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1

Renal involvement in autoimmune connective tissue diseases  

PubMed Central

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

2013-01-01

2

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

PubMed

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

Braunstein, Inbal; Werth, Victoria

2013-01-01

3

Neutrophilic skin lesions in autoimmune connective tissue diseases: nine cases and a literature review.  

PubMed

The pathophysiology of neutrophilic dermatoses (NDs) and autoimmune connective tissue diseases (AICTDs) is incompletely understood. The association between NDs and AICTDs is rare; recently, however, a distinctive subset of cutaneous lupus erythematosus (LE, the prototypical AICTD) with neutrophilic histological features has been proposed to be included in the spectrum of lupus. The aim of our study was to test the validity of such a classification. We conducted a monocentric retrospective study of 7028 AICTDs patients. Among these 7028 patients, a skin biopsy was performed in 932 cases with mainly neutrophilic infiltrate on histology in 9 cases. Combining our 9 cases and an exhaustive literature review, pyoderma gangrenosum, Sweet syndrome (n = 49), Sweet-like ND (n = 13), neutrophilic urticarial dermatosis (n = 6), palisaded neutrophilic granulomatous dermatitis (n = 12), and histiocytoid neutrophilic dermatitis (n = 2) were likely to occur both in AICTDs and autoinflammatory diseases. Other NDs were specifically encountered in AICTDs: bullous LE (n = 71), amicrobial pustulosis of the folds (n = 28), autoimmunity-related ND (n = 24), ND resembling erythema gyratum repens (n = 1), and neutrophilic annular erythema (n = 1). The improvement of AICTDS neutrophilic lesions under neutrophil targeting therapy suggests possible common physiopathological pathways between NDs and AICTDs. PMID:25546688

Hau, Estelle; Vignon Pennamen, Marie-Dominique; Battistella, Maxime; Saussine, Anne; Bergis, Maud; Cavelier-Balloy, Benedicte; Janier, Michel; Cordoliani, Florence; Bagot, Martine; Rybojad, Michel; Bouaziz, Jean-David

2014-12-01

4

Evaluation of a Multiplex ELISA for Autoantibody Profiling in Patients with Autoimmune Connective Tissue Diseases  

PubMed Central

The performance of immunoassays for the detection of autoantibodies is of critical importance in the diagnosis and assessment of patients with autoimmune connective tissue diseases (ACTD). Our objective was to compare the features of two multiplexed assays—INNO-LIA ANA and Gennova-PictArray ENA ELISA—for measurement of multiple autoantibodies and their utility as a clinical tool in ACTD diagnosis. The antigens included SS-A/Ro (60 and 52), SSB/La, Sm, Sm/RNP, CENP-B, Jo-1, and Scl-70. Stored sera from 85 ACTD patients and 80 controls consisting of patients with vasculitis, rheumatoid arthritis and infectious diseases, as well as healthy subjects were analyzed jointly with clinical and laboratory data. Agreement between the two methods varied between 58 and 99% (Cohen's kappa: 0.21–0.71) mostly for SSA and SSB. The frequency of specific autoantibodies measured using the two methods was more variable for SSA, SSB, and RNP/Sm. There were a higher number of ambiguous results when using INNO-LIA. The optimized cut-off values of the Gennova-PictArray resulted in over 99% specificities in samples obtained from the control group. Sensitivity patterns were more accurate in Gennova-PictArray than in INNO-LIA, as suggested in previously reported studies. A third method could be applied to determine which of the two methods is more accurate. PMID:24527209

Caro Pérez, Alejandro; Kumble, Sarita; Kumble, Krishnanand D.; Alonso Cańizal, M. Consuelo; Jiménez Jiménez, Luis M.; Alonso Díez, Lorena; Durán Parejo, Pilar

2014-01-01

5

Mixed connective tissue disease, myositis and systemic lupus erythematosus : Immunological and genetic studies in three related rheumatic autoimmune studies.  

E-print Network

??Mixed connective tissue disease (MCTD), polymyositis (PM)/ dermatomyositis (DM) and systemic lupus erythematosus (SLE) are chronic, rheumatic, systemic inflammatory disorders. The disorders depend on several… (more)

Bakri Hassan, Adla

2002-01-01

6

Antithyroglobulin monoclonal and autoantibodies cross-react with an orbital connective tissue membrane antigen: a possible mechanism for the association of ophthalmopathy with autoimmune thyroid disorders.  

PubMed Central

The possibility that Graves' ophthalmopathy and autoimmune thyroid disorders may be associated because of autoimmune reactions against antigens shared between human orbital and thyroid tissues was investigated using anti-thyroglobulin (Tg) monoclonal and autoantibodies. Eleven of 16 mouse monoclonal antibodies (MCAB) tested reacted, in an enzyme-linked immunosorbent assay (ELISA), with an antigen in human orbital connective tissue membranes (OCTmem), but not with the OCT soluble fraction, or with membrane or soluble fractions of human eye muscle, lacrimal gland or skin connective tissue. The anti-OCTmem activity was absorbed by OCTmem and Tg, but not by liver membranes or bovine serum albumin (BSA). In preliminary studies four out of 113 human MCAB against thyroid or orbital tissue antigens showed reactivity restricted to Tg and OCTmem. Sera from approximately 50% of patients with autoimmune thyroid disorders, with or without ophthalmopathy, also reacted with OCTmem. The autoantibody activity correlated closely with serum titres of antithyroglobulin but not with the presence, duration, or severity of the eye disease. The OCTmem reactivity was absorbed by Tg, thyroid membranes, and OCTmem but not liver membranes, membranes prepared from other orbital tissues, or BSA. The OCTmem-Tg shared antigen site appeared not to be native thyroglobulin since, (i) MCAB and serum autoantibodies did not react with the cytosol fraction of OCT, and (ii) because the membrane antigen was not solubilizable. Because not all patients with ophthalmopathy have detectable anti-Tg antibodies and, conversely, because not all patients with detectable anti-Tg antibodies develop ophthalmopathy it is unlikely that autoimmunity against a OCTmem-Tg shared antigen is the primary mechanism of Graves' ophthalmopathy, although this possibility has not been excluded. On the other hand the reaction of anti-Tg autoantibodies with OCT membranes may be a model for other autoimmune reactions against other thyroid-orbital tissue-shared antigens. While the pathogenesis of Graves' ophthalmopathy is likely to be multifactorial, humoral and cellular reactions against primary orbital antigens, thyroid-orbitol tissue shared antigens, or both, are likely to play important roles. PMID:3841305

Kuroki, T; Ruf, J; Whelan, L; Miller, A; Wall, J R

1985-01-01

7

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 ...

8

Undifferentiated Connective Tissue Disease  

MedlinePLUS

... vessels. Examples of connective tissue diseases include lupus , scleroderma , rheumatoid arthritis , Sjögren's syndrome , myositis , and vasculitis . There ... connective tissue diseases, such as lupus, Sjögren's or scleroderma. More UCTD Information Causes Diagnosis Symptoms Treatment Print ...

9

[Connective tissue dysplasia].  

PubMed

The article presents a diagnosis of dysplasia of connective tissue in athletes, where the most important are the methods of clinical assessment using diagnostic tests and rating scales manifestation of connective tissue dysplasia. Evaluation of patients with suspected connective tissue dysplasia should include inspection of an ophthalmologist, orthopedic trauma, cardiology. Should also be carried out by criteria diagnosis degree of connective tissue dysplasia by T. Y. Smolnova (2003) (Large and small diagnostic criteria), which include: increased skin extensibility, joint hypermobility (sprain, dislocation and subluxation, flat feet), muscle hypotonia, a hereditary predisposition to the disease, evaluation of signs joint hypermobility (Beighton criteria). If during routine medical examination revealed athletes with manifestations of connective tissue dysplasia, they are subject to a more in-depth examination and observation. Early diagnosis of connective tissue dysplasia allows not only to plan the training process, but also reduces the trauma of athletes. PMID:23350142

Piantkovski?, A S

2012-01-01

10

Connective tissue tumors.  

PubMed

Connective tissue consists of collagen, elastic fibers and ground substances produced by fibrocytes. These cells are usually spindle-shaped with slender nuclei and bipolar cytoplasmic extensions. Apart from labeling for vimentin and variable reactivity for factor XIIIa and CD34, fibrocytes are immunonegative. Electron microscopy reveals prominent endoplasmic reticulum, but is otherwise indistinct. Lesions with fibrocytic differentiation can be divided into five categories: scars, keloids, dermatofibromas, nodular fasciitis, and superficial fibromatoses are inflammatory lesions. Thereby, dermatofibromas and their subcutaneous/deep soft tissue counterpart nodular fasciitis can present with a wide variety of clinicopathologic variants which may be misinterpreted as malignancies. Prurigo nodularis, chondrodermatitis nodularis helicis, acanthoma fissuratum, and knuckle pads are hyperplasias; fibroma molle, fibrous papules, connective tissue nevi, and elastofibroma are hamartomas; and fibroma of tendon sheath, pleomorphic fibroma, and giant cell tumor of tendon sheath are benign neoplasms. Deep fibromatoses, dermatofibrosarcoma protuberans, giant cell fibroblastoma, giant cell angiofibroma, hyalinizing spindle cell tumor with giant rosettes, solitary fibrous tumor, myxofibrosarcoma, low-grade fibromyxoid sarcoma, acral myxoinflammatory fibroblastic sarcoma, and classical fibrosarcoma, are malignant neoplasms, that is fibrosarcomas of variable malignant potential. Lesions dominated by myocytes/ myofibroblasts, e.g. cutaneous myofibroma/infantile myofibromatosis, or by macrophages, e.g. xanthogranulomas, are not part of this chapter. PMID:12079232

Zelger, Bernhard

2002-01-01

11

The Role of Dendritic Cells in Tissue-Specific Autoimmunity  

PubMed Central

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

Langridge, William

2014-01-01

12

Heritable Disorders of Connective Tissue  

Microsoft Academic Search

\\u000a The molecular composition and organization of connective tissue, known as the extracellular matrix, are extraordinarily complex. Much remains unknown about the number, structure, map location, and regulation of genes that\\u000a control synthesis, organization, and metabolism of this ubiquitous tissue. However, the genes that specify several hundred\\u000a proteins involved in connective tissue metabolism and skeletal development have been mapped (1). Mutations

Reed Edwin Pyeritz

13

Heritable Disorders of Connective Tissue  

Microsoft Academic Search

\\u000a \\u000a \\u000a \\u000a \\u000a  \\u000a \\u000a The genes that specify the hundreds of proteins involved in connective tissue have been mapped.\\u000a \\u000a \\u000a \\u000a \\u000a  \\u000a \\u000a The heritable disorders of connective tissue (HDCT) show both considerable variability within and among families and genetic\\u000a heterogeneity.\\u000a \\u000a \\u000a \\u000a \\u000a  \\u000a \\u000a ? Phenotypes used: (1) disorders of fibrous elements, such as osteogenesis imperfecta and Marfan?s syndrome, (2) disorders\\u000a of proteogylcan metabolism, such as mucopolysaccharidoses, (3)

REED EDWIN PYERITZ

14

CELLULAR CONTROL OF CONNECTIVE TISSUE MATRIX TENSION†  

PubMed Central

The biomechanical behavior of connective tissue in response to stretching is generally attributed to the molecular composition and organization of its extracellular matrix. It also is becoming apparent that fibroblasts play an active role in regulating connective tissue tension. In response to static stretching of the tissue, fibroblasts expand within minutes by actively remodeling their cytoskeleton. This dynamic change in fibroblast shape contributes to the drop in tissue tension that occurs during viscoelastic relaxation. We propose that this response of fibroblasts plays a role in regulating extracellular fluid flow into the tissue, and protects against swelling when the matrix is stretched. This article reviews the evidence supporting possible mechanisms underlying this response including autocrine purinergic signaling. We also discuss fibroblast regulation of connective tissue tension with respect to lymphatic flow, immune function and cancer. PMID:23444198

Langevin, Helene M.; Nedergaard, Maiken; Howe, Alan

2013-01-01

15

Cerebriform connective tissue nevus of lumbar.  

PubMed

Connective tissue nevi represents a kind of hamartoma, and coalescence of the lesions in a cerebriform mode in the lumbar region without Proteus syndrome is rarely seen. Here, we report a 26-year-old woman presenting with nodules and plaques in her left lumbar region of 26 years in duration. Histopathological examination and Masson-trichrome stain showed increased dermal collagen bundles in a haphazard array. The diagnosis of connective tissue nevi was made. This is the first case report on cerebriform connective tissue nevi without Proteus syndrome in the lumbar region. PMID:25512235

Chen, Jinbo; Chen, Liuqing; Duan, Yiqun; Li, Dongsheng; Dong, Bilin

2015-02-01

16

Action of hyperoxia on connective tissue  

NASA Technical Reports Server (NTRS)

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.

Shimkevich, L. L.

1973-01-01

17

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 | ...

18

Vasculitis associated with connective tissue disorders  

Microsoft Academic Search

Vasculitis associated with connective tissue disorders is an important cause of secondary vasculitis about which little is\\u000a written. When vasculitis occurs in the setting of a preexisting connective tissue disorder, it often correlates with disease\\u000a severity and portends a poorer prognosis. It may involve virtually any organ system and present in a myriad of ways. Prompt\\u000a recognition and treatment of

Mittie K. Doyle

2006-01-01

19

Vasculitis in the connective tissue diseases  

Microsoft Academic Search

Vasculitides in the setting of connective tissue diseases are generally thought to be infrequent and relatively little is\\u000a written about them. They are, however, important both because they may pose diagnostic and therapeutic challenges and affect\\u000a prognosis. In each of the connective tissue diseases, vasculitis can present in various clinical and pathologic forms adding\\u000a to their diagnostic and therapeutic difficulties.

Luis Felipe Flores-Suárez; Donato Alarcón-Segovia

2000-01-01

20

Evidence of Connective Tissue Involvement in Acupuncture  

Microsoft Academic Search

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

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

2002-01-01

21

BIOLOGICAL FRAMEWORKS FOR ENGINEERS Session #19 [cm: Connective tissues  

E-print Network

ME411/511 BIOLOGICAL FRAMEWORKS FOR ENGINEERS Session #19 [cm: Connective tissues] General Objectives: Connective tissues are a group of tissues which bind structures together and provide a framework Mechanics of connective tissues and systems Central Framework: Connective tissues provide the mechanical

Sniadecki, Nathan J.

22

BIOLOGICAL FRAMEWORKS FOR ENGINEERS Session #19 [cm: Connective tissues  

E-print Network

ME498/599 BIOLOGICAL FRAMEWORKS FOR ENGINEERS Session #19 [cm: Connective tissues] General Objectives: Connective tissues are a group of tissues which bind structures together and provide a framework Mechanics of connective tissues and systems Central Framework: Connective tissues provide the mechanical

Sniadecki, Nathan J.

23

Growth hormone and connective tissue in exercise.  

PubMed

Over the last few years, growth hormone (GH) has become increasingly popular as doping within different sports. However, the precise mechanisms behind the ergogenic (performance enhancing) effects of GH in athletes are still being debated. Besides a well-documented stimulatory effect of GH on carbohydrate and fatty acid metabolism, and a possible anabolic effect on myofibrillar muscle protein, we suggest a role for GH as an anabolic agent in connective tissue in human skeletal muscle and tendon. Given the importance of the connective tissue for the function of skeletal muscle and tendon, a strengthening effect of GH on connective tissue could fit with the ergogenic effect of GH experienced by athletes. This review examines the endogenous secretion of GH and its mediators in relation to exercise. Furthermore, we consider the effect of endogenous GH and administered recombinant human GH (rhGH) on both myofibrillar and connective tissue protein synthesis, thus offering an alternative explanation for the ergogenic effect of GH. Finally, we suggest a possible therapeutic role for rhGH in clinical management of the frequently suffered injuries in the connective tissue. PMID:15998337

Doessing, S; Kjaer, M

2005-08-01

24

Cutaneous Connective Tissue Diseases: Epidemiology, Diagnosis, and Treatment  

PubMed Central

Connective tissue diseases (CTDs) are a group of clinical disorders that have an underlying autoimmune pathogenesis. These include a diverse set of diseases such as relapsing polychondritis, rheumatoid arthritis, and eosinophilic fasciitis, along with more common entities like Sjogren’s syndrome, dermatomyositis, scleroderma, and lupus erythematosus. The latter three will be the focus of this review, as they constitute the most significant and common CTD with cutaneous manifestations. The cutaneous signs often represent the preliminary stages of disease and the presenting clinical symptoms. Therefore, comprehensive knowledge of CTD manifestations is essential for accurate diagnosis, better assessment of prognosis, and effective management. Although the precise etiologies of CTDs remain obscure, recent advances have allowed for further understanding of their pathogenesis and improved disease classifications. In addition, there have been developments in therapeutic options for CTDs. This review provides an overview of the epidemiology, clinical presentations, and current treatment options of cutaneous lupus erythematous, dermatomyositis and scleroderma. PMID:21218179

Reddy, Bobby Y.; Hantash, Basil M.

2010-01-01

25

The respiratory system in connective tissue diseases.  

PubMed

Adolescents with connective tissue diseases (CTDs) are at risk for community-acquired and opportunistic respiratory tract infections; it is mandatory to consider an infectious etiology in the differential diagnosis. The authors highlight the respiratory manifestations of the more common CTDs seen in adolescence, and also discuss useful diagnostic tests and drug regimens. PMID:10961258

McDowell, K; Millard, S L

1998-02-01

26

Eosinophilic vasculitis in connective tissue disease  

Microsoft Academic Search

Background: Neutrophilic and lymphocytic vascular inflammation is common in vasculitis associated with connective tissue disease (CTD). We recently identified eight patients with CTD and eosinophilic vasculitis.Objective: The purpose of this study was to characterize a variant form of vasculitis in CTD with eosinophilic infiltration.Methods: Of 98 CTD patients with cutaneous necrotizing vasculitis, eight were found with predominantly eosinophilic vascular infiltration.

Ko-Ron Chen; W. P Daniel Su; Mark R Pittelkow; Doyt L Conn; Terry George; Kristin M Leiferman

1996-01-01

27

Immunological features of diffuse connective tissue diseases  

Microsoft Academic Search

Diffuse connective tissue diseases (DCTD) represent an heterogeneous group of disorders characterized by systemic inflammatory reactions that are currently classified on clinical grounds. Their aetiopathogenesis is largely unknown and appears to be very complex, associating exogenous factors with an immunogenetic predisposition. In the last decade, studies on human leukocyte antigen (HLA)-disease associations and antinuclear antibodies have provided some useful clues

G. R. Burgio; A. Martini

1990-01-01

28

Some connective tissue disorders of the lung.  

PubMed Central

Many connective tissue disorders involve the lungs. The same clinical syndrome may be associated with several distinctive types of pathology in different patients. Fibrosing alveolitis is a common feature of a number of different syndromes. An hypothesis is set out in schematic form which may help to account for some of these differences and emphasizes the potential importance of the pulmonary vasculature in pathogenesis. Images Figure 3 Figure 4 Figure 5 Figure 8 Figure 9 PMID:3074281

Turner-Warwick, M.

1988-01-01

29

Latest advances in connective tissue disorders  

PubMed Central

The connective tissue disorders comprise a number of related conditions that include systemic lupus erythematosus (SLE) and the antiphospholipid (Hughes) syndrome, scleroderma, myositis and Sjögren’s syndrome. They are characterized by autoantibody production and other immune-mediated dysfunction. There are common clinical and serological features with some patients having multiple overlapping connective tissue disorders. The latest advances include new approaches to therapy, including more focused utilization of existing therapies and the introduction of biological therapies in SLE, more precise protocols for assessment of severe disease manifestations such as in interstitial lung disease and pulmonary artery hypertension in scleroderma, new antibodies for disease characterization in myositis and new approaches to patient assessment in Sjögren’s syndrome. B cells have a critical role in most, if not all of these disorders such that B-cell depletion or suppression of B-cell activating cytokines improves disease in many patients. In particular, the introduction of rituximab, a monoclonal antibody targeting the CD20 molecule on B cells, into clinical practice for rheumatoid arthritis and B-cell lymphoma has been a key driver of experimental approaches to therapy in connective tissue disorders. Genetic studies also suggest a role for the innate immune system in disease pathogenesis, suggesting further future targets for biological therapies over the next few years. PMID:23904866

Rao, Vijay

2013-01-01

30

Effect of ionizing radiations on connective tissue. [Review  

Microsoft Academic Search

The effects of ionizing radiations on connective tissue in lung, heart, vasculature, kidney, skin, and skeletal tissues are reviewed. Special emphasis is given to the effect of ionizing radiations on vasculo-connective tissue and fibrotic changes following radiation-induced injury to organs and tissues. In order to put the subject matter in proper prospective, the general biochemistry, physiology, and pathology of connective

K. I. Altman; G. B. Gerber

1980-01-01

31

Connective tissue alterations in Fkbp10-/- mice.  

PubMed

Osteogenesis imperfecta (OI) is an inherited brittle bone disorder characterized by bone fragility and low bone mass. Loss of function mutations in FK506-binding protein 10 (FKBP10), encoding the FKBP65 protein, result in recessive OI and Bruck syndrome, of which the latter is additionally characterized by joint contractures. FKBP65 is thought to act as a collagen chaperone, but it is unknown how loss of FKBP65 affects collagen synthesis and extracellular matrix formation. We evaluated the developmental and postnatal expression of Fkbp10 and analyzed the consequences of its generalized loss of function. Fkbp10 is expressed at low levels in E13.5 mouse embryos, particularly in skeletal tissues, and steadily increases through E17.5 with expression in not only skeletal tissues, but also in visceral tissues. Postnatally, expression is limited to developing bone and ligaments. In contrast to humans, with complete loss of function mutations, Fkbp10(-/-) mice do not survive birth, and embryos present with growth delay and tissue fragility. Type I calvarial collagen isolated from these mice showed reduced stable crosslink formation at telopeptide lysines. Furthermore, Fkbp10(-/-) mouse embryonic fibroblasts show retention of procollagen in the cell layer and associated dilated endoplasmic reticulum. These data suggest a requirement for FKBP65 function during embryonic connective tissue development in mice, but the restricted expression postnatally in bone, ligaments and tendons correlates with the bone fragility and contracture phenotype in humans. PMID:24777781

Lietman, Caressa D; Rajagopal, Abbhirami; Homan, Erica P; Munivez, Elda; Jiang, Ming-Ming; Bertin, Terry K; Chen, Yuqing; Hicks, John; Weis, MaryAnn; Eyre, David; Lee, Brendan; Krakow, Deborah

2014-09-15

32

Connective tissue disease features after thallium poisoning.  

PubMed

We present 5 patients in whom thallium poisoning (1) mimicked systemic lupus erythematosus (SLE) with positive antinuclear antibodies; (2) caused a SLE-like illness with positive antinuclear antibodies and rheumatoid factor that was followed by a persistent chronic polyarthritis; (3) mimicked SLE with negative antinuclear antibodies and no residual disease; (4) caused arthralgia, Raynaud's phenomenon and palmar erythema with negative antinuclear antibodies followed by keratoconjunctivitis sicca; and (5) triggered the onset of SLE with diffuse proliferative glomerulonephritis. Although the notion exists that thallium poisoning may simulate seronegative SLE, these associations between connective tissue diseases and thallium poisoning have not been previously recorded. PMID:2787403

Alarcón-Segovia, D; Amigo, M C; Reyes, P A

1989-02-01

33

[Interstitial lung disease in connective tissue disorders].  

PubMed

After immunosuppressive-induced infections, interstitial lung disease (ILD) is one of the most serious pulmonary complications associated with connective tissue diseases (CTD). Although it is common for ILD to be diagnosed concurrent with or after CTD, some patients will present with ILD years prior to receiving a diagnosis of CTD. The clinical approach involves an examination of the extrathoracic symptoms (suggestive of CTD) and the evaluation of respiratory disability. Nonspecific interstitial pneumonia is the most common histological finding in patients with CTD. The management of patients with CTD-associated ILD is optimized by multidisciplinary collaboration. ILD-CTD are treated through anti-inflammatory medication, immunosuppressants and biological agents. PMID:25362775

Carmier, Delphine; Diot, Élisabeth; Guilleminault, Laurent; Marchand-Adam, Sylvain

2014-09-01

34

Ultrastructural Connective Tissue Aberrations in Patients With Intracranial Aneurysms  

Microsoft Academic Search

Background and Purpose—An unknown connective tissue defect might predispose for the development and rupture of intracranial aneurysms in some patients. This study of connective tissue samples of a series of patients with intracranial aneurysms investigates the morphology of the extracellular matrix with methods that are currently used in the routine diagnosis of inherited connective tissue disorders. Methods—Skin biopsies from 21

Caspar Grond-Ginsbach; Holger Schnippering; Ingrid Hausser; Ralf Weber; Inge Werner; Hans H. Steiner; Nina Lüttgen; Otto Busse; Armin Grau; Tobias Brandt

35

Biomarkers of connective tissue disease in patients with intracranial aneurysms  

Microsoft Academic Search

Connective tissue defects may play a significant role in the development of intracranial aneurysms (IAs). Multiorgan connective tissue disorders may, therefore, indicate a risk of IA development. We investigated biomarkers of connective tissue disease in patients with IAs. A series of 62 patients with IAs was studied by physical examination, echocardiography, ultrasound examination of the kidneys and abdomen, and microscopic

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

2010-01-01

36

Fibroblast involvement in soft connective tissue calcification.  

PubMed

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

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

2013-01-01

37

Fibroblast involvement in soft connective tissue calcification  

PubMed Central

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

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

2013-01-01

38

Relationship of acupuncture points and meridians to connective tissue planes  

Microsoft Academic Search

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.

Helene M. Langevin; Jason A. Yandow

2002-01-01

39

The relationship between connective tissue abnormality and pelvic floor dysfunction.  

E-print Network

??The University of Manchester, Doctor of Medicine, 2013Gemma FaulknerThe relationship between connective tissue abnormality and pelvic floor dysfunctionPerineal descent (PD) is a sign of connective… (more)

Faulkner, Gemma

2013-01-01

40

[Interstitial lung disease related to systemic connective tissue diseases].  

PubMed

Interstitial lung disease (ILD) is one of the most frequent and most serious complications of connective tissue diseases such as systemic sclerosis, systemic lupus erythematosus, dermato- and polymyositis, Sjogren's syndrome, or mixed connective tissue disease. Diagnosis of ILD is often delayed in patients with connective tissue diseases because of the systemic character of the primary condition, restricted physical activity of the patient and insufficient awareness of the physycian. The aim of the current review is to present the up-to-date information on ethiopathology, classification, diagnosis and treatment of ILD in patients with connective tissue diseases. PMID:16786776

Fiedorczyk, Ma?gorzata; Rojewska, Joanna; Kowal-Bielecka, Otylia; Sierakowski, Stanis?aw

2005-01-01

41

Skin Involvement in Systemic Autoimmune Diseases  

Microsoft Academic Search

Autoimmune diseases present with varied and broad-ranging cutaneous manifestations. Connective tissue disorders have a plethora of skin manifestations such as rheumatoid nodules in rheumatoid arthritis, psoriatic plaques in psoriatic arthritis, acne and pustulosis in SAPHO syndrome, livedo reticularis and ulceration in antiphospholipid antibody syndrome and xerosis in Sjögren syndrome. Cutaneous manifestations of autoimmune vasculitides such as polyarteritis nodosa, Kawasaki disease,

Shadi Rashtak; Mark R. Pittelkow

2008-01-01

42

Connective tissue growth factor in tumor pathogenesis  

PubMed Central

Key roles for connective tissue growth factor (CTGF/CCN2) are demonstrated in the wound repair process where it promotes myofibroblast differentiation and angiogenesis. Similar mechanisms are active in tumor-reactive stroma where CTGF is expressed. Other potential roles include prevention of hypoxia-induced apoptosis and promoting epithelial-mesenchymal transistion (EMT). CTGF expression in tumors has been associated to both tumor suppression and progression. For example, CTGF expression in acute lymphoblastic leukemia, breast, pancreas and gastric cancer correlates to worse prognosis whereas the opposite is true for colorectal, lung and ovarian cancer. This discrepancy is not yet understood. High expression of CTGF is a hallmark of ileal carcinoids, which are well-differentiated endocrine carcinomas with serotonin production originating from the small intestine and proximal colon. These tumors maintain a high grade of differentiation and low proliferation. Despite this, they are malignant and most patients have metastatic disease at diagnosis. These tumors demonstrate several phenotypes potentially related to CTGF function namely: cell migration, absent tumor cell apoptosis, as well as, reactive and well vascularised myofibroblast rich stroma and fibrosis development locally and in distal organs. The presence of CTGF in other endocrine tumors indicates a role in the progression of well-differentiated tumors. PMID:23259759

2012-01-01

43

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

PubMed Central

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

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

44

Myofibroblasts and mechano-regulation of connective tissue remodelling  

Microsoft Academic Search

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

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

2002-01-01

45

Raynaud’s phenomenon in undifferentiated connective tissue disease (UCTD)  

Microsoft Academic Search

The aim of this study was to ascertain which clinical and immunological factors are associated with Raynaud’s phenomenon (RP) in patients with undifferentiated connective tissue disease (UCTD) and to investigate microvascular involvement. A total of 78 patients were evaluated. They all showed symptoms suggestive of a connective tissue disorder (CTD), but did not fulfil the criteria for any of the

Rossella De Angelis; Angela Cerioni; Patrizia Del Medico; Patrizia Blasetti

2005-01-01

46

Smooth Muscle-Mediated Connective Tissue Remodeling in Pulmonary Hypertension  

Microsoft Academic Search

Abnormal accumulation of connective tissue in blood vessels contributes to alterations in vascular physiology associated with disease states such as hypertension and atherosclerosis. Elastin synthesis was studied in blood vessels from newborn calves with severe pulmonary hypertension induced by alveolar hypoxia in order to investigate the cellular stimuli that elicit changes in pulmonary arterial connective tissue production. A two- to

Robert P. Mecham; Loren A. Whitehouse; David S. Wrenn; William C. Parks; Gail L. Griffin; Robert M. Senior; Edmond C. Crouch; Kurt R. Stenmark; Norbert F. Voelkel

1987-01-01

47

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 bindevævs- sygdomme, som fører til aortic aneurysms og dissections. En automatisk og præcis metode til

48

Perioperative Management of Patients with Connective Tissue Disease  

PubMed Central

Diseases of the connective tissue are a varied group of disorders with major musculoskeletal manifestations such as joint pain and loss of function. As a consequence of the accompanying inflammatory joint disease, such patients often require surgery. Due to the protean organ-related consequences of these conditions, patients who suffer from chronic connective tissue disease are a highly challenging population in the perioperative context. This paper reviews the management of such patients in this clinical setting. PMID:22294961

Goodman, Susan M.; Figgie, Mark P.

2010-01-01

49

Lung function abnormalities in different connective tissue diseases  

Microsoft Academic Search

Summary  \\u000aLung volumes, forced expiratory flow-volume curves, diffusing capacity indexes, and arterial blood gases were measured in 72 non-smoking patients with various connective tissue diseases (13 with rheumatoid arthritis, 17 with systemic lupus erythematosus, 25 with progressive systemic sclerosis, 10 with primary Sjögren's syndrome, 4 with polymyositis, and 3 with mixed connective tissue disease). Small airways disease and a diffusion

C. Vitali; G. Viegi; S. Tassoni; A. Tavoni; P. Paoletti; E. Bibolotti; C. Ferri; S. Bombardieri

1986-01-01

50

Connective tissue disorders in patients with spontaneous intracranial hypotension  

Microsoft Academic Search

Objective: Spontaneous intracranial hypotension (SIH) is caused by spinal cerebrospinal fluid (CSF) leakage. An underlying connective tissue disorder has been hypothesized to cause dural weakness and predisposition to CSF leak. We conducted a case-controlled study to investigate the role of connective tissue disorders in SIH patients.Methods: We recruited 55 consecutive SIH patients (38 F, 17 M; mean age, 40.8 ±

Fang-Chun Liu; Jong-Ling Fuh; Yen-Feng Wang; Shuu-Jiun Wang

2011-01-01

51

Macrophage Turnover in Inflamed Connective Tissue  

Microsoft Academic Search

It has previously been shown that macrophages in various types of inflamed tissue proliferate, whereas macrophages on subcutaneously inserted glass cover slips showed little such activity. This discrepancy suggested that macrophage proliferation in inflammation might be a complex and variable process. The present investigation indicates that inflammatory macrophages that have entered the mitotic cycle fall into one of three categories;

G. B. Ryan; W. G. Spector

1970-01-01

52

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

PubMed Central

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

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

2015-01-01

53

FIBROBLAST CYTOSKELETAL REMODELING CONTRIBUTES TO CONNECTIVE TISSUE TENSION  

PubMed Central

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

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

2011-01-01

54

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

PubMed Central

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

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

2013-01-01

55

Quantification and molecular characterization of regulatory T cells in connective tissue diseases.  

PubMed

The aim of our study was to investigate and characterize regulatory T cells (Treg) in peripheral blood of patients with connective tissue diseases (Systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome, poly- and dermatomyositis) as compared with blood from healthy controls. Treg cells were quantified and phenotypically characterized by flow cytometry while the expression level of Foxp3 mRNA was evaluated by real time PCR. A reduced percentage of peripheral blood Treg cells was found in patients than in controls, irrespective of the type of connective tissue disease. Treg cells, especially those expressing one of the phenotypical markers, seemed to differ not only between patients and healthy controls but also among types of diseases. Additionally, the presence of autoantibodies as well as disease activity appeared to be correlated with particular Treg cell populations, especially those expressing one of the examined phenotypical markers. Correlations with therapy suggested that glucocorticoids plus antimalarial or other immunosuppressor drugs diminished the percentage of Treg cells, especially of those with memory phenotype. These findings indicated dysregulations at the level of Treg cells and suggested an involvement of these cells in the pathology of connective tissue diseases. Moreover, our data are in agreement with the suggestion that Treg cells could be therapeutic targets for some autoimmune diseases. PMID:18800250

Banica, Leontina; Besliu, Alina; Pistol, Gina; Stavaru, Crina; Ionescu, Ruxandra; Forsea, Ana-Maria; Tanaseanu, Cristina; Dumitrache, Sergiu; Otelea, Dan; Tamsulea, Isabela; Tanaseanu, Stefanita; Chitonu, Cristina; Paraschiv, Simona; Balteanu, Monica; Stefanescu, Maria; Matache, Cristiana

2009-01-01

56

Hypericin-mediated selective photomodification of connective tissues  

NASA Astrophysics Data System (ADS)

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.

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

2014-12-01

57

Reactions of connective tissue to mineral trioxide aggregate and amalgam.  

PubMed

The purpose of this study was to evaluate the subcutaneous connective tissue reactions to ProRoot, mineral trioxide aggregate (MTA; Dentsply), and Oralloy, high-copper amalgam (Coltene). These materials were placed in polyethylene tubes and implanted into dorsal connective tissue of Wistar albino rats, and tissue biopsies were collected and histologically examined 7, 15, 30, 60, and 90 days after the implantation procedure. The presence of inflammation, predominant cell type, calcification, and thickness of fibrous connective tissue were recorded. Scores were defined as follows: 0, none or few inflammatory cells, no reaction; 1, < 25 cells, mild reaction; 2, 25 to 125 cells, moderate reaction; 3, > or = 125 cells, severe reaction. Fibrous capsule was categorized as "thin" when thickness was < 150 microm and "thick" at > 150 microm. Necrosis and formation of calcification were recorded. Both materials were well tolerated by the tissues in a 90-day evaluation period. One notable finding is the presence of dystrophic calcification in connective tissue adjacent to MTA; this finding is consistent with the hypothesis of hard tissue induction by this material. PMID:14977305

Yaltirik, Mehmet; Ozbas, Hakan; Bilgic, Bilge; Issever, Halim

2004-02-01

58

SELF TOLERANCE AND LOCALIZED AUTOIMMUNITY Mouse Models of Autoimmune Disease that Suggest Tissue-specific Suppressor T CellsAre Involved In SelfTolerance  

Microsoft Academic Search

Organ-localizedautoimmune diseasessuch as thyroiditis(10),oophoritis(11, 12),gastritis (13),orchitis(8),and prostatitis (14)can be induced insome strains ofmice by thymectomy (Tx)'atthecriticalneonatalage withoutany additional treatment (15).In the presentexperiments,we studiedwhether or not active tissue-specific suppressorT cellsexistinnormal adultmice forthe maintenance of selftolerance. We used two mouse models, autoimmune prostatitisand gastritis .The prostateisa suitableorgan for such analysisbecause prostate- specificantigen(s)isprobably expressed in adult males,but not inneonatally orchitomized(Orx) males and females(14).Conversely,thestomach

OSAMU TAGUCHI; YASUAKI NISHIZUKA

59

Characteristics of mouse adipose tissue-derived stem cells and therapeutic comparisons between syngeneic and allogeneic adipose tissue-derived stem cell transplantation in experimental autoimmune thyroiditis.  

PubMed

Previously, we found that the intravenous administration of human adipose tissue-derived mesenchymal stem cells was a promising therapeutic option for autoimmune thyroiditis even when the cells were transplanted into a xenogeneic model without an immunosuppressant. Therefore, we explored the comparison between the therapeutic effects of syngeneic and allogeneic adipose tissue-derived stem cells on an experimental autoimmune thyroiditis mouse model. Experimental autoimmune thyroiditis was induced in C57BL/6 mice by immunization with porcine thyroglobulin. Adipose tissue-derived stem cells derived from C57BL/6 mice (syngeneic) or BALB/c mice (allogeneic) or saline as a vehicle control were administered intravenously four times weekly. Blood and tissue samples were collected 1 week after the last transplantation. Adipose tissue-derived stem cells from mice were able to differentiate into multiple lineages in vitro; however, mouse adipose tissue-derived stem cells did not have immunophenotypes identical to those from humans. Syngeneic and allogeneic administrations of adipose tissue-derived stem cells reduced thyroglobulin autoantibodies and the inflammatory immune response, protected against lymphocyte infiltration into the thyroid, and restored the Th1/Th2 balance without any adverse effects. However, different humoral immune responses were observed for infused cells from different stem cell sources. The strongest humoral immune response was induced by xenogeneic transplantation, followed by allogeneic and syngeneic administration, in that order. The stem cells were mostly found in the spleen, not the thyroid. This migration might be because the stem cells primarily function in systemic immune modulation, due to being given prior to disease induction. In this study, we confirmed that there were equal effects of adipose tissue-derived stem cells in treating autoimmune thyroiditis between syngeneic and allogeneic transplantations. PMID:23485102

Choi, Eun Wha; Shin, Il Seob; Park, So Young; Yoon, Eun Ji; Kang, Sung Keun; Ra, Jeong Chan; Hong, Sung Hwa

2014-01-01

60

Multiple Unilateral Zosteriform Connective Tissue Nevi on the Trunk  

PubMed Central

Connective tissue nevus is not a true tumor, but rather a hamartoma involving various components of connective tissue. It presents as a slow-growing, painless, flesh-colored, or pink nodule or plaque that is evident from childhood. While any region of the body may be affected, there is a predilection for the trunk and extremities. A 20-month-old girl presented with three ipsilateral confluent popular plaques with zosteriform distribution that had formed over the previous 17 months on the left chest and abdomen. The patient remained asymptomatic. Unlike all previously reported cases demonstrating a single lesion, we report a connective tissue nevi in a child who presented with multiple unilateral zosteriform lesions, an unusual pattern of distribution without evidence of tuberous sclerosis complex. PMID:22148061

Choi, Young Jun; Lee, Seung Jae; Choi, Chong Won; Kim, Won-Serk

2011-01-01

61

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

PubMed

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

Kapandji, A-I

2012-10-01

62

Antibodies to hnRNP core protein A1 in connective tissue diseases.  

PubMed

We investigated the specificity of circulating autoantibodies to a heterogeneous nuclear ribonuclear protein A1 (hnRNP A1), obtained by recombinant DNA technique, in different rheumatic diseases: systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), scleroderma, primary Sjogren's syndrome (SS), idiopathic Raynaud (IR), mixed connective tissue disease (MCTD), and healthy donors. All sera were tested by ELISA on hnRNP A1 protein. Positive values were obtained in 22% SLE, 19% scleroderma, 10% IR, 40% (2/5) MCTD, 5% SS, and 50% RA patients. The majority of patients reacted with the aminoterminal part (UP1) of hnRNP A1; however, some RA patients reacted also with the carboxy-terminal part that shows partial homology with keratin. Therefore, hnRNP A1 (UP1) can be considered a target of antinuclear autoimmunity in various rheumatic disorders. PMID:2745573

Astaldi Ricotti, G C; Bestagno, M; Cerino, A; Negri, C; Caporali, R; Cobianchi, F; Longhi, M; Maurizio Montecucco, C

1989-05-01

63

Bioreactors for Connective Tissue Engineering: Design and Monitoring Innovations  

NASA Astrophysics Data System (ADS)

The challenges for the tissue engineering of connective tissue lie in creating off-the-shelf tissue constructs which are capable of providing organs for transplantation. These strategies aim to grow a complex tissue with the appropri ate mechanical integrity necessary for functional load bearing. Monolayer culture systems lack correlation with the in vivo environment and the naturally occur ring cell phenotypes. Part of the development of more recent models is to create growth environments or bioreactors which enable three-dimensional culture. Evidence suggests that in order to grow functional load-bearing tissues in a bioreactor, the cells must experience mechanical loading stimuli similar to that experienced in vivo which sets out the requirements for mechanical loading bioreactors. An essential part of developing new bioreactors for tissue growth is identifying ways of routinely and continuously measuring neo-tissue formation and in order to fully identify the successful generation of a tissue implant, the appropriate on-line monitoring must be developed. New technologies are being developed to advance our efforts to grow tissue ex vivo. The bioreactor is a critical part of these develop ments in supporting growth of biological implants and combining this with new advances in the detection of tissue formation allows us to refine our protocols and move nearer to off-the-shelf implants for clinical applications.

Haj, A. J. El; Hampson, K.; Gogniat, G.

64

Diagnosis and Treatment of Connective Tissue Disease-Associated Interstitial Lung Disease  

PubMed Central

Interstitial lung disease (ILD) is one of the most serious pulmonary complications associated with connective tissue diseases (CTDs), resulting in significant morbidity and mortality. Although the various CTDs associated with ILD often are considered together because of their shared autoimmune nature, there are substantial differences in the clinical presentations and management of ILD in each specific CTD. This heterogeneity and the cross-disciplinary nature of care have complicated the conduct of prospective multicenter treatment trials and hindered our understanding of the development of ILD in patients with CTD. In this update, we present new information regarding the diagnosis and treatment of patients with ILD secondary to systemic sclerosis, rheumatoid arthritis, dermatomyositis and polymyositis, and Sjögren syndrome. We review information on risk factors for the development of ILD in the setting of CTD. Diagnostic criteria for CTD are presented as well as elements of the clinical evaluation that increase suspicion for CTD-ILD. We review the use of medications in the treatment of CTD-ILD. Although a large, randomized study has examined the impact of immunosuppressive therapy for ILD secondary to systemic sclerosis, additional studies are needed to determine optimal treatment strategies for each distinct form of CTD-ILD. Finally, we review new information regarding the subgroup of patients with ILD who meet some, but not all, diagnostic criteria for a CTD. A careful and systematic approach to diagnosis in patients with ILD may reveal an unrecognized CTD or evidence of autoimmunity in those previously believed to have idiopathic ILD. PMID:23460159

Strek, Mary E.

2013-01-01

65

[The Marfan syndrome and related connective tissue disorders].  

PubMed

The Marfan syndrome is an inherited disorder of the connective tissue which is mainly caused by a mutation in the fibrillin-1 gene. The defect in the connective tissue protein can lead to several organ dysfunctions. For the life expectancy, the cardiovascular aspect is of paramount importance. Patients with Marfan syndrome may develop aortic aneurysms and valvular heart defects. The risk of aortic aneurysms consists in the development of aortic dissection or rupture with their fatal consequences. Besides the cardiovascular manifestation, the skeletal and ocular system can also be affected. The skeletal manifestation is often characterised by long limbs, arachnodactyly, and abnormal joint flexibility along with other signs. Patients may also have dislocated lenses, ectasia of the dural sac, stretch marks, spontaneous pneumothorax, recurrent hernia, or a family history suspicious for Marfan. During the past years, other related connective tissue disorders with analogous organ manifestation have been described (e.g., Loeys-Dietz syndrome). In this article we present the basic knowledge about these connective tissue disorders, and we mention new insights in the recently explored pathophysiology of the disorder which is a possible target for future medical treatment options. Furthermore, recent new concepts for the prophylactic treatment of the aortic manifestation are explained. PMID:19554831

Siepe, Matthias; Löffelbein, Florian

2009-06-01

66

Metalloproteinase inhibitors and the prevention of connective tissue breakdown  

Microsoft Academic Search

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

T. E. Cawston

1996-01-01

67

Electron Microscopy: Attachment Sites between Connective Tissue Cells  

Microsoft Academic Search

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

Russell Ross; Theodore K. Greenlee Jr.

1966-01-01

68

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

Microsoft Academic Search

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

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

2000-01-01

69

Ultrastructure of vascular and connective tissue changes in primary syphilis  

Microsoft Academic Search

Electron microscopical studies of primary syphilitic lesions showed intensive changes in the capillaries in the form of endothelial proliferation and extensive infilitration of different cells in the surrounding connective tissue. The degenerative changes in axon terminals could explain the painless course of primary induration.

T Wrzolkowa; J Kozakiewicz

1980-01-01

70

Occult connective tissue diseases mimicking idiopathic interstitial pneumonias  

Microsoft Academic Search

In patients with interstitial lung disease (ILD), the diagnosis of idiopathic interstitial pneumonia is usually made after excluding, among other conditions, connective tissue diseases (CTDs). Although in most patients with a CTD and respiratory symptoms, the systemic nature of the disease is obvious, the ILD-related manifestations in CTDs may often dominate the clinical picture or precede systemic findings and thus

G. E. Tzelepis; S. P. Toya; H. M. Moutsopoulos

2008-01-01

71

Association of systemic and thyroid autoimmune diseases  

Microsoft Academic Search

Objective: There are few large cohort studies available on the association of systemic and thyroid autoimmune diseases. In this study,\\u000a we wished to determine the association of Hashimoto’s thyroiditis (HT) and Graves’ disease (GD) with systemic autoimmune diseases.\\u000a Methods: One thousand five hundred and seventeen patients with systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic\\u000a sclerosis (SSc), mixed connective tissue

Zoltán Szekanecz; Katalin Dankó; Emese Kiss; Nóra Anna Szabó; Gabriella Sz?cs; Margit Zeher; Gyula Szegedi; Gyula Bakó; László Czirják

2006-01-01

72

Sustained deep-tissue pain alters functional brain connectivity  

PubMed Central

Recent functional brain connectivity studies have contributed to our understanding of the neurocircuitry supporting pain perception. However, evoked-pain connectivity studies have employed cutaneous and/or brief stimuli, which induce sensations that differ appreciably from the clinical pain experience. Sustained myofascial pain evoked by pressure cuff affords an excellent opportunity to evaluate functional connectivity change to more clinically-relevant sustained deep-tissue pain. Connectivity in specific networks known to be modulated by evoked pain (sensorimotor, salience, dorsal attention, fronto-parietal control and default mode networks; SMN, SLN, DAN, FCN and DMN) was evaluated with functional-connectivity MRI, both at rest and during a sustained (6-minute) pain state in healthy adults. We found that pain was stable with no significant changes of subjects’ pain ratings over the stimulation period. Sustained pain reduced connectivity between the SMN and the contralateral leg primary sensorimotor (S1/M1) representation. Such SMN-S1/M1 connectivity decreases were also accompanied by and correlated with increased SLN-S1/M1 connectivity, suggesting recruitment of activated S1/M1 from SMN to SLN. Sustained pain also increased DAN connectivity to pain processing regions such as mid-cingulate cortex, posterior insula and putamen. Moreover, greater connectivity during pain between contralateral S1/M1 and posterior insula, thalamus, putamen, and amygdala, was associated with lower cuff pressures needed to reach the targeted pain sensation. These results demonstrate that sustained pain disrupts resting S1/M1 connectivity by shifting it to a network known to process stimulus salience. Furthermore, increased connectivity between S1/M1 and both sensory and affective processing areas may be an important contribution to inter-individual differences in pain sensitivity. PMID:23718988

Kim, Jieun; Loggia, Marco L.; Edwards, Robert; Wasan, Ajay D.; Gollub, Randy L.; Napadow, Vitaly

2013-01-01

73

Stress reactions in connective tissues: a molecular hypothesis.  

PubMed

The proper qualitative and quantitative stimuli necessary to maintain bone, cartilage, tendon, and ligament ability to bear load has yet to be completely elucidated. Substantially greater investigation of these requirements has been accomplished for muscle than for dense and ordinary connective tissues; inferential proposals from these muscle observations have been made regarding connective tissues. This hypothesis postulates there is a highly structured inter-relationship in terms of the homeostatic stimuli which are shared in common by these different tissues as suggested by the close anatomic and functional relationship they have evolved. The evolutionary influence of man's exercise patterns upon these stimuli, their mode of transduction into adaptive cellular response, and the vulnerability to over-use injury their loss creates is hypothesized. PMID:1787826

Gordon, G A

1991-11-01

74

Acute Fibrinous and Organizing Pneumonia and Undifferentiated Connective Tissue Disease: A Case Report  

PubMed Central

Acute fibrinous and organizing pneumonia (AFOP), recently described, is a histologic pattern characterized by the presence of fibrin “balls” within alveolar spaces. The term undifferentiated connective tissue disease (UCTD) is used to identify autoimmune systemic diseases that do not fulfill the criteria to be classified as a definitive connective tissue disease. The AFOP has never been reported in association with UCTD. The present reported case is a 39-year-old Caucasian, female with dry cough and progressive dyspnea. Eight months later, she was diagnosed with “organizing pneumonia” based on clinical history and radiologic images. She manifested Raynaud's Phenomenon, sicca syndrome, boot and gloves neuropathic pain, and previous hypothyroidism. Antinuclear antibody, rheumatoid factor, and specific autoantibodies were negative. Salivary gland biopsy and electroneuromyiography were normal. The capillaroscopy showed a “scleroderma” pattern with capillary deletion and ectasia. She experienced clinical and radiologic worsening. Despite being submitted to cyclophosphamide pulse, she developed hemorrhage and then died. Thoracotomy pulmonary specimen showed histological pattern of AFOP. This paper shows a rare association of AFOP with UCTD. PMID:22957292

Valim, Valéria; Rocha, Roberta Hora; Couto, Roberta Barcelos; Paixăo, Thaysa Simőes; Serrano, Érica Vieira

2012-01-01

75

Smooth Muscle-Mediated Connective Tissue Remodeling in Pulmonary Hypertension  

NASA Astrophysics Data System (ADS)

Abnormal accumulation of connective tissue in blood vessels contributes to alterations in vascular physiology associated with disease states such as hypertension and atherosclerosis. Elastin synthesis was studied in blood vessels from newborn calves with severe pulmonary hypertension induced by alveolar hypoxia in order to investigate the cellular stimuli that elicit changes in pulmonary arterial connective tissue production. A two- to fourfold increase in elastin production was observed in pulmonary artery tissue and medial smooth muscle cells from hypertensive calves. This stimulation of elastin production was accompanied by a corresponding increase in elastin messenger RNA consistent with regulation at the transcriptional level. Conditioned serum harvested from cultures of pulmonary artery smooth muscle cells isolated from hypertensive animals contained one or more low molecular weight elastogenic factors that stimulated the production of elastin in both fibroblasts and smooth muscle cells and altered the chemotactic responsiveness of fibroblasts to elastin peptides. These results suggest that connective tissue changes in the pulmonary vasculature in response to pulmonary hypertension are orchestrated by the medial smooth muscle cell through the generation of specific differentiation factors that alter both the secretory phenotype and responsive properties of surrounding cells.

Mecham, Robert P.; Whitehouse, Loren A.; Wrenn, David S.; Parks, William C.; Griffin, Gail L.; Senior, Robert M.; Crouch, Edmond C.; Stenmark, Kurt R.; Voelkel, Norbert F.

1987-07-01

76

Clinical Evaluation of Papilla Reconstruction Using Subepithelial Connective Tissue Graft  

PubMed Central

Objective: The aesthetics of the patient can be improved by surgical reconstruction of interdental papilla by using an advanced papillary flap interposed with subepithelial connective tissue graft. Materials and Methods: A total of fifteen sites from ten patients having black triangles/papilla recession in the maxillary anterior region were selected and subjected to presurgical evaluation. The sites were treated with interposed subepithelial connective tissue graft placed under a coronally advance flap. The integrity of the papilla was maintained by moving the whole of gingivopapillary unit coronally. The various parameters were analysed at different intervals. Results: There was a mean decrease in the papilla presence index score and distance from contact point to gingival margin, but it was statistically not significant. Also, there is increase in the width of the keratinized gingiva which was statistically highly significant. Conclusion: Advanced papillary flap with interposed sub–epithelial connective tissue graft can offer predictable results for the reconstruction of interdental papilla. If papilla loss occurs solely due to soft-tissue damage, reconstructive techniques can completely restore it; but if due to periodontal disease involving bone loss, reconstruction is generally incomplete and multiple surgical procedures may be required. PMID:25386529

Kaushik, Alka; PK, Pal; Chopra, Deepak; Chaurasia, Vishwajit Rampratap; Masamatti, Vinaykumar S; DK, Suresh; Babaji, Prashant

2014-01-01

77

Radiotherapy of spontaneous fibrous connective-tissue sarcomas in animals.  

PubMed

The clinical records and follow-up data obtained over 13 years on the results of radiotherapy of spontaneous fibrous connective-tissue sarcomas in dogs, cats, and horses were reviewed. The results obtained from the treatment of fibrosarcomas and sarcoids of horses indicated that radiation administered with 60Co is important in the medical and surgical management of these tumors. Fibrous connective-tissue sarcomas in horses were radioresponsive. When radiotherapy was applied postoperatively, the probability of a 2-year cure approached 50% for all prescribed radiation doses of less than 2,000 to greater than 4,000 rads. If radiation doses of 4,500-6,000 rads were used, a 2-year cure rate may approach or exceed 60%. PMID:1255767

Hilmas, D E; Gillette, E L

1976-02-01

78

Abnormalities of connective tissue components in lesional and non-lesional tissue of patients with pseudoxanthoma elasticum  

Microsoft Academic Search

Pseudoxanthoma elasticum (PXE) is a disorder of connective tissue in which abnormalities of elastic tissue and collagen are found. The purpose of this study was to examine the ultrastructure and distribution of connective tissue components in lesional and non-lesional skin of patients by means of indirect immunofluorescence, electron microscopy and indirect immunoelectron microscopy. Prominent abnormalities of elastic tissue were seen

M. Lebwohl; E. Schwartz; G. Lemlich; O. Lovelace; F. Shaikh-Bahai; R. Fleischmajer

1993-01-01

79

Mutations of activin-receptor-like kinase 1 ( ALK-1 ) are not found in patients with pulmonary hypertension and underlying connective tissue disease  

Microsoft Academic Search

Pulmonary arterial hypertension is a recognized clinical component of systemic autoimmune diseases, especially systemic sclerosis.\\u000a Mutations in the bone morphogenetic protein receptor 2 gene reported in sporadic and familial primary pulmonary arterial hypertension\\u000a have failed to be detected in patients with either scleroderma spectrum disease or underlying connective tissue diseases.\\u000a Activin receptor-like kinase 1 (ALK-1) gene has recently been linked

Albert Selva-O’Callaghan; Eva Balada; Silvia Serrano-Acedo; Carmen Pilar Simeon Aznar; Josep Ordi-Ros

2007-01-01

80

Aortic Connective Tissue in Ageing—A Biochemical Study  

Microsoft Academic Search

The biochemical analysis of samples of aortic connective tissue was carried out in 22 subjects from 9 to 84 years old.Aortic samples were taken at necropsy performed after sudden or, more often, traumatic death. The results suggest that aging of the aorta is accompanied by an increase both in collagen content and in total sugar content when expressed as mg\\/cm2

Lupo Andreotti; Alessandro Bussotti; Daniele Cammelli; Francesco di Giovine; Salvatore Sampognaro; Gaetana Sterrantino; Giuseppe Varcasia; Paolo Arcangeli

1985-01-01

81

Early Cellular Reactions in Mechanically Stimulated Gingival Connective Tissue  

Microsoft Academic Search

Aim: The aim of this study was to describe early cellular reactions occuring in mechnically stimulated gingival connective tissue. Material and Method: Elastic bands were inserted between the maxillary first and second molars of male rats aged 8 weeks, which were pulse-labeled with 3H-thymidine and subsequently killed in groups together with labeled control animals after periods of 1-168 hours. Autoradiographs

Andrej Zentner; Konstantinos Panagiotis; Thomas Heaney

2001-01-01

82

Chloroquine cardiotoxicity mimicking connective tissue disease heart involvement.  

PubMed

The authors report a case of rare chloroquine cardiotoxicity mimicking connective tissue disease heart involvement in a 56-year-old woman with mixed connective tissue disease (MCTD) manifested suddenly as third degree A-V block with QT(c) interval prolongation and short torsade de pointes runs ultimately degenerating into ventricular fibrillation. Immunological tests suggested an MCTD flare, implying that cardiac arrest had resulted from myocardial involvement by MCTD. However, QT(c) prolongation is not a characteristic of cardiomyopathy caused by connective tissue disease, unless anti-Ro/SSA positivity is present, but that was not the case. Therefore, looking for another cause of QT(c) prolongation the possibility of chloroquine cardiotoxicity emerged, which the patient had been receiving for almost two years in supramaximal doses. Biopsy of the deltoid muscle was performed, because in chloroquine toxicity, specific lesions are present both in the skeletal muscle and in the myocardium, and electron microscopy revealed the accumulation of cytoplasmic curvilinear bodies, which are specific to antimalarial-induced myocyte damage and are absent in all other muscle diseases, except neuronal ceroid lipofuscinosis. Thus, the diagnosis of chloroquine cardiotoxicity was established. It might be advisable to supplement the periodic ophthalmological examination, which is currently the only recommendation for patients on long-term chloroquine therapy, with ECG screening. PMID:23409733

Vereckei, András; Fazakas, Adám; Baló, Timea; Fekete, Béla; Molnár, Mária Judit; Karádi, István

2013-04-01

83

Occult connective tissue diseases mimicking idiopathic interstitial pneumonias.  

PubMed

In patients with interstitial lung disease (ILD), the diagnosis of idiopathic interstitial pneumonia is usually made after excluding, among other conditions, connective tissue diseases (CTDs). Although in most patients with a CTD and respiratory symptoms, the systemic nature of the disease is obvious, the ILD-related manifestations in CTDs may often dominate the clinical picture or precede systemic findings and thus mimic idiopathic interstitial pneumonia. With the exception of systemic lupus erythematosus, all CTDs may imitate chronic idiopathic interstitial pneumonias. In this setting, clues to an underlying CTD may be entirely absent or include subtle findings from various systems, including skin, vascular and musculoskeletal system or internal organs. Since nonspecific interstitial pneumonia is a relatively frequent histological pattern in CTDs, biopsy reports of nonspecific interstitial pneumonia should also prompt a search for an underlying CTD. Ultimately, diagnosis of a CTD requires confirmation with immunological testing; interpretation of the various laboratory tests should always be carried out in conjunction with clinical findings. The present article reviews specific clinical aspects of connective tissue disease-related interstitial lung disease that may help differentiate it from idiopathic interstitial pneumonia, especially when interstitial lung disease is the predominant or sole manifestation of an occult connective tissue disease. PMID:18166591

Tzelepis, G E; Toya, S P; Moutsopoulos, H M

2008-01-01

84

Gingival dimensions after root coverage with free connective tissue grafts.  

PubMed

Traumatic injury in the presence of a thin and narrow zone of gingival tissue may lead to gingival recession. Especially in class I and II recessions, root coverage may be accomplished with connective tissue grafts. In order to prevent recurrent recession, altering gingival dimensions width and thickness might be of advantage. In the present study, dimensions of gingiva were followed for 1 year after root coverage with connective tissue grafts. The study population consisted of 18 patients with a total of 28 class I or II recessions. Gingival width and depth of the recession were measured with a caliper, and thickness of the marginal tissue with an ultrasonic device. Periodontal probing depth was determined with a pressure-controlled electronic probe. Mean (+/-sd) recession depth at baseline was 3.1+/-1.4 mm. After 12 months, coverage amounted to 74+/-30%. Width of gingiva rose from 2.1+/-1.0 mm to 3.2+/-1.4 mm, whereas thickness was increased from 0.8+/-0.3 mm to 1.5+/-0.7 mm, on average. No significant alteration of periodontal probing depth was observed but a mean gain of clinical attachment of 1.7+/-1.1 mm was ascertained. In a multiple regression analysis, recession depth and presence of the recession in the maxilla, but not tooth type significantly influenced relative root coverage (R2=0.34, p<0.01). Attachment gain after surgery depended on baseline attachment loss and was negatively influenced by smoking. The present results point to the possibility of doubling gingival thickness after root coverage with connective tissue grafts. PMID:9650881

Müller, H P; Eger, T; Schorb, A

1998-05-01

85

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

Microsoft Academic Search

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

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

1996-01-01

86

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

E-print Network

Ontogenetic Changes in Fibrous Connective Tissue Organization in the Oval Squid, Sepioteuthis in the organization and volume fraction of collagenous connective tissues were examined in the mantle of Sepioteuthis, the organization of connective tissue fibers is crucial for providing structural reinforcement, controlling shape

Kier, William M.

87

The role of connective tissue growth factor in skeletal growth and development  

E-print Network

The role of connective tissue growth factor in skeletal growth and development Reem A. Kanaan1 Gloucestershire Royal Hospital, U.K. Source of support: Self financing Summary Connective tissue growth factor-61, CTGF, NOV family; CTGF ­ connective tissue growth factor; Cyr61/CCN1 ­ cysteine-rich 61; NOV/CCN3

88

The Arrangement and Function of Octopus Arm Musculature and Connective Tissue  

E-print Network

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 and connective tissue fibers surrounding a central axial nerve cord. Three primary muscle fiber orientations were

Kier, William M.

89

The Association Between Connective Tissue Laxity and the Risk of an Abdominal Aortic Aneurysm  

Microsoft Academic Search

Aims: to investigate whether connective tissue laxity is associated with abdominal aortic aneurysms (AAA). Methods: a nested case control study in a population-based screening programme. The presence of pes planus, scoliosis, pectus deformities, flexible auricular cartilages and Gorling's sign were combined with the Beighton joint mobility score to form a connective tissue laxity score. The association between connective tissue laxity

ABM Wilmink; CRG Quick; C Sff Hubbard; NE Day

2000-01-01

90

Connective Tissue Growth Factor: Expression in Human Skin In Vivo and Inhibition by Ultraviolet Irradiation  

Microsoft Academic Search

Connective tissue growth factor, which is induced by transforming growth factor ?, has been reported to mediate the stimulatory actions of transforming growth factor ? on type I procollagen synthesis. Connective tissue growth factor is expressed in fibrotic disease such as scleroderma, where it is believed to promote abnormal deposition of collagen. Connective tissue growth factor expression has not been

Taihao Quan; Tianyuan He; Sewon Kang; John J. Voorhees; Gary J. Fisher

2002-01-01

91

An ultrastructural study of connective tissue in mollusc integument: II. Gastropoda  

Microsoft Academic Search

We studied the ultrastructure of the subepidermal connective tissue (SEC) in different zones of the integument in terrestrial, marine and freshwater gastropods (eight species). In all cases, the SEC was a layer of loose connective tissue between the basal membrane (BM) of the epidermis and the connective tissue of the deeper muscle layers. It was of monotonous structure and not

A. Bairati; M. Comazzi; M. Gioria

2001-01-01

92

Sustained deep-tissue pain alters functional brain connectivity Jieun Kim a,  

E-print Network

Sustained deep-tissue pain alters functional brain connectivity Jieun Kim a, , Marco L. Loggia a connec- tivity change to more clinically relevant sustained deep-tissue pain. Connectivity in specific connectivity a b s t r a c t Recent functional brain connectivity studies have contributed to our understanding

Napadow, Vitaly

93

Connective Tissue Disease-associated Interstitial Lung Disease: A review  

PubMed Central

Interstitial lung disease (ILD) is commonly encountered in patients with connective tissue diseases (CTD). Besides the lung parenchyma, the airways, pulmonary vasculature and structures of the chest wall may all be involved, depending on the type of CTD. As a result of this so-called multi-compartment involvement, airflow limitation, pulmonary hypertension, vasculitis and extrapulmonary restriction can occur alongside fibro-inflammatory parenchymal abnormalities in CTD. Rheumatoid arthritis (RA), systemic sclerosis (SSc), poly-/dermatomyositis (PM/DM), Sjögren’s syndrome (SjS), systemic lupus erythematosus (SLE), and undifferentiated (UCTD) as well as mixed connective tissue disease (MCTD) can all be associated with the development of ILD. Non-specific interstitial pneumonia (NSIP) is the most commonly observed histopathological pattern in CTD-ILD, but other patterns including usual interstitial pneumonia (UIP), organizing pneumonia (OP), diffuse alveolar damage (DAD) and lymphocytic interstitial pneumonia (LIP) may occur. Although the majority of patients with CTD-ILD experience stable or slowly advancing ILD, a small yet significant group exhibits a more severe and progressive course. Randomized placebo-controlled trials evaluating the efficacy of immunomodulatory treatments have been conducted only in SSc-associated ILD. However, clinical experience suggests that a handful of immunosuppressive medications are potentially effective in a sizeable portion of patients with ILD caused by other CTDs. In this manuscript, we review the clinical characteristics and management of the most common CTD-ILDs. PMID:23125954

Gutsche, Markus; Rosen, Glenn D.; Swigris, Jeffrey J.

2012-01-01

94

Connective tissue disease-associated pulmonary arterial hypertension  

PubMed Central

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.

Howard, Luke S.

2015-01-01

95

Transitional Connective Tissue Diseases: Description of Four Cases.  

PubMed

The term overlap syndromes (OS) is used to define a group of disorders characterized by the presence, in the same patient, of clinical features typical for more than one definite connective tissue disease (CTD). To show that patients may not only have an overlap of two or more CTDs but may also change their disease phenotype from that of a definite CTD to another. Patients and methods Retrospective analysis of medical records of four patients with a disease duration of about thirty years and a transition from a well definite CTD into another. The first patient was diagnosed, at the beginning of the 1980s, as affected by diffuse cutaneous systemic sclerosis (dcSSc) and developed systemic lupus erythematosus (SLE) twenty-five years later. The second and the third patients were diagnosed with SLE at the beginning of their disease: the second patient developed, in the course of her disease, an overlap syndrome (OS) SSc/rheumatoid arthritis (RA) and the third SSc and finally microscopic polyangiitis (MPA). The fourth patient was diagnosed as primary Sjögren's syndrome (SS) then as rheumatoid arthritis (RA) and finally developed SLE. Patients may not only show an overlap of two or more CTDs but also a transition from a well definite CTD into another. We propose the term "transitional connective tissue diseases" (TCTDs) to define their disease. A higher number of patients may allow us to better identify this new subgroup of CTDs and probably, also, predictors of evolution. PMID:24720645

Susanna, Cappelli; Philippe, Guilpain; Randone Silvia, Bellando; Ginevra, Fiori; Francesca, Bartoli; Jelena, Blagojevic; Francesca, Nacci; Maria Letizia, Conforti; Francesca, Braschi; Loic, Guillevin; Cerinic Marco, Matucci

2014-02-28

96

Connective Tissue Disease-associated Interstitial Lung Disease: A review.  

PubMed

Interstitial lung disease (ILD) is commonly encountered in patients with connective tissue diseases (CTD). Besides the lung parenchyma, the airways, pulmonary vasculature and structures of the chest wall may all be involved, depending on the type of CTD. As a result of this so-called multi-compartment involvement, airflow limitation, pulmonary hypertension, vasculitis and extrapulmonary restriction can occur alongside fibro-inflammatory parenchymal abnormalities in CTD. Rheumatoid arthritis (RA), systemic sclerosis (SSc), poly-/dermatomyositis (PM/DM), Sjögren's syndrome (SjS), systemic lupus erythematosus (SLE), and undifferentiated (UCTD) as well as mixed connective tissue disease (MCTD) can all be associated with the development of ILD. Non-specific interstitial pneumonia (NSIP) is the most commonly observed histopathological pattern in CTD-ILD, but other patterns including usual interstitial pneumonia (UIP), organizing pneumonia (OP), diffuse alveolar damage (DAD) and lymphocytic interstitial pneumonia (LIP) may occur. Although the majority of patients with CTD-ILD experience stable or slowly advancing ILD, a small yet significant group exhibits a more severe and progressive course. Randomized placebo-controlled trials evaluating the efficacy of immunomodulatory treatments have been conducted only in SSc-associated ILD. However, clinical experience suggests that a handful of immunosuppressive medications are potentially effective in a sizeable portion of patients with ILD caused by other CTDs. In this manuscript, we review the clinical characteristics and management of the most common CTD-ILDs. PMID:23125954

Gutsche, Markus; Rosen, Glenn D; Swigris, Jeffrey J

2012-09-21

97

Cell-based and biomaterial approaches to connective tissue repair  

NASA Astrophysics Data System (ADS)

Connective tissue injuries of skin, tendon and ligament, heal by a reparative process in adults, filling the wound site with fibrotic, disorganized scar tissue that poorly reflects normal tissue architecture or function. Conversely, fetal skin and tendon have been shown to heal scarlessly. Complete regeneration is not intrinsically ubiquitous to all fetal tissues; fetal diaphragmatic and gastrointestinal injuries form scars. In vivo studies suggest that the presence of fetal fibroblasts is essential for scarless healing. In the orthopaedic setting, adult anterior cruciate ligament (ACL) heals poorly; however, little is known about the regenerative capacity of fetal ACL or fetal ACL fibroblasts. We characterized in vitro wound healing properties of fetal and adult ACL fibroblasts demonstrating that fetal ACL fibroblasts migrate faster and elaborate greater quantities of type I collagen, suggesting the healing potential of the fetal ACL may not be intrinsically poor. Similar to fetal ACL fibroblasts, fetal dermal fibroblasts also exhibit robust cellular properties. We investigated the age-dependent effects of dermal fibroblasts on tendon-to-bone healing in rat supraspinatus tendon injuries, a reparative injury model. We hypothesized delivery of fetal dermal fibroblasts would increase tissue organization and mechanical properties in comparison to adult dermal fibroblasts. However, at 1 and 8 weeks, the presence of dermal fibroblasts, either adult or fetal, had no significant effect on tissue histology or mechanical properties. There was a decreasing trend in cross-sectional area of repaired tendons treated with fetal dermal fibroblasts in comparison to adult, but this finding was not significant in comparison to controls. Finally, we synthesized a novel polysaccharide, methacrylated methylcellulose (MA-MC), and fabricated hydrogels using a well-established photopolymerization technique. We characterized the physical and mechanical properties of MA-MC hydrogels in vitro as well as in a subcutaneous mouse model. Stable MA-MC hydrogels, of varying weight percentages, demonstrated tunable swelling and mechanical properties in the absence of cytotoxic degradation products. In vivo, 6wt% MA-MC hydrogels maintained their shape and mechanical integrity while eliciting a minimal inflammatory response; highly desirable properties for soft tissue reconstruction. These cellulose-based photopolymerizable hydrogels can be further optimized for drug delivery and tissue engineering applications to enhance wound repair.

Stalling, Simone Suzette

98

Glutamic acid decarboxylase (anti-GAD) & tissue transglutaminase (anti-TTG) antibodies in patients with thyroid autoimmunity  

PubMed Central

Background & objectives: Several autoimmune disorders have been reported to be associated with autoimmune thyroiditis and may coexist with other organ-specific autoantibodies. The aim of the present study was to evaluate the presence of tissue transglutaminase (anti-TTG) and glutamic acid decarboxylase (anti-GAD) antibodies in patients suffering from autoimmune thyroiditis as diagnosed by anti-thyroid peroxidase (anti-TPO) antibodies, which may indicate high risk for developing celiac disease or type 1 diabetes mellitus. Methods: Five thousand children and 2800 adults were screening as part of a general health examination done on a voluntary basis in four different parts of Delhi. A total of 577 subjects positive for anti-TPO antibody constituted the cases. Equal number of age and sex matched anti-TPO antibody negative controls were randomly selected from the same cohort to form paired case control study. The cases and controls were further divided into two groups as follows: group-1 (children and adolescent <18 yr), group-2 (adults >18 yr). Serum samples of cases and controls were analysed for thyroid function test (FT3, FT4, and TSH), anti-TTG and anti-GAD antibodies. Results: A total of 1154 subjects (577 cases and 577 controls) were included in this study. Hypothyroidism was present in 40.2 per cent (232) cases compared to only 4.7 per cent (27) in controls (P<0.001). Anti-TTG and anti-GAD antibodies were present in 6.9 and 12.5 per cent subjects among cases compared to 3.5 per cent (P=0.015) and 4.3 per cent (P=0.001) in controls, respectively. Only anti-GAD antibody were significantly positive in cases among children and adolescents (P =0.0044) and adult (P=0.001) compared to controls. Levels of anti-TTG and anti-GAD antibodies increased with increasing titre of anti-TPO antibody. Interpretation & conclusions: Our findings showed high positivity of anti-GAD and anti-TTG antibodies among subjects with thyroid autoimmunity. It is, therefore, important to have high clinical index of suspicion for celiac disease or type 1 diabetes mellitus in patients with autoimmune thyroiditis. PMID:23481055

Marwaha, R.K.; Garg, M.K.; Tandon, N.; Kanwar, Ratnesh; Narang, A.; Sastry, A.; Saberwal, A.; Bhadra, Kuntal

2013-01-01

99

Chest High Resolution Computed Tomography Findings in Connective Tissue Diseases  

PubMed Central

Background Lung disorders are important for prognosis of connective tissue disease (CTD). Thus, chest radiography, High Resolution Computed Tomography (HRCT) of the chest and ultrasonic echocardiogram are suggested after the diagnosis of these conditions. The purpose of this study was to evaluate chest HRCT findings in patients with CTD. Materials and Methods In this descriptive cross-sectional study, we evaluated HRCT findings in patients with (CTD) hospitalized in Imam Reza Hospital in Mashhad from 2006 - 2011. Patients’ age, sex, type of rheumatic disease and HRCT results were collected and analyzed by SPSS version 16.0 software. Results Out of 75 patients (78.67% females, 21.33% males with a mean age of 41.6 years), 56% had respiratory symptoms. Scleroderma was the most common disease (38.6%) followed by rheumatoid arthritis (26.6%) and systemic lupus erythematosus (14.6%). Interstitial tissue involvement of the lung was the most frequent finding in patients with scleroderma, dermatomyositis, polymyositis and Sjogren's syndrome (48.3%, 57.1%, 60% and 66.7%, respectively). Pleural thickening was the most common finding in patients with rheumatoid arthritis (45%). Pleural effusion was the most frequent finding in patients with systemic lupus erythematosus (45.4%). Lymphadenopathy and bronchiectasis had the lowest prevalence (1.3%). Conclusion Our data shows that interstitial tissue involvement, pleural thickening and pleural effusion are common in patients with rheumatic diseases which is consistent with some previous studies. PMID:25191473

Farrokh, Donya; Javanbakht, Aida; Raufi, Elahe

2013-01-01

100

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

PubMed

Pulmonary complications are an important extra-articular feature of autoimmune rheumatic diseases and a major cause of mortality. The underlying pathogenesis probably involves multiple cellular compartments, including the epithelium, lung fibroblasts, and the innate and adaptive immune system. Heterogeneity in the extent and progression of lung fibrosis probably reflects differences in underlying pathogenic mechanisms. Growing understanding of the key pathogenic drivers of lung fibrosis might lead to the development of more effective targeted therapies to replicate the treatment advances in other aspects of these diseases. Interstitial lung disease (ILD) in connective tissue disease (CTD) is characterized using the classification of the idiopathic interstitial pneumonias. Systemic sclerosis is most frequently associated with ILD and, in most of these patients, ILD manifests as a histological pattern of nonspecific interstitial pneumonia. Conversely, in rheumatoid arthritis, the pattern of ILD is most often usual interstitial pneumonia. The key goals of clinical assessment of patients with both ILD and CTD are the detection of ILD and prognostic evaluation to determine which patients should be treated. Data from treatment trials in systemic sclerosis support the use of immunosuppressive therapy, with the treatment benefit largely relating to the prevention of progression of lung disease. PMID:25266451

Wells, Athol U; Denton, Christopher P

2014-12-01

101

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

PubMed

The extracellular matrix network of skeletal muscle and tendon connective tissue is primarily composed of collagen and connects the muscle contractile protein to the bones in the human body. The mechanical properties of the connective tissue are important for the effectiveness of which the muscle force is transformed into movement. Periods of unloading and exercise affect the synthesis rate of connective tissue collagen protein, whereas only sparse information exits regarding collagen protein degradation. It is likely, though, that changes in both collagen protein synthesis and degradation are required for remodeling of the connective tissue internal structure that ultimately results in altered mechanical properties of the connective tissue. Both unloading and exercise lead to increased production of growth factors and inflammatory mediators that are involved in connective tissue remodeling. Despite the fact that non-steroidal anti-inflammatory drugs seem to inhibit the healing process of connective tissue and the stimulating effect of exercise on connective tissue protein synthesis, these drugs are often consumed in relation to connective tissue injury and soreness. However, the potential effect of non-steroidal anti-inflammatory drugs on connective tissue needs further investigation. PMID:24195606

Dideriksen, Kasper

2014-04-01

102

Increases in circulating and lymphoid tissue interleukin-10 in autoimmune lymphoproliferative syndrome are associated with disease expression.  

PubMed

Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder in which genetic defects in proteins that mediate lymphocyte apoptosis, most often Fas, are associated with enlargement of lymph nodes and the spleen and a variety of autoimmune manifestations. Some patients with ALPS have relatives with these same apoptotic defects, however, who are clinically well. This study showed that the circulating levels of interleukin 10 (IL-10) were significantly higher (P <.001) in 21 patients with ALPS than in healthy controls. Moreover, the peripheral blood mononuclear cells (PBMCs) and lymphoid tissues of these patients with ALPS contained significantly higher levels of IL-10 messenger RNA (mRNA; P <.001 and P <.01, respectively). By fractionating PBMC populations, disproportionately high concentrations of IL-10 mRNA were found in the CD4(-)CD8(-) T-cell population, expansion of which is virtually pathognomonic for ALPS. Immunohistochemical staining showed intense IL-10 protein signals in lymph node regions known to contain CD4(-)CD8(-) T cells. Nonetheless, in vitro studies showed no influence of IL-10 on the survival of CD4(-)CD8(-) T cells. Overexpression of IL-10 in patients with inherited apoptotic defects is strongly associated with the overt manifestations of ALPS. PMID:11342444

Lopatin, U; Yao, X; Williams, R K; Bleesing, J J; Dale, J K; Wong, D; Teruya-Feldstein, J; Fritz, S; Morrow, M R; Fuss, I; Sneller, M C; Raffeld, M; Fleisher, T A; Puck, J M; Strober, W; Jaffe, E S; Straus, S E

2001-05-15

103

Skin involvement in systemic autoimmune diseases.  

PubMed

Autoimmune diseases present with varied and broad-ranging cutaneous manifestations. Connective tissue disorders have a plethora of skin manifestations such as rheumatoid nodules in rheumatoid arthritis, psoriatic plaques in psoriatic arthritis, acne and pustulosis in SAPHO syndrome, livedo reticularis and ulceration in antiphospholipid antibody syndrome and xerosis in Sjögren syndrome. Cutaneous manifestations of autoimmune vasculitides such as polyarteritis nodosa, Kawasaki disease, Henoch-Schönlein purpura, cryoglobulinemic vasculitis, Behcet disease, Wegener granulomatosis, microscopic polyangiitis and Churg-Strauss syndrome range from papules, subcutaneous nodules and livedo reticularis, to palpable purpura, hemorrhagic bulla and ulcerating lesions. Pathological skin manifestations in autoimmune endocrinopathies include pretibial myxedema/dermopathy in Graves' disease, diabetic dermopathy and necrobiosis lipoidica in type I autoimmune diabetes mellitus, candidiasis, ectodermal dysplasia, vitiligo and alopecia areata in APECED and uniform hyperpigmentation of the skin in Addison's disease. Autoimmune gastrointestinal disorders such as inflammatory bowel disease (with erythema nodosum), gluten-sensitive enteropathy (with dermatitis herpetiformis), autoimmune hepatitis and primary biliary cirrhosis (with jaundice and pruritus), hematologic/oncologic disorders such as acute and chronic graft-versus-host disease (with skin manifestations ranging from pruritic maculopapular eruptions and lichen planus-like lesions to generalized scleroderma), and paraneoplastic autoimmune dermatoses are discussed as well. PMID:18460895

Rashtak, Shadi; Pittelkow, Mark R

2008-01-01

104

Fibroblast spreading induced by connective tissue stretch involves intracellular redistribution of ?- and ?-actin  

Microsoft Academic Search

Mechanical stretching of connective tissue occurs with normal movement and postural changes, as well as treatments including physical therapy, massage and acupuncture. Connective tissue fibroblasts were recently shown to respond actively to short-term mechanical stretch (minutes to hours) with reversible cytoskeletal remodeling, characterized by extensive cell spreading and lamellipodia formation. In this study, we have examined the effect of tissue

Helene M. Langevin; Kirsten N. Storch; Marilyn J. Cipolla; Sheryl L. White; Thomas R. Buttolph; Douglas J. Taatjes

2006-01-01

105

Development of the connective tissue stroma in the fetal portion of the human placenta  

Microsoft Academic Search

The author studied the development of the connective tissues in the primary and secondary chorionic villi from the earliest stages to term. He found in the former that the reticular tissue was transformed quite early into loose connective tissue in which collagen fibers came to predominate. The stroma of the terminal villi retained its reticular nature much longer. Up to

V. P. Zhuk

1957-01-01

106

The expression of matrix metalloproteinases in placental tissue depends on the severity of undifferentiated connective tissue dysplasia.  

PubMed

Immunohistochemical study of MMP-2 and MMP-9 expression in placental tissue of pregnant patients with undifferentiated connective tissue dysplasia of different severity showed that more severe condition was associated with higher expression of these MMP, this underlying the development of pregnancy and labor complications. The most pronounced elevation of the studied MMP levels was found in the basal plate decidual cells in women with undifferentiated connective tissue dysplasia of more than 18 score. PMID:24319705

Dubova, E A; Klimantsev, I V; Pavlov, K A; Kulikova, G V; Kan, N E; Shchyogolev, A I; Sukhikh, G T

2013-11-01

107

Biomarkers in connective tissue disease-associated interstitial lung disease.  

PubMed

This article reviews major biomarkers in serum and bronchoalveolar lavage fluid (BALF) with respect to their diagnostic and prognostic value in connective tissue disease-associated interstitial lung disease (CTD-ILD). In some CTD such as systemic sclerosis (SSc), the incidence of ILD is up to two-third of patients, and currently ILD represents the leading cause of death in SSc. Because of the extremely variable incidence and outcome of ILD in CTD, progress in the discovery and validation of biomarkers for diagnosis, prognosis, patients' subtyping, response to treatment, or as surrogate endpoints in clinical trials is extremely important. In contrast to idiopathic interstitial pneumonias, autoantibodies play a crucial role as biomarkers in CTD-ILD because their presence is strictly linked to the pathogenesis and tissue damage. Patterns of autoantibodies, for instance, anticitrullinated peptide antibodies in rheumatoid arthritis or aminoacyl-tRNA synthetases (ARS) in polymyositis/dermatomyositis, have been found to correlate with the presence and occasionally with the course of ILD in CTD. Besides autoantibodies, an increase in serum or BALF of a biomarker of pulmonary origin may be able to predict or reflect the development of fibrosis, the impairment of lung function, and ideally also the prognosis. Promising biomarkers are lung epithelium-derived proteins such as KL-6 (Krebs von den Lungen-6), SP-D (surfactant protein-D), SP-A (surfactant protein-A), YKL-40 (chitinase-3-like protein 1 [CHI3L1] or cytokines such as CCL18 [chemokine (C-C) motif ligand 18]). In the future, genetic/epigenetic markers, such as human leukocyte antigen (HLA) haplotypes, single nucleotide polymorphisms, and micro-RNA, may help to identify subtypes of patients with different needs of management and treatment strategies. PMID:24668534

Bonella, Francesco; Costabel, Ulrich

2014-04-01

108

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

PubMed Central

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

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

2014-01-01

109

Progressive reactive lymphoid connective tissue disease and development of autoantibodies in scavenger receptor A5-deficient mice.  

PubMed

Scavenger receptor A5 (SCARA5) is a member of the class A scavenger receptors, with most similarity to SCARA1 (SR-A) and SCARA2 (MARCO), which are primarily expressed by macrophages and dendritic cells, in which they participate in clearance of various polyanionic macromolecules, pollution particles, and pathogens. The biological role of SCARA5 has been unknown. Herein, we show that SCARA5 is an endocytotic receptor whose ligand repertoire includes the typical scavenger receptor ligands, whole bacteria, and purified Gram-negative bacterial lipopolysaccharide. In contrast to expression of SCARA1 and SCARA2 in immune cells, SCARA5 is found in a subset of fibroblast-like cells in the interstitial stroma of most organs, with additional expression in the epithelial cells of testis and choroid plexus. SCARA5-null mice develop with age lymphoid cell accumulation in many organs, in particular the lungs, and show decreased endocytotic function in fibroblasts. Furthermore, about one-third of the mice develop antinuclear antibodies. These disturbances are reminiscent of those found in many human autoimmune connective tissue disorders, which suggests that defects in fibroblast SCARA5 can underlie some forms of autoimmune disease. PMID:23499552

Ojala, Juha Risto Matias; Pikkarainen, Timo; Elmberger, Göran; Tryggvason, Karl

2013-05-01

110

Fas and Fas Ligand Expressed on Cells of the Immune System, not on the Target Tissue, Control Induction of Experimental Autoimmune Uveitis  

Microsoft Academic Search

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

Jennifer L. Wahlsten; Heather L. Gitchell; Chi-Chao Chan; Barbara Wiggert; Rachel R. Caspi

111

Connective tissue growth factor is a substrate of ADAM28  

SciTech Connect

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.

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

112

Insights Into the Molecular Mechanism of Chronic Fibrosis: The Role of Connective Tissue Growth Factor in Scleroderma  

Microsoft Academic Search

Connective tissue growth factor (CCN2), a member of the CCN family of proteins, is a cysteine-rich matricellular protein. Connective tissue growth factor is not normally expressed in dermal fibroblasts unless induced. The most potent inducer of connective tissue growth factor thus far identified is transforming growth factor ?. Connective tissue growth factor, however, is constitutively overexpressed by fibroblasts present in

Andrew Leask; Christopher P. Denton; David J. Abraham

2004-01-01

113

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

E-print Network

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 ...

Fan, Vivian H. (Vivian Hanbing)

2006-01-01

114

Aging of connective tissues: experimental facts and theoretical considerations.  

PubMed

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

Labat-Robert, J; Robert, L

2014-01-01

115

Connective tissue growth factor induces cardiac hypertrophy through Akt signaling  

SciTech Connect

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.

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

116

Inhibition of rheumatoid arthritis by blocking connective tissue growth factor  

PubMed Central

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

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

2014-01-01

117

Angiotensin II Increases Connective Tissue Growth Factor in the Kidney  

PubMed Central

Connective tissue growth factor (CTGF) has been described as a novel fibrotic mediator. CTGF is overexpressed in several kidney diseases and is induced by different factors involved in renal injury. Angiotensin II (AngII) participates in the pathogenesis of kidney damage, contributing to fibrosis; however, whether AngII regulates CTGF in the kidney has not been explored. Systemic infusion of AngII into normal rats for 3 days increased renal CTGF mRNA and protein levels. At day 7, AngII-infused rats presented overexpression of CTGF in glomeruli, tubuli, and renal arteries, as well as tubular injury and elevated fibronectin deposition. Only treatment with an AT1 receptor antagonist, but not an AT2, diminished CTGF and fibronectin overexpression and ameliorated tubular damage. In rats with immune complex nephritis, renal overexpression of CTGF was diminished by the ACE inhibitor quinapril, correlated with a diminution in fibrosis. In cultured renal cells (mesangial and tubular epithelial cells) AngII, via AT1, increased CTGF mRNA and protein production, and a CTGF antisense oligonucleotide decreased AngII-induced fibronectin synthesis. Our data show that AngII regulates CTGF in the kidney and cultured in mesangial and tubular cells. This novel finding suggests that CTGF could be a mediator of the profibrogenic effects of AngII in the kidney. PMID:14578193

Rupérez, Monica; Ruiz-Ortega, Marta; Esteban, Vanesa; Lorenzo, Óscar; Mezzano, Sergio; Plaza, Juan Jose; Egido, Jesús

2003-01-01

118

Telomerase activity in connective tissue diseases: elevated in rheumatoid arthritis, but markedly decreased in systemic sclerosis  

Microsoft Academic Search

Telomerase is a reverse transcriptase enzyme contributing to the maintenance of the telomeric structure by adding telomere\\u000a repeat sequences to chromosomal ends, thus compensating for its shortening. Telomerase activity which is common in cancers\\u000a and human germ line tissue, may also be increased, although to a lesser extent, in systemic autoimmune diseases. We aimed\\u000a to evaluate telomerase activity in a

Figen Tarhan; Filiz Vural; Buket Kosova; Kenan Aksu; Ozgur Cogulu; Gokhan Keser; Cumhur Gündüz; Murat Tombuloglu; Gonca Oder; Emin Karaca; Eker Doganavsargil

2008-01-01

119

Connective tissue graft combined with autogenous bone graft in the treatment of peri-implant soft and hard tissue defect.  

PubMed

The use of dental implants to improve functional and esthetic demands of dentition has increased significantly over the past two decades. Soft and hard tissue management is one of the factors contributing to improved esthetic results. This report describes the correction of an esthetic problem in a single implant combined connective tissue graft and autogenous bone graft. Four months after the surgical procedure, it could be observed that the combination of connective tissue graft and autogenous bone graft resulted in the augmentation of hard and soft tissue in the peri-implant area with favorable esthetic outcomes. PMID:25279396

Deliberador, Tatiana Miranda; Vieira, Juliana Souza; Bonacin, Rodrigo; Storrer, Carmen L Mueller; Santos, Felipe Rychuv; Giovanini, Allan Fernando

2015-02-01

120

Distinct phenotypes in mixed connective tissue disease: subgroups and survival.  

PubMed

The aim of the present study was to assess the autoantibody profile, dominant clinical symptoms and cluster characteristics of different mixed connective tissue disease (MCTD phenotypes. Two-hundred-and-one patients with MCTD were followed-up longitudinally. Five clinical parameters, Raynaud's phenomenon, pulmonary artery hypertension (PAH), myositis, interstitial lung disease (ILD), erosive arthritis and five auto-antibodies besides anti-U1RNP, antiendothelial cell antibodies (AECA), anti-CCP, anti-cardiolipin (anti-CL), anti-SSA/SSB and IgM rheumatoid factor (RF) were selected for cluster analysis. The mean age of patients was 52.9 ± 12.4 years and the mean follow-up of the disease was 12.5 ± 7.2 years. Patients were classified into three cluster groups. Cluster 1 with 77 patients, cluster 2 with 79 patients and cluster 3 with 45 patients. In cluster 1 the prevalence of PAH (55.8%; p < 0.001), Raynaud's phenomenon (92.2%; p < 0.001) and livedo reticularis (24.6%, p < 0.001) was significantly greater than in cluster 2 and 3. In cluster 2, the incidence of ILD (98.7%; p < 0.001), myositis (77.2%; p < 0.001), and esophageal dysmotility (89.8%; p < 0.001) was significantly greater than that in cluster 1 and 3. In cluster 3, anti-CCP antibodies were present in 31 of 45 patients (68.8%) with erosions. Anti-CCP antibodies were present in 37 of 42 patients (88.0%) with erosions. PAH, angina, venous thrombosis was observed in cluster 1 and pulmonary fibrosis in cluster 2, musculosceletal damage, gastrointestinal symptoms and osteoporotic fractures were most frequent in cluster 3. Cumulative survival assessment indicated cluster 1 patients having the worst prognosis. Cluster analysis is valuable to differentiate among various subsets of MCTD and useful prognostic factor regarding the disease course. PMID:22864236

Szodoray, P; Hajas, A; Kardos, L; Dezso, B; Soos, G; Zold, E; Vegh, J; Csipo, I; Nakken, B; Zeher, M; Szegedi, G; Bodolay, E

2012-11-01

121

Comparison of human adult stem cells from adipose tissue and bone marrow in the treatment of experimental autoimmune encephalomyelitis  

PubMed Central

Introduction While administration of ex vivo culture-expanded stem cells has been used to study immunosuppressive mechanisms in multiple models of autoimmune diseases, less is known about the uncultured, nonexpanded stromal vascular fraction (SVF)-based therapy. The SVF is composed of a heterogeneous population of cells and has been used clinically to treat acute and chronic diseases, alleviating symptoms in a range of tissues and organs. Methods In this study, the ability of human SVF cells was compared with culture-expanded adipose stem cells (ASCs) and bone-derived marrow stromal cells (BMSCs) as a treatment of myelin oligodendrocyte glycoprotein (35–55)-induced experimental autoimmune encephalitis in C57Bl/6J mice, a well-studied multiple sclerosis model (MS). A total of 1?×?106 BMSCs, ASCs, or SVF cells were administered intraperitoneally concomitantly with the induction of disease. Mice were monitored daily for clinical signs of disease by three independent, blinded investigators and rated on a scale of 0 to 5. Spinal cords were obtained after euthanasia at day 30 and processed for histological staining using luxol fast blue, toluidine blue, and hematoxylin and eosin to measure myelin and infiltrating immune cells. Blood was collected from mice at day 30 and analyzed by enzyme-linked immunosorbent assay to measure serum levels of inflammatory cytokines. Results The data indicate that intraperitoneal administration of all cell types significantly ameliorates the severity of disease. Furthermore, the data also demonstrate, for the first time, that the SVF was as effective as the more commonly cultured BMSCs and ASCs in an MS model. All cell therapies also demonstrated a similar reduction in tissue damage, inflammatory infiltrates, and sera levels of IFN? and IL-12. While IFN? levels were reduced to comparable levels between treatment groups, levels of IL-12 were significantly lower in SVF-treated than BMSC-treated or ASC-treated mice. Conclusions Based on these data, it is evident that SVF cells have relevant therapeutic potential in an animal model of chronic MS and might represent a valuable tool for stem cell-based therapy in chronic inflammatory disease of the central nervous system. SVF offers advantages of direct and rapid isolation procedure in a xenobiotic-free environment. PMID:24405805

2014-01-01

122

Loss of the lupus autoantigen Ro52/Trim21 induces tissue inflammation and systemic autoimmunity by disregulating the IL-23–Th17 pathway  

PubMed Central

Ro52/Trim21 is targeted as an autoantigen in systemic lupus erythematosus and Sjögren's syndrome. Polymorphisms in the Ro52 gene have been linked to these autoimmune conditions, but the molecular mechanism by which Ro52 may promote development of systemic autoimmune diseases has not been explored. To address this issue, we generated Ro52-null mice (Ro52?/?), which appear phenotypically normal if left unmanipulated. However, Ro52?/? mice develop severe dermatitis extending from the site of tissue injury induced by ear tags. The affected mice further develop several signs of systemic lupus with hypergammaglobulinemia, autoantibodies to DNA, proteinuria, and kidney pathology. Ro52, which was recently identified as an E3 ligase, mediates ubiquitination of several members of the interferon regulatory factor (IRF) family, and the Ro52-deficient mice have an enhanced production of proinflammatory cytokines that are regulated by the IRF transcription factors, including cytokines involved in the Th17 pathway (interleukin [IL] 6, IL-12/IL-23p40, and IL-17). Loss of IL-23/IL-17 by genetic deletion of IL-23/p19 in the Ro52?/? mice conferred protection from skin disease and systemic autoimmunity. These data reveal that the lupus-associated Ro52 protein is an important negative regulator of proinflammatory cytokine production, and they provide a mechanism by which a defective Ro52 function can lead to tissue inflammation and systemic autoimmunity through the IL-23–Th17 pathway. PMID:19635858

Espinosa, Alexander; Dardalhon, Valerie; Brauner, Susanna; Ambrosi, Aurelie; Higgs, Rowan; Quintana, Fransisco J.; Sjöstrand, Maria; Eloranta, Maija-Leena; Ní Gabhann, Joan; Winqvist, Ola; Sundelin, Birgitta; Jefferies, Caroline A.; Rozell, Björn; Kuchroo, Vijay K.

2009-01-01

123

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

PubMed Central

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

2011-01-01

124

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

Microsoft Academic Search

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

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

1996-01-01

125

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

NASA Technical Reports Server (NTRS)

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.

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

1994-01-01

126

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

Microsoft Academic Search

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

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

1985-01-01

127

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

PubMed Central

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

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

2012-01-01

128

Structural and functional peculiarities of mast cells in undifferentiated connective tissue dysplasia.  

PubMed

We performed an immunomorphological study of mast cells from undamaged skin in women with phenotypical evidence of undifferentiated connective tissue dysplasia syndrome, patients of cosmetological clinics. It was found that the numerical density of mast cells containing chymase granules in this condition 1.7-fold surpassed the corresponding parameter in patients without signs of connective tissue dysplasia syndrome, which probably was a result of compensatory and adaptive reaction aimed at activation of the synthesis of the connective tissue extracellular matrix components. It was hypothesized that increased content of chymase-positive mast cells in the skin of patients with connective tissue dysplasia syndrome contributed to the formation of associated arterial hypertension. PMID:22235414

Luzgina, N G; Potapova, O V; Shkurupiy, V A

2011-04-01

129

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

Microsoft Academic Search

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

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

1985-01-01

130

Mixed connective tissue disease presenting as a peculiar myositis with poor muscle regeneration  

Microsoft Academic Search

Mixed connective tissue disease (MCTD) is a rheumatological disease which has to be distinguished from other entities causing\\u000a inflammatory myopathy. The usual clinical presentation of inflammatory myopathy associated with connective tissue disease\\u000a is not different from isolated polymyositis or dermatomyositis, i.e., subacute onset of proximal weakness affecting both upper\\u000a and lower girdle with high serum CK level. Here we report

Giorgio Tasca; Massimiliano Mirabella; Alfredo Berrettini; Mauro Monforte; Pietro Attilio Tonali; Enzo Ricci

2011-01-01

131

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

Microsoft Academic Search

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

Flavia V Castelino; John Varga

2010-01-01

132

INTRODUCTION Articular cartilage is the dense connective tissue that functions  

E-print Network

collagen fibril network enmeshed in a gel of highly charged proteogly- can (PG) molecules. The composition and architecture of the matrix (Maroudas, 1979) and the tissue's high water content (70-80% of wet weight) enable was sig- nificantly affected by the presence or absence of matrix, as were the physical properties

Buschmann, Michael

133

Metals and kidney autoimmunity.  

PubMed Central

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

Bigazzi, P E

1999-01-01

134

Effects of microgravity on rat bone, cartlage and connective tissues  

NASA Technical Reports Server (NTRS)

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.

Doty, S.

1990-01-01

135

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

PubMed

We aimed to assess the frequency of connective tissue abnormalities among patients with cerebrospinal fluid (CSF) leaks in a prospective study using a large cohort of patients. We enrolled a consecutive group of 50 patients, referred for consultation because of CSF leak. All patients have been carefully examined for the presence of connective tissue abnormalities, and based on findings, patients underwent genetic testing. Ancillary diagnostic studies included echocardiography, eye exam, and histopathological examinations of skin and dura biopsies in selected patients. We identified nine patients with heritable connective tissue disorders, including Marfan syndrome, Ehlers-Danlos syndrome and other unclassified forms. In seven patients, spontaneous CSF leak was the first noted manifestation of the genetic disorder. We conclude that spontaneous CSF leaks are associated with a spectrum of connective tissue abnormalities and may be the first noted clinical presentation of the genetic disorder. We propose that there is a clinical basis for considering spontaneous CSF leak as a clinical manifestation of heritable connective tissue disorders, and we suggest that patients with CSF leaks should be screened for connective tissue and vascular abnormalities. PMID:22929030

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

2013-04-01

136

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

PubMed Central

We aimed to assess the frequency of connective tissue abnormalities among patients with cerebrospinal fluid (CSF) leaks in a prospective study using a large cohort of patients. We enrolled a consecutive group of 50 patients, referred for consultation because of CSF leak. All patients have been carefully examined for the presence of connective tissue abnormalities, and based on findings, patients underwent genetic testing. Ancillary diagnostic studies included echocardiography, eye exam, and histopathological examinations of skin and dura biopsies in selected patients. We identified nine patients with heritable connective tissue disorders, including Marfan syndrome, Ehlers–Danlos syndrome and other unclassified forms. In seven patients, spontaneous CSF leak was the first noted manifestation of the genetic disorder. We conclude that spontaneous CSF leaks are associated with a spectrum of connective tissue abnormalities and may be the first noted clinical presentation of the genetic disorder. We propose that there is a clinical basis for considering spontaneous CSF leak as a clinical manifestation of heritable connective tissue disorders, and we suggest that patients with CSF leaks should be screened for connective tissue and vascular abnormalities. PMID:22929030

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

2013-01-01

137

Connective Tissue Growth Factor Is Crucial to Inducing a Profibrotic Environment in \\  

Microsoft Academic Search

The individual susceptibility to pulmonary fibrosis (PF) remains a mystery, suggesting a role for genetic predisposition. The patho- genesis of PF involves a multitude of factors mediating crosstalk between various tissue components. Some factors, such as trans- forming growth factor , are recognized as key elements in the process, whereas the role of others, such as connective tissue growth factor

Philippe Bonniaud; Gail Martin; Peter J. Margetts; Kjetil Ask; Jennifer Robertson; Jack Gauldie; Martin Kolb

2004-01-01

138

Biochemical Analysis of Dermal Connective Tissue in Subjects Affected by Primary Uncomplicated Varicose Veins  

Microsoft Academic Search

Biochemical analysis of dermal connective tissue was carried out in 14 sub jects affected by primary uncomplicated varicose veins and 14 controls. Skin samples were taken, according to fixed criteria, from operation pieces of total mastectomy for breast cancer.The results suggest that the dermal tissue in these subjects is just thinner than that of controls, confirming previous similar clinical findings.The

Lupo Andreotti; Daniele Cammelli; Salvatore Sampognaro; Andrea Allori; Daniele Baldoni; Alessandro Bussotti; Paolo Cortini; Francesco Di Giovine; Gaetana Sterrantino

1985-01-01

139

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

Microsoft Academic Search

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

Andrew Leask; Alan Holmes; David J. Abraham

2002-01-01

140

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

Microsoft Academic Search

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

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

1995-01-01

141

Quantitative light and electron microscopical studies of the epithelial-connective tissue junction in intraoral mucosae.  

PubMed

The present study was designed to clarify the morphological nature of epithelial-connective tissue attachment by quantitative comparison of palatal and buccal mucosae. Tissue samples were obtained from ferrets and, following a strict sampling regime, sections were obtained for quantitative light and electron microscopy. Electron micrographs from the epithelial-connective tissue junction were subjected to analysis by serological intersection counting. Quantitative results show that palatal epithelium has a comparatively convoluted interface, and is twice as thick as buccal epithelium. Stereological data are presented for relative surface area of basal plasma membrane occupied by hemidesmosomes, mean hemidesmosomal diameter and numerical density of hemidesmosomes per unit area of basal plasma membrane. Larger hemidesmosomes are found in the palatal epithelium. Results suggest that a prominent rete-ridge pattern, as seen in the palatal epithelium, along with a greater specialized surface for adhesion, may be responsible for providing epithelial-connective tissue stability in regions subjected to high mechanical stress. PMID:7143437

Bale, E; White, F H

1982-10-01

142

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

PubMed Central

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

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

2014-01-01

143

Autoantibodies specific for apoptotic U1-70K are superior serological markers for mixed connective tissue disease.  

PubMed

Modifications occurring on autoantigens during cell death have been proposed to have a role in the initiation of autoimmune diseases. Patients suffering from mixed connective tissue disease (MCTD) produce autoantibodies directed to U1 small nuclear ribonucleoprotein (snRNP), and antibodies against a 70 kDa protein component, the U1-70K (70K) protein, are the most prominent. During apoptosis, 70K is cleaved by caspase-3 to a 40 kDa product, which remains associated with the complex. Autoantibodies preferentially recognizing the apoptotic form of 70K have been described previously, and an apoptosis-specific epitope on 70K has been identified. This study shows that 29 of 53 (54%) MCTD sera preferentially recognize the apoptotic form of 70K over intact 70K. Moreover, we show that antibodies directed to an apoptosis-specific epitope on 70K are more specifically associated with MCTD than other anti-70K antibodies, suggesting that apoptotic 70K is a better antigen for the detection of these antibodies in MCTD patients. Longitudinal analysis of 12 MCTD patients showed in several patients that early sera are relatively enriched with antibodies recognizing an apoptosis-specific epitope, and that the levels of these apoptosis-specific antibodies decrease in time. These findings indicate that the early detection of apoptotic 70K is of considerable interest for anti-U1 snRNP-positive patients. PMID:15743477

Hof, Daniëlle; Cheung, Kalok; de Rooij, Dirk-Jan R A M; van den Hoogen, Frank H; Pruijn, Ger J M; van Venrooij, Walther J; Raats, Jos M H

2005-01-01

144

Saudi Guidelines on the Diagnosis and Treatment of Pulmonary Hypertension: Pulmonary arterial hypertension associated with connective tissue diseases.  

PubMed

The explosive growth of medical literature on pulmonary hypertension (PH) has led to a steady increase in awareness of this disease within the medical community during the past decade. The recent revision of the classification of PH is presented in in the main guidelines. Group 1 PH or pulmonary arterial hypertension (PAH) is a heterogeneous group and includes PH due to inheritable, drug-induced, and toxin-induced causes and to such underlying systemic causes as connective tissue diseases, human immunodeficiency viral infection, portal hypertension, congenital heart disease, and schistosomiasis. Systemic sclerosis (SSc) is an autoimmune multisystem disorder, which affects over 240 persons per million in the United States.[1] Its manifestations are not confined to the skin but may also involve the lungs, kidneys, peripheral circulation, musculoskeletal system, gastrointestinal tract, and heart. The outcome of PAH associated with SSc is worse when compared to other subtypes of PAH. In this review, we summarize available information about the pulmonary vascular and cardiac manifestations of SSc with special emphasis on their prognostic implications as well as the peculiarity of their detection. PMID:25076994

Boueiz, Adel; Hassoun, Paul M

2014-07-01

145

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

PubMed

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

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

2014-11-15

146

Cells of the connective tissue differentiate and migrate into pollen sacs  

NASA Astrophysics Data System (ADS)

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.

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

2002-01-01

147

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

PubMed Central

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

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

2009-01-01

148

Pathophysiological model for chronic low back pain integrating connective tissue and nervous system mechanisms.  

PubMed

Although chronic low back pain (cLBP) is increasingly recognized as a complex syndrome with multifactorial etiology, the pathogenic mechanisms leading to the development of chronic pain in this condition remain poorly understood. This article presents a new, testable pathophysiological model integrating connective tissue plasticity mechanisms with several well-developed areas of research on cLBP (pain psychology, postural control, neuroplasticity). We hypothesize that pain-related fear leads to a cycle of decreased movement, connective tissue remodeling, inflammation, nervous system sensitization and further decreased mobility. In addition to providing a new, testable framework for future mechanistic studies of cLBP, the integration of connective tissue and nervous system plasticity into the model will potentially illuminate the mechanisms of a variety of treatments that may reverse these abnormalities by applying mechanical forces to soft tissues (e.g. physical therapy, massage, chiropractic manipulation, acupuncture), by changing specific movement patterns (e.g. movement therapies, yoga) or more generally by increasing activity levels (e.g. recreational exercise). Non-invasive measures of connective tissue remodeling may eventually become important tools to evaluate and follow patients with cLBP in research and clinical practice. An integrative mechanistic model incorporating behavioral and structural aspects of cLBP will strengthen the rationale for a multidisciplinary treatment approach including direct mechanical tissue stimulation, movement reeducation, psychosocial intervention and pharmacological treatment to address this common and debilitating condition. PMID:16919887

Langevin, Helene M; Sherman, Karen J

2007-01-01

149

Recurrent Compartment Syndrome in a Patient with Clinical Features of a Connective Tissue Disorder  

PubMed Central

Arterial complications are common in vascular type Ehlers-Danlos Syndrome (EDS), accounting for 66% of first complications. Several cases in the literature have documented acute compartment syndrome (ACS) following vascular rupture in vascular type EDS. Other disorders of connective tissue have also demonstrated vascular fragility, leading to arterial aneurysm and rupture, but there have been no documented cases of ACS. Here, we report on a female patient with a history of recurrent compartment syndrome who exhibits some clinical findings seen in hypermobile and vascular EDS; however she does not meet clinical and molecular diagnostic criteria for either of them. We further review the literature on ACS in heritable connective tissue disorders and suggest that compartment syndrome may rarely complicate other heritable disorders of connective tissue. PMID:23633393

Barajas, Brenda D; Sun, Angela; Rimoin, David L; Reinstein, Eyal

2013-01-01

150

Recurrent compartment syndrome in a patient with clinical features of a connective tissue disorder.  

PubMed

Arterial complications are common in vascular type Ehlers-Danlos syndrome (EDS), accounting for 66% of first complications. Several cases in the literature have documented acute compartment syndrome (ACS) following vascular rupture in vascular type EDS. Other disorders of connective tissue have also demonstrated vascular fragility, leading to arterial aneurysm and rupture, but there have been no documented cases of ACS. Here, we report on a female patient with a history of recurrent compartment syndrome who exhibits some clinical findings seen in hypermobile and vascular EDS; however she does not meet clinical and molecular diagnostic criteria for either of them. We further review the literature on ACS in heritable connective tissue disorders and suggest that compartment syndrome may rarely complicate other heritable disorders of connective tissue. PMID:23633393

Barajas, Brenda D; Sun, Angela; Rimoin, David L; Reinstein, Eyal

2013-06-01

151

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

SciTech Connect

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.

Schwarz, Richard I. (Oakland, CA)

2002-08-13

152

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

PubMed Central

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

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

2011-01-01

153

THE ROLE OF THE CONNECTIVE TISSUE GROUND SUBSTANCES (MUCOPOLYSACCHARIDES) IN ALLERGIC INJURY  

PubMed Central

The basic histologic reactions of the classic allergic diseases and of several systemic diseases in which allergic mechanisms appear to operate are described and illustrated. Particular attention is drawn to the ground substances—mucopolysaccharides—which constitute important elements of connective tissue and vascular structure. The intimate locus of the allergic reaction appears to be in and to involve a swelling of such substances. It is suggested that antibodies (and possibly antigens) may be attached to these mucinous ground substances of the connective tissues. ImagesABCDEFGHIJKL PMID:14886731

Rinehart, James F.

1951-01-01

154

Foreign Body in the Oral Cavity Mimicking a Benign Connective Tissue Tumor  

PubMed Central

Foreign bodies may be embedded in the oral cavity either by traumatic injury or iatrogenically. The commonly encountered iatrogenic foreign bodies are restorative materials like amalgam, obturation materials, broken instruments, needles, and impression materials. This paper describes an asymptomatic presentation of a foreign body in the oral mucosa which clinically appeared like a benign connective tissue tumor. PMID:23634307

Ram, Saravanan; Sedghizadeh, Parish P.

2013-01-01

155

Doppler-Echo Evaluation of Left Ventricular Diastolic Filling in Patients with Mixed Connective Tissue Disease  

Microsoft Academic Search

Left ventricular diastolic function was assessed in 17 patients (2 males and 15 females; mean age 44 ± 9 years) with mixed connective tissue disease (MCTD) and 18 sex-and age-matched healthy control subjects (2 males and 16 females; mean age 44 ± 8 years) by means of M-mode and pulsed Doppler echocardiography. None had clinical evidence of overt myocardial disease

Wing-Hung Leung; Kee-Lam Wong; Chu-Pak Lau; Cheuk-Kit Wong; Chun-Ho Cheng; Yau-Ting Tai

1990-01-01

156

Tetracyclines Inhibit Connective Tissue Breakdown: New Therapeutic Implications for an Old Family of Drugs  

Microsoft Academic Search

Tetracyclines have long been considered useful adjuncts in peridontal therapy based on their antimicrobial efficacy against putative periodontopathogens. However, recently these drugs were found to inhibit mammalian collagenases and several other matrix metalloproteinases (MMPs) by a mechanism independent of their antimicrobial activity. Evidence is presented that this property may be therapeutically useful in retarding pathologic connective tissue breakdown, including bone

Lorne M. Golub; N. S. Ramamurthy; Thomas F. McNamara; Robert A. Greenwald; Barry R. Rifkin

1991-01-01

157

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

NASA Technical Reports Server (NTRS)

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.

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

1995-01-01

158

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

Microsoft Academic Search

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

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

1984-01-01

159

Tetracyclines Inhibit Connective Tissue Breakdown by Multiple Non-Antimicrobial Mechanisms  

Microsoft Academic Search

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

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

1998-01-01

160

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

Microsoft Academic Search

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

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

1996-01-01

161

Angiotensin II Induces Connective Tissue Growth Factor Gene Expression via Calcineurin-Dependent Pathways  

Microsoft Academic Search

Connective tissue growth factor (CTGF) is a polypep- tide implicated in the extracellular matrix synthesis. Previous studies have provided evidence that angio- tensin II (Ang II) promotes collagen synthesis and regulates collagen degradation. We investigated whether or not CTGF mediates the profibrotic effects of Ang II in the heart and kidneys and the role of calcineurin-dependent pathways in CTGF gene

Piet Finckenberg; Kaija Inkinen; Juhani Ahonen; Saara Merasto; Marjut Louhelainen; Heikki Vapaatalo; Dominik Müller; Detlev Ganten; Friedrich Luft; Eero Mervaala

2003-01-01

162

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

Microsoft Academic Search

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

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

2003-01-01

163

Connective Tissue Growth Factor Is a Mediator of Angiotensin II-Induced Fibrosis  

Microsoft Academic Search

Background—Angiotensin II (Ang II) participates in the development of fibrosis during vascular damage. Connective tissue growth factor (CTGF) is a novel fibrotic mediator. However, the potential link between CTGF and Ang II has not been investigated. Methods and Results—In vivo Ang II effects were studied by systemic infusion into normal rats to evaluate CTGF and extracellular matrix protein (ECM) expression

Mónica Rupérez; Óscar Lorenzo; Luis Miguel Blanco-Colio; Vanesa Esteban; Jesús Egido; Marta Ruiz-Ortega

164

Effect of Ticlopidine on Platelet-Derived Microparticles in Patients with Connective Tissue Diseases  

Microsoft Academic Search

We evaluated the plasma concentrations of platelet activation markers and platelet-derived microparticles (PMP) in patients with connective tissue diseases complaining of peripheral circulation disorders (n = 16) and studied the effect of ticlopidine hydrochloride (ticlopidine) on PMP generation. There were significant differences in the levels of PMP and a platelet activation marker between before and after treatment with ticlopidine (PMP:

Hideo Kagawa; Shosaku Nomura; Minori Nagahama; Yoshio Ozaki; Shirou Fukuhara; E. Martini; P. LaTorre; R. Cioni; R. Lucchetti; S. Fedi; G. Pepe; T. Aspelin; O. Rřise; H. Takami; R. Nakahata; S. Basili; M. Vieri; F. Martini; G. Labbadia; A. Bellomo; C. Cordova

1999-01-01

165

Different types of connective tissue alterations associated with cervical artery dissections  

Microsoft Academic Search

This study describes the technical handling and the diagnostic evaluation of skin biopsies in order to standardize the assessment of the delicate morphologic abnormalities that are found in patients with spontaneous cervical artery dissections (sCAD). Skin biopsies from 126 patients with sCAD and from 29 healthy relatives were analyzed. The morphology of the connective tissue was normal in 54 patients

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

2004-01-01

166

Association of Cervical Artery Dissection with Connective Tissue Abnormalities in Skin and Arteries  

Microsoft Academic Search

Spontaneous cervical artery dissections (sCAD) often occur in otherwise healthy individuals without known risk factors for stroke and frequently develop spontaneously without relevant trauma. An underlying arteriopathy leading to a so-called ’weakness of the vessel wall’ and predisposing certain individuals to dissection has often been postulated. Therefore, the morphology of connective tissue, a main component of vessel wall and environment,

T. Brandt; M. Morcher; I. Hausser

2005-01-01

167

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

Microsoft Academic Search

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

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

168

Safety and efficacy of iloprost for the treatment of ischaemic digits in paediatric connective tissue diseases  

Microsoft Academic Search

Objective. We analysed our experience with the use of iloprost for the treatment of critical ischaemic digits (ID) in children with connective tissue diseases (CTD) in order to assess its safety and efficacy. Methods. This was a retrospective analysis of paediatric patients with CTD who were treated with iloprost for critical ID resistant to conventional therapy. Information on demographics, clinical

F. Zulian; F. Corona; V. Gerloni; F. Falcini; A. Buoncompagni; M. Scarazatti; G. Martini; F. Zacchello

2004-01-01

169

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

Microsoft Academic Search

AIM: To clarify whether perimuscular connective tissue contains more lymphatic vessels than the shallower layers in human gallbladders. METHODS: Lymphatic vessels were stained immunohistochemically with monoclonal antibody D2-40, which is a specifi c marker of lymphatic endothelium, in representative sections of 12 normal human gallbladders obtained at the time of resection for colorectal carcinoma liver metastases. In individual gallbladder specimens,

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

170

Increased chylomicron triglyceride hydrolysis by connective tissue flow in perfused rat hindlimb: implications for lipid storage  

Microsoft Academic Search

Skeletal muscle has two circulatory routes, nutri- tive (in contact with muscle) and non-nutritive (part of which is located in the connective tissue), and the balance of flow between the two is controlled by neural input and circulating vasomodulators. The purpose of this study was to assess muscle triglyceride hydrolysis given that the two circuits may have a differing vascular

L. H. Clerk; M. E. Smith; S. Rattigan; M. G. Clark

171

Fibrosis in connective tissue disease: the role of the myofibroblast and fibroblast-epithelial cell interactions  

Microsoft Academic Search

Fibrosis, characterized by excessive extracellular matrix accumulation, is a common feature of many connective tissue diseases, notably scleroderma (systemic sclerosis). Experimental studies suggest that a complex network of intercellular interactions involving endothelial cells, epithelial cells, fibroblasts and immune cells, using an array of molecular mediators, drives the pathogenic events that lead to fibrosis. Transforming growth factor-? and endothelin-1, which are

Thomas Krieg; David Abraham; Robert Lafyatis

2007-01-01

172

Treprostinil, a Prostacyclin Analogue, in Pulmonary Arterial Hypertension Associated With Connective Tissue Disease  

Microsoft Academic Search

Study objectives: To assess the efficacy and safety of continuous subcutaneous infusion of treprostinil, a stable prostacyclin analogue, for treating pulmonary arterial hypertension (PAH) in patients with connective tissue disease (CTD). Design: Two multicenter, randomized, double-blind, placebo-controlled, prospective trials of treprostinil vs placebo in 470 patients with PAH. Patients: A subset of 90 patients with PAH and CTD, including systemic

Ronald J. Oudiz; Robert J. Schilz; Robyn J. Barst; Nazzareno Galie ´; Stuart Rich; Lewis J. Rubin; Gerald Simonneau

173

Circulating lupus type anticoagulant and pulmonary hypertension associated with mixed connective tissue disease  

Microsoft Academic Search

Summary We report the case of a young woman, with mixed connective tissue disease (MCTD), associated with disabling pulmonary hypertension and presence of the “lupus anticoagulant”. The “lupus anticoagulant”, an antibody directed against phospholipid components, was linked in our patient to extensive thrombophlebitis and premature labor. Raynaud's phenomenon progressed towards finger necrosis in spite of optimal vasodilating treatment. The part

P. Hainaut; E. Lavenne; J. M. Magy; E. G. Lebacq

1986-01-01

174

Mediastinal lymphadenopathy and pulmonary arterial hypertension in mixed connective tissue disease  

SciTech Connect

A case of mixed connective tissue disease (MCTD) is presented in which mediastinal lymphadenopathy was the most prominent radiological finding detected by plain chest radiographs and computed tomography. Pulmonary arterial hypertension, which is a rare and often fatal complication of MCTD, also developed in this patient.

Guit, G.L.; Shaw, P.C.; Ehrlich, J.; Kroon, H.M.; Oudkerk, M.

1985-02-01

175

Skeletal Overexpression of Connective Tissue Growth Factor Impairs Bone Formation and Causes Osteopenia  

Microsoft Academic Search

Connective tissue growth factor (CTGF), a member of the CCN family of proteins, is expressed in skeletal cells, and the ctgf null mutation leads to neonatal lethality due to defects in skeletal development. To define the function of CTGF in the postnatal skeleton, we created transgenic mice overexpressing CTGF un- der the control of the human osteocalcin promoter. CTGF trans-

Anna Smerdel-Ramoya; Stefano Zanotti; Lisa Stadmeyer; Deena Durant; Ernesto Canalis

2008-01-01

176

Bioactive glass and connective tissue graft used to treat intrabony periodontal defects.  

PubMed

Different techniques and materials can be used to treat intrabony periodontal defects caused by periodontal diseases. This case report presents an intrabony periodontal defect with bioactive glass and connective tissue graft used as a barrier. Probing depth and clinical attachment gain were reduced at 6 and 12 months post-treatment. PMID:23823350

Deliberador, Tatiana Miranda; Trotta, Daniel Rizzo; Klug, Luis Gustavo; Zielak, Joao Cesar; Giovanini, Allan Fernando

2013-07-01

177

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...

178

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

Microsoft Academic Search

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

J. Spranger; Gregor Mendel; Circle Greenwood

2001-01-01

179

Rn for treatment of periocular fibrous connective tissue sarcomas in the horse.  

PubMed

Twelve periocular fibrous connective tissue sarcomas in 11 horses were treated with 222Rn. Follow-up periods ranged from 1 to 6 years; the overall nonrecurrence rate at 12 months after therapy was 92%. Two lesions recurred 2 years after treatment, and 1 after 3 years. One of the former lesions has not recurred after a 2nd 222Rn treatment. PMID:7056684

Frauenfelder, H C; Blevins, W E; Page, E H

1982-02-01

180

Aberrant Type I Interferon Regulation in Autoimmunity: Opposite Directions in MS and SLE, Shaped by Evolution and Body Ecology  

PubMed Central

Studying the action of mechanisms of type I interferon (IFN) provides the insight to elucidate the cause and therapy for autoimmune diseases. There are high IFN responses in some diseases such as connective tissue diseases, but low responses in multiple sclerosis. Distinct IFN features lead us to understand pathology of a spectrum of autoimmune diseases and help us to search genetic changes, gene expression, and biomarkers for diagnosis, disease progression, and treatment response. PMID:24062747

Reder, Anthony T.; Feng, Xuan

2013-01-01

181

The potential for studying the effects of microgravity on connective tissue by small angle light scattering  

NASA Astrophysics Data System (ADS)

In order to address the effects of microgravity on living tissue, we must examine and understand tissue response on a molecular level. Doing so requires the development of quantitative techniques for characterizing tissue behavior on the micrometer scale under both normal and reduced gravitational fields. It has been demonstrated that small angle light scattering holds great promise in this regard. Small angle light scattering (SALS) has been used to probe tissue microstructure on the micron and sub-micron length scales. Quantitative information on feature geometry, dimension and orientation was obtained. Here, we discuss the application of small angle light scattering techniques to the study of connective tissue. Two terrestrial situations relevant to future microgravity studies were considered: the anisotropic behavior of collagen fibers in rabbit tendon in response to increasing load; and, the variation in collagen structure in healthy and arthritic human cartilage. SALS allowed quantitative determination of both fiber diameter and degree of orientation, providing a level of information beyond that obtainable by light and electron microscopies. The primary advantages of SALS over these techniques lies in its quantitative nature and reduced sample preparation requirements. SALS requires neither vacuum or the use of dyes, eliminating important potential sources of artifacts. Results from these studies compare favorably with microscopy studies and demonstrate the importance of the quantitative nature of the technique. In addition, these results also demonstrate the potential of SALS for providing quantitative analysis of effects of microgravity on structural and connective tissue.

McNamara, K.; Bellare, A.; Shortkroff, S.; Dahlgren, E.

182

Functional properties and connective tissue content of pediatric human detrusor muscle.  

PubMed

The functional properties of human pediatric detrusor smooth muscle are poorly described, in contrast to those of adult tissue. Characterization is necessary for more informed management options of bladder dysfunction in children. We therefore compared the histological, contractile, intracellular Ca2+ concentration responses and biomechanical properties of detrusor biopsy samples from pediatric (3-48 mo) and adults (40-60 yr) patients who had functionally normal bladders and were undergoing open surgery. The smooth muscle fraction of biopsies was isolated to measure proportions of smooth muscle and connective tissue (van Gieson stain); in muscle strips, isometric tension to contractile agonists or electrical field stimulation and their passive biomechanical properties; in isolated myocytes, intracellular Ca2+ concentration responses to agonists. Pediatric detrusor tissue compared with adult tissue showed several differences: a smaller smooth muscle-to-connective tissue ratio, similar contractures to carbachol or ?,?-methylene ATP when corrected for smooth muscle content, and similar intracellular Ca2+ transients to carbachol, ?,?-methylene ATP, raised K+ concentration or caffeine, but smaller nerve-mediated contractions and greater passive stiffness with slower stress relaxation. In particular, there were significant atropine-resistant nerve-mediated contractions in pediatric samples. Detrusor smooth muscle from functionally normal pediatric human bladders is less contractile than that from adult bladders and exhibits greater passive stiffness. Reduced bladder contractile function is not due to reduced smooth muscle contractility but to greater connective tissue deposition and to functional denervation. Significant atropine resistance in pediatric detrusor, unlike in adult tissue, demonstrates a different profile of functional neurotransmitter activation. These data have implications for the management of pediatric bladder function by therapeutic approaches. PMID:25209864

Johal, Navroop; Wood, Dan N; Wagg, Adrian S; Cuckow, Peter; Fry, Christopher H

2014-11-01

183

Outcome of pregnancy in patients with autoimmune rheumatic disease before the disease onset  

Microsoft Academic Search

The outcomes of 419 pregnancies of 154 unselected patients with various auto-immune diseases, including 390 pregnancies before the disease onset, were studied retrospectively. The patients comprised 40 with systemic lupus erythematosus (SLE), 72 with rheumatoid arthritis, 21 with primary Sjögren's syndrome (1 degree SS), 14 with progressive systemic sclerosis (PSS), and seven with mixed connective tissue disease. The histories of

A Siamopoulou-Mavridou; M N Manoussakis; A K Mavridis; H M Moutsopoulos

1988-01-01

184

The "washing line" suture technique for securing the Subepithelial Connective Tissue Graft.  

PubMed

Following tooth extraction, resorption of the buccal wall of the socket will occur; this will be true for both the maxilla and the mandible. Where the extraction site is surrounded by natural dentition, the loss of the buccal alveolar plate can degrade the visual aesthetics of an implant-supported prosthetic rehabilitation. To aid the harmonization of the hard and soft tissue morphology, both hard and soft tissue augmentation can be carried out either consecutively with an extraction/immediate implant placement or prior to an implant placement in the delayed scenario. The contemporary method of increasing soft tissue volume is to use the Subepithelial Connective Tissue (auto) Graft (the SCTG). The graft requires fixation, otherwise it can be extruded from the recipient site. This article presents a novel suturing technique which can confidently secure the SCTG, thus resisting its dislodgement. PMID:25020220

McCrea, Shane J J

2014-07-01

185

An ultrastructural study of connective tissue in mollusc integument: II. Gastropoda.  

PubMed

We studied the ultrastructure of the subepidermal connective tissue (SEC) in different zones of the integument in terrestrial, marine and freshwater gastropods (eight species). In all cases, the SEC was a layer of loose connective tissue between the basal membrane (BM) of the epidermis and the connective tissue of the deeper muscle layers. It was of monotonous structure and not differentiated into layers such as are found in mammalian dermis. The extracellular matrix (ECM) consisted of a network of collagen fibrils of variable diameter, with abundant anchoring devices and proteoglycans. In six species, variables quantities of haemocyanin were present within haemocoelic sinuses present in the SEC. The thickness and density of the BM varied from species to species, as well as within species in the various zones of integument. The ultrastructure of the lamina densa (LD) was indistinguishable from that of BM in bivalves and similar to that in mammals, although basotubules and double pegs were absent. An irregularly spaced lamina lucida was usually present and was often shot thorough with filaments and small protrusions of the LD that connected with epithelial plasma membrane or with hemidesmosomes. A lamina fibroreticularis was not present. LD protrusions characterize the connection between BM and the ECM of SEC. In the terrestrial gastropods, a spongy matrix with ultrastructure closely similar to LD occupied large tracts of the SEC. In the mantle region of Arion rufus, the integumental SEC contained large cavities filled with spherical concretions, probably representing rudiments of a shell. In the mantle where the integument contained abundant muscle fibres, the BM was thick and directly connected to the ECM of the SEC which consisted of compact laminae of collagen fibrils with abundant anchoring devices. Along the edge of the foot of Patella ulyssiponensis, the SEC contained a layer of paramyosinic muscle fibres adhering to the epidermis. No differences or gradations in integumental SEC structure could be related to the phylogenetic position of the species examined. PMID:11949779

Bairati, A; Comazzi, M; Gioria, M

2001-10-01

186

Protease phenotype of constitutive connective tissue and of induced mucosal mast cells in mice is regulated by the tissue  

PubMed Central

Mouse mast cells (MCs) express a large number of serine proteases including tryptases, mouse mast cell protease (mMCP)-6 and -7; chymases, mMCP-1, -2, and -4; and an elastase, mMCP-5; along with carboxypeptidase-A3 (CPA3). In helminth-infected mouse intestine, distinct protease phenotypes are observed for connective tissue MCs (CTMCs) (mMCP-4+–7+, and CPA3+) and mucosal MCs (MMCs) (mMCP-1+ and 2+). To determine whether the protease phenotype was regulated by the tissue, we compared the phenotype of constitutive CTMCs and induced MMCs in trachea and large airways in antigen-sensitized unchallenged and challenged mice to MCs in skin and helminthic-infected intestine. We found that in the trachea, unlike in skin and intestine, CTMCs and MMCs both express all six serine proteases and CPA3 (mMCP-1+, -2+, 4+–7+, CPA3+). This phenotype also holds for the lung CTMCs in the proximal bronchi, whereas the induced MMCs express only four proteases, mMCP-1, -2, -6, and -7. Thus, the T-cell–dependent induction of MMCs in trachea, large bronchi, and small intestine provides numbers but does not determine the protease phenotype. Furthermore, the CTMCs, which are constitutive, also show striking differences at these tissue sites, supporting the view that the differences in expression are tissue directed and not dependent on inflammation. PMID:21825171

Xing, Wei; Austen, K. Frank; Gurish, Michael F.; Jones, Tatiana G.

2011-01-01

187

Blood vessels surrounded by connective tissue (perivascular space) in the brain of Lepidosteus (Ganoidei) and some teleost fishes  

Microsoft Academic Search

Blood vessels surrounded by unusually wide perivascular spaces rich in connective tissue were observed in the brain of Lepidosteus (Ganoidei). Connective-tissue sheaths measuring up to 13 µm in width enclose arterioles and venules (40–70 µm in diameter), and even capillaries may be encompassed by a cuff formed by collagen fibers. Blood vessels with wide perivascular spaces are mainly located in

G. Merker; A. Oksche; H. O. Hofer

1974-01-01

188

Transcriptional landscapes of emerging autoimmunity: transient aberrations in the targeted tissue’s extracellular milieu precede immune responses in Sjögren’s syndrome  

PubMed Central

Introduction Our understanding of autoimmunity is skewed considerably towards the late stages of overt disease and chronic inflammation. Defining the targeted organ’s role during emergence of autoimmune diseases is, however, critical in order to define their etiology, early and covert disease phases and delineate their molecular basis. Methods Using Sjögren’s syndrome (SS) as an exemplary rheumatic autoimmune disease and temporal global gene-expression profiling, we systematically mapped the transcriptional landscapes and chronological interrelationships between biological themes involving the salivary glands’ extracellular milieu. The time period studied spans from pre- to subclinical and ultimately to onset of overt disease in a well-defined model of spontaneous SS, the C57BL/6.NOD-Aec1Aec2 strain. In order to answer this aim of great generality, we developed a novel bioinformatics-based approach, which integrates comprehensive data analysis and visualization within interactive networks. The latter are computed by projecting the datasets as a whole on a priori-defined consensus-based knowledge. Results Applying these methodologies revealed extensive susceptibility loci-dependent aberrations in salivary gland homeostasis and integrity preceding onset of overt disease by a considerable amount of time. These alterations coincided with innate immune responses depending predominantly on genes located outside of the SS-predisposing loci Aec1 and Aec2. Following a period of transcriptional stability, networks mapping the onset of overt SS displayed, in addition to natural killer, T- and B-cell-specific gene patterns, significant reversals of focal adhesion, cell-cell junctions and neurotransmitter receptor-associated alterations that had prior characterized progression from pre- to subclinical disease. Conclusions This data-driven methodology advances unbiased assessment of global datasets an allowed comprehensive interpretation of complex alterations in biological states. Its application delineated a major involvement of the targeted organ during the emergence of experimental SS. PMID:24286337

2013-01-01

189

Telomere dysfunction, autoimmunity and aging.  

PubMed

Immune aging is associated with loss of critical immune functions, such as host protection from infection and malignancy. Unexpectedly, immunosenescence also renders the host susceptible to inflammation, which may translate into tissue-damaging disease as the senescent immune system loses its ability to maximize inflammatory protection while minimizing inflammatory injury. On the other hand, chronic inflammation associated with immune-mediated disease represents a profound stress factor for the immune system, affecting cellular turn-over, replication and exhaustion. Immune cell longevity is tightly connected to the functional integrity of telomeres which are regulated by cell multiplication, exposure to oxidative stress and DNA repair mechanisms. Lymphocytes are amongst the few cell types that can actively elongate telomeres through the action of telomerase. In patients with the autoimmune disease rheumatoid arthritis (RA), telomerase deficiency is associated with prematurity of immune aging. Patients with RA have other defects in DNA repair mechanisms, including the kinase Ataxia telangiectasia mutated (ATM), critically involved in the repair of DNA double strand breaks. ATM deficiency in RA shortens lymphocyte survival. Dynamics of telomeric length and structure are beginning to be understood and have distinct patterns in different autoimmune diseases, suggesting a multitude of molecular mechanisms defining the interface between chronic immune stimulation and progressive aging of the immune system. PMID:22396899

Hohensinner, Philipp J; Goronzy, Jörg J; Weyand, Cornelia M

2011-12-01

190

Autoimmune thyroid disorders.  

PubMed

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

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

2015-02-01

191

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

PubMed

Mixed connective tissue disease (MCTD) is an overlap syndrome first defined in 1972 by Sharp et al. In this original study, the portrait emerged of a connective tissue disorder sharing features of systemic lupus erythematosus, systemic sclerosis (scleroderma) and polymyositis. Scleroderma renal crisis (SRC) is an extremely infrequent but serious complication that can occur in MCTD. The histologic picture of SRC is that of a thrombotic micro-angiopathic process. Renal biopsy plays an important role in confirming the clinical diagnosis, excluding overlapping/superimposed diseases that might lead to acute renal failure in MCTD patients, helping to predict the clinical outcome and optimizing patient management. We herewith report a rare case of SRC in a patient with MCTD and review the relevant literature. PMID:24969199

Vij, Mukul; Agrawal, Vinita; Jain, Manoj

2014-07-01

192

Actinic granuloma. An annular connective tissue disorder affecting sun- and heat-damaged (elastotic) skin.  

PubMed

Ring-shaped inflammatory lesions sometimes develop in the abnormal "elastotic" connective tissues of skin damaged by sun and heat. The lesions, which commence as papules and nodules, enlarge very slowly and may persist for years. Microscopical sections show that there is an infiltrate composed mainly of foreign-body giant cells, the cells being engaged in digesting and absorbing the abnormal elastotic fibers. The disorder, which occurs on several continents, should probably be regarded as a phenomenon of repair within damaged connective tissue. The name actinic granuloma indicates its external or environmental origin and distinguishes it from other granulomas with which it is constantly being confused. Actinic granuloma and granuloma annulare appear to be related. In granuloma annulare, a productive and resorptive process also occurs, but its nature remains obscure. Actinic granuloma may be misdiagnosed as "atypical necrobiosis lipoidica" or as a sarcoidosis. The subject of actinic damage to blood vessels deserves study. PMID:1122146

O'Brien, J P

1975-04-01

193

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

PubMed Central

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

Hoffjan, S.

2012-01-01

194

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

Microsoft Academic Search

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

Gary R. Grotendorst

1997-01-01

195

Infection-related morbidity and mortality in patients with connective tissue diseases: a systematic review  

Microsoft Academic Search

Patients suffering from connective tissue diseases (CTDs) constitute an important subgroup of immunosuppressed patients at\\u000a risk for developing serious infections. Prophylactic antibiotic administration may decrease infection-related morbidity and\\u000a mortality burden in patients with CTD, though one needs first to evaluate the overall effect of infection on morbidity and\\u000a mortality in such patients and the presence of adequate prognostic\\/risk factors for

Matthew E. Falagas; Katerina G. Manta; Gregoria I. Betsi; Georgios Pappas

2007-01-01

196

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

Microsoft Academic Search

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

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

2002-01-01

197

Histochemical and ultrastructural characteristics of the endometrial connective tissue stroma from mice continuously fed diethylstilbestrol  

Microsoft Academic Search

Summary  Histochemical and transmission electron microscopy were utilized to examine the endometrial connective tissue stroma of mice\\u000a continuously fed diethylstilbestrol (DES). Virgin female mice were continuously fed diets containing 0, 320, or 640 ppb DES\\u000a from 4 weeks of age until moribund. All animals reported on in this study were between 622 to 762 days of age when sacrificed.\\u000a Light microscopy

Robert J. Wordinger; Benjamin Highman; James W. Townsend; David L. Greenman

1984-01-01

198

Prenatal nicotine exposure increases connective tissue expression in foetal monkey pulmonary vessels  

Microsoft Academic Search

Prenatal nicotine exposure increases connective tissue expression in foetal monkey pulmonary vessels. H.S. Sekhon, B.J. Proskocil, J.A. Clark, E.R. Spindel. #ERS Journals Ltd 2004. ABSTRACT: Among the many deleterious effects of maternal smoking during pregnancy on foetal development, is a higher incidence of persistent pulmonary hypertension. The recent identification of nicotinic acetylcholine receptors (nAChR) on cells of the pulmonary vessel

H. S. Sekhon; B. J. Proskocil; J. A. Clark; E. R. Spindel

2004-01-01

199

Connective tissue growth factor induces apoptosis via caspase 3 in cultured human aortic smooth muscle cells  

Microsoft Academic Search

Connective tissue growth factor (CTGF) stimulates proliferation of fibroblasts and endothelial cells, but nothing is known about its role in smooth muscle cells. In this study, the effects of recombinant human CTGF (r-hCTGF, 0.5–10 ?g\\/ml) on cultured human aortic vascular smooth muscle cells were investigated. r-hCTGF significantly reduced cell viability, increased apoptosis, and augmented caspase 3 activity. Moreover, r-hCTGF-induced apoptosis

Keiichi Hishikawa; Toshio Nakaki; Tomoko Fujii

2000-01-01

200

Vascular and connective tissue features in 5 Italian patients with homocystinuria  

Microsoft Academic Search

Homocystinuria is a metabolic disorder associated with defects in genes encoding for methionine metabolism enzymes. Vascular and connective tissue manifestations such as deep venous thrombosis, ectopia lentis and skeletal alterations are the major clinical features.We investigated the clinical manifestations of 5 Italian homocystinuric patients, performed mutation screening analysis on cystationine beta-synthase (CBS) gene and searched for genotype\\/phenotype correlations.We detected mild

Lucia Evangelisti; Laura Lucarini; Monica Attanasio; Maria Cristina Porciani; Eloisa Romano; Domenico Prisco; Gian Franco Gensini; Rosanna Abbate; Guglielmina Pepe

2009-01-01

201

Genetic diseases of the extracellular matrix: more than just connective tissue disorders  

Microsoft Academic Search

The rapidly increasing knowledge about the molecular biology of the extracellular matrix has changed the concepts for the\\u000a pathomechanisms of heritable connective tissue diseases. The spectrum of genetic matrix disorders is much broader than previously\\u000a thought and now also includes diseases of organs such as the kidney, eye, and muscles. In addition, evidence is emerging that\\u000a certain ”acquired” diseases may

Leena Bruckner-Tuderman; P. Bruckner

1998-01-01

202

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

Microsoft Academic Search

The objective of this study was to evaluate the efficacy of connective tissue massage to improve blood circulation and intermittent claudication symptoms in type 2 diabetic patients. A ran- domized, placebo-controlled trial was undertaken. Ninety-eight type 2 diabetes patients with stage I or II-a peripheral arterial disease (PAD) (Leriche-Fontaine classification) were random- ly assigned to a massage group or to

Adelaida Maria Castro-Sanchez; Carmen Moreno-Lorenzo; Guillermo A. Mataran-Penarrocha; Belen Feriche-Fernandez-Castanys; Genoveva Granados-Gamez; JoseManuel Quesada-Rubio

2009-01-01

203

Von willebrand factor antigen in assessment of vasculitis in patients with connective tissue diseases  

Microsoft Academic Search

Von Willebrand factor antigen (vWF:Ag) is synthesized and secreted by endothelial cells. In the present study we tried to assess the relationship between plasma level of vWF:Ag and vascular damage in patients with vasculitis. The study was carried out on 59 patients with connective tissue diseases. Vasculitis was diagnosed by biopsies of the skin. The patients with vasculitis had a

J. Kloczko; A. Kuryliszyn-Moskal; K. Bernacka; M. Bielawiec; B. Cylwik; P. Radziwon

1994-01-01

204

Value of Finger Arterial Blood Pressure in Diagnosis of Vascular Changes in Some Connective Tissue Diseases  

Microsoft Academic Search

This study was performed in 60 patients with the following connective tissue diseases: rheumatoid arthritis (RA—20 patients), systemic lupus erythematosus (SLE—20), and progressive systemic sclerosis (scleroderma=PSS-20). Twenty normal persons served as controls.All patients and controls were subjected to complete history taking, complete physical examination, and laboratory investigations including: rheumatoid fac tor, anti-DNA, LE cell test, antinuclear factor (ANF), and ECG.Finger

Mohamed El-Sayed Salem; Amira Hassan El-Girby; Nadia Ahmed Abd El-Moneim; Selim Ahmed Khalil

1993-01-01

205

Autoantibodies to angiotensin-converting enzyme 2 in patients with connective tissue diseases  

Microsoft Academic Search

INTRODUCTION: Angiotensin-converting enzyme (ACE) 2, a homolog of ACE, converts angiotensin (Ang) II into Ang(1-7), and the vasoprotective effects of Ang(1-7) have been documented. We explored the hypothesis that serum autoantibodies to ACE2 predispose patients with connective tissue diseases to constrictive vasculopathy, pulmonary arterial hypertension (PAH), or persistent digital ischemia. METHODS: Serum was examined from 42 patients with systemic lupus

Yuko Takahashi; Shiori Haga; Yukihito Ishizaka; Akio Mimori

2010-01-01

206

Mixed connective tissue disease presenting with progressive scleroderma symptoms in a 10-year-old girl  

PubMed Central

Mixed connective tissue disease (MCTD) is a systemic inflammatory disease affecting connective tissue with the underlying autoimmunological mechanism. The core of MCTD is an appearance of symptoms of several other inflammatory diseases of connective tissue – systemic lupus erythematosus, systemic scleroderma, poly- or dermatomyositis, rheumatoid arthritis at the same time, accompanied by a high level of anti-ribonucleoprotein antibodies (anti-U1RNP). The disease was described more than 40 years ago by Sharp et al. During recent years, many efforts to better understand clinical and serological features of MCTD have been made. Diagnosis of MCTD can be difficult. Obligatory international diagnostic criteria are required to be fulfilled. Several versions of such criteria have been proposed, but the most widely used one was described by Kasukawa. There is no consensus about treatment – a choice of drugs depends on symptoms. We present a case of a 10-year-old girl with sclerodactyly and trophic damages of fingers accompanied by symptoms of Raynaud's phenomenon. After an almost 2-year course of the disease, a diagnosis of MCTD has been established. PMID:24353496

Latu?kiewicz-Potemska, Joanna; Biernacka-Zieli?ska, Ma?gorzata; Sta?czyk, Jerzy; Smolewska, El?bieta

2013-01-01

207

From detecting astrocyte connectivity to uncovering drug effects in living tissues  

E-print Network

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

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

2013-01-01

208

Recalcitrant hypocalcaemia in autoimmune enteropathy.  

PubMed

Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome is a monogenic disorder associated with autoimmune destruction of both endocrine and nonendocrine tissues. The classic triad includes candidiasis, hypoparathyroidism, and Addison disease. Up to 25% of patients with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome also have gastrointestinal manifestations, which can have an impact on the management of other aspects of the disease. The management of the case discussed was challenging because of the complex interplay between the manifestations and treatment of his hypoparathyroidism, Addison disease, and autoimmune enteropathy. Attempts at management of hypocalcemia were largely unsuccessful until the introduction of immunosuppressive therapy for autoimmune enteropathy. This case supports early consideration of immunosuppression in this condition. PMID:25404718

Geyer, Myfanwy; Fairchild, Jan; Moore, David; Moore, Lynette; Henning, Paul; Tham, Elaine

2014-12-01

209

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

PubMed

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

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

210

Autoantibodies Produced at the Site of Tissue Damage Provide Evidence of Humoral Autoimmunity in Inclusion Body Myositis  

PubMed Central

Inclusion body myositis (IBM) belongs to a group of muscle diseases known as the inflammatory myopathies. The presence of antibody-secreting plasma cells in IBM muscle implicates the humoral immune response in this disease. However, whether the humoral immune response actively contributes to IBM pathology has not been established. We sought to investigate whether the humoral immune response in IBM both in the periphery and at the site of tissue damage was directed towards self-antigens. Peripheral autoantibodies present in IBM serum but not control serum recognized self-antigens in both muscle tissue and human-derived cell lines. To study the humoral immune response at the site of tissue damage in IBM patients, we isolated single plasma cells directly from IBM-derived muscle tissue sections and from these cells, reconstructed a series of recombinant immunoglobulins (rIgG). These rIgG, each representing a single muscle-associated plasma cell, were examined for reactivity to self-antigens. Both, flow cytometry and immunoblotting revealed that these rIgG recognized antigens expressed by cell lines and in muscle tissue homogenates. Using a mass spectrometry-based approach, Desmin, a major intermediate filament protein, expressed abundantly in muscle tissue, was identified as the target of one IBM muscle-derived rIgG. Collectively, these data support the view that IBM includes a humoral immune response in both the periphery and at the site of tissue damage that is directed towards self-antigens. PMID:23071619

Ray, Arundhati; Amato, Anthony A.; Bradshaw, Elizabeth M.; Felice, Kevin J.; DiCapua, Daniel B.; Goldstein, Jonathan M.; Lundberg, Ingrid E.; Nowak, Richard J.; Ploegh, Hidde L.; Spooner, Eric; Wu, Qian

2012-01-01

211

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

PubMed Central

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

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

2012-01-01

212

A method for simultaneous fluorometry and rheology of connective tissue in bulk meat.  

PubMed

A probe tipped with optical fibres was mounted on the load cell of a compression tester and pushed into well-aged beef rib roasts (Canada Grade AAA, n=6, 33±3.6days post-mortem). Fluorescence (F; excitation 365nm, emission >420nm) and reflectance (R; 365nm) were measured through single optical fibres. Diffuse R was measured using different fibres for illumination and detection, thus responding to tissue between the two fibres. Replication was by a matrix pattern of penetrations on single roasts. For example, in a typical roast, F was correlated with the force of penetration (mean r=0.86±0.06, n=20, all P<0.001). R was less (P<0.001) strongly correlated with penetration force (mean r=0.46±0.10, n=20, all P<0.001). F signals from connective tissue contained less peaks than R signals from both connective and adipose tissue (respectively, 2.75±0.43 versus 5.57±0.67peakscm(-1), P<0.001, n=20 pairs) and F peaks were wider than R peaks (respectively, 3.54±0.88 versus 1.38±0.19mm, P<0.001, n=20 pairs). For the spinales dorsi aponeurosis, the depth at which peak force was reached was strongly correlated with the depths at which both peak F and peak R were reached (r=0.98, P<0.001, n=20 for both). Diffuse R was only weakly correlated with penetration force (mean r=0.29±0.12 with only 5/10 correlations significant P<0.001). This new method showed the primary resistance to dorso-ventral penetrometry of well-aged beef rib roasts originated from connective tissue. PMID:22063886

Swatland, H J

2005-08-01

213

Imaging of autoimmune diseases.  

PubMed

Autoimmune diseases represent a heterogeneous group of pathologies with a wide range of immunological changes and clinical presentations. The clinical onset of the disease commonly occurs when signs and symptoms of target tissue hypofunction appear; complications can also be present. The aim of an imaging diagnostic technique in this context is to correctly evaluate the disease extent and severity for appropriate treatment and to follow up the efficacy of therapy. In addition, identification of subjects at risk and the preclinical diagnosis may allow disease prevention. Ultrasound (US), conventional radiology and computed tomography (CT) are often used for a detailed morphological study of tissues involved; magnetic resonance (MRI) may also demonstrate biochemical and structural tissue changes. Nuclear medicine techniques are known for their sensitivity and specificity and in recent years an expanding field is represented by the development of radiolabelled receptor ligands. New radiopharmaceuticals able to bind in vivo to specific receptors have been introduced allowing the non invasive detection of changes in affected tissues. The relevant criteria to choose different diagnostic approaches in several autoimmune diseases are discussed in this review. In particular the role and contribution of nuclear medicine for the study of autoimmune diseases have been described. PMID:10230286

Procaccini, E; Chianelli, M; Pantano, P; Signore, A

1999-03-01

214

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

PubMed

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

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

2015-01-01

215

Brain leukocyte infiltration initiated by peripheral inflammation or experimental autoimmune encephalomyelitis occurs through pathways connected to the CSF-filled compartments of the forebrain and midbrain  

PubMed Central

Background Cerebrospinal fluid (CSF) has been considered as a preferential pathway of circulation for immune cells during neuroimmune surveillance. In order to evaluate the involvement of CSF-filled spaces in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis, we performed a time-course analysis of immune cell association with the CSF-containing ventricles, velae, and cisterns in two active models of this disease. Methods Guinea-pig spinal cord homogenate-induced EAE in rat and myelin oligodendrocyte glycoprotein-induced EAE in mouse were used. Leukocyte distribution and phenotypes were investigated by immunohistochemistry in serial sections of brain areas of interest, as well as in CSF withdrawn from rat. Immune cells associated with the choroid plexuses were quantified. Results Freund’s adjuvant-induced peripheral inflammation in the absence of brain antigen led to a subtle but definite increase in the number of myeloid cells in the extraventricular CSF spaces. In both rats and mice, EAE was characterized by a sustained and initial infiltration of lymphocytes and monocytes within forebrain/midbrain fluid-filled compartments such as the velum interpositum and ambient cisterns, and certain basal cisterns. Leukocytes further infiltrated periventricular and pericisternal parenchymal areas, along perivascular spaces or following a downward CSF-to-tissue gradient. Cells quantified in CSF sampled from rats included lymphocytes and neutrophils. The distinctive pattern of cell distribution suggests that both the choroid plexus and the vessels lying in the velae and cisterns are gates for early leukocyte entry in the central nervous system. B-cell infiltration observed in the mouse model was restricted to CSF-filled extraventricular compartments. Conclusion These results identified distinctive velae and cisterns of the forebrain and midbrain as preferential sites of immune cell homing following peripheral and early central inflammation and point to a role of CSF in directing brain invasion by immune cells during EAE. PMID:22870891

2012-01-01

216

Connective tissue responses to some heavy metals. I. Sodium loaded ion exchange beads as a control: histology and ultrastructure.  

PubMed

Ion exchange resin beads (Amberlite IR-120) were implanted into loose connective tissue as the vehicle for cations in both control and experimental studies. Beads were loaded with sodium for control purposes or with the metal of interest for subsequent experimental studies. When single control beads were implanted in the loose connective tissue of the rat pinna, they were well accepted by tissue and permitted rapid healing. The bead implantation initially produced minimal inflammatory disruption and subsequent repair at the bead-tissue interface which rapidly matured leaving no fibro-collagenous capsule. Some minor geometric rearrangement occurred in the alignment of the connective tissue to compensate for the physical presence of the bead. This system provides a valid control for studies of the effects of metal cations on tissue inflammation and repair--free from anionic complications, surface phenomena or systemic interference. PMID:3620327

Ellender, G; Ham, K N

1987-06-01

217

Molecular Regulation of CCN2 in the Intervertebral Disc: Lessons Learned from Other Connective Tissues  

PubMed Central

Connective tissue growth factor (CCN2/CTGF) plays an important role in extracellular matrix synthesis, especially in skeletal tissues such as cartilage, bone, and the intervertebral disc. As a result there is a growing interest in examining the function and regulation of this important molecule in the disc. This review discusses the regulation of CCN2 by TGF-? and hypoxia, two critical determinants that characterize the disc microenvironment, and discusses known functions of CCN2 in the disc. The almost ubiquitous regulation of CCN2 by TGF-?, including that seen in the disc, emphasizes the importance of the TGF-?-CCN2 relationship, especially in terms of extracellular matrix synthesis. Likewise, the unique cross-talk between CCN2 and HIF-1 in the disc highlights the tissue and niche specific mode of regulation. Taken together the current literature supports an anabolic role for CCN2 in the disc and its involvement in the maintenance of tissue homeostasis during both health and disease. Further studies of CCN2 in this tissue may reveal valuable targets for the biological therapy of disc degeneration. PMID:23567513

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

2013-01-01

218

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

PubMed Central

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

Dalessandri, Tim; Strid, Jessica

2014-01-01

219

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

PubMed Central

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

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

2014-01-01

220

The autoimmune diseases  

SciTech Connect

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.

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

1985-01-01

221

A Bilateral Pediculated Palatal Periosteal Connective Tissue Flap for Coverage of Large Bone Grafts in the Anterior Maxillary Region  

PubMed Central

Introduction: Coverage of bone grafts is very important in reconstructive surgery. In edentulous alveolar ridges this coverage is particularly important for supporting dental prostheses. Here we present the case of a patient with a large deficient maxillary anterior region that was reconstructed with a bilateral palatal submucosal periosteal connective tissue flap: a soft tissue reserve for upper jaw reconstructive surgeries. The bilateral pediculated palatal periosteal connective tissue flap was used for coverage of a large bone graft in the anterior maxillary region. Conclusion: Palatal submucosa can be used as a soft tissue reserve in upper jaw reconstructions. PMID:24303400

Rahpeyma, Amin; khajeh Ahmadi, Saeedeh; Reza Hosseini, Vahid; Azimi, Hamidreza

2012-01-01

222

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

E-print Network

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 ...

Marcantonio, Nicholas A. (Nicholas Alexander)

2008-01-01

223

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

PubMed Central

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

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

2012-01-01

224

[Association of Sjögren's syndrome and mixed connective tissue disease (Sharp's syndrome) in an adolescent (author's transl)].  

PubMed

The authors present the case of an adolescent who, despite his youth and relatively unaffected lacrimo-salivary secretion, was classified within the context of Sjögren's syndrom on the basis of paraclinical investigations, in particular the detection of salivary and lacrimal immunoglobulins. During a long course, the progresssive appearance of new lupoid type signs led to further complex immunological examinations, including examination for anti-E.C.T. antibodies. This case would appear to be an incomplete Sharp's syndrome and should be classified amongst the mixed connective tissue diseases. PMID:309169

Rouchon, C; Ghozlan, E; Laudenbach, P; Briault, F

1978-01-01

225

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

PubMed Central

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

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

226

A new experimental method for hiatal reinforcement using connective tissue patch transfer.  

PubMed

The closure of a large hiatal hernia still represents a challenge for the surgeon. Mesh reinforcement of a hiatoplasty generally decreases recurrence rate. An artificial mesh is cheaper compared with a biologic one, but has a higher complication rate. Our aim was to introduce a new biologic reinforcement method with less expenses. During organ donation for transplantation, tissue islets from pericardium and fascia lata were cryopreserved in a tissue bank. Later, the grafts were transplanted on the diaphragm of mongrel dogs. After 1, 3, and 6 months, the animals were sacrificed, and the transplanted patches were macroscopically and microscopically examined. There were no macroscopic signs of inflammation, abcedation, or significant adhesion formation. The grafts were well recognizable, with palpable thickening and moderate shrinkage. Microscopically, an organization process with fibrosis, neovascularization, and peritoneal integration could be observed. Reinforcement of a hiatoplasty with connective tissue transfer either with cryopreserved or autologous tissue is a good option. This is a cheap and easy method, which should also be tested in human interventions. PMID:21951298

Vereczkei, A; Varga, G; Tornoczky, T; Papp, A; Horvath, Ö P

2012-07-01

227

Scleroderma Renal Crisis and Concurrent Isolated Pulmonary Hypertension in Mixed Connective Tissue Disease and Overlap Syndrome: Report of Two Cases  

Microsoft Academic Search

:   We here report on scleroderma renal crisis (SRC) appearing concurrently with isolated pulmonary hypertension (IPHT), that\\u000a is, pulmonary hypertension without interstitial lung disease with fibrosis, in a patient with mixed connective tissue disease\\u000a (MCTD) and in one with overlap syndrome or undifferentiated connective tissue disease (UCTD). To the best of our knowledge\\u000a there are only five previous reports on

G. N. Andersen; J. Vasko

2002-01-01

228

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

PubMed

Controlled reduction of the connective tissue contribution to cooked meat toughness is an objective that would have considerable financial impact in terms of added product value. The amount of intramuscular connective tissue in a muscle appears connected to its in vivo function, so reduction of the overall connective tissue content is not thought to be a viable target. However, manipulation of the state of maturity of the collagenous component is a biologically viable target; by increasing connective tissue turnover, less mature structures can be produced that are functional in vivo but more easily broken down on cooking at temperatures above 60°C, thus improving cooked meat tenderness. Recent work using cell culture models of fibroblasts derived from muscle and myoblasts has identified a range of factors that alter the activity of the principal enzymes responsible for connective tissue turnover, the matrix metalloproteinases (MMP). Fibroblasts cultured from 3 different skeletal muscles from the same animal show different cell proliferation and MMP activity, which may relate to the different connective tissue content and architecture in functionally different muscles. Expression of MMP by fibroblasts is increased by vitamins that can counter the negative effects of oxidative stress on new collagen synthesis. Preliminary work using in situ zymography of myotubes in culture also indicates increased MMP activity in the presence of epinephrine and reactive oxidative species. Comparison of the relative changes in MMP expression from muscle cells vs. fibroblasts shows that myoblasts are more responsive to a range of stimuli. Muscle cells are likely to produce more of the total MMP in muscle tissue as a whole, and the expression of latent forms of the enzymes (i.e., pro-MMP) may vary between oxidative and glycolytic muscle fibers within the same muscle. The implication is that the different muscle fiber composition of different muscles eaten as meat may influence the potential for manipulation of their connective tissue turnover. PMID:21890505

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

2012-03-01

229

The modelling of mononuclear phagocyte—connective tissue adhesion in vitro: application to disclose a specific inhibitory effect of Leishmania infection  

Microsoft Academic Search

In this work, we have developed an adhesion assay to study interactions between mononuclear phagocytes and connective tissue in vitro and show its potential use to study diseases caused by intracellular microorganisms. The assay reproduces most of the characteristics of macrophage adhesion to connective tissue in vivo, such as: preferential adhesion to inflamed connective tissue, divalent cation and integrin dependence,

Djalma G. F. Carvalhal; Aryon Barbosa; Micely D'El-Rei Hermida; Jorge Clarencio; Nathanael F. Pinheiro; Patricia S. T. Veras; Washington L. C. dos-Santos

2004-01-01

230

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

NASA Astrophysics Data System (ADS)

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

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

2008-04-01

231

Gender and Ocular Manifestations of Connective Tissue Diseases and Systemic Vasculitides  

PubMed Central

Ocular manifestations are present in many connective tissue diseases which are characterized by an immune system that is directed against self. In this paper, we review the ocular findings in various connective tissue diseases and systemic vasculitides and highlight gender differences in each disease. In rheumatoid arthritis, we find that dry eyes affect women nine times more than men. The other extra-articular manifestations of rheumatoid arthritis affect women three times more commonly than men. Systemic lupus erythematosus can involve all ocular structures and women are nine times more affected than men. Systemic sclerosis is a rare disease but, again, it is more common in women with a female to male ratio of 8?:?1. Polymyositis and dermatomyositis also affect women more commonly than men but no gender differences have been found in the incidence or disease course in the systemic vasculitides associated with antineutrophil cytoplasmic antibody such as granulomatosis with polyangiitis (GPA, formerly known as Wegener's granulomatosis). Finally, Behcet's disease is more common in males, and male gender is a risk factor for Behcet's disease. There is a slight female preponderance in sarcoidosis with female gender carrying a worse prognosis in the outcome of ocular disease. PMID:24757559

Choudhary, Maria M.; Hajj-Ali, Rula A.; Lowder, Careen Y.

2014-01-01

232

Leucine Supplementation Accelerates Connective Tissue Repair of Injured Tibialis Anterior Muscle  

PubMed Central

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

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

233

High prevalence of eosinophilic esophagitis in patients with inherited connective tissue disorders  

PubMed Central

Background Eosinophilic esophagitis (EoE) is an emerging chronic inflammatory disease mediated by immune hypersensitization to multiple foods and strongly associated with atopy and esophageal remodeling. Objective We provide clinical and molecular evidence indicating a high prevalence of EoE in patients with inherited connective tissue disorders (CTDs). Methods We examined the rate of EoE among patients with CTDs and subsequently analyzed esophageal mRNA transcript profiles in patients with EoE with or without CTD features. Results We report a cohort of 42 patients with EoE with a CTD-like syndrome, representing 0.8% of patients with CTDs and 1.3% of patients with EoE within our hospital-wide electronic medical record database and our EoE research registry, respectively. An 8-fold risk of EoE in patients with CTDs (relative risk, 8.1; 95% confidence limit, 5.1-12.9; ?21 = 112.0; P < 10?3) was present compared with the general population. Esophageal transcript profiling identified a distinct subset of genes, including COL8A2, in patients with EoE and CTDs. Conclusion There is a remarkable association of EoE with CTDs and evidence for a differential expression of genes involved in connective tissue repair in this cohort. Thus, we propose stratification of patients with EoE and CTDs into a subset referred to as EoE-CTD. PMID:23608731

Abonia, J. Pablo; Wen, Ting; Stucke, Emily M.; Grotjan, Tommie; Griffith, Molly S.; Kemme, Katherine A.; Collins, Margaret H.; Putnam, Philip E.; Franciosi, James P.; von Tiehl, Karl F.; Tinkle, Brad T.; Marsolo, Keith A.; Martin, Lisa J.; Ware, Stephanie M.; Rothenberg, Marc E.

2013-01-01

234

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

SciTech Connect

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.

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

1988-04-01

235

Transcription factor redundancy and tissue-specific regulation: evidence from functional and physical network connectivity.  

PubMed

Two major transcriptional regulators of Caenorhabditis elegans bodywall muscle (BWM) differentiation, hlh-1 and unc-120, are expressed in muscle where they are known to bind and regulate several well-studied muscle-specific genes. Simultaneously mutating both factors profoundly inhibits formation of contractile BWM. These observations were consistent with a simple network model in which the muscle regulatory factors drive tissue-specific transcription by binding selectively near muscle-specific targets to activate them. We tested this model by measuring the number, identity, and tissue-specificity of functional regulatory targets for each factor. Some joint regulatory targets (218) are BWM-specific and enriched for nearby HLH-1 binding. However, contrary to the simple model, the majority of genes regulated by one or both muscle factors are also expressed significantly in non-BWM tissues. We also mapped global factor occupancy by HLH-1, and created a genetic interaction map that identifies hlh-1 collaborating transcription factors. HLH-1 binding did not predict proximate regulatory action overall, despite enrichment for binding among BWM-specific positive regulatory targets of hlh-1. We conclude that these tissue-specific factors contribute much more broadly to the transcriptional output of muscle tissue than previously thought, offering a partial explanation for widespread HLH-1 occupancy. We also identify a novel regulatory connection between the BWM-specific hlh-1 network and the hlh-8/twist nonstriated muscle network. Finally, our results suggest a molecular basis for synthetic lethality in which hlh-1 and unc-120 mutant phenotypes are mutually buffered by joint additive regulation of essential target genes, with additional buffering suggested via newly identified hlh-1 interacting factors. PMID:22730465

Kuntz, Steven G; Williams, Brian A; Sternberg, Paul W; Wold, Barbara J

2012-10-01

236

Transcription factor redundancy and tissue-specific regulation: Evidence from functional and physical network connectivity  

PubMed Central

Two major transcriptional regulators of Caenorhabditis elegans bodywall muscle (BWM) differentiation, hlh-1 and unc-120, are expressed in muscle where they are known to bind and regulate several well-studied muscle-specific genes. Simultaneously mutating both factors profoundly inhibits formation of contractile BWM. These observations were consistent with a simple network model in which the muscle regulatory factors drive tissue-specific transcription by binding selectively near muscle-specific targets to activate them. We tested this model by measuring the number, identity, and tissue-specificity of functional regulatory targets for each factor. Some joint regulatory targets (218) are BWM-specific and enriched for nearby HLH-1 binding. However, contrary to the simple model, the majority of genes regulated by one or both muscle factors are also expressed significantly in non-BWM tissues. We also mapped global factor occupancy by HLH-1, and created a genetic interaction map that identifies hlh-1 collaborating transcription factors. HLH-1 binding did not predict proximate regulatory action overall, despite enrichment for binding among BWM-specific positive regulatory targets of hlh-1. We conclude that these tissue-specific factors contribute much more broadly to the transcriptional output of muscle tissue than previously thought, offering a partial explanation for widespread HLH-1 occupancy. We also identify a novel regulatory connection between the BWM-specific hlh-1 network and the hlh-8/twist nonstriated muscle network. Finally, our results suggest a molecular basis for synthetic lethality in which hlh-1 and unc-120 mutant phenotypes are mutually buffered by joint additive regulation of essential target genes, with additional buffering suggested via newly identified hlh-1 interacting factors. PMID:22730465

Kuntz, Steven G.; Williams, Brian A.; Sternberg, Paul W.; Wold, Barbara J.

2012-01-01

237

Age-related deregulation of Aire and peripheral tissue antigen genes in the thymic stroma of non-obese diabetic (NOD) mice is associated with autoimmune type 1 diabetes mellitus (DM1)  

Microsoft Academic Search

Gene expression of peripheral tissue antigens (PTAs) in stromal medullary thymic epithelial cells (mTECs) is a key process\\u000a to the negative selection of autoreactive thymocytes. This phenomenon was termed “promiscuous gene expression” (PGE), which\\u000a is partially controlled by the Aire gene. Nevertheless, reasons for the correlation of Aire and PTAs with the emergence of\\u000a autoimmune diseases are largely unknown, though

Thaís A. Fornari; Paula B. Donate; Claudia Macedo; Márcia M. C. Marques; Danielle A. Magalhăes; Geraldo A. S. Passos

2010-01-01

238

Computer-assisted analysis of the extracellular matrix of connective tissue  

NASA Astrophysics Data System (ADS)

The new computerized imaging, circular polarized light microscopy technique was developed to measure the orientation of collagen fibers in images of serial sections of connective tissue. The system consists of a modified Olympus BX50 polarized microscope, a Sony AVC-D7 video camera, and a Silicon Graphics Indy computer. Both methods required the initial segmentation of fibers and used binary images. Segments of fiber midlines were traced with vertical and horizontal scanlines, or alternately the whole midlines were identified recursively from the Euclidean Distance Map of the image suing the novel definition of the Medial Axis Transform. The last technique produced connected midlines of the fibers and handled sinuous fibers well. The fiber midlines produced by this technique were traversed by a midline traversal algorithm , and the orientation distribution was obtained by least squares line fitting. The accuracy of the developed techniques was evaluated against synthetic images, composed of straight lines and sinuous curves. Kupier's statistic was used to evaluate the consistency of the fiber orientation calculations. Statistical analysis of the results showed, that the proposed Medial Axis Transform with Hilditch's connectivity preserving skeletonization produced the most accurate results. The developed method was used to measure collagen fiber orientation in microscopy images of canine meniscus, porcine aortic valve leaflet, bovine pericardium and bio- textiles.

Krucinski, Slawomir; Krucinska, Izabella; Veeravanallur, Srinivasan; Slot, Krzysztof

1997-04-01

239

Integrin ?1: A Mechanosignaling Sensor Essential for Connective Tissue Deposition by Fibroblasts  

PubMed Central

Significance There is no effective drug treatment for fibrosis (i.e., pathological scarring). Identifying the fundamental mechanisms responsible for normal and pathological connective tissue deposition is likely to yield novel insights into how to control fibrotic conditions. Recent Advances An increasing body of evidence suggests a link between mechanical tension and the development of scar tissue. Integrins are the cell surface receptors that mediate interactions between the cell and the surrounding extracellular matrix (ECM). Recent evidence has suggested that, in fibroblasts, the integrin ?1–subunit plays an essential role in mechanosignaling and in dermal homeostasis, repair, and fibrosis. The mechanism underlying these activities of integrin ?1 appears to involve its ability to (1) mediate activation of latent transforming growth factor beta-1 via ECM contraction and (2) modulate collagen production via a focal adhesion kinase/rac1/nicotinamide adenine dinucleotide phosphate oxidase (NOX)/reactive oxygen species (ROS) pathway. Moreover, the integrin ?1–binding protein CCN2, a secreted matricellular protein located within the cellular microenvironment, is required for dermal fibrogenesis. Critical Issues Mechanical tension is a key feature underlying the development of scar tissue. The mechanosignaling sensor integrin ?1 is an essential, central mediator of dermal fibrosis, wound healing, and homeostasis. Future Directions Drugs targeting the molecular mechanism underlying integrin ?1–mediated signaling may represent a novel therapeutic approach for treating fibroproliferative disorders. Clinical trials directly testing this hypothesis are warranted. PMID:24527339

Leask, Andrew

2013-01-01

240

Autoimmune Pancreatitis.  

PubMed

Autoimmune pancreatitis (AIP) is a rare, heterogeneous, fibroinflammatory disorder of the pancreas. It has gained increasing recognition due to a presentation that can mimic difficult to treat disorders such as pancreatic cancer, cholangiocarcinoma and primary sclerosing cholangitis. In contrast, autoimmune pancreatitis is a benign disease that is very responsive to therapy with corticosteroids. There are two types of AIP. Type 1 disease is the most common worldwide and is associated with extrapancreatic manifestations and elevated levels of IgG4-positive cells. Type 2 AIP is characterized by a paucity of IgG4-positive cells, and is more difficult to diagnose. This review provides an update on the diagnosis, pathophysiology and treatment of AIP, with special emphasis on the two subtypes. PMID:24040625

Ketwaroo, Gyanprakash A; Sheth, Sunil

2013-04-01

241

Autoimmune pancreatitis  

PubMed Central

Autoimmune pancreatitis (AIP) is a rare, heterogeneous, fibroinflammatory disorder of the pancreas. It has gained increasing recognition due to a presentation that can mimic difficult-to-treat disorders such as pancreatic cancer, cholangiocarcinoma and primary sclerosing cholangitis. In contrast, autoimmune pancreatitis is a benign disease that is very responsive to therapy with corticosteroids. There are two types of AIP. Type 1 disease is the most common worldwide and is associated with extrapancreatic manifestations and elevated levels of IgG4-positive cells. Type 2 AIP is characterized by a paucity of IgG4-positive cells and is more difficult to diagnose. This review provides an update on the diagnosis, pathophysiology and treatment of AIP, with special emphasis on the two subtypes. PMID:24040625

Ketwaroo, Gyanprakash A.; Sheth, Sunil

2013-01-01

242

Autoimmune pancreatitis.  

PubMed

Autoimmune pancreatitis (AIP) is a rare, heterogeneous, fibroinflammatory disorder of the pancreas. It has gained increasing recognition due to a presentation that can mimic difficult-to-treat disorders such as pancreatic cancer, cholangiocarcinoma and primary sclerosing cholangitis. In contrast, autoimmune pancreatitis is a benign disease that is very responsive to therapy with corticosteroids. There are two types of AIP. Type 1 disease is the most common worldwide and is associated with extrapancreatic manifestations and elevated levels of IgG4-positive cells. Type 2 AIP is characterized by a paucity of IgG4-positive cells and is more difficult to diagnose. This review provides an update on the diagnosis, pathophysiology and treatment of AIP, with special emphasis on the two subtypes. PMID:24759664

Ketwaroo, Gyanprakash A; Sheth, Sunil

2013-07-01

243

[Autoimmune thrombophilia].  

PubMed

Antibodies against phospholipids and phospholipid-binding proteins, especially anti-cardiolipin and anti-beta2-glycoprotein I antibodies, are important diagnostic markers of autoimmune thrombophilia. These autoantibodies are quite common among patients with systemic lupus erythematosus but can also be found in individuals without concurrent rheumatic conditions. Apart from thromboembolic disease, these antibodies are linked to recurring fetal loss and intrauterine fetal death. In patients with recurring thrombotic events in whom anti-phospholipid antibodies or prolonged aPTT (as a sign of lupus anticoagulant activity) is found, long-term or even lifelong anticoagulation therapy should be considered. Habitual spontaneous abortions and other obstetric complications are often preventable with LMW heparin in combination with low-dose acetylsalicylic acid. In this review, we outline a diagnostic strategy for uncovering autoimmune thrombophilia supplemented with functional and genetic tests for hypercoagulability. PMID:16109186

Heegaard, Niels H H; Locht, Henning

2005-08-01

244

Relationship of CD146 expression to activation of circulating T cells: exploratory studies in healthy donors and patients with connective tissue diseases  

PubMed Central

The endothelial cell adhesion molecule, CD146, is expressed on ? 2% of normal circulating T cells, correlating with T cell activation, endothelial interactions and T helper type 17 (Th17) effector functions. In this study, we have characterized CD146 expression in circulating T cells from healthy controls and patients with stable, well-controlled autoimmune connective tissue diseases (CTDs). In vitro, anti-CD3/anti-CD28 stimulation induced CD146 expression in both CD4 and CD8 T cells. In healthy controls and CTD patients, CD146 was associated with expression of recent and chronic activation markers (CD25+, OX-40+, CD69+, CD27–) and was confined to CD45RO+/RA–/CD28+ populations within the CD4 subset. Except for CD69, these markers were not associated with CD146 in the CD8 subset. Surprisingly, most CTD patients exhibited no T cell hyperactivation ex vivo. In five of five patients with secondary Sjögren's syndrome circulating T cells appeared activated despite therapy, and CD146 up-regulation, associated with activation markers, was observed both on CD4 and CD8 T cells. There was no association between CD146 and putative pro-atherogenic T cell subsets. In conclusion, the relationship of CD146 expression to T cell activation differs between T cell subsets in healthy subjects and correlates with systemic hyperactivity, where present, in patients with CTDs, as exemplified by the patients with secondary Sjögren's syndrome in this study. PMID:23738744

Hadjinicolaou, A V; Wu, L; Fang, B; Watson, P A; Hall, F C; Busch, R

2013-01-01

245

Connectivity.  

PubMed

The connectivity of neuronal systems is their most fundamental characteristic. Here, we focus on recent developments in understanding structural and functional connectivity at the macroscale, which is accessible with current imaging technology. Structural connectivity is examined via diffusion weighted imaging methods, of which diffusion tensor imaging is the most frequently used. Many cross-sectional and an increasing number of longitudinal studies using diffusion tensor imaging have been recently conducted over the period of development starting with newborns. Functional connectivity has been studied through task-based functional magnetic resonance imaging, and increasingly through studies on task-free functional imaging, also known as resting state functional imaging. The study of intrinsic functional connectivity beginning during fetal life reveals the developmental organization of intrinsic connectivity networks such as the default mode network, the dorsal attention network, the frontal-parietal executive control network, as well as primary cortical networks. As methods of examining both structural and functional connectivity mature, they increasingly inform our understanding of the development of connectivity in service of the long-term goal of delineating the substrates of much of developmental psychopathology. PMID:23943564

Castellanos, Francisco Xavier; Cortese, Samuele; Proal, Erika

2014-01-01

246

Connectivity  

ERIC Educational Resources Information Center

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.…

Grush, Mary, Ed.

2006-01-01

247

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

PubMed

The authors report a rare case of a female patient with mixed connective tissue disease (MCTD) with coexisting antiphospholipid syndrome (APS). Five years after the diagnosis of MCTD high concentrations of anticardiolipin (anti-CL) and anti-?2-glycoprotein (anti-?2GPI) autoantibodies were present in the patient's serum without thrombotic events. Epstein-Barr virus (EBV) reactivation provoked APS, with the clinical manifestations of livedo reticularis, digital gangrene and leg ulcers. Skin biopsy from the necrotic area showed multiple fibrin microthrombi in the superficial vessels. Corticosteroid pulse therapy, and plasma exchange in combination with synchronized cyclophosphamide was administered, which led to improvement of the digital gangrenes, while no new lesions developed. The number of CD27high plasma cells decreased, and the previous high levels of autoantibodies also normalized in the peripheral blood. In the case of MCTD with coexisting APS combination therapy, including plasmapheresis has beneficial effects. PMID:24795068

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

2014-09-01

248

Photothermal effects in connective tissues mediated by laser-activated gold nanorods.  

PubMed

We report a study on the application of laser-activated nanoparticles in the direct welding of connective tissues, which may become a valuable technology in biomedicine. We use colloidal gold nanorods as new near-infrared chromophores to mediate functional photothermal effects in the eye lens capsules. Samples obtained ex vivo from porcine eyes are treated to simulate heterotransplants with 810-nm diode laser radiation in association with a stain of gold nanorods of aspect ratio approximately 4. This stain is applied at the interface between a patch of capsule from a donor eye and the capsule of a recipient eye. Then, by administration of laser pulses of 40 msec and approximately 100-140 J/cm(2), we achieved the local denaturation of the endogenous collagen filaments, which reveals that the treated area reached temperatures above 50 degrees C. The thermal damage is confined within 50-70 mum in a radial distance from the irradiated area. PMID:19223241

Ratto, Fulvio; Matteini, Paolo; Rossi, Francesca; Menabuoni, Luca; Tiwari, Neha; Kulkarni, Sulabha K; Pini, Roberto

2009-06-01

249

Effects of connective tissue growth factor (CTGF) gene silencing on the radiosensitivity of glioblastoma  

PubMed Central

The effects of connective tissue growth factor (CTGF) gene silencing on the radiosensitivity of glioblastoma cells (GBM) were investigated. The lentivirus-mediated short hairpin RNA (shRNA) expression vector targeting CTGF was constructed and transinfected into U87MG human GBM cell line. The CTGF gene expression in U87MG cells was significantly down-regulated. After irradiation with 6 MV X-rays at a dose rate of 2.5 Gy/min, the clonogenicity, proliferation and migration of U87MG cells were assayed in vitro. The survival, proliferation and migration of U87MG cells were all remarkably inhibited by CTGF silencing (p < 0.05 vs control). Our results demonstrate that CTGF is important for GBM and CTGF gene silencing can be a potential tool to enhance the sensitivity of GBM to radiotherapy. PMID:25356109

Han, Na; Shahveranov, Allahverdi; Cheng, Yi; Qin, Kai; Yu, Shi-Ying; Zhang, Meng-Xian

2014-01-01

250

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

PubMed

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

Wilson, Golder N

2014-05-01

251

Spontaneous Esophageal Perforation in a Patient with Mixed Connective Tissue Disease  

PubMed Central

Spontaneous esophageal perforation is a rare and life-threatening disorder. Failure to diagnosis within the first 24-48 hours of presentation portends a poor prognosis. A patient with mixed connective tissue disease (MCTD) on low-dose prednisone and methotrexate presented moribund with chest and shoulder pain, a left hydropneumothorax, progressive respiratory failure and shock. Initial management focussed on presumed community acquired pneumonia (CAP) in a patient on immunosuppressants. Bilateral yeast empyemas were treated and attributed to immunosuppression. On day 26, the patient developed mediastinitis, and the diagnosis of esophageal perforation was first considered. A review of the literature suggests that the diagnosis and management of spontaneous esophageal perforation could have been more timely and the outcome less catastrophic. PMID:22279514

Lyman, David

2011-01-01

252

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

PubMed Central

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

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

253

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

PubMed

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

Leask, Andrew

2013-08-01

254

Structural and biochemical characteristics of bovine intramuscular connective tissue and beef quality.  

PubMed

The aim of the study was to evaluate the impact of structural and biochemical characteristics of muscle intramuscular connective tissue on beef quality. The experimental design was based on three muscles of three breeds sampled as fresh material and cooked at 55°C (Longissimus thoracis and Semimembranosus) or at 70°C (Semimembranosus and Biceps femoris) for quality assessment. The results showed that muscle characteristics influence beef quality differently from one muscle to another. In grilled LT, proteoglycan content contributed negatively to juiciness, and intramuscular lipids were linked positively to tenderness, flavour, residues and overall liking scores. In grilled SM, cross-link and lipid contents were involved in beef quality. In BF cooked to 70°C, perimysial branch points were negatively linked to tenderness. In SM cooked to 70°C, perimysial area was involved in beef quality. These results should allow a better understanding of the factors involved in background toughness, in juiciness and flavour of meat. PMID:23793095

Dubost, Annabelle; Micol, Didier; Picard, Brigitte; Lethias, Claire; Andueza, Donato; Bauchart, Dominique; Listrat, Anne

2013-11-01

255

Cutaneous Manifestations of Mixed Connective Tissue Disease: Study from a Tertiary Care Hospital in Eastern India  

PubMed Central

Context: Mixed connective tissue disorder is an uncommon disease. Some scientists are reluctant to recognize it as a separate entity. Some others have defined this ailment. Cutaneous features of this condition are unique. Researchers from India have described these features to relate to those described in the studies from other parts of the globe. Aims: This study aims to delineate the skin manifestations of clearly defined mixed connective tissue disease (MCTD) patients, to compare them with those established as overlap syndrome, and to relate them with studies from other parts of the globe. Settings and Design: Successive patients who fulfilled the specific criteria for MCTD presenting in the skin outpatient department of a tertiary care hospital in eastern India were clinically examined from 2009 for 3 years. Materials and Methods: The number of participants was 23 and the dermatological features of these were compared with 22 patients with overlap syndrome. The antibody to uridine-rich U1 ribonucleoprotein was measured for all patients. Statistical Analysis Used: SPSS (Version 17) and MedCalc (Version 11.6). Results: The Male: Female ratio among the MCTD patients was 1:6.67 and that of the overlap syndrome was 1:10. Twenty patients of the MCTD group presented with synovitis as against only seven in the overlap group. Raynaud's phenomenon was present in some of the subjects. Puffy fingers were rare in our study. Facial numbness was reported by four of those suffering from MCTD. Antinuclear antibody (ANA) was essentially of a speckled pattern in this disease Conclusions: Cutaneous indicators of MCTD are distinct from overlap syndrome. Knowledge of these manifestations prevalent in a region may lead to early diagnosis of the disease. PMID:24470658

Sen, Sumit; Sinhamahapatra, Pradyot; Choudhury, Supriyo; Gangopadhyay, Anusree; Bala, Sanchaita; Sircar, Geetabali; Chatterjee, Gobinda; Ghosh, Alakendu

2014-01-01

256

Recommendations for Screening and Detection of Connective-Tissue Disease Associated Pulmonary Arterial Hypertension  

PubMed Central

Objectives Pulmonary arterial hypertension (PAH) affects up to 15% of patients with connective tissue diseases (CTD). Previous recommendations developed as part of larger efforts in PAH did not provide detailed recommendations for patients with CTD-PAH. Therefore, we sought to develop recommendations for screening and early detection of CTD-PAH. Methods We performed a systematic review for the screening and diagnosis of PAH in CTD by searching the literature. Using the RAND/UCLA methodology, we developed case scenarios followed by 2 stages of voting—first international experts from a variety of specialties voted anonymously on the appropriateness of each case scenario and then the experts met in a face-to-face meeting to discuss and resolve discrepant votes to arrive at consensus recommendations. Results The key recommendations state that patients with systemic sclerosis (SSc) should be screened for PAH. In addition, mixed connective tissue diseases (MCTD) or other CTD’s with scleroderma features should also be screened for PAH (scleroderma-spectrum disorder). Initial screening evaluation in patients with SSc and scleroderma-spectrum disorders include pulmonary function test (PFT) including diffusion capacity carbon monoxide (DLCO), transthoracic echocardiogram (TTE), and NT- Pro BNP. In SSc and spectrum disorders, TTE and PFT should be performed on annual basis. The full screening panel (TTE, PFT, and NT-ProBNP) should be performed as soon as any new signs or symptoms are present. Conclusion We provide consensus-based, evidence-driven recommendations for screening and early detection of CTD-PAH. It is our hope that these recommendations will lead to earlier detection of CTD-PAH and ultimately improve patient outcomes. PMID:24022584

Khanna, Dinesh; Gladue, Heather; Channick, Richard; Chung, Lorinda; Distler, Oliver; Furst, Daniel E.; Hachulla, Eric; Humbert, Marc; Langleben, David; Mathai, Stephen C.; Saggar, Rajeev; Visovatti, Scott; Altorok, Nezam; Townsend, Whitney; FitzGerald, John; McLaughlin, Vallerie

2013-01-01

257

Permeability of connective tissue linings isolated from implanted capsules; implications for interstitial pressure measurements.  

PubMed

Quantification of the permeability of connective tissue linings isolated from implanted capsules was achieved by two types of experiments. The objective of the first type was to determine the restriction offered by the lining to diffusion of 125I-labeled human serum albumin. The restricted diffusion coefficient of albumin with respect to the connective tissue lining the luminal capsule surface (internal lining) averaged 3.0 times 10-7 plus or minus 0.4 times 10-7 cm2/sec in ten experiments indicating that the rate if migration of albumin across the structure was 35% of its free diffusion rate in water. In contrast, the albumin diffusion coefficient obtained for the abluminal (external) lining suggested that diffusion of albumin through this structure was 73% of the free diffusion rate in water. The objective of the second type of experiment was to determine solute reflection coefficients for inulin, serum albumin, and gamma-globulin with respect to the internal and external linings. For the internal lining, the reflection coefficients were: inulin 0.07, albumin0.23, and gamma-globulin 0.53. The external lining showed greater leakiness as evidenced by its lower reflection coefficient for a given molecule and its higher hydraulic conductivity. An equivalent pore calculation resulted in a calculated pore radius of 250-350 angstrom for the internal lining and a calculated pore radius of 500-600 angstrom for the external lining. The ineffectiveness of the leaky capsule lining in transmitting oncotic pressure suggests that under normal conditions the capsule measures interstitial hydrostatic pressure rather than oncotic pressure. PMID:1116223

Granger, H J; Taylor, A E

1975-01-01

258

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

PubMed Central

The objective of this study was to evaluate the efficacy of connective tissue massage to improve blood circulation and intermittent claudication symptoms in type 2 diabetic patients. A randomized, placebo-controlled trial was undertaken. Ninety-eight type 2 diabetes patients with stage I or II-a peripheral arterial disease (PAD) (Leriche-Fontaine classification) were randomly assigned to a massage group or to a placebo group treated using disconnected magnetotherapy equipment. Peripheral arterial circulation was determined by measuring differential segmental arterial pressure, heart rate, skin temperature, oxygen saturation and skin blood flow. Measurements were taken before and at 30?min, 6 months and 1 year after the 15-week treatment. After the 15-week program, the groups differed (P < .05) in differential segmental arterial pressure in right lower limb (lower one-third of thigh, upper and lower one-third of leg) and left lower limb (lower one-third of thigh and upper and lower one-third of leg). A significant difference (P < .05) was also observed in skin blood flow in digits 1 and 4 of right foot and digits 2, 4 and 5 of left foot. ANOVA results were significant (P < .05) for right and left foot oxygen saturation but not for heart rate and temperature. At 6 months and 1 year, the groups differed in differential segmental arterial pressure in upper third of left and right legs. Connective tissue massage improves blood circulation in the lower limbs of type 2 diabetic patients at stage I or II-a and may be useful to slow the progression of PAD. PMID:19933770

Castro-Sánchez, Adelaida María; Moreno-Lorenzo, Carmen; Matarán-Peńarrocha, Guillermo A.; Feriche-Fernández-Castanys, Belen; Granados-Gámez, Genoveva; Quesada-Rubio, José Manuel

2011-01-01

259

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 ...

260

Connective Tissue Growth Factor Is Required for Skeletal Development and Postnatal Skeletal Homeostasis in Male Mice  

PubMed Central

Connective tissue growth factor (CTGF), a member of the cysteine-rich 61 (Cyr 61), CTGF, nephroblastoma overexpressed (NOV) (CCN) family of proteins, is synthesized by osteoblasts, and its overexpression inhibits osteoblastogenesis and causes osteopenia. The global inactivation of Ctgf leads to defective endochondral bone formation and perinatal lethality; therefore, the consequences of Ctgf inactivation on the postnatal skeleton are not known. To study the function of CTGF, we generated Ctgf+/LacZ heterozygous null mice and tissue-specific null Ctgf mice by mating Ctgf conditional mice, where Ctgf is flanked by lox sequences with mice expressing the Cre recombinase under the control of the paired-related homeobox gene 1 (Prx1) enhancer (Prx1-Cre) or the osteocalcin promoter (Oc-Cre). Ctgf+/LacZ heterozygous mice exhibited transient osteopenia at 1 month of age secondary to decreased trabecular number. A similar osteopenic phenotype was observed in 1-month-old Ctgf conditional null male mice generated with Prx1-Cre, suggesting that the decreased trabecular number was secondary to impaired endochondral bone formation. In contrast, when the conditional deletion of Ctgf was achieved by Oc-Cre, an osteopenic phenotype was observed only in 6-month-old male mice. Osteoblast and osteoclast number, bone formation, and eroded surface were not affected in Ctgf heterozygous or conditional null mice. In conclusion, CTGF is necessary for normal skeletal development but to a lesser extent for postnatal skeletal homeostasis. PMID:20534727

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

2010-01-01

261

In vitro selection and characterization of deoxyribonucleic acid aptamers against connective tissue growth factor.  

PubMed

Connective tissue growth factor (CTGF) is a secreted matricellular protein possessing complex biological functions. CTGF modulates a number of signaling pathways that are involved in cell adhesion, migration, angiogenesis, myofibroblast activation, extracellular matrix deposition and tissue remodeling. Aptamers are oligonucleic acid chains or polypeptides that bind with specific target molecules hence have the potential to be used in the detection and blockade of the targets. In this study, we selected CTGF-targeting DNA aptamers by using systematic evolution of ligands by exponential enrichment (SELEX). After 8 iterative rounds of selection, cloning, DNA sequencing and affinity determination, six aptamers with high affinities to CTGF were obtained. Among them, one (C-ap17P) binds with the N-terminal region (aa 1-190) and the other five (C-ap11, 12, 14, 15 and 18) bind with the C-terminal region (aa 191-350) of hCTGF specifically. The biological stability assay indicated that a representative aptamer, C-ap17P, could keep its integrity at a rather high level for at least 24 h in complete DMEM cell culture medium. These CTGF aptamers might be used as a easy and fast detection tool for CTGF and be developed as CTGF-specific inhibitors for both research works and clinical applications. PMID:25603056

Li, Shuang; Huo, Yongwei; Tian, Hong; Zhang, Qiannan; Lv, Yifei; Hao, Zhiming

2015-02-20

262

Connective Tissue Growth Factor Overexpression in Cardiomyocytes Promotes Cardiac Hypertrophy and Protection against Pressure Overload  

PubMed Central

Connective tissue growth factor (CTGF) is a secreted protein that is strongly induced in human and experimental heart failure. CTGF is said to be profibrotic; however, the precise function of CTGF is unclear. We generated transgenic mice and rats with cardiomyocyte-specific CTGF overexpression (CTGF-TG). To investigate CTGF as a fibrosis inducer, we performed morphological and gene expression analyses of CTGF-TG mice and rat hearts under basal conditions and after stimulation with angiotensin II (Ang II) or isoproterenol, respectively. Surprisingly, cardiac tissues of both models did not show increased fibrosis or enhanced gene expression of fibrotic markers. In contrast to controls, Ang II treated CTGF-TG mice displayed preserved cardiac function. However, CTGF-TG mice developed age-dependent cardiac dysfunction at the age of 7 months. CTGF related heart failure was associated with Akt and JNK activation, but not with the induction of natriuretic peptides. Furthermore, cardiomyocytes from CTGF-TG mice showed unaffected cellular contractility and an increased Ca2+ reuptake from sarcoplasmatic reticulum. In an ischemia/reperfusion model CTGF-TG hearts did not differ from controls. Our data suggest that CTGF itself does not induce cardiac fibrosis. Moreover, it is involved in hypertrophy induction and cellular remodeling depending on the cardiac stress stimulus. Our new transgenic animals are valuable models for reconsideration of CTGF's profibrotic function in the heart. PMID:19707545

Panek, Anna N.; Posch, Maximilian G.; Alenina, Natalia; Ghadge, Santhosh K.; Erdmann, Bettina; Popova, Elena; Perrot, Andreas; Geier, Christian; Morano, Rainer Dietz Ingo; Bader, Michael; Özcelik, Cemil

2009-01-01

263

Recombinant expression, purification, and functional characterisation of connective tissue growth factor and nephroblastoma-overexpressed protein.  

PubMed

The CCN family of proteins, especially its prominent member, the Connective tissue growth factor (CTGF/CCN2) has been identified as a possible biomarker for the diagnosis of fibrotic diseases. As a downstream mediator of TGF-?1 signalling, it is involved in tissue scarring, stimulates interstitial deposition of extracellular matrix proteins, and promotes proliferation of several cell types. Another member of this family, the Nephroblastoma-Overexpressed protein (NOV/CCN3), has growth-inhibiting properties. First reports further suggest that these two CCN family members act opposite to each other in regulating extracellular matrix protein expression and reciprocally influence their own expression when over-expressed. We have established stable HEK and Flp-In-293 clones as productive sources for recombinant human CCN2/CTGF. In addition, we generated an adenoviral vector for recombinant expression of rat NOV and established protocols to purify large quantities of these CCN proteins. The identity of purified human CCN2/CTGF and rat CCN3/NOV was proven by In-gel digest followed by ESI-TOF/MS mass spectrometry. The biological activity of purified proteins was demonstrated using a Smad3-sensitive reporter gene and BrdU proliferation assay in permanent cell line EA•hy 926 cells. We further demonstrate for the first time that both recombinant CCN proteins are N-glycosylated. PMID:21209863

Bohr, Wilhelm; Kupper, Michael; Hoffmann, Kurt; Weiskirchen, Ralf

2010-01-01

264

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

SciTech Connect

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 fibroblasts both in vitro and in vivo. Specifically, the neodymium-yttrium-aluminum-garnet (Nd: YAG) laser was shown to selectively suppress collagen production both in fibroblast cultures and in normal skin in vivo, thus suggesting that this laser modality may be useful for the treatment of fibrotic conditions such as keloids and hypertrophic scars. Furthermore, two low-energy lasers, helium-neon (He-Ne) and gallium-arsenide (Ga-As), were shown to stimulate collagen production in human skin fibroblast cultures, suggesting that these lasers could be used for enhancement of wound healing processes. These experimental approaches illustrate the future possibilities for applying lasers for the modulation of various biologic functions of cells in tissues and attest to the potential role of lasers in the treatment of cutaneous disorders.

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

1984-12-01

265

Subcutaneous Connective Tissue Reactions to Various Endodontic Biomaterials: An Animal Study  

PubMed Central

Background and aims Biocompatibility of root-end filling materials is a matter of debate. The aim of this study was to compare the biocompatibility of a variety of commercial ProRoot WMTA cements and a resin-based cement (Geristore®) with different pH values of setting reaction and different aluminum contents, implanted into the subcutaneous connective tissue of rats at various time intervals. Materials and methods Fifty Sprague-Dawley rats were used in this study. Polyethylene tubes were filled with Angelus WMTA, ProRoot WMTA, Bioaggregate, and Geristore. Empty control tubes were implanted into subcutaneous tissues and harvested at 7-, 14-, 28- and 60-day intervals. Tissue sections of 5 ?m were stained with hematoxylin and eosin and observed under a light microscope. Inflammatory reactions were categorized as 0, none (without inflammatory cells); 1, mild (inflammatory cells ?25); 2, moderate (25–125 inflammatory cells); and 3, severe (>125 inflammatory cells). Statistical analysis was performed with Kruskal-Wallis and Mann Whitney U tests. Results ProRoot WMTA and Angelus elicited significantly less inflammation than other materials (P<0.05). After 7 days, however, all the materials induced significantly more inflammation than the controls (P<0.05). Angelus-MTA group exhi-bited no significant differences from the Bioaggregate group (P=0.15); however, ProRoot WMTA elicited significantly less inflammation than Bioaggregate (P=0.02). Geristore induced significantly more inflammation than other groups (P<0.05). Conclusion Geristore induced an inflammatory response higher than ProRoot WMTA; therefore, it is not recommended for clinical use. PMID:23486841

Saghiri, Mohammad Ali; Tanideh, Nader; Garcia-Godoy, Franklin; Lotfi, Mehrdad; Karamifar, Kasra; Amanat, Dariush

2013-01-01

266

Slowing the Onset of Hypoxia Increases Colony Forming Efficiency of Connective Tissue Progenitor Cells In Vitro  

PubMed Central

Background Survival and colony formation by transplanted tissue derived connective tissue progenitor cells (CTPs) are thought to be important factors in the success of clinical tissue engineering strategies for bone regeneration. Transplantation of cells into defects larger than a few millimeters expose cells to a profoundly hypoxic environment. This study tested the hypothesis that delaying the onset of hypoxia will improve the survival and performance of CTPs in vitro. Methods To mimic declines seen in an avascular in vivo bone defect, colony forming efficiency by marrow derived nucleated cells was assessed under osteogenic conditions. Variation in the rate of oxygen decline from an oxygen tension of 21% to 0.1% oxygen was explored using an incubator with programmable active control of gas concentrations. The effect of doping cultures with defined concentrations of RBCs was also used to evaluate the potential for RBCs to serve as a natural buffer in the setting of declining oxygen levels. Results A delay in onset of hypoxia over 96 hours resulted in a 3-fold increase in the relative colony forming efficiency (rCFE) of CTPs as compared to an immediate onset of hypoxia. The presence of RBCs in vitro inhibited the rCFE of CTPs. Given the negative effects of RBCs, methods of RBC removal were evaluated and compared for their effectiveness of RBC removal and retention of colony forming efficiency. Conclusions These data suggest that conditions of hypoxia compromise colony forming efficiency in marrow derived CTPs. However, slowing the rate of decline of oxygen preserved colony forming efficiency at levels achieved in a stable normoxic (3% O2) environment. These data also suggest that RBCs are detrimental to the rCFE of CTPs and that buffy coat is an effective and preferred method for removing RBCs from marrow aspirates while preserving CTPs. These findings may inform clinical strategies for CTP transplantation. PMID:24371519

Caralla, Tonya N.; Boehm, Cynthia A.; Patterson, Thomas E.; Muschler, George F.

2013-01-01

267

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

PubMed Central

AIM: To determine the utility of connective tissue growth factor (CCN2/CTGF) for assessing hepatic fibrosis in hepatitis B virus (HBV)-induced chronic liver diseases (CLD-B). METHODS: Enzyme-linked immunosorbent assay was used to measure CCN2 in sera from 107 patients with chronic hepatitis B (CHB) and 39 patients with HBV-induced active liver cirrhosis and 30 healthy individuals. Liver samples from 31 patients with CHB, 8 patients with HBV-induced liver cirrhosis and 8 HBV carriers with normal liver histology were examined for transforming growth factor ?-1 (TGF-?1) or CCN2 mRNA levels by in situ hybridization, and computer image analysis was performed to measure integrated optimal density (IOD) of CCN2 mRNA-positive cells in liver tissues. Histological inflammation grading and fibrosis staging were evaluated by H and E staining and Van Gieson’s method. RESULTS: Serum CCN2 concentrations were, respectively, 4.0- or 4.9-fold higher in patients with CHB or active liver cirrhosis as compared to healthy individuals (P < 0.01). There was good consistency between the levels of CCN2 in sera and CCN2 mRNA expression in liver tissues (r = 0.87, P < 0.01). The levels of CCN2 in sera were increased with the enhancement of histological fibrosis staging in patients with CLD-B (r = 0.85, P < 0.01). Serum CCN2 was a reliable marker for the assessment of liver fibrosis, with areas under the receiver operating characteristic (ROC) curves (AUC) of 0.94 or 0.85 for, respectively, distinguishing normal liver controls from patients with F1 stage liver fibrosis or discriminating between mild and significant fibrosis. CONCLUSION: Detection of serum CCN2 in patients with CLD-B may have clinical significance for assessment of severity of hepatic fibrosis. PMID:22611323

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

2012-01-01

268

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 ...

269

Autoimmune Epilepsy  

PubMed Central

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

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

270

Gene Expression and Distribution of Connective Tissue Growth Factor (CCN2\\/CTGF) During Secondary Ossification Center Formation  

Microsoft Academic Search

CCN2\\/connective tissue growth factor (CCN2\\/CTGF) is a critical signaling modulator of mesenchymal tissue development. This study investigated the localization and expression of CCN2\\/CTGF as a factor supporting angiogenesis and chondrogenesis during development of secondary ossification centers in the mouse tibial epiphysis. Formation of the secondary ossification center was initiated by cartilage canal formation and blood vessel invasion at 7 days

Morihiko Oka; Satoshi Kubota; Seiji Kondo; Takanori Eguchi; Chisa Kuroda; Kazumi Kawata; Shogo Minagi; Masaharu Takigawa

2007-01-01

271

Mercury species in lymphoid and non-lymphoid tissues after exposure to methyl mercury: Correlation with autoimmune parameters during and after treatment in susceptible mice  

SciTech Connect

Methylmercury (MeHg) is present in the environment as a result of the global cycling of mercury, although anthropogenic sources may dramatically increase the availability in confined geographical areas. Accumulation of MeHg in the aquatic food chain is the dominating way of exposure in mammals, which accumulate MeHg in all organs, including Brain. Demethylation has been described in the organs, especially in phagocytic cells, but mainly in the flora of the intestinal tract. While most of the inorganic mercury (Hg{sup 2+}) formed in the intestine is excreted, a fraction is reabsorbed which together with the local demethylation increases the organ Hg{sup 2+} concentration. MeHg is a well-known immunosuppressive agent, while Hg{sup 2+} is associated with immunostimulation and autoimmunity especially in genetically susceptible rodents, creating a syndrome, i.e. mercury-induced autoimmunity (HgIA). This study aimed at exploring the effect of MeHg with regard to HgIA, and especially the immunological events after stopping treatment, correlated with the presence of MeHg and Hg{sup 2+} in the organs. Treatment of A.SW mice for 30 days with 4.2 mg MeHg/L drinking water (corresponding to approximately 420 {mu}g Hg/kg body weight/day) caused all the HgIA features observed after primary treatment with inorganic Hg, except systemic immune complex deposits. The total Hg concentration was 5-fold higher in the kidneys as compared with lymph nodes, but the fraction of Hg{sup 2+} was similar (17-20%). After stopping treatment, the renal and lymph node MeHg concentration declined according to first order kinetics during the initial 4-6 weeks, but then slower. A similar decline in the organ Hg{sup 2+} concentration occurred during the initial 2 weeks after stopping treatment but then ceased, causing the Hg{sup 2+} concentration to exceed that of MeHg in the lymph nodes and kidneys after 3 and 8 weeks, respectively. The selective increase in lymph node Hg{sup 2+} fraction is likely to be due to demethylation of MeHg in the macrophage-rich lymphoid tissue. The major autoantibody in HgIA, anti-fibrillarin antibodies, tended to increase during the initial 6 weeks after stopping treatment, while all other HgIA features including antichromatin antibodies declined to control levels after 2-4 weeks. This indicates differences in either dose requirement or induction mechanisms for the different HgIA parameters. The selective accumulation of Hg{sup 2+} in lymph nodes following MeHg treatment should be taken into account when the effect of MeHg on the immune system is evaluated.

Havarinasab, Said [Molecular and Immunological Pathology (AIR), Department of Molecular and Clinical Medicine, Linkoeping University, SE-581 85 Linkoeping (Sweden); Bjoern, Erik [Department of Chemistry, Analytical Chemistry, Umea University, SE-901 87 Umea (Sweden); Nielsen, Jesper B. [Department of Environmental Medicine, University of Southern Denmark, DK-5230 Odense (Denmark); Hultman, Per [Molecular and Immunological Pathology (AIR), Department of Molecular and Clinical Medicine, Linkoeping University, SE-581 85 Linkoeping (Sweden)]. E-mail: perhu@imk.liu.se

2007-05-15

272

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

PubMed Central

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

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

273

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

PubMed Central

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

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

2014-01-01

274

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

PubMed

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

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

2015-04-01

275

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)

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.

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

1990-01-01

276

Tetracyclines Inhibit Connective Tissue Breakdown: NewTherapeutic Implications for anOldFamily ofDrugs  

Microsoft Academic Search

Tetracyclines havelong beenconsidered useful adjuncts inperidontal therapy based ontheir antimicrobial efficacy against putative periodontopathogens. However, recently these drugs werefound toinhibit mammalian collagenases andseveral other matrix metalloproteinases (MMPs)byamechanism independent of their antimicrobial activity. Evidence ispresented that this property maybetherapeutically useful inretarding pathologic connective tissue breakdown, including boneresorption. Theexperiments leading tothis discovery aredescribed andpossible mechanisms areaddressed, including thespecificity oftetracyclines' anti-collagenase activity, therole

Robert A. Greenwald; Barry R. Rifkin

277

Histological and histomorphometrical study of connective tissue around calcium phosphate coated titanium dental implants in a canine model  

Microsoft Academic Search

Connective tissue reaction and collagen fiber orientation were evaluated on the calcium phosphate coated implants made by ion beam assisted deposition, and compared with the uncoated titanium implants. Twelve implants of each group were randomly placed in mandibles after 3 months of premolars extraction in beagle dogs. All the implants were firmly anchored in the bone and had no clinical signs

Bao Hong Zhao; Inho Han; Hai Lan Feng; Wei Bai; Fu-Zhai Cui; In-Seop Lee

2007-01-01

278

Undifferentiated connective tissue disease: Natural history and evolution into definite CTD assessed in 84 patients initially diagnosed as early UCTD  

Microsoft Academic Search

Connective tissue diseases (CTDs) are chronic multisystemic inflammatory disorders whose indicative signs or symptoms have a high sensitivity but poor specificity in predicting the evolution into a given CTD. We have analysed 84 consecutive patients initially diagnosed as having an early undifferentiated CTD (early UCTD) with the aim of verifying the evolution into one definite CTD and of evaluating the

M. G. Danieli; P. Fraticelli; A. Salvi; A. Gabrielli; G. Danieli

1998-01-01

279

Pulmonary artery pressure variation in patients with connective tissue disease: 24 hour ambulatory pulmonary artery pressure monitoring  

Microsoft Academic Search

BACKGROUNDThe specific contribution of secondary pulmonary hypertension to the morbidity and mortality of patients with underlying lung disease can be difficult to assess from single measurements of pulmonary artery pressure. We have studied patients with secondary pulmonary hypertension using an ambulatory system for measuring continuous pulmonary artery pressure (PAP). We chose to study patients with connective tissue disease because they

D A Raeside; G Chalmers; J Clelland; R Madhok; A J Peacock

1998-01-01

280

Detection of Luse bodies, spiralled collagen, dysplastic collagen, and intracellular collagen in rheumatoid connective tissues: an electron microscopic study  

Microsoft Academic Search

BACKGROUND--Rheumatoid arthritis is a chronic inflammatory disease leading to alterations of the extracellular matrix in tendons, ligaments, and cartilage. The structural changes of the collagenous systems in rheumatoid connective tissues are largely unknown, however. METHODS--Thirty four samples of menisci, 36 cruciate ligaments, and four tendons were taken during joint surgery in patients with rheumatoid arthritis. Eighteen menisci, 35 ligaments, and

M F Neurath

1993-01-01

281

Connective tissue growth factor in pterygium: simultaneous presence with vascular endothelial growth factor - possible contributing factor to conjunctival scarring  

Microsoft Academic Search

Background. Various growth factors have been detected in pterygium and been associated with its vasculogenesis. The basic pathophysiological mechanisms responsible especially for the fibrotic activity in pterygium are, however, not yet known. Connective tissue growth factor (CTGF) has been shown to be substantially involved in various processes of fibrosis. We report on the presence of CTGF in pterygium and its

Gysbert van Setten; Miltos Aspiotis; Timothy D. Blalock; Gary Grotendorst; Gregory Schultz

2003-01-01

282

Adhesion molecules mediating neutrophil migration to arthritis in vivo and across endothelium and connective tissue barriers in vitro  

Microsoft Academic Search

Neutrophils, or polymorphonuclear leukocytes (PMNLs), migrate through vascular endothelium and in connective tissue during inflammation. In rats with adjuvant arthritis, migration to joints of radiolabeled (111In) blood PMNLs was examined to define the role of specific selectin and integrin adhesion molecules in this process. Based on monoclonal antibody studies, P-selectin was required for normal PMNL migration to the joints. Although

A. C. Issekutz

1998-01-01

283

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

E-print Network

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

Konofagou, Elisa E.

284

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

PubMed Central

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

Li, Qiaoli; Jiang, Qiujie; Uitto, Jouni

2013-01-01

285

Connective tissue disease-associated pulmonary arterial hypertension in Chinese patients.  

PubMed

We sought to investigate the characteristics, survival and risk factors for mortality in Chinese patients with connective tissue disease (CTD)-associated pulmonary arterial hypertension (APAH) in modern therapy era. 129 consecutive adult patients who visited one of three referral centres in China with a diagnosis of CTD-APAH confirmed by right heart catheterisation during the previous 5 years were enrolled. The end-point was all-cause death or data censoring. Systemic lupus erythematosus was the most common underlying CTD (49%) and systemic sclerosis just accounted for 6% in this cohort. The overall survival at 1 and 3 years was 92% and 80%, respectively. Pericardial effusion, a shorter 6-min walk distance, lower mixed venous oxygen saturation, higher pulmonary vascular resistance (PVR) and alkaline phosphatase (ALP), and lower total cholesterol levels were all associated with a higher risk of death among the study population. Higher PVR and ALP were independent predictors of mortality. In conclusion, unlike in western patients, systemic lupus erythematosus is the most common underlying disease in Chinese patients with CTD-APAH. The survival of Chinese patients with CTD-APAH in the modern treatment era is similar to that in western countries. Elevated PVR and ALP are independent risk factors for poor outcomes. PMID:24791829

Hao, Yan-Jie; Jiang, Xin; Zhou, Wei; Wang, Yong; Gao, Lan; Wang, Yu; Li, Guang-Tao; Hong, Tao; Huo, Yong; Jing, Zhi-Cheng; Zhang, Zhuo-Li

2014-10-01

286

The Mechanical Properties of the Rabbit Carpal Tunnel Subsynovial Connective Tissue  

PubMed Central

The rabbit model is commonly used to study carpal tunnel syndrome (CTS). It has been proposed that the subsynovial connective tissue (SSCT) in the carpal tunnel may play a role in the etiology of CTS, but the material properties of the rabbit SSCT are unknown. The purpose of this study was to develop a method to measure the shear properties of the rabbit SSCT. In six rabbit cadaver forepaws, the excursion of the third digit flexor digitorum superficialis (FDS) and load to failure of the SSCT were measured in a custom device. The mean excursion to full flexion in this model was 7.08 mm (SD 0.77). The mean shearing force at full flexion was 317 mN (SD 166). At full flexion percentage of maximum shear force in the SSCT was 54.5% (SD 19.4). The mean energy absorbed at full flexion was 0.29 mJ (SD 0.31). The mean excursion needed to reach 5% of the maximum shear force was 3.04 mm (SD 0.99). The testing model presented in this study demonstrates structural parameters to evaluate the shear properties of the SSCT in a rabbit model. The data presented could be used for estimating sample sizes in a more comprehensive study of the effect of CTS on the SSCT properties. PMID:17631885

Yamaguchi, Taihei; Osamura, Naoki; Zhao, Chunfeng; Zobitz, Mark E.; An, Kai-Nan; Amadio, Peter C.

2008-01-01

287

Connective tissue mineralization in Abcc6-/- mice, a model for pseudoxanthoma elasticum.  

PubMed

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

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

2012-05-01

288

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

PubMed

This in vitro study was designed to investigate the molecular mechanisms of paraquat-induced damage using cultured human fetal lung fibroblasts (MRC-5 cells), in order to promote the development of improved therapies for paraquat poisoning. Paraquat's effects on proliferation were examined by flow cytometry, on viscoelasticity by the micropipette aspiration technique, and on connective tissue growth factor (CTGF) expression by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Paraquat was found to significantly reduce the proliferation index of MRC-5 cells in a concentration-dependent manner (p < 0.05) and to significantly impair the viscoelastic properties in a time-independent manner (p < 0.05). Exposure to paraquat led to a significant and time-dependent increase in CTGF expression (p < 0.05) and induced changes in the morphology and biomechanical characteristics of the MRC-5 cells. These findings not only provide novel insights into the mechanisms of paraquat-induced lung fibrosis but may represent useful targets of improved molecular-based therapies for paraquat poisoning. PMID:24556028

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

2014-12-01

289

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

PubMed

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

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

2014-11-01

290

[Clinical study of interstitial lung disease in mixed connective tissue disease].  

PubMed

Mixed connective tissue disease (MCTD) is characterized by a combination of clinical features of progressive systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, polymyositis/dermatomyositis, with a high anti-snRNP antibody titer. Respiratory manifestations, such as interstitial lung disease (ILD), are not well-described. Thirteen patients who met the diagnostic criteria for MCTD and showed ILD on high-resolution CT were analysed retrospectively. A restrictive pattern was found in 73% of cases and TLCO abnormalities in 90%. Exercise hypoxemia was observed in nine out of ten cases. The CT-scan pattern was compatible with non-specific interstitial pneumonia in seven cases and with usual interstitial pneumonia in five. Bronchoalveolar lavage showed lymphocytic alveolitis in two patients, neutrophil alveolitis in eight. Fifty percent ILD patients respond to steroids and immunosuppressive drugs. Progressive ILD (six in 13; 46%) compared with non-progressive ILD associated more systemic sclerosis manifestations (p<0.05). Progressive ILD tend to have more frequent pulmonary hypertension, neutrophilic alveolitis and honey combing pattern. MCTD-ILD characteristics are not specific. When systemic sclerosis manifestations are present, MCTD-ILD seems to associate more frequently pulmonary hypertension and progressive ILD. PMID:20359616

Colin, G; Nunes, H; Hatron, P-Y; Cadranel, J; Tillie, I; Wallaert, B

2010-03-01

291

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

PubMed

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

Elmansour, Imane; Chiheb, Soumia; Benchikhi, Hakima

2014-01-01

292

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

PubMed Central

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

Elmansour, Imane; Chiheb, Soumia; Benchikhi, Hakima

2014-01-01

293

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

PubMed

Chronic kidney disease (CKD), marked by a progressive loss in renal function, is a leading cause of hemodialysis initiation and cardiovascular disease (CVD). There are currently 13.3 million patients with CKD and 300 thousand patients are currently undergoing hemodialysis in Japan. Therefore, preventing the initiation of dialysis and reducing the risk of cardiovascular death are high-priority issues from the viewpoint of public health and economic implications. Understanding the molecular mechanism responsible for the progression of CKD and cardiovascular damage regarding crosstalk between the kidney and cardiovascular system is an important issue in controlling the pathogenesis of CKD-CVD. However, the mechanisms involved in CKD-CVD are not well understood. This hinders the development of new treatment strategies. We have been investigating the role of protein bound uremic toxins, that are difficult to remove by hemodialysis, on the onset and progression of CKD and CVD. The relationship between their redox properties and the pathogenesis of CKD-CVD was examined. In this review, we focus on two sulfate conjugated uremic toxins, namely, indoxyl sulfate (IS) and p-cresyl sulfate (PCS), and summarize recent studies that provide new insights on the molecular mechanisms responsible for uremic toxin-induced oxidative tissue damage via a cardiovascular-renal connection. PMID:23903229

Watanabe, Hiroshi

2013-01-01

294

Connective tissue growth factor associated with oncogenic activities and drug resistance in glioblastoma multiforme.  

PubMed

Connective tissue growth factor (CTGF or CCN2) is a secreted protein that belongs to the CCN [cysteine-rich CYR61/CTGF/nephroblastoma-overexpressed gene] family. These proteins have been implicated in various biological processes, including stimulation of cell proliferation, migration, angiogenesis and tumorigenesis. In a previous study, we found that CTGF mRNA was elevated in primary gliomas, and a significant correlation existed between CTGF mRNA levels versus tumor grade, histology and patient survival. In this study, the role of CTGF in glioma tumorigenesis was explored. Forced expression of CTGF in glioblastoma multiforme (GBM) cells accelerated their growth in liquid culture and soft agar, stimulated cells migration in Boyden chamber assays and significantly increased their ability to form large, vascularized tumors in nude mice. CTGF induced the expression of the antiapoptotic proteins, Bcl-xl, Survivin and Flip. Overexpression of CTGF caused the U343 GBM cells to survive for longer than 40 days in serum-free medium and resist antitumor drugs including tumor necrosis factor (TNF), TNF-related apoptosis-inducing ligand, VELCADE (bortezomib, proteasome inhibitor) and temozolomide. Our data suggest that CTGF plays an important role in glioma progression, by supporting tumor cells survival and drug resistance. PMID:20162579

Yin, Dong; Chen, Weikai; O'Kelly, James; Lu, Daning; Ham, Michelle; Doan, Ngan B; Xie, Dong; Wang, Charles; Vadgama, Jay; Said, Jonathan W; Black, Keith L; Koeffler, H Phillip

2010-11-15

295

Induction of Ovarian Primordial Follicle Assembly by Connective Tissue Growth Factor CTGF  

PubMed Central

Primordial follicle assembly is a process that occurs when oocyte nests break down to form individual primordial follicles. The size of this initial pool of primordial follicles in part determines the reproductive lifespan of the female. Connective tissue growth factor (CTGF) was identified as a potential regulatory candidate for this process in a previous microarray analysis of follicle development. The current study examines the effects of CTGF and associated transforming growth factor beta 1 (TGF?-1) on follicle assembly. Ovaries were removed from newborn rat pups and placed in an organ culture system. The ovaries treated with CTGF for two days were found to have an increased proportion of assembled follicles. CTGF was found to regulate the ovarian transcriptome during primordial follicle assembly and an integrative network of genes was identified. TGF?-1 had no effect on primordial follicle assembly and in combination with CTGF decreased oocyte number in the ovary after two days of culture. Over ten days of treatment only the combined treatment of CTGF and TGF?-1 was found to cause an increase in the proportion of assembled follicles. Interestingly, treatment with TGF?-1 alone resulted in fewer total oocytes in the ovary and decreased the primordial follicle pool size after ten days of culture. Observations indicate that CTGF alone or in combination with TGF?-1 stimulates primordial follicle assembly and TGF?-1 can decrease the primordial follicle pool size. These observations suggest the possibility of manipulating primordial follicle pool size and influencing female reproductive lifespan. PMID:20886044

Schindler, Ryan; Nilsson, Eric; Skinner, Michael K.

2010-01-01

296

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

PubMed Central

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

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

297

[Assessment methods of autoantibodies in autoimmune diseases].  

PubMed

In most of the autoimmune diseases, a humoral and cellular immune response is characteristically seen, with autoantibodies and cells directed to distinct intracellular antigens. This phenomenon can be shown in systemic diseases like sclerosis, systemic lupus erythematosus, Sjogren's syndrome, mixed connective tissue disease, polymyositis and rheumatoid arthritis. It is also evident that autoantibodies are present in many the autoimmune diseases (called organ-specific) like for example Hashimoto, Graves-Basedow or Addison disease. The presence of autoantibodies is important items to be considered in establishing a diagnosis and because of that autoantibodies are included in the diagnostic criteria of many autoimmune diseases. They are useful prognostic markers in some situations and facilitate clinical and treatment follow-up. Since year 1950 (discovering of the first autoantibody--classical rheumatoid factor IgM class) many new methods like: immunoelectrophoresis, counter-electrophoresis, double and radial immunodiffusion in gels, immunoagglutination and haemolytic methods have been used for autoantibodies assessment. It seems to us the indirect immunofluorescence method (IIF) was a most powerful, sensitive and comprehensive test for screening of autoantibodies, until an immunoenzymatic (EIA) methods (ELISA, Western-blotting) in late 60-s was worked out. The immunoenzymatic tests are very useful because of their simplicity and reliability. But there is one more excellent test hybrid named "Colorzyme" (presented by Immuno-Concept Corporation from USA) worked out by combining of the EIA and IIF tests. Instead of FITC-conjugates (like in IIF) a HRP-conjugates for developing of typical ANA-test based on glass fixed Hep-2 cells have been used. The nuclear type of pattern we get using "Colorzyme" test are very strong, nit and rich in details. The prevalence of the "Colorzyme" test relies on that it can be properly done and interpreted by unexperienced technician. More and more new-founded resources of marker autoantibodies and methods force to introduction into standardization both methods and specimens on which they are marked. PMID:14750264

Zabek, Jakub

2002-01-01

298

Large leg ulcers due to autoimmune diseases  

PubMed Central

Summary Background Large leg ulcers (LLU) may complicate autoimmune diseases. They pose a therapeutic challenge and are often resistant to treatment. To report three cases of autoimmune diseases complicated with LLU. Case Report Case 1. A 55-year old woman presented with long-standing painful LLU due to mixed connective tissue disease (MCTD). Biopsy from the ulcer edge showed small vessel vasculitis. IV methylprednisolone (MethP) 1 G/day, prednisolone (PR) 1mg/kg, monthly IV cyclophosphamide (CYC), cyclosporine (CyA) 100mg/day, IVIG 125G, ciprofloxacin+IV Iloprost+enoxaparin+aspirin (AAVAA), hyperbaric oxygen therapy (HO), maggot debridement and autologous skin transplantation were performed and the LLU healed. Case 2. A 45-year old women with MCTD developed multiple LLU’s with non-specific inflammation by biopsy. MethP, PR, hydroxychloroquine (HCQ), azathioprine (AZA), CYC, IVIG, AAVAA failed. Treatment for underlying the LLU tibial osteomyelitis and addition of CyA was followed by the LLU healing. Case 3. A 20-year-old man with history of polyarteritis nodosa (PAN) developed painful LLU’s due to small vessel vasculitis (biopsy). MethP, PR 1 mg/kg, CYC, CyA 100 mg/d, AAVAA failed. MRSA sepsis and relapse of systemic PAN developed. IV vancomycin, followed by ciprofloxacin, monthly IVIG (150 g/for 5 days) and infliximab (5 mg/kg) were instituted and the LLU’s healed. Conclusions LLU are extremely resistant to therapy. Combined use of multiple medications and services are needed for healing of LLU due to autoimmune diseases. PMID:21169912

Rozin, Alexander P.; Egozi, Dana; Ramon, Yehuda; Toledano, Kohava; Braun-Moscovici, Yolanda; Markovits, Doron; Schapira, Daniel; Bergman, Reuven; Melamed, Yehuda; Ullman, Yehuda; Balbir-Gurman, Alexandra

2011-01-01

299

Amplification of autoimmune disease by infection  

PubMed Central

Reports of infection with certain chronic persistent microbes (herpesviruses or Chlamydiae) in human autoimmune diseases are consistent with the hypothesis that these microbes are reactivated in the setting of immunodeficiency and often target the site of autoimmune inflammation. New experimental animal models demonstrate the principle. A herpesvirus or Chlamydia species can be used to infect mice with induced transient autoimmune diseases. This results in increased disease severity and even relapse. The evidence suggests that the organisms are specifically imported to the inflammatory sites and cause further tissue destruction, especially when the host is immunosuppressed. We review the evidence for the amplification of autoimmune inflammatory disease by microbial infection, which may be a general mechanism applicable to many human diseases. We suggest that patients with autoimmune disorders receiving immunosuppressing drugs should benefit from preventive antiviral therapy. PMID:15743493

Posnett, David N; Yarilin, Dmitry

2005-01-01

300

Survival analysis and risk factors for mortality in connective tissue disease-associated pneumomediastinum.  

PubMed

The aim of this study was to analyze the characteristics of patients with diffuse connective tissue diseases (CTDs) complicated by pneumomediastinum and identify the risk factors associated with increased mortality in these patients. Twenty-eight patients with CTD-associated pneumomediastinum, who were admitted to our hospital from January 1997 to June 2012, were prospectively studied. Their demographic characteristics, time to death, and potential risk factors were assessed. Survival curves were depicted by the Kaplan-Meier method. Univariate and multivariate survival analyses were performed by Cox regression. Of the 28 patients, 21 had dermatomyositis; two, polymyositis; three, systemic lupus erythematosus; one, polyarteritis nodosa; and one, undifferentiated CTD. The mean follow-up period was 1,461 days (54-5,264). The cumulative estimated Kaplan-Meier survival rate was 68 % at 1 week, 50 % at 1 month, and 43 % at 1 year. According to univariate analysis, higher serum albumin level (HR 0.87, 95 % CI 0.78-0.98), "slow air leak" (defined as time to progression of dyspnea [newly acquired respiratory failure, mechanical ventilation required, or decrease in PaO2 >30 mmHg after pneumomediastinum]) >3 days (HR 0.07, 95 % CI 0.02-0.34), and early initiation of immunosuppressive agents (within 1 month of steroid therapy; HR 0.27, 95 % CI 0.09-0.81) were associated with better prognosis. Final regression analysis revealed that slow air leak was associated with a lower mortality risk. We found that slow air leak was independently associated with better prognosis. Furthermore, most patients (86 %) who survived for at least 1 month following the pneumomediastinum event subsequently survived beyond 1 year. PMID:24871160

Zhang, Lu; Shen, Min; Zhang, Fengchun; Tang, Fulin

2014-12-01

301

Frequency of development of connective tissue disease in statin-users versus nonusers.  

PubMed

Statins have pleiotropic properties that may affect the development of connective tissue diseases (CTD). The objective of this study was to compare the risk of CTD diagnoses in statin users and nonusers. This study was a propensity score-matched analysis of adult patients (30 to 85 years old) in the San Antonio military medical community. The study was divided into baseline (October 1, 2003 to September 30, 2005), and follow-up (October 1, 2005 to March 5, 2010) periods. Statin users received a statin prescription during fiscal year 2005. Nonusers did not receive a statin at any time during the study. The outcome measure was the occurrence of 3 diagnosis codes of the International Classification of Diseases, 9th Revision, Clinical Modification consistent with CTD. We described co-morbidities during the baseline period using the Charlson Comorbidity Index. We created a propensity score based on 41 variables. We then matched statin users and nonusers 1:1, using a caliper of 0.001. Of 46,488 patients who met study criteria (13,640 statin users and 32,848 nonusers), we matched 6,956 pairs of statin users and nonusers. Matched groups were similar in terms of patient age, gender, incidence of co-morbidities, total Charlson Comorbidity Index, health care use, and medication use. The odds ratio for CTD was lower in statin users than nonusers (odds ratio: 0.80; 95% confidence interval: 0.64 to 0.99; p = 0.05). Secondary analysis and sensitivity analysis confirmed these results. In conclusion, statin use was associated with a lower risk of CTD. PMID:23764243

Schmidt, Thomas; Battafarano, Daniel F; Mortensen, Eric M; Frei, Christopher R; Mansi, Ishak

2013-09-15

302

Infection-related morbidity and mortality in patients with connective tissue diseases: a systematic review.  

PubMed

Patients suffering from connective tissue diseases (CTDs) constitute an important subgroup of immunosuppressed patients at risk for developing serious infections. Prophylactic antibiotic administration may decrease infection-related morbidity and mortality burden in patients with CTD, though one needs first to evaluate the overall effect of infection on morbidity and mortality in such patients and the presence of adequate prognostic/risk factors for infection development. Studies focusing on infection-related morbidity and mortality in patients with CTD were reviewed. Data on disease type, therapeutic regimens used, including corticosteroid dose and method of administration as well as other immunosuppressive agents, and outcome were extracted to evaluate the existence of specific treatment patterns predisposing to infection as well as infectious disease-related morbidity and mortality in patients with CTD. Thirty-nine studies focusing on infection incidence and/or outcome in patients with CTD were identified and analyzed; the majority of the reviewed studies (20) included patients with systemic lupus erythematosus (SLE). The mortality attributed to infection was 5.2%, while the overall mortality was 20%. There were no adequate data on the specific effect patterns of corticosteroid and immunosuppressant treatment on infection risk. Pneumocystis jiroveci (carinii) pneumonia, evaluated independently, exhibited significant mortality in patients with Wegener's granulomatosis, polymyositis/dermatomyositis, and SLE. In conclusion, infectious diseases are a major cause of mortality in patients with CTD. However, treatment-related factors predisposing to serious infections have not been adequately outlined. In addition, there are no data regarding the effect of prophylactic practices involving antibiotic administration in morbidity and mortality. PMID:17186117

Falagas, Matthew E; Manta, Katerina G; Betsi, Gregoria I; Pappas, Georgios

2007-05-01

303

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

PubMed Central

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

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

2012-01-01

304

TissuesTissues TissuesTissues group of similar cell types thatgroup of similar cell types that  

E-print Network

has four basic types of tissue:tissue: EpithelialEpithelial ConnectiveConnective Muscle TissuesTissues­­ Connective TissueConnective Tissue Loosely organized and composed ofLoosely organizedUsually binds organs or tissues to one anotherone another #12;3 TissuesTissues ­­ Connective TissueConnective

Cochran-Stafira, D. Liane

305

Autoimmune Cytopenias In Common Variable Immunodeficiency  

PubMed Central

Common variable immunodeficiency (CVID) is a humoral immunodeficiency whose primary diagnostic features include hypogammaglobulinemia involving two or more immunoglobulin isotypes and impaired functional antibody responses in the majority of patients. While increased susceptibility to respiratory and other infections is a common thread that binds a large cross-section of CVID patients, the presence of autoimmune complications in this immunologically and clinically heterogeneous disorder is recognized in up to two-thirds of patients. Among the autoimmune manifestations reported in CVID (20–50%; Chapel et al., 2008; Cunningham-Rundles, 2008), autoimmune cytopenias are by far the most common occurring variably in 4–20% (Michel et al., 2004; Chapel et al., 2008) of these patients who have some form of autoimmunity. Association of autoimmune cytopenias with granulomatous disease and splenomegaly has been reported. The spectrum of autoimmune cytopenias includes thrombocytopenia, anemia, and neutropenia. While it may seem paradoxical “prima facie” that autoimmunity is present in patients with primary immune deficiencies, in reality, it could be considered two sides of the same coin, each reflecting a different but inter-connected facet of immune dysregulation. The expansion of CD21 low B cells in CVID patients with autoimmune cytopenias and other autoimmune features has also been previously reported. It has been demonstrated that this unique subset of B cells is enriched for autoreactive germline antibodies. Further, a correlation has been observed between various B cell subsets, such as class-switched memory B cells and plasmablasts, and autoimmunity in CVID. This review attempts to explore the most recent concepts and highlights, along with treatment of autoimmune hematological manifestations of CVID. PMID:22837758

Podjasek, Jenna C.; Abraham, Roshini S.

2012-01-01

306

Leaky gut and autoimmune diseases.  

PubMed

Autoimmune diseases are characterized by tissue damage and loss of function due to an immune response that is directed against specific organs. This review is focused on the role of impaired intestinal barrier function on autoimmune pathogenesis. Together with the gut-associated lymphoid tissue and the neuroendocrine network, the intestinal epithelial barrier, with its intercellular tight junctions, controls the equilibrium between tolerance and immunity to non-self antigens. Zonulin is the only physiologic modulator of intercellular tight junctions described so far that is involved in trafficking of macromolecules and, therefore, in tolerance/immune response balance. When the zonulin pathway is deregulated in genetically susceptible individuals, autoimmune disorders can occur. This new paradigm subverts traditional theories underlying the development of these diseases and suggests that these processes can be arrested if the interplay between genes and environmental triggers is prevented by re-establishing the zonulin-dependent intestinal barrier function. Both animal models and recent clinical evidence support this new paradigm and provide the rationale for innovative approaches to prevent and treat autoimmune diseases. PMID:22109896

Fasano, Alessio

2012-02-01

307

Structural changes in connective tissues caused by a moderate laser heating  

SciTech Connect

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.

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

308

Structural changes in connective tissues caused by a moderate laser heating  

NASA Astrophysics Data System (ADS)

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 °C and adipose tissue samples to 75 °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 °C and adipose tissue to 90 — 110 °C leads to a partial reversible denaturation of proteins and to oxidation of fats.

Bagratashvili, Viktor N.; Bagratashvili, N. V.; Ignat'eva, Natalia Yu; Lunin, Valery V.; Grokhovskaya, T. E.; Averkiev, S. V.; Sviridov, A. P.; Shakh, G. Sh

2002-10-01

309

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)

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.

Vailas, Arthur C.; Martinez, Daniel A.

1999-01-01

310

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)

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.

Vailas, Arthur C.; Martinez, Daniel A.

1999-01-01

311

Regulation of angiogenesis and endothelial cell function by connective tissue growth factor (CTGF) and cysteine-rich 61 (CYR61)  

Microsoft Academic Search

Connective tissue growth factor (CTGF) and cysteine-rich 61 (CYR61) are prototypical members of the CCN family which also contains nephroblastoma overexpressed (NOV) and Wnt-induced secreted proteins-1, -2 and -3 (WISP-1, -2, -3). These proteins function as extracellular matrix (ECM)-associated signaling molecules that contain structural modules allowing them to bind directly with other moieties in the pericellular environment. Although multiple target

David R. Brigstock

2002-01-01

312

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

Microsoft Academic Search

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

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

2009-01-01

313

The connective tissue framework in the normal prostate, B.P.H and prostate cancer: analysis by scanning electron microscopy after cellular digestion  

Microsoft Academic Search

The objective of this study was twofold: (1) to determine if a cellular digestion process can facilitate examination of the\\u000a morphology of the connective tissue framework of the prostate, and (2) to examine the connective tissue framework in normal\\u000a prostate tissue, benign prostatic hyperplasia (BPH) and prostate cancer. Ten prostate glands were examined. Using the Ohtani\\u000a method of digestion, the

Colin Morrison; John Thornhill; Eoin Gaffney

2000-01-01

314

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

PubMed Central

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

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

2013-01-01

315

Connective tissue diseases in primary biliary cirrhosis: A population-based cohort study  

PubMed Central

AIM: To establish the frequency and clinical features of connective tissue diseases (CTDs) in a cohort of Chinese patients with primary biliary cirrhosis (PBC). METHODS: Three-hundred and twenty-two Chinese PBC patients were screened for the presence of CTD, and the systemic involvement was assessed. The differences in clinical features and laboratory findings between PBC patients with and without CTD were documented. The diversity of incidence of CTDs in PBC of different countries and areas was discussed. For the comparison of normally distributed data, Student’s t test was used, while non-parametric test (Wilcoxon test) for the non-normally distributed data and 2 × 2 ?2 or Fisher’s exact tests for the ratio. RESULTS: One-hundred and fifty (46.6%) PBC patients had one or more CTDs. The most common CTD was Sjögren’s syndrome (SS, 121 cases, 36.2%). There were nine cases of systemic sclerosis (SSc, 2.8%), 12 of systemic lupus erythematosus (SLE, 3.7%), nine of rheumatoid arthritis (RA, 2.8%), and 10 of polymyositis (PM, 3.1%) in this cohort. Compared to patients with PBC only, the PBC + SS patients were more likely to have fever and elevated erythrocyte sedimentation rate (ESR), higher serum immunoglobulin G (IgG) levels and more frequent rheumatoid factor (RF) and interstitial lung disease (ILD) incidences; PBC + SSc patients had higher frequency of ILD; PBC + SLE patients had lower white blood cell (WBC) count, hemoglobin (Hb), platelet count, ?-glutamyl transpeptidase and immunoglobulin M levels, but higher frequency of renal involvement; PBC + RA patients had lower Hb, higher serum IgG, alkaline phosphatase, faster ESR and a higher ratio of RF positivity; PBC + PM patients had higher WBC count and a tendency towards myocardial involvement. CONCLUSION: Besides the common liver manifestation of PBC, systemic involvement and overlaps with other CTDs are not infrequent in Chinese patients. When overlapping with other CTDs, PBC patients manifested some special clinical and laboratory features which may have effect on the prognosis. PMID:23964148

Wang, Li; Zhang, Feng-Chun; Chen, Hua; Zhang, Xuan; Xu, Dong; Li, Yong-Zhe; Wang, Qian; Gao, Li-Xia; Yang, Yun-Jiao; Kong, Fang; Wang, Ke

2013-01-01

316

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

PubMed Central

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

2012-01-01

317

Frequency of Autoantibodies and Connective Tissue Diseases in Chinese Patients with Optic Neuritis  

PubMed Central

Background Optic neuritis (ON) is often associated with other clinical or serological markers of connective tissue diseases (CTDs). To date, the effects of autoantibodies on ON are not clear. Purpose To assess the prevalence, clinical patterns, and short outcomes of autoantibodies and Sjögren’s syndrome (SS) involvement in Chinese ON patients and evaluate the relationship between ON, including their subtypes, and autoantibodies. Methods A total of 190 ON patients were divided into recurrent ON (RON), bilