone formation, and contains connective tissue progenitors (CTPs), a heterogeneous ...

  19. Connections

    MedlinePLUS

    ... Press Releases News Archives FCA Blog Contact Us Frequently Asked Questions Professional Inquiry Form Publication Order Form - A A + A You are here Home » Caregiver Connect Connections Newsletter Printer-friendly version FCA's Connections newsletter focuses on issues and information ...

  20. Connective Tissue Fibroblast Properties Are Position-Dependent during Mouse Digit Tip Regeneration

    PubMed Central

    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 cells that are associated with their regenerative capabilities. PMID:23349966

  1. Local delivery of nitric oxide: targeted delivery of therapeutics to bone and connective tissues

    PubMed Central

    Nichols, Scott P.; Storm, Wesley L.; Koh, Ahyeon; Schoenfisch, Mark H.

    2012-01-01

    Non-invasive treatment of injuries and disorders affecting bones and connective tissue is a significant challenge facing the medical community. A treatment route that has recently been proposed is nitric oxide (NO) therapy. Nitric oxide plays several roles in physiology with many conditions lacking adequate levels of NO. As NO is a radical, localized delivery via NO donors is essential to promoting biological activity. Herein, we review current literature related to therapeutic NO delivery in the treatment of bone, skin and tendon repair. PMID:22433782

  2. Detection of human and murine common idiotypes of DNA antibodies in tissues and sera of patients with autoimmune diseases.

    PubMed

    Watts, R A; Ravirajan, C T; Wilkinson, L S; Williams, W; Griffiths, M; Butcher, D; Horsfall, A T; Staines, N A; Isenberg, D A

    1991-02-01

    The expression in tissue and serum of a panel of murine and human common DNA antibody idiotypes (Ids) (BEG 2, PR 4, F-423, I-402, II-28, IV-228, V-88) has been investigated. The murine V-88 Id was detected in eight out of 10 and the human BEG 2 Id in five out of 10 labial biopsies from patients with Sjögren's syndrome. The murine F-423, I-402 and IV-228 Ids were identified in one out of 10 biopsies. In each case the pattern of staining was similar with staining of the acinar basement membrane and a cell population. Using double-labelling immunohistochemistry this cell population were identified as plasma cells. No staining was seen in four normal labial biopsies. The V-88 Id was detected on the epithelial aspect of the thickened basement membrane in three out of nine renal biopsies from patients with systemic lupus erythematosus (SLE). None of the other Ids (BEG 2, PR4, IV-228, F-423 or I-402) could be detected in renal tissue. None of the Ids were found in skin biopsies from SLE patients. Id V-88 may, like the 16/6 Id to which it is phenotypically related, play a role in the pathogenesis of renal lesions in SLE. The BEG 2 Id could be detected in the serum of patients with rheumatoid arthritis (RA) and active untreated tuberculosis. Ids II-28, V-88 and I-402 were elevated in serum from patients with Sjögren's syndrome and II-28 Id in serum from patients with myositis and RA. None of the Ids were elevated in serum from patients with SLE. Apart from the BEG 2 Id, none of the Ids were elevated in serum from patients with tuberculosis or Gram-negative infections. The presence of murine Ids in human tissue and serum suggests that they are cross-species idiotypes and have been conserved through evolution. PMID:1993360

  3. Genome-Wide Transcriptional Profiling Reveals Connective Tissue Mast Cell Accumulation in Bronchopulmonary Dysplasia

    PubMed Central

    Bhattacharya, Soumyaroop; Go, Diana; Krenitsky, Daria L.; Huyck, Heidi L.; Solleti, Siva Kumar; Lunger, Valerie A.; Metlay, Leon; Srisuma, Sorachai; Wert, Susan E.; Pryhuber, Gloria S.

    2012-01-01

    Rationale: Bronchopulmonary dysplasia (BPD) is a major complication of premature birth. Risk factors for BPD are complex and include prenatal infection and O2 toxicity. BPD pathology is equally complex and characterized by inflammation and dysmorphic airspaces and vasculature. Due to the limited availability of clinical samples, an understanding of the molecular pathogenesis of this disease and its causal mechanisms and associated biomarkers is limited. Objectives: Apply genome-wide expression profiling to define pathways affected in BPD lungs. Methods: Lung tissue was obtained at autopsy from 11 BPD cases and 17 age-matched control subjects without BPD. RNA isolated from these tissue samples was interrogated using microarrays. Standard gene selection and pathway analysis methods were applied to the data set. Abnormal expression patterns were validated by quantitative reverse transcriptase–polymerase chain reaction and immunohistochemistry. Measurements and Main Results: We identified 159 genes differentially expressed in BPD tissues. Pathway analysis indicated previously appreciated (e.g., DNA damage regulation of cell cycle) as well as novel (e.g., B-cell development) biological functions were affected. Three of the five most highly induced genes were mast cell (MC)-specific markers. We confirmed an increased accumulation of connective tissue MCTC (chymase expressing) mast cells in BPD tissues. Increased expression of MCTC markers was also demonstrated in an animal model of BPD-like pathology. Conclusions: We present a unique genome-wide expression data set from human BPD lung tissue. Our data provide information on gene expression patterns associated with BPD and facilitated the discovery that MCTC accumulation is a prominent feature of this disease. These observations have significant clinical and mechanistic implications. PMID:22723293

  4. Cytosolic aconitase activity sustains adipogenic capacity of adipose tissue connecting iron metabolism and adipogenesis.

    PubMed

    Moreno, María; Ortega, Francisco; Xifra, Gemma; Ricart, Wifredo; Fernández-Real, José Manuel; Moreno-Navarrete, José María

    2015-04-01

    To gain insight into the regulation of intracellular iron homeostasis in adipose tissue, we investigated the role of iron regulatory protein 1/cytosolic aconitase 1 (ACO1). ACO1 gene expression and activity increased in parallel to expression of adipogenic genes during differentiation of both murine 3T3-L1 cells and human preadipocytes. Lentiviral knockdown (KD) of Aco1 in 3T3-L1 preadipocytes led to diminished cytosolic aconitase activity and isocitrate dehydrogenase 1 (NADP(+)), soluble (Idh1) mRNA levels, decreased intracellular NADPH:NADP ratio, and impaired adipogenesis during adipocyte differentiation. In addition, Aco1 KD in fully differentiated 3T3-L1 adipocytes decreased lipogenic, Idh1, Adipoq, and Glut4 gene expression. A bidirectional cross-talk was found between intracellular iron levels and ACO1 gene expression and protein activity. Although iron in excess, known to increase reactive oxygen species production, and iron depletion both resulted in decreased ACO1 mRNA levels and activity, Aco1 KD led to reduced gene expression of transferrin receptor (Tfrc) and transferrin, disrupting intracellular iron uptake. In agreement with these findings, in 2 human independent cohorts (n = 85 and n = 38), ACO1 gene expression was positively associated with adipogenic markers in subcutaneous and visceral adipose tissue. ACO1 gene expression was also positively associated with the gene expression of TFRC while negatively linked to ferroportin (solute carrier family 40 (iron-regulated transporter), member 1) mRNA levels. Altogether, these results suggest that ACO1 activity is required for the normal adipogenic capacity of adipose tissue by connecting iron, energy metabolism, and adipogenesis.-Moreno, M., Ortega, F., Xifra, G., Ricart, W., Fernández-Real, J. M., Moreno-Navarrete, J. M. Cytosolic aconitase activity sustains adipogenic capacity of adipose tissue connecting iron metabolism and adipogenesis. PMID:25550467

  5. Calcium salts deposition in rat connective tissue after the implantation of calcium hydroxide-containing sealers.

    PubMed

    Holland, Roberto; de Souza, Valdir; Nery, Mauro Juvenal; Bernabé, o Felicio Estrada; Filho, José Arlindo Otoboni; Junior, Eloi Dezan; Murata, Sueli Satomi

    2002-03-01

    This study was conducted to observe the rat subcutaneous connective tissue reaction to implanted dentin tubes that were filled with mineral trioxide aggregate, Sealapex, Calciobiotic Root Canal Sealer (CRCS), Sealer 26, and the experimental material, Sealer Plus. The animals were sacrificed after 7 and 30 days, and the specimens were prepared for histological analysis after serial sections with a hard-tissue microtome. The undecalcified sections were examined with polarized light after staining according to the Von Kossa technique for calcium. At the tube openings, there were Von Kossa-positive granules that were birefringent to polarized light. Next to these granulations, there was irregular tissue, like a bridge, that was Von Kossa-positive. The dentin walls of the tubes exhibited a structure highly birefringent to polarized light, usually like a layer, in the tubules. These results were observed with all the studied materials, except the CRCS, which didn't exhibit any kind of mineralized structure. The results suggest that among the materials studied, the CRCS could have the least possibility of encouraging hard tissue deposition. PMID:12017174

  6. Pulmonary veno-occlusive disease: the bęte noire of pulmonary hypertension in connective tissue diseases?

    PubMed

    O'Callaghan, Dermot S; Dorfmuller, Peter; Jaďs, Xavier; Mouthon, Luc; Sitbon, Olivier; Simonneau, Gérald; Humbert, Marc; Montani, David

    2011-01-01

    Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension that may develop in patients with connective tissue diseases (CTD). Most cases have been reported in patients with systemic sclerosis, though associations with systemic lupus erythematosis and mixed connective tissue disease have also been described. PVOD is characterised by progressive obstruction of small pulmonary veins and venules that leads to increased pulmonary vascular resistance, right heart failure and premature death. Distinguishing PVOD from pulmonary arterial hypertension (PAH) is often difficult, though use of a diagnostic algorithm may improve diagnostic accuracy and preclude recourse to lung biopsy. The finding of normal left-heart filling pressures in the context of radiological studies suggestive of pulmonary oedema is an important diagnostic clue, particularly if this clinical scenario coincides with the introduction of vasodilator therapy. There are no approved treatments for the disorder, though cautious use of PAH specific therapy may improve short-term outcomes in selected idiopathic PVOD cases. This review summarises the epidemiologic, clinico-pathologic and imaging characteristics of PVOD in the setting of CTD and discusses potential management approaches. PMID:21211937

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

    PubMed Central

    Pereira, Marcelo G.; Silva, Meiricris T.; Carlassara, Eduardo O. C.; Gonçalves, Dawit A.; Abrahamsohn, Paulo A.; Kettelhut, Isis C.; Moriscot, Anselmo S.; Aoki, Marcelo S.; Miyabara, Elen H.

    2014-01-01

    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-? receptor type I (T?R-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 T?R-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. PMID:25268835

  8. Clinical outcome and changes in connective tissue metabolism after intravaginal slingplasty in stress incontinent women.

    PubMed

    Falconer, C; Ekman-Ordeberg, G; Malmström, A; Ulmsten, U

    1996-01-01

    The intravaginal slingplasty procedure (IVS) was carried out on 75 patients with genuine stress urinary incontinence. The main aims of the operation are to create an artificial pubourethral ligament and to tighten the suburethral vaginal wall. An important ingredient in the supportive structures of the genitourinary region is fibrous connective tissue, consisting mainly of collagen. To analyse this component biopsies were obtained transvaginally, close to the position of the sling, both preoperatively and 2 years after surgery, from 6 patients. Collagen was analysed for concentration and extractability. Extractability by pepsin digestion was increased by 60% 2 years following surgery. Postoperative follow-up studies from 12 months to 3 years showed complete restoration of continence in 63 patients (84%) and considerable improvement in 4 others (5%). The 8 failures (9%) were all related to early rejection of the sling. The IVS procedure is an attractive surgical procedure as it necessitates minimum invasion and can be performed under local anesthesia, with a short hospital stay and sick-leave period. The enhanced collagen extractability indicates a changed metabolism, most likely induced by the implanted sling, resulting in a restoration of the elastic properties of the connective tissue. PMID:8913830

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

    PubMed

    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. PMID:3372758

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

    SciTech Connect

    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.

  11. 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)

    PubMed Central

    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 (PD), clinical attachment level (CAL), attached gingiva (AG), residual probing depth (RPD) and % of Root coverage(%RC). Measurements were taken at baseline, three months and six months. A standard surgical procedure was used for both Group A and Group B. Data were recorded and statistical analysis was done for both intergroup and intragroup. Results: At end of six months % RC obtained were 84.47% (Group A) and 81.67% (Group B). Both treatments resulted in statistically significant improvement in clinical parameters. When compared, no statistically significant difference was found between both groups except in RPD, where it was significantly greater in Group A. Conclusions: GTR technique has advantages over subepithelial connective tissue graft for shallow Miller’s Class I defects and this procedure can be used to avoid patient discomfort and reduce treatment time. Key words:Collagen membrane, comparative split mouth study, gingival recession, subepithelial connective tissue graft, guided tissue regeneration (GTR). PMID:25136420

  12. The dorsomedian connective tissue band in the lumbar epidural space of humans: an anatomical study using epiduroscopy in autopsy cases.

    PubMed

    Blomberg, R

    1986-07-01

    An anatomical study of the lumbar epidural space in 48 autopsy subjects was made using a method of endoscopy developed by the author called epiduroscopy. In every case there was a dorsal connective tissue band in the midline of the epidural space between the dura mater and the flaval ligaments. The appearance of the band varied from strands of connective tissue to a complete membrane. This connection fixed the dura mater to the flaval ligaments and also narrowed the epidural space in the midline. PMID:3717614

  13. Autoimmune response in experimental hippocampal pathology

    Microsoft Academic Search

    A. V. Martynenko; S. V. Magaeva; L. A. Basharova; M. V. Martynenko

    1986-01-01

    Previous investigations have shown that in pathology of the main part of the limbic system of the brain, autoimmune responses to brain tissue antigens (TA) are induced [2]. The aim of this investigation was to study the possibility of synthesis of autoantibodies to NA and 5-HT and autoimmune responses to antigens of the hippocampus and viscera. EXPERIMENTAL METHOD Experiments were

  14. Tissue types (image)

    MedlinePLUS

    There are 4 basic types of tissue: connective tissue, epithelial tissue, muscle tissue, and nervous tissue. Connective tissue supports other tissues and binds them together (bone, blood, and lymph tissues). Epithelial tissue ...

  15. [Autoimmune thyroid disease--clinical symptoms of associated autoimmunity].

    PubMed

    Djurica, Snezana; Trbojevi?, Bozo; Milosevi?, Dragoslav P; Markovi?, Natasa

    2005-10-01

    Autoimmune diseases are manifested in a broad spectrum. Classic examples of organ-specific autoimmune disease include Addison's disease, insulin-dependent type-1 Diabetes mellitus, Grave's disease (MGB), and Hashimoto thyroiditis (HT). The initial report of this autoimmune thyroid disease (AITD) dates back to Hakira Hashimoto (1912). In HT, as an organ-specific autoimmune disease, massive infiltration of lymphoid cells and parenchyma destruction are a consistent feature. The infiltration appears to be immune-mediated, primarily lymphocytic (T helper, T suppressor cells), NK cells and B cells. The pathological characteristics of AITD include development of the goitre (atrophic form is not so frequent), impaired thyroid gland function (from hyperthyroidism to subclinical and manifested hypothyroidism) and the formation of antithyroidal antibodies against thyroglobulin (AbTg) and the microsomal antigen (Ab TPO). There is a very good correlation between the antibodies against TPO and the histological findings. Morbus Graves Basedow is characterized by autoimmune hyperthyroidism with goitre, and infiltrative orbitopathy. Autoantibodies against the TSH-receptor molecule on the plasma membrane of the thyroid gland follicles cause a nonphysiological activation and an increase of the cellular function. Besides this hyperthyroidal condition, an autoimmune attack against the retrobulbar tissue leading to endocrine orbitopathy, can be noted in about 40% of patients suffering from MGB. PMID:16405252

  16. Autoimmune liver disease panel

    MedlinePLUS

    Liver disease test panel - autoimmune ... Autoimmune disorders are a possible cause of liver disease. The most common of these diseases are autoimmune hepatitis and primary biliary cirrhosis. This group of tests helps your health care provider ...

  17. Plasmapheresis and Autoimmune Disease

    MedlinePLUS

    ... the booklet in this Web page . Plasmapheresis and Autoimmune Disease Many diseases, including myasthenia gravis, Lambert-Eaton ... and others, are caused by a so-called autoimmune, or self-immune, process. In autoimmune conditions, the ...

  18. Pulmonary hypoplasia in the connective tissue growth factor (Ctgf) null mouse.

    PubMed

    Baguma-Nibasheka, Mark; Kablar, Boris

    2008-02-01

    Connective tissue growth factor (CTGF) is a mediator of growth factor activity, and Ctgf knockouts die at birth from respiratory failure due to skeletal dysplasia. Previous microarray analysis revealed Ctgf down-regulation in the hypoplastic lungs of amyogenic mouse embryos. This study, therefore, examined pulmonary development in Ctgf-/- mouse fetuses to investigate if respiration could also have been impaired by lung abnormalities. The Ctgf-/- lungs were hypoplastic, with reduced cell proliferation and increased apoptosis. PDGF-B, its receptor and IGF-I, were markedly attenuated and the TTF-1 gradient lost. Type II pneumocyte differentiation was perturbed, the cells depicting excessive glycogen retention and diminished lamellar body and nuclear size, though able to synthesize surfactant-associated protein. However, type I pneumocyte differentiation was not affected by Ctgf deletion. Our findings indicate that the absence of Ctgf and/or its protein product, CTGF, may induce pulmonary hypoplasia by both disrupting basic lung developmental processes and restricting thoracic expansion. PMID:18213577

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

    PubMed Central

    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

    2014-01-01

    Summary 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. PMID:25343123

  20. Exome analysis of connective tissue dysplasia: death and rebirth of clinical genetics?

    PubMed

    Wilson, Golder N

    2014-05-01

    Exome results are reported for two patients with connective tissue dysplasia, one refining a clinical diagnosis of Ehlers-Danlos to Marfan syndrome, the other suggesting arthrogryposis derived from maternofetal Stickler syndrome. Patient 1 had mutations in transthyretin (TTR), fibrillin (FBN1), and a calcium channel (CACNA1A) gene suggesting diagnoses of transthyretin amyloidosis, Marfan syndrome, and familial hemiplegic migraines, respectively. Patient 2 presented with arthrogryposis that was correlated with his mother's habitus and arthritis once COL2A1 mutations suggestive of Stickler syndrome were defined. Although DNA results often defy prediction by the best of clinicians, these patients illustrate needs for ongoing clinical scholarship (e.g., to delineate guidelines for management of mutations like that for hyperekplexia in Patient 2) and for interpretation of polygenic change that is optimized by clinical genetic/syndromology experience (e.g., suggesting acetazolamide therapy for Patient 1 and explaining arthrogryposis in Patient 2). PMID:24664531

  1. CCN2: a mechanosignaling sensor modulating integrin-dependent connective tissue remodeling in fibroblasts?

    PubMed

    Leask, Andrew

    2013-08-01

    Tensegrity (tensional integrity) is an emerging concept governing the structure of the body. Integrin-mediated mechanical tension is essential for connective tissue function in vivo. For example, in adult skin fibroblasts, the integrin ?1 subunit mediates adhesion to collagen and fibronectin. Moreover, integrin ?1, through its abilities to activate latent TGF?1 and promote collagen production through focal adhesion kinase/rac1/nicotinamide adenine dinucleotide phosphate oxidase (NOX)/reactive oxygen species (ROS), is essential for dermal homeostasis, repair and fibrosis. The integrin ?1-interacting protein CCN2, a member of the CCN family of proteins, is induced by TGF?1; yet, CCN2 is not a simple downstream mediator of TGF?1, but instead synergistically promote TGF?1-induced adhesive signaling and fibrosis. Due to its selective ability to sense mechanical forces in the microenvironment, CCN2 may represent an exquisitely precise target for therapeutic intervention. PMID:23729366

  2. AntiInterferon Autoantibodies in Autoimmune Polyendocrinopathy Syndrome Type 1

    Microsoft Academic Search

    Anthony Meager; Kumuthini Visvalingam; Pärt Peterson; Kaidi Möll; Astrid Murumägi; Kai Krohn; Petra Eskelin; Jaakko Perheentupa; Eystein Husebye; Yoshihisa Kadota; Nick Willcox

    2006-01-01

    BackgroundThe autoimmune regulator (AIRE) gene influences thymic self-tolerance induction. In autoimmune polyendocrinopathy syndrome type 1 (APS1; OMIM 240300), recessive AIRE mutations lead to autoimmunity targetting endocrine and other epithelial tissues, although chronic candidiasis usually appears first. Autoimmunity and chronic candidiasis can associate with thymomas as well. Patients with these tumours frequently also have high titre immunoglobulin G autoantibodies neutralising type

  3. Autoimmune Epilepsy

    PubMed Central

    Quek, Amy M. L.; Britton, Jeffrey W.; McKeon, Andrew; So, Elson; Lennon, Vanda A.; Shin, Cheolsu; Klein, Christopher J.; Watson, Robert E.; Kotsenas, Amy L.; Lagerlund, Terrence D.; Cascino, Gregory D.; Worrell, Gregory A.; Wirrell, Elaine C.; Nickels, Katherine C.; Aksamit, Allen J.; Noe, Katherine H.; Pittock, Sean J.

    2013-01-01

    Objective To describe clinical characteristics and immunotherapy responses in patients with autoimmune epilepsy. Design Observational, retrospective case series. Setting Mayo Clinic Health System. Patients Thirty-two patients with an exclusive (n=11) or predominant (n = 21) seizure presentation in whom an autoimmune etiology was suspected (on the basis of neural autoantibody [91%], inflammatory cerebrospinal fluid [31%], or magnetic resonance imaging suggesting inflammation [63%]) were studied. All had partial seizures: 81% had failed treatment with 2 or more anti-epileptic drugs and had daily seizures and 38% had seizure semiologies that were multifocal or changed with time. Head magnetic resonance imaging was normal in 15 (47%) at onset. Electroencephalogram abnormalities included interictal epileptiform discharges in 20; electrographic seizures in 15; and focal slowing in 13. Neural autoantibodies included voltage-gated potassium channel complex in 56% (leucine-rich, glioma-inactivated 1 specific, 14; contactin-associated proteinlike 2 specific, 1); glutamic acid decarboxylase 65 in 22%; collapsin response-mediator protein 5 in 6%; and Ma2, N-methyl-D-aspartate receptor, and ganglionic acetylcholine receptor in 1 patient each. Intervention Immunotherapy with intravenous methylprednisolone; intravenous immune globulin; and combinations of intravenous methylprednisolone, intravenous immune globulin, plasmapheresis, or cyclo-phosphamide. Main Outcome Measure Seizure frequency. Results After a median interval of 17 months (range, 3–72 months), 22 of 27 (81%) reported improvement postimmunotherapy; 18 were seizure free. The median time from seizure onset to initiating immunotherapy was 4 months for responders and 22 months for nonresponders (P<.05). All voltage-gated potassium channel complex antibody–positive patients reported initial or lasting benefit (P<.05). One voltage-gated potassium channel complex antibody–positive patient was seizure free after thyroid cancer resection; another responded to antiepileptic drug change alone. Conclusion When clinical and serological clues suggest an autoimmune basis for medically intractable epilepsy, early-initiated immunotherapy may improve seizure outcome. PMID:22451162

  4. Cold acclimation alters the connective tissue content of the zebrafish (Danio rerio) heart.

    PubMed

    Johnson, Amy C; Turko, Andy J; Klaiman, Jordan M; Johnston, Elizabeth F; Gillis, Todd E

    2014-06-01

    Thermal acclimation can alter cardiac function and morphology in a number of fish species, but little is known about the regulation of these changes. The purpose of the present study was to determine how cold acclimation affects zebrafish (Danio rerio) cardiac morphology, collagen composition and connective tissue regulation. Heart volume, the thickness of the compact myocardium, collagen content and collagen fiber composition were compared between control (27°C) and cold-acclimated (20°C) zebrafish using serially sectioned hearts stained with Picrosirius Red. Collagen content and fiber composition of the pericardial membrane were also examined. Cold acclimation did not affect the volume of the contracted heart; however, there was a significant decrease in the thickness of the compact myocardium. There was also a decrease in the collagen content of the compact myocardium and in the amount of thick collagen fibers throughout the heart. Cold-acclimated zebrafish also increased expression of the gene transcript for matrix metalloproteinase 2, matrix metalloproteinase 9, tissue inhibitor of metalloproteinase 2 and collagen Type I ?1. We propose that the reduction in the thickness of the compact myocardium as well as the change in collagen content may help to maintain the compliance of the ventricle as temperatures decrease. Together, these results clearly demonstrate that the zebrafish heart undergoes significant remodeling in response to cold acclimation. PMID:24577447

  5. Hyaluronan as a novel marker for rapid selection of connective tissue progenitors.

    PubMed

    Caralla, Tonya; Boehm, Cynthia; Hascall, Vincent; Muschler, George

    2012-12-01

    Connective Tissue Progenitors (CTPs) in bone and marrow tissue are an important therapeutic target for bone regeneration. Concentration and selection of CTPs from the heterogenous population of cells in bone marrow remains a challenge due to their low prevalence. This study identifies surface-bound hyaluronan (HA), a component of the in vivo niche for CTPs, and evaluates HA as a useful surface marker for positive selection of CTPs. Mononuclear cells from bone marrow were labeled and magnetically separated on the basis of hyaluronan binding. HA(+++), HA(+) and HA(-) fractions were cultured and assayed for colony formation using a quantitative image-processing system. A mean of 2.7% of cells were retained in the HA(+++) fraction and were enriched by 3.4-fold (range of 95% CI: 2.3-4.8) in CTP prevalence when compared to the unselected buffy-coated bone marrow aspirate (BCM). In addition, colonies formed by HA(+++) CTPs demonstrated greater proliferation (more cells per colony) and greater alkaline phosphatase activity than CTP colonies derived from unselected BCM. These data demonstrate that one or more subsets of human marrow-derived CTPs retain a HA rich matrix on their surface at the time of harvest. HA(+++) CTPs may offer a useful cell population for regenerative therapies. PMID:22699817

  6. The effect of tenotomy and immobilisation on intramuscular connective tissue. A morphometric and microscopic study in rat calf muscles.

    PubMed

    Józsa, L; Kannus, P; Thöring, J; Reffy, A; Järvinen, M; Kvist, M

    1990-03-01

    The effect of tenotomy and of immobilisation in lengthened and shortened positions on the intramuscular connective tissue of the calf muscles of the rat was studied morphometrically and with a scanning electron microscope. Both tenotomy and immobilisation produced a marked increase in both the endomysial and the perimysial collagen networks, with a simultaneous decrease in intramuscular capillary density. The increase in connective tissue volume was more pronounced and occurred more rapidly in the soleus, which consists mainly of type I, slow-twitch fibres than in the gastrocnemius, which is mainly of type II, fast-twitch fibres. The relative volume of connective tissue increased in parallel with the duration of immobilisation or after tenotomy. There was slightly more increase after immobilisation in a shortened rather than in a lengthened position. PMID:2312572

  7. Autoimmune thyroiditis: Centennial jubilee of a social disease and its comorbidity.

    PubMed

    Churilov, L P; Stroev, Yu I; Serdyuk, I Yu; Kaminova-Mudzhikova, O M; Belyaeva, I V; Gvozdetsky, A N; Nitsa, N A; Mikhailova, L R

    2014-06-01

    The history of autoimmune thyroiditis (AIT) and its role in pathophysiology of transition from adolescent hypothalamic syndrome (obesity with rose striae) into early metabolic syndrome is reviewed. Marfanoid phenotype and chronic disequilibrium between local, autacoid-mediated and systemic, hormone-mediated regulation, typical for inherited connective tissue disorders, may promote this transition. Pathogenetic roles of hyperprolactinemia and cytokine misbalance are evaluated and discussed in its pathogenesis. PMID:24274975

  8. Analysis of patient acceptance following treatment of Miller's class II gingival recession with acellular dermal matrix and connective tissue graft

    PubMed Central

    Goyal, Niti; Gupta, Rajan; Pandit, Nymphea; Dahiya, Parveen

    2014-01-01

    Objective: Obtaining predictable and aesthetic root coverage has become an important part of periodontal therapy. The search for the appropriate root coverage techniques has resulted in many different approaches. The goal of this study was to evaluate the degree of patient acceptance with acellular dermal matrix (ADM) allograft in the treatment of buccal gingival recession and to compare it with subepithelial connective tissue graft. Materials and Methods: Thirty patients with Miller's class II recessions were treated and randomly assigned to the test group (ADM) and control group (subepithelial connective tissue graft). All patients underwent full periodontal evaluation and pre-surgical preparation, including oral hygiene instructions and scaling and root planing. The exposed roots were thoroughly planed and covered by a graft without any further root treatment. Results were evaluated based on the parameters measuring patient satisfaction and clinical outcome after 6 months of the surgical procedure. Results: Postoperatively, significant root coverage, reduction in probing depth, gain in clinical attachment level, and increase in widths of keratinized tissue and attached gingiva were observed on intra-group comparison. There was no significant difference in any of the parameters between test and control groups. Conclusion: The subepithelial connective tissue graft and ADM graft were able to successfully treat gingival recession defects; however, the ADM showed better patient acceptance than the connective tissue graft. PMID:25024550

  9. Connectivity

    ERIC Educational Resources Information Center

    Grush, Mary, Ed.

    2006-01-01

    Connectivity has dramatically changed the landscape of higher education IT. From "on-demand" services for net-gen students and advanced eLearning systems for faculty, to high-performance computing grid resources for researchers, IT now provides more networked services than ever to connect campus constituents to each other and to the world.…

  10. Connective Tissue Growth Factor(CTGF, CCN2) – A Marker, Mediator and Therapeutic Target for Renal Fibrosis

    Microsoft Academic Search

    Mysore K. Phanish; S. K. Winn; M. E. C. Dockrell

    2010-01-01

    Connective tissue growth factor (CTGF, CCN2) is a key mediator of tissue fibrosis. CCN2 plays an important role in the development of glomerular and tubulointerstitial fibrosis in progressive kidney diseases. In this review, we discuss the biology of CCN2 with a focus on the regulation of CCN2 gene, cellular mechanisms of profibrotic CCN2 effects and the current in vivo and

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

    NASA Technical Reports Server (NTRS)

    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.

  12. Postulating a Role for Connective Tissue Elements in Inferior Oblique Muscle Overaction (An American Ophthalmological Society Thesis)

    PubMed Central

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

    2013-01-01

    Purpose: To compare the localization and density of collagens I, IV, VI, and elastin, the major protein components of connective tissue, in the inferior oblique muscle of patients with overelevation in adduction and in controls and to characterize changes that develop following surgery. Biomechanical studies suggest that the connective tissue matrix plays a critical role in extraocular muscle function, determining tensile strength and force transmission during contraction. Methods: Prospective laboratory-based case-control study of inferior oblique muscle specimens from 31 subjects: 16 with primary inferior oblique overaction, 6 with craniofacial dysostosis, and 9 normal controls. Collagen I, IV, VI, and elastin were localized and quantified using immunohistochemical staining. Densities were compared using analysis of variance and post hoc comparisons. Results: In primary inferior oblique overaction, all connective tissue components in unoperated specimens were elevated compared to controls (P<.0001). Previously operated muscles showed normal levels of collagens IV and VI (P>.27) but increased collagen I. In unoperated craniofacial dysostosis specimens, only elastin was elevated (P=.03), whereas density of collagens IV and VI was lower in previously operated vs unoperated specimens (P=.015). Conclusions: Elevated collagen and elastin levels in the cohort with primary inferior oblique overaction are consistent with the clinical finding of muscle stiffness. Contrarily, normal connective tissue densities in craniofacial dysostosis support the hypothesis that overelevation in this group reflects anomalous muscle vectors rather than tissue changes. Surgical intervention was associated with changes in the connective tissue matrix in both cohorts. These results have ramifications for treating patients with overelevation in adduction. PMID:24385670

  13. “Trophoblast islands of the chorionic connective tissue” (TICCT): A novel placental histologic feature

    PubMed Central

    Hong, J.-S.; Romero, R.; Kusanovic, J.P.; Kim, J.-S.; Lee, J.; Jin, M.; El Azzamy, H.; Lee, D.-C.; Topping, V.; Ahn, S.; Jacques, S.; Qureshi, F.; Chaiworapongsa, T.; Hassan, S.S.; Korzeniewski, S. J.; Than, N.G.; Kim, C.J.

    2013-01-01

    Introduction We found isolated or clustered trophoblasts in the chorionic connective tissue of the extraplacental membranes, and defined this novel histologic feature as the “trophoblast islands of the chorionic connective tissue” (TICCT). This study was conducted to determine the clinical significance of TICCT. Methods Immunohistochemistry for cytokeratin-7 was performed on the chorioamniotic membranes (N=2155) obtained from singleton pregnancies of 1199 uncomplicated term and 956 preterm deliveries. The study groups comprised 1236 African-American and 919 Hispanic women. Gestational age ranged from 24+0 weeks to 41+6 weeks. Multiple logistic regression analysis was performed to investigate the magnitude of association between patient characteristics and the presence of TICCT. Results The likelihood of TICCT was significantly associated with advancing gestational age both in term (OR: 1.29, 95% CI: 1.16–1.45, p<0.001) and preterm deliveries (OR: 1.19, 95% CI: 1.07–1.32, p=0.001). Hispanic women were less likely than African-American women to have TICCT across gestation in term (OR: 0.23, 95% CI: 0.18–0.31, p<0.001) and preterm pregnancies (OR: 0.41, 95% CI: 0.29–0.58, p<0.001). Women with a female fetus were significantly more likely to have TICCT than women with a male fetus, in both term (OR: 1.64, 95% CI: 1.28–2.11, p<0.001) and preterm gestations (OR: 2.04, 95% CI: 1.46–2.85, p<0.001). TICCT was 40% less frequent in the presence of chronic placental inflammation [term (OR: 0.60, 95% CI: 0.45–0.81, p=0.001) and preterm gestations (OR: 0.58, 95% CI: 0.40–0.84, p=0.003)] and in parous women at term (OR: 0.60, 95% CI: 0.44–0.81, p=0.001). Conclusions Our findings suggest that the duration of pregnancy, fetal sex, and parity may influence the behavior of extravillous trophoblast and placental mesenchymal cells. PMID:23453248

  14. The cytotoxic evaluation of mineral trioxide aggregate and bioaggregate in the subcutaneous connective tissue of rats

    PubMed Central

    Acar, Gözde; Yalcin, Yagmur; Dindar, Seckin; Sancakli, Hande; Erdemir, Ugur

    2013-01-01

    Objectives: The purpose of this study was to evaluate and compare the cytotoxic effects of ProRoot MTA and DiaRoot BA, a bioceramic nanoparticulate cement, on subcutaneous rat tissue. Study Design: Fifty Sprouge Dawley rats were used in this study. Polyethylene tubes filled with ProRoot MTA and DiaRoot BioAggregate, along with a control group of empty, were implanted into dorsal connective tissue of rats for 7, 15, 30, 60, and 90 days. After estimated time intervals the rats were sacrificed. The specimens were fixed, stained with hematoxylin and eosin, and then evaluated under a light microscope for inflammatory reactions and mineralization. Results: All groups evoked a severe to moderate chronic inflammatory reaction at 7 and 15 days, which decreased with time. Both the MTA and BioAggregate groups showed similar inflammatory reactions, except at 90 days when MTA showed statistically significant greater inflammation (p>0.05). The MTA group showed foreign body reaction at all times. Compared to BioAggregate, MTA showed significantly more foreign body reaction at 60 and 90 days (p<0.0001). After 30 days foreign body reaction of BioAggregate decreased significantly. Both MTA and BioAggregate groups showed similar necrosis at 7 and 15 days (p=0.094 and p=0.186 respectively). No necrosis was observed after 15 days. Similarly there was no fibrosis after 30 days for both MTA and BioAggregate groups (p>0.05). Conclusions: Since DiaRoot BioAggregate showed significantly better results than MTA, we can conclude that it is more biocompatible. However, further studies are required to confirm this result. Key words:Biocompatibility, mineral trioxide aggregate, bioAggregate. PMID:23722144

  15. Stress transfer in collagen fibrils reinforcing connective tissues: effects of collagen fibril slenderness and relative stiffness.

    PubMed

    Goh, Kheng Lim; Meakin, Judith R; Aspden, Richard M; Hukins, David W L

    2007-03-21

    Unlike engineering fibre composite materials which comprise of fibres that are uniform cylindrical in shape, collagen fibrils reinforcing the proteoglycan-rich (PG) gel in the extra-cellular matrices (ECMs) of connective tissues are taper-ended (paraboloidal in shape). In an earlier paper we have discussed how taper of a fibril leads to an axial stress up-take which differs from that of a uniform cylindrical fibre and implications for fibril fracture. The present paper focuses on the influence of fibre aspect ratio, q (slenderness), and Young's modulus (stiffness), relative to that of the gel phase, E(R), on the magnitude of the axial tensile stresses generated within a fibril and wider implications on failure at tissue level. Fibre composite models were evaluated using finite element (FE) and mathematical analyses. When the applied force is low, there is elastic stress transfer between the PG gel and a fibril. FE modelling shows that the stress in a fibril increases with E(R) and q. At higher applied forces, there is plastic stress transfer. Mathematical modelling predicts that the stress in a fibril increases linearly with q. For small q values, fibrils may be regarded as fillers with little ability to provide tensile reinforcement. Large q values lead to high stress in a fibril. Such high stresses are beneficial provided they do not exceed the fracture stress of collagen. Modulus difference regulates the strain energy release density, u, for interfacial rupture; large E(R) not only leads to high stress in a fibril but also insures against interfacial rupture by raising the value of u. PMID:17123548

  16. Investigating the association between polymorphisms in connective tissue growth factor and susceptibility to colon carcinoma

    PubMed Central

    AHMAD, ABRAR; ASKARI, SHLEAR; BEFEKADU, RAHEL; HAHN-STRÖMBERG, VICTORIA

    2015-01-01

    There have been numerous studies on the gene expression of connective tissue growth factor (CTGF) in colorectal cancer, however very few have investigated polymorphisms in this gene. The present study aimed to determine whether single nucleotide polymorphisms (SNPs) in the CTGF gene are associated with a higher susceptibility to colon cancer and/or an invasive tumor growth pattern. The CTGF gene was genotyped for seven SNPs (rs6918698, rs1931002, rs9493150, rs12526196, rs12527705, rs9399005 and rs12527379) by pyrosequencing. Formalin-fixed paraffin-embedded tissue samples (n=112) from patients diagnosed with colon carcinoma, and an equal number of blood samples from healthy controls, were selected for genomic DNA extraction. The complexity index was measured using images of tumor samples (n=64) stained for cytokeratin-8. The images were analyzed and correlated with the identified CTGF SNPs and clinicopathological parameters of the patients, including age, gender, tumor penetration, lymph node metastasis, systemic metastasis, differentiation and localization of tumor. It was demonstrated that the frequency of the SNP rs6918698 GG genotype was significantly associated (P=0.05) with an increased risk of colon cancer, as compared with the GC and CC genotypes. The other six SNPs (rs1931002, rs9493150, rs12526196, rs12527705, rs9399005 and rs12527379) exhibited no significant difference in the genotype and allele frequencies between patients diagnosed with colon carcinoma and the normal healthy population. A trend was observed between genotype variation at rs6918698 and the complexity index (P=0.052). The complexity index and genotypes for any of the studied SNPs were not significantly correlated with clinical or pathological parameters of the patients. These results indicate that the rs6918698 GG genotype is associated with an increased risk of developing colon carcinoma, and genetic variations at the rs6918698 are associated with the growth pattern of the tumor. The present results may facilitate the identification of potential biomarkers of the disease in addition to drug targets. PMID:25502877

  17. Investigating the association between polymorphisms in connective tissue growth factor and susceptibility to colon carcinoma.

    PubMed

    Ahmad, Abrar; Askari, Shlear; Befekadu, Rahel; Hahn-Strömberg, Victoria

    2015-04-01

    There have been numerous studies on the gene expression of connective tissue growth factor (CTGF) in colorectal cancer, however very few have investigated polymorphisms in this gene. The present study aimed to determine whether single nucleotide polymorphisms (SNPs) in the CTGF gene are associated with a higher susceptibility to colon cancer and/or an invasive tumor growth pattern. The CTGF gene was genotyped for seven SNPs (rs6918698, rs1931002, rs9493150, rs12526196, rs12527705, rs9399005 and rs12527379) by pyrosequencing. Formalin?fixed paraffin?embedded tissue samples (n=112) from patients diagnosed with colon carcinoma, and an equal number of blood samples from healthy controls, were selected for genomic DNA extraction. The complexity index was measured using images of tumor samples (n=64) stained for cytokeratin?8. The images were analyzed and correlated with the identified CTGF SNPs and clinicopathological parameters of the patients, including age, gender, tumor penetration, lymph node metastasis, systemic metastasis, differentiation and localization of tumor. It was demonstrated that the frequency of the SNP rs6918698 GG genotype was significantly associated (P=0.05) with an increased risk of colon cancer, as compared with the GC and CC genotypes. The other six SNPs (rs1931002, rs9493150, rs12526196, rs12527705, rs9399005 and rs12527379) exhibited no significant difference in the genotype and allele frequencies between patients diagnosed with colon carcinoma and the normal healthy population. A trend was observed between genotype variation at rs6918698 and the complexity index (P=0.052). The complexity index and genotypes for any of the studied SNPs were not significantly correlated with clinical or pathological parameters of the patients. These results indicate that the rs6918698 GG genotype is associated with an increased risk of developing colon carcinoma, and genetic variations at the rs6918698 are associated with the growth pattern of the tumor. The present results may facilitate the identification of potential biomarkers of the disease in addition to drug targets. PMID:25502877

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

    PubMed Central

    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

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

    PubMed Central

    Li, Qiaoli; Jiang, Qiujie; Uitto, Jouni

    2013-01-01

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

  20. Imaging the Effect of Acupuncture Needling On Human Connective Tissue in Vivo E.E. Konofagou1

    E-print Network

    Konofagou, Elisa E.

    Imaging the Effect of Acupuncture Needling On Human Connective Tissue in Vivo E.E. Konofagou1 , G, Burlington, VT, USA; E-mail: ek2191@columbia.edu Abstract - The therapeutic effects of acupuncture have been estimation techniques are used in order to understand the effect of acupuncture. It is expected

  1. The Kruppel-like factor KLF15 inhibits connective tissue growth factor (CTGF) expression in cardiac fibroblasts

    Microsoft Academic Search

    Baiqiu Wang; Saptarsi M. Haldar; Yuan Lu; Osama A. Ibrahim; Sudeshna Fisch; Susan Gray; Andrew Leask; Mukesh K. Jain

    2008-01-01

    Cardiac fibrosis is a hallmark feature of pathologic remodeling of the heart in response to hemodynamic or neurohormonal stress. Accumulating evidence implicates connective tissue growth factor (CTGF) as a key mediator of this process. Our group has previously identified Kruppel-Like Factor 15 (KLF15) as an important regulator of cardiac remodeling in response to stress; however, the role of this transcription

  2. Six1 is not involved in limb tendon development, but is expressed in limb connective tissue under Shh regulation

    Microsoft Academic Search

    Marie-Ange Bonnin; Christine Laclef; Régis Blaise; Sophie Eloy-Trinquet; Frédéric Relaix; Pascal Maire; Delphine Duprez

    2005-01-01

    Mice deficient for the homeobox gene Six1 display defects in limb muscles consistent with the Six1 expression in myogenic cells. In addition to its myogenic expression domain, Six1 has been described as being located in digit tendons and as being associated with connective tissue patterning in mouse limbs. With the aim of determining a possible involvement of Six1 in tendon

  3. Searching for Subtle Features of Laxity of Connective Tissue in Patients with Ruptured Intracranial Aneurysms: A Pilot Study

    Microsoft Academic Search

    Rob H. A. Wolswijk; Ynte M. Ruigrok; Gabriel J. E. Rinkel; Eva H. Brilstra; Raoul H. H. Engelbert

    2007-01-01

    Background: A disruption of the extracellular matrix (ECM) of the intracranial arterial wall is a likely contributing factor in the pathogenesis of intracranial aneurysms. If this is a generalized process, patients with subarachnoid haemorrhage (SAH) may have subtle signs of a general laxity of the connective tissue. We performed a pilot study to assess general laxity in SAH patients and

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

    PubMed

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

    2015-04-01

    Stimulation of endogenous ?-cell expansion could facilitate regeneration in patients with diabetes. In mice, connective tissue growth factor (CTGF) is expressed in embryonic ?-cells and in adult ?-cells during periods of expansion. We discovered that in embryos CTGF is necessary for ?-cell proliferation, and increased CTGF in ?-cells promotes proliferation of immature (MafA(-)) insulin-positive cells. CTGF overexpression, under nonstimulatory conditions, does not increase adult ?-cell proliferation. In this study, we tested the ability of CTGF to promote ?-cell proliferation and regeneration after partial ?-cell destruction. ?-Cell mass reaches 50% recovery after 4 weeks of CTGF treatment, primarily via increased ?-cell proliferation, which is enhanced as early as 2 days of treatment. CTGF treatment increases the number of immature ?-cells but promotes proliferation of both mature and immature ?-cells. A shortened ?-cell replication refractory period is also observed. CTGF treatment upregulates positive cell-cycle regulators and factors involved in ?-cell proliferation, including hepatocyte growth factor, serotonin synthesis, and integrin ?1. Ex vivo treatment of whole islets with recombinant human CTGF induces ?-cell replication and gene expression changes consistent with those observed in vivo, demonstrating that CTGF acts directly on islets to promote ?-cell replication. Thus, CTGF can induce replication of adult mouse ?-cells given a permissive microenvironment. PMID:25392241

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

    PubMed Central

    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

  6. [Possible applications bisoprolol for heart rate control in young patients with connective tissue dysplasia].

    PubMed

    Nechaeva, G I; Drokina, O V

    2014-01-01

    To assess the efficacy and safety of bisoprolol to monitor heart rate (HR) in young patients with connective tissue dysplasia (CTD) examined 58 patients (22,3 + 3,47 years, 38 men). Bisoprolol drug was administered at an initial dose of 1.25 mg/day, with a further increase to 2.5 mg/day in 2 weeks, etc. to achieve the level of heart rate 59-69 beats/min. Average effective dose was 7.27 ± 2.08 mg/day. Target heart rate,improvement of health and the pumping function of the heart, reducing the activation of the sympathetic nervous system and of anxiety achieved the absolute majority of patients. During treatment unit observed transient manifestations of general weakness, headache, episodes of vertigo in the selection of the dose, cases of bradycardia and hypotension pathological registered for the time of ingestion. Thus, the use of mandatory bisoprolol gradual careful titration, starting with 1.25 mg/day as a means to control the heart rate in young patients with CTD with sinus tachycardia, the manifestations of autonomic nervous system dysfunction, safely and effectively in relation to adverse orthostatic reactions. PMID:25177888

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

    PubMed

    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

  8. Connective Tissue Mineralization in Abcc6?/? Mice, a Model for Pseudoxanthoma Elasticum

    PubMed Central

    Kavukcuoglu, N. Beril; Li, Qiaoli; Pleshko, Nancy; Uitto, Jouni

    2012-01-01

    Pseudoxanthoma elasticum (PXE) is a heritable multisystem disorder characterized by ectopic mineralization. However, the structure of the mineral deposits, their interactions with the connective tissue matrix, and the details of the progressive maturation of the mineral crystals are currently unknown. In this study, we examined the mineralization processes in Abcc6?/? mice, a model system for PXE, by energy dispersive X-ray, and Fourier transform infrared imaging spectroscopy (FT-IRIS). The results indicated that the principal components of the mineral deposits were calcium and phosphate which co-localized within the histologically demonstrable lesions determined by topographic mapping. The Ca/P ratio increased in samples with progressive mineralization reaching the value comparable to that in endochondral bone. A progressive increase in mineralization was also reflected by increased mineral-to-matrix ratio determined by FT-IRIS. Determination of the mineral phases by FT-IRIS suggested progressive maturation of the mineral deposits from amorphous calcium phosphate to hydroxyapatite. These results provide critical information of the mechanisms of mineralization in PXE, with potential pharmacologic implications. PMID:22421595

  9. Japanese diagnostic criteria for mixed connective tissue disease in Caucasian patients.

    PubMed

    Doria, A; Ghirardello, A; de Zambiasi, P; Ruffatti, A; Gambari, P F

    1992-02-01

    Preliminary Japanese diagnostic criteria for the classification of mixed connective tissue disease (MCTD) were tested in a group of 32 Caucasian patients with this disease. Many clinical and laboratory similarities were found between Caucasian and Japanese patients. However, polyarthritis was more frequent in the Caucasians, while finger and hand swelling, DLCO reduction and muscle involvement were more frequent in the Japanese. In Caucasians the sensitivity of this criteria set was 87%, very similar to that found in the Japanese group (88%), and the specificity was 94%, higher than that of Japanese (87%). The difference resulted from the higher specificity of anti-nRNP antibody positivity in the Caucasian patients, probably due to the use of counterimmunoelectrophoresis in the detection of this antibody. The Japanese criteria seem more useful than others because they allow the use of techniques other than passive hemagglutination in detecting the anti-nRNP antibody. In our experience, such criteria also contribute to a better definition of MCTD in Caucasian patients. PMID:1629824

  10. Direct determination of fatty acids in fish tissues: quantifying top predator trophic connections.

    PubMed

    Parrish, Christopher C; Nichols, Peter D; Pethybridge, Heidi; Young, Jock W

    2015-01-01

    Fatty acids are a valuable tool in ecological studies because of the large number of unique structures synthesized. They provide versatile signatures that are being increasingly employed to delineate the transfer of dietary material through marine and terrestrial food webs. The standard procedure for determining fatty acids generally involves lipid extraction followed by methanolysis to produce methyl esters for analysis by gas chromatography. By directly transmethylating ~50 mg wet samples and adding an internal standard it was possible to greatly simplify the analytical methodology to enable rapid throughput of 20-40 fish tissue fatty acid analyses a day including instrumental analysis. This method was verified against the more traditional lipid methods using albacore tuna and great white shark muscle and liver samples, and it was shown to provide an estimate of sample dry mass, total lipid content, and a condition index. When large fatty acid data sets are generated in this way, multidimensional scaling, analysis of similarities, and similarity of percentages analysis can be used to define trophic connections among samples and to quantify them. These routines were used on albacore and skipjack tuna fatty acid data obtained by direct methylation coupled with literature values for krill. There were clear differences in fatty acid profiles among the species as well as spatial differences among albacore tuna sampled from different locations. PMID:25376156

  11. Significance of Pulmonary Arterial Pressure as a Prognostic Indicator in Lung-Dominant Connective Tissue Disease

    PubMed Central

    Suzuki, Atsushi; Taniguchi, Hiroyuki; Watanabe, Naohiro; Kondoh, Yasuhiro; Kimura, Tomoki; Kataoka, Kensuke; Matsuda, Toshiaki; Yokoyama, Toshiki; Sakamoto, Koji; Nishiyama, Osamu; Hasegawa, Yoshinori

    2014-01-01

    Background Lung-dominant connective tissue disease (LD-CTD) is a new concept for classifying the subset of patients with interstitial pneumonia who have clinical features suggesting an associated CTD, but whose features fall short of a clear diagnosis of CTD under the current rheumatologic classification systems. The impact of mean pulmonary arterial pressure (MPAP) in LD-CTD has not been sufficiently elucidated. Objectives To evaluate the survival impact of MPAP measured during the initial evaluation in patients with LD-CTD. Methods We retrospectively analyzed the initial evaluation data of 100 LD-CTD patients undergoing pulmonary function test, 6-min walk test (6MWT), and right heart catheterization (RHC). Results The mean MPAP was 16.2±4.4 mm Hg, and 18 patients had MPAP?20 mm Hg. A univariate Cox proportional hazard model showed that MPAP and several variables have a statistically significant impact on survival. With stepwise, multivariate Cox proportional analysis, MPAP (HR ?=?1.293; 95% CI 1.130–1.480; p<0.001) and mean forced vital capacity (FVC) % predicted (HR?=?0.958; 95% CI 0.930–0.986; p?=?0.004) were shown to be independent determinants of survival. Conclusions Higher MPAP and lower %FVC at the initial evaluation were significant independent prognostic factors of LD-CTD. MPAP evaluation provides additional information of disease status and will help physicians to predict mortality in LD-CTD. PMID:25268705

  12. FEV1 over time in patients with connective tissue disease-related bronchiolitis

    PubMed Central

    Fernández Pérez, Evans R.; Krishnamoorthy, Mahalakshmi; Brown, Kevin K.; Huie, Tristan J.; Fischer, Aryeh; Solomon, Joshua J.; Meehan, Richard T.; Olson, Amy L.; Achcar, Rosane Duarte; Swigris, Jeffrey J.

    2013-01-01

    Summary Background Fibrosis or inflammation of the bronchioles is a well-known manifestation of connective tissue disease (CTD). However, the natural history of CTD-related bronchiolitis is largely unknown. Methods We analyzed consecutive patients evaluated at National Jewish Health (Denver, CO) from 1998 to 2008 with CTD and surgical lung biopsy-confirmed bronchiolitis. Linear mixed effects models were used to estimate the longitudinal postbronchodilator FEV1 %predicted (%pred) course and differences between subjects with or without constrictive bronchiolitis (CB). Results Of 28 subjects with a mean age of 53 ± 9 years, fourteen (50%) had CB. The most common CTD diagnosis was rheumatoid arthritis (n = 14; 50%). There were no significant differences in demographics, smoking status, underlying CTD diagnoses, 6-min walk distance, dyspnea score or drug therapy between subjects with CB and those with cellular bronchiolitis. Three subjects with CB (11%) and four with cellular bronchiolitis (14%) died. Compared with subjects with CB, those with cellular bronchiolitis had higher mean FEV1 %pred at all times. There were no significant differences in FEV1 %pred slope within- or between-groups (CB vs. cellular bronchiolitis) preceding surgical lung biopsy or afterward. Conclusion Subjects with CTD-related CB had lower FEV1 %pred values than those with CTD-related cellular bronchiolitis at all time points, but FEV1 %pred remained stable over time in both groups regardless of therapy received. PMID:23582575

  13. Connective Tissue Growth Factor Is Necessary for Retinal Capillary Basal Lamina Thickening in Diabetic Mice

    PubMed Central

    Kuiper, Esther J.; van Zijderveld, Rogier; Roestenberg, Peggy; Lyons, Karen M.; Goldschmeding, Roel; Klaassen, Ingeborg; Van Noorden, Cornelis J.F.; Schlingemann, Reinier O.

    2008-01-01

    Experimental prevention of basal lamina (BL) thickening of retinal capillaries ameliorates early vascular changes caused by diabetes. Connective tissue growth factor (CTGF) is upregulated early in diabetes in the human retina and is a potent inducer of expression of BL components. We hypothesize that CTGF is causally involved in diabetes-induced BL thickening of retinal capillaries. To test this hypothesis, we compared the effects of streptozotocin (STZ)-induced diabetes on retinal capillary BL thickness between wild-type mice (CTGF+/+) and mice lacking one functional CTGF allele (CTGF+/?). Differences in BL thickness were calculated by quantitative analysis of electron microscopic images of transversally sectioned capillaries in and around the inner nuclear layer of the retina. We show that BL thickening was significant in diabetic CTGF+/+ mice compared with control CTGF+/+ mice, whereas diabetes did not significantly induce BL thickening in CTGF+/? mice. We conclude that CTGF expression is necessary for diabetes-induced BL thickening and suggest that reduction of CTGF levels may be protective against the development of diabetic retinopathy. (J Histochem Cytochem 56:785–792, 2008) PMID:18474939

  14. Angiogenesis is not impaired in connective tissue growth factor (CTGF) knock-out mice.

    PubMed

    Kuiper, Esther J; Roestenberg, Peggy; Ehlken, Christoph; Lambert, Vincent; van Treslong-de Groot, Henny Bloys; Lyons, Karen M; Agostini, Hans-Jürgen T; Rakic, Jean-Marie; Klaassen, Ingeborg; Van Noorden, Cornelis J F; Goldschmeding, Roel; Schlingemann, Reinier O

    2007-11-01

    Connective tissue growth factor (CTGF) is a member of the CCN family of growth factors. CTGF is important in scarring, wound healing, and fibrosis. It has also been implicated to play a role in angiogenesis, in addition to vascular endothelial growth factor (VEGF). In the eye, angiogenesis and subsequent fibrosis are the main causes of blindness in conditions such as diabetic retinopathy. We have applied three different models of angiogenesis to homozygous CTGF(-/-) and heterozygous CTGF(+/-) mice to establish involvement of CTGF in neovascularization. CTGF(-/-) mice die around birth. Therefore, embryonic CTGF(-/-), CTGF(+/-), and CTGF(+/+) bone explants were used to study in vitro angiogenesis, and neonatal and mature CTGF(+/-) and CTGF(+/+) mice were used in models of oxygen-induced retinopathy and laser-induced choroidal neovascularization. Angiogenesis in vitro was independent of the CTGF genotype in both the presence and the absence of VEGF. Oxygen-induced vascular pathology in the retina, as determined semi-quantitatively, and laser-induced choroidal neovascularization, as determined quantitatively, were also not affected by the CTGF genotype. Our data show that downregulation of CTGF levels does not affect neovascularization, indicating distinct roles of VEGF and CTGF in angiogenesis and fibrosis in eye conditions. PMID:17625227

  15. Connective tissue growth factor is necessary for retinal capillary basal lamina thickening in diabetic mice.

    PubMed

    Kuiper, Esther J; van Zijderveld, Rogier; Roestenberg, Peggy; Lyons, Karen M; Goldschmeding, Roel; Klaassen, Ingeborg; Van Noorden, Cornelis J F; Schlingemann, Reinier O

    2008-08-01

    Experimental prevention of basal lamina (BL) thickening of retinal capillaries ameliorates early vascular changes caused by diabetes. Connective tissue growth factor (CTGF) is upregulated early in diabetes in the human retina and is a potent inducer of expression of BL components. We hypothesize that CTGF is causally involved in diabetes-induced BL thickening of retinal capillaries. To test this hypothesis, we compared the effects of streptozotocin (STZ)-induced diabetes on retinal capillary BL thickness between wild-type mice (CTGF+/+) and mice lacking one functional CTGF allele (CTGF+/-). Differences in BL thickness were calculated by quantitative analysis of electron microscopic images of transversally sectioned capillaries in and around the inner nuclear layer of the retina. We show that BL thickening was significant in diabetic CTGF+/+ mice compared with control CTGF+/+ mice, whereas diabetes did not significantly induce BL thickening in CTGF+/- mice. We conclude that CTGF expression is necessary for diabetes-induced BL thickening and suggest that reduction of CTGF levels may be protective against the development of diabetic retinopathy. PMID:18474939

  16. Angiogenesis Is Not Impaired in Connective Tissue Growth Factor (CTGF) Knock-out Mice

    PubMed Central

    Kuiper, Esther J.; Roestenberg, Peggy; Ehlken, Christoph; Lambert, Vincent; van Treslong-de Groot, Henny Bloys; Lyons, Karen M.; Agostini, Hans-Jürgen T.; Rakic, Jean-Marie; Klaassen, Ingeborg; Van Noorden, Cornelis J. F.; Goldschmeding, Roel; Schlingemann, Reinier O.

    2007-01-01

    Connective tissue growth factor (CTGF) is a member of the CCN family of growth factors. CTGF is important in scarring, wound healing, and fibrosis. It has also been implicated to play a role in angiogenesis, in addition to vascular endothelial growth factor (VEGF). In the eye, angiogenesis and subsequent fibrosis are the main causes of blindness in conditions such as diabetic retinopathy. We have applied three different models of angiogenesis to homozygous CTGF?/? and heterozygous CTGF+/? mice to establish involvement of CTGF in neovascularization. CTGF?/? mice die around birth. Therefore, embryonic CTGF?/?, CTGF+/?, and CTGF+/+ bone explants were used to study in vitro angiogenesis, and neonatal and mature CTGF+/? and CTGF+/+ mice were used in models of oxygen-induced retinopathy and laser-induced choroidal neovascularization. Angiogenesis in vitro was independent of the CTGF genotype in both the presence and the absence of VEGF. Oxygen-induced vascular pathology in the retina, as determined semi-quantitatively, and laser-induced choroidal neovascularization, as determined quantitatively, were also not affected by the CTGF genotype. Our data show that downregulation of CTGF levels does not affect neovascularization, indicating distinct roles of VEGF and CTGF in angiogenesis and fibrosis in eye conditions. PMID:17625227

  17. Autoimmune hepatitis.

    PubMed

    Mieli-Vergani, Giorgina; Vergani, Diego

    2011-06-01

    Autoimmune hepatitis (AIH) is an inflammatory liver disease that mainly affects females. It is characterized histologically by interface hepatitis, biochemically by increased aspartate and alanine aminotransferase levels, and serologically by the presence of autoantibodies and increased levels of immunoglobulin G. AIH affects both adults and children, and is particularly aggressive in the latter group. It is a relatively rare but devastating disease, which progresses rapidly unless immunosuppressive treatment is started promptly. With appropriate treatment 80% of patients achieve remission and long-term survival. Those patients who progress to end-stage liver disease because they are unresponsive or nonadherent to treatment, and those with fulminant liver failure (encephalopathy grade II-IV) at diagnosis, require liver transplantation. Seropositivity for smooth muscle and/or antinuclear antibodies defines type 1 AIH, while positivity for liver kidney microsomal type 1 antibodies defines type 2 AIH. The primary cause of AIH is unknown; however, considerable knowledge about the mechanisms of liver damage involved has been gathered over the past 30 years, which is likely to provide the basis for specific modes of treatment and a possible cure. PMID:21537351

  18. Regulation of pancreatic inflammation by connective tissue growth factor (CTGF/CCN2)

    PubMed Central

    Charrier, Alyssa; Chen, Ruju; Kemper, Sherri; Brigstock, David R

    2014-01-01

    Pancreatitis is caused by long-term heavy alcohol consumption, which results in injury and death of pancreatic acinar cells (PAC). The PAC play a pivotal role in mediating early inflammatory responses but the underlying mechanisms remain poorly understood. Treatment of C57BL/6 mice with ethanol and cerulein resulted in increased staining for acinar interleukin-1? (IL-1?), chemokine (C-C motif) ligand 3 (CCL3), or connective tissue growth factor (CTGF/CCN2) by Day 16 and this was associated with increased infiltration of F4/80-positive macrophages and increased expression of pancreatic CTGF/CCN2 mRNA. Compared with wild-type Swiss Webster mice, ethanol treatment of pan-green fluorescent protein (GFP)-CTGF/CCN2 transgenic mice caused enhanced acinar staining for GFP or CTGF/CCN2 and a significant increase in pancreatic infiltration of F4/80-positive macrophages or NIMP-R14-positive neutrophils. Treatment of primary mouse PAC or the rat AR42J PAC line with ethanol or CTGF/CCN2 resulted in enhanced expression of IL-1? or CCL3. Conditioned medium from CTGF/CCN2-treated AR42J cells induced chemotaxis in NR8383 macrophages and this response was abrogated in a dose-dependent manner by addition of BX471, an inhibitor of chemokine (C-C motif) receptor 1. These results reveal that acinar CTGF/CCN2 plays a novel role in alcohol-induced inflammatory processes in the pancreas by increasing infiltration of macrophages and neutrophils and increasing acinar production of inflammatory mediators such as IL-1? or CCL3. The early production of CTGF/CCN2 by PAC to drive inflammation is distinct from its previously reported production by pancreatic stellate cells to drive fibrosis at later stages of pancreatic injury. PMID:24754049

  19. Anti-endothelial cell antibodies in connective tissue diseases associated with pulmonary arterial hypertension

    PubMed Central

    Liu, Xiao-Dan; Guo, Sheng-Yu; Yang, Li-Li; Zhang, Xiao-Li; Fu, Wen-Yi

    2014-01-01

    Objective To investigate the prevalence of anti-endothelial cell antibodies (AECA) in connective tissue diseases (CTD) associated with pulmonary arterial hypertension (PAH) and to corroborate the pathologic function of AECA in PAH-associated CTDs. Methods AECA were detected by cellular enzyme-linked immunosorbent assay (ELISA) in sera of 19 PAH-associated CTD patients, 22 CTD patients without PAH involvement, and 20 age- and sex-matched healthy individuals as controls. Using IgG purified from the sera of AECA-positive, AECA-negative, and healthy subjects, the effects of AECA on the expression of ICAM-1 and the chemokine regulated upon activation normal T-cell expressed and secreted (RANTES) in cultured endothelial cells were also evaluated. Results A total of 12 of the 19 (63.2%) CTD patients with PAH, 9 of the 22 (40.9%) CTD patients without PAH, and 1 of the 20 (5%) healthy controls were positive for AECA, which were calculated as ELISA ratio (ER) values. ER values in PAH-associated CTD patients were significantly higher than those with CTD without PAH (3.68±2.05 versus 1.67±1.07, P<0.001). IgG purified from AECA-positive sera induced a significantly increased level of ICAM-1 expression after 48 h incubation (795.2±32.5 pg/mL) compared with AECA-negative or healthy control IgG (231.5±27.1 and 192.8±33.4 pg/mL, respectively; P<0.001). In addition, RANTES production by cultured human pulmonary arterial endothelial cells (HPAECs) increased in both a time- and concentration-dependent manner in response to incubation with purified AECA-positive IgG. Conclusions AECA could be involved in CTD and might participate in the pathogenesis of PAH-associated CTD. PMID:24822109

  20. Mycophenolate Mofetil Improves Lung Function in Connective Tissue Disease-associated Interstitial Lung Disease

    PubMed Central

    Fischer, Aryeh; Brown, Kevin K.; Du Bois, Roland M.; Frankel, Stephen K.; Cosgrove, Gregory P.; Fernandez-Perez, Evans R.; Huie, Tristan J.; Krishnamoorthy, Mahalakshmi; Meehan, Richard T.; Olson, Amy L.; Solomon, Joshua J.; Swigris, Jeffrey J.

    2013-01-01

    Objective Small series suggest mycophenolate mofetil (MMF) is well tolerated and may be an effective therapy for connective tissue disease-associated interstitial lung disease (CTD-ILD). We examined the tolerability and longitudinal changes in pulmonary physiology in a large and diverse cohort of patients with CTD-ILD treated with MMF. Methods We identified consecutive patients evaluated at our center between January 2008 and January 2011 and prescribed MMF for CTD-ILD. We assessed safety and tolerability of MMF and used longitudinal data analyses to examine changes in pulmonary physiology over time, before and after initiation of MMF. Results We identified 125 subjects treated with MMF for a median 897 days. MMF was discontinued in 13 subjects. MMF was associated with significant improvements in estimated percentage of predicted forced vital capacity (FVC%) from MMF initiation to 52, 104, and 156 weeks (4.9% ± 1.9%, p = 0.01; 6.1% ± 1.8%, p = 0.0008; and 7.3% ± 2.6%, p = 0.004, respectively); and in estimated percentage predicted diffusing capacity (DLCO%) from MMF initiation to 52 and 104 weeks (6.3% ± 2.8%, p = 0.02; 7.1% ± 2.8%, p = 0.01). In the subgroup without usual interstitial pneumonia (UIP)-pattern injury, MMF significantly improved FVC% and DLCO%, and in the subgroup with UIP-pattern injury, MMF was associated with stability in FVC% and DLCO%. Conclusion In a large diverse cohort of CTD-ILD, MMF was well tolerated and had a low rate of discontinuation. Treatment with MMF was associated with either stable or improved pulmonary physiology over a median 2.5 years of followup. MMF appears to be a promising therapy for the spectrum of CTD-ILD. PMID:23457378

  1. Exercise training in pulmonary arterial hypertension associated with connective tissue diseases

    PubMed Central

    2012-01-01

    Introduction The objective of this prospective study was to assess short- and long-term efficacy of exercise training (ET) as add-on to medical therapy in patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-APAH). Methods Patients with invasively confirmed CTD-APAH received ET in-hospital for 3 weeks and continued at home for 12 weeks. Efficacy parameters have been evaluated at baseline and after 15 weeks by blinded-observers. Survival rate has been evaluated in a follow-up period of 2.9 ± 1.9 years. Results Twenty-one consecutive patients were included and assessed at baseline, and after 3 weeks, 14 after 15 weeks. Patients significantly improved the mean distance walked in 6 minutes compared to baseline by 67 ± 52 meters after 3 weeks (p < 0.001) and by 71 ± 35 meters after 15 weeks (p = 0.003), scores of quality of life (p < 0.05), heart rate at rest, peak oxygen consumption, oxygen saturation and maximal workload. Systolic pulmonary artery pressure and diastolic systemic blood pressure improved significantly after 3 weeks of ET. The 1- and 2-year overall-survival rates were 100%, the 3-year survival 73%. In one patient lung transplantation was performed 6 months after ET. Conclusion ET as add-on to medical therapy is highly effective in patients with CTD-APAH to improve work capacity, quality of life and further prognostic relevant parameters and possibly improves the 1-, 2- and 3-year survival rate. Further randomized controlled studies are needed to confirm these results. Trial registration ClinicalTrials.gov: NCT00491309. PMID:22709477

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

    PubMed Central

    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 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. PMID:25738829

  3. Effect of Connective Tissue Growth Factor on Protein Kinase Expression and Activity in Human Corneal Fibroblasts

    PubMed Central

    Radhakrishnan, Siva S.; Blalock, Timothy D.; Robinson, Paulette M.; Secker, Genevieve; Daniels, Julie; Grotendorst, Gary R.; Schultz, Gregory S.

    2012-01-01

    Purpose. To investigate signal transduction pathways for connective tissue growth factor (CTGF) in human corneal fibroblasts (HCF). Methods. Expression of 75 kinases in cultures of serum-starved (HCF) were investigated using protein kinase screens, and changes in levels of phosphorylation of 31 different phosphoproteins were determined at 0, 5, and 15 minutes after treatment with CTGF. Levels of phosphorylation of three signal transducing phosphoproteins (extracellular regulated kinase 1 [ERK1], extracellular regulated kinase 2 [ERK2] [MAPKs], and signal transducer and activator of transcription 3 [STAT3]) were measured at nine time points after exposure to CTGF using Western immunoblots. Inhibition of Ras, MEK1/2 (MAPKK), and ERK1/2, on CTGF-stimulated fibroblast proliferation and collagen gel contraction was assessed using selective inhibitors farnesylthiosalicylic acid, PD-98059, and SB203580, respectively. Results. Thirty two of the 75 kinases (43%) evaluated by the kinase screen were detected in extracts of quiescent HCF, suggesting these kinases are available to respond acutely to CTGF exposure. Addition of CTGF increased levels of phosphorylation of five phosphoproteins (ERK1 and 2, MEK1/2 [MAPKK], STAT3, and SAPK/JNK), and decreased levels of phosphorylation of 14 phosphoproteins (including protein kinases B and C) after 5 and 15 minutes. Further analysis of ERK1 and 2 and STAT3 phosphorylation showed rapid increases within 1 minute of CTGF exposure that peaked between 5 and 10 minutes then returned to pretreatment levels by 30 minutes. Treatment of HCF with selective inhibitors of Ras, MEK 1/2, and ERK1/2 individually blocked both CTGF induced cell proliferation, and collagen gel contraction. Conclusions. Results from protein kinase screens and selective kinase inhibitors demonstrate Ras/MEK/ERK/STAT3 pathway is required for CTGF signaling in HCF. PMID:23139271

  4. Lung disease with anti-CCP antibodies but not rheumatoid arthritis or connective tissue disease

    PubMed Central

    Fischer, Aryeh; Solomon, Joshua J.; du Bois, Roland M.; Deane, Kevin D.; Olson, Amy L.; Fernandez-Perez, Evans R.; Huie, Tristan J.; Stevens, Allen D.; Gill, Mary B.; Rabinovitch, Avi M.; Lynch, David A.; Burns, David A.; Pineiro, Isabel S.; Groshong, Steve D.; Duarte Achcar, Rosane D.; Brown, Kevin K.; Martin, Richard J.; Swigris, Jeffrey J.

    2013-01-01

    Summary Objective We sought to characterize a novel cohort of patients with lung disease, anti-cyclic citrullinated peptide (CCP) antibody positivity, without rheumatoid arthritis (RA) or other connective tissue disease (CTD). Methods The study sample included 74 subjects with respiratory symptoms, evaluated January 2008–January 2010 and found to have a positive anti-CCP antibody but no evidence for RA or other CTD. Each underwent serologic testing, pulmonary physiology testing, and thoracic high-resolution computed tomography (HRCT) scan as part of routine clinical evaluation. Results The majority of subjects were women, and most were former cigarette smokers. Four distinct radiographic phenotypes were identified: isolated airways disease (54%), isolated interstitial lung disease (ILD) (14%), mixed airways disease and ILD (26%), and combined pulmonary fibrosis with emphysema (7%). This cohort had a predominance of airways disease, either in isolation or along with a usual interstitial pneumonia-pattern of ILD. Among subjects with high-titer anti-CCP positivity (n=33), three developed the articular manifestations of RA during a median follow-up of 449 days. Conclusion We have described a unique cohort of patients with anti-CCP antibody positivity and lung disease in the absence of existing RA or other CTD. The lung phenotypic characteristics of this cohort resemble those of established RA and a few of these patients have developed articular RA within a short period of follow-up. The implications of a positive anti-CCP antibody among patients with lung disease but not RA are not yet known, but we believe requires further investigation. PMID:22503074

  5. Downregulation of Connective Tissue Growth Factor by Three-Dimensional Matrix Enhances Ovarian Carcinoma Cell Invasion

    PubMed Central

    Barbolina, Maria V.; Adley, Brian P.; Kelly, David L.; Shepard, Jaclyn; Fought, Angela J.; Scholtens, Denise; Penzes, Peter; Shea, Lonnie D.; Sharon Stack, M

    2010-01-01

    Epithelial ovarian carcinoma (EOC) is a leading cause of death from gynecologic malignancy, due mainly to the prevalence of undetected metastatic disease. The process of cell invasion during intra-peritoneal anchoring of metastatic lesions requires concerted regulation of many processes, including modulation of adhesion to the extracellular matrix and localized invasion. Exploratory cDNA microarray analysis of early response genes (altered after 4 hours of 3-dimensional collagen culture) coupled with confirmatory real-time RT-PCR, multiple three-dimensional cell culture matrices, Western blot, immunostaining, adhesion, migration, and invasion assays were used to identify modulators of adhesion pertinent to EOC progression and metastasis. cDNA microarray analysis indicated a dramatic downregulation of connective tissue growth factor (CTGF) in EOC cells placed in invasion-mimicking conditions (3-dimensional type I collagen). Examination of human EOC specimens revealed that CTGF expression was absent in 46% of the tested samples (n=41), but was present in 100% of normal ovarian epithelium samples (n=7). Reduced CTGF expression occurs in many types of cells and may be a general phenomenon displayed by cells encountering a 3D environment. CTGF levels were inversely correlated with invasion such that downregulation of CTGF increased, while its upregulation reduced, collagen invasion. Cells adhered preferentially to a surface comprised of both collagen I and CTGF relative to either component alone using ?6?1 and ?3?1 integrins. Together these data suggest that downregulation of CTGF in EOC cells may be important for cell invasion through modulation of cell-matrix adhesion. PMID:19382180

  6. Chondromodulin-I and tenomodulin: a new class of tissue-specific angiogenesis inhibitors found in hypovascular connective tissues.

    PubMed

    Shukunami, Chisa; Oshima, Yusuke; Hiraki, Yuji

    2005-07-29

    In tissues and/or organs of mesenchymal origin, the vasculature is usually well developed. However, there are certain hypovascular tissues that exhibit powerful anti-angiogenic resistance, implying the presence of tissue-type specific inhibitors of angiogenesis. Hyaline cartilage is one example, and several anti-angiogenic factors have been purified from cartilage. We previously identified chondromodulin-I (ChM-I) as a tissue-specific inhibitor of angiogenesis in fetal bovine cartilage. ChM-I is specifically expressed in the avascular regions of the growth-plate and cartilaginous bone rudiments in embryos. Recently, we cloned a novel type II transmembrane protein, tenomodulin (TeM), having a domain homologous to ChM-I at its C-terminus. TeM turned out to be expressed specifically in other hypovascular structures in the mesenchyme, such as the epimysium, tendon, and ligaments. In this overview, we discuss the structural characteristics of this class of anti-angiogenic molecules and their pathophysiological role in the control of vascularity. PMID:15950187

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

    NASA Technical Reports Server (NTRS)

    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. Purpose: 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, medial gastrocnemius and tibialis anterior by obtaining pre-flight and post-flight small biopsy specimens in collaboration with Dr. V. Reggie Edgerton's laboratory at the University of California at Los Angeles.

  8. 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

    NASA Technical Reports Server (NTRS)

    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.

  9. Structural changes in connective tissues caused by a moderate laser heating

    SciTech Connect

    Bagratashvili, Viktor N; Bagratashvili, N V; Sviridov, A P; Shakh, G Sh [Institute of Laser and Information Technologies, Russian Academy of Sciences, Troitsk, Moscow Region (Russian Federation); Ignat'eva, Natalia Yu; Lunin, Valery V; Grokhovskaya, T E; Averkiev, S V [Department of Chemistry, M.V. Lomonosov Moscow State University, Moscow (Russian Federation)

    2002-10-31

    The structural changes in adipose and fibrous tissues caused by 2- and 3-W IR laser irradiation are studied by the methods of IR and Raman spectroscopy and differential scanning calorimetry. It is shown that heating of fibrous tissue samples to 50 {sup 0}C and adipose tissue samples to 75 {sup 0}C by IR laser radiation changes the supramolecular structure of their proteins and triacylglycerides, respectively, without the intramolecular bond breaking. Heating of fibrous tissue to 70 {sup 0}C and adipose tissue to 90 - 110 {sup 0}C leads to a partial reversible denaturation of proteins and to oxidation of fats.

  10. Autoimmune Lymphoproliferative Syndrome (ALPS)

    MedlinePLUS

    ... JavaScript on. Read more information on enabling JavaScript. Autoimmune Lymphoproliferative Syndrome (ALPS) Top Banner Content Area Skip Content Marketing Share this: Main Content Area Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder ...

  11. Toxicology of Autoimmune Diseases

    PubMed Central

    Hultman, Per; Kono, Dwight H.

    2010-01-01

    Susceptibility to most autoimmune diseases is dependent on polygenic inheritance, environmental factors, and poorly defined stochastic events. One of the significant challenges facing autoimmune disease research is in identifying the specific events that trigger loss of tolerance and autoimmunity. Although many intrinsic factors, including age, sex, and genetics, contribute to autoimmunity, extrinsic factors such as drugs, chemicals, microbes, or other environmental factors can also act as important initiators. This review explores how certain extrinsic factors, namely drugs and chemicals, can promote the development of autoimmunity, focusing on a few better characterized agents that, in most instances, have been shown to produce autoimmune manifestations in human populations. Mechanisms of autoimmune disease induction are discussed in terms of research obtained using specific animal models. Although a number of different pathways have been delineated for drug/chemical-induced autoimmunity some similarities do exist and a working model is proposed. PMID:20078109

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

    PubMed

    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. PMID:25740901

  13. Changes in connective tissue in patients with pelvic organ prolapse—a review of the current literature

    Microsoft Academic Search

    M. H. Kerkhof; L. Hendriks; H. A. M. Brölmann

    2009-01-01

    Little is known about the pathophysiology of pelvic organ prolapse (POP). In 1996, Jackson presented a hypothesis on pelvic\\u000a floor connective tissue that tried to explain the development of POP on a molecular level. The objective of this review is\\u000a to test the hypothesis against recent literature. The method used was a review of literature. The association between POP\\u000a and

  14. Connective tissue growth factor mediates transforming growth factor b-induced collagen synthesis: down- regulation by cAMP

    Microsoft Academic Search

    MATTHEW R. DUNCAN; KEN S. FRAZIER; SUSAN ABRAMSON; SHAWN WILLIAMS; HELENE KLAPPER; XINFAN HUANG; GARY R. GROTENDORST

    Connective tissue growth factor (CTGF) is a cysteine-rich peptide synthesized and secreted by fibroblastic cells after activation with transforming growth factor beta (TGF-b) that acts as a downstream mediator of TGF-b-induced fibroblast proliferation. We performed in vitro and in vivo studies to determine whether CTGF is also essential for TGF-b-induced fibroblast collagen synthesis. In vitro studies with normal rat kidney

  15. Mixed connective tissue disease associated with antineutrophil cytoplasmic antibodies against proteinase-3 and systemic atherosclerosis: a case report

    Microsoft Academic Search

    Masato Kanazawa; Yoko Wada; Tsukasa Ohno; Hian In; Kazuaki Yahata; Junko Izumi; Hisao Tanaka; Satoshi Ito; Mitsuhiro Ueno; Masaaki Nakano; Fumitake Gejyo

    2004-01-01

    A 47-year-old woman presented with facial spasm, swollen fingers and Raynaud’s phenomenon due to cerebrovascular disorder and mixed connective tissue disease (MCTD). Although she was positive for both antineutrophil cytoplasmic antibodies against proteinase-3 (PR3-ANCA) and anti-U1 RNP antibodies, she did not meet the American College of Rheumatology classification criteria for Wegener’s granulomatosis (WG). Physical and histopathological examinations revealed severe systemic

  16. Perspectives on autoimmunity

    SciTech Connect

    Cohen, I.R.

    1987-01-01

    The contents of this book are: HLA and Autoimmunity; Self-Recognition and Symmetry in the Immune System; Immunology of Insulin Dependent Diabetes Mellitus; Multiple Sclerosis; Autoimmunity and Immune Pathological Aspects of Virus Disease; Analyses of the Idiotypes and Ligand Binding Characteristics of Human Monoclonal Autoantibodies to DNA: Do We Understand Better Systemic Lupus Erythematosus. Autoimmunity and Rheumatic Fever; Autoimmune Arthritis Induced by Immunization to Mycobacterial Antigens; and The Interaction Between Genetic Factors and Micro-Organisms in Ankylosing Spondylitis: Facts and Fiction.

  17. Autoimmunity and primary biliary cirrhosis.

    PubMed

    Mackay, I R

    2000-08-01

    The history of primary biliary cirrhosis (PBC) began in 1851, with autoimmunity introduced in 1958 and expanded from the 1960s on. In PBC, autoantibodies are present to mitochondria-located antigens (AMA) and to nuclear-located antigens (ANA). The AMA react with E2 subunits of three members of the 2-oxoacid dehydrogenase complex family, but most frequently with pyruvate dehydrogenase complex (PDC); the inner lipoyl domain of PDC-E2 contains a major B- and T-cell epitope. The ANA react with three nuclear components, centromeric proteins, nuclear dot proteins and nuclear pore complex. Autoimmune diseases including PBC reflect a failure in mechanisms of self-tolerance which is developed in central lymphoid tissues in embryonic life by deletion of self-reactive lymphocytes, and maintained in peripheral tissues in post-natal life by regulatory processes. Primary biliary cirrhosis has not yet been identified with failure in any one particular tolerance mechanism. Genetic influences are revealed by familial occurrences and by associations with HLA alleles, and environmental influences by epidemiological data. A lead to pathogenesis is the accumulation uniquely in PBC of PDC-E2-like material at the plasma membrance of biliary epithelial cells (BECs). Although the origin of this accumulation of PDC-E2 at the surface of BECs is uncertain, it provides a credible 'tissue-specific' target for an autoimmune attack by T and B lymphocytes at the site of the actual pathology. PMID:10976012

  18. [Systemic autoimmune disorders and pregnancy].

    PubMed

    Kiss, Emese; Kiss, Csaba György; Poór, Gyula

    2011-10-23

    The coincidence of systemic autoimmune diseases and pregnancy may modify the outcome of the disease and the pregnancy due to the background immunologic and hormonal processes. The great majority of patients with autoimmune diseases are young females in their reproductive years, willing to have babies. Consequently, we have to prepare for this special situation. Our concept on childbearing in autoimmune women has changed within the last 30 years. Earlier, systemic lupus erythematosus flared in about 50% of patients during pregnancy, but the flare rate has significantly decreased recently. This improvement can be attributed to increased attention to low diseases activity at the time of conception, which might reduce to the half of the risk for flare. Tight control of patients and appropriate use of corticosteroids also contribute to the better results. The adequate use of anti-thrombotic agents resulted in a significant amelioration of pregnancy outcome in antiphospholipid syndrome. The earlier use of methotrexate and the introduction of tumor necrosis factor-alpha inhibitors in the treatment of rheumatoid arthritis have changed the natural characteristics of the disease. The increase in remission rate indirectly has beneficial effect on the number of planned and carried out pregnancies. Authors review the connection between systemic autoimmune disorders and pregnancy as well as the possibilities of medical treatment of such diseases during pregnancy. PMID:21983397

  19. Neonatal autoimmune diseases: a critical review.

    PubMed

    Chang, Christopher

    2012-05-01

    Neonatal autoimmune diseases are distinctly rare. Most neonatal autoimmune diseases result from the transplacental transfer of maternal antibodies directed against fetal or neonatal antigens in various tissues. In neonatal lupus, the heart seems to be particularly susceptible. Primary autoimmunity in newborns, with the exception of familial autoinflammatory diseases, is virtually non-existent. The pathophysiologic basis for the development of neonatal autoimmunity is not entirely clear, but differences in the neonatal immune system compared with the adult immune system, as well as unique characteristics of target antigens in the newborn period may be important factors. Neonatal lupus is the most common presentation of autoimmunity in the newborn. But the characteristics defining neonatal lupus are not well defined and the presentation of neonatal lupus differs from that of classical lupus. Other neonatal autoimmune diseases involving the interaction between maternal antibodies and fetal/neonatal antigens include neonatal anti-phospholipid syndrome, Behcet's disease, neonatal autoimmune thyroid disease, neonatal polymyositis and dermatomyositis, neonatal scleroderma and neonatal type I diabetes mellitus. While autoantibodies have been detected in patients with neonatal autoimmune disease, the pathogenic role of autoantibodies has not been well defined. Other mechanisms may play a role in the development of neonatal autoimmunity, including fetal/maternal microchimerism and aberrant apoptosis of fetal cells. The autoinflammatory syndromes are a completely different category, but are also included in discussion of neonatal autoimmune diseases. The autoinflammatory syndromes include the cryopyrin associated periodic syndromes (CAPS) - familial cold autoinflammatory syndrome (FCAS), neonatal onset multisystem inflammatory disease (NOMID) and Muckle-Wells syndrome, which all share a common pathophysiologic mechanism. PMID:22402339

  20. Connective tissue growth factor gene expression and decline in renal function in lupus nephritis

    PubMed Central

    TACHAUDOMDACH, CHIRAPORN; KANTACHUVESIRI, SURASAK; CHANGSIRIKULCHAI, SIRIBHA; WIMOLLUCK, SURANGKANA; PINPRADAP, KOSET; KITIYAKARA, CHAGRIYA

    2012-01-01

    In lupus nephritis (LN), kidney inflammation may be followed by fibrosis and progressive decline in function. Transforming growth factor (TGF)-? is a notable mediator of fibrosis, but it has other beneficial roles, thus indicating a need for alternate therapeutic targets for inhibition of fibrosis. Connective tissue growth factor (CTGF) acts as a downstream mediator of TGF-? in promoting fibrosis, without mediating the immunosuppressive effects of TGF-?. Animal studies show that CTGF may have important roles in renal fibrosis, but data are limited in human subjects. The present study tested the hypothesis that renal CTGF mRNA expression is related to TGF-?1 and collagen I expression and is predictive of renal function deterioration in patients with LN (n=39). Gene expression was measured using multiplex real-time quantitative RT-PCR and renal function was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) glomerular filtration rate (GFR) equation. Decline in GFR was assessed by regression of GFR at biopsy to 1 year following biopsy. CTGF mRNA expression was significantly correlated with TGF-?1 and collagen I. GFR at biopsy was 89.2±39.2 ml/ min. Renal CTGF mRNA expression correlated inversely with baseline GFR. Renal CTGF mRNA was significantly higher in patients with moderate to severe CKD compared to those in the milder CKD group (low GFR 4.92±4.34 vs. high GFR 1.52±1.94, p<0.005). CTGF mRNA was also higher in patients with subsequent decline in GFR [GFR decline (5.19±4.46) vs. no GFR decline (1.79±1.97); P<0.01]. In conclusion, renal expression of CTGF was positively related to TGF-?1 and collagen I in patients with LN. Furthermore, high CTGF mRNA expression was associated with poor GFR at baseline and subsequent deterioration of kidney function. CTGF expression in the kidney may serve as an early marker for renal disease progression and could be evaluated as a target for therapeutic intervention to prevent renal failure in LN. PMID:22969957

  1. Cardiovascular Involvement in Connective Tissue Disease: The Role of Interstitial Lung Disease

    PubMed Central

    Wang, XiaoBing; Lou, MeiNa; Li, Yongji; Ye, WenJing; Zhang, ZhiYong; Jia, Xiufen; Shi, HongYing; Zhu, XiaoChun; Wang, LiangXing

    2015-01-01

    Objective The aim of this study was to assess cardiovascular involvement in patients with connective tissue disease (CTD), and determine whether interstitial lung disease (ILD) in these patients is associated with elevated cardiovascular risk. Methods This study evaluated a retrospective cohort of 436 CTD patients admitted to a large teaching hospital in Zhejiang province, China, along with an additional 436 participants of an annual community health screening conducted in the physical examination center who served as age- and gender-matched controls. Demographic, clinical, serologic and imaging characteristics, as well as medications used by each participant were recorded. Cardiovascular involvement was defined by uniform criteria. Correlations between clinical/serologic factors and cardiovascular involvement were determined by univariate and multivariate analyses. Results CTD patients had a significantly higher cardiovascular involvement rate than controls (64.7% vs 23.4%), with higher rates of diabetes, hypertension, and hyperlipidemia, elevated systolic and diastolic pressures, C-reactive protein, total cholesterol, and low-density lipoprotein cholesterol, and lower albumin and high-density lipoprotein cholesterol (all p < 0.05). Furthermore, CTP patients with cardiovascular involvement were significantly older, had higher systolic and diastolic pressures, C-reactive protein, glucose, and uric acid, higher rates of diabetes, hypertension, and use of moderate- to high-dose glucocorticoids, and longer disease duration compared to patients without involvement (all p < 0.05). Moreover, CTD in patients with cardiovascular involvement was more likely to be complicated by ILD (p < 0.01), which manifested as a higher alveolar inflammation score (p < 0.05). In the multivariate analysis, cardiovascular involvement in CTD patients was associated with age, systolic pressure, body mass index, uric acid, disease duration > 2 years, use of moderate- to high-dose glucocorticoids, and ILD with a high alveolar inflammation score. Conclusion Cardiovascular involvement is increased in CTD patients, and is associated with ILD with a higher alveolar inflammation score. Thus, early-stage echocardiography and CT scans should be used to detect potential cardiovascular complications in these patients. PMID:25775471

  2. Connective Tissue Growth Factor (CTGF/CCN2) Is Negatively Regulated during Neuron-Glioblastoma Interaction

    PubMed Central

    Feitosa, Natalia M.; Faria, Jane Cristina O.; Coelho-Aguiar, Juliana M.; de Souza, Jorge Marcondes; Neto, Vivaldo Moura; Abreu, José Garcia

    2013-01-01

    Connective-tissue growth factor (CTGF/CCN2) is a matricellular-secreted protein involved in complex processes such as wound healing, angiogenesis, fibrosis and metastasis, in the regulation of cell proliferation, migration and extracellular matrix remodeling. Glioblastoma (GBM) is the major malignant primary brain tumor and its adaptation to the central nervous system microenvironment requires the production and remodeling of the extracellular matrix. Previously, we published an in vitro approach to test if neurons can influence the expression of the GBM extracellular matrix. We demonstrated that neurons remodeled glioma cell laminin. The present study shows that neurons are also able to modulate CTGF expression in GBM. CTGF immnoreactivity and mRNA levels in GBM cells are dramatically decreased when these cells are co-cultured with neonatal neurons. As proof of particular neuron effects, neonatal neurons co-cultured onto GBM cells also inhibit the reporter luciferase activity under control of the CTGF promoter, suggesting inhibition at the transcription level. This inhibition seems to be contact-mediated, since conditioned media from embryonic or neonatal neurons do not affect CTGF expression in GBM cells. Furthermore, the inhibition of CTGF expression in GBM/neuronal co-cultures seems to affect the two main signaling pathways related to CTGF. We observed inhibition of TGF? luciferase reporter assay; however phopho-SMAD2 levels did not change in these co-cultures. In addition levels of phospho-p44/42 MAPK were decreased in co-cultured GBM cells. Finally, in transwell migration assay, CTGF siRNA transfected GBM cells or GBM cells co-cultured with neurons showed a decrease in the migration rate compared to controls. Previous data regarding laminin and these results demonstrating that CTGF is down-regulated in GBM cells co-cultured with neonatal neurons points out an interesting view in the understanding of the tumor and cerebral microenvironment interactions and could open up new strategies as well as suggest a new target in GBM control. PMID:23383241

  3. Predictors of mortality in connective tissue disease-associated pulmonary arterial hypertension: a cohort study

    PubMed Central

    2012-01-01

    Introduction Pulmonary arterial hypertension (PAH) is a major cause of mortality in connective tissue disease (CTD). We sought to quantify survival and determine factors predictive of mortality in a cohort of patients with CTD-associated PAH (CTD-PAH) in the current era of advanced PAH therapy. Methods Patients with right heart catheter proven CTD-PAH were recruited from six specialised PAH treatment centres across Australia and followed prospectively. Using survival methods including Cox proportional hazards regression, we modelled for all-cause mortality. Independent variables included demographic, clinical and hemodynamic data. Results Among 117 patients (104 (94.9%) with systemic sclerosis), during 2.6 ± 1.8 (mean ± SD) years of follow-up from PAH diagnosis, there were 32 (27.4%) deaths. One-, two- and three-year survivals were 94%, 89% and 73%, respectively. In multiple regression analysis, higher mean right atrial pressure (mRAP) at diagnosis (hazard ratio (HR) = 1.13, 95% CI: 1.04 to 1.24, P = 0.007), lower baseline six-minute walk distance (HR = 0.64, 95% CI: 0.43 to 0.97, P = 0.04), higher baseline World Health Organization functional class (HR = 3.42, 95% CI: 1.25 to 9.36, P = 0.04) and presence of a pericardial effusion (HR = 3.39, 95% CI: 1.07 to 10.68, P = 0.04) were predictive of mortality. Warfarin (HR = 0.20, 95% CI: 0.05 to 0.78, P = 0.02) and combination PAH therapy (HR = 0.20, 95% CI: 0.05 to 0.83, P = 0.03) were protective. Conclusions In this cohort of CTD-PAH patients, three-year survival was 73%. Independent therapeutic predictors of survival included warfarin and combination PAH therapy. Our findings suggest that anticoagulation and combination PAH therapy may improve survival in CTD-PAH. This observation merits further evaluation in randomised controlled trials. PMID:23039366

  4. Connective tissue dysplasia in five new patients with NF1 microdeletions: further expansion of phenotype and review of the literature

    PubMed Central

    Mensink, K A; Ketterling, R P; Flynn, H C; Knudson, R A; Lindor, N M; Heese, B A; Spinner, R J; Babovic?Vuksanovic, D

    2006-01-01

    Approximately 5% of patients with neurofibromatosis type 1 (NF1) have deletions of the entire NF1 gene. The phenotype usually includes early onset, large number of neurofibromas, presence of congenital anomalies, cognitive deficiency, and variable dysmorphic features and growth abnormalities. Connective tissue abnormalities are not generally recognised as a part of NF1 microdeletion syndrome, but mitral valve prolapse, joint laxity, and/or soft skin on the palms have been reported in a few patients. We describe clinical findings in six newly diagnosed patients with NF1 microdeletions, five of whom presented with connective tissue abnormalities. A literature review of the clinical findings associated with NF1 microdeletion was also performed. Our report confirms that connective tissue dysplasia is common in patients with NF1 microdeletions. Given the potential for associated cardiac manifestation, screening by echocardiogram may be warranted. Despite the large number (>150) of patients with known NF1 microdeletions, the clinical phenotype remains incompletely defined. Additional reports of patients with NF1 microdeletions, including comprehensive clinical and molecular information, are needed to elucidate possible genotype–phenotype correlation. PMID:16467218

  5. Spatial arrangement of the heart muscle fascicles and intramyocardial connective tissue in the Spanish fighting bull (Bos taurus).

    PubMed Central

    Sánchez-Quintana, D; Climent, V; Garcia-Martinez, V; Rojo, M; Hurlé, J M

    1994-01-01

    The spatial arrangement of the muscle fascicles and intramyocardial connective tissue was examined in the ventricles of the heart of the Spanish fighting bull (Bos taurus). In both ventricles, the muscle fascicles of the myocardium are arranged in 3 main directions, forming 3 muscle layers within the ventricular wall. The preferentially vertical arrangement of the muscle fascicles in the superficial and deep layers at the level of the fibrous aortic rings and the base of the semilunar valve leaflets suggests that these fascicles are actively involved in valvular dynamics. After controlled digestion of myocytes and elastic fibres with NaOH, a 3-dimensional arrangement of the scaffolding of connective tissue that supports the muscle fascicles and myocytes was observed. The arrangement and structure of this scaffolding may influence the order of contraction of muscle fascicles in different layers of the ventricle. In addition, differences were observed between the connective tissue scaffolding surrounding the myocytes of the 2 ventricles; these variations were correlated with the different biomechanical properties. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 8 Fig. 9 Fig. 10 PMID:8014119

  6. [A connective tissue tumor in the mussel Mytilus trossulus from a polluted region of Nakhodka Bay, the Sea of Japan].

    PubMed

    Usheva, L N; Frolova, L T

    2000-01-01

    A tumor was found for the first time in a mussel Mytilus trossulus from a heavily polluted area of Nakhodka Bay, Sea of Japan. Tumor cells were found in the connective tissue of different organs and also in gill vessels and hemal sinuses of the visceral mass. They were both attached and diffuse. The tumor was at an advanced stage, replacing the normal connective tissue cells, and formed nodes. The tumor cells were polymorphic, with a high nucleocytoplasmic ratio, and had a prominent nucleolus. The size of their nuclei was three to five times that of the nuclei of agranular hemocytes. The mitotic activity of the tumor cells was more than an order of magnitude higher than in the normal cells: the mean mitotic index was 1.4 +/- 0.5%, ranging from 0.97 to 2.3% in different organs. The mitotic indices in the connective tissue cells of three normal mussels were 0, 0, and 0.12%. A significant proportion (up to 78%) of the mitotic cells were at metaphase. The frequency of abnormal mitoses was 17%. Metaphases with displaced (often multiple) chromosomes constituted 71% of abnormal mitoses; anaphases, 8%; and tri- and tetrapolar mitoses, 11%. The tumor described is similar to diffuse sarcomatoid diseases of mussels from other geographical regions. PMID:10732366

  7. Circulating Protein Fragments of Cartilage and Connective Tissue Degradation Are Diagnostic and Prognostic Markers of Rheumatoid Arthritis and Ankylosing Spondylitis

    PubMed Central

    Bay-Jensen, Anne C.; Wichuk, Stephanie; Byrjalsen, Inger; Leeming, Diana J.; Morency, Nathalie; Christiansen, Claus; Karsdal, Morten A.; Maksymowych, Walter P.

    2013-01-01

    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. PMID:23365672

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

    PubMed Central

    Pawlowski, Przemyslaw; Eckstein, Anja; Johnson, Kristian; Chyczewski, Lech; Mysliwiec, Janusz

    2014-01-01

    Purpose. To assess FGF-?, TGF-?, 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-?, TGF-?, 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-? expression was seen in all GO. Increased FGF-? 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-? and TGF-? expression may contribute to tissue remodeling, fibrosis, and perpetuation of inflammation in the orbital tissue of GO especially in severe GO. PMID:25309050

  9. Reactions of connective tissue to amalgam, intermediate restorative material, mineral trioxide aggregate, and mineral trioxide aggregate mixed with chlorhexidine.

    PubMed

    Sumer, Mahmut; Muglali, Mehtap; Bodrumlu, Emre; Guvenc, Tolga

    2006-11-01

    The aim of this study was to histopathologically examine the biocompatibility of the high-copper amalgam, intermediate restorative material (IRM), mineral trioxide aggregate (MTA), and MTA mixed with chlorhexidine (CHX). This study was conducted to observe the rat subcutaneous connective tissue reaction to the implanted tubes filled with amalgam, IRM, MTA, and MTA mixed with CHX. The animals were sacrificed 15, 30, and 60 days after the implantation procedure. The implant sites were excised and prepared for histological evaluation. Sections of 5 to 6 microm thickness were cut by a microtome and stained with hemotoxylin eosin and examined under a light microscope. The inflammatory reactions were categorized as weak (none or few inflammatory cells < or =25 cells), moderate (>25 cells), and severe (a lot of inflammatory cells not to be counted, giant cells, and granulation tissue). Thickness of fibrous capsules measured five different areas by the digital imaging and the mean values were scored. Amalgam, IRM, and MTA mixed with CHX caused a weak inflammatory response on days 15, 30, and 60. MTA provoked an initial severe inflammatory response that subsided at the 30 and 60 day study period. A clear fibrous capsule was observed beginning from the 15 days in all of the groups. Within the limits of this study, amalgam, IRM, MTA, and MTA mixed with CHX materials were surrounded by fibrous connective tissue indicated that they were well tolerated by the tissues, therefore, MTA/CHX seemed to be biocompatible. PMID:17055915

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

    PubMed

    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. PMID:24437605

  11. Comparison of ADM and Connective Tissue Graft as the Membrane in Class II Furcation Defect Regeneration: A Randomized Clinical Trial.

    PubMed

    Esfahanian, Vahid; Farhad, Shirin; Sadighi Shamami, Mehrnaz

    2014-01-01

    Background and aims. Furcally-involved teeth present unique challenges to the success of periodontal therapy and influence treatment outcomes. This study aimed to assess to compare use of ADM and connective tissue membrane in class II furcation defect regeneration. Materials and methods. 10 patient with 2 bilaterally class II furcation defects in first and/or second maxilla or man-dibular molar without interproximal furcation involvement, were selected. Four weeks after initial phase of treatment, before and thorough the surgery pocket depth (PD), clinical attachment level to stent (CAL-S), free gingival margin to stent(FGM-S) , crestal bone to stent (Crest-S), horizontal defect depth to stent (HDD-S) and vertical defect depth to stent (VDD-S) and crestal bone to defect depth measured from stent margin. Thereafter, one side randomly treated using connective tissue and DFDBA (study group) and opposite side received ADM and DFDBA (control group). After 6 months, soft and hard tissue parameters measured again in re-entry. Results. Both groups presented improvements after therapies (P & 0.05). No inter-group differences were seen in PD re-duction (P = 0.275), CAL gain (P = 0.156), free gingival margin (P = 0.146), crest of the bone (P = 0.248), reduction in horizontal defects depth (P = 0.139) and reduction in vertical defects depth (P = 0.149). Conclusion. Both treatments modalities have potential of regeneration without any adverse effect on healing process. Connective tissue grafts did not have significant higher bone fill compared to that of ADM. PMID:25093054

  12. Comparison of ADM and Connective Tissue Graft as the Membrane in Class II Furcation Defect Regeneration: A Randomized Clinical Trial

    PubMed Central

    Esfahanian, Vahid; Farhad, Shirin; Sadighi Shamami, Mehrnaz

    2014-01-01

    Background and aims. Furcally-involved teeth present unique challenges to the success of periodontal therapy and influence treatment outcomes. This study aimed to assess to compare use of ADM and connective tissue membrane in class II furcation defect regeneration. Materials and methods. 10 patient with 2 bilaterally class II furcation defects in first and/or second maxilla or man-dibular molar without interproximal furcation involvement, were selected. Four weeks after initial phase of treatment, before and thorough the surgery pocket depth (PD), clinical attachment level to stent (CAL-S), free gingival margin to stent(FGM-S) , crestal bone to stent (Crest-S), horizontal defect depth to stent (HDD-S) and vertical defect depth to stent (VDD-S) and crestal bone to defect depth measured from stent margin. Thereafter, one side randomly treated using connective tissue and DFDBA (study group) and opposite side received ADM and DFDBA (control group). After 6 months, soft and hard tissue parameters measured again in re-entry. Results. Both groups presented improvements after therapies (P & 0.05). No inter-group differences were seen in PD re-duction (P = 0.275), CAL gain (P = 0.156), free gingival margin (P = 0.146), crest of the bone (P = 0.248), reduction in horizontal defects depth (P = 0.139) and reduction in vertical defects depth (P = 0.149). Conclusion. Both treatments modalities have potential of regeneration without any adverse effect on healing process. Connective tissue grafts did not have significant higher bone fill compared to that of ADM. PMID:25093054

  13. Sirolimus for Autoimmune Disease of Blood Cells

    ClinicalTrials.gov

    2014-10-17

    Autoimmune Pancytopenia; Autoimmune Lymphoproliferative Syndrome (ALPS); Evans Syndrome; Idiopathic Thrombocytopenic Purpura; Anemia, Hemolytic, Autoimmune; Autoimmune Neutropenia; Lupus Erythematosus, Systemic; Inflammatory Bowel Disease; Rheumatoid Arthritis

  14. Autoimmunity, Not a Developmental Defect, is the Cause for Subfertility of Autoimmune Regulator (Aire) Deficient Mice.

    PubMed

    Kekäläinen, E; Pöntynen, N; Meri, S; Arstila, T P; Jarva, H

    2015-05-01

    Autoimmune regulator's (AIRE) best characterized role is in the generation immunological tolerance, but it is also involved in many other processes such as spermatogenesis. Loss-of-function mutations in AIRE cause a disease called autoimmune polyendocrinopathy, candidiasis and ectodermal dystrophy (APECED; also called autoimmune polyendocrinopathy syndrome type 1, APS-1) that is dominated by various autoimmune manifestations, mainly endocrinopathies. Both patients with APECED and Aire(-/-) mice suffer from varying levels of infertility, but it is not clear if it is a result of an autoimmune tissue damage or more of a developmental defect. In this study, we wanted to resolve whether or not the reduced fertility of Aire(-/-) mice is dependent on the adaptive immune system and therefore a manifestation of autoimmunity in these mice. We generated lymphopenic mice without Aire expression that were devoid of the autoimmune manifestations previously reported in immunocompetent Aire(-/-) mice. These Aire(-/-) Rag1(-/-) mice regained full fertility. This confirms that the development of infertility in Aire(-/-) mice requires a functional adaptive immune system. We also show that only the male Aire(-/-) mice are subfertile, whereas Aire(-/-) females produce litters normally. Moreover, the male subfertility can be adoptively transferred with lymphocytes from Aire(-/-) donor mice to previously fertile lymphopenic Aire(-/-) recipients. Our data show that subfertility in Aire(-/-) mice is dependent on a functional adaptive immune system thus confirming its autoimmune aetiology. PMID:25689230

  15. Analytical and numerical analyses of the micromechanics of soft fibrous connective tissues

    E-print Network

    Gal deBotton; Tal Oren

    2012-01-02

    State of the art research and treatment of biological tissues require accurate and efficient methods for describing their mechanical properties. Indeed, micromechanics motivated approaches provide a systematic method for elevating relevant data from the microscopic level to the macroscopic one. In this work the mechanical responses of hyperelastic tissues with one and two families of collagen fibers are analyzed by application of a new variational estimate accounting for their histology and the behaviors of their constituents. The resulting, close form expressions, are used to determine the overall response of the wall of a healthy human coronary artery. To demonstrate the accuracy of the proposed method these predictions are compared with corresponding 3-D finite element simulations of a periodic unit cell of the tissue with two families of fibers. Throughout, the analytical predictions for the highly nonlinear and anisotropic tissue are in agreement with the numerical simulations.

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

    PubMed

    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 positive change in [Formula: see text] and [Formula: see text] with increases in [Formula: see text]-the findings lend support to the hypotheses, implicating the implicit dependence of UV-induced cross-links on [Formula: see text] and [Formula: see text] for directing tissue stiffness and resilience. From a practical perspective, the study is a step in the direction to establish a UV irradiation treatment protocol for effective control of exogenous cross-linking in connective tissues. PMID:24419559

  17. Transforming Growth Factor-? (TGF-?) Expression is Increased in the Subsynovial Connective Tissues of Patients with Idiopathic Carpal Tunnel Syndrome

    PubMed Central

    Chikenji, Takako; Gingery, Anne; Zhao, Chunfeng; Passe, Sandra M.; Ozasa, Yasuhiro; Larson, Dirk; An, Kai-Nan; Amadio, Peter C.

    2014-01-01

    Non-inflammatory fibrosis of the subsynovial connective tissue (SSCT) is a hallmark of carpal tunnel syndrome (CTS). The etiology of this finding and its relationship to the development of CTS remain poorly understood. Recent studies have found that transforming growth factor-? (TGF-?) plays a central role in fibrosis. The purpose of this study was to investigate the expression of TGF-? and connective tissue growth factor (CTGF), a downstream mediator of TGF-?, in the pathogenesis of CTS. We compared SSCT specimens from 26 idiopathic CTS patients with specimens from 10 human cadaver controls with no previous diagnosis of CTS. Immunohistochemistry was performed to determine levels TGF-?1, CTGF, collagen 1(Col1) and collagen 3 (Col3) expression. TGF-?1(P<0.01), CTGF (P<0.01), and Col3 (P<0.01) were increased in SSCT of CTS patients compared with control tissue. In addition, a strong positive correlation was found between TGF-?1 and CTGF, (R2=0.80, p<0.01) and a moderate positive correlation between Col3 and TGF-?1 (R2=0.49, p<0.01). These finding suggest that there is an increased expression of TGF-? and CTGF, a TGF-? regulated protein, and that this TGF-? activation may be responsible for SSCT fibrosis in CTS patients. PMID:24014274

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

    PubMed

    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 TGF?s 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-elastic extracellular matrixes, and interact closely with tropoelastin and integrins. Not only do microfibrils provide structural integrity 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 mediate both inflammatory and fibrotic processes to enable effective tissue repair and play roles in pathogenesis of Ehlers-Danlos, heart disease, and regeneration and recovery of musculo-tendinous tissue. One of the roles of thrombospondin 1 is activation of TGF?. Increased expression of thrombospondin and TGF? activity was observed in fibrotic skin disorders such as keloids and scleroderma. Cartilage oligomeric matrix protein (COMP) or thrombospondin-5 is primarily present in the cartilage. High levels of COMP are present in fibrotic scars and systemic sclerosis of the skin, and in tendon, especially with physical activity, loading and post-injury. It plays a role in vascular wall remodeling and has been found in atherosclerotic plaques as well. PMID:24443019

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

    PubMed

    Marafetti, Lucas E; Romeo, Horacio E

    2014-11-15

    The participation of sympathetic nerve fibers in the innervation of the nasal-associated lymphoid tissues (NALT) was investigated in hamsters. Vesicular monoamine transporter 2 (VMAT2), an established sympathetic marker, is expressed in all neurons of superior cervical ganglia (SCG). In addition, VMAT2 -immunoreactive nerve fibers were localized in the NALT as well as in adjacent anatomical structures of the upper respiratory tract. Unilateral surgical ablation of the SCG abolished VMAT2 innervation patterns ipsilaterally while the contra lateral side is unaffected. These results provide the anatomical substrate for a neuroimmune connection in the NALT. PMID:25281233

  20. Development of intraspinal ectopic endometrial tissue in connection with tethered cord syndrome.

    PubMed

    Cui, Ling-ling; Cao, Ji-bin; Fan, Guo-guang; Lin, Xu-yong; Xu, Ke

    2014-01-01

    We herein report a rare case of intraspinal ectopic endometrial tissue associated with tethered cord syndrome. The patient underwent MR imaging of the lumbar spine and CT spinal angiography. Asymptomatic dysraphism was also detected, including spinal bifida, low-lying conus medullaris, spinal meningocele and a lumbosacral lipoma. Venous reflux obstruction was also suggested. The patient underwent L2-S1 laminectomy and microdecompression of the lesion. The histological and immunohistochemical features were characteristic of ectopic endometrial tissue. Since the surgery, no neurological signs have been noted, either during or outside the patient's menstrual periods. The two-month follow-up MRI scans showed a regression of the lesion. PMID:25447661

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

    SciTech Connect

    Kubota, Jun [Gunma University School of Medicine, Department of Nuclear Medicine (Japan); Tsunemura, Mami [Gunma University School of Medicine, Department of Diagnostic Radiology (Japan); Amano, Shigeko [Gunma University School of Medicine, Department of Nuclear Medicine (Japan); Tokizawa, Shigemi [Gunma University School of Medicine, Department of Hygiene and Virology (Japan); Oowada, Susumu [Gunma University School of Medicine, Department of Second Surgery (Japan); Shinkai, Hiroko [Gunma Health Foundation (Japan); Maehara, Yasunobu [Gunma University School of Medicine, Department of Diagnostic Radiology (Japan); Endo, Keigo [Gunma University School of Medicine, Department of Nuclear Medicine (Japan)

    1997-05-15

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

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

    PubMed

    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 ??smooth muscle actin (??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. PMID:25815693

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

    PubMed Central

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

    2013-01-01

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

  4. Analysis of connective tissues by laser capture microdissection and reverse transcriptase-polymerase chain reaction

    Microsoft Academic Search

    Robin Jacquet; Jennifer Hillyer; William J. Landis

    2005-01-01

    Studies of gene expression from bone, cartilage, and other tissues are complicated by the fact that their RNA, collected and pooled for analysis, often represents a wide variety of composite cells distinct in individual phenotype, age, and state of maturation. Laser capture microdissection (LCM) is a technique that allows specific cells to be isolated according to their phenotype, condition, or

  5. Autoimmune effector memory T cells: the bad and the good

    PubMed Central

    Devarajan, Priyadharshini; Chen, Zhibin

    2014-01-01

    Immunological memory is a hallmark of adaptive immunity, a defense mechanism endowed to vertebrates during evolution. However, an autoimmune pathogenic role of memory lymphocytes is also emerging with accumulating evidence, despite reasonable skepticism on their existence in a chronic setting of autoimmune damage. It is conceivable that autoimmune memory would be particularly harmful since memory cells would constantly “remember” and attack the body's healthy tissues. It is even more detrimental given the resistance of memory T cells to immunomodulatory therapies. In this review, we focus on self-antigen-reactive CD4+ effector memory T (TEM) cells, surveying the evidence for the role of the TEM compartment in autoimmune pathogenesis. We will also discuss the role of TEM cells in chronic and acute infectious disease settings and how they compare to their counterparts in autoimmune diseases. With their long-lasting potency, the autoimmune TEM cells could also play a critical role in anti-tumor immunity, which may be largely based on their reactivity to self-antigens. Therefore, although autoimmune TEM cells are “bad” due to their role in relentless perpetration of tissue damage in autoimmune disease settings, they are unlikely a by-product of industrial development along the modern surge of autoimmune disease prevalence. Rather, they may be a product of evolution for their “good” in clearing damaged host cells in chronic infections and malignant cells in cancer settings. PMID:24203440

  6. Autoimmune primary ovarian insufficiency.

    PubMed

    Silva, C A; Yamakami, L Y S; Aikawa, N E; Araujo, D B; Carvalho, J F; Bonfá, E

    2014-01-01

    Primary ovarian insufficiency (POI) is defined as sustained amenorrhea, increased follicle-stimulating hormone and low estrogen levels, whereas diminished ovarian reserve (DOR) is characterized as regular menses and alterations of ovarian reserve tests. POI of autoimmune origin may be associated with adrenal autoimmunity, non-adrenal autoimmunity or isolated. This autoimmune disease is characterized by serum ovarian, adrenocortical or steroidogenic cell autoantibodies. POI of adrenal autoimmune origin is the most frequent type observed in 60-80% of patients. Clinically, amenorrhea is the hallmark of POI, however before menstruation stops completely, irregular cycles occur. Infertility, hot flushes, vaginal atrophy, and dyspareunia are also common. Autoimmune oophoritis is characterized by mononuclear inflammatory cell infiltrate in the theca cells of growing follicles, with early stage follicles without lymphocytic infiltration. This infiltrate includes plasma, B and T-cells. A novel classification criterion for autoimmune POI/DOR is proposed subdividing in three distinct categories (possible, probable and confirmed) according to autoantibodies, autoimmune disease and ovarian histology. Unfortunately, up to date guidelines for the treatment of autoimmune oophoritis are not available. Strategies to POI treatment include hormone replacement and infertility therapy. Assisted conception with donated oocytes has been proven to achieve pregnancy by intra cytoplasmic sperm injection in POI women. PMID:24418305

  7. NK Cell Autoreactivity and Autoimmune Diseases

    PubMed Central

    Poggi, Alessandro; Zocchi, Maria Raffaella

    2014-01-01

    Increasing evidences have pointed out the relevance of natural killer (NK) cells in organ-specific and systemic autoimmune diseases. NK cells bear a plethora of activating and inhibiting receptors that can play a role in regulating reactivity with autologous cells. The activating receptors recognize natural ligands up-regulated on virus-infected or stressed or neoplastic cells. Of note, several autoimmune diseases are thought to be linked to viral infections as one of the first event in inducing autoimmunity. Also, it is conceivable that autoimmunity can be triggered when a dysregulation of innate immunity occurs, activating T and B lymphocytes to react with self-components. This would imply that NK cells can play a regulatory role during adaptive immunity; indeed, innate lymphoid cells (ILCs), comprising the classical CD56+ NK cells, have a role in maintaining or alternating tissue homeostasis secreting protective and/or pro-inflammatory cytokines. In addition, NK cells display activating receptors involved in natural cytotoxicity and the activating isoforms of receptors for HLA class I that can interact with healthy host cells and induce damage without any evidence of viral infection or neoplastic-induced alteration. In this context, the interrelationship among ILC, extracellular-matrix components, and mesenchymal stromal cells can be considered a key point for the control of homeostasis. Herein, we summarize evidences for a role of NK cells in autoimmune diseases and will give a point of view of the interplay between NK cells and self-cells in triggering autoimmunity. PMID:24550913

  8. [Anti-TNFalpha therapy in systemic autoimmune and/or inflammatory diseases].

    PubMed

    Régent, Alexis; Mouthon, Luc

    2009-05-01

    TNFalpha plays a crucial role in the physiopathology of a large number of auto-immune and/or inflammatory systemic diseases. In addition to authorized indications including rheumatoid arthritis, ankylosing spondylitis, Crohn disease, ulcerative colitis, psoriatic arthritis and plaque psoriasis, TNFalpha blockers have been tested in a wide range of auto-immune and/or inflammatory diseases. TNFalpha blockers might be an option in refractory ANCA-associated vasculitis, sarcoďdosis, adult onset Still disease, Behçet disease, AA amyloďdosis and TRAPS. However, pertaining to the limited number of prospective randomized trails available, the small number of patients included and the poor methodology, it is difficult to define their place in the therapeutic strategy in these conditions. The therapeutic effect of TNFalpha blockers is often suspensive and disease flares are frequently observed during sustained treatment, as in the case of Behçet's disease. Published data do not support the use of TNFalpha blockers in connective tissue diseases. PMID:19349142

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

    PubMed Central

    Castori, Marco

    2012-01-01

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

  10. Molecular Mechanism for Connective Tissue Destruction by Dipeptidyl Aminopeptidase IV Produced by the Periodontal Pathogen Porphyromonas gingivalis

    PubMed Central

    Kumagai, Yumi; Yagishita, Hisao; Yajima, Ayako; Okamoto, Tatsuya; Konishi, Kiyoshi

    2005-01-01

    Porphyromonas gingivalis is a pathogen associated with adult periodontitis. It produces dipeptidyl aminopeptidase IV (DPPIV), which may act as a virulence factor by contributing to the degradation of connective tissue. We investigated the molecular mechanism by which DPPIV contributes to the destruction of connective tissue. DPPIV itself did not show gelatinase or collagenase activity toward human type I collagen, but it promoted the activity of the host-derived matrix metalloproteinase 2 (MMP-2) (gelatinase) and MMP-1 (collagenase). DPPIV bound to fibronectin and mediated the adhesion of P. gingivalis to fibronectin. Mutant DPPIV with catalytic Ser mutagenized to Ala (DPPSA) did not accelerate the degradation of collagen and gelatin by MMPs but retained fibronectin-binding activity. The adhesion of human gingival fibroblasts and NIH 3T3 cells to fibronectin was inhibited by DPPIV. Strain 4351ADPPSA exhibited an intermediate level of virulence in mice, between that of the strain expressing wild-type DPPIV (4351ADPP) and that of the strain harboring only the plasmid vector (4351AVEC). It is suggested that both activity promoting the degradation of collagen and gelatin and binding to fibronectin are required for full virulence. These results reveal novel biological functions of DPPIV and suggest a pathological role in the progression of periodontitis. PMID:15845467

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

    PubMed Central

    Yu, Lilei; Zhou, Xiaohui; Yang, Kang

    2014-01-01

    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 ?t 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. PMID:25214713

  12. Influence of Oxygen Concentration and Mechanical Factors on Differentiation of Connective Tissues in vitro

    Microsoft Academic Search

    C. Andrew L. Bassett; Ingeborg Herrmann

    1961-01-01

    MARCHAND1 postulated that osteoblasts may differentiate from mesenchymal cells. Recently, it was observed that a strain of cells, derived from adult skeletal muscle, elaborated in tissue culture a sub-stance that appeared to be chondro-osteoid2. Since the factors responsible for this cell behaviour were unknown, investigation of the effects of varying mechanical and nutritional factors on a reproducible in vitro system

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

    PubMed Central

    2013-01-01

    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. PMID:23374322

  14. Matrix Metalloproteinase-dependent turnover of cartilage, synovial membrane, and connective tissue is elevated in rats with collagen induced arthritis

    PubMed Central

    2012-01-01

    Background Rheumatoid arthritis is a disease affecting the extracellular matrix of especially synovial joints. The thickness of the synovial membrane increases and surrounding tissue degrades, leading to altered collagen balance in the tissues. In this study, we investigated the altered tissue balance of cartilage, synovial membrane, and connective tissue in collagen induced arthritis (CIA) in rats. Methods Six newly developed ELISAs quantifying MMP-derived collagen degradation (C1M, C2M, and C3M) and formation (P1NP, P2NP, and P3NP) was used to detect cartilage turnover in rats with CIA. Moreover, CTX-II was used to detect alternative type II collagen degradation and as control of the model. 10 Lewis rats were injected with porcrine type II collagen twice with a 7 day interval and 10 rats was injected with 0.05 M acetic acid as control. The experiment ran for 26 days. Results A significant increase in the degradation of type I, II, and III collagen (C1M, C2M, and C3M, respectively) was detected on day 22 (P?=?0.0068, P?=?0.0068, P?tissues of the synovial joints, leading to increased pain and degeneration of the synovial joints. PMID:22992383

  15. Human Cytomegalovirus and Autoimmune Disease

    PubMed Central

    2014-01-01

    Human cytomegalovirus (HCMV) represents a prototypic pathogenic member of the ?-subgroup of the herpesvirus family. A range of HCMV features like its lytic replication in multiple tissues, the lifelong persistence through periods of latency and intermitting reactivation, the extraordinary large proteome, and extensive manipulation of adaptive and innate immunity make HCMV a high profile candidate for involvement in autoimmune disorders. We surveyed the available literature for reports on HCMV association with onset or exacerbation of autoimmune disease. A causative linkage between HCMV and systemic lupus erythematosus (SLE), systemic sclerosis (SSc), diabetes mellitus type 1, and rheumatoid arthritis (RA) is suggested by the literature. However, a clear association of HCMV seroprevalence and disease could not be established, leaving the question open whether HCMV could play a coresponsible role for onset of disease. For convincing conclusions population-based prospective studies must be performed in the future. Specific immunopathogenic mechanisms by which HCMV could contribute to the course of autoimmune disease have been suggested, for example, molecular mimicry by UL94 in SSc and UL83/pp65 in SLE patients, as well as aggravation of joint inflammation by induction and expansion of CD4+/CD28? T-cells in RA patients. Further studies are needed to validate these findings and to lay the grounds for targeted therapeutic intervention. PMID:24967373

  16. Molecular Diagnosis in Autoimmune Skin Blistering Conditions

    PubMed Central

    Otten, J.V.; Hashimoto, T.; Hertl, M.; Payne, A.S.; Sitaru, C.

    2014-01-01

    Blister formation in skin and mucous membranes results from a loss of cell-cell or cell-matrix adhesion and is a common outcome of pathological events in a variety of conditions, including autoimmune and genetic diseases, viral and bacterial infections, or injury by physical and chemical factors. Autoantibodies against structural components maintaining cell-cell and cell-matrix adhesion induce tissue damage in autoimmune blistering diseases. Detection of these autoantibodies either tissue-bound or circulating in serum is essential to diagnose the autoimmune nature of disease. Various immunofluorescence methods as well as molecular immunoassays, including enzyme-linked immunosorbent assay and immunoblotting, belong to the modern diagnostic algorithms for these disorders. There is still a considerable need to increase awareness of the rare autoimmune blistering diseases, which often show a severe, chronic-relapsing course, among physicians and the public. This review article describes the immunopathological features of autoimmune bullous diseases and the molecular immunoassays currently available for their diagnosis and monitoring. PMID:24160488

  17. Autoimmunity: Alopecia Areata

    Microsoft Academic Search

    Maria Hordinsky; Marna Ericson

    2004-01-01

    Strong direct and indirect evidence supports an autoimmune etiology for alopecia areata. T lymphocytes that have been shown to be oligoclonal and autoreactive are predominantly present in the peribulbar inflammatory infiltrate. Alopecia areata frequently occurs in association with other autoimmune diseases, such as thyroiditis and vitiligo, and autoantibodies to follicular components have been detected. Finally, the use of immune modulating

  18. Autoimmune polyendocrine syndromes.

    PubMed

    Cutolo, Maurizio

    2014-02-01

    Autoimmune polyendocrine syndromes (APS), also called polyglandular autoimmune syndromes (PGAS), are a heterogeneous group of rare diseases characterized by autoimmune activity against more than one endocrine organs, although non-endocrine organs can be affected. The two major autoimmune polyendocrine syndromes, (type1-type2/APS-1 and APS-2), both have Addison's disease as a prominent component. Further autoimmune polyendocrine syndromes include APS3 and APS4. The major autoimmune polyendocrine syndromes have a strong genetic component with the type 2 syndrome occurring in multiple generations and the type I syndrome in siblings. It is well recognized that more than 20years may elapse between the onset on one endocrinopathy and the diagnosis of the next, for example, almost 40-50% of subjects with Addison's disease will develop an associated endocrinopathy. The discovery of the polyendocrine autoimmune syndromes offered the possibility to understand autoimmune disorders with particular interest for type 1A diabetes and the neuroendocrine immunology (NEI) is further contributing to understand the links. PMID:24055063

  19. Update in Endocrine Autoimmunity

    PubMed Central

    Anderson, Mark S.

    2008-01-01

    Context: The endocrine system is a common target in pathogenic autoimmune responses, and there has been recent progress in our understanding, diagnosis, and treatment of autoimmune endocrine diseases. Synthesis: Rapid progress has recently been made in our understanding of the genetic factors involved in endocrine autoimmune diseases. Studies on monogenic autoimmune diseases that include endocrine phenotypes like autoimmune polyglandular syndrome type 1 and immune dysregulation, polyendocrinopathy, enteropathy, X-linked have helped reveal the role of key regulators in the maintenance of immune tolerance. Highly powered genetic studies have found and confirmed many new genes outside of the established role of the human leukocyte antigen locus with these diseases, and indicate an essential role of immune response pathways in these diseases. Progress has also been made in identifying new autoantigens and the development of new animal models for the study of endocrine autoimmunity. Finally, although hormone replacement therapy is still likely to be a mainstay of treatment in these disorders, there are new agents being tested for potentially treating and reversing the underlying autoimmune process. Conclusion: Although autoimmune endocrine disorders are complex in etiology, these recent advances should help contribute to improved outcomes for patients with, or at risk for, these disorders. PMID:18842982

  20. Neuroendocrinology of autoimmunity

    Microsoft Academic Search

    Michael Harbuz

    2002-01-01

    The HPA axis is fundamental for long-term survival and protection from the ravages of autoimmune disease. Continuing investigations suggest that the hypothesis linking susceptibility to autoimmune dissease and a hyporesponsive HPA axis is somewhat simplistic. Instead, data from a number of different human diseases and from preclinical studies in a variety of models have suggested a more complicated picture. Alterations

  1. Progesterone and autoimmune disease.

    PubMed

    Hughes, Grant C

    2012-05-01

    Sexual dimorphism in human immune systems is most apparent in the female predominance of certain autoimmune diseases (ADs) like systemic lupus erythematosus (SLE). Epidemiologic, observational and experimental evidence strongly suggest sex steroids are important modulators of genetic risk in human AD. In this regard, the roles of progesterone (Pg), an immunomodulatory female sex steroid, are poorly understood. Several lines of investigation indicate Pg and synthetic progestins impact risk of AD and immune-mediated injury in different ways depending on their concentrations and their engagement of various Pg receptors expressed in immune organs, immune cells or tissues targeted by immune attack. At low physiologic levels, Pg may enhance interferon-alpha (IFN-?) pathways important in SLE pathogenesis. Commonly used synthetic progestins may have the opposite effect. At pregnancy levels, Pg may suppress disease activity in rheumatoid arthritis (RA) and multiple sclerosis (MS) via inhibition of T helper type 1 (Th1) and Th17 pathways and induction of anti-inflammatory molecules. Importantly, Pg's immunomodulatory effects differ from those of estrogens and androgens. An additional layer of complexity arises from apparent interdependence of sex hormone signaling pathways. Identifying mechanisms by which Pg and other sex steroids modulate risk of AD and immune-mediated injury will require clarification of their cellular and molecular targets in vivo. These future studies should be informed by recent genetic discoveries in human AD, particularly those revealing their sex-specific genetic associations. PMID:22193289

  2. Integrin-extracellular matrix interactions in connective tissue remodeling and osteoblast differentiation

    NASA Technical Reports Server (NTRS)

    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.

  3. Autoimmune Cholangitis: A Variant Syndrome of Autoimmune Hepatitis

    PubMed Central

    Sharma, Brij; Raina, Sujeet; Sharma, Rajesh

    2014-01-01

    Autoimmune cholangitis (AIC) or autoimmune cholangiopathy is a chronic inflammation of liver and a variant syndrome of autoimmune hepatitis (AIH). We present a case of an adult female who had biochemical features of cholestasis and transaminasemia but aminotransferases were not in the hepatitis range and had histological evidence of bile duct injury which was subsequently diagnosed as autoimmune cholangitis. PMID:25374727

  4. Ovarian autoimmune disease: clinical concepts and animal models.

    PubMed

    Warren, Bryce D; Kinsey, William K; McGinnis, Lynda K; Christenson, Lane K; Jasti, Susmita; Stevens, Anne M; Petroff, Brian K; Petroff, Margaret G

    2014-11-01

    The ovary is not an immunologically privileged organ, but a breakdown in tolerogenic mechanisms for ovary-specific antigens has disastrous consequences on fertility in women, and this is replicated in murine models of autoimmune disease. Isolated ovarian autoimmune disease is rare in women, likely due to the severity of the disease and the inability to transmit genetic information conferring the ovarian disease across generations. Nonetheless, autoimmune oophoritis is often observed in association with other autoimmune diseases, particularly autoimmune adrenal disease, and takes a toll on both society and individual health. Studies in mice have revealed at least two mechanisms that protect the ovary from autoimmune attack. These mechanisms include control of autoreactive T cells by thymus-derived regulatory T cells, as well as a role for the autoimmune regulator (AIRE), a transcriptional regulator that induces expression of tissue-restricted antigens in medullary thymic epithelial cells during development of T cells. Although the latter mechanism is incompletely defined, it is well established that failure of either results in autoimmune-mediated targeting and depletion of ovarian follicles. In this review, we will address the clinical features and consequences of autoimmune-mediated ovarian infertility in women, as well as the possible mechanisms of disease as revealed by animal models. PMID:25327908

  5. Type 1 diabetes and polyglandular autoimmune syndrome: A review.

    PubMed

    Hansen, Martin P; Matheis, Nina; Kahaly, George J

    2015-02-15

    Type 1 diabetes (T1D) is an autoimmune disorder caused by inflammatory destruction of the pancreatic tissue. The etiopathogenesis and characteristics of the pathologic process of pancreatic destruction are well described. In addition, the putative susceptibility genes for T1D as a monoglandular disease and the relation to polyglandular autoimmune syndrome (PAS) have also been well explored. The incidence of T1D has steadily increased in most parts of the world, especially in industrialized nations. T1D is frequently associated with autoimmune endocrine and non-endocrine diseases and patients with T1D are at a higher risk for developing several glandular autoimmune diseases. Familial clustering is observed, which suggests that there is a genetic predisposition. Various hypotheses pertaining to viral- and bacterial-induced pancreatic autoimmunity have been proposed, however a definitive delineation of the autoimmune pathomechanism is still lacking. In patients with PAS, pancreatic and endocrine autoantigens either colocalize on one antigen-presenting cell or are expressed on two/various target cells sharing a common amino acid, which facilitates binding to and activation of T cells. The most prevalent PAS phenotype is the adult type 3 variant or PAS type III, which encompasses T1D and autoimmune thyroid disease. This review discusses the findings of recent studies showing noticeable differences in the genetic background and clinical phenotype of T1D either as an isolated autoimmune endocrinopathy or within the scope of polyglandular autoimmune syndrome. PMID:25685279

  6. Type 1 diabetes and polyglandular autoimmune syndrome: A review

    PubMed Central

    Hansen, Martin P; Matheis, Nina; Kahaly, George J

    2015-01-01

    Type 1 diabetes (T1D) is an autoimmune disorder caused by inflammatory destruction of the pancreatic tissue. The etiopathogenesis and characteristics of the pathologic process of pancreatic destruction are well described. In addition, the putative susceptibility genes for T1D as a monoglandular disease and the relation to polyglandular autoimmune syndrome (PAS) have also been well explored. The incidence of T1D has steadily increased in most parts of the world, especially in industrialized nations. T1D is frequently associated with autoimmune endocrine and non-endocrine diseases and patients with T1D are at a higher risk for developing several glandular autoimmune diseases. Familial clustering is observed, which suggests that there is a genetic predisposition. Various hypotheses pertaining to viral- and bacterial-induced pancreatic autoimmunity have been proposed, however a definitive delineation of the autoimmune pathomechanism is still lacking. In patients with PAS, pancreatic and endocrine autoantigens either colocalize on one antigen-presenting cell or are expressed on two/various target cells sharing a common amino acid, which facilitates binding to and activation of T cells. The most prevalent PAS phenotype is the adult type 3 variant or PAS type III, which encompasses T1D and autoimmune thyroid disease. This review discusses the findings of recent studies showing noticeable differences in the genetic background and clinical phenotype of T1D either as an isolated autoimmune endocrinopathy or within the scope of polyglandular autoimmune syndrome. PMID:25685279

  7. [SEM studies on the connective tissue cores of the lingual papillae of the northern goshawk (Accipiter gentilis)].

    PubMed

    Emura, Shoichi; Okumura, Toshihiko; Chen, Huayue

    2008-09-01

    The lingual papillae and their connective tissue cores (CTCs) of the northern goshawk were examined by scanning electron microscopy (SEM). The length of the tongue was approximately 2.5 cm. The median groove divided the body of the tongue into symmetrical parts. At a point approximately 2/3 of the length, there were large conical papillae between the body and the root of the tongue, the apices of which were pointed towards the posterior part of the tongue. Under the light microscopy, the filiform papillae of the dorsal surface in the lingual body showed the desquamate cells of non-keratinized epithelium. There were openings of the lingual glands on the anterior part and root of the tongue. The lingual papillae and their CTCs of the northern goshawk had a structure similar to those of the white tailed eagle and black kite. PMID:18807946

  8. Development of diagnostic and treatment strategies for glaucoma through understanding and modification of scleral and lamina cribrosa connective tissue

    PubMed Central

    Quigley, Harry A.; Cone, Frances E.

    2013-01-01

    There is considerable evidence that the state of ocular connective tissues and their response in glaucomatous disease affects the degree of glaucoma damage. Both experimental and clinical data suggest that improved diagnostic and prognostic information could be derived from assessment of the mechanical responsiveness of the sclera and lamina cribrosa to intraocular pressure (IOP). Controlled mutagenesis of the sclera has produced a mouse strain that is relatively resistant to increased IOP. Alteration of the baseline scleral state could be accomplished through either increased cross-linking of fibrillar components or their reduction. The sclera is a dynamic structure, altering its structure and behavior in response to IOP change. The biochemical pathways that control these responses are fertile areas for new glaucoma treatments. PMID:23535950

  9. The existence of Merkel cells in the lingual connective tissue of the Surinam caiman, Caiman crocodilus crocodilus (order Crocodilia).

    PubMed

    Yoshie, S; Yokosuka, H; Kanazawa, H; Fujita, T

    1999-03-01

    The tongue of the Surinam caiman (a reptilian species) was studied by light microscopy including immunohistochemistry for protein gene product 9.5 (PGP 9.5), and transmission electron microscopy. The connective tissue immediately under taste buds housed a cluster of cells immunoreactive for PGP 9.5. These cells synapsed on nerves, and their cytoplasm contained characteristic granules of 90 nm in the mean diameter, glycogen particles, and bundles of intermediate filaments. In light of these ultrastructural features, they were identified as Merkel cells. The Merkel cells were also surrounded by Schwann cells. These findings indicate that the present Merkel cell-neurite-Schwann cell complex is comparable to the avian Merkel corpuscle. On the basis of the granule localization in the cytoplasm, the caiman Merkel cell was presumed to be involved in not only mechanoreception but also endocrine or paracrine functions. PMID:10223746

  10. Deformation of the Normal Monkey Optic Nerve Head Connective Tissue Following Acute IOP Elevation within 3-D Histomorphometric Reconstructions

    PubMed Central

    Yang, Hongli; Downs, J. Crawford; Sigal, Ian A.; Roberts, Michael D.; Thompson, Hillary; Burgoyne, Claude F.

    2010-01-01

    Purpose To characterize optic nerve head (ONH) connective tissue deformation following acute (15 or 30 minutes) intraocular pressure (IOP) elevation within six adult normal monkeys using 3-D histomorphometry. Methods Trephinated ONH and peripapillary sclera from both eyes of six monkeys, each perfusion fixed with one eye at IOP 10 mmHg and the other at IOP 30 or 45 mmHg by anterior chamber manometer were serial sectioned, 3-D reconstructed, 3-D delineated and quantified using standard parameters. For each monkey, inter-eye differences (high IOP eye minus IOP 10 eye) for each parameter were calculated and compared by ANOVA and EPIDmax both overall and regionally. EPIDmax deformations for each parameter were defined to be those statistically significant differences that exceeded the maximum physiologic inter-eye difference within six bilaterally normal monkeys of a previous report. Results Regional EPIDmax laminar thinning, posterior bowing of the peripapillary sclera, thinning and expansion of the scleral canal were present in most high IOP eyes and were colocalized in those demonstrating the most deformation. Laminar deformation was minimal and not only posterior but in some cases anterior in the high IOP eyes. No increase in deformation was seen in the IOP-45 versus the IOP-30 eyes. Conclusion ONH connective tissue alterations following acute IOP elevation involve regional thinning, stretching and deformation of the lamina cribrosa and peripapillary sclera which are minimal to modest in magnitude. The time-dependent character of these alterations, as well as their compressive, expansile, and shear effects on the contained axons, astrocytes, laminar and posterior ciliary circulations remain to be determined. PMID:19628739

  11. Autoimmune Thyroid Disorders

    PubMed Central

    Iddah, M. A.; Macharia, B. N.

    2013-01-01

    Purpose of Review. Studies have been published in the field of autoimmune thyroid diseases since January 2005. The review is organized into areas of etiology, autoimmune features, autoantibodies, mechanism of thyroid cell injury, B-cell responses, and T-cell responses. Also it reviews the diagnosis and the relationship between autoimmune thyroid disease, neoplasm, and kidney disorders. Recent Findings. Autoimmune thyroid diseases have been reported in people living in different parts of the world including North America, Europe, Baalkans, Asia, Middle East, South America, and Africa though the reported figures do not fully reflect the number of people infected per year. Cases are unrecognized due to inaccurate diagnosis and hence are treated as other diseases. However, the most recent studies have shown that the human autoimmune thyroid diseases (AITDs) affect up to 5% of the general population and are seen mostly in women between 30 and 50 years. Summary. Autoimmune thyroid disease is the result of a complex interaction between genetic and environmental factors. Overall, this review has expanded our understanding of the mechanism involved in pathogenesis of AITD and the relationship between autoimmune thyroid disease, neoplasm, and kidney disease. It has opened new lines of investigations that will ultimately result in a better clinical practice. PMID:23878745

  12. A comparative evaluation of the effectiveness of subpedicle acellular dermal matrix allograft with subepithelial connective tissue graft in the treatment of isolated marginal tissue recession: A clinical study

    PubMed Central

    Shori, Tony; Kolte, Abhay; Kher, Vishal; Dharamthok, Swarup; Shrirao, Tushar

    2013-01-01

    Introduction: The most common problem encountered in our day to day practice is exposed root surface or a tooth getting long. The main indication for root coverage procedures are esthetics and/or cosmetic demands followed by the management of root hypersensitivity, root caries or when it hampers proper plaque removal. Over the years, various techniques have been used to achieve root coverage. Aim and Objectives: The aim of this study was to compare the effectiveness of subpedicle acellular dermal matrix allograft (ADMA) with subepithelial connective tissue graft (SCTG) in the treatment of isolated marginal tissue recession. Materials and Methods: Twenty systemically healthy patients aged between 18 to 50 years (mean age29.7±4.35 years) with a recession defect on the labial and the buccal surfaces of any teeth were selected for the study. Ten patients received the test treatment (ADMA), ten patients received the control treatment (SCTG). Clinical recordings assessed at baseline, three months and six months post surgery, included Plaque index (PI), Papillary bleeding index (PBI), Gingival recession (REC), Probing pocket depth (PPD), Clinical attachment level (CAL) and Width of keratinized gingival (WKG). Results: Test group (ADMA) showed 86.93% mean root coverage while control group (SCTG) showed 84.72% at six months post surgery. Mean increase in the width of keratinized gingiva was significantly greater in the SCTG group (3.3±0.48mm) compared to ADMA group (2.4±0.51mm). Conclusion: Both the treatment produced a significant reduction in gingival recession and probing pocket depth and significant gain in clinical attachment level and width of keratinised gingiva. PMID:23633778

  13. Connective Tissue Disease Following Hepatitis B Vaccination; Topiramate-Associated Fatal Heat Stroke; Ramelteon-Induced Autoimmune Hepatitis; Acute Oxaliplatin-Induced Thrombotic Thrombocytopenic Purpura

    PubMed Central

    2014-01-01

    The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration’s (FDA’s) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA’s MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner. PMID:24715739

  14. Connective tissue disease following hepatitis B vaccination; topiramate-associated fatal heat stroke; ramelteon-induced autoimmune hepatitis; acute oxaliplatin-induced thrombotic thrombocytopenic purpura.

    PubMed

    Mancano, Michael A

    2014-03-01

    The purpose of this feature is to heighten awareness of specific adverse drug reactions (ADRs), discuss methods of prevention, and promote reporting of ADRs to the US Food and Drug Administration's (FDA's) MedWatch program (800-FDA-1088). If you have reported an interesting, preventable ADR to MedWatch, please consider sharing the account with our readers. Write to Dr. Mancano at ISMP, 200 Lakeside Drive, Suite 200, Horsham, PA 19044 (phone: 215-707-4936; e-mail: mmancano@temple.edu). Your report will be published anonymously unless otherwise requested. This feature is provided by the Institute for Safe Medication Practices (ISMP) in cooperation with the FDA's MedWatch program and Temple University School of Pharmacy. ISMP is an FDA MedWatch partner. PMID:24715739

  15. Changes in bone tissue under conditions of hypokinesia and in connection with age

    NASA Technical Reports Server (NTRS)

    Podrushnyak, E. P.; Suslov, E. I.

    1980-01-01

    X-ray micrography was used to study the optical density of the blackening of X-ray photographs made of five bones in 9 young people (ages 24 to 29) before and after strict bed rest for 16 to 37 days. Photometric studies of the X-ray film determined the relative concentration of bone structure before and after hypokinesia. In addition, the bone tissues of 25 cadavers of practically healthy individuals (aged 18 to 70) who died from injuries were investigated using X-ray structural analysis. Results show that the reaction to the state of hypokinesia is not uniform in different individuals and is quite often directly reversed. It was established that pronounced osteoporosis can be found in a relatively short time after conditions of hypokinesia in healthy young individuals. Results show that the stabilization of the crystalline structure of hydroxyapatite, especially its crystal formation, is finished by the age of 20 to 25. From 25 to 60, the crystal lattice remains in stable condition but X-ray analysis shows a reduction in the hydroxyapatite density.

  16. Relation between regional echo intensity and myocardial connective tissue in chronic left ventricular disease.

    PubMed Central

    Shaw, T R; Logan-Sinclair, R B; Surin, C; McAnulty, R J; Heard, B; Laurent, G J; Gibson, D G

    1984-01-01

    Cross sectional echocardiograms were recorded within one week of death in seven patients with valvular heart disease, four with coronary artery disease, and nine with congenital heart disease. Regional echo amplitude was measured from the cross sectional display by constructing histograms of pixel intensity. Parietal pericardium was used as an internal standard for setting the gain of the instrument. At necropsy myocardium was taken from the free wall of the left ventricle, the papillary muscles, and the septum. Fibrosis was assessed histologically and biochemically as hydroxyproline content. In individual samples histological and biochemical estimates were correlated. In all regions other than the septum in patients with left ventricular hypertrophy, log [collagen] correlated with median pixel intensity. The amplitude of reflected echoes from the hypertrophied septum was significantly higher than that from other samples but was similarly correlated with collagen content. Agreement between echo amplitude and histological grade was significantly less good. Thus in chronic left ventricular disease myocardial collagen content appears to be the major determinant of regional echo intensity. Reproducibility of measurements and more rigorous definition of tissue abnormalities will, however, require further study. Images PMID:6689920

  17. Autoimmunity and the Gut

    PubMed Central

    Campbell, Andrew W.

    2014-01-01

    Autoimmune diseases have increased dramatically worldwide since World War II. This is coincidental with the increased production and use of chemicals both in industrial countries and agriculture, as well as the ease of travel from region to region and continent to continent, making the transfer of a pathogen or pathogens from one part of the world to another much easier than ever before. In this review, triggers of autoimmunity are examined, principally environmental. The number of possible environmental triggers is vast and includes chemicals, bacteria, viruses, and molds. Examples of these triggers are given and include the mechanism of action and method by which they bring about autoimmunity. PMID:24900918

  18. Commensal microbiota influence systemic autoimmune responses.

    PubMed

    Van Praet, Jens T; Donovan, Erin; Vanassche, Inge; Drennan, Michael B; Windels, Fien; Dendooven, Amélie; Allais, Liesbeth; Cuvelier, Claude A; van de Loo, Fons; Norris, Paula S; Kruglov, Andrey A; Nedospasov, Sergei A; Rabot, Sylvie; Tito, Raul; Raes, Jeroen; Gaboriau-Routhiau, Valerie; Cerf-Bensussan, Nadine; Van de Wiele, Tom; Eberl, Gérard; Ware, Carl F; Elewaut, Dirk

    2015-02-12

    Antinuclear antibodies are a hallmark feature of generalized autoimmune diseases, including systemic lupus erythematosus and systemic sclerosis. However, the processes underlying the loss of tolerance against nuclear self-constituents remain largely unresolved. Using mice deficient in lymphotoxin and Hox11, we report that approximately 25% of mice lacking secondary lymphoid organs spontaneously develop specific antinuclear antibodies. Interestingly, we find this phenotype is not caused by a defect in central tolerance. Rather, cell-specific deletion and in vivo lymphotoxin blockade link these systemic autoimmune responses to the formation of gut-associated lymphoid tissue in the neonatal period of life. We further demonstrate antinuclear antibody production is influenced by the presence of commensal gut flora, in particular increased colonization with segmented filamentous bacteria, and IL-17 receptor signaling. Together, these data indicate that neonatal colonization of gut microbiota influences generalized autoimmunity in adult life. PMID:25599993

  19. Experiment K-7-29: Connective Tissue Studies. Part 1; Rat Skin, Normal and Repair

    NASA Technical Reports Server (NTRS)

    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.

  20. Restricting dietary magnesium accelerates ectopic connective tissue mineralization in a mouse model of pseudoxanthoma elasticum (Abcc6?/?)

    PubMed Central

    Jiang, Qiujie; Uitto, Jouni

    2012-01-01

    Ectopic mineralization, linked to a number of diseases, is a major cause of morbidity and mortality in humans. Pseudoxanthoma elasticum (PXE) is a heritable multisystem disorder characterized by calcium phosphate deposition in various tissues. The mineral content of diet has been suggested to modify the disease severity in PXE. The aim of this study is to explore the role of diet with reduced magnesium in modifying tissue mineralization in a mouse model of PXE. Abcc6?/? mice were placed on either standard rodent diet (control) or an experimental diet low in magnesium at weaning (4 wks) and examined for mineralization in the skin and internal organs at the ages of 1.5, 2 or 6 months by computerized morphometric analysis of histopathologic sections and by chemical assay of calcium and phosphate. Experimental Abcc6?/? mice demonstrated an accelerated, early-onset mineralization of connective tissues, as compared to control mice. Wild-type or heterozygous mice on experimental diet did not show evidence of mineralization up to 6 months of age. All mice on experimental diet showed decreased urinary calcium, increased urinary phosphate and elevated parathyroid serum levels. However, no difference in bone density at 6 months of age was noted. Our findings indicate that the mineral content, particularly magnesium, can modify the extent and the onset of mineralization in Abcc6?/? mice, and suggest that dietary magnesium levels may contribute to the phenotypic variability of PXE. The control of mineralization by dietary magnesium may have broader implications in general population in the context of vascular mineralization. PMID:22897576

  1. [Evaluation of systemic involving of the connective tissue in children with different localisation of isolated abnormal chords of the left ventricle (ACLV)].

    PubMed

    Kondrashova, V H; She?ko, L P; Kondrashova, N S

    2014-01-01

    Evaluation of the systemic involving of the connective tissue (SICT) under the new Ghent nosology (2010) showed that in children with isolated ACLV born to parents exposed to the Chernobyl disaster, its expression is associated with their location and quantity. The degree of systemic involvement of connective tissue is confirmed by the results of the analysis of features echostructure of isolated ACLV (the presence of thickening and calcification), echomorphometry, assessment of systolic (hypokinetic organization of the central hemodynamics), and the relaxation functions of the heart (initiation of diastolic dysfunction). High level of SICT (score greater than 5) indicates systemic damage to the body and particularly the heart, which requires dynamic monitoring and preventive measures. Found that the diagnostic and monitoring of children with isolated ACLV may be based on registration of systemic involvement of connective tissue with the calculation of points under the new Ghent nosology of 2010. PMID:25286592

  2. Costimulator B7-1 confers antigen-presenting-cell function to parenchymal tissue and in conjunction with tumor necrosis factor alpha leads to autoimmunity in transgenic mice.

    PubMed Central

    Guerder, S; Picarella, D E; Linsley, P S; Flavell, R A

    1994-01-01

    Tolerance to peripheral antigens is thought to result from the inability of parenchymal tissue to stimulate T cells--an inability that is believed to relate to the lack of expression of the costimulatory signal(s) required for T-cell activation. To test this model, we generated transgenic mice expressing costimulatory molecule B7-1 on the B cells of the pancreas. We find that islets from these transgenic mice are immunogenic for naive T cells in vitro and in vivo. Nonetheless, mice expressing the costimulator B7-1 specifically on beta cells do not develop diabetes, suggesting that expression of the B7-1 costimulator is not sufficient to abrogate the tolerance to peripheral antigens. We have reported that tumor necrosis factor alpha subunit (TNF-alpha) expressed by beta cells leads to a local inflammation but no islet destruction. Strikingly, however, the combination of a local inflammation due to the expression of the cytokine TNF-alpha and the expression of B7-1 results in tissue destruction and diabetes. Images PMID:7515187

  3. Stress proteins, autoimmunity, and autoimmune disease.

    PubMed

    Winfield, J B; Jarjour, W N

    1991-01-01

    At birth, the immune system is biased toward recognition of microbial antigens in order to protect the host from infection. Recent data suggest that an important initial line of defense in this regard involves autologous stress proteins, especially conserved peptides of hsp60, which are presented to T cells bearing gamma delta receptors by relatively nonpolymorphic class lb molecules. Natural antibodies may represent a parallel B cell mechanism. Through an evolving process of "physiological" autoreactivity and selection by immunodominant stress proteins common to all prokaryotes, B and T cell repertoires expand during life to meet the continuing challenge of infection. Because stress proteins of bacteria are homologous with stress proteins of the host, there exists in genetically susceptible individuals a constant risk of autoimmune disease due to failure of mechanisms for self-nonself discrimination. That stress proteins actually play a role in autoimmune processes is supported by a growing body of evidence which, collectively, suggests that autoreactivity in chronic inflammatory arthritis involves, at least initially, gamma delta cells which recognize epitopes of the stress protein hsp60. Alternate mechanisms for T cell stimulation by stress proteins undoubtedly also exist, e.g., molecular mimicry of the DR beta third hypervariable region susceptibility locus for rheumatoid arthritis by a DnaJ stress protein epitope in gram-negative bacteria. While there still is confusion with respect to the most relevant stress protein epitopes, a central role for stress proteins in the etiology of arthritis appears likely. Furthermore, insight derived from the work thus far in adjuvant-induced arthritis already is stimulating analyses of related phenomena in autoimmune diseases other than those involving joints. Only limited data are available in the area of humoral autoimmunity to stress proteins. Autoantibodies to a number of stress proteins have been identified in SLE and rheumatoid arthritis, but their pathogenetic significance remains to be established. Nevertheless, the capacity of certain stress proteins to bind to multiple proteins in the nucleus and cytoplasm both physiologically and during stress or injury to cells, suggests that stress proteins may be important elements in the "immunogenic particle" concept of the origin of antinuclear and other autoantibodies. In short, this fascinating group of proteins, so mysterious only a few years ago, has impelled truly extraordinary new lines of investigation into the nature of autoimmunity and autoimmune disease. PMID:2055095

  4. Alopecia Areata is a T-Lymphocyte Mediated Autoimmune Disease: Lesional Human T-Lymphocytes Transfer Alopecia Areata to Human Skin Grafts on SCID Mice

    Microsoft Academic Search

    Amos Gilhar; Raya Shalaginov; Bedia Assy; Sima Serafimovich; Richard S Kalish

    1999-01-01

    Much evidence suggests that alopecia areata is a tissue restricted autoimmune disease. Alopecia areata responds to immunosuppressive agents, and is associated with other tissue restricted autoimmune diseases, including autoimmune thyroiditis and vitiligo. Furthermore, hair regrows when involved scalp is transplanted to nude mice. This study was undertaken to determine whether alopecia areata is mediated by T lymphocytes. Involved scalp from

  5. Structure and function of blood and connective tissue cells of the fresh water pulmonate Lymnaea stagnalis studied by electron microscopy and enzyme histochemistry

    Microsoft Academic Search

    T. Sminia

    1972-01-01

    The morphology and the ultrastructure of the blood and connective tissue cells of Lymnaea stagnalis were studied. Special attention was paid to the role of these cells in the cellular defense mechanism (phagocytosis). This problem was investigated in injection experiments with enzyme histochemistry and electron microscopy.

  6. A Comparison of the Size Distribution of Collagen Fibrils in Connective Tissues as a Function of Age and a Possible Relation between Fibril Size Distribution and Mechanical Properties

    Microsoft Academic Search

    D. A. D. Parry; G. R. G. Barnes; A. S. Craig

    1978-01-01

    Data on the distribution of collagen fibril diameters in various connective tissues have been collected and analysed for common features. The diameter distributions of the collagen fibrils at birth and in the foetal stages of development are unimodal, whereas at maturity the mass-average diameter of the collagen fibrils is generally larger than at birth and the distributions of fibril sizes

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

    PubMed

    Raman, Maya; Mathew, Saleena

    2014-08-01

    The chemical composition and evaluation of Indian squid (Loligo duvauceli) mantle, epidermal connective tissue and tentacle is investigated in this current study. It is observed that squid mantle contains 22.2% total protein; 63.5% of the total protein is myofibrillar protein. The unique property of squid myofibrillar protein is its water solubility. Squid mantle contains 12.0% total collagen. Epidermal connective tissue has highest amounts of total collagen (17.8%). SDS-PAGE of total collagen identified high molecular weight ?-, ?- and ?- sub-chains. Amino acid profile analysis indicates that mantle and tentacle contain essential amino acids. Arginine forms a major portion of mantle collagen (272.5 g/100 g N). Isoleucine, glutamic acid and lysine are other amino acids that are found in significantly high amounts in the mantle. Sulphur containing cystine is deficit in mantle collagen. Papain digest of mantle and epidermal connective tissue is rich in uronic acid, while papain digest, collagenase digest and urea digest of epidermal connective tissue has significant amounts of sialic acid (25.2, 33.2 and 99.8 ?mol /100 g, respectively). PAS staining of papain digest, collagenase digest and urea digest also identify the association of hexoses with low molecular weight collagen fragments. Histochemical sectioning also emphasized the localized distribution of collagen in epidermal and dermal region and very sparse fibres traverse the myotome bundles. PMID:25114341

  8. Probing the mystery of Chinese medicine meridian channels with special emphasis on the connective tissue interstitial fluid system, mechanotransduction, cells durotaxis and mast cell degranulation

    Microsoft Academic Search

    Peter Chin Wan Fung; Peter Chin; Wan Fung

    2009-01-01

    This article hypothesizes that the Chinese medicine meridian system is a special channel network comprising of skin with abundant nerves and nociceptive receptors of various types, and deeper connective tissues inside the body with the flowing interstitial fluid system. These meridian channels provide efficient migratory tracks mainly due to durotaxis (also including chemotaxis) for mast cells, fibroblasts and other cells

  9. Scanning electron-microscope observations of the perikaryal projections of rabbit spinal ganglion neurons after enzymatic removal of connective tissue and satellite cells

    Microsoft Academic Search

    E. Pannese; M. Ledda; V. Conte; P. Procacci; S. Matsuda

    1990-01-01

    The true surface of rabbit spinal ganglion neurons has been made directly accessible to scanning electronmicroscope observation after removal of both the connective tissue and satellite cells that normally cover it. The neuronal surface is characterized by a profusion of slender projections whose shapes have been determined and whose length and width have been quantified. Controls carried out with transmission

  10. CCN2/Connective Tissue Growth Factor Is Essential for Pericyte Adhesion and Endothelial Basement Membrane Formation during Angiogenesis

    PubMed Central

    Huang, Bau-Lin; van Handel, Ben; Hofmann, Jennifer J.; Chen, Tom T.; Choi, Aaron; Ong, Jessica R.; Benya, Paul D.; Mikkola, Hanna; Iruela-Arispe, M. Luisa; Lyons, Karen M.

    2012-01-01

    CCN2/Connective Tissue Growth Factor (CTGF) is a matricellular protein that regulates cell adhesion, migration, and survival. CCN2 is best known for its ability to promote fibrosis by mediating the ability of transforming growth factor ? (TGF?) to induce excess extracellular matrix production. In addition to its role in pathological processes, CCN2 is required for chondrogenesis. CCN2 is also highly expressed during development in endothelial cells, suggesting a role in angiogenesis. The potential role of CCN2 in angiogenesis is unclear, however, as both pro- and anti-angiogenic effects have been reported. Here, through analysis of Ccn2-deficient mice, we show that CCN2 is required for stable association and retention of pericytes by endothelial cells. PDGF signaling and the establishment of the endothelial basement membrane are required for pericytes recruitment and retention. CCN2 induced PDGF-B expression in endothelial cells, and potentiated PDGF-B-mediated Akt signaling in mural (vascular smooth muscle/pericyte) cells. In addition, CCN2 induced the production of endothelial basement membrane components in vitro, and was required for their expression in vivo. Overall, these results highlight CCN2 as an essential mediator of vascular remodeling by regulating endothelial-pericyte interactions. Although most studies of CCN2 function have focused on effects of CCN2 overexpression on the interstitial extracellular matrix, the results presented here show that CCN2 is required for the normal production of vascular basement membranes. PMID:22363445

  11. Identification of the connective tissues synthesized by the venous and arterial endothelia of the human umbilical cord: a comparative study.

    PubMed Central

    Levene, C. I.; Bartlet, C. P.; Heale, G.

    1988-01-01

    Immunocytochemistry has been used to identify endothelial cells in sections of human umbilical cord and in cultures of the venous and arterial endothelium, using Factor VIII and Ulex europaeus as endothelial markers. The connective tissue components, including various collagen types, fibronectin and laminin, were identified and localized in the cord and in both venous and arterial cultured endothelium. Interstitial collagens synthesized by the cultured cells were isolated and quantified. Angiogenic ability was examined. The effect of a noxious stimulus, 24 h hypoxia, was quantified in cultured venous endothelium. The results showed that cultured arterial endothelium possesses a vacuolated cytoplasm which is absent in venous endothelium. The major collagens observed in venous culture were types III and V; the latter was found mainly in the cell layer. Venous endothelium was angiogenic. It responded to hypoxia by producing fewer cells, more protein/10(6) cells but less collagen, both in absolute terms and as a percentage of protein/10(6) cells, thus behaving like cultured porcine and bovine aortic endothelium. Fibronectin was the major 'glue' associated with endothelium. We conclude that culture can reveal the synthetic potential of endothelium which the cord itself does not often show; moreover culture appears essential to demonstrate that arterial and venous endothelium behave differently from each other. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 PMID:3377961

  12. Reaction of Rat Subcutaneous Connective Tissue to Resin Composites Polymerized with Different Light Curing Units and Different Lightening Methods

    PubMed Central

    Feiz, Atiyeh; Arbabzadeh Zavareh, Farahnaz; Mohammad Razavi, Seyed; Badrian, Hamid; Dolatyar, Sepideh; Vajihi, Mansoureh

    2012-01-01

    The aim of the study was to determine and compare the reaction of rat subcutaneous connective tissue to resin composites polymerized with different lights curing and lightening methods. In this in vivo study, 20 mature Wister Albino rats were used. The composite discs, 4?mm in diameter and 2?mm thick, were cured by QTH or LED light curing units with 4 different lightning methods (full power QTH, full power LED, pulse LED, and ramp LED). Five resin composite discs were implanted in each rat, so that 4 of 5 discs for implantation of cured composite discs differently and central one as control without implantation. After sacrificing at 7, 14, 30, and 60 days the inflammatory grade, fibrosis, and necrosis were determined. Freedman and Cochran tests were used to analyze the data using SPSS software ver. 15. The results of the study showed significant differences in inflammation grade and fibrosis among control group and 4 experimental groups at day 14 (P < 0.05). In necrosis, there was no significant difference among 4 groups in different times (P > 0.05). In conclusion, neither the type of light curing units (LED or QTH) nor the lightening methods can affect the grade of inflammatory reaction. PMID:22761617

  13. The Kruppel-like factor KLF15 inhibits connective tissue growth factor (CTGF) expression in cardiac fibroblasts.

    PubMed

    Wang, Baiqiu; Haldar, Saptarsi M; Lu, Yuan; Ibrahim, Osama A; Fisch, Sudeshna; Gray, Susan; Leask, Andrew; Jain, Mukesh K

    2008-08-01

    Cardiac fibrosis is a hallmark feature of pathologic remodeling of the heart in response to hemodynamic or neurohormonal stress. Accumulating evidence implicates connective tissue growth factor (CTGF) as a key mediator of this process. Our group has previously identified Kruppel-Like Factor 15 (KLF15) as an important regulator of cardiac remodeling in response to stress; however, the role of this transcription factor in cardiac fibrosis has not been reported. Here we provide evidence that treatment of neonatal rat ventricular fibroblasts (NRVFs) with the potent pro-fibrotic agent Transforming Growth Factor-beta1 (TGFbeta1) strongly reduces KLF15 expression while inducing the pro-fibrotic factor CTGF. Adenoviral overexpression of KLF15 inhibits basal and TGFbeta1-induced CTGF expression in NRVFs. Furthermore, hearts from KLF15-/- mice subjected to aortic banding exhibited increased CTGF levels and fibrosis. From a mechanistic standpoint, KLF15 inhibits basal and TGFbeta1-mediated induction of the CTGF promoter. Chromatin Immunoprecipitation (ChIP) and electrophoretic mobility shift assays demonstrate that KLF15 inhibits recruitment of the co-activator P/CAF to the CTGF promoter with no significant effect on Smad3-DNA binding. Consistent with this observation, KLF15 mediated repression of the CTGF promoter is rescued by P/CAF overexpression. Our result implicates KLF15 as a novel negative regulator of CTGF expression and cardiac fibrosis. PMID:18586263

  14. Expression variations of connective tissue growth factor in pulmonary arteries from smokers with and without chronic obstructive pulmonary disease

    PubMed Central

    Zhou, Si-jing; Li, Min; Zeng, Da-xiong; Zhu, Zhong-ming; Hu, Xian-Wei; Li, Yong-huai; Wang, Ran; Sun, Geng-yun

    2015-01-01

    Cigarette smoking contributes to the development of pulmonary hypertension (PH) complicated with chronic obstructive pulmonary disease (COPD), and the pulmonary vascular remodeling, the structural basis of PH, could be attributed to abnormal proliferation of pulmonary artery smooth muscle cells (PASMCs).In this study, morphometrical analysis showed that the pulmonary vessel wall thickness in smoker group and COPD group was significantly greater than in nonsmokers. In addition, we determined the expression patterns of connective tissue growth factor (CTGF) and cyclin D1 in PASMCs harvested from smokers with normal lung function or mild to moderate COPD, finding that the expression levels of CTGF and cyclin D1 were significantly increased in smoker group and COPD group. In vitro experiment showed that the expression of CTGF, cyclin D1 and E2F were signi?cantly increased in human PASMCs (HPASMCs) treated with 2% cigarette smoke extract (CSE), and two CTGF siRNAs with different mRNA hits successfully attenuated the upregulated cyclin D1 and E2F, and significantly restored the CSE-induced proliferation of HPASMCs by causing cell cycle arrest in G0. These ?ndings suggest that CTGF may contribute to the pathogenesis of abnormal proliferation of HPASMCs by promoting the expression of its downstream effectors in smokers with or without COPD. PMID:25708588

  15. Antiproliferative factor regulates connective tissue growth factor (CTGF/CCN2) expression in T24 bladder carcinoma cells

    PubMed Central

    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

  16. Reconceiving autoimmunity: An overview.

    PubMed

    Tauber, Alfred I

    2014-05-29

    Three interconnected positions are advocated: (1) although serving as a useful model, the immune self does not exist as such; (2) instead of a self/nonself demarcation, the immune system 'sees' itself, i.e., it does not ignore the 'self' or attack the 'other;' but exhibits a spectrum of responses, which when viewed from outside the system appear as discrimination of 'self' and 'nonself' based on certain criteria of reactivity. When immune reactions are conceived in terms of normal physiology and open exchange with the environment, where borders dividing host and foreign are elusive and changing, host defense is only part of the immune system's functions, which actually comprise two basic tasks: protection, i.e., to preserve host integrity, and maintenance of organismic identity. And thus (3) if the spectrum of immunity is enlarged, differentiating low reactive 'autoimmune' reactions from activated immune responses against the 'other' is only a matter of degree. Simply, all immunity is 'autoimmunity,' and the pathologic state of immunity directed at normal constituents of the organism is a particular case of dis-regulation, which appropriately is designated, autoimmune. Other uses of 'autoimmunity' and its congeners function as the semantic remnants of Burnet's original self/nonself theory and should be replaced. A new nomenclature is proposed, concinnity, which more accurately designates the physiology of the animal's ordinary housekeeping economy mediated by the immune system than 'autoimmunity' when used to describe such normal functions. PMID:24880023

  17. Autoimmunity and asbestos exposure.

    PubMed

    Pfau, Jean C; Serve, Kinta M; Noonan, Curtis W

    2014-01-01

    Despite a body of evidence supporting an association between asbestos exposure and autoantibodies indicative of systemic autoimmunity, such as antinuclear antibodies (ANA), a strong epidemiological link has never been made to specific autoimmune diseases. This is in contrast with another silicate dust, crystalline silica, for which there is considerable evidence linking exposure to diseases such as systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis. Instead, the asbestos literature is heavily focused on cancer, including mesothelioma and pulmonary carcinoma. Possible contributing factors to the absence of a stronger epidemiological association between asbestos and autoimmune disease include (a) a lack of statistical power due to relatively small or diffuse exposure cohorts, (b) exposure misclassification, (c) latency of clinical disease, (d) mild or subclinical entities that remain undetected or masked by other pathologies, or (e) effects that are specific to certain fiber types, so that analyses on mixed exposures do not reach statistical significance. This review summarizes epidemiological, animal model, and in vitro data related to asbestos exposures and autoimmunity. These combined data help build toward a better understanding of the fiber-associated factors contributing to immune dysfunction that may raise the risk of autoimmunity and the possible contribution to asbestos-related pulmonary disease. PMID:24876951

  18. Undifferentiated Connective Tissue Disease

    MedlinePLUS

    ... Sign Up for e-Newsletters Enter your email address to receive health tips, recent research findings and news about National Jewish Health. ... Divisions Top Docs More Programs & Services Services Directory ...

  19. Epigenetics and Autoimmune Diseases

    PubMed Central

    Quintero-Ronderos, Paula; Montoya-Ortiz, Gladis

    2012-01-01

    Epigenetics is defined as the study of all inheritable and potentially reversible changes in genome function that do not alter the nucleotide sequence within the DNA. Epigenetic mechanisms such as DNA methylation, histone modification, nucleosome positioning, and microRNAs (miRNAs) are essential to carry out key functions in the regulation of gene expression. Therefore, the epigenetic mechanisms are a window to understanding the possible mechanisms involved in the pathogenesis of complex diseases such as autoimmune diseases. It is noteworthy that autoimmune diseases do not have the same epidemiology, pathology, or symptoms but do have a common origin that can be explained by the sharing of immunogenetic mechanisms. Currently, epigenetic research is looking for disruption in one or more epigenetic mechanisms to provide new insights into autoimmune diseases. The identification of cell-specific targets of epigenetic deregulation will serve us as clinical markers for diagnosis, disease progression, and therapy approaches. PMID:22536485

  20. Inflammasomes and autoimmunity

    PubMed Central

    Shaw, Patrick J.; McDermott, Michael F.; Kanneganti, Thirumala-Devi

    2010-01-01

    The NOD-like receptor (NLR) family members are cytosolic sensors of microbial components and danger signals. A subset of NLRs control inflammasome assembly that results in caspase-1 activation and, in turn, IL-1? and IL-18 production. Excessive inflammasome activation can cause autoinflammatory disorders, including the hereditary periodic fevers. Autoinflammatory and autoimmune diseases form a disease spectrum of aberrant, immune-mediated inflammation against self, through innate and adaptive immunity. However, the role of inflammasomes in autoimmune disease is less clear than in autoinflammation, despite the numerous effects IL-1? and IL-18 can have on shaping adaptive immunity. We summarize the role of inflammasomes in autoimmune disorders, highlight the need for a better understanding of inflammasomes in these conditions and offer suggestions for future research directions. PMID:21163704

  1. Inflammasomes and autoimmunity.

    PubMed

    Shaw, Patrick J; McDermott, Michael F; Kanneganti, Thirumala-Devi

    2011-02-01

    The NOD-like receptor (NLR) family members are cytosolic sensors of microbial components and danger signals. A subset of NLRs control inflammasome assembly that results in caspase-1 activation and, in turn, IL-1? and IL-18 production. Excessive inflammasome activation can cause autoinflammatory disorders, including the hereditary periodic fevers. Autoinflammatory and autoimmune diseases form a disease spectrum of aberrant, immune-mediated inflammation against self, through innate and adaptive immunity. However, the role of inflammasomes in autoimmune disease is less clear than in autoinflammation, despite the numerous effects IL-1? and IL-18 can have on shaping adaptive immunity. We summarize the role of inflammasomes in autoimmune disorders, highlight the need for a better understanding of inflammasomes in these conditions and offer suggestions for future research directions. PMID:21163704

  2. Leukocyte trafficking in experimental autoimmune uveitis in vivo

    Microsoft Academic Search

    Adrian Parnaby-Price; Miles R. Stanford; John Biggerstaff; Lucy Howe; Roy A. Whiston; John Marshall; Graham R. Wallace

    1998-01-01

    Leukocyte trafficking from blood into tissue is a fundamental process in immune surveil- lance and the immune response to stimuli. Experi- mental autoimmune uveitis (EAU) is an animal model for posterior uveitis and is mediated by T lymphocytes and macrophages that infiltrate the posterior segment of the eye. To analyze leukocyte migration into retinal tissue during the course of EAU,

  3. Evaluation of autoimmune phenomena in patients with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS).

    PubMed

    Stagi, Stefano; Rigante, Donato; Lepri, Gemma; Bertini, Federico; Matucci-Cerinic, Marco; Falcini, Fernanda

    2014-12-01

    The pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) are basically characterized by obsessive-compulsive symptoms and/or tics triggered by group-A beta-hemolytic Streptococcus infections. Poor data are available about the clear definition of PANDAS's autoimmune origin. The aim of our study was to evaluate the prevalence of autoimmune phenomena, including thyroid function abnormalities, specific celiac disease antibodies, and positivity of organ- or nonorgan-specific autoantibodies in a large cohort of Caucasian children and adolescents with PANDAS. Seventy-seven consecutive patients (59 males, 18 females; mean age 6.3±2.5 years, range 2.0-14.5 years) strictly fulfilling the clinical criteria for PANDAS diagnosis were recruited. In all subjects we evaluated serum concentrations of free-T3, free-T4, thyrotropin, and the following auto-antibodies: anti-thyroperoxidase, anti-thyroglobulin, anti-thyrotropin receptor, anti-gliadin, anti-endomysium, anti-tissue transglutaminase, anti-nuclear, anti-smooth muscle, anti-extractable nuclear antigens, anti-phospholipid, plus lupus-like anticoagulant. The results were compared with those obtained from 197 age- and sex-matched healthy controls (130 males, 67 females; mean age 6.8±2.9 years, range 2.3-14.8 years). The frequencies of subclinical (3.8% vs 3.6%) and overt hypothyroidism (1.2% vs 0%), autoimmune thyroiditis (2.46% vs 1.14%), celiac disease (1.2% vs 0.05%), and positivity of organ- and nonorgan-specific autoantibodies (5.1% vs 4.8%) were not statistically significant between patients with PANDAS and controls. Evaluating the overall disease duration, we did not observe any significant difference between patients with (3.4±2.15 years) and without (3.4±2.89 years) autoimmune abnormalities. However, PANDAS patients with autoimmune diseases or positivity for any organ- and nonorgan-specific antibodies showed significantly higher anti-streptolysin O and anti-DNAse B titers, as well as a history of more frequent throat infections than controls (p<0.0001). Abnormalities of thyroid function and thyroid autoimmune diseases, as well as the association with celiac disease or organ- and nonorgan-specific autoimmunity seem not more frequent in children and adolescents with PANDAS than in healthy controls. A potential relationship between autoimmunity and PANDAS should be assessed further in larger studies. Children and adolescents with PANDAS should not be actually screened for thyroid function, celiac disease and/or autoimmune diseases. PMID:25151976

  4. Altered Expression of Autoimmune Regulator in Infant Down Syndrome Thymus, a Possible Contributor to an Autoimmune Phenotype

    PubMed Central

    Lundberg, Vanja; Lindgren, Susanne; Gudmundsdottir, Judith; Sandström, Kerstin; Kämpe, Olle; Annerén, Göran; Gustafsson, Jan; Sunnegĺrdh, Jan; van der Post, Sjoerd; Telemo, Esbjörn; Berglund, Martin; Ekwall, Olov

    2014-01-01

    Down syndrome (DS), caused by trisomy of chromosome 21, is associated with immunological dysfunctions such as increased frequency of infections and autoimmune diseases. Patients with DS share clinical features, such as autoimmune manifestations and specific autoantibodies, with patients affected by autoimmune polyendocrine syndrome type 1. Autoimmune polyendocrine syndrome type 1 is caused by mutations in the autoimmune regulator (AIRE) gene, located on chromosome 21, which regulates the expression of tissue-restricted Ags (TRAs) in thymic epithelial cells. We investigated the expression of AIRE and TRAs in DS and control thymic tissue using quantitative PCR. AIRE mRNA levels were elevated in thymic tissue from DS patients, and trends toward increased expression of the AIRE-controlled genes INSULIN and CHRNA1 were found. Immunohistochemical stainings showed altered cell composition and architecture of the thymic medulla in DS individuals with increased frequencies of AIRE-positive medullary epithelial cells and CD11c-positive dendritic cells as well as enlarged Hassall’s corpuscles. In addition, we evaluated the proteomic profile of thymic exosomes in DS individuals and controls. DS exosomes carried a broader protein pool and also a larger pool of unique TRAs compared with control exosomes. In conclusion, the increased AIRE gene dose in DS could contribute to an autoimmune phenotype through multiple AIRE-mediated effects on homeostasis and function of thymic epithelial cells that affect thymic selection processes. PMID:25038256

  5. Stress and Autoimmune Thyroid Diseases

    Microsoft Academic Search

    Marcello Bagnasco; Irene Bossert; Giampaola Pesce

    2006-01-01

    Autoimmune thyroid diseases (AITD) are the far most common autoimmune disorders, their prevalence in Western countries exceeding 5% of the general population. In the large majority of individual cases the clinical impact of AITD is not severe, however, their widespread diffusion renders them a significant health problem. AITD are heterogeneous in their clinical presentation: the two main forms are autoimmune

  6. Autoimmune hemolytic anemia: From lab to bedside.

    PubMed

    Chaudhary, R K; Das, Sudipta Sekhar

    2014-01-01

    Autoimmune hemolytic anemia (AIHA) is not an uncommon clinical disorder and requires advanced, efficient immunohematological and transfusion support. Many AIHA patients have underlying disorder and therefore, it is incumbent upon the clinician to investigate these patients in detail, as the underlying condition can be of a serious nature such as lymphoproliferative disorder or connective tissue disorder. Despite advances in transfusion medicine, simple immunohematological test such as direct antiglobulin test (DAT) still remains the diagnostic hallmark of AIHA. The sensitive gel technology has enabled the immunohematologist not only to diagnose serologically such patients, but also to characterize red cell bound autoantibodies with regard to their class, subclass and titer in a rapid and simplified way. Detailed characterization of autoantibodies is important, as there is a relationship between in vivo hemolysis and strength of DAT; red cell bound multiple immunoglobulins, immunoglobulin G subclass and titer. Transfusing AIHA patient is a challenge to the immunohematologist as it is encountered with difficulties in ABO grouping and cross matching requiring specialized serological tests such as alloadsorption or autoadsorption. At times, it may be almost impossible to find a fully matched unit to transfuse these patients. However, transfusion should not be withheld in a critically ill patient even in the absence of compatible blood. The "best match" or "least incompatible units" can be transfused to such patients under close supervision without any serious side-effects. All blood banks should have the facilities to perform the necessary investigations required to issue "best match" packed red blood cells in AIHA. Specialized techniques such as elution and adsorption, which at times are helpful in enhancing blood safety in AIHA should be established in all transfusion services. PMID:24678166

  7. Autoimmune hemolytic anemia: From lab to bedside

    PubMed Central

    Chaudhary, R. K.; Das, Sudipta Sekhar

    2014-01-01

    Autoimmune hemolytic anemia (AIHA) is not an uncommon clinical disorder and requires advanced, efficient immunohematological and transfusion support. Many AIHA patients have underlying disorder and therefore, it is incumbent upon the clinician to investigate these patients in detail, as the underlying condition can be of a serious nature such as lymphoproliferative disorder or connective tissue disorder. Despite advances in transfusion medicine, simple immunohematological test such as direct antiglobulin test (DAT) still remains the diagnostic hallmark of AIHA. The sensitive gel technology has enabled the immunohematologist not only to diagnose serologically such patients, but also to characterize red cell bound autoantibodies with regard to their class, subclass and titer in a rapid and simplified way. Detailed characterization of autoantibodies is important, as there is a relationship between in vivo hemolysis and strength of DAT; red cell bound multiple immunoglobulins, immunoglobulin G subclass and titer. Transfusing AIHA patient is a challenge to the immunohematologist as it is encountered with difficulties in ABO grouping and cross matching requiring specialized serological tests such as alloadsorption or autoadsorption. At times, it may be almost impossible to find a fully matched unit to transfuse these patients. However, transfusion should not be withheld in a critically ill patient even in the absence of compatible blood. The “best match” or “least incompatible units” can be transfused to such patients under close supervision without any serious side-effects. All blood banks should have the facilities to perform the necessary investigations required to issue “best match” packed red blood cells in AIHA. Specialized techniques such as elution and adsorption, which at times are helpful in enhancing blood safety in AIHA should be established in all transfusion services. PMID:24678166

  8. Celiac Disease-Associated Autoimmune Endocrinopathies

    PubMed Central

    Kumar, Vijay; Rajadhyaksha, Manoj; Wortsman, Jacobo

    2001-01-01

    Celiac disease (CD) is an autoimmune disorder induced by gluten intake in genetically susceptible individuals. It is characterized by the presence of serum antibodies to endomysium, reticulin, gliadin, and tissue transglutaminase. The incidence of CD in various autoimmune disorders is increased 10- to 30-fold in comparison to the general population, although in many cases CD is clinically asymptomatic or silent. The identification of such cases with CD is important since it may help in the control of type I diabetes or endocrine functions in general, as well as in the prevention of long-term complications of CD, such as lymphoma. It is believed that CD may predispose an individual to other autoimmune disorders such as type I diabetes, autoimmune thyroid, and other endocrine diseases and that gluten may be a possible trigger. The onset of type I diabetes at an early age in patients with CD, compared to non-CD, and the prevention or delay in onset of diabetes by gluten-free diet in genetically predisposed individuals substantiates this antigen trigger hypothesis. Early identification of CD patients in highly susceptible population may result in the treatment of subclinical CD and improved control of associated disorders. PMID:11427410

  9. Scurfy mice: A model for autoimmune disease

    SciTech Connect

    Godfrey, V.L.

    1993-01-01

    Autoimmune disease-the condition in which the body attacks its own tissue-has been an object of public concern recently. Former President George Bush and his wife Barbara both are afflicted with Graves' disease in which the body's own immune system attakcs the thyroid gland. The safety of breast implants was called into question because of evidence that some recipients had developed autoimmune disorders such a rheumatoid arthritis, systemic lupus erythematosus, and scleroderma. Women, the media pointed out, have a higher-than-average incidence of many autoimmune disorders. These events suggest the need to know more about what makes the immune system work so well and what makes it go awry. At ORNL's Biology Division, progress is being in understanding the underlying causes of immune disease by studying mice having a disease that causes them to be underdeveloped; to have scaly skin, small ears, and large spleens; to open their eyes late; and to die early. These [open quotes]scurfy[close quotes]mice are helping us better understand the role of the thymus gland in autoimmune disease.

  10. Probe penetration in relation to the connective tissue attachment level: influence of tine shape and probing force.

    PubMed

    Bulthuis, H M; Barendregt, D S; Timmerman, M F; Loos, B G; van der Velden, U

    1998-05-01

    Previous research has shown that probing force and probe tine shape influence the clinically assessed probing depth. The purpose of the present study was to investigate the effect of tine shape and probing force on probe penetration, in relation to the microscopically assessed attachment level in untreated periodontal disease. In 22 patients, scheduled for partial or full mouth tooth extraction and no history of periodontal treatment, 135 teeth were selected. At mesial and distal sites of the teeth reference marks were cut. Three probe tines, mounted in a modified Florida Probe handpiece, were tested: a tapered, a parallel and a ball-ended; tip-diameter 0.5 mm. The three tines were distributed at random over the sites. At each site increasing probing forces of 0.10 N, 0.15 N, 0.20 N, 0.25 N were used. After extraction, the teeth were cleaned and stained for connective tissue fiber attachment. The distance between the reference mark and the attachment level was determined using a stereomicroscope. The results showed that the parallel and ball-ended tine measured significantly beyond the microscopically assessed attachment level at all force levels; with increasing forces, the parallel tine measured 0.96 to 1.38 mm and the ball-ended tine 0.73 to 1.06 mm deeper. The tapered tine did not deviate significantly from the microscopic values at the forces of 0.15, 0.20 and 0.25 N. It can be concluded that for the optimal assessment of the attachment level in inflamed periodontal conditions, a tapered probe with a tip diameter of 0.5 mm and exerting a probing force of 0.25 N may be most suitable. PMID:9650880

  11. Clinical and Immunologic Manifestations of Mixed Connective Tissue Disease in a Miami Population Compared to a Midwestern US Caucasian Population

    PubMed Central

    Maldonado, Marcos E.; Perez, Magdalena; Pignac-Kobinger, Judith; Marx, Emily Triana; Tozman, Elaine M.; Greidinger, Eric L.; Hoffman, Robert W.

    2010-01-01

    Objective A cross-sectional study of mixed connective tissue disease (MCTD) was performed to determine if there were identifiable differences in the clinical expression of MCTD associated with race or ethnicity. Methods Miami, Florida, and Midwestern US (Missouri) Caucasian MCTD cohorts were studied. Clinical and laboratory features of the 2 MCTD cohorts were compared. A concurrently collected cohort of Sm-positive patients with systemic lupus erythematosus (SLE) was studied as a control. Disease activity and severity and functional status were measured. CD4+CD25high-expressing T-regulatory cells were enumerated and serum soluble L selectin was measured as biomarkers of disease activity. Results The Miami and Missouri Caucasian MCTD groups, while differing from the SLE group, were largely similar; however, gastroesophageal reflux, sclerodactyly, and malar rash were significantly more frequent in the Missouri MCTD group and alopecia was more frequent in the Miami MCTD group. Significant clinical and laboratory differences were found between the Miami MCTD and Miami SLE groups despite similar disease duration, activity, severity and functional status. Raynaud's phenomenon (RP), hand swelling, synovitis, myositis, and sclerodactyly were all significantly more common in RNP-positive MCTD versus Sm-positive SLE subjects. Conclusion Ethnic differences were observed in the frequency of end-organ involvement in the Miami MCTD versus the Missouri Caucasian MCTD groups. Clinical and laboratory features of all MCTD groups were clearly different from the SLE group, despite similar disease activity, disease severity, and functional status. Disease activity measures appeared to behave similarly as valid measures of disease activity in SLE and MCTD. PMID:18260175

  12. Connective tissue growth factor inhibition attenuates left ventricular remodeling and dysfunction in pressure overload-induced heart failure.

    PubMed

    Szabó, Zoltán; Magga, Johanna; Alakoski, Tarja; Ulvila, Johanna; Piuhola, Jarkko; Vainio, Laura; Kivirikko, Kari I; Vuolteenaho, Olli; Ruskoaho, Heikki; Lipson, Kenneth E; Signore, Pierre; Kerkelä, Risto

    2014-06-01

    Connective tissue growth factor (CTGF) is involved in the pathogenesis of various fibrotic disorders. However, its role in the heart is not clear. To investigate the role of CTGF in regulating the development of cardiac fibrosis and heart failure, we subjected mice to thoracic aortic constriction (TAC) or angiotensin II infusion, and antagonized the function of CTGF with CTGF monoclonal antibody (mAb). After 8 weeks of TAC, mice treated with CTGF mAb had significantly better preserved left ventricular (LV) systolic function and reduced LV dilatation compared with mice treated with control immunoglobulin G. CTGF mAb-treated mice exhibited significantly smaller cardiomyocyte cross-sectional area and reduced expression of hypertrophic marker genes. CTGF mAb treatment reduced the TAC-induced production of collagen 1 but did not significantly attenuate TAC-induced accumulation of interstitial fibrosis. Analysis of genes regulating extracellular matrix proteolysis showed decreased expression of plasminogen activator inhibitor-1 and matrix metalloproteinase-2 in mice treated with CTGF mAb. In contrast to TAC, antagonizing the function of CTGF had no effect on LV dysfunction or LV hypertrophy in mice subjected to 4-week angiotensin II infusion. Further analysis showed that angiotensin II-induced expression of hypertrophic marker genes or collagens was not affected by treatment with CTGF mAb. In conclusion, CTGF mAb protects from adverse LV remodeling and LV dysfunction in hearts subjected to pressure overload by TAC. Antagonizing the function of CTGF may offer protection from cardiac end-organ damage in patients with hypertension. PMID:24688123

  13. Schwann cells but not olfactory ensheathing cells inhibit CNS myelination via the secretion of connective tissue growth factor.

    PubMed

    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. PMID:24259589

  14. Connective tissue growth factor/CCN2-null mouse embryonic fibroblasts retain intact transforming growth factor-{beta} responsiveness

    SciTech Connect

    Mori, Yasuji; Hinchcliff, Monique; Wu, Minghua; Warner-Blankenship, Matthew [Division of Rheumatology, Northwestern University Feinberg School of Medicine, 240 E Huron Street, Chicago, IL 60611 (United States); Lyons, Karen M. [OH/UCLA Department of Orthopedic Surgery, David Geffen School of Medicine, UCLA, Los Angeles, CA (United States); Varga, John [Division of Rheumatology, Northwestern University Feinberg School of Medicine, 240 E Huron Street, Chicago, IL 60611 (United States)], E-mail: j-varga@northwestern.edu

    2008-03-10

    Background: The matricellular protein connective tissue growth factor (CCN2) has been implicated in pathological fibrosis, but its physiologic role remains elusive. In vitro, transforming growth factor-{beta} (TGF-{beta}) induces CCN2 expression in mesenchymal cells. Because CCN2 can enhance profibrotic responses elicited by TGF-{beta}, it has been proposed that CCN2 functions as an essential downstream signaling mediator for TGF-{beta}. To explore this notion, we characterized TGF-{beta}-induced activation of fibroblasts from CCN2-null (CCN2{sup -/-}) mouse embryos. Methods: The regulation of CCN2 expression was examined in vivo in a model of fibrosis induced by bleomycin. Cellular TGF-{beta} signal transduction and regulation of collagen gene expression were examined in CCN2{sup -/-} MEFs by immunohistochemistry, Northern, Western and RT-PCR analysis, immunocytochemistry and transient transfection assays. Results: Bleomycin-induced skin fibrosis in the mouse was associated with substantial CCN2 up-regulation in lesional fibroblasts. Whereas in vitro proliferation rate of CCN2{sup -/-} MEFs was markedly reduced compared to wild type MEFs, TGF-{beta}-induced activation of the Smad pathways, including Smad2 phosphorylation, Smad2/3 and Smad4 nuclear accumulation and Smad-dependent transcriptional responses, were unaffected by loss of CCN2. The stimulation of COL1A2 and fibronectin mRNA expression and promoter activity, and of corresponding protein levels, showed comparable time and dose-response in wild type and CCN2{sup -/-} MEFs, whereas stimulation of alpha smooth muscle actin and myofibroblast transdifferentiation showed subtle impairment in MEFs lacking CCN2. Conclusion: Whereas endogenous CCN2 plays a role in regulation of proliferation and TGF-{beta}-induced myofibroblast transdifferentiation, it appears to be dispensable for Smad-dependent stimulation of collagen and extracellular matrix synthesis in murine embryonic fibroblasts.

  15. MDSC in autoimmunity

    Microsoft Academic Search

    James G. Cripps; James D. Gorham

    2011-01-01

    Myeloid derived suppressor cells (MDSC) were first described nearly two decades ago. Until recently, however, descriptions of MDSC populations were found almost exclusively in animal models of cancer or in cancer patients. Over the last few years, an increasing number of reports have been published describing populations of myeloid cells with MDSC-like properties in murine models of autoimmune disease. In

  16. A Whole-Brain Voxel Based Measure of Intrinsic Connectivity Contrast Reveals Local Changes in Tissue Connectivity with Anesthetic without A Priori Assumptions on Thresholds or Regions of Interest

    PubMed Central

    Martuzzi, Roberto; Ramani, Ramachandran; Qiu, Maolin; Shen, Xilin; Papademetris, Xenophon; Constable, R. Todd

    2011-01-01

    The analysis of spontaneous fluctuations of functional magnetic resonance imaging (fMRI) signals has recently gained attention as a powerful tool for investigating brain circuits in a non-invasive manner. Correlation-based connectivity analysis investigates the correlations of spontaneous fluctuations of the fMRI signal either between a single seed region of interest (ROI) and the rest of the brain or between multiple ROIs. To do this, a priori knowledge is required for defining the ROI(s) and without such knowledge functional connectivity fMRI cannot be used as an exploratory tool for investigating the functional organization of the brain and its modulation under the different conditions. In this work we examine two indices that provide voxel based maps reflecting the intrinsic connectivity contrast (ICC) of individual tissue elements without the need for defining ROIs and hence require no a priori information or assumptions. These voxel based ICC measures can also be used to delineate regions of interest for further functional or network analyses. The indices were applied to the study of sevoflurane anesthesia-induced alterations in intrinsic connectivity. In concordance with previous studies, the results show that sevoflurane affects different brain circuits in a heterogeneous manner. In addition ICC analyses revealed changes in regions not previously identified using conventional ROI connectivity analyses, probably because of an inappropriate choice of the ROI in the earlier studies. This work highlights the importance of such voxel based connectivity methodology. PMID:21763437

  17. Internal Tissue Adhesive Approved

    MedlinePLUS

    ... on this page, please enable JavaScript. Internal Tissue Adhesive Approved TissuGlu connects tissue flaps stemming from surgery ... and Drug Administration has approved the first tissue adhesive for internal use. Known as TissuGlu, surgeons can ...

  18. Peroxisome proliferator-activated receptor-gamma gene expression in orbital adipose/connective tissues is increased during the active stage of Graves' ophthalmopathy.

    PubMed

    Mimura, Lídia Y; Villares, Sandra M F; Monteiro, Mário L R; Guazzelli, Isabel C; Bloise, Walter

    2003-09-01

    The mechanisms involved in the increase of orbital retro-ocular adipose tissue that occurs in Graves' ophthalmopathy (GO) are still unclear. In this condition, the orbital tissue shows glycosaminoglycans deposition produced by activated fibroblasts capable of undergoing adipocytic differentiation. Many genes are involved in adipogenic mechanisms including the transcription factor peroxisome proliferator-activated receptor-gamma (PPAR-gamma). We evaluated the level of expression of the PPAR-gamma gene in normal and GO orbital adipose/connective tissue specimens using a quantitative and sensitive reverse transcription (RT) competitive polymerase chain reaction (PCR) assay. Our results show that the expression of PPAR-gamma was significantly greater in adipose/connective tissue from patients in the active stage of GO than in controls (150.8 +/- 103.9 and 24.0 +/- 4.9 amol/micro g of total RNA respectively, p < 0.05), while there was no significant difference between patients with inactive GO (58.8 +/- 40.6 aM/microg total RNA) and controls. These results suggest that increased PPAR-gamma gene expression in the active stage of GO may be dependent on the inflammatory process in this disease. We speculate that the increased orbital fat tissue observed in GO may be a consequence of the anti-inflammatory PPAR-gamma action. PMID:14588098

  19. Degradation of connective tissue matrices by macrophages. II. Influence of matrix composition on proteolysis of glycoproteins, elastin, and collagen by macrophages in culture

    SciTech Connect

    Jones, P.A. (Univ. of Southern California, Los Angeles); Werb, Z.

    1980-12-01

    Thioglycollate-elicited mouse peritoneal macrophages were cultured in contact with the mixture of extracellular matrix proteins produced by rat smooth muscle cells in culture. Both live macrophages and their conditioned media hydrolyzed glycoproteins, elastin, and collagen. Live macrophages also degraded extracellular connective tissue proteins secreted by endothelial cells and fibroblasts. The glycoproteins in the matrix markedly inhibited the rate of digestion of the other macromolecules, particularly elastin. When plasminogen was added to the matrix, activation of plasminogen to plasmin resulted in the hydrolysis of the glycoprotein components, which then allowed the macrophage elastase easier access to its substrate, elastin. Thus, although plasmin has no direct elastinolytic activity, its presence accelerated the rate of hydrolysis of elastin and therefore the rate of matrix degradation. These findings may be important in an understanding of disease states, such as emphysema and atherosclerosis, that are characterized by the destruction of connective tissue.

  20. Irbesartan Ameliorates Diabetic Nephropathy by Reducing the Expression of Connective Tissue Growth Factor and Alpha-Smooth-Muscle Actin in the Tubulointerstitium of Diabetic Rats

    Microsoft Academic Search

    Xiaojun Ren; Guangju Guan; Gang Liu; Gaohong Liu

    2009-01-01

    The effect of irbesartan on the expression of connective tissue growth factor (CTGF) and ?-smooth-muscle actin (?-SMA) in the renal tubulointerstitium of diabetic rats was investigated in our study. Diabetes was induced in male Wistar rats by intraperitoneal administration of streptozotocin (STZ), 60 mg·kg–1 body weight. The rats were then randomized to a diabetic group (DM) and an irbesartan therapy

  1. Aesthetic management of gingival recession by root biomodification with carbon dioxide laser and subepithelial connective tissue graft with lateral repositioned flap technique.

    PubMed

    Rastogi, Pavitra Kumar; Lal, Nand; Garg, Nimit; Anand, Vishal; Singhal, Rameshwari

    2012-01-01

    Localised gingival recessions continue to represent an important aesthetic condition requiring treatment in periodontics. Various techniques have been tried to treat exposed root surfaces to improve aesthetics with high percentage of success and minimal discomfort. Root biomodification is done to improve the predictability of these procedures. This clinical report describes periodontal plastic procedure involving subepithelial connective tissue graft with lateral repositioned flap technique and root biomodification with CO(2) laser for the management of gingival recession. PMID:22778454

  2. The HNK-1 epitope in the inner connective tissue layer of the human ciliary body in exfoliation syndrome and various types of glaucoma

    Microsoft Academic Search

    Marita Uusitalo; Tero Kivelfi; Ahti Tarkkanen

    1994-01-01

    Possible changes in the expression of the HNK-1 carbohydrate epitope in the inner connective tissue layer of the human ciliary body, located between the ciliary epithelium and muscle, was studied using 2 formalin-fixed, paraffin-embedded eyes with exfoliation syndrome, 33 eyes with different types of glaucoma, and 21 morphologically normal control eyes. A strong immunoreaction delineating cell processes was observed in

  3. Cytotoxic and anti-proliferative effects of high-energy pulsed ultrasound (HEPUS) on human squamous cell carcinoma cells as compared to connective tissue fibroblasts

    Microsoft Academic Search

    H. Iro; B. A. Völklein; F. Waldfahrer; T. Schneider; R. E. Riedlinger; J. Zenk

    1998-01-01

    The cytotoxic and anti-proliferative effects of high-energy pulsed ultrasound (HEPUS) on human squamous cell carcinoma cells\\u000a cloned from the hypopharynx (FaDu) and benign connective tissue cells (fibroblasts) were investigated in vitro. Sonication\\u000a was carried out using an experimental piezoelectric, self-focusing burst-signal transducer. To increase the induction of cavitation,\\u000a the transducer used was specifically designed to produce multiple oscillations with a

  4. Inhibition of Integrin-Linked Kinase via a siRNA Expression Plasmid Attenuates Connective Tissue Growth Factor-Induced Human Proximal Tubular Epithelial Cells to Mesenchymal Transition

    Microsoft Academic Search

    Bi-Cheng Liu; Min-Xia Li; Jian-Dong Zhang; Xiao-Cong Liu; Xiao-Liang Zhang; Aled O. Phillips

    2008-01-01

    Background: Increasing evidence suggests that connective tissue growth factor (CTGF) is involved in the epithelial-to-mesenchymal transition (EMT). The exact intracellular events that drive this process, however, are not fully understood. In this study, we investigated the role of integrin-linked kinase (ILK) in mediating CTGF-induced EMT. Methods: The expression of ?-smooth muscle actin (?-SMA) and E-cadherin upon the stimulation by recombinant

  5. Chemical analysis of the formation of calcium carbonate and its influence on calcium hydroxide pastes in connective tissue of the dog--Part II.

    PubMed

    Estrela, C; Pesce, H F

    1997-01-01

    The objective of this research was to chemically analyze calcium hydroxide pastes added to three hydrosoluble vehicles having different acid-base characteristics by implanting polyethylene tubes in subcutaneous connective tissue in dogs, evaluating the formation of calcium carbonate over a period of 7, 30, 45, and 60 days. The three vehicles were saline, anesthetic, and polyethylene glycol 400. Determination of the formation of calcium carbonate was evaluated by volumetry of neutralization using hydrochloric acid for titration. PMID:9485637

  6. Integrin Mediated Adhesion of Osteoblasts to Connective Tissue Growth Factor (CTGF/CCN2) Induces Cytoskeleton Reorganization and Cell Differentiation

    PubMed Central

    Hendesi, Honey; Barbe, Mary F.; Safadi, Fayez F.; Monroy, M. Alexandra; Popoff, Steven N.

    2015-01-01

    Pre-osteoblast adhesion and interaction with extracellular matrix (ECM) proteins through integrin receptors result in activation of signaling pathways regulating osteoblast differentiation. Connective tissue growth factor (CTGF/CCN2) is a matricellular protein secreted into the ECM. Prior studies in various cell types have shown that cell adhesion to CTGF via integrin receptors results in activation of specific signaling pathways that regulate cell functions, such as differentiation and cytoskeletal reorganization. To date, there are no studies that have examined whether CTGF can serve as an adhesive substrate for osteoblasts. In this study, we used the MC3T3-E1 cell line to demonstrate that CTGF serves as an adhesive matrix for osteoblasts. Anti-integrin blocking experiments and co-immunoprecipitation assays demonstrated that the integrin ?v?1 plays a key role in osteoblast adhesion to a CTGF matrix. Immunofluorescence staining of osteoblasts cultured on a CTGF matrix confirmed actin cytoskeletal reorganization, enhanced spreading, formation of focal adhesions, and activation of Rac1. Alkaline phosphatase (ALP) staining and activity assays, as well as Alizarin red staining demonstrated that osteoblast attachment to CTGF matrix enhanced maturation, bone nodule formation and matrix mineralization. To investigate whether the effect of CTGF on osteoblast differentiation involves integrin-mediated activation of specific signaling pathways, we performed Western blot, chromatin immunoprecipitation (ChIP) and qPCR assays. Osteoblasts cultured on a CTGF matrix showed increased total and phosphorylated (activated) forms of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK). Inhibition of ERK blocked osteogenic differentiation in cells cultured on a CTGF matrix. There was an increase in runt-related transcription factor 2 (Runx2) binding to the osteocalcin gene promoter, and in the expression of osteogenic markers regulated by Runx2. Collectively, the results of this study are the first to demonstrate CTGF serves as a suitable matrix protein, enhancing osteoblast adhesion (via ?v?1 integrin) and promoting cell spreading via cytoskeletal reorganization and Rac1 activation. Furthermore, integrin-mediated activation of ERK signaling resulted in increased osteoblast differentiation accompanied by an increase in Runx2 binding to the osteocalcin promoter and in the expression of osteogenic markers. PMID:25714841

  7. Autosomal dominant Marfan-like connective-tissue disorder with aortic dilation and skeletal anomaslies not linked to the Fibrillin genes

    SciTech Connect

    Boileau, C.; Coulon, M.; Alexandre, J.-A.; Junien, C. (Laboratorie Central de Biochimie et de Genetique Moleculaire (France)); Jondeau, G.; Delorme, G.; Dubourg, O.; Bourdarias, J.-P. (CHU Ambroise Pare, Boulogne (France)); Babron, M.-C.; Bonaieti-Pellie, C. (INSERM, Chateau de Longchamp, Paris (France)); Sakai, L. (Shriners' Hospital for Crippled Children, Portland, OR (United States)); Melki, J. (Hopital Necker-Enfants Malades, Paris (France))

    1993-07-01

    The authors describe a large family with a connective-tissue disorder that exhibits some of the skeletal and cardiovascular features seen in Marfan syndrome. However, none of the 19 affected individuals displayed ocular abnormalities and therefore did not comply with recognized criteria for this disease. These patients could alternatively be diagnosed as MASS (mitral valve, aorta, skeleton, and skin) phenotype patients or represent a distinct clinical entity, i.e., a new autosomal dominant connective-tissue disorder. The fibrillin genes located on chromosomes 15 and 5 are clearly involved in the classic form of Marfan syndrome and a clinically related disorder (congenital contractural arachnodactyly), respectively. To test whether one of these genes was also implicated in this French family, the authors performed genetic analyses. Blood samples were obtained for 56 family members, and four polymorphic fibrillin gene markers, located on chromosomes 15 (Fib15) and 5 (Fib5), respectively, were tested. Linkage between the disease allele and the markers of these two genes was excluded with lod scores of [minus]11.39 (for Fib15) and [minus]13.34 (for Fib5), at 0 = .001, indicating that the mutation is at a different locus. This phenotype thus represents a new connective-tissue disorder, overlapping but different from classic Marfan syndrome. 33 refs., 1 fig. 2 tabs.

  8. Mechanisms of autoimmune liver disease.

    PubMed

    Baier, Julia L C; Mattner, Jochen

    2014-11-01

    The immune system of the liver is characterized by a predominant innate component. Several innate immune cell populations have been implicated in the pathogenesis of immune-mediated hepatic diseases, which are frequently associated with systemic symptoms or with co-morbidities affecting other organ systems. Thus, next to tissue-specific factors, general tolerance mechanisms are affected in devastating hepatic disorders like primary sclerosing cholangitis (PSC), autoimmune hepatitis (AIH), or primary biliary cirrhosis (PBC). The innate immune cell populations abundantly detected within the liver and endowed with potent immunomodulatory capacities include innate lymphoid cells (ILCs) and natural killer T (NKT) cells. While both ILCs and NKT cells can be activated by different cytokines and/or chemokines, NKT cells also respond to (glyco-) lipid antigens engaging their canonical, semi-invariant TCR. Once activated, ILCs and NKT cells release copious amounts of Th1, Th2, and/or Th17 cytokines that shape subsequent innate and adaptive immune responses. Those immunomodulatory features as well as the recently described antigen-presenting capacity of ILCs and/or the bi-directional functional role of NKT cells might not only underlie the pathogenic mechanisms in the respective disorders, but also provide promising targets for clinical intervention. We will discuss these novel aspects as well as the role of alarmin-like cytokines such as IL-33 in the context of ILC and NKT cell activation and the consequences for the induction and progress of hepatic tissue damage and fibrosis. PMID:25425466

  9. [Autoimmune hemolytic anemia].

    PubMed

    Marmont, A; Zanella, A

    2000-10-01

    Autoimmune hemolytic anemias (AIHAs) are the most ancient and well known example of clinical autoimmunity. They may be still distinguished in two main groups, that is with "warm" or "cold" antibodies, according to the optimal temperature at which they react with the erythrocyte antigens in vivo and in vitro. There is also a subgroup where both kinds of autoantibodies coexist. AIHAs may be idiopathic or secondary. The immunologic techniques for the demonstration of the antibodies are well established, but one must remember that there are infrequent cases with negative DAT (Coombs) test when performed with conventional procedures. The fundamental concepts of therapy are discussed, and the detailed review of the principal procedures is performed, including blood transfusions (when and how), plasma exchanges, high-dose immunoglobulins, glycocorticosteroids, splenectomy, cytotoxic agents and stem cell transplantation, autologous and allogeneic. PMID:11072741

  10. Subepithelial connective tissue graft associated with apicoectomy and root-end fillings in the treatment of deep localized gingival recession with apex root exposure: case report.

    PubMed

    Kahn, Sergio; Egreja, Andre Medina Coeli; Barceleiro, Marcos de Oliveira

    2009-08-01

    Periodontal reconstructive surgery procedures seek to correct mucogingival defects, including gingival recession. This case report describes the use of a subepithelial connective tissue graft (SCTG) associated with root-end fillings using mineral trioxide aggregate (MTA) for the treatment of Miller Class II recession with root apex exposure. A partial-thickness double pedicle flap was made, followed by root preparation with curette and bur finishing. The exposed root apex was removed and the canal was filled with MTA. An SCTG taken from the palate was placed over the root surface and covered with the double pedicle flap. Twelve months after treatment, a reduction from 11 mm to 1 mm in gingival recession was achieved, covering 91% of the root. Repair in the periapical region was determined with radiographs. A 1.0-mm probing depth was measured, and no bleeding was observed on probing. There was an adequate keratinized tissue band, along with esthetic tissue contour and coloration. This case report serves as an example of how the grafting of subepithelial connective tissue can be successfully accomplished in tandem with MTA for the treatment of isolated Miller Class II gingival recession with root apex exposure. (Int J Periodontics Restorative Dent 2009;29:445-449.). PMID:19639065

  11. Etiopathogenesis of insulin autoimmunity.

    PubMed

    Kanatsuna, Norio; Papadopoulos, George K; Moustakas, Antonis K; Lenmark, Ake

    2012-01-01

    Autoimmunity against pancreatic islet beta cells is strongly associated with proinsulin, insulin, or both. The insulin autoreactivity is particularly pronounced in children with young age at onset of type 1 diabetes. Possible mechanisms for (pro)insulin autoimmunity may involve beta-cell destruction resulting in proinsulin peptide presentation on HLA-DR-DQ Class II molecules in pancreatic draining lymphnodes. Recent data on proinsulin peptide binding to type 1 diabetes-associated HLA-DQ2 and -DQ8 is reviewed and illustrated by molecular modeling. The importance of the cellular immune reaction involving cytotoxic CD8-positive T cells to kill beta cells through Class I MHC is discussed along with speculations of the possible role of B lymphocytes in presenting the proinsulin autoantigen over and over again through insulin-carrying insulin autoantibodies. In contrast to autoantibodies against other islet autoantigens such as GAD65, IA-2, and ZnT8 transporters, it has not been possible yet to standardize the insulin autoantibody test. As islet autoantibodies predict type 1 diabetes, it is imperative to clarify the mechanisms of insulin autoimmunity. PMID:22567309

  12. Leptin in autoimmune diseases.

    PubMed

    Procaccini, Claudio; Pucino, Valentina; Mantzoros, Christos S; Matarese, Giuseppe

    2015-01-01

    The past twenty years of research on leptin has provided crucial information on the link between metabolic state and immune system function. Adipocytes influence not only the endocrine system but also the immune response, through several cytokine-like mediators known as adipokines, which include leptin. Initially described as an antiobesity hormone, leptin has subsequently been shown also to influence hematopoiesis, thermogenesis, reproduction, angiogenesis, and more importantly immune homeostasis. As a cytokine, leptin can affect thymic homeostasis and the secretion of acute-phase reactants such as interleukin-1 (IL-1) and tumor-necrosis factor-alpha (TNF-?). Leptin links nutritional status and proinflammatory T helper 1 (Th1) immune responses and the decrease in leptin plasma concentration during food deprivation leads to impaired immune function. Conversely, elevated circulating leptin levels in obesity appear to contribute to the low-grade inflammatory background which makes obese individuals more susceptible to increased risk of developing cardiovascular diseases, diabetes, or degenerative disease including autoimmunity and cancer. In this review, we provide an overview of recent advances on the role of leptin in the pathogenesis of several autoimmune disorders that may be of particular relevance in the modulation of the autoimmune attack through metabolic-based therapeutic approaches. PMID:25467840

  13. Epilepsy in systemic autoimmune disorders.

    PubMed

    Valencia, Ignacio

    2014-09-01

    Autoimmunity and inflammation have been implicated as causative factors of seizures and epilepsy. Autoimmune disorders can affect the central nervous system as an isolated syndrome or be part of a systemic disease. Examples of systemic autoimmune disorders include systemic lupus erythematosus, antiphospholipid syndrome, rheumatic arthritis, and Sjögren syndrome. Overall, there is a 5-fold increased risk of seizures and epilepsy in children with systemic autoimmune disorders. Various etiologic factors have been implicated in causing the seizures in these patients, including direct inflammation, effect on blood vessels (vasculitis), and production of autoantibodies. Potential treatments for this autoimmune injury include steroids, immunoglobulins, and other immune-modulatory therapies. A better understanding of the mechanisms of epileptogenesis in patients with systemic autoimmune diseases could lead to targeted treatments and better outcomes. PMID:25510945

  14. Quantitative three-dimensional methodology to assess volumetric and profilometric outcome of subepithelial connective tissue grafting at pontic sites: a prospective pilot study.

    PubMed

    González-Martín, Oscar; Veltri, Mario; Moráguez, Osvaldo; Belser, Urs C

    2014-01-01

    The aim of this study was to describe a technique for the assessment of soft tissue volumetric and profilometric changes. The technique has been applied at the alveolar contour of mild to moderate horizontal ridge defects after soft tissue augmentation at pontic sites. A quantitative three-dimensional (3D) analysis based on laser scanning was used for the measurement of volume gain and horizontal changes of alveolar profile 5 months after a subepithelial connective tissue graft using a pouch approach in five patients. All the surgical sites healed uneventfully. A mean soft tissue volume increase of 35.9 mm3 was measured 5 months after the grafting procedure. The linear measurements showed that, in the area where the augmentation was performed, the distance between the preoperative vestibular profile and the postoperative one ranged from 0.16 to 2 mm. The described quantitative measurements based on 3D laser scanning appear to be an effective method for assessment of soft tissue changes in future studies. Additionally, within the limitation of a small sample size, the present data suggest that the investigated surgical technique can be considered when corrections of mild to moderate alveolar horizontal ridge atrophies at maxillary lateral incisor edentulous gaps are necessary. PMID:25171038

  15. JOURNAL OF BIOLOGICAL RHYTHMS / June 2001Bartness et al. / PRV-REVEALED SCN PERIPHERAL CONNECTIONS SCN Efferents to Peripheral Tissues

    E-print Network

    Demas, Greg

    system innervation of the pineal gland and the sympathetic outflow from brain to white adipose tissue tobecontrolledsolelybyhypothalamic stimulating/inhibiting factors. Key words tract tracing, pseudorabies virus, pineal gland, adipose

  16. Targeting dendritic cell function during systemic autoimmunity to restore tolerance.

    PubMed

    Mackern-Oberti, Juan P; Vega, Fabián; Llanos, Carolina; Bueno, Susan M; Kalergis, Alexis M

    2014-01-01

    Systemic autoimmune diseases can damage nearly every tissue or cell type of the body. Although a great deal of progress has been made in understanding the pathogenesis of autoimmune diseases, current therapies have not been improved, remain unspecific and are associated with significant side effects. Because dendritic cells (DCs) play a major role in promoting immune tolerance against self-antigens (self-Ags), current efforts are focusing at generating new therapies based on the transfer of tolerogenic DCs (tolDCs) during autoimmunity. However, the feasibility of this approach during systemic autoimmunity has yet to be evaluated. TolDCs may ameliorate autoimmunity mainly by restoring T cell tolerance and, thus, indirectly modulating autoantibody development. In vitro induction of tolDCs loaded with immunodominant self-Ags and subsequent cell transfer to patients would be a specific new therapy that will avoid systemic immunosuppression. Herein, we review recent approaches evaluating the potential of tolDCs for the treatment of systemic autoimmune disorders. PMID:25229821

  17. Targeting Dendritic Cell Function during Systemic Autoimmunity to Restore Tolerance

    PubMed Central

    Mackern-Oberti, Juan P.; Vega, Fabián; Llanos, Carolina; Bueno, Susan M.; Kalergis, Alexis M.

    2014-01-01

    Systemic autoimmune diseases can damage nearly every tissue or cell type of the body. Although a great deal of progress has been made in understanding the pathogenesis of autoimmune diseases, current therapies have not been improved, remain unspecific and are associated with significant side effects. Because dendritic cells (DCs) play a major role in promoting immune tolerance against self-antigens (self-Ags), current efforts are focusing at generating new therapies based on the transfer of tolerogenic DCs (tolDCs) during autoimmunity. However, the feasibility of this approach during systemic autoimmunity has yet to be evaluated. TolDCs may ameliorate autoimmunity mainly by restoring T cell tolerance and, thus, indirectly modulating autoantibody development. In vitro induction of tolDCs loaded with immunodominant self-Ags and subsequent cell transfer to patients would be a specific new therapy that will avoid systemic immunosuppression. Herein, we review recent approaches evaluating the potential of tolDCs for the treatment of systemic autoimmune disorders. PMID:25229821

  18. The Dopaminergic System in Autoimmune Diseases

    PubMed Central

    Pacheco, Rodrigo; Contreras, Francisco; Zouali, Moncef

    2014-01-01

    Bidirectional interactions between the immune and the nervous systems are of considerable interest both for deciphering their functioning and for designing novel therapeutic strategies. The past decade has brought a burst of insights into the molecular mechanisms involved in neuroimmune communications mediated by dopamine. Studies of dendritic cells (DCs) revealed that they express the whole machinery to synthesize and store dopamine, which may act in an autocrine manner to stimulate dopamine receptors (DARs). Depending on specific DARs stimulated on DCs and T cells, dopamine may differentially favor CD4+ T cell differentiation into Th1 or Th17 inflammatory cells. Regulatory T cells can also release high amounts of dopamine that acts in an autocrine DAR-mediated manner to inhibit their suppressive activity. These dopaminergic regulations could represent a driving force during autoimmunity. Indeed, dopamine levels are altered in the brain of mouse models of multiple sclerosis (MS) and lupus, and in inflamed tissues of patients with inflammatory bowel diseases or rheumatoid arthritis (RA). The distorted expression of DARs in peripheral lymphocytes of lupus and MS patients also supports the importance of dopaminergic regulations in autoimmunity. Moreover, dopamine analogs had beneficial therapeutic effects in animal models, and in patients with lupus or RA. We propose models that may underlie key roles of dopamine and its receptors in autoimmune diseases. PMID:24711809

  19. Fueling Autoimmunity: Type I Interferon in Autoimmune Diseases

    PubMed Central

    Di Domizio, Jeremy; Cao, Wei

    2013-01-01

    Summary In recent years, active research using genomic, cellular and animal modeling approaches has revealed the fundamental forces driving the development of autoimmune diseases. Type I IFN (IFN) imprints unique molecular signatures in a list of autoimmune diseases. IFN is induced by diverse nucleic acid-containing complexes, which trigger innate immune activation of plasmacytoid dendritic cells (pDCs). IFN primes, activates or differentiates various leukocyte populations to promote autoimmunity. Accordingly, IFN signaling is essential for the initiation and/or progression of lupus in several experimental models. However, the heterogeneous nature of SLE requires better characterization on how IFN pathways are activated and subsequently promote the advancement of autoimmune diseases. Given the central role of type I IFN, various strategies are devised to target these cytokines or related pathways to curtail the progression of autoimmune diseases. PMID:23445195

  20. The Protein Precursors of Peptides That Affect the Mechanics of Connective Tissue and/or Muscle in the Echinoderm Apostichopus japonicus

    PubMed Central

    Elphick, Maurice R.

    2012-01-01

    Peptides that cause muscle relaxation or contraction or that modulate electrically-induced muscle contraction have been discovered in the sea cucumber Apostichopus japonicus (Phylum Echinodermata; Class Holothuroidea). By analysing transcriptome sequence data, here the protein precursors of six of these myoactive peptides (the SALMFamides Sticho-MFamide-1 and -2, NGIWYamide, stichopin, GN-19 and GLRFA) have been identified, providing novel insights on neuropeptide and endocrine-type signalling systems in echinoderms. The A. japonicus SALMFamide precursor comprises eight putative neuropeptides including both L-type and F-type SALMFamides, which contrasts with previous findings from the sea urchin Strongylocentrotus purpuratus where L-type and F-type SALMFamides are encoded by different genes. The NGIWYamide precursor contains five copies of NGIWYamide but, unlike other NG peptide-type neuropeptide precursors in deuterostomian invertebrates, the NGIWYamide precursor does not have a C-terminal neurophysin domain, indicating loss of this character in holothurians. NGIWYamide was originally discovered as a muscle contractant, but it also causes stiffening of mutable connective tissue in the body wall of A. japonicus, whilst holokinins (PLGYMFR and derivative peptides) cause softening of the body wall. However, the mechanisms by which these peptides affect the stiffness of body wall connective tissue are unknown. Interestingly, analysis of the A. japonicus transcriptome reveals that the only protein containing the holokinin sequence PLGYMFR is an alpha-5 type collagen. This suggests that proteolysis of collagen may generate peptides (holokinins) that affect body wall stiffness in sea cucumbers, providing a novel perspective on mechanisms of mutable connective tissue in echinoderms. PMID:22952987

  1. Administration of vitamin K does not counteract the ectopic mineralization of connective tissues in Abcc6?/? mice, a model for pseudoxanthoma elasticum

    PubMed Central

    Grand-Pierre, Alix E; Schurgers, Leon J

    2011-01-01

    Pseudoxanthoma elasticum (PXE) is a heritable multisystem disorder manifesting with ectopic calcification of peripheral connective tissues, caused by mutations in the ABCC6 gene. Alterations in vitamin K metabolism have been suggested to contribute to the pathomechanisms of the mineralization process. In this study we administered vitamin K or its glutathione conjugate (K3-GSH) into Abcc6?/? mice that recapitulate features of PXE. Oral administration of vitamin K2, in dosages that vastly exceed the amounts in control diet or the recommended amounts for humans, did not alter the ectopic mineralization in Abcc6?/? mice. Similarly, intravenous administration of K3-GSH did not alter the degree of mineralization. Testing of vitamin K2, K3 and K3-GSH in an in vitro calcification system provided no evidence of mineralization inhibition. Collectively, our data suggest that vitamin K deficiency in the peripheral tissues is not a simple explanation for development of mineral deposits in PXE. PMID:21304270

  2. Mesenchymal stem cells and progenitor cells in connective tissue engineering and regenerative medicine: is there a future for transplantation?

    Microsoft Academic Search

    Andres Hilfiker; Cornelia Kasper; Ralf Hass; Axel Haverich

    2011-01-01

    Purpose  Transplantation surgery suffers from a shortage of donor organs worldwide. Cell injection and tissue engineering (TE), thus\\u000a emerge as alternative therapy options. The purpose of this article is to review the progress of TE technology, focusing on\\u000a mesenchymal stem cells (MSC) as a cell source for artificial functional tissue.\\u000a \\u000a \\u000a \\u000a \\u000a Results  MSC from many different sources can be minimally invasively harvested: peripheral

  3. An autoimmune myositis-overlap syndrome associated with autoantibodies to nuclear pore complexes: description and long-term follow-up of the anti-nup syndrome.

    PubMed

    Senécal, Jean-Luc; Isabelle, Catherine; Fritzler, Marvin J; Targoff, Ira N; Goldstein, Rose; Gagné, Michel; Raynauld, Jean-Pierre; Joyal, France; Troyanov, Yves; Dabauvalle, Marie-Christine

    2014-11-01

    Autoimmune myositis encompasses various myositis-overlap syndromes, each being identified by the presence of serum marker autoantibodies. We describe a novel myositis-overlap syndrome in 4 patients characterized by the presence of a unique immunologic marker, autoantibodies to nuclear pore complexes. The clinical phenotype was characterized by prominent myositis in association with erosive, anti-CCP, and rheumatoid factor-positive arthritis, trigeminal neuralgia, mild interstitial lung disease, Raynaud phenomenon, and weight loss. The myositis was typically chronic, relapsing, and refractory to corticosteroids alone, but remitted with the addition of a second immunomodulating drug. There was no clinical or laboratory evidence for liver disease. The prognosis was good with 100% long-term survival (mean follow-up 19.5 yr).By indirect immunofluorescence on HEp-2 cells, sera from all 4 patients displayed a high titer of antinuclear autoantibodies (ANA) with a distinct punctate peripheral (rim) fluorescent pattern of the nuclear envelope characteristic of nuclear pore complexes. Reactivity with nuclear pore complexes was confirmed by immunoelectron microscopy. In a cohort of 100 French Canadian patients with autoimmune myositis, the nuclear pore complex fluorescent ANA pattern was restricted to these 4 patients (4%). It was not observed in sera from 393 adult patients with systemic sclerosis (n?=?112), mixed connective tissue disease (n?=?35), systemic lupus (n?=?94), rheumatoid arthritis (n?=?45), or other rheumatic diseases (n?=?107), nor was it observed in 62 normal adults.Autoantibodies to nuclear pore complexes were predominantly of IgG isotype. No other IgG autoantibody markers for defined connective tissue diseases or overlap syndromes were present, indicating a selective and highly focused immune response. In 3 patients, anti-nuclear pore complex autoantibody titers varied in parallel with myositis activity, suggesting a pathogenic link to pathophysiology. The nuclear pore complex proteins, that is, nucleoporins (nup), recognized by these sera were heterogeneous and included Nup358/RanBP2 (n?=?2 patients), Nup90 (n?=?1), Nup62 (n?=?1), and gp210 (n?=?1). Taken together the data suggest that nup autoantigens themselves drive the anti-nup autoimmune response. Immunogenetically, the 4 patients shared the DQA1*0501 allele associated with an increased risk for autoimmune myositis.In conclusion, we report an apparent novel subset of autoimmune myositis in our population of French Canadian patients with connective tissue diseases. This syndrome is recognized by the presence of a unique immunologic marker, autoantibodies to nuclear pore complexes that react with nups, consistent with an "anti-nup syndrome." PMID:25500708

  4. Structural Changes in Intramuscular Connective Tissue During the Fattening of Japanese Black Cattle: Effect of Marbling on Beef Tenderization1

    Microsoft Academic Search

    T. Nishimura; A. Hattori; K. Takahashi

    2010-01-01

    We investigated changes in structures and mechanical properties of the intramuscular con- nective tissue during the fattening of Japanese Black steers, using the cell maceration method for scanning electron microscopy. During the early fattening period, from 9 to 20 mo of age, collagen fibrils of the endomysium in longissimus muscle associated more closely with each other, and collagen fibers in

  5. Connecting fractional anisotropy from medical images with mechanical anisotropy of a hyperviscoelastic fibre-reinforced constitutive model for brain tissue

    PubMed Central

    Giordano, Chiara; Kleiven, Svein

    2014-01-01

    Brain tissue modelling has been an active area of research for years. Brain matter does not follow the constitutive relations for common materials and loads applied to the brain turn into stresses and strains depending on tissue local morphology. In this work, a hyperviscoelastic fibre-reinforced anisotropic law is used for computational brain injury prediction. Thanks to a fibre-reinforcement dispersion parameter, this formulation accounts for anisotropic features and heterogeneities of the tissue owing to different axon alignment. The novelty of the work is the correlation of the material mechanical anisotropy with fractional anisotropy (FA) from diffusion tensor images. Finite-element (FE) models are used to investigate the influence of the fibre distribution for different loading conditions. In the case of tensile–compressive loads, the comparison between experiments and simulations highlights the validity of the proposed FA–k correlation. Axon alignment affects the deformation predicted by FE models and, when the strain in the axonal direction is large with respect to the maximum principal strain, decreased maximum deformations are detected. It is concluded that the introduction of fibre dispersion information into the constitutive law of brain tissue affects the biofidelity of the simulations. PMID:24258158

  6. Spontaneous activation of RNA-sensing pathways in autoimmune disease

    PubMed Central

    Crampton, Steve P; Bolland, Silvia

    2013-01-01

    Multiple intracellular RNA sensing innate immune pathways have been linked to autoimmune disease. RNA-related ligands taken up by the endocytic pathway activate TLRs, and affect primarily immune cells. This type of activation is enhanced by nucleic acid-specific antibodies and induces an inflammatory program. In contrast, spontaneous activation of cytoplasmic RNA sensing pathways target mostly non-hematopoietic tissues and their effect on autoimmune disease is secondary to the release of interferon in the circulation. The fact that pathologies result from spontaneous activation of innate pathways implies that endogenous RNA ligands that might be sensed as pathogenic are commonly found in both immune and non-immune cells. PMID:24455767

  7. Ionizing radiation and autoimmunity: Induction of autoimmune disease in mice by high dose fractionated total lymphoid irradiation and its prevention by inoculating normal T cells

    SciTech Connect

    Sakaguchi, N.; Sakaguchi, S. (Stanford Univ. School of Medicine, CA (United States) Scripps Research Institute, La Jolla, CA (United States) PRESTO, JRDC, Institute of Phical and Chemical Research, Tsukuba, Ibaraki (Japan)); Miyai, K. (Univ. of California, San Diego, LA Jolla, CA (United States))

    1992-11-01

    Ionizing radiation can functionally alter the immune system and break self-tolerance. High dose (42.5 Gy), fractionated (2.5 Gy 17 times) total lymphoid irradiation (TLI) on mice caused various organ-specific autoimmune diseases, such as gastritis, thyroiditis, and orchitis, depending on the radiation dosages, the extent of lymphoid irradiation, and the genetic background of the mouse strains. Radiation-induced tissue damage is not the primary cause of the autoimmune disease because irradiation of the target organs alone failed to elicit the autoimmunity and shielding of the organs from irradiation was unable to prevent it. In contrast, irradiation of both the thymus and the peripheral lymphoid organs/tissues was required for efficient induction of autoimmune disease by TLI. TLI eliminated the majority of mature thymocytes and the peripheral T cells for 1 mo, and inoculation of spleen cell, thymocyte, or bone marrow cell suspensions (prepared from syngeneic nonirradiated mice) within 2 wk after TLI effectively prevented the autoimmune development. Depletion of T cells from the inocula abrogated the preventive activity. CD4[sup +] T cells mediated the autoimmune prevention but CD8[sup +] T cells did not. CD4[sup +] T cells also appeared to mediate the TLI-induced autoimmune disease because CD4[sup +] T cells from disease-bearing TLI mice adoptively transferred the autoimmune disease to syngeneic naive mice. Taken together, these results indicate that high dose, fractionated ionizing radiation on the lymphoid organs/tissues can cause autoimmune disease by affecting the T cell immune system, rather than the target self-Ags, presumably by altering T cell-dependent control of self-reactive T cells. 62 refs., 9 figs., 2 tabs.

  8. Academic and molecular matrices: A study of the transformations of connective tissue research at the University of Manchester (1947–1996)?

    PubMed Central

    García-Sancho, Miguel

    2011-01-01

    This paper explores the different identities adopted by connective tissue research at the University of Manchester during the second half of the 20th century. By looking at the long-term redefinition of a research programme, it sheds new light on the interactions between different and conflicting levels in the study of biomedicine, such as the local and the global, or the medical and the biological. It also addresses the gap in the literature between the first biomedical complexes after World War II and the emergence of biotechnology. Connective tissue research in Manchester emerged as a field focused on new treatments for rheumatic diseases. During the 1950s and 60s, it absorbed a number of laboratory techniques from biology, namely cell culture and electron microscopy. The transformations in scientific policy during the late 70s and the migration of Manchester researchers to the US led them to adopt recombinant DNA methods, which were borrowed from human genetics. This resulted in the emergence of cell matrix biology, a new field which had one of its reference centres in Manchester. The Manchester story shows the potential of detailed and chronologically wide local studies of patterns of work to understand the mechanisms by which new biomedical tools and institutions interact with long-standing problems and existing affiliations. PMID:21486662

  9. Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials

    PubMed Central

    Saketkoo, Lesley Ann; Mittoo, Shikha; Huscher, Dörte; Khanna, Dinesh; Dellaripa, Paul F; Distler, Oliver; Flaherty, Kevin R; Frankel, Sid; Oddis, Chester V; Denton, Christopher P; Fischer, Aryeh; Kowal-Bielecka, Otylia M; LeSage, Daphne; Merkel, Peter A; Phillips, Kristine; Pittrow, David; Swigris, Jeffrey; Antoniou, Katerina; Baughman, Robert P; Castelino, Flavia V; Christmann, Romy B; Christopher-Stine, Lisa; Collard, Harold R; Cottin, Vincent; Danoff, Sonye; Highland, Kristin B; Hummers, Laura; Shah, Ami A; Kim, Dong Soon; Lynch, David A; Miller, Frederick W; Proudman, Susanna M; Richeldi, Luca; Ryu, Jay H; Sandorfi, Nora; Sarver, Catherine; Wells, Athol U; Strand, Vibeke; Matteson, Eric L; Brown, Kevin K; Seibold, James R

    2014-01-01

    Rationale Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. Methods The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology—a non-profit international organisation dedicated to consensus methodology in identification of outcome measures—conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). Results A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Conclusion Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field. PMID:24368713

  10. Three-Dimensional Aspects of the Lingual Papillae and Their Connective Tissue Cores in the Tongue of Rats: A Scanning Electron Microscope Study

    PubMed Central

    Reginato, Gabriela de Souza; Watanabe, Ii-sei; Ciena, Adriano Polican

    2014-01-01

    The aim of the present study was to describe the tridimensional morphological characteristics of the lingual papillae and their connective tissue cores (CTCs) in Sprague Dawley rats. Four types of papillae were reported on the dorsal surface. Filiform papillae were distributed on the tongue surface and after epithelial maceration a conic and multifilamentary shape of the CTCs was revealed. Fungiform papillae were reported on the rostral and middle regions covered by a squamous epithelium. After the removal of the epithelium, the shape of a volcano with the taste orifice at its top was noted. Foliate papillae were composed of five pairs of epithelial folds situated on the lateral-caudal margin of the tongue. After the removal of the epithelium, they were shown to be limited by thin laminar projections. The vallate papilla with an oval shape was present in the caudal region and delimited by an incomplete groove. The morphological characteristics of the lingual papillae of Sprague Dowley rats, three-dimensional SEM images, and the types of papillae on the dorsal surface were similar to those reported previously in other rodent mammals. The maceration technique revealed the details of extracellular matrix with varied shapes form of connective tissue cores. PMID:25436229

  11. Adult Stem Cell Therapy for Autoimmune Disease

    PubMed Central

    Choi, Eun Wha

    2009-01-01

    Many studies of autologous hematopoietic stem cell transplantation (HSCT) and allogeneic HSCT have been conducted for autoimmune disease in various animal models. Because of the substantial risk of morbidity and mortality associated with allogeneic bone marrow transplantation, autologous transplants justified trying this approach in patient with severe autoimmune disease who were refractory to current treatments. Remission was achieved in some of the patients and some of them relapsed. Recently, many in vitro studies have reported that mesenchymal stem cells (MSC) have immunomodulatory properties and immunosuppressive effects on MHC-mismatched lymphocytes proliferation by inhibiting naďve, memory and activated T cells, B cell, NK cells and dendritic cells. In addition, adipose tissue-derived MSC (AT-MSC) are becoming an alternative source of MSC for therapeutic applications because adipose tissues are abundant, easily accessible, easily obtainable with little patient discomfort and large amounts of AT-MSC can be easily obtained. A large body of in vitro research has shown that AT-MSC have same or similar immunomodulatory effects with bone marrow derived MSC. Drawing on this finding, the increasing numbers of researchers have turned on their attention to preclinical studies on AT-MSC. As this new path of research evolves with subsequent reports, MSC would make a significant contribution to stem cell therapy or combination therapy for ameliorating symptoms and curing autoimmune disease. By searching and studying the appropriate therapeutic gene, the therapeutic gene transfected stem cell therapy will be able to acquire the synergy effect and the combined advantage of gene therapy and stem cell therapy. PMID:24855531

  12. Mineralization of the connective tissue: a complex molecular process leading to age-related loss of function.

    PubMed

    Shindyapina, Anastasia V; Mkrtchyan, Garik V; Gneteeva, Tatiana; Buiucli, Sveatoslav; Tancowny, B; Kulka, M; Aliper, Alexander; Zhavoronkov, Alexander

    2014-04-01

    Age-related metastatic mineralization of soft tissues has been considered a passive and spontaneous process. Recent data have demonstrated that calcium salt deposition in soft tissues could be a highly regulated process. Although calcification occurs in any tissue type, vascular calcification has been of particular interest due to association with atherosclerosis, chronic kidney disease (CKD), and osteoporosis. Different mechanisms underlying calcium apatite accumulation are explored with these age-related disorders. In the case of atherosclerotic plaques, oxy-lipids trigger release of the pro-inflammatory cytokines and inflammation that activate calcification processes in aorta intimae. In CKD patients, renal failure alters the balance between calcium and phosphate levels usually regulated by fibroblast growth factor-23 (FGF23), Klotho, and vitamin D, and vascular smooth muscle cells (VSMCs) begin to explore an osteoblastosteoblast-like phenotype. Calcification could affect extracellular matrix along with VSMCs. Collagen is a major component of extracellular matrix and its modifications accumulate with age. The formation of cross-links between collagen fibers is regulated by the action of lysine hydroxylases and lysyl oxidase and could occur spontaneously. Oxidation-induced advanced glycation end products (AGEs) are a major type of spontaneous cross-links that accelerate with age and may result in tissue stiffness, problems with recycling, and potential accumulation of calcium apatite. Applying strategies for clearing the AGEs proposed by de Grey may be more difficult in the highly mineralized extracellular matrix. We performed bioinformatic analysis of the molecular pathways underlying calcification in atherosclerotic and CKD patients, signaling pathways of collagen cross-links formation, and bone mineralization, and we propose new potential targets and review drugs for calcification treatment. PMID:23902273

  13. Annual cycle of expression of connective tissue polypeptide markers in the mantle of the mussel Mytilus galloprovincialis

    Microsoft Academic Search

    A. T. Mikhailov; M. Torrado; J. Méndez; M. J. López

    1996-01-01

    We suggest that gonad development in the mantle tissue of the bivalve molluscMytilus galloprovincialis Lmk. is an example of epithelial\\/mesenchymal interactions (i.e. soma\\/germline interactions) and morphogenesis in the adult state. According to this concept, the aim of the present study was to use biochemical and immunochemical methods for identifying and characterizing the mantle cell polypeptide markers whose expression is seasonally

  14. Controlled Compaction with Ruthenium-catalyzed Photochemical Cross-linking of Fibrin-based Engineered Connective Tissue

    PubMed Central

    Syedain, Zeeshan H.; Bjork, Jason; Sando, Lillian; Tranquillo, Robert T.

    2009-01-01

    Tissue engineering utilizing fibrin gel as a scaffold has the advantage of creating a completely biological replacement. Cells seeded in a fibrin gel can induce fibril alignment by traction forces when subjected to appropriate mechanical constraints. While gel compaction is key to successful tissue fabrication, excessive compaction can result due to low gel stiffness. This study investigated using ruthenium-catalyzed photo-cross-linking as a method to increase gel stiffness in order to minimize over-compaction. Cross-links between the abundant tyrosine molecules that comprise fibrin were created upon exposure to blue light. Cross-linking was effective in increasing the stiffness of the fibrin gel by 93% with no adverse effects on cell viability. Long-term culture of cross-linked tubular constructs revealed no detrimental effects on cell proliferation or collagen deposition due to cross-linking. After 4 weeks of cyclic distension, the cross-linked samples were more than twice as long as non-cross-linked controls, with similar cell and collagen contents. However, the cross-linked samples required a longer incubation period to achieve a UTS and modulus comparable to controls. This study shows that photo-cross-linking is an attractive option to stiffen the initial fibrin gel and thereby reduce cell-induced compaction, which can allow for longer incubation periods and thus more tissue growth without compaction below a useful size. PMID:19782397

  15. Age-associated differences in triceps surae muscle composition and strength – an MRI-based cross-sectional comparison of contractile, adipose and connective tissue

    PubMed Central

    2014-01-01

    Background In human skeletal muscles, the aging process causes a decrease of contractile and a concomitant increase of intramuscular adipose (IMAT) and connective (IMCT) tissues. The accumulation of non-contractile tissues may contribute to the significant loss of intrinsic muscle strength typically observed at older age but their in vivo quantification is challenging. The purpose of this study was to establish MR imaging-based methods to quantify the relative amounts of IMCT, IMAT and contractile tissues in young and older human cohorts, and investigate their roles in determining age-associated changes in skeletal muscle strength. Methods Five young (31.6?±?7.0 yrs) and five older (83.4?±?3.2 yrs) Japanese women were subject to a detailed MR imaging protocol, including Fast Gradient Echo, Quantitative Fat/Water (IDEAL) and Ultra-short Echo Time (UTE) sequences, to determine contractile muscle tissue and IMAT within the entire Triceps Surae complex, and IMCT within both heads of the Gastrocnemius muscle. Specific force was calculated as the ratio of isometric plantarflexor force and the physiological cross-sectional area of the Triceps Surae complex. Results In the older cohort, total Triceps Surae volume was smaller by 17.5%, while the relative amounts of Triceps Surae IMAT and Gastrocnemius IMCT were larger by 55.1% and 48.9%, respectively. Differences of 38.6% and 42.1% in plantarflexor force and specific force were observed. After subtraction of IMAT and IMCT from total muscle volume, differences in intrinsic strength decreased to 29.6%. Conclusions Our data establishes that aging causes significant changes in skeletal muscle composition, with marked increases in non-contractile tissues. Such quantification of the remodeling process is likely to be of functional and clinical importance in elucidating the causes of the disproportionate age-associated decrease of force compared to that of muscle volume. PMID:24939372

  16. Autoimmune Thyroid Diseases in Children

    PubMed Central

    Cappa, Marco; Bizzarri, Carla; Crea, Francesca

    2011-01-01

    The two major autoimmune thyroid diseases (ATDs) include Graves' disease (GD) and autoimmune thyroiditis (AT); both of which are characterized by infiltration of the thyroid by T and B cells reactive to thyroid antigens, by the production of thyroid autoantibodies and by abnormal thyroid function (hyperthyroidism in GD and hypothyroidism in AT). While the exact etiology of thyroid autoimmunity is not known, it is believed to develop when a combination of genetic susceptibility and environmental encounters leads to breakdown of tolerance. It is important to recognize thyroid dysfunction at an early stage by maintaining an appropriate index of suspicion. PMID:21209713

  17. Rheumatic symptoms in autoimmune thyroiditis.

    PubMed

    Tagoe, Clement E

    2015-02-01

    Autoimmune thyroiditis (ATD) is generally regarded as a classic example of single organ autoimmunity with a high association with endocrine thyroid disorders. However, it is closely associated with several autoimmune diseases including rheumatologic syndromes and has long been known to have several rheumatic manifestations particularly in association with hypothyroidism. More recently, it has also been implicated in rheumatologic syndromes in the absence of hypothyroidism or subclinical hypothyroidism. There is also an emerging body of evidence that ATD is highly linked to chronic generalized pain syndromes including fibromyalgia. This review examines the rheumatic symptoms of ATD described in the current literature and discusses the clinical relevance of ATD in general rheumatology. PMID:25618571

  18. Pivotal Roles of GM-CSF in Autoimmunity and Inflammation

    PubMed Central

    Shiomi, Aoi; Usui, Takashi

    2015-01-01

    Granulocyte macrophage-colony stimulating factor (GM-CSF) is a hematopoietic growth factor, which stimulates the proliferation of granulocytes and macrophages from bone marrow precursor cells. In autoimmune and inflammatory diseases, Th17 cells have been considered as strong inducers of tissue inflammation. However, recent evidence indicates that GM-CSF has prominent proinflammatory functions and that this growth factor (not IL-17) is critical for the pathogenicity of CD4+ T cells. Therefore, the mechanism of GM-CSF-producing CD4+ T cell differentiation and the role of GM-CSF in the development of autoimmune and inflammatory diseases are gaining increasing attention. This review summarizes the latest knowledge of GM-CSF and its relationship with autoimmune and inflammatory diseases. The potential therapies targeting GM-CSF as well as their possible side effects have also been addressed in this review.

  19. Model connective-tissue systems. A study of polyion–mobile ion and of excluded-volume interactions of proteoglycans

    PubMed Central

    Comper, Wayne D.; Preston, Barry N.

    1974-01-01

    The osmotic pressure of solutions of sulphated proteoglycans isolated from the intervertebral discs of animals of various ages was determined. The behaviour of the solutions in salt-added systems was investigated in terms of the Donnan distribution of the mobile ions. It is evident that this effect is the dominating factor in explaining the observed nonidealities. Although marked variations in the compositions of the proteoglycan, with regard to their chondroitin sulphate and keratan sulphate content and hence charge content, occur with increasing age of parent tissue, the osmotic activities of the various preparations are very similar. This is explained by the `fixation' of the counterions in such a way as to counteract any change in the charge content of the polyion; an `osmotic buffering' effect. The swelling behaviour of gelatin gels containing the proteoglycan preparations has been measured. In all cases pressures in excess of the sum of the osmotic pressures of the individual components are observed. However, the magnitude of the excess decreases with increasing age of the parent tissue. It is suggested that the age changes, as reflected by a decrease in water content of the gel system, are not the result of changes in the osmotic properties of the individual components but rather reflect changes in the entropic interaction of the proteoglycan with the gelatin matrix. The relevance of this observation to the situation in vivo is discussed. PMID:4282705

  20. Retroviruses and autoimmune rheumatic diseases.

    PubMed Central

    Kalden, J R; Gay, S

    1994-01-01

    In autoimmune rheumatic diseases, retroviruses have been repeatedly discussed as important etiologic factors. However, despite a considerable amount of indirect evidence that retroviruses might indeed be involved in triggering or perpetuating autoimmune rheumatic diseases, clear cut direct evidence is still missing. Studies on arthropathies associated with HIV-1 or HTLV-1 infection as well as new experimental animal models like the Tax transgene mice and new data from the MLR/lpr mouse model might help to answer the questions how and by what mechanisms retroviral infection may lead to autoimmune rheumatic diseases. From data obtained in the MLR/lpr mouse it seems obvious that a potential link of retroviruses, apoptosis and autogenes to autoimmune diseases opens exciting new approaches to the study of rheumatic disease pathogenesis. PMID:7923867

  1. American Autoimmune Related Diseases Association

    MedlinePLUS

    ... for Updates Join Our Email List For Email Marketing you can trust. Contact AARDA National Office 22100 ... to develop an autoimmune disease? Do you need diagnostic tips? Download article here About AARDA Mission Statement ...

  2. Associated Autoimmunity in Addison's Disease

    Microsoft Academic Search

    Pierre M. J. Zelissen; Egbert J. E. G. Bast; Ronald J. M. Croughs

    1995-01-01

    As the last extensive series of patients with Addison's disease and coincident autoimmune phenomena were published approximately two decades ago, we studied the cause of the disease, the prevalence of autoimmune disorders and the frequency of occurrence of autoantibodies in 91 patients (31 men and 60 women, mean age 45.3-years-old, range 12–77) with Addison's disease.The cause of Addison's disease in

  3. Autoimmune neutropenia preceding Helicobacter pylori-negative MALT lymphoma with nodal dissemination

    PubMed Central

    Harada, Saori; Yamazaki, Sho; Nakamura, Fumihiko; Morita, Ken; Yoshimi, Akihide; Shinozaki-Ushiku, Aya; Fukayama, Masashi; Kurokawa, Mineo

    2014-01-01

    Autoimmune neutropenia (AIN), resulting from granulocyte-specific autoantibodies, is much less frequent than other autoimmune hematologic disorders including autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). These autoimmune disorders may precede, synchronize, or follow collagen disorders, viral infections, and lymphoid neoplasms. Herein we present the first case of AIN in association with Helicobacter pylori-negative mucosa-associated lymphoid tissue (MALT) lymphoma with nodal dissemination. In our case, AIN, accompanied by ITP, occurred prior to the clinical manifestation of lymphoma. AIN and ITP were well managed afterwards, but they relapsed in accordance with the recurrence of lymphoma. The administration of prednisolone at 0.5 mg/kg daily alleviated the cytopenias within a week. In general, combination chemotherapy is performed for the treatment of lymphoma-associated autoimmune hematologic disorders and indeed seems to be effective. Our case indicates that corticosteroid monotherapy may be effective for lymphoma-associated AIN especially when AIN precedes the onset of lymphoma. PMID:25337296

  4. Autoimmune neutropenia preceding Helicobacter pylori-negative MALT lymphoma with nodal dissemination.

    PubMed

    Harada, Saori; Yamazaki, Sho; Nakamura, Fumihiko; Morita, Ken; Yoshimi, Akihide; Shinozaki-Ushiku, Aya; Fukayama, Masashi; Kurokawa, Mineo

    2014-01-01

    Autoimmune neutropenia (AIN), resulting from granulocyte-specific autoantibodies, is much less frequent than other autoimmune hematologic disorders including autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). These autoimmune disorders may precede, synchronize, or follow collagen disorders, viral infections, and lymphoid neoplasms. Herein we present the first case of AIN in association with Helicobacter pylori-negative mucosa-associated lymphoid tissue (MALT) lymphoma with nodal dissemination. In our case, AIN, accompanied by ITP, occurred prior to the clinical manifestation of lymphoma. AIN and ITP were well managed afterwards, but they relapsed in accordance with the recurrence of lymphoma. The administration of prednisolone at 0.5 mg/kg daily alleviated the cytopenias within a week. In general, combination chemotherapy is performed for the treatment of lymphoma-associated autoimmune hematologic disorders and indeed seems to be effective. Our case indicates that corticosteroid monotherapy may be effective for lymphoma-associated AIN especially when AIN precedes the onset of lymphoma. PMID:25337296

  5. T-cell Responses to Myelin Antigens in Multiple Sclerosis; Relevance of the Predominant Autoimmune Reactivity to Myelin Oligodendrocyte Glycoprotein

    Microsoft Academic Search

    Nicole Kerlero de Rosbo; Avraham Ben-Nun

    1998-01-01

    Until recently, the search for the ‘culprit’ autoantigen towards which deleterious autoimmunity is directed in multiple sclerosis (MS) centered mostly on myelin basic protein (MBP) and proteolipid (PLP), the two most abundant protein components of central nervous system (CNS) myelin, the target tissue for the autoimmune attack in MS. Although such research has yielded important data, furthering our understanding of

  6. Optimum temperature in juvenile salmonids: connecting subcellular indicators to tissue function and whole-organism thermal optimum.

    PubMed

    Anttila, Katja; Casselman, Matthew T; Schulte, Patricia M; Farrell, Anthony P

    2013-01-01

    Temperature affects processes at all levels of biological organization, but it is unclear whether processes at different levels have similar thermal optima (T(opt)). Here, we compare the T(opt) for aerobic scope, a whole-organism measure of performance, with both the Arrhenius breakpoint temperature for maximum heart rate (HR-ABT), a measure of tissue level performance, and the temperature at which AMP-activated protein kinase (AMPK) is phosphorylated in the heart, an indicator of an increase in dependence on anaerobic energy metabolism at the cellular level in juvenile rainbow trout Oncorhynchus mykiss. The T(opt) for aerobic scope was 19°C, with aerobic scope being maintained at ?90% of maximum (termed a "T(opt) window") from 16.5° to 20.5°C. HR-ABT occurred at [Formula: see text], while the profile of AMPK phosphorylation started to change from baseline at 19°C, suggesting that these processes have similar thermal sensitivities as a fish is warmed to T(opt). The effects of temperature on AMPK phosphorylation were also measured in coho salmon Oncorhynchus kisutch hearts and compared with previously published values for HR-ABT and aerobic scope T(opt). AMPK phosphorylation in coho hearts began to change at temperatures above 17°C, which again is comparable with the published T(opt) for aerobic scope (17°C) and HR-ABT ([Formula: see text]) in these individuals. Thus, the thermal sensitivity of these subcellular, tissue, and whole-organism functions are highly correlated in both rainbow trout and coho salmon and may depend on each other. PMID:23434784

  7. Oral pamidronate prevents high-dose glucocorticoid-induced lumbar spine bone loss in premenopausal connective tissue disease (mainly lupus) patients.

    PubMed

    Nzeusseu Toukap, A; Depresseux, G; Devogelaer, J-P; Houssiau, F A

    2005-01-01

    Glucocorticoid (GC)-induced osteoporosis contributes to chronic damage in patients suffering from connective tissue diseases (CTD) such as systemic lupus erythematosus (SLE). In this study, performed in an highly selected cohort of premenopausal female CTD (mostly lupus) patients, given high-dose GC therapy for severe disease, we show that lumbar spine bone loss can be averted by treatment with oral disodium pamidronate combined with calcium salts and vitamin D3 supplements and not by calcium salts and vitamin D3 supplements alone. We stress the need for optimal GC-induced bone loss prevention therapy in premenopausal patients, a too often neglected issue in patients whose survival has dramatically improved over the last decades. PMID:16130506

  8. Diagnosis of autoimmune pancreatitis

    PubMed Central

    Matsubayashi, Hiroyuki; Kakushima, Naomi; Takizawa, Kohei; Tanaka, Masaki; Imai, Kenichiro; Hotta, Kinichi; Ono, Hiroyuki

    2014-01-01

    Autoimmune pancreatitis (AIP) is a distinct form of chronic pancreatitis that is increasingly being reported. The presentation and clinical image findings of AIP sometimes resemble those of several pancreatic malignancies, but the therapeutic strategy differs appreciably. Therefore, accurate diagnosis is necessary for cases of AIP. To date, AIP is classified into two distinct subtypes from the viewpoints of etiology, serum markers, histology, other organ involvements, and frequency of relapse: type 1 is related to IgG4 (lymphoplasmacytic sclerosing pancreatitis) and type 2 is related to a granulocytic epithelial lesion (idiopathic duct-centric chronic pancreatitis). Both types of AIP are characterized by focal or diffuse pancreatic enlargement accompanied with a narrowing of the main pancreatic duct, and both show dramatic responses to corticosteroid. Unlike type 2, type 1 is characteristically associated with increasing levels of serum IgG4 and positive serum autoantibodies, abundant infiltration of IgG4-positive plasmacytes, frequent extrapancreatic lesions, and relapse. These findings have led several countries to propose diagnostic criteria for AIP, which consist of essentially similar diagnostic items; however, several differences exist for each country, mainly due to differences in the definition of AIP and the modalities used to diagnose this disease. An attempt to unite the diagnostic criteria worldwide was made with the publication in 2011 of the international consensus diagnostic criteria for AIP, established at the 2010 Congress of the International Association of Pancreatology (IAP). PMID:25469024

  9. Defective Initiation of Glycosaminoglycan Synthesis due to B3GALT6 Mutations Causes a Pleiotropic Ehlers-Danlos-Syndrome-like Connective Tissue Disorder

    PubMed Central

    Malfait, Fransiska; Kariminejad, Ariana; Van Damme, Tim; Gauche, Caroline; Syx, Delfien; Merhi-Soussi, Faten; Gulberti, Sandrine; Symoens, Sofie; Vanhauwaert, Suzanne; Willaert, Andy; Bozorgmehr, Bita; Kariminejad, Mohamad Hasan; Ebrahimiadib, Nazanin; Hausser, Ingrid; Huysseune, Ann; Fournel-Gigleux, Sylvie; De Paepe, Anne

    2013-01-01

    Proteoglycans are important components of cell plasma membranes and extracellular matrices of connective tissues. They consist of glycosaminoglycan chains attached to a core protein via a tetrasaccharide linkage, whereby the addition of the third residue is catalyzed by galactosyltransferase II (?3GalT6), encoded by B3GALT6. Homozygosity mapping and candidate gene sequence analysis in three independent families, presenting a severe autosomal-recessive connective tissue disorder characterized by skin fragility, delayed wound healing, joint hyperlaxity and contractures, muscle hypotonia, intellectual disability, and a spondyloepimetaphyseal dysplasia with bone fragility and severe kyphoscoliosis, identified biallelic B3GALT6 mutations, including homozygous missense mutations in family 1 (c.619G>C [p.Asp207His]) and family 3 (c.649G>A [p.Gly217Ser]) and compound heterozygous mutations in family 2 (c.323_344del [p.Ala108Glyfs?163], c.619G>C [p.Asp207His]). The phenotype overlaps with several recessive Ehlers-Danlos variants and spondyloepimetaphyseal dysplasia with joint hyperlaxity. Affected individuals’ fibroblasts exhibited a large decrease in ability to prime glycosaminoglycan synthesis together with impaired glycanation of the small chondroitin/dermatan sulfate proteoglycan decorin, confirming ?3GalT6 loss of function. Dermal electron microcopy disclosed abnormalities in collagen fibril organization, in line with the important regulatory role of decorin in this process. A strong reduction in heparan sulfate level was also observed, indicating that ?3GalT6 deficiency alters synthesis of both main types of glycosaminoglycans. In vitro wound healing assay revealed a significant delay in fibroblasts from two index individuals, pointing to a role for glycosaminoglycan defect in impaired wound repair in vivo. Our study emphasizes a crucial role for ?3GalT6 in multiple major developmental and pathophysiological processes. PMID:23664118

  10. Defective initiation of glycosaminoglycan synthesis due to B3GALT6 mutations causes a pleiotropic Ehlers-Danlos-syndrome-like connective tissue disorder.

    PubMed

    Malfait, Fransiska; Kariminejad, Ariana; Van Damme, Tim; Gauche, Caroline; Syx, Delfien; Merhi-Soussi, Faten; Gulberti, Sandrine; Symoens, Sofie; Vanhauwaert, Suzanne; Willaert, Andy; Bozorgmehr, Bita; Kariminejad, Mohamad Hasan; Ebrahimiadib, Nazanin; Hausser, Ingrid; Huysseune, Ann; Fournel-Gigleux, Sylvie; De Paepe, Anne

    2013-06-01

    Proteoglycans are important components of cell plasma membranes and extracellular matrices of connective tissues. They consist of glycosaminoglycan chains attached to a core protein via a tetrasaccharide linkage, whereby the addition of the third residue is catalyzed by galactosyltransferase II (?3GalT6), encoded by B3GALT6. Homozygosity mapping and candidate gene sequence analysis in three independent families, presenting a severe autosomal-recessive connective tissue disorder characterized by skin fragility, delayed wound healing, joint hyperlaxity and contractures, muscle hypotonia, intellectual disability, and a spondyloepimetaphyseal dysplasia with bone fragility and severe kyphoscoliosis, identified biallelic B3GALT6 mutations, including homozygous missense mutations in family 1 (c.619G>C [p.Asp207His]) and family 3 (c.649G>A [p.Gly217Ser]) and compound heterozygous mutations in family 2 (c.323_344del [p.Ala108Glyfs(?)163], c.619G>C [p.Asp207His]). The phenotype overlaps with several recessive Ehlers-Danlos variants and spondyloepimetaphyseal dysplasia with joint hyperlaxity. Affected individuals' fibroblasts exhibited a large decrease in ability to prime glycosaminoglycan synthesis together with impaired glycanation of the small chondroitin/dermatan sulfate proteoglycan decorin, confirming ?3GalT6 loss of function. Dermal electron microcopy disclosed abnormalities in collagen fibril organization, in line with the important regulatory role of decorin in this process. A strong reduction in heparan sulfate level was also observed, indicating that ?3GalT6 deficiency alters synthesis of both main types of glycosaminoglycans. In vitro wound healing assay revealed a significant delay in fibroblasts from two index individuals, pointing to a role for glycosaminoglycan defect in impaired wound repair in vivo. Our study emphasizes a crucial role for ?3GalT6 in multiple major developmental and pathophysiological processes. PMID:23664118

  11. In situ localization of two fibrillar collagens in two compact connective tissues by immunoelectron microscopy after cryotechnical processing.

    PubMed

    Nicolas, G; Gaill, F; Zylberberg, L

    1997-01-01

    Two fibrillar collagens, the worm cuticular collagen and the vertebrate Type I fish scale collagen, both organized in a compact tissue, were localized by immunogold electron microscopy in resin sections after freeze-fixation and freeze-substitution. Identification of these two fibrillar collagens failed with the use of postembedding labelling after conventional electron microscopic processing. Positive labeling of the Type I collagen was observed in sections of fish scales freeze-fixed by either slam-freezing or high-pressure freezing, freeze-substituted in acetone with or without osmium tetroxide, and embedded in LR White. The worm cuticular collagen was detected in sections of cuticle that were freeze-fixed, freeze-substituted (necessarily with osmium tetroxide added to acetone), and embedded in either LR White or Epon. It was also detected in specimens pre-fixed by aldehydes before freeze-fixation. The Type I fish scale collagen appears to be more sensitive than the fibrillar cuticular collagen of worms to the procedures employed for postembedding immunoelectron microscopy. Our results have shown that freeze-fixation and freeze-substitution preserved the antigenicity of the fibrillar collagens organized in a compact three-dimensional network, whereas immunolabeling failed after conventional electron microscopic procedures. These cryostabilization techniques appear to be of value to improve the immunolocalization of collagens. PMID:9010476

  12. Immune-Neuroendocrine Interactions and Autoimmune Diseases

    PubMed Central

    Jara, Luis J.; Navarro, Carmen; Medina, Gabriela; Vera-Lastra, Olga; Blanco, Francisco

    2006-01-01

    The relationship between immune-neuroendocrine system is firmly established. The messengers of this connection are hormones, neuropeptides, neurotransmitters and cytokines. The immune-neuroendocrine system have the capacity to synthesize and release these molecules, which, in turn, can stimulate or suppress the activity of immune or neuroendocrine cells by binding to receptors. In fact, hormones, neuropeptides and neurotransmitters participate in innate and adaptive immune response.Autoimmune rheumatic diseases (ARD) are characterized by aberrant production of pro-inflammatory cytokines, which are a potent activator of the HPA axis. In consequence, high levels of pro-inflammatory hormones such as estrogens and prolactin, and low levels of glucocorticoids, an anti-inflammatory hormone, have been described in the active phase of ARD. In addition, high levels of pro-inflammatory hormones and cytokines have also been frequently detected in organ involvement of patients with ARD, suggesting an abnormal local neuroendocrine immune interaction. There is evidence that hormonal changes may appear before the symptomatic phase of the disease. Therefore, it is possible that a pro-inflammatory hormone favors the rupture of tolerance, which is a key feature of autoimmune diseases. The interactions between the immune-neuroendocrine system have a major impact on our understanding of the pathogenic mechanisms, diagnosis and therapy of ARD. PMID:17162354

  13. Type 1 diabetes and autoimmunity.

    PubMed

    Kawasaki, Eiji

    2014-10-01

    Type 1 diabetes (T1D) is an organ-specific autoimmune disease caused by the autoimmune response against pancreatic ? cells. T1D is often complicated with other autoimmune diseases, and anti-islet autoantibodies precede the clinical onset of disease. The most common coexisting organ-specific autoimmune disease in patients with T1D is autoimmune thyroid disease, and its frequency is estimated at > 90% among patients with T1D and autoimmune diseases. The prevalence of anti-thyroid antibodies in children with T1D at disease onset is about 20% and is particularly common in girls. Furthermore, patients with anti-thyroid antibodies are 18 times more likely to develop thyroid disease than patients without anti-thyroid antibodies. Therefore, for early detection of autoimmune thyroid disease in children with T1D, measurement of anti-thyroid antibodies and TSH at T1D onset and in yearly intervals after the age of 12 yr is recommended. Anti-islet autoantibodies are predictive and diagnostic markers for T1D. The most frequently detected autoantibodies in Japanese patients are GAD autoantibodies (~80%) followed by IA-2 autoantibodies (~60%), insulin autoantibodies (~55%) and ZnT8 autoantibodies (~50%). In a combined analysis, 94% of Japanese patients with T1D can be defined as having type 1A diabetes. Furthermore, autoantibodies to ZnT8 and IA-2 are associated with childhood-onset and acute-onset patients. Thus, it is important to develop a diagnostic strategy for patients with type 1A diabetes in consideration of the age or mode of disease onset. PMID:25374439

  14. Type 1 Diabetes and Autoimmunity

    PubMed Central

    Kawasaki, Eiji

    2014-01-01

    Abstract. Type 1 diabetes (T1D) is an organ-specific autoimmune disease caused by the autoimmune response against pancreatic ? cells. T1D is often complicated with other autoimmune diseases, and anti-islet autoantibodies precede the clinical onset of disease. The most common coexisting organ-specific autoimmune disease in patients with T1D is autoimmune thyroid disease, and its frequency is estimated at > 90% among patients with T1D and autoimmune diseases. The prevalence of anti-thyroid antibodies in children with T1D at disease onset is about 20% and is particularly common in girls. Furthermore, patients with anti-thyroid antibodies are 18 times more likely to develop thyroid disease than patients without anti-thyroid antibodies. Therefore, for early detection of autoimmune thyroid disease in children with T1D, measurement of anti-thyroid antibodies and TSH at T1D onset and in yearly intervals after the age of 12 yr is recommended. Anti-islet autoantibodies are predictive and diagnostic markers for T1D. The most frequently detected autoantibodies in Japanese patients are GAD autoantibodies (~80%) followed by IA-2 autoantibodies (~60%), insulin autoantibodies (~55%) and ZnT8 autoantibodies (~50%). In a combined analysis, 94% of Japanese patients with T1D can be defined as having type 1A diabetes. Furthermore, autoantibodies to ZnT8 and IA-2 are associated with childhood-onset and acute-onset patients. Thus, it is important to develop a diagnostic strategy for patients with type 1A diabetes in consideration of the age or mode of disease onset. PMID:25374439

  15. Celiac sprue: a unique autoimmune disorder

    PubMed Central

    Rashtak, Shadi; Marietta, Eric V; Murray, Joseph A

    2011-01-01

    Celiac sprue (CS) is a gluten-sensitive enteropathy with many autoimmune features. CS involves multiple organs through immune and nonimmune processes, and is frequently associated with other autoimmune disorders. This article reviews the co-occurrence of CS with autoimmune disorders of the cutaneous, nervous, endocrine, musculoskeletal, gastrointestinal and cardiovascular systems. The types of autoimmune disorders associated with CS and the prevalence of CS in other autoimmune disorders are also discussed. A brief review of the literature on the potential mechanisms behind these associations and the therapeutic effects of a gluten-free diet for autoimmune comorbidities in CS is also provided. PMID:20477645

  16. Evaluation of root coverage with and without connective tissue graft for the treatment of single maxillary gingival recession using an image analysis system: a randomized controlled clinical trial.

    PubMed

    Lops, Diego; Gobbato, Luca; Nart, Jose; Guazzo, Riccardo; Ho, Daniel K; Bressan, Eriberto

    2015-01-01

    The aim of this prospective randomized clinical study was to evaluate, by means of an image analysis system, the efficacy of two different surgical procedures for the treatment of Miller Class I and II maxillary gingival recession. Patients treated for maxillary gingival recession were recruited and randomly divided into two groups: patients who received a coronally advanced flap with connective tissue graft (CAF + CTG) or CAF alone. Outcome parameters included complete root coverage, recession reduction, and keratinized tissue amount. Twenty-five patients completed the 12-month follow-up period. Patients in the CAF + CTG group showed a better primary outcome- gingival recession at 12 months-than CAF patients (P = .0001). Gingival recession at 12 months had a median of 0.5 (interquartile range [IQR] 0.5 to 0.6) in the CAF + CTG group and a median of 1.0 (IQR 0.9 to 1.1) in the CAF group. CAF + CTG and CAF groups had similar complete root coverage at 6 and 12 months. Recession and keratinized tissue width significantly decreased over time (P < .0001), with no effect of treatment or of treatment over time. Buccal probing depth had similar values over time (P = .28) and in the two groups (P = .52). Buccal clinical attachment level had similar values in the two groups (P = .87); moreover, mesial and distal clinical attachment levels did not show any variation over time (P = .88 and P = .68, respectively). By means of a computerized image analysis system better outcomes in terms of recession reduction after 12 months of follow-up were measured for maxillary gingival recessions treated with CAF and CTG. Adjunctive application of a CTG under a CAF increased the probability of achieving complete root coverage in maxillary Miller Class I and II defects (61.5% versus 83.3%; P = .38). Both treatments were equally effective in providing a consistent reduction of the baseline recession. PMID:25738345

  17. Autoimmune pancreatitis can develop into chronic pancreatitis

    PubMed Central

    2014-01-01

    Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung’s and Santorini’s ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct. PMID:24884922

  18. Murine Genotype Influences the Specificity, Magnitude and Persistence of Murine Mercury-Induced Autoimmunity

    Microsoft Academic Search

    Per Hultman; Shannon J. Turley; Sverker Eneström; Ulf Lindh; Michael K. Pollard

    1996-01-01

    Genetic factors are major contributors in determining the susceptibility to systemic autoimmune diseases. We studied the influence of genotype on systemic autoimmunity by treating female mice of the H-2sstrains SJL\\/N, SJL\\/J, A.SW, and B10.S with mercuric chloride (HgCl2) for 10 weeks and then following autoantibody and tissue immune deposits during the subsequent 12 months. All strains developed antinucleolar antibodies (ANoA)

  19. Alopecia Areata: Autoimmunity—The Evidence Is Compelling

    Microsoft Academic Search

    Richard S. Kalish; Amos Gilhar; Richard E. Kalish

    2003-01-01

    There is strong evidence indicating that alopecia areata is a tissue-specific, autoimmune disease. Hair loss is associated with a perifollicular lymphocytic infiltrate made up primarily of CD4+ cells, along with a CD8+ intrafollicular infiltrate. Evidence of immune activation includes expression of HLA-DR; HLA-A,B,C; and ICAM-1 on the follicular epithelium. It is likely that the follicular expression of HLA-DR and ICAM-1

  20. Cartilage as a target of autoimmunity: a thin layer.

    PubMed

    Frisenda, Silvia; Perricone, Carlo; Valesini, Guido

    2013-03-01

    The articular cartilage is an important component of human organism that has elasticity, low-friction surface, and ability to withstand great physical forces. The structure consists of collagens and proteoglycans, whereas non-collagenous proteins are needed for the organization and modulation of the molecular networks. The structural elements of the cartilage are typical to that tissue and could, in part, account for the localization of the inflammatory response to the joint. For this reason cartilage is of particular interest in autoimmunity as it may represent a source of antigens. It is well known that sensitization with collagens can produce autoimmune rheumatic diseases in experimental models. So far, the cartilage proteins that have been clearly characterized to be arthritogenic in experimental models involve types II and XI collagen, cartilage oligomeric matrix protein, and aggrecan. It is likely that these proteins are also recognized at different stages in the development of rheumatoid arthritis and in other autoimmune diseases. The mechanisms determining the trigger of a cartilage-specific immune response, its development and outcome are poorly understood. Most likely, the distribution and concentration of a specific cartilage protein may play a role by eliciting an autoimmune response. Indeed, the inflammatory processes lead to tissue damage mediated by the intervention of several factors such as autoantibodies, cytokines as well as cells of the innate an adaptive immunity. For this reason, even previously-considered degenerative diseases, such as osteoarthritis, should now be re-evaluated as at least partly inflammatory-driven. Thus, the objective of this review is to describe the clinical conditions sustained by the immune-mediated reactions to cartilage, which represents the target organ in a number of autoimmune diseases. PMID:23201917

  1. Type 1 autoimmune pancreatitis

    PubMed Central

    2011-01-01

    Before the concept of autoimmune pancreatitis (AIP) was established, this form of pancreatitis had been recognized as lymphoplasmacytic sclerosing pancreatitis or non-alcoholic duct destructive chronic pancreatitis based on unique histological features. With the discovery in 2001 that serum IgG4 concentrations are specifically elevated in AIP patients, this emerging entity has been more widely accepted. Classical cases of AIP are now called type 1 as another distinct subtype (type 2 AIP) has been identified. Type 1 AIP, which accounts for 2% of chronic pancreatitis cases, predominantly affects adult males. Patients usually present with obstructive jaundice due to enlargement of the pancreatic head or thickening of the lower bile duct wall. Pancreatic cancer is the leading differential diagnosis for which serological, imaging, and histological examinations need to be considered. Serologically, an elevated level of IgG4 is the most sensitive and specific finding. Imaging features include irregular narrowing of the pancreatic duct, diffuse or focal enlargement of the pancreas, a peri-pancreatic capsule-like rim, and enhancement at the late phase of contrast-enhanced images. Biopsy or surgical specimens show diffuse lymphoplasmacytic infiltration containing many IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. A dramatic response to steroid therapy is another characteristic, and serological or radiological effects are normally identified within the first 2 or 3 weeks. Type 1 AIP is estimated as a pancreatic manifestation of systemic IgG4-related disease based on the fact that synchronous or metachronous lesions can develop in multiple organs (e.g. bile duct, salivary/lacrimal glands, retroperitoneum, artery, lung, and kidney) and those lesions are histologically identical irrespective of the organ of origin. Several potential autoantigens have been identified so far. A Th2-dominant immune reaction and the activation of regulatory T-cells are assumed to be involved in the underlying immune reaction. IgG4 antibodies have two unique biological functions, Fab-arm exchange and a rheumatoid factor-like activity, both of which may play immune-defensive roles. However, the exact role of IgG4 in this disease still remains to be clarified. It seems important to recognize this unique entity given that the disease is treatable with steroids. PMID:22151922

  2. Autoimmune disease and hair loss.

    PubMed

    Moghadam-Kia, Siamak; Franks, Andrew G

    2013-01-01

    Once systemic disease is in remission, it is prudent to recognize the importance of alopecia in the patient's overall sense of well-being and quality-of-life clinical outcome. Scarring alopecia (scalp discoid lupus erythematosus) can be the presenting manifestation of lupus in more than half of affected individuals. Diffuse nonscarring alopecia in lupus is usually responsive to treatment of the systemic disease. Severe, often intractable burning pruritus of the scalp is a frequent complaint in dermatomyositis. Lichen planopilaris may mimic other autoimmune forms of scarring alopecia. Alopecia can also be caused by medications used to treat systemic autoimmune disease and fibromyalgia. PMID:23159178

  3. Autoimmune Myocarditis, Valvulitis, and Cardiomyopathy

    PubMed Central

    Myers, Jennifer M.; Cunningham, Madeleine W.; Fairweather, DeLisa; Huber, Sally A.

    2013-01-01

    Cardiac myosin-induced autoimmune myocarditis (EAM) is a model of inflammatory heart disease initiated by CD4+ T cells (Smith and Allen 1991; Li, Heuser et al. 2004). It is a paradigm of the immune-mediated cardiac damage believed to play a role in the pathogenesis of a subset of postinfectious human cardiomyopathies (Rose, Herskowitz et al. 1993). Myocarditis is induced in susceptible mice by immunization with purified cardiac myosin (Neu, Rose et al. 1987) or specific peptides derived from cardiac myosin (Donermeyer, Beisel et al. 1995; Pummerer, Luze et al. 1996) (see Basic Protocol 1), or by adoptive transfer of myosin-reactive T cells (Smith and Allen 1991) (see Alternate Protocol). Myocarditis has been induced in Lewis rats by immunization with purified rat or porcine cardiac myosin (Kodama, Matsumoto et al. 1990; Li, Heuser et al. 2004) (see Basic Protocol 2) or S2-16 peptide (Li, Heuser et al. 2004), or by adoptive transfer of T cells stimulated by specific peptides derived from cardiac myosin (Wegmann, Zhao et al. 1994). Myocarditis begins 12 to 14 days after the first immunization, and is maximal after 21 days. Other animal models commonly used to study myocarditis development include the pathogen-induced models in which disease is initiated by viral infection. The first murine model of acute viral myocarditis causes sudden death via viral damage to cardiomyocytes (Huber, Gauntt et al. 1998; Horwitz, La Cava et al. 2000; Fong 2003; Fuse, Chan et al. 2005; Fairweather and Rose 2007; Cihakova and Rose 2008) whereas the second model is based on inoculation with heart-passaged coxsackievirus B3 (CVB3) that includes damaged heart proteins (Fairweather, Frisancho-Kiss et al. 2004; Fairweather D 2004; Fairweather and Rose 2007; Cihakova and Rose 2008) In addition to the protocols used to induce EAM in mice and rats, support protocols are included for preparing purified cardiac myosin using mouse or rat heart tissue (see Support Protocol 1), preparing purified cardiac myosin for injection (see Support Protocol 2), and collecting and assessing hearts by histopathological means (see Support Protocol 3). PMID:23564686

  4. Bone Marrow Transplantation for Autoimmune Diseases

    Microsoft Academic Search

    Susumu Ikehara

    1998-01-01

    Bone marrow transplantation (BMT) is now becoming a powerful strategy for the treatment of patients with autoimmune diseases. Using various animal models for autoimmune diseases, we have previously found that allogeneic BMT (not autologous BMT) can be used to treat autoimmune diseases such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), immune thrombocytic purpura, insulin-dependent diabetes mellitus (IDDM), chronic glomerulonephritis,

  5. Autoimmune liver disease: overlap and outliers

    Microsoft Academic Search

    Mary K Washington

    2007-01-01

    The three main categories of autoimmune liver disease are autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC); all are well-defined entities with diagnosis based upon a constellation of clinical, serologic, and liver pathology findings. Although these diseases are considered autoimmune in nature, the etiology and possible environmental triggers of each remain obscure. The characteristic morphologic patterns

  6. Aicardi-Goutičres syndrome: a model disease for systemic autoimmunity.

    PubMed

    Lee-Kirsch, M A; Wolf, C; Günther, C

    2014-01-01

    Systemic autoimmunity is a complex disease process that results from a loss of immunological tolerance characterized by the inability of the immune system to discriminate self from non-self. In patients with the prototypic autoimmune disease systemic lupus erythematosus (SLE), formation of autoantibodies targeting ubiquitous nuclear antigens and subsequent deposition of immune complexes in the vascular bed induces inflammatory tissue injury that can affect virtually any organ system. Given the extraordinary genetic and phenotypic heterogeneity of SLE, one approach to the genetic dissection of complex SLE is to study monogenic diseases, for which a single gene defect is responsible. Considerable success has been achieved from the analysis of the rare monogenic disorder Aicardi-Goutičres syndrome (AGS), an inflammatory encephalopathy that clinically resembles in-utero-acquired viral infection and that also shares features with SLE. Progress in understanding the cellular and molecular functions of the AGS causing genes has revealed novel pathways of the metabolism of intracellular nucleic acids, the major targets of the autoimmune attack in patients with SLE. Induction of autoimmunity initiated by immune recognition of endogenous nucleic acids originating from processes such as DNA replication/repair or endogenous retro-elements represents novel paradigms of SLE pathogenesis. These findings illustrate how investigating rare monogenic diseases can also fuel discoveries that advance our understanding of complex disease. This will not only aid the development of improved tools for SLE diagnosis and disease classification, but also the development of novel targeted therapeutic approaches. PMID:23786362

  7. Type 1 Regulatory T cells (Tr1) in autoimmunity

    PubMed Central

    Pot, Caroline; Apetoh, Lionel; Kuchroo, Vijay K.

    2011-01-01

    The ability of IL-10 producing Type 1 regulatory T cells (Tr1) to restrain the activation of effector immune cells during autoimmune responses underscores their essential role in maintaining immune tolerance. While mouse studies have demonstrated that increasing the numbers and/or function of Tr1 cells could improve the course of autoimmune diseases, the inability to generate Tr1 cells in vitro in large numbers has hampered identification of the molecular mechanisms responsible for their differentiation. Interleukin-27 (IL-27), a member of the IL-12 heterodimeric cytokine family, was identified as an important cytokine that suppresses effector TH17 cells and promotes the generation of Tr1 cells. Tr1 cells dampen autoimmunity and tissue inflammation partly through their secretion of the immunosuppressive cytokine IL-10. Here we review the molecular mechanisms involved in IL-27-induced Tr1 cell differentiation, with a focus on the role of two transcription factors, the aryl hydrocarbon receptor (AhR) and c-Maf. We also discuss how ligands that bind to AhR and affect the biology of IL-27-induced Tr1 cells can be exploited as a therapeutic approach to alleviate human autoimmune diseases. PMID:21840222

  8. Temporal expression profile and distribution pattern indicate a role of connective tissue growth factor (CTGF/CCN-2) in diabetic nephropathy in mice.

    PubMed

    Roestenberg, Peggy; van Nieuwenhoven, Frans A; Joles, Jaap A; Trischberger, Claudia; Martens, Paula P; Oliver, Noelynn; Aten, Jan; Höppener, Jo W; Goldschmeding, Roel

    2006-06-01

    Connective tissue growth factor (CTGF) is overexpressed in diabetic nephropathy (DN) and has therefore been implicated in its pathogenesis. The objective of the present study was to determine the tissue distribution of increased CTGF expression and the relationship of plasma, urinary, and renal CTGF levels to the development and severity of DN. We studied the relationship between CTGF and renal pathology in streptozotocin (STZ)-induced diabetes in C57BL/6J mice. Diabetic and age-matched control mice were killed after 1, 2, 4, and 9 wk of diabetes. In addition, key parameters of diabetes and DN were analyzed in 10-mo-old diabetic ob/ob mice and their ob/+ littermates. STZ-induced diabetic mice showed a significantly increased urinary albumin excretion after 1 wk and increased mesangial matrix score after 2 wk. Increased renal fibronectin, fibronectin ED-A, and collagen IValpha1 expression, as well as elevated plasma creatinine levels, were observed after 9 wk. After 2 wk, CTGF mRNA was upregulated threefold in the renal cortex. By 9 wk, CTGF mRNA was also increased in the heart and liver. In contrast, transforming growth factor-beta1 mRNA content was significantly increased only in the kidney by 9 wk. Renal CTGF expression was mainly localized in podocytes and parietal glomerular epithelial cells, and less prominent in mesangial cells. In addition, plasma CTGF levels and urinary CTGF excretion were increased in diabetic mice. Moreover, albuminuria strongly correlated with urinary CTGF excretion (R = 0.83, P < 0.0001). Increased CTGF expression was also demonstrated in type 2 diabetic ob/ob mice, which points to a causal relationship between diabetes and CTGF and thus argues against a role of STZ in this process. The observed relationship of podocyte and urinary CTGF to markers of DN suggests a pathogenic role of CTGF in the development of DN. PMID:16380465

  9. Topographic distribution of the different cell types, connective tissue and vascular tissue/lumina within a functional bovine corpus luteum and its association with breed, type of fixation protocol and stage during the cycle.

    PubMed

    Cools, S; Van den Broeck, W; De Vliegher, S; Piepers, S; Hostens, M; Opsomer, G

    2013-08-01

    In the present study, we analysed the effect of fixative, breed, luteal stage and location on the nuclear density, volume density of connective tissue and vascular tissue/lumina within a bovine luteal gland in view of the development of an in vivo sampling technique to longitudinally monitor luteal histophysiology. The inner zone defined as the zone geometrically closest to the centre of the gland shows a significantly lower nuclear density (for all cell types) and a higher volume density of collagen fibres and vessels when compared with the outer zone (p < 0.001). The nuclear density in luteal glands from Holstein-Friesian cows is not significantly different from that in Belgian Blue cows, nor is it in stage II vs stage III glands. The collagen fibre content was significantly lower in glands of Belgian Blue cows (p = 0.01) and in younger glands (p = 0.003). Hence, it seems that the lower nuclear density in the inner zone was compensated by a higher amount of collagen fibres. As the type of fixative applied has a significant effect on the nuclear density of the different cell types, the present study warrants future research to further optimize the fixation protocol. As a conclusion, we can state that the topographic difference in nuclear distribution for the different cell types in a bovine luteal gland is only significant when comparing the inner vs the outer zone. This implies that if a sample representative for the whole gland has to be taken, for example, when taking an in vivo sample, it is necessary that the biopsy goes through the inner zone and contains the total diameter of the gland. PMID:23281851

  10. Autoimmune Etiology of Generalized Vitiligo

    Microsoft Academic Search

    I. Le Poole; R. Luiten

    2008-01-01

    Vitiligo is characterized by progressive skin depigmentation resulting from an autoimmune response targeting epidermal melanocytes. Melanocytes are particularly immunogenic by virtue of the contents of their melanosomes, generating the complex radical scavenging molecule melanin in a process that involves melanogenic enzymes and structural components, including tyrosinase, MART-1, gp100, TRP-2 and TRP-1. These molecules are also prime targets of the immune

  11. Paraneoplastic Autoimmunity in Thymus Tumors

    PubMed Central

    Schultz, Anja; Wilisch, Annette; Helmreich, Markus; Nenninger, Regina; Müller-Hermelink, Hans Konrad

    1998-01-01

    Autoimmune phenomena are more frequent in thymic epithelial tumors (TET) than in any other human tumor. Mysthenia gravis (MG) is by far the most common autoimmune disease in thymoma patients. MG is characterized by muscle weakness due to autoantibodies against the acetylcholine receptor (AChR), and CD4 +AChR-specific T cells play a pivotal role for the production of these autoantibodies. About 10% of MG patients have a thymoma and, interestingly, only such thymomas exhibit an MG association that maintains thymuslike morphological and functional features with respect to the homing and differentiation of immature T cells. Since AChR protein is not expressed in thymomas, the specificity of the autoimmunity in thymoma-associated MG is thought to be determined by nonreceptor proteins with AChR epitopes. Such proteins are overexpressed in cortical-type MG-associated thymomas, and medullary thymomas express these proteins at barely detectable levels. Aside from this quantitative difference, the pathogenesis of anti-AChR autoimmunity might be qualitatively different in these thymoma subtypes. Our findings suggest that an antigen-specific abnormal Tcell selection by cortical-type TET may contribute to the pathogenesis of paraneoplastic MG. In contrast, an abnormal (intratumorous) activation of autoreactive T cells may be operative in medullary thymomas. PMID:9716914

  12. Gene Therapy for Autoimmune Disorders

    Microsoft Academic Search

    C. H. Evans; S. C. Ghivizzani; T. J. Oligino; P. D. Robbins

    2000-01-01

    Although many autoimmune disorders do not have a strong genetic basis, their treatment may nevertheless be improved by gene therapies. Most strategies seek to transfer genes encoding immunomodulatory products that will alter host immune responses in a beneficial manner. Used in this fashion, genes serve as biological delivery vehicles for the products they encode. By this means gene therapy overcomes

  13. Helicobacter pylori and gastric autoimmunity.

    PubMed

    D'Elios, Mario Milco; Bergman, Mathijs P; Amedei, Amedeo; Appelmelk, Ben J; Del Prete, Gianfranco

    2004-12-01

    Host specific T-cell response is critical for the outcome of Helicobacter pylori infection. In genetically susceptible individuals, H. pylori can activate gastric CD4+ Th1 cells that recognize cross-reactive epitopes shared by H. pylori proteins and self H+, K+-ATPase, leading to gastric autoimmunity via molecular mimicry. PMID:15596126

  14. Helicobacter pylori and gastric autoimmunity

    Microsoft Academic Search

    Mario Milco D’Elios; Mathijs P. Bergman; Amedeo Amedei; Ben J. Appelmelk; Gianfranco Del Prete

    2004-01-01

    Host specific T-cell response is critical for the outcome of Helicobacter pylori infection. In genetically susceptible individuals, H. pylori can activate gastric CD4+ Th1 cells that recognize cross-reactive epitopes shared by H. pylori proteins and self H+, K+-ATPase, leading to gastric autoimmunity via molecular mimicry.

  15. Change in activity of some protective reactions of the connective tissue during development and resolution of subcutaneously transplanted brown-pearce carcinoma under conditions of decortication and dibasol action

    Microsoft Academic Search

    K. P. Balitskii

    1964-01-01

    The problem of the changes in the reactivity of an organism during progressive carcinogenesis, about the role which the nervous and the connective tissue system plays in this process, is inadequately elucidated in the literature [3-6]. Taking into account the practical importance of investigating the interaction between an organism and a tumor during retrogression of malignant neoplasms, we studied the

  16. In-Vivo Nonlinear Optical Microscopy (NLOM) of Epithelial-Connective Tissue Interface (ECTI) Reveals Quantitative Measures of Neoplasia in Hamster Oral Mucosa

    PubMed Central

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

    2015-01-01

    The epithelial-connective tissue interface (ECTI) plays an integral role in epithelial neoplasia, including oral squamous cell carcinoma (OSCC). This interface undergoes significant alterations due to hyperproliferating epithelium that supports the transformation of normal epithelium to precancers and cancer. We present a method based on nonlinear optical microscopy to directly assess the ECTI and quantify dysplastic alterations using a hamster model for oral carcinogenesis. Neoplastic and non-neoplastic normal mucosa were imaged in-vivo by both multiphoton autofluorescence microscopy (MPAM) and second harmonic generation microscopy (SHGM) to obtain cross-sectional reconstructions of the oral epithelium and lamina propria. Imaged sites were biopsied and processed for histopathological grading and measurement of ECTI parameters. An ECTI shape parameter was calculated based on deviation from the linear geometry (?Linearity) seen in normal mucosa was measured using MPAM-SHGM and histology. The ECTI was readily visible in MPAM-SHGM and quantitative shape analysis showed ECTI deformation in dysplasia but not in normal mucosa. ?Linearity was significantly (p < 0.01) higher in dysplasia (0.41±0.24) than normal (0.11±0.04) as measured in MPAM-SHGM and results were confirmed in histology which showed similar trends in ?Linearity. Increase in ?Linearity was also statistically significant for different grades of dysplasia. In-vivo ?Linearity measurement alone from microscopy discriminated dysplasia from normal tissue with 87.9% sensitivity and 97.6% specificity, while calculations from histology provided 96.4% sensitivity and 85.7% specificity. Among other quantifiable architectural changes, a progressive statistically significant increase in epithelial thickness was seen with increasing grade of dysplasia. MPAM-SHGM provides new noninvasive ways for direct characterization of ECTI which may be used in preclinical studies to investigate the role of this interface in early transformation. Further development of the method may also lead to new diagnostic approaches to differentiate non-neoplastic tissue from precancers and neoplasia, possibly with other cellular and layer based indicators of abnormality. PMID:25633927

  17. Autoimmunity as a Candidate for the Etiopathogenesis of Meniere's Disease: Detection of Autoimmune Reactions and Diagnostic Biomarker Candidate

    PubMed Central

    Kim, Sung Huhn; Kim, Jin Young; Lee, Hyun Jin; Gi, Mia; Kim, Bo Gyung; Choi, Jae Young

    2014-01-01

    Meniere's disease is an inner ear disorder that can manifest as fluctuating vertigo, sensorineural hearing loss, tinnitus, and aural fullness. However, the pathologic mechanism of Meniere's disease is still unclear. In this study, we evaluated autoimmunity as a potential cause of Meniere's disease. In addition we tried to find useful biomarker candidates for diagnosis. We investigated the protein composition of human inner ear fluid using liquid column mass spectrometry, the autoimmune reaction between circulating autoantibodies in patient serum and multiple antigens using the Protoarray system, the immune reaction between patient serum and mouse inner ear tissues using western blot analysis. Nine proteins, including immunoglobulin and its variants and interferon regulatory factor 7, were found only in the inner ear fluid of patients with Meniere's disease. Enhanced immune reactions with 18 candidate antigens were detected in patients with Meniere's disease in Protoarray analysis; levels of 8 of these antigens were more than 10-fold higher in patients than in controls. Antigen-antibody reactions between mouse inner ear proteins with molecular weights of 23–48 kDa and 63–75 kDa and patient sera were detected in 8 patients. These findings suggest that autoimmunity could be one of the pathologic mechanisms behind Meniere's disease. Multiple autoantibodies and antigens may be involved in the autoimmune reaction. Specific antigens that caused immune reactions with patient's serum in Protoarray analysis can be candidates for the diagnostic biomarkers of Meniere's disease. PMID:25330336

  18. DARC shuttles inflammatory chemokines across the blood–brain barrier during autoimmune central nervous system inflammation

    PubMed Central

    Minten, Carsten; Alt, Carsten; Gentner, Melanie; Frei, Elisabeth; Deutsch, Urban; Lyck, Ruth; Schaeren-Wiemers, Nicole; Rot, Antal

    2014-01-01

    The Duffy antigen/receptor for chemokines, DARC, belongs to the family of atypical heptahelical chemokine receptors that do not couple to G proteins and therefore fail to transmit conventional intracellular signals. Here we show that during experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, the expression of DARC is upregulated at the blood–brain barrier. These findings are corroborated by the presence of a significantly increased number of subcortical white matter microvessels staining positive for DARC in human multiple sclerosis brains as compared to control tissue. Using an in vitro blood–brain barrier model we demonstrated that endothelial DARC mediates the abluminal to luminal transport of inflammatory chemokines across the blood–brain barrier. An involvement of DARC in experimental autoimmune encephalomyelitis pathogenesis was confirmed by the observed ameliorated experimental autoimmune encephalomyelitis in Darc?/? C57BL/6 and SJL mice, as compared to wild-type control littermates. Experimental autoimmune encephalomyelitis studies in bone marrow chimeric Darc?/? and wild-type mice revealed that increased plasma levels of inflammatory chemokines in experimental autoimmune encephalomyelitis depended on the presence of erythrocyte DARC. However, fully developed experimental autoimmune encephalomyelitis required the expression of endothelial DARC. Taken together, our data show a role for erythrocyte DARC as a chemokine reservoir and that endothelial DARC contributes to the pathogenesis of experimental autoimmune encephalomyelitis by shuttling chemokines across the blood–brain barrier. PMID:24625696

  19. Few Foxp3? regulatory T cells are sufficient to protect adult mice from lethal autoimmunity.

    PubMed

    Mayer, Christian T; Ghorbani, Peyman; Kühl, Anja A; Stüve, Philipp; Hegemann, Maike; Berod, Luciana; Gershwin, M Eric; Sparwasser, Tim

    2014-10-01

    Foxp3 specifies the Treg cell lineage and is indispensable for immune tolerance. Accordingly, rare Foxp3 mutations cause lethal autoimmunity. The mechanisms precipitating more prevalent human autoimmune diseases are poorly understood, but involve a combination of genetic and environmental factors. Many autoimmune diseases associate with a partial Treg-cell dysfunction, yet mouse models reflecting such complex pathophysiological processes are rare. Around 95% of Foxp3(+) Treg cells can be specifically depleted in bacterial artifical chromosome (BAC)-transgenic Depletion of REGulatory T cells (DEREG) mice through diphtheria toxin (DT) treatment. However, Treg-cell depletion fails to cause autoimmunity in adult DEREG mice for unclear reasons. By crossing Foxp3(GFP) knock-in mice to DEREG mice, we introduced additional genetic susceptibility that does not affect untreated mice. Strikingly, DT treatment of DEREG × Foxp3(GFP) mice rapidly causes autoimmunity characterized by blepharitis, tissue damage, and autoantibody production. This inflammatory disease is associated with augmented T-cell activation, increased Th2 cytokine production and myeloproliferation, and is caused by defective Treg-cell homeostasis, preventing few DT-insensitive Treg cells from repopulating the niche after Treg-cell depletion. Our study provides important insights into self-tolerance. We further highlight DEREG × Foxp3(GFP) mice as a model to investigate the role of environmental factors in precipitating autoimmunity. This may help to better understand and treat human autoimmunity. PMID:25042334

  20. Undifferentiated Connective Tissue Disease at risk for systemic sclerosis (SSc) (so far referred to as very early/early SSc or pre-SSc).

    PubMed

    Valentini, Gabriele

    2015-03-01

    In the last few years, a number of studies have been published on a condition characterized by Raynaud's phenomenon (RP) associated with systemic sclerosis (SSc) marker autoantibodies and/or scleroderma-type capillaroscopic abnormalities and referred to as very early/early SSc. The present review is devoted to analyze pathophysiologic, clinical, and evolutive aspects of the condition that would induce to label it as Undifferentiated Connective Tissue Disease at risk for SSc and to split it into 3 subsets (i.e. RP associated to marker autoantibodies and scleroderma-type capillaroscopic abnormalities; RP associated to marker autoantibodies in the absence of scleroderma-type capillaroscopic abnormalities; and RP associated to scleroderma-type capillaroscopic abnormalities without any detectable marker autoantibody), which have been shown to carry different degrees of risk, but not the certainty, to develop overt SSc over time. This nosographic approach is instrumental to plan future studies devoted to investigate validated biomarkers heralding the development of major vascular disease manifestations as well as skin and/or organ fibrosis in patients at risk. PMID:25461837

  1. Antisense inhibition of connective tissue growth factor (CTGF/CCN2) mRNA limits hypertrophic scarring without affecting wound healing in vivo.

    PubMed

    Sisco, Mark; Kryger, Zol B; O'Shaughnessy, Kristina D; Kim, Peter S; Schultz, Greg S; Ding, Xian-Zhong; Roy, Nakshatra K; Dean, Nicholas M; Mustoe, Thomas A

    2008-01-01

    Augmented expression of connective tissue growth factor (CTGF/CCN2) is observed in healing wounds and in a variety of fibrotic disorders. It appears to enhance many of the effects of transforming growth factor-beta and has been shown to have independent fibrogenic functions. Despite these observations, its importance to dermal wound healing and the transition from wound to scar remains poorly defined. In this study, we use established rabbit models to evaluate the roles of CTGF in dermal wound healing and hypertrophic scarring. We show that CTGF mRNA demonstrates persistent up-regulation in hypertrophic scars. Treatment of wounds with antisense oligonucleotides to CTGF has no measurable effect on early wound closure. However, antisense therapy significantly limits subsequent hypertrophic scarring. Inhibition of CTGF is associated with a marked reduction in the number of myofibroblasts in scars and decreased transcription of TIMP-1 and types I and III collagen. These findings confirm CTGF to be a key mediator of hypertrophic scarring in this model. Its effect on myofibroblasts in this setting suggests a mechanism whereby it plays this role. Its limited participation in early healing implies that it may be a useful and specific target for modulating hypertrophic scarring following injury. PMID:19128261

  2. Characterisation of novel fungal and bacterial protease preparations and evaluation of their ability to hydrolyse meat myofibrillar and connective tissue proteins.

    PubMed

    Ryder, Kate; Ha, Minh; Bekhit, Alaa El-Din; Carne, Alan

    2015-04-01

    The catalytic capability of four commercially available food-grade fungal and bacterial protease preparations (AFP, FPII, F60K and HT) was evaluated over a range of pH, temperature and substrate conditions using esterase and caseinolytic activity assays and time course hydrolysis over 120 and 60 min of myofibrillar and connective tissue proteins, respectively. The protease preparations displayed similar casein hydrolysis kinetics and were active in hydrolysing BODIPY-FL casein to varying extents at postmortem aging meat pH (5.0-6.0). All of the four proteases exhibited selective hydrolytic activity towards meat myofibrillar proteins including myosin and actin. Significant hydrolysis of two meat tenderisation protein markers troponin T and desmin by the four proteases was detected by western blot. The results obtained indicate that the new fungal protease preparations AFP and FPII, bacterial protease preparation HT and the new source of fungal protease preparation F60K have potential for use in meat tenderising applications. PMID:25442543

  3. Reconciling healthcare professional and patient perspectives in the development of disease activity and response criteria in connective tissue disease-related interstitial lung diseases.

    PubMed

    Saketkoo, Lesley Ann; Mittoo, Shikha; Frankel, Sid; LeSage, Daphne; Sarver, Catherine; Phillips, Kristine; Strand, Vibeke; Matteson, Eric L

    2014-04-01

    Interstitial lung diseases (ILD), including those related to connective tissue disease (CTD), and idiopathic pulmonary fibrosis (IPF) carry high morbidity and mortality. Great efforts are under way to develop and investigate meaningful treatments in the context of clinical trials. However, efforts have been challenged by a lack of validated outcome measures and by inconsistent use of measures in clinical trials. Lack of consensus has fragmented effective use of strategies in CTD-ILD and IPF, with a history of resultant difficulties in obtaining agency approval of treatment interventions. Until recently, the patient perspective to determine domains and outcome measures in CTD-ILD and IPF had never been applied. Efforts described here demonstrate unequivocally the value and influence of patient involvement on core set development. Regarding CTD-ILD, this is the first OMERACT working group to directly address a manifestation/comorbidity of a rheumatic disease (ILD) as well as a disease not considered rheumatic (IPF). The OMERACT 11 proceedings of the CTD-ILD Working Group describe the forward and lateral process to include both the medical and patient perspectives in the urgently needed identification of a core set of preliminary domains and outcome measures in CTD-ILD and IPF. PMID:24488412

  4. Comparative Morphology of the Papillae Linguales and their Connective Tissue Cores in the Tongue of the Greater Japanese Shrew-mole, Urotrichus talpoides

    PubMed Central

    Yoshimura, K; Shindo, J; Kageyama, I

    2013-01-01

    The external morphology of the papillae linguales (papillae filiformes, papillae fungiformes and papillae vallatae) and their connective tissue cores (CTCs) of the greater Japanese shrew-mole (Urotrichus talpoides) were analysed by optical and scanning electron microscopy. Papillae filiformes were distributed over the dorsal surface of the apex linguae, and on the rostral and caudal regions of the corpus linguae but were less numerous in the mid-region. They were absent from the radix linguae. A pair of oval papillae vallatae was situated at the border between the corpus linguae and the radix linguae. Papillae foliatae were absent. The epithelial surface of each papilla filiformis consisted of a circular concavity, a ring-like wall and either a single thumb-like process or 2–3 slender pointed processes, depending on their location. The morphology of the CTCs of the papillae filiformes also varied regionally. The papillae linguales of the Japanese shrew-mole were morphologically similar to those of other Talpidae and Soricidae, including the common shrew, particularly with respect to the papillae filiformes in the mid- and caudal regions of the corpus linguae. PMID:22571539

  5. Reconciling Healthcare Professional and Patient Perspectives in the Development of Disease Activity and Response Criteria in Connective Tissue Disease Related Interstitial Lung Diseases

    PubMed Central

    Saketkoo, LA; Mittoo, S; Frankel, S; LeSage, D; Sarver, C; Phillips, K; Strand, V; Matteson, EL

    2015-01-01

    Interstitial lung diseases (ILD), including connective tissue disease (CTD) related and idiopathic pulmonary fibrosis (IPF), carry a high morbidity and mortality. Great efforts are underway to develop and investigate meaningful treatments in the context of clinical trials. However, these efforts have been challenged by the lack of validated outcome measures and inconsistent use of measures in the context of clinical trials. This lack of consensus has fragmented effective use of investigative in CTD-ILD and IPF with a history of resultant difficulties in agency approval of treatment interventions. Patient perspective in determination of domains and outcome measures in CTD-ILD and IPF, prior to this effort, has never occurred. These efforts demonstrate unequivocally the value and impact of patient involvement on core set development. Regarding CTD-ILD, this is the first OMERACT working group to directly address a manifestation/co-morbidity of a rheumatic disease (ILD) as well as a disease not considered rheumatic (IPF). The OMERACT 11 proceedings of the CTD-ILD Working Group describe the forward and lateral process to include both the medical and patient perspectives in the urgently needed identification of a core set of preliminary domains and outcome measures in CTD-ILD and IPF. PMID:24488412

  6. Targeting connective tissue growth factor (CTGF) in acute lymphoblastic leukemia pre-clinical models: anti-CTGF monoclonal antibody attenuates leukemia growth

    PubMed Central

    Battula, Venkata Lokesh; Korchin, Borys; Shi, Yuexi; Chen, Ye; Spong, Suzanne; Thomas, Deborah A.; Kantarjian, Hagop; Lock, Richard B; Andreeff, Michael; Konopleva, Marina

    2013-01-01

    Connective tissue growth factor (CTGF/CCN2) is involved in extracellular matrix production, tumor cell proliferation, adhesion, migration and metastasis. Recent studies have shown that CTGF expression is elevated in precursor-B acute lymphoblastic leukemia (ALL) and that increased expression of CTGF is associated with inferior outcome in B-ALL. In this study, we characterized the functional role and downstream signaling pathways of CTGF in ALL cells. First, we utilized lentiviral shRNA to knock-down CTGF in RS4;11 and REH ALL cells expressing high levels of CTGF mRNA. Silencing of CTGF resulted in significant suppression of leukemia cell growth compared to control vector, which was associated with AKT/mTOR inactivation and increased levels of cyclin-dependent kinase inhibitor p27. CTGF knockdown sensitized ALL cells to vincristine and methotrexate. Treatment with an anti-CTGF monoclonal antibody, FG-3019, significantly prolonged survival of mice injected with primary xenograft B-ALL cells when co-treated with conventional chemotherapy (vincristine, L-asparaginase and dexamethasone). Data suggest that CTGF represents a targetable molecular aberration in B-ALL, and blocking CTGF signaling in conjunction with administration of chemotherapy may represent a novel therapeutic approach for ALL patients. PMID:24154679

  7. Comparative morphological study on the stereo-structure of the lingual papillae and their connective tissue cores of the American beaver (Castor canadensis).

    PubMed

    Shindo, Junji; Yoshimura, Ken; Kobayashi, Kan

    2006-02-01

    The lingual papillae and the connective tissue cores (CTC) of the American beaver were examined by light and scanning electron microscopy. The tongue of American beaver was about 9 cm in length, 3.5 cm in width, and has a lingual prominence. Four types of papillae (filiform, fungiform, vallate and foliate papillae) were observed. The filiform papillae can be classified into three types (filiform, large filiform and dorm-like papillae). Filiform papillae distributed on the anterior tongue and posterior of the lingual prominence consisted of a posterior thick main process and several small accessory processes. After removal of the epithelium, the CTCs of the filiform papillae had U-shaped, horseshoe-like primary cores with 10-15 rod-shaped small accessory cores. Large filiform papillae were distributed at the anterior margin of the lingual prominence. Dome-like papillae were distributed at the top of lingual prominence. Fungiform papillae were observed two types. Fungiform papillae, which were distributed at the anterior tongue, were round shaped. Fungiform papillae of the posterior of the lingual prominence were large and surrounded with a papillary groove. At the posterior of the tongue, three vallate papillae were arranged in a triangular pattern. Foliate papillae were on 22 to 25 parallel ridges and grooves. PMID:16526571

  8. Transforming growth factor ?2 (TGF-?2)-induced connective tissue growth factor (CTGF) expression requires sphingosine 1-phosphate receptor 5 (S1P5) in human mesangial cells.

    PubMed

    Wünsche, Christin; Koch, Alexander; Goldschmeding, Roel; Schwalm, Stephanie; Meyer Zu Heringdorf, Dagmar; Huwiler, Andrea; Pfeilschifter, Josef

    2015-05-01

    Transforming growth factor ?2 (TGF-?2) is well known to stimulate the expression of pro-fibrotic connective tissue growth factor (CTGF) in several cell types including human mesangial cells. The present study demonstrates that TGF-?2 enhances sphingosine 1-phosphate receptor 5 (S1P5) mRNA and protein expression in a time and concentration dependent manner. Pharmacological and siRNA approaches reveal that this upregulation is mediated via activation of classical TGF-? downstream effectors, Smad and mitogen-activated protein kinases. Most notably, inhibition of Gi with pertussis toxin and downregulation of S1P5 by siRNA block TGF-?2-stimulated upregulation of CTGF, demonstrating that Gi coupled S1P5 is necessary for TGF-?2-triggered expression of CTGF in human mesangial cells. Overall, these findings indicate that TGF-?2 dependent upregulation of S1P5 is required for the induction of pro-fibrotic CTGF by TGF-?. Targeting S1P5 might be an attractive novel approach to treat renal fibrotic diseases. PMID:25601519

  9. Autoimmunity in trypanosome infections

    PubMed Central

    MacKenzie, A. R.; Boreham, P. F. L.

    1974-01-01

    Ten rabbits infected with Trypanosoma (Trypanozoon) brucei showed a substantial increase in a natural anti-tissue autoantibody and Wassermann antibody. Absorptions suggest that the liver and Wassermann antibodies are distinct. The liver antibody reacts equally well with homologous and autologous liver. Absorption with trypanosomes and liver show that cross-reacting trypanosomal antibodies are not responsible for the liver activity. These antibodies will contribute to the raised IgM levels of rabbit trypanosomiasis and may be important in this respect but the precise extent of the contribution is not known. It is suggested that a depression of certain T-cell functions may release antibody secreting B-cell descendants from T-cell control resulting in elevated IgM. PMID:4211823

  10. Immunomodulatory strategies prevent the development of autoimmune emphysema

    PubMed Central

    2010-01-01

    Background The presence of anti-endothelial cell antibodies and pathogenic T cells may reflect an autoimmune component in the pathogenesis of emphysema. Whether immune modulatory strategies can protect against the development of emphysema is not known. Methods Sprague Dawley rats were immunized with human umbilical vein endothelial cells (HUVEC) to induce autoimmune emphysema and treated with intrathymic HUVEC-injection and pristane. Measurements of alveolar airspace enlargement, cytokine levels, immuno histochemical, western blot analysis, and T cell repertoire of the lung tissue were performed. Results The immunomodulatory strategies protected lungs against cell death as demonstrated by reduced numbers of TUNEL and active caspase-3 positive cells and reduced levels of active caspase-3, when compared with lungs from HUVEC-immunized rats. Immunomodulatory strategies also suppressed anti-endothelial antibody production and preserved CNTF, IL-1alpha and VEGF levels. The immune deviation effects of the intrathymic HUVEC-injection were associated with an expansion of CD4+CD25+Foxp3+ regulatory T cells. Pristane treatment decreased the proportion of T cells expressing receptor beta-chain, V?16.1 in the lung tissue. Conclusions Our data demonstrate that interventions classically employed to induce central T cell tolerance (thymic inoculation of antigen) or to activate innate immune responses (pristane treatment) can prevent the development of autoimmune emphysema. PMID:21162738

  11. Peroxisome Proliferator-Activated Receptor-? in Thyroid Autoimmunity

    PubMed Central

    Ferrari, Silvia Martina; Fallahi, Poupak; Vita, Roberto; Benvenga, Salvatore

    2015-01-01

    Peroxisome proliferator-activated receptor- (PPAR-) ? expression has been shown in thyroid tissue from patients with thyroiditis or Graves' disease and furthermore in the orbital tissue of patients with Graves' ophthalmopathy (GO), such as in extraocular muscle cells. An increasing body of evidence shows the importance of the (C-X-C motif) receptor 3 (CXCR3) and cognate chemokines (C-X-C motif) ligand (CXCL)9, CXCL10, and CXCL11, in the T helper 1 immune response and in inflammatory diseases such as thyroid autoimmune disorders. PPAR-? agonists show a strong inhibitory effect on the expression and release of CXCR3 chemokines, in vitro, in various kinds of cells, such as thyrocytes, and in orbital fibroblasts, preadipocytes, and myoblasts from patients with GO. Recently, it has been demonstrated that rosiglitazone is involved in a higher risk of heart failure, stroke, and all-cause mortality in old patients. On the contrary, pioglitazone has not shown these effects until now; this favors pioglitazone for a possible use in patients with thyroid autoimmunity. However, further studies are ongoing to explore the use of new PPAR-? agonists in the treatment of thyroid autoimmune disorders. PMID:25722716

  12. Autoimmune markers are undetectable in end stage idiopathic dilated cardiomyopathy.

    PubMed Central

    de Leeuw, N; Melchers, W J; Ruiter, D J; Caforio, A L; Balk, A H; de Jonge, N; Galama, J M

    1999-01-01

    BACKGROUND: Autoreactive humoral and cellular immune responses may be involved in the pathogenesis of idiopathic dilated cardiomyopathy (IDC). Certain human leucocyte antigens (HLA) could also be linked to the development of IDC. AIM: To determine whether various markers of autoimmunity are present in the final phase of the disease, to substantiate the role of an autoimmune process in IDC. METHODS: 37 patients with end stage IDC were studied, together with 39 patients with end stage heart disease of known aetiology who were included for comparison. Multiple myocardial tissue samples from the explanted heart of each patient were evaluated (immuno)histologically. An indirect immunofluorescence assay was used to screen patient serum samples for the presence of heart specific autoantibodies. HLA class I and II frequencies were determined in each group and compared with HLA frequencies from healthy blood donors. RESULTS: Only scanty small mononuclear cell infiltrates were present in myocardial tissue of seven patients with IDC and of 11 patients with heart disease of known cause. The majority of these inflammatory cells were negative for T cell markers. All blood specimens were negative for heart specific autoantibodies and there was no apparent association of IDC with particular HLA phenotypes. CONCLUSIONS: These findings suggest that an active autoimmune process is not involved in the end stage of IDC. Images PMID:10674030

  13. The immunomodulator FTY720 and its phosphorylated derivative activate the Smad signalling cascade and upregulate connective tissue growth factor and collagen type IV expression in renal mesangial cells

    PubMed Central

    Xin, Cuiyan; Ren, Shuyu; Eberhardt, Wolfgang; Pfeilschifter, Josef; Huwiler, Andrea

    2005-01-01

    The immunomodulating agent FTY720 is a substrate for the sphingosine kinase and the phosphorylated form is able to bind to sphingosine 1-phosphate (S1P) receptors. In this study, we show that exposure of renal mesangial cells to phospho-FTY720 leads to a rapid and transient activation of several protein kinase cascades, including the mitogen- and stress-activated protein kinases. The nonphosphorylated FTY720 also increased MAPK phosphorylation, but with a reduced potency and a more delayed time course. In addition, phospho-FTY720 and FTY720 are able to increase phosphorylation of Smad proteins which are classical members of the transforming growth factor-? (TGF-?) signalling device, thus suggesting a crosstalk between FTY720 and TGF-? signalling. Pretreatment with the S1P3 receptor antagonist suramin inhibits FTY720 and phospho-FTY720-induced Smad phosphorylation, whereas pertussis toxin pretreatment, which blocks Gi/0 proteins, has no effect on Smad phosphorylation. Since TGF-? is a potent profibrotic cytokine in mesangial cells and upregulates the connective tissue growth factor (CTGF) and collagen as important hallmarks in the fibrotic sequelae, we investigated whether FTY720 and phospho-FTY720 are able to mimic these effects of TGF-?. Indeed, FTY720 and phospho-FTY720 markedly upregulate CTGF and collagen type IV protein expressions. In addition, the tissue inhibitor of metalloproteinase-1 is transcriptionally activated by FTY720, whereas cytokine-induced matrix metalloproteinase-9 is down-regulated by FTY720. Depletion of the TGF-? receptor type II by the siRNA transfection technique blocks not only Smad phosphorylation but also CTGF upregulation. Similarly, Smad-4 depletion by siRNA transfection also abrogates CTGF upregulation induced by FTY720 and phospho-FTY720. In summary, our data show that FTY720 and phospho-FTY720 not only activate the Smad signalling cascade in mesangial cells, but also upregulate the expression of CTGF and collagen. These findings suggest that FTY720 may have additional effects besides the established immunomodulatory action and, importantly, a profibrotic activity has to be considered in future experimental approaches. PMID:16299553

  14. AUTOPHAGY: HIGHLIGHTING A NOVEL PLAYER IN THE AUTOIMMUNITY SCENARIO

    PubMed Central

    Lleo, Ana; Invernizzi, Pietro; Selmi, Carlo; Coppel, Ross L.; Alpini, Gianfranco; Podda, Mauro; Mackay, Ian R.; Gershwin, M. Eric

    2007-01-01

    Autophagy is a physiological cellular mechanism that degrades and recycles proteins and other molecules to maintain an adequate amino acid level during nutritional starvation of the cell. Autophagy is involved in cellular homeostasis and differentiation, as well as in tissue remodeling, aging, cancer, and other diseases. Under particular environmental conditions, autophagy can also be a contributor to programmed cell death, or can act as a defense mechanism for the elimination of intracellular bacteria and viruses. According to recent experimental data, autophagy may be implicated in autoimmunity by promotion of major histocompatibility complex (MHC) class II presentation of cytosolic antigens and control of T lymphocyte homeostasis, and its induction by Th1 cytokines and perhaps by specific serum autoantibodies. We review herein the role of autophagy in immune function and its possible contribution to breakdown of tolerance and development of autoimmunity. PMID:17693057

  15. Autoimmune diseases and reproductive aging

    PubMed Central

    Bove, Riley

    2013-01-01

    As the population ages, more individuals with autoimmune diseases are experiencing reproductive senescence. Understanding the impact of menopause and age-related androgen decline on disease onset and course, as well as the potential for hormonal interventions, is critically important. In men, lupus erythematosis (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS) are associated with lower androgen levels. However, the impact of age-related declines in testosterone, as well as of testosterone replacement, on disease course remains underexplored. In women, the course of all three diseases with onset after the age of menopause differs from that with onset before menopause. Early age at menopause is associated with increased disease risk, and after menopause, disease course changes in SLE and RA. Less is known about MS. This article summarizes what is known about the relationship between reproductive aging and autoimmune diseases in men and women, and highlights areas for further investigation. PMID:23522436

  16. Autoimmune diseases and reproductive aging.

    PubMed

    Bove, Riley

    2013-11-01

    As the population ages, more individuals with autoimmune diseases are experiencing reproductive senescence. Understanding the impact of menopause and age-related androgen decline on disease onset and course, as well as the potential for hormonal interventions, is critically important. In men, lupus erythematosis (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS) are associated with lower androgen levels. However, the impact of age-related declines in testosterone, as well as of testosterone replacement, on disease course remains underexplored. In women, the course of all three diseases with onset after the age of menopause differs from that with onset before menopause. Early age at menopause is associated with increased disease risk, and after menopause, disease course changes in SLE and RA. Less is known about MS. This article summarizes what is known about the relationship between reproductive aging and autoimmune diseases in men and women, and highlights areas for further investigation. PMID:23522436

  17. Animal Models of Autoimmune Neuropathy

    PubMed Central

    Soliven, Betty

    2014-01-01

    The peripheral nervous system (PNS) comprises the cranial nerves, the spinal nerves with their roots and rami, dorsal root ganglia neurons, the peripheral nerves, and peripheral components of the autonomic nervous system. Cell-mediated or antibody-mediated immune attack on the PNS results in distinct clinical syndromes, which are classified based on the tempo of illness, PNS component(s) involved, and the culprit antigen(s) identified. Insights into the pathogenesis of autoimmune neuropathy have been provided by ex vivo immunologic studies, biopsy materials, electrophysiologic studies, and experimental models. This review article summarizes earlier seminal observations and highlights the recent progress in our understanding of immunopathogenesis of autoimmune neuropathies based on data from animal models. PMID:24615441

  18. Correlations between beta-cells' calcium dynamics reveal differences in functional connectivity patterns in islets of Langerhans from pancreas tissue slices under low and high levels of glucose

    NASA Astrophysics Data System (ADS)

    Stožer, Andraž; Gosak, Marko; Korošak, Dean; Yakubo, Kousuke; Dolenšek, Jure; Marhl, Marko; Rupnik, Marjan Slak

    2012-08-01

    In the last decade, approach developed in the frame of complex network theory has presented very successful and popular tools for studying the structure and functioning of complex systems. A particularly attractive avenue in this context is the analysis of biological systems, since structural principles of complex networks have been identified at all scales of functioning of living organisms. In the present paper, we propose the construction of a complex network representation of a pancreatic islet. In this compact microorgan, under physiological conditions the release of the single most important anabolic hormone insulin is robustly controlled by an efficient cell-to-cell communication mediated by gap junctions. Here, we extract networks of insulin releasing beta-cells from experimentally measured time series data on calcium dynamics and from positional information obtained by confocal laser-scanning functional imaging of islets in acute pancreatic tissue slices. In particular, connectivity patterns are determined on the basis of correlations between calcium dynamics in the islet. The extracted networks are then scrutinized with conventional tools for network analysis, whereby particular importance is devoted to comparison of the network structure under low and high glucose levels, i.e. physiologically resting and stimulating conditions, respectively. We show that the cellular dynamics is more correlated under stimulation and that the networks obtained in both regimes display a different organization. The range of interactions among beta cells is significantly shorter in the case of a higher stimulation. Our results thus provide novel insights into the relationship between network topology and functional organization of pancreatic islets.

  19. Gene expression profiling of connective tissue growth factor (CTGF) stimulated primary human tenon fibroblasts reveals an inflammatory and wound healing response in vitro

    PubMed Central

    Nickel, Joachim; Mueller, Thomas D.; Kneitz, Susanne; Gebhardt, Susanne; ter Vehn, Tobias Meyer; Schlunck, Guenther; Sebald, Walter

    2011-01-01

    Purpose The biologic relevance of human connective tissue growth factor (hCTGF) for primary human tenon fibroblasts (HTFs) was investigated by RNA expression profiling using affymetrixTM oligonucleotide array technology to identify genes that are regulated by hCTGF. Methods Recombinant hCTGF was expressed in HEK293T cells and purified by affinity and gel chromatography. Specificity and biologic activity of hCTGF was confirmed by biosensor interaction analysis and proliferation assays. For RNA expression profiling HTFs were stimulated with hCTGF for 48h and analyzed using affymetrixTM oligonucleotide array technology. Results were validated by real time RT–PCR. Results hCTGF induces various groups of genes responsible for a wound healing and inflammatory response in HTFs. A new subset of CTGF inducible inflammatory genes was discovered (e.g., chemokine [C-X-C motif] ligand 1 [CXCL1], chemokine [C-X-C motif] ligand 6 [CXCL6], interleukin 6 [IL6], and interleukin 8 [IL8]). We also identified genes that can transmit the known biologic functions initiated by CTGF such as proliferation and extracellular matrix remodelling. Of special interest is a group of genes, e.g., osteoglycin (OGN) and osteomodulin (OMD), which are known to play a key role in osteoblast biology. Conclusions This study specifies the important role of hCTGF for primary tenon fibroblast function. The RNA expression profile yields new insights into the relevance of hCTGF in influencing biologic processes like wound healing, inflammation, proliferation, and extracellular matrix remodelling in vitro via transcriptional regulation of specific genes. The results suggest that CTGF potentially acts as a modulating factor in inflammatory and wound healing response in fibroblasts of the human eye. PMID:21245951

  20. Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor OGR1 in human airway smooth muscle cells

    SciTech Connect

    Matsuzaki, Shinichi [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan)] [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Ishizuka, Tamotsu, E-mail: tamotsui@showa.gunma-u.ac.jp [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan)] [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Yamada, Hidenori; Kamide, Yosuke; Hisada, Takeshi; Ichimonji, Isao; Aoki, Haruka; Yatomi, Masakiyo [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan)] [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Komachi, Mayumi [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan)] [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan); Tsurumaki, Hiroaki; Ono, Akihiro; Koga, Yasuhiko [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan)] [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Dobashi, Kunio [Gunma University Graduate School of Health Sciences, Maebashi 371-8511 (Japan)] [Gunma University Graduate School of Health Sciences, Maebashi 371-8511 (Japan); Mogi, Chihiro; Sato, Koichi; Tomura, Hideaki [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan)] [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan); Mori, Masatomo [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan)] [Department of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi 371-8511 (Japan); Okajima, Fumikazu [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan)] [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan)

    2011-10-07

    Highlights: {yields} The involvement of extracellular acidification in airway remodeling was investigated. {yields} Extracellular acidification alone induced CTGF production in human ASMCs. {yields} Extracellular acidification enhanced TGF-{beta}-induced CTGF production in human ASMCs. {yields} Proton-sensing receptor OGR1 was involved in acidic pH-stimulated CTGF production. {yields} OGR1 may play an important role in airway remodeling in asthma. -- Abstract: Asthma is characterized by airway inflammation, hyper-responsiveness and remodeling. Extracellular acidification is known to be associated with severe asthma; however, the role of extracellular acidification in airway remodeling remains elusive. In the present study, the effects of acidification on the expression of connective tissue growth factor (CTGF), a critical factor involved in the formation of extracellular matrix proteins and hence airway remodeling, were examined in human airway smooth muscle cells (ASMCs). Acidic pH alone induced a substantial production of CTGF, and enhanced transforming growth factor (TGF)-{beta}-induced CTGF mRNA and protein expression. The extracellular acidic pH-induced effects were inhibited by knockdown of a proton-sensing ovarian cancer G-protein-coupled receptor (OGR1) with its specific small interfering RNA and by addition of the G{sub q/11} protein-specific inhibitor, YM-254890, or the inositol-1,4,5-trisphosphate (IP{sub 3}) receptor antagonist, 2-APB. In conclusion, extracellular acidification induces CTGF production through the OGR1/G{sub q/11} protein and inositol-1,4,5-trisphosphate-induced Ca{sup 2+} mobilization in human ASMCs.

  1. Identification and cloning of a connective tissue growth factor-like cDNA from human osteoblasts encoding a novel regulator of osteoblast functions.

    PubMed

    Kumar, S; Hand, A T; Connor, J R; Dodds, R A; Ryan, P J; Trill, J J; Fisher, S M; Nuttall, M E; Lipshutz, D B; Zou, C; Hwang, S M; Votta, B J; James, I E; Rieman, D J; Gowen, M; Lee, J C

    1999-06-11

    We have identified and cloned a novel connective tissue growth factor-like (CTGF-L) cDNA from primary human osteoblast cells encoding a 250-amino acid single chain polypeptide. Murine CTGF-L cDNA, encoding a polypeptide of 251 amino acids, was obtained from a murine lung cDNA library. CTGF-L protein bears significant identity ( approximately 60%) to the CCN (CTGF, Cef10/Cyr61, Nov) family of proteins. CTGF-L is composed of three distinct domains, an insulin-like growth factor binding domain, a von Willebrand Factor type C motif, and a thrombospondin type I repeat. However, unlike CTGF, CTGF-L lacks the C-terminal domain implicated in dimerization and heparin binding. CTGF-L mRNA ( approximately 1.3 kilobases) is expressed in primary human osteoblasts, fibroblasts, ovary, testes, and heart, and a approximately 26-kDa protein is secreted from primary human osteoblasts and fibroblasts. In situ hybridization indicates high expression in osteoblasts forming bone, discrete alkaline phosphatase positive bone marrow cells, and chondrocytes. Specific binding of 125I-labeled insulin-like growth factors to CTGF-L was demonstrated by ligand Western blotting and cross-linking experiments. Recombinant human CTGF-L promotes the adhesion of osteoblast cells and inhibits the binding of fibrinogen to integrin receptors. In addition, recombinant human CTGF-L inhibits osteocalcin production in rat osteoblast-like Ros 17/2.8 cells. Taken together, these results suggest that CTGF-L may play an important role in modulating bone turnover. PMID:10358067

  2. Thrombin induced connective tissue growth factor expression in rat vascular smooth muscle cells via the PAR-1/JNK/AP-1 pathway

    PubMed Central

    Ko, Wen-chin; Chen, Bing-chang; Hsu, Ming-jen; Tsai, Chia-ti; Hong, Chuang-ye; Lin, Chien-huang

    2012-01-01

    Aim: To investigate the signaling pathways involved in thrombin-induced connective tissue growth factor (CTGF) expression in rat vascular smooth muscle cells (VSMCs). Methods: Experiments were preformed on primary rat aortic smooth muscle cells (RASMCs) and a rat VSMC line (A10). CTGF protein levels were measured using Western blotting. Luciferase reporter genes and dominant negative mutants (DNs) were used to investigate the signaling pathways mediating the induction of CTGF expression by thrombin. Results: Thrombin (0.3–3.0 U/mL) caused a concentration- and time-dependent increase in CTGF expression in both RASMCs and A10 cells. Pretreating A10 cells with the protease-activated receptor 1 (PAR-1) antagonist SCH79797 (0.1 ?mol/L) significantly blocked thrombin-induced CTGF expression, while the PAR-4 antagonist tcY-NH2 (30 ?mol/L) had no effect. The PAR-1 agonist SFLLRN-NH2 (300 ?mol/L) induced CTGF expression, while the PAR-4 agonist GYPGQV-NH2 (300 ?mol/L) had no effect. Thrombin (1 U/mL) caused time-dependent phosphorylation of c-Jun N-terminal kinase (JNK). Pretreating with the JNK inhibitor SP600125 (3–30 ?mol/L) or transfection with DNs of JNK1/2 significantly attenuated thrombin-induced CTGF expression. Thrombin (0.3–3.0 U/mL) increased activator protein-1 (AP-1)-luciferase activity, which was inhibited by the JNK inhibitor SP600125. The AP-1 inhibitor curcumin (1–10 ?mol/L) concentration-dependently attenuated thrombin-induced CTGF expression. Conclusion: Thrombin acts on PAR-1 to activate the JNK signaling pathway, which in turn initiates AP-1 activation and ultimately induces CTGF expression in VSMCs. PMID:22212430

  3. Differential immunoglobulin class-mediated responses to components of the U1 small nuclear ribonucleoprotein in Systemic Lupus Erythematosus and Mixed Connective Tissue Disease

    PubMed Central

    Mesa, Annia; Somarelli, Jason A.; Wu, Wensong; Martinez, Laisel; Blom, Melissa B.; Greidinger, Eric L.; Herrera, Rene J.

    2013-01-01

    Summary Objective To determine whether patients with Systemic Lupus Erythematosus (SLE) and Mixed Connective Tissue Disease (MCTD) possess differential IgM-and IgG-specific reactivity against peptides from the U1 small nuclear ribonucleoprotein particle (U1 snRNP). Methods The IgM- and IgG-mediated responses against 15 peptides from subunits of the U1 snRNP were assessed by indirect ELISAs in sera from patients with SLE and MCTD and healthy individuals (n = 81, 41 and 31, respectively). Additionally, 42 laboratory tests and 40 clinical symptoms were evaluated to uncover potential differences. Binomial logistic regression analyses (BLR) were performed to construct models to support the independent nature of SLE and MCTD. Receiver Operating Characteristic (ROC) curves corroborated the classification power of the models. Results We analyzed IgM and IgG anti-U1 snRNP titers to classify SLE and MCTD patients. IgG anti-U1 snRNP reactivity segregates SLE and MCTD from non-disease controls with an accuracy of 94.1% while IgM-specific anti-U1 snRNP responses distinguish SLE from MCTD patients with an accuracy of 71.3%. Comparison of the IgG and IgM anti-U1 snRNP approach with clinical tests used for diagnosing SLE and MCTD revealed that our method is the best classification tool of those analyzed (p ? 0.0001). Conclusions Our IgM anti-U1 snRNP system along with lab tests and symptoms provide additional molecular and clinical evidence to support the hypothesis that SLE and MCTD may be distinct syndromes. PMID:24158973

  4. The level of connective tissue growth factor in sera of patients with hepatitis B virus strongly correlates with stage of hepatic fibrosis.

    PubMed

    Guo-Qiu, Wu; Nai-Feng, Liu; Xiao-Bo, Van; Linxian, Li; Chen, Zhang; Lixia, Gou; Zhao, Liu

    2010-02-01

    Connective tissue growth factor (CTGF) plays a crucial role in the formation and development of hepatic fibrosis. The aim of this study was to establish a method for CTGF determination in order to investigate the level of CTGF in the sera of patients with hepatitis B virus, and to assess the correlation between CTGF concentration and stage of hepatic fibrosis. A CTGF C-terminal region gene was obtained by RT-PCR of human mesangial kidney cells and inserted into pET-32a((+)) vector. Recombinant protein was obtained by expression and purification of the fused protein. Polyclonal and monoclonal antibodies were prepared to establish a sandwich ELISA method. CTGF levels in 18 healthy serum samples and 83 serum samples from patients with hepatitis B virus were assessed. A simple, sensitive, and noninvasive method of determining CTGF levels was successfully established. CTGF levels in the sera of patients with hepatitis B were significantly increased compared controls (p < 0.001). There was a strong correlation between CTGF concentration and fibrotic stage (r = 0.8906, p < 0.005). No significant association was found between CTGF level and the grade of hepatic inflammation (p > 0.05). The area under the receiver operating characteristic (ROC) curves of CTGF was 0.681 for identification of significant fibrosis, and 0.759 for the diagnosis of middle- and late-stage fibrosis. Accuracy of CTGF assessment was independent of age, renal function, liver function, platelet count, or other biochemical markers of liver fibrosis (all p > 0.05). No significant correlation was found between CTGF and several humoral factors associated with liver fibrosis (all p > 0.05). The levels of CTGF in the sera of patients with hepatitis B were strongly associated with the stages of hepatic fibrosis, and CTGF may become a useful diagnostic aid in assessing hepatic fibrosis. PMID:20121404

  5. MicroRNA?133b inhibits connective tissue growth factor in colorectal cancer and correlates with the clinical stage of the disease.

    PubMed

    Guo, Yihang; Li, Xiaorong; Lin, Changwei; Zhang, Yi; Hu, Gui; Zhou, Jianyu; Du, Juan; Gao, Kai; Gan, Yi; Deng, Hao

    2015-04-01

    Accumulating evidence indicates that dysregulation of microRNA?133b (miR?133b) is an important step in the development of certain types of human cancer and contributes to tumorigenesis. Altered expression of miR?133b has been reported in colon carcinoma, but its association with clinical stage in colorectal cancer (CRC) has remained elusive. Connective tissue growth factor (CTGF), a potentially promising candidate gene for interaction with miR?133b, was screened using microarray analysis. The expression of miR?133b and CTGF was evaluated using reverse transcription?quantitative polymerase chain reaction and western blot analysis. The regulatory effects of miR?133b on CTGF were evaluated using a dual?luciferase reporter assay. CTGF was identified as a functional target of miR?133b. The results demonstrated low expression of miR?133b in CRC specimens with poor cell differentiation (P=0.011), lymph node metastasis (P=0.037) and advanced clinical stages (stage III or IV vs. I or II; P=0.036). Furthermore, there was a significant association between a high level of expression of CTGF mRNA and an advanced clinical stage (stage III or IV vs. I or II; P=0.015) and lymph node metastasis (P=0.034). CTGF expression was negatively regulated by miR?133b in the human colorectum, suggesting that miR?133b and CTGF may be candidate therapeutic targets in colorectal cancer. PMID:25501363

  6. Rho-dependent inhibition of the induction of connective tissue growth factor (CTGF) by HMG CoA reductase inhibitors (statins)

    PubMed Central

    Eberlein, Michael; Heusinger-Ribeiro, Juliane; Goppelt-Struebe, Margarete

    2001-01-01

    It was supposed that inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG CoA) reductase (statins) might inhibit the expression of the fibrosis-related factor CTGF (connective tissue growth factor) by interfering with the isoprenylation of Rho proteins. The human renal fibroblast cell line TK173 was used as an in vitro model system to study the statin-mediated modulation of the structure of the actin cytoskeleton and of the expression of CTGF mRNA. Incubation of the cells with simvastatin or lovastatin time-dependently and reversibly changed cell morphology and the actin cytoskeleton with maximal effects observed after about 18?h. Within the same time period, statins reduced the basal expression of CTGF and interfered with CTGF induction by lysophosphatidic acid (LPA) or transforming growth factor beta. Simvastatin and lovastatin proved to be much more potent than pravastatin (IC50 1–3??M compared to 500??M). The inhibition of CTGF expression was prevented when the cells were incubated with mevalonate or geranylgeranylpyrophosphate (GGPP) but not by farnesylpyrophosphate (FPP). Specific inhibition of geranylgeranyltransferase-I by GTI-286 inhibited LPA-mediated CTGF expression whereas an inhibitor of farnesyltransferases FTI-276 was ineffective. Simvastatin reduced the binding of the small GTPase RhoA to cellular membranes. The effect was prevented by mevalonate and GGPP, but not FPP. These data are in agreement with the hypothesis that interference of statins with the expression of CTGF mRNA is primarily due to interference with the isoprenylation of RhoA, in line with previous studies, which have shown that RhoA is an essential mediator of CTGF induction. The direct interference of statins with the synthesis of CTGF, a protein functionally related to the development of fibrosis, may thus be a novel mechanism underlying the beneficial effects of statins observed in renal diseases. PMID:11487529

  7. A novel integrin ?5?1 binding domain in module 4 of connective tissue growth factor (CCN2/CTGF) promotes adhesion and migration of activated pancreatic stellate cells

    PubMed Central

    Gao, R; Brigstock, D R

    2006-01-01

    Background Connective tissue growth factor (CCN2) is upregulated in pancreatic fibrosis and desmoplastic pancreatic tumours. CCN2 interacts with integrin ?5?1 on pancreatic stellate cells (PSC) in which it stimulates fibrogenesis, adhesion, migration, and proliferation. Aim To determine the structural domain(s) in CCN2 that interact with integrin ?5?1 to regulation PSC functions. Methods Primary activated rat PSC were tested for their adherence to isoforms of CCN2 comprising modules 1–4 (CCN21–4), modules 3–4 (CCN23–4), module 3 alone (CCN23), or module 4 alone (CCN24). Adhesion studies were performed in the presence of EDTA, divalent cations, anti?integrin ?5?1 antibodies, CCN2 synthetic peptides, or heparin, or after pretreatment of the cells with heparinase, chondroitinase, or sodium chlorate. CCN2 integrin ?5?1 binding was analysed in cell free systems. The ability of CCN21–4, CCN23–4, or CCN24 to stimulate PSC migration was evaluated in the presence of anti?integrin ?5?1 or heparin. Results PSC adhesion was stimulated by CCN21–4, CCN23–4, or CCN24 and supported by Mg2+ but not Ca2+. CCN24 supported PSC adhesion or migration were blocked by anti?integrin ?5?1 antibodies or by treatment of cells with heparinase or sodium chlorate. A direct interaction between CCN24 and integrin ?5?1 was demonstrated in cell free assays. The sequence GVCTDGR in module 4 mediated the binding between CCN24 and integrin ?5?1 as well as CCN24 mediated PSC adhesion and migration. Conclusions A GVCTDGR sequence in module 4 of CCN2 is a novel integrin ?5?1 binding site that is essential for CCN2 stimulated functions in PSC and which represents a new therapeutic target in PSC mediated fibrogenesis. PMID:16361307

  8. Extraintestinal manifestations of autoimmune pancreatitis.

    PubMed

    Milosavljevic, Tomica; Kostic-Milosavljevic, Mirjana; Jovanovic, Ivan; Krstic, Miodrag

    2012-01-01

    The term autoimmune pancreatitis (AIP) was first used in Japan in 1995 to describe a newly recognized form of chronic pancreatitis, after the description of Yoshida and colleagues. But Sarles in 1961, first described a form of idiopathic chronic inflammatory sclerosis of the pancreas, suspected to be due to an autoimmune process. AIP has become a widely accepted term because clinical, serologic, histologic, and immunohistochemical findings suggest an autoimmune mechanism. Most affected patients have hypergammaglobulinemia and increased serum levels of IgG, particularly IgG4. Recently published International Consensus Diagnostic Criteria for Autoimmune Pancreatitis include Guidelines of the International Association of Pancreatology, classifying AIP into types 1 and 2, using five cardinal features of AIP, namely imaging of pancreatic parenchyma and duct, serology, other organ involvement, pancreatic histology, and an optional criterion of response to steroid therapy. Extrapancreatic presentations can include sclerosing cholangitis, retroperitoneal fibrosis, sclerosing sialadenitis (Küttner tumor), lymphadenopathy, nephritis, and interstitial pneumonia. Increased IgG4+ plasma cell infiltrate has been reported in sclerosing lesions from other organ sites, including inflammatory pseudotumors of the liver, breast, mediastinum, orbit, and aorta, and it has been observed with hypophysitis and IgG4-associated prostatitis. Abundant IgG4+ plasma cells were also confirmed in Riedel thyroiditis, sclerosing mesenteritis, and inflammatory pseudotumor of the orbit and stomach. Extrapancreatic lesions could be synchronously or metachronously diagnosed with AIP, sharing the same pathological conditions, showing also a favorable result to corticosteroid therapy and distinct differentiation between IgG4-related diseases from the inherent lesions of the corresponding organs. PMID:22722443

  9. Infections and Autoimmunity: A Panorama

    Microsoft Academic Search

    V. Pordeus; M. Szyper-Kravitz; R. A. Levy; N. M. Vaz; Y. Shoenfeld

    2008-01-01

    For more than 2,000 years, it was thought that malignant spirits caused diseases. By the end of nineteenth century, these\\u000a beliefs were displaced by more modern concepts of disease, namely, the formulation of the “germ theory,” which asserted that\\u000a bacteria or other microorganisms caused disease. With the emergence of chronic degenerative and of autoimmune diseases in\\u000a the last century, the causative

  10. Experimental Autoimmune Encephalomyelitis in Primates

    Microsoft Academic Search

    Paul A. Smith; Sandra Amor; Bert A. ’tHart

    Due to their genetic and immunological proximity to humans, the common marmoset, Callithrix jacchus, provides an important bridge between rodent-based research and the human disease. Experimental autoimmune encephalomyelitis\\u000a (EAE) induced in the outbred common marmoset provides a highly reproducible model of multiple sclerosis (MS) phenotypically\\u000a characterised by neurological deficits, inflammatory lesions of the cerebral white matter and spinal cord, primary

  11. Pancreatic Tuberculosis or Autoimmune Pancreatitis

    PubMed Central

    Saif, Muhammad Wasif

    2014-01-01

    Introduction. Isolated pancreatic and peripancreatic tuberculosis is a challenging diagnosis due to its rarity and variable presentation. Pancreatic tuberculosis can mimic pancreatic carcinoma. Similarly, autoimmune pancreatitis can appear as a focal lesion resembling pancreatic malignancy. Endoscopic ultrasound-guided fine needle aspiration provides an effective tool for differentiating between benign and malignant pancreatic lesions. The immune processes involved in immunoglobulin G4 related systemic diseases and tuberculosis appear to have some similarities. Case Report. We report a case of a 59-year-old Southeast Asian male who presented with fever, weight loss, and obstructive jaundice. CT scan revealed pancreatic mass and enlarged peripancreatic lymph nodes. Endoscopic ultrasound-guided fine needle aspiration confirmed the presence of mycobacterium tuberculosis. Patient also had high immunoglobulin G4 levels suggestive of autoimmune pancreatitis. He was started on antituberculosis medications and steroids. Clinically, he responded to treatment. Follow-up imaging showed findings suggestive of chronic pancreatitis. Discussion. Pancreatic tuberculosis and autoimmune pancreatitis can mimic pancreatic malignancy. Accurate diagnosis is imperative as unnecessary surgical intervention can be avoided. Endoscopic ultrasound-guided fine needle aspiration seems to be the diagnostic test of choice for pancreatic masses. Long-term follow-up is warranted in cases of chronic pancreatitis. PMID:24839445

  12. HYPERAUTOFLUORESCENT RING IN AUTOIMMUNE RETINOPATHY

    PubMed Central

    LIMA, LUIZ H.; GREENBERG, JONATHAN P.; GREENSTEIN, VIVIENNE C.; SMITH, R. THEODORE; SALLUM, JULIANA M. F.; THIRKILL, CHARLES; YANNUZZI, LAWRENCE A.; TSANG, STEPHEN H.

    2015-01-01

    Purpose To report the presence of a hyperautofluorescent ring and corresponding spectral-domain optical coherence tomography (SD-OCT) features seen in patients with autoimmune retinopathy. Methods All eyes were evaluated by funduscopic examination, full-fleld electroretinography, fundus autofluorescence, and SD-OCT. Further confirmation of the diagnosis was obtained with immunoblot and immunohistochemistry testing of the patient’s serum. Humphrey visual fields and microperimetry were also performed. Results Funduscopic examination showed atrophic retinal pigment epithelium (RPE) associated with retinal artery narrowing but without pigment deposits. The scotopic and photopic full-field electroretinograms were nondetectable in three patients and showed a cone–rod pattern of dysfunction in one patient. Fundus autofluorescence revealed a hyperautofluorescent ring in the parafoveal region, and the corresponding SD-OCT demonstrated loss of the photoreceptor inner segment–outer segment junction with thinning of the outer nuclear layer from the region of the hyperautofluorescent ring toward the retinal periphery. The retinal layers were generally intact within the hyperautofluorescent ring, although the inner segment–outer segment junction was disrupted, and the outer nuclear layer and photoreceptor outer segment layer were thinned. Conclusion This case series revealed the structure of the hyperautofluorescent ring in autoimmune retinopathy using SD-OCT. Fundus autofluorescence and SD-OCT may aid in the diagnosis of autoimmune retinopathy and may serve as a tool to monitor its progression. PMID:22218149

  13. The Autoimmune Model of Schizophrenia

    PubMed Central

    Adams, D. D.; Knight, J. G.; Ebringer, A.

    2012-01-01

    Schizophrenia is of mysterious causation. It is not infectious, not congenital, but shows familial aggregation, the Mendelian genetics indicating involvement of multiple codominant genes with incomplete penetrance. This is the pattern for autoimmune diseases, such as Graves' disease of the thyroid, where forbidden clones of B lymphocytes develop, and cause thyrotoxicosis by secreting autoantibodies that react with the thyroid gland's receptor for thyroid-stimulating hormone from the pituitary gland. In 1982, Knight postulated that autoantibodies affecting the function of neurons in the limbic region of the brain are a possible cause of schizophrenia. Today, this is even more probable, with genes predisposing to schizophrenia having being found to be immune response genes, one in the MHC and two for antibody light chain V genes. Immune response genes govern the immune repertoire, dictating the genetic risk of autoimmune diseases. The simplest test for an autoimmune basis of schizophrenia would be trial of immunosuppression with prednisone in acute cases. The urgent research need is to find the microbial trigger, as done by Ebringer for rheumatoid arthritis and for ankylosing spondylitis. This could lead to prophylaxis of schizophrenia by vaccination against the triggering microbe. PMID:23738211

  14. Linking iodine with autoimmune thyroiditis.

    PubMed Central

    Rose, N R; Rasooly, L; Saboori, A M; Burek, C L

    1999-01-01

    A great deal of circumstantial evidence has linked iodine with the rising incidence of autoimmune thyroiditis in the United States. In our investigations, we have shown directly that T cells from humans with chronic lymphocytic thyroiditis proliferate in the presence of iodinated but not in the presence of noniodinated human thyroglobulin. Moreover, the proliferative response is restored when the thyroglobulin is iodinated artificially in vitro. Using a panel of monoclonal antibodies, we found evidence that the presence of iodine induces a number of stereochemical changes in the conformation of the molecule, resulting in the loss of some antigenic determinants and the appearance of others. One prominent determinant was associated with the iodine-containing amino acid thyroxine. Both the number and position of the iodine substituents determine the precise specificity of this epitope. A new model for the study of the role of iodine in inducing thyroid autoimmunity has become available in the form of the nonobese diabetic (NOD)-H2(h4) mouse. This animal develops autoimmune thyroiditis spontaneously but in relatively low prevalence. However, if iodine is added to the drinking water, the prevalence and severity of the thyroid lesions increase markedly. The immune response is specific for thyroglobulin, both in terms of the antibody response and T-cell proliferation. In fact, the appearance of lesions can be predicted by the presence of thyroglobulin-specific IgG2b antibody. The disease, moreover, can be transferred adoptively, using spleen cells from iodine-fed donors treated in vitro with iodinated thyroglobulin. The effects of iodine feeding are greater in conventional animals compared with those maintained under specific pathogen-free conditions. Based on T-cell proliferation, it appears that the NOD-H2(h4) strain of mice has innately a greater response to murine thyroglobulin than do other mouse strains and that the proliferation is increased even more by feeding iodine. We suggest, therefore, that the presence of iodine increases the autoantigenic potency of thyroglobulin, a major pathogenic antigen in the induction of autoimmune thyroiditis. This animal model provides a unique opportunity for investigating in detail the mechanisms by which an environmental agent can trigger a pathogenic autoimmune response in a susceptible host. PMID:10502541

  15. The Diagnostic Challenges of Autoimmune Pancreatitis

    PubMed Central

    Papp, Kata; Angst, Eliane; Seidel, Stefan; Flury-Frei, Renata; Hetzer, Franc Heinrich

    2015-01-01

    Autoimmune pancreatitis is a rare but important differential diagnosis from pancreatic cancer. This autoimmune disease can mimic pancreatic cancer by its clinical symptoms, including weight loss and jaundice. Furthermore imaging findings may include a mass of the pancreas. Here we present the case of a 67-year-old male patient diagnosed with autoimmune pancreatitis but showing the well-known symptoms of pancreatic cancer. This emphasizes the difficulties of histological findings and the importance of the correct diagnostic process. PMID:25802499

  16. Genetics Home Reference: Autoimmune polyglandular syndrome, type 1

    MedlinePLUS

    ... PubMed Recent literature OMIM Genetic disorder catalog Conditions > Autoimmune polyglandular syndrome, type 1 On this page: Description ... names Glossary definitions Reviewed August 2007 What is autoimmune polyglandular syndrome, type 1? Autoimmune polyglandular syndrome, type ...

  17. Multiple Autoimmune Syndromes Associated with Psoriasis: A Rare Clinical Presentation

    PubMed Central

    Masood, Sadia; Sajid, Sara; Jafferani, Asif; Tabassum, Saadia; Ansar, Sobia

    2014-01-01

    Autoimmune diseases are known to have association with each other but it is very rare to see multiple autoimmune diseases in one patient. The combination of at least three autoimmune diseases in the same patient is referred to as multiple autoimmune syndrome. The case we are reporting features multiple autoimmune syndrome with five different conditions. The patient had type 1 diabetes mellitus, autoimmune hemolytic anemia, systemic lupus erythematosus, vitiligo, and psoriasis. Psoriasis has rarely been reported previously under the spectrum of autoimmune syndrome. Although the relationship of autoimmune conditions with each other has been explored in the past, this case adds yet another dimension to the unique evolution of autoimmune pathologies. The patient presented with a combination of five autoimmune diseases, which makes it consistent type three multiple autoimmune syndromes with the addition of psoriasis. The current case is unique in this aspect that the combination of these five autoimmune disorders has never been reported in the past. PMID:24715941

  18. Increased levels of anti-heat-shock protein 60 (anti-Hsp60) indicate endothelial dysfunction, atherosclerosis and cardiovascular diseases in patients with mixed connective tissue disease.

    PubMed

    Bodolay, Edit; Prohászka, Zoltan; Paragh, Gyorgy; Csip?, Istvan; Nagy, Gabor; Laczik, Renata; Demeter, Nora; Zöld, Eva; Nakken, Britt; Szegedi, Gyula; Szodoray, Peter

    2014-10-01

    Heat-shock protein 60 (Hsp60) has been shown to provoke inflammation, and anti-Hsp60 may facilitate the development of atherosclerosis. In this study, we have investigated 30 patients with mixed connective tissue disease (MCTD) and assessed anti-Hsp60 and their relationship to cardiovascular diseases (CVD). Out of 30 patients with MCTD, 15 had CVDs. Anti-Hsp60 antibody was determined by enzyme-linked immunosorbent assay. Since endothelial dysfunction and accelerated atherosclerosis are characteristic to MCTD, a wide array of MCTD-, endothelial dysfunction- and CVD-associated parameters was investigated: serum lipid levels, paraoxonase activity (PON1), rich nuclear ribonucleoprotein U1 (anti-U1RNP), anti-endothelial cell antibodies, anti-cardiolipin and anti-?2-glycoprotein I antibody isotypes (anti-CL and anti-?2GPI), endothelin-1 (ET-1) levels, also intima-media thickness (IMT), a quantitative indicator of atherosclerosis. In MCTD, anti-Hsp60 antibody levels were significantly higher than in healthy individuals (p < 0.02). MCTD patients with CVD had significantly higher levels of anti-Hsp60 compared to MCTD without CVD (p = 0.001). Patients with MCTD had significantly lower high-density lipoprotein cholesterol (p = 0.02) and PON activity (p < 0.001), and significantly increased systolic (p < 0.0002) and diastolic (p < 0.001) blood pressure compared to healthy individuals. Anti-U1RNP levels (p < 0.002) and IMT were higher in patients compared to controls (p = 0.002). The CVD-positive MCTD patients had increased anti-Hsp60 (p < 0.0013), anti-CL IgG (p = 0.0005), ET-1 serum concentration (p < 0.05) and IMT levels (p < 0.001) compared to MCTD patients without CVD. Anti-Hsp60 showed a strong correlation with anti-oxLDL (r = 0.36, p = 0.01) and serum ET-1 (r = 0.62, p < 0.001) and negative correlation with PON activity (r = -0.47, p = 0.01). Anti-Hsp60 indicates endothelial injury, CVD, and can function as a novel atherosclerotic risk factor, also a valuable diagnostic marker in patients with MCTD. PMID:24838263

  19. Light and scanning electron microscopic study on the lingual papillae and their connective tissue cores of the Cape hyrax Procavia capensis

    PubMed Central

    Yoshimura, Ken; Hama, Natsuki; Shindo, Junji; Kobayashi, Kan; Kageyama, Ikuo

    2008-01-01

    We examined the epithelial surface and connective tissue cores (CTCs) of each lingual papilla on the Paenungulata, Cape hyrax (Procavia capensis), by scanning electron microscopy and light microscopy. The tongue consisted of a lingual apex, lingual body and lingual root. Filiform, fungiform and foliate papillae were observed on the dorsal surface of the tongue; however, fungiform papillae were quite diminished on the lingual prominence. Moreover, no clearly distinguishable vallate papillae were found on the tongue. Instead of vallate papillae, numerous dome-like large fungiform papillae were arranged in a row just in front of the rather large foliate papillae. Foliate papillae were situated in the one-third postero-lateral margin of the lingual body. The epithelium of filiform papillae was covered by a keratinized layer with kerato-hyaline granules, whereas weak keratinization was observed on the interpapillary epithelium. The external surface of the filiform papillae was conical in shape. CTCs of the filiform papillae were seen as a hood-like core with a semicircular concavity in the anterior portion of each core. Large filiform papillae were distributed on the lingual prominence. The CTCs of large filiform papillae after exfoliation of their epithelium consisted of a concave primary core and were associated with several small protrusions. The surface of fungiform papillae was smooth and dome-like. After removal of the epithelium, CTCs appeared as a flower bud-like primary core and were associated with several protrusions that were arranged on the rim of the primary core. Several taste buds were found on the top of the dorsal part of the epithelium of both fungiform and large fungiform papillae. Well-developed foliate papillae were seen and numerous taste buds could be observed in the lateral wall of the epithelium in a slit-like groove. The morphological characteristics of the tongue of the Cape hyrax had similarities with other Paenungulata such as Sirenia. However, three-dimensional characteristics, especially CTCs of lingual papillae, exhibited multiple similarities with rodents, insectivores and artiodactyls. PMID:18713236

  20. Role of major histocompatibility complex class II in the development of autoimmune type 1 diabetes and thyroiditis in rats

    Microsoft Academic Search

    N Yokoi; S Hidaka; S Tanabe; M Ohya; M Ishima; Y Takagi; N Masui; S Seino

    2012-01-01

    Although the MHC class II ‘u’ haplotype is strongly associated with type 1 diabetes (T1D) in rats, the role of MHC class II in the development of tissue-specific autoimmune diseases including T1D and autoimmune thyroiditis remains unclear. To clarify this, we produced a congenic strain carrying MHC class II ‘a’ and ‘u’ haplotypes on the Komeda diabetes-prone (KDP) genetic background.

  1. ADAM17 at the interface between inflammation and autoimmunity.

    PubMed

    Lisi, Sabrina; D'Amore, Massimo; Sisto, Margherita

    2014-11-01

    The discovery of the disintegrin and metalloproteinase 17 (ADAM17), originally identified as tumor necrosis factor-a converting enzyme (TACE) for its ability as sheddase of TNF-? inspired scientists to attempt to elucidate the molecular mechanisms underlying ADAM17 implication in diseased conditions. In recent years, it has become evident that this protease can modify many non matrix substrates, such as cytokines (e.g. TNF-?), cytokine receptors (e.g. IL-6R and TNF-R), ligands of ErbB (e.g. TGF-? and amphiregulin) and adhesion proteins (e.g. Lselectin and ICAM-1). Several recent studies have described experimental model system to better understand the role of specific signaling molecules, the interplay of different signals and tissue interactions in regulating ADAM17-dependent cleavage of most relevant substrates in inflammatory diseases. The central question is whether ADAM17 can influence the outcome of inflammation and if so, how it performs this regulation in autoimmunity, since inflammatory autoimmune diseases are often characterized by deregulated metalloproteinase activities. This review will explore the latest research on the influence of ADAM17 on the progression of inflammatory processes linked to autoimmunity and its role as modulator of inflammation. PMID:25171914

  2. Lectins, agglutinins, and their roles in autoimmune reactivities.

    PubMed

    Vojdani, Aristo

    2015-01-01

    Lectins are carbohydrate-binding proteins present throughout nature that act as agglutinins. Approximately 30% of our food contains lectins, some of which may be resistant enough to digestion to enter the circulation. Because of their binding properties, lectins can cause nutrient deficiencies, disrupt digestion, and cause severe intestinal damage when consumed in excess by an individual with dysfunctional enzymes. These effects are followed by disruption of intestinal barrier integrity, which is the gateway to various autoimmunities. Shared amino acid motifs between dietary lectins, exogenous peptides, and various body tissues may lead to cross-reactivity, resulting in the production of antibodies against lectin and bacterial antigens, followed by autoimmunity. The detection of immunoglobulin G (IgG) or immunoglobulin A (IgA) antibodies against specific lectins may serve as a guide for the elimination of these lectins from the diet. It is proposed that this process can reduce the peripheral antigenic stimulus and, thereby, result in a diminution of disease symptoms in some-but not all-patients with autoimmune disorders. PMID:25599185

  3. Thymoma with Autoimmune Hemolytic Anemia

    PubMed Central

    Suzuki, Kensuke; Inomata, Minehiko; Shiraishi, Shiori; Hayashi, Ryuji; Tobe, Kazuyuki

    2014-01-01

    A 38-year-old Japanese male was referred to our hospital with abnormal chest X-ray results and severe Coombs-positive hemolytic anemia. He was diagnosed with a stage IV, WHO type A thymoma and was treated with oral prednisolone (1 mg/kg/day) and subsequent chemotherapy. After chemotherapy, the patient underwent surgical resection of the thymoma. Hemolysis rapidly disappeared and did not return after the discontinuation of oral corticosteroids. Corticosteroid therapy may be preferable to chemotherapy or thymoma surgical resection in the management of autoimmune hemolytic anemia with thymoma. PMID:25722666

  4. Good, bad and beautiful—the role of dendritic cells in autoimmunity

    Microsoft Academic Search

    Steffen Jung

    2004-01-01

    Autoimmunity results from a deficiency in tolerance establishment, i.e. a failure of the organism to eliminate or functionally neutralize auto-reactive lymphocytes. Dendritic cells (DC) are specialized migratory antigen presenting cells (APC), found as sentinels in peripheral tissues and lymphoid organs that allow the organism to mount rapid and efficient protective immune responses against pathogenic invaders. However, the antigenic spectrum presented

  5. Recognition of self and altered self by T cells in autoimmunity and allergy

    PubMed Central

    Yin, Lei; Dai, Shaodong; Clayton, Gina; Gao, Wei; Wang, Yang; Kappler, John; Marrack, Philippa

    2014-01-01

    T cell recognition of foreign peptide antigen and tolerance to self peptides is key to the proper function of the immune system. Usually, in the thymus T cells that recognize self MHC + self peptides are deleted and those with the potential to recognize self MHC + foreign peptides are selected to mature. However there are exceptions to these rules. Autoimmunity and allergy are two of the most common immune diseases that can be related to recognition of self. Many genes work together to lead to autoimmunity. Of those, particular MHC alleles are the most strongly associated, reflecting the key importance of MHC presentation of self peptides in autoimmunity. T cells specific for combinations of self MHC and self peptides may escape thymus deletion, and thus be able to drive autoimmunity, for several reasons: the relevant self peptide may be presented at low abundance in the thymus but at high level in particular peripheral tissues; the relevant self peptide may bind to MHC in an unusual register, not present in the thymus but apparent elsewhere; finally the relevant self peptide may be post translationally modified in a tissue specific fashion. In some types of allergy, the peptide + MHC combination may also be fully derived from self. However the combination in question may be modified by the presence of other ligands, such as small drug molecules or metal ions. Thus these types of allergies may act like the post translationally modified peptides involved some types of autoimmunity. PMID:23307779

  6. Invited Review Autoimmunity in Chagas heart disease

    E-print Network

    Engman, David M.

    Invited Review Autoimmunity in Chagas heart disease J.S. Leon, D.M. Engman* Northwestern University of Chagas heart disease is controversial. In this paper, we address the following questions regarding the genesis of autoimmunity in Chagas heart disease: (i) What mechanism(s) are potentially responsible

  7. Vectors for the treatment of autoimmune disease

    Microsoft Academic Search

    D J Gould; P Favorov

    2003-01-01

    Gene therapy has been applied in a variety of experimental models of autoimmunity with some success. In this article, we outline recent developments in gene therapy vectors, discuss advantages and disadvantages of each, and highlight their recent applications in autoimmune models. We also consider progress in vector targeting and components for regulating transgene expression, which will both improve gene therapy

  8. Macrophage Activation Syndrome in Autoimmune Disease

    Microsoft Academic Search

    Sean Deane; Carlo Selmi; Suzanne S. Teuber; M. Eric Gershwin

    2010-01-01

    Macrophage activation syndrome (MAS) is a phenomenon characterized by cytopenia, organ dysfunction, and coagulopathy associated with an inappropriate activation of macrophages. Current diagnostic criteria are imprecise, but the syndrome is now recognized as a form of hemophagocytic lymphohistiocytosis that is characteristically associated with autoimmune diatheses. The diagnosis of incipient MAS in patients with autoimmune disease requires a high index of

  9. Helicobacter pylori and skin autoimmune diseases

    PubMed Central

    Magen, Eli; Delgado, Jorge-Shmuel

    2014-01-01

    Autoimmune skin diseases are characterized by dysregulation of the immune system resulting in a loss of tolerance to skin self-antigen(s). The prolonged interaction between the bacterium and host immune mechanisms makes Helicobacter pylori (H. pylori) a plausible infectious agent for triggering autoimmunity. Epidemiological and experimental data now point to a strong relation of H. pylori infection on the development of many extragastric diseases, including several allergic and autoimmune diseases. H. pylori antigens activate cross-reactive T cells and induce autoantibodies production. Microbial heat shock proteins (HSP) play an important role of in the pathogenesis of autoimmune diseases because of the high level of sequence homology with human HSP. Eradication of H. pylori infection has been shown to be effective in some patients with chronic autoimmune urticaria, psoriasis, alopecia areata and Schoenlein-Henoch purpura. There is conflicting and controversial data regarding the association of H. pylori infection with Behçet’s disease, scleroderma and autoimmune bullous diseases. No data are available evaluating the association of H. pylori infection with other skin autoimmune diseases, such as vitiligo, cutaneous lupus erythematosus and dermatomyositis. The epidemiological and experimental evidence for a possible role of H. pylori infection in skin autoimmune diseases are the subject of this review. PMID:24587626

  10. Diagnosis and classification of autoimmune gastritis.

    PubMed

    Toh, Ban-Hock

    2014-01-01

    Autoimmune gastritis is a silent and highly prevalent disease that only becomes clinically manifested with progression to corpus atrophy and development of iron deficient or B12-deficient (pernicious) anaemia. Autoimmune gastritis is associated with autoimmune thyroiditis and type 1 diabetes mellitus. Corpus atrophy may be complicated by gastric carcinoids and gastric cancer. Laboratory diagnosis of autoimmune gastritis rests on serum biomarkers of antibody to parietal cell H/K ATPase and intrinsic factor and corpus atrophy on serum biomarkers of gastrin and pepsinogen levels. Subjects with asymptomatic parietal cell antibody should be regularly assessed for serum biomarkers for progression to corpus atrophy, development of iron and B12 deficiency anaemia and for associated autoimmune thyroiditis and type 1 diabetes mellitus. PMID:24424193

  11. Polyglandular autoimmune syndrome disguised as mental illness.

    PubMed

    Wei, Randy; Chang, Allen; Rockoff, Aaron

    2013-01-01

    Our case acts to highlight the numerous presentations of polyglandular autoimmune syndromes. A 62-year-old Taiwanese woman with a history of schizophrenia presented to our emergency department with a brain tumour causing her headaches. She was admitted due to severe anaemia, and after further investigation, the patient was discovered to have pernicious anaemia and autoimmune thyroiditis-consistent with the diagnosis of polyglandular autoimmune syndrome IIIb. Her underlying primary psychiatric diagnosis was then questioned. The diagnosis of her endocrinopathies were likely delayed for many years due to the psychiatric disorder which may have been due to her long-standing autoimmune hypothyroidism and/or vitamin B12 deficiency. Initial treatment brought about major behavioural improvement, and encourages physicians to investigate secondary causes of psychosis and other coexisting autoimmune diseases when a patient presents with one endocrinopathy. PMID:23632176

  12. Environmental estrogen bisphenol A and autoimmunity.

    PubMed

    Jochmanová, I; Lazúrová, Z; Rudnay, M; Ba?ová, I; Mareková, M; Lazúrová, I

    2015-04-01

    Over the past few years, there has been evidence of the increasing prevalence of autoimmune diseases. Autoimmune diseases consist of many complex disorders of unknown etiology resulting in immune responses to self-antigens. The immune system, and its function, is under complex and integrated control and its disruption can be triggered by multiple factors. Autoimmunity development is influenced by multiple factors and is thought to be a result of interactions between genetic and environmental factors. Here, we review the role of a specific environmental factor, bisphenol A (BPA), in the pathogenesis of autoimmune diseases. BPA belongs to the group of environmental estrogens that have been identified as risk factors involved in the development of autoimmune diseases. PMID:25801882

  13. Autoimmune hepatitis. Part A: pathogenesis.

    PubMed

    Czaja, Albert J

    2007-10-01

    Autoimmune hepatitis is a consequence of a triggering antigen and genetic factors that favor the presentation of autoantigens, polymorphisms that affect immunocyte activation and durability, cytokine alterations that promote proliferation of liver-infiltrating cytotoxic T cells, and perturbations in the number and function of immune-regulatory cell populations, including T regulatory cells and natural killer T cells. The triggering epitope is probably a short sequence peptide that is common in multiple infectious or toxic agents. Homologies between this epitope and self-antigens (molecular mimicry) may stimulate humoral and cellular responses that are cross-reactive. Sensitized immunocytes extend and perpetuate the inflammation through imprecise targeting of self-antigens that resemble foreign antigens (promiscuous behavior). The occurrence and clinical phenotype of the disease may relate to genetic susceptibility factors that favor protracted exposure to indigenous etiological agents, and these genetic factors can vary in different geographical regions and ethnic groups. The clinical phenotype within a population can be modified further by genetic polymorphisms that are not disease specific and that affect immunocyte activation, differentiation, proliferation and programmed death (apoptosis). Autoimmune hepatitis is a model of autoreactivity that reflects multiple disturbances in the counter-regulatory mechanisms essential for immune homeostasis. PMID:19072440

  14. The autoimmune concept of atherosclerosis

    PubMed Central

    Grundtman, Cecilia; Wick, Georg

    2011-01-01

    Purpose of review This review summarizes the recent data on the ‘Autoimmune Concept of Atherosclerosis’, according to which the first stage of this disease is due to an autoimmune reaction against arterial endothelial cells expressing heat shock protein 60 (HSP60) and adhesion molecules when stressed by classical atherosclerosis risk factors. Special emphasis is put on oxidized low-density lipoproteins as early endothelial stressors. Recent findings Plasma cholesterol and LDL levels considered ‘normal’ by the medical community are possibly too high from an evolutionary viewpoint. The proinflammatory milieu at sites of early atherosclerotic lesions could be conducive to oxidation of LDL in situ. LDL oxidation can also take place at nonvascular sites or in the circulation under general proinflammatory conditions explaining its proatherosclerotic role in ‘normocholesterolemic’ individuals. Summary We hypothesize that the plasma cholesterol and LDL levels currently considered normal are evolutionarily too high. Cholesterol and/or oxidized low-density lipoprotein, even as a mild HSP60-inducing endothelial stressor, function as a ubiquitous risk factor. If this hypothesis is true, most members of developed societies might be at risk to develop atherosclerotic plaques at anti-HSP60-immunity-triggered intimal inflammatory foci, irrespective of the primary risk-factor(s). PMID:21881502

  15. Cardiovascular Involvement in Autoimmune Diseases

    PubMed Central

    Amaya-Amaya, Jenny

    2014-01-01

    Autoimmune diseases (AD) represent a broad spectrum of chronic conditions that may afflict specific target organs or multiple systems with a significant burden on quality of life. These conditions have common mechanisms including genetic and epigenetics factors, gender disparity, environmental triggers, pathophysiological abnormalities, and certain subphenotypes. Atherosclerosis (AT) was once considered to be a degenerative disease that was an inevitable consequence of aging. However, research in the last three decades has shown that AT is not degenerative or inevitable. It is an autoimmune-inflammatory disease associated with infectious and inflammatory factors characterized by lipoprotein metabolism alteration that leads to immune system activation with the consequent proliferation of smooth muscle cells, narrowing arteries, and atheroma formation. Both humoral and cellular immune mechanisms have been proposed to participate in the onset and progression of AT. Several risk factors, known as classic risk factors, have been described. Interestingly, the excessive cardiovascular events observed in patients with ADs are not fully explained by these factors. Several novel risk factors contribute to the development of premature vascular damage. In this review, we discuss our current understanding of how traditional and nontraditional risk factors contribute to pathogenesis of CVD in AD. PMID:25177690

  16. IP-10 in autoimmune thyroiditis.

    PubMed

    Ruffilli, I; Ferrari, S M; Colaci, M; Ferri, C; Fallahi, P; Antonelli, A

    2014-08-01

    The interferon-?-inducible protein 10 (IP-10) was initially identified as a chemokine that is induced by interferon (IFN)-?. IP-10 exerts its function through binding to chemokine (C-X-C motif) receptor 3 (CXCR3). IP-10 and its receptor, CXCR3, appear to contribute to the pathogenesis of many autoimmune diseases, organ specific (such as type 1 diabetes, Graves' disease and ophthalmopathy), or systemic (such as systemic lupus erythematosus, mixed cryoglobulinemia, Sjogren syndrome, or systemic sclerosis). The secretion of IP-10 by (CD)4+, CD8+, and natural killer is dependent on IFN-?. Under the influence of IFN-?, IP-10 is secreted by thyrocytes. Determination of high level of IP-10 in peripheral fluids is therefore a marker of a T helper 1 orientated immune response. High levels of circulating IP-10, have been shown in patients with autoimmune thyroiditis (AT). Among patients with AT, IP-10 levels were significantly higher in those with a hypoechoic ultrasonographic pattern, which is a sign of a more severe lympho-monocytic infiltration, and in those with hypothyroidism. For these reasons, it has been postulated that IP-10 could be a marker of a stronger and more aggressive inflammatory response in the thyroid, subsequently leading to thyroid destruction and hypothyroidism. Further studies are needed to investigate whether IP-10 is a novel therapeutic target in AT. PMID:24977661

  17. Susceptibility Genes in Thyroid Autoimmunity

    PubMed Central

    Ban, Yoshiyuki; Tomer, Yaron

    2005-01-01

    The autoimmune thyroid diseases (AITD) are complex diseases which are caused by an interaction between susceptibility genes and environmental triggers. Genetic susceptibility in combination with external factors (e.g. dietary iodine) is believed to initiate the autoimmune response to thyroid antigens. Abundant epidemiological data, including family and twin studies, point to a strong genetic influence on the development of AITD. Various techniques have been employed to identify the genes contributing to the etiology of AITD, including candidate gene analysis and whole genome screening. These studies have enabled the identification of several loci (genetic regions) that are linked with AITD, and in some of these loci, putative AITD susceptibility genes have been identified. Some of these genes/loci are unique to Graves' disease (GD) and Hashimoto's thyroiditis (HT) and some are common to both the diseases, indicating that there is a shared genetic susceptibility to GD and HT. The putative GD and HT susceptibility genes include both immune modifying genes (e.g. HLA, CTLA-4) and thyroid specific genes (e.g. TSHR, Tg). Most likely, these loci interact and their interactions may influence disease phenotype and severity. PMID:15712599

  18. Hygiene hypothesis and autoimmune diseases.

    PubMed

    Rook, Graham A W

    2012-02-01

    Throughout the twentieth century, there were striking increases in the incidences of many chronic inflammatory disorders in the rich developed countries. These included autoimmune disorders such as Type 1 diabetes and multiple sclerosis. Although genetics and specific triggering mechanisms such as molecular mimicry and viruses are likely to be involved, the increases have been so rapid that any explanation that omits environmental change is incomplete. This chapter suggests that a series of environmental factors, most of them microbial, have led to a decrease in the efficiency of our immunoregulatory mechanisms because we are in a state of evolved dependence on organisms with which we co-evolved (and that had to be tolerated) as inducers of immunoregulatory circuits. These organisms ("Old Friends") are depleted from the modern urban environment. Rather than considering fetal programming by maternal microbial exposures, neonatal programming, the hygiene hypothesis, gut microbiota, and diet as separate and competing hypotheses, I attempt here to integrate these ideas under a single umbrella concept that can provide the missing immunoregulatory environmental factor that is needed to explain the recent increases in autoimmune disease. PMID:22090147

  19. [Pneumococcal septicemia in functional asplenia: first manifestation of systemic autoimmune disease?].

    PubMed

    Germing, U; Fischer, R; Bauser, U; Schneider, M; Aul, C

    1999-02-01

    A 35 year old female was admitted into the hospital because of rapid onset fever and chills. Streptococcus pneumoniae could be isolated from blood as the responsible pathogen for septicemia. Necroses of fingers and feet occurred. The clinical signs of an overwhelming post-splenectomy infection (OPSI) were evident. High-dose penicillin was administered and the patient recovered. Howell-Jolly-bodies were seen in peripheral blood smears. A spleen within normal size could be demonstrated in CT and sonography. Angiologic findings showed intact splenic arteries and a normal vein, whereas the small splenic vessels were rare. MRT of the spleen using Endorem (Fe), showed only a minimal uptake of the RES. In a scintigram of spleen and liver using 320 MBq Tc-99m nanokoll, the spleen was not visible. Thus, functional asplenia was demonstrated by Howell-Jolly-Bodies and by image methods. An increased antinuclear antibody level and a Sm-antibody lead to the diagnosis of undifferentiated connective tissue disease. As far as we know this is the first case that functional asplenia was the first symptom of a systemic autoimmune disease. PMID:10198987

  20. Characteristics of filiform, fungiform and vallate papillae and surface of interface epithelium-connective tissue of the maned sloth tongue mucosa (Bradypus torquatus, Iliger, 1811): Light and Scanning Electron Microscopy Study.

    PubMed

    Benetti, E J; Pícoli, L C; Guimarăes, J P; Motoyama, A A; Miglino, M A; Watanabe, L-S

    2009-02-01

    The study of lingual surfaces and the surface of interface epithelium-connective tissue of the tongue of Bradypus torquatus was performed by employing the light and scanning electron microscopy (SEM) techniques. The results revealed that the rostral part of the tongue presents a round apex and covered by filiform and fungiform lingual papillae and a ventral smooth surface. It was observed that the epithelial layer of the dorsal surface possesses the basal, spinosum, granular and cornified epithelial cells. The lamina propria is characterized by a dense connective tissue forming the long, short and round papillae. Numerous typical filiform papillae are located especially in the rostral part intermingled for few fungiform papillae, which were revealed in three-dimensional SEM images. Usually, the fungiform papillae are located in the border of rostral apex of the tongue exhibiting the rounded form. They are covered by keratinized epithelial cells. In the fungiform papillae, several taste pores were observed on the surface. The vallate papillae presented numerous taste buds in the wall of epithelial cells, being that the major number of taste buds is located on the superior half of vallate papilla. The taste pores are surrounded by several laminae of keratinized epithelial cells. The samples treated with NaOH solution and examined by SEM revealed, after removal of the epithelial layer, the dense connective core in original disposition, presenting different sizes and shapes. The specimens stained with Picrosirius and examined by polarized light microscopy revealed the connective tissue, indicating the collagen fibres type I and type III. PMID:19143682

  1. Autoimmunity in Chagas Disease Cardiopathy: Biological Relevance of a Cardiac Myosin-Specific Epitope Crossreactive to an Immunodominant Trypanosoma cruzi Antigen

    Microsoft Academic Search

    Edecio Cunha-Neto; Marcia Duranti; Arthur Gruber; Bianca Zingales; Iara de Messias; Noedir Stolf; Giovanni Bellotti; Manoel E. Patarroyo; Fulvio Pilleggi; Jorge Kalil

    1995-01-01

    Heart tissue destruction in chronic Chagas disease cardiopathy (CCC) may be caused by autoimmune recognition of heart tissue by a mononuclear cell infiltrate decades after Trypanosoma cruzi infection. Indirect evidence suggests that there is antigenic crossreactivity between T. cruzi and heart tissue. As there is evidence for immune recognition of cardiac myosin in CCC, we searched for a putative myosin-crossreactive

  2. A Few Autoreactive Cells in an Autoimmune Infiltrate Control a Vast Population of Nonspecific Cells: A Tale of Smart Bombs and the Infantry

    Microsoft Academic Search

    Lawrence Steinman

    1996-01-01

    Inflammatory infiltrates in tissue-specific autoimmune disease comprise a collection of T cells with specificity for an antigen in the target organ. These specific cells recruit a population of nonspecific T cells and macrophages. The rare tissue-specific T cells in the infiltrate have the capacity to regulate both the influx and the efflux of cells from the tissue. Administration of an

  3. Insulin autoimmune syndrome induced by methimazole in a Korean girl with Graves' disease

    PubMed Central

    Lee, Sun Hee; Oh, Seung Hwan

    2013-01-01

    Hypoglycemia was detected in a 15-year-old girl due to loss of consciousness. She was diagnosed with Graves' disease and was being treated with methimazole for the past 4 months. A paradoxically increased insulin levels was found when she suffered from the hypoglycemic episode. An imaging study showed no mass lesion in the pancreas, and insulin antibodies were found in the serum. She was diagnosed with insulin autoimmune syndrome. Her HLA typing was performed, and it revealed HLA-DRB1 *04:06. The patient was treated with a corticosteroid for 2 months. After discontinuing the steroid, the insulin antibody titer decreased dramatically, and she did not have any episode of hypoglycemia since. This is the first report of insulin autoimmune syndrome in a Korean girl, and we have revealed the connection between HLA type and insulin autoimmune syndrome in Korea. PMID:24904848

  4. Autoimmune blistering dermatoses as systemic diseases.

    PubMed

    Vassileva, Snejina; Drenovska, Kossara; Manuelyan, Karen

    2014-01-01

    Autoimmune blistering dermatoses are examples of skin-specific autoimmune disorders that can sometimes represent the cutaneous manifestation of a multiorgan disease due to potential common pathogenic mechanisms. As soon as a distinct autoimmune blistering dermatosis is diagnosed, it is imperative to consider its potential systemic involvement, as well as the autoimmune and inflammatory conditions that are frequently associated with it. In paraneoplastic pemphigus/paraneoplastic autoimmune multiorgan syndrome, the internal organs (particularly the lungs) are affected by the autoimmune injury. Pemphigus erythematosus may manifest with overlapping serologic and immunohistologic features of lupus erythematosus. In patients with bullous pemphigoid, there is a greater prevalence of neurologic disease, possibly caused by cross-reactivity of the autoantibodies with isoforms of bullous pemphigoid antigens expressed in the skin and brain. Anti-laminin 332 pemphigoid shows an increased risk for adenocarcinomas. Patients with anti-p200 pemphigoid often suffer from psoriasis. A rare form of pemphigoid with antibodies against the ?5 chain of type IV collagen is characterized by underlying nephropathia. Particularly interesting is the association of linear IgA disease or epidermolysis bullosa acquisita with inflammatory bowel disease. Dermatitis herpetiformis is currently regarded as the skin manifestation of gluten sensitivity. Bullous systemic lupus erythematosus is part of the clinical spectrum of systemic lupus erythematosus, a prototypic autoimmune disease with multisystem involvement. PMID:24767184

  5. Extracellular Matrix Remodeling: The Common Denominator in Connective Tissue DiseasesPossibilities for Evaluation and Current Understanding of the Matrix as More Than a Passive Architecture, but a Key Player in Tissue Failure

    PubMed Central

    Nielsen, Mette J.; Sand, Jannie M.; Henriksen, Kim; Genovese, Federica; Bay-Jensen, Anne-Christine; Smith, Victoria; Adamkewicz, Joanne I.; Christiansen, Claus; Leeming, Diana J.

    2013-01-01

    Abstract Increased attention is paid to the structural components of tissues. These components are mostly collagens and various proteoglycans. Emerging evidence suggests that altered components and noncoded modifications of the matrix may be both initiators and drivers of disease, exemplified by excessive tissue remodeling leading to tissue stiffness, as well as by changes in the signaling potential of both intact matrix and fragments thereof. Although tissue structure until recently was viewed as a simple architecture anchoring cells and proteins, this complex grid may contain essential information enabling the maintenance of the structure and normal functioning of tissue. The aims of this review are to (1) discuss the structural components of the matrix and the relevance of their mutations to the pathology of diseases such as fibrosis and cancer, (2) introduce the possibility that post-translational modifications (PTMs), such as protease cleavage, citrullination, cross-linking, nitrosylation, glycosylation, and isomerization, generated during pathology, may be unique, disease-specific biochemical markers, (3) list and review the range of simple enzyme-linked immunosorbent assays (ELISAs) that have been developed for assessing the extracellular matrix (ECM) and detecting abnormal ECM remodeling, and (4) discuss whether some PTMs are the cause or consequence of disease. New evidence clearly suggests that the ECM at some point in the pathogenesis becomes a driver of disease. These pathological modified ECM proteins may allow insights into complicated pathologies in which the end stage is excessive tissue remodeling, and provide unique and more pathology-specific biochemical markers. PMID:23046407

  6. Transmethylation in immunity and autoimmunity.

    PubMed

    Lawson, Brian R; Eleftheriadis, Theodoros; Tardif, Virginie; Gonzalez-Quintial, Rosana; Baccala, Roberto; Kono, Dwight H; Theofilopoulos, Argyrios N

    2012-04-01

    The activation of immune cells is mediated by a network of signaling proteins that can undergo post-translational modifications critical for their activity. Methylation of nucleic acids or proteins can have major effects on gene expression as well as protein repertoire diversity and function. Emerging data indicate that indeed many immunologic functions, particularly those of T cells, including thymic education, differentiation and effector function are highly dependent on methylation events. The critical role of methylation in immunocyte biology is further documented by evidence that autoimmune phenomena may be curtailed by methylation inhibitors. Additionally, epigenetic alterations imprinted by methylation can also exert effects on normal and abnormal immune responses. Further work in defining methylation effects in the immune system is likely to lead to a more detailed understanding of the immune system and may point to the development of novel therapeutic approaches. PMID:22364920

  7. Immunomodulatory vaccination in autoimmune disease.

    PubMed

    Urbanek-Ruiz, Irene; Ruiz, Pedro J; Steinman, Lawrence; Fathman, C Garrison

    2002-06-01

    The development of vaccines is arguably the most significant achievement in medicine to date. The practice of innoculation with the fluid from a sore to protect from a disease actually dates back to ancient China; however, with the introduction of Jenner's smallpox vaccine, and greater understanding of the immune system, vaccines have become specific and systematic. Traditional vaccines have used killed pathogens (hepatitis A and the Salk polio vaccines), immunogenic subunits of a given pathogen (hepatitis B subunit vaccine), or live attenuated pathogens (measles, mumps, rubella, Sabin polio vaccines) to generate protective immunity. Currently, a new generation of vaccines that use the genetic material of a pathogen to elicit protective immunity are being developed. Although the most widespread and successful use of vaccines today remains in the arena of infectious diseases, manipulations of immune responses to protect against cancers, neurologic diseases, and autoimmunity are being explored rigorously. PMID:12092460

  8. Autoimmune pancreatitis: a surgical dilemma.

    PubMed

    Saavedra-Perez, David; Vaquero, Eva C; Ayuso, Juan R; Fernandez-Cruz, Laureano

    2014-12-01

    Autoimmune pancreatitis (AIP) is defined as a particular form of pancreatitis that often manifests as obstructive jaundice associated with a pancreatic mass or an obstructive bile duct lesion, and that has an excellent response to corticosteroid treatment. The prevalence of AIP worldwide is unknown, and it is considered as a rare entity. The clinical and radiological presentation of AIP can mimic bilio-pancreatic cancer, presenting difficulties for diagnosis and obliging the surgeon to balance decision-making between the potential risk presented by the misdiagnosis of a deadly disease against the desire to avoid unnecessary major surgery for a disease that responds effectively to corticosteroid treatment. In this review we detail the current and critical points for the diagnosis, classification and treatment for AIP, with a special emphasis on surgical series and the methods to differentiate between this pathology and bilio-pancreatic cancer. PMID:25066570

  9. Recent Advances in Autoimmune Pancreatitis

    PubMed Central

    Uchida, Kazushige; Fukui, Toshiro; Matsushita, Mitsunobu; Takaoka, Makoto

    2008-01-01

    Although the pathogenesis of autoimmune pancreatitis remains unclear, this report presents recent evidence of the clinical aspects of this disease: mild abdominal symptoms, usually without acute attacks of pancreatitis; occasional presence of obstructive jaundice; elevated levels of serum gammaglobulin, immunoglobulin (Ig)G, or IgG4; presence of autoantibodies; diffuse enlargement of the pancreas; irregular narrowing of the pancreatic duct (sclerosing pancreatitis), often with intrapancreatic biliary stenosis or coexisting biliary lesions (sclerosing cholangitis similar to primary sclerosing cholangitis) seen on endoscopic retrograde cholangiopancreatography; fibrotic changes with lymphocyte and IgG4-positive plasmacyte infiltration and obliterative phlebitis; occasional association with other systemic lesions (such as sialadenitis), retroperitoneal fibrosis, and interstitial renal tubular disorders; and response to steroid therapy. Based upon these findings, several sets of diagnostic criteria have been proposed. Further studies and international consensus for diagnostic criteria and pathogenetic mechanisms are needed. PMID:21904518

  10. Liver transplantation and autoimmune hepatitis.

    PubMed

    Tanaka, Tomohiro; Sugawara, Yasuhiko; Kokudo, Norihiro

    2015-02-01

    Liver Transplantation (LT) is an effective treatment for patients with end-stage liver disease including autoimmune hepatitis (AIH). Indication for LT for AIH does not differ basically from other liver diseases including both acute and chronic types of disease progression, although it is reported to be an infrequent indication for LT worldwide due to the therapeutic advances of immunosuppression. The outcome following LT is feasible, with current patient and graft survival exceeding 75% at 5 years. Recurrent and de-novo AIH posttranslant has also been reported; and this seems to have important clinical implications because its management differs from the standard treatment for allograft rejection. In this review, we discuss the characteristics of AIH, focusing on the indication for LT and issues raised following LT. PMID:25674386

  11. Immunotherapeutic strategies in autoimmune uveitis

    PubMed Central

    Papotto, Pedro Henrique; Marengo, Eliana Blini; Sardinha, Luiz Roberto; Goldberg, Anna Carla; Rizzo, Luiz Vicente

    2014-01-01

    Autoimmune uveitis is an organ-specific disorder characterized by irreversible lesions to the eye that predominantly affect people in their most productive years and is among the leading causes of visual deficit and blindness. Currently available therapies are effective in the treatment of a wide spectrum of uveitis, but are often associated with severe side effects. Here, we review ongoing research with promising immunomodulatory therapeutic strategies, describing their specific features, interactions and the responses triggered by the targeted immune molecules that aim to minimize clinical complications and the likelihood of disease relapse. We first review the main features of the disease, diagnostic tools, and traditional forms of therapy, as well as the animal models predominantly used to understand the pathogenesis and test the novel intervention approaches aiming to control the acute immune and inflammatory responses and to dampen chronic responses. Both exploratory research and clinical trials have targeted either the blockade of effector pathways or of their companion co-stimulatory molecules. Examples of targets are T cell receptors (CD3), their co-stimulatory receptors (CD28, CTLA-4) and corresponding ligands (B7-1 and B7-2, also known as CD80 and CD86), and cytokines like IL-2 and their receptors. Here, we summarize the available evidence on effectiveness of these treatments in human and experimental uveitis and highlight a novel CD28 antagonist monovalent Fab? antibody, FR104, which has shown preclinical efficacy suppressing effector T cells while enhancing regulatory T cell function and immune tolerance in a humanized graft-versus-host disease (GVHD) mice model and is currently being tested in a mouse autoimmune uveitis model with encouraging results. PMID:24833504

  12. Pemphigus autoimmunity: Hypotheses and realities

    PubMed Central

    Grando, Sergei A

    2011-01-01

    The goal of contemporary research in pemphigus vulgaris and pemphigus foliaceus is to achieve and maintain clinical remission without corticosteroids. Recent advances of knowledge on pemphigus autoimmunity scrutinize old dogmas, resolve controversies, and open novel perspectives for treatment. Elucidation of intimate mechanisms of keratinocyte detachment and death in pemphigus has challenged the monopathogenic explanation of disease immunopathology. Over 50 organ-specific and non-organ-specific antigens can be targeted by pemphigus autoimmunity, including desmosomal cadherins and other adhesion molecules, PERP cholinergic and other cell membrane (CM) receptors, and mitochondrial proteins. The initial insult is sustained by the autoantibodies to the cell membrane receptor antigens triggering the intracellular signaling by Src, epidermal growth factor receptor kinase, protein kinases A and C, phospholipase C, mTOR, p38 MAPK, JNK, other tyrosine kinases, and calmodulin that cause basal cell shrinkage and ripping desmosomes off the CM. Autoantibodies synergize with effectors of apoptotic and oncotic pathways, serine proteases, and inflammatory cytokines to overcome the natural resistance and activate the cell death program in keratinocytes. The process of keratinocyte shrinkage/detachment and death via apoptosis/oncosis has been termed apoptolysis to emphasize that it is triggered by the same signal effectors and mediated by the same cell death enzymes. The natural course of pemphigus has improved due to a substantial progress in developing of the steroid-sparing therapies combining the immunosuppressive and direct anti-acantholytic effects. Further elucidation of the molecular mechanisms mediating immune dysregulation and apoptolysis in pemphigus should improve our understanding of disease pathogenesis and facilitate development of steroid-free treatment of patients. PMID:21939410

  13. Is Multiple Sclerosis an Autoimmune Disease?

    PubMed Central

    Wootla, Bharath; Eriguchi, Makoto; Rodriguez, Moses

    2012-01-01

    Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS) with varied clinical presentations and heterogeneous histopathological features. The underlying immunological abnormalities in MS lead to various neurological and autoimmune manifestations. There is strong evidence that MS is, at least in part, an immune-mediated disease. There is less evidence that MS is a classical autoimmune disease, even though many authors state this in the description of the disease. We show the evidence that both supports and refutes the autoimmune hypothesis. In addition, we present an alternate hypothesis based on virus infection to explain the pathogenesis of MS. PMID:22666554

  14. Phosphodiesterase 4-targeted treatments for autoimmune diseases

    PubMed Central

    2013-01-01

    Advancements in phosphodiesterase (PDE)-targeted therapies have shown promise in recent years for treating patients with a variety of autoimmune diseases. This review summarizes the development of PDE4 inhibitors and the associated literature with a focus on treatments for autoimmune diseases. After the initial investigations of the prototypic PDE inhibitor, rolipram, more selective inhibitors targeting the PDE4 isozyme have been developed. With phase II and phase III clinical trials currently underway to evaluate the safety and efficacy of the latest generation of PDE4 inhibitors, namely apremilast, a new class of treatments may be around the corner for patients suffering from chronic, autoimmune diseases. PMID:23557064

  15. Phosphodiesterase 4-targeted treatments for autoimmune diseases.

    PubMed

    Kumar, Neal; Goldminz, Ari M; Kim, Noori; Gottlieb, Alice B

    2013-01-01

    Advancements in phosphodiesterase (PDE)-targeted therapies have shown promise in recent years for treating patients with a variety of autoimmune diseases. This review summarizes the development of PDE4 inhibitors and the associated literature with a focus on treatments for autoimmune diseases. After the initial investigations of the prototypic PDE inhibitor, rolipram, more selective inhibitors targeting the PDE4 isozyme have been developed. With phase II and phase III clinical trials currently underway to evaluate the safety and efficacy of the latest generation of PDE4 inhibitors, namely apremilast, a new class of treatments may be around the corner for patients suffering from chronic, autoimmune diseases. PMID:23557064

  16. [Autoimmune hemolytic anemia and CREST syndrome].

    PubMed

    Jordana, R; Tolosa, C; Selva, A; Ordi, J

    1990-05-19

    There are few studies addressing the frequency and etiology of anemia in progressive systemic sclerosis. Anemia is present in about 25% of these patients. Among the implicated causes are ferropenia, generally associated with gastrointestinal hemorrhage, and renal failure. In a considerable number of patients, the specific etiology of anemia remained unknown. We report a 59-year-old female with autoimmune hemolytic anemia and incomplete CREST syndrome. We emphasize the rarity of autoimmune hemolysis as a cause of anemia in systemic sclerosis, and we discuss its significance as indirectly supporting the possible autoimmune pathogenesis of that condition. PMID:2201843

  17. Autoimmune cytopenias in chronic lymphocytic leukemia.

    PubMed

    Visco, Carlo; Barcellini, Wilma; Maura, Francesco; Neri, Antonino; Cortelezzi, Agostino; Rodeghiero, Francesco

    2014-11-01

    Chronic lymphocytic leukemia (CLL) is frequently complicated by secondary autoimmune cytopenias (AIC) represented by autoimmune hemolytic anemia (AIHA), immune thrombocytopenia (ITP), pure red cell aplasia, and autoimmune granulocytopenia. The distinction of immune cytopenias from cytopenias due to bone marrow infiltration, usually a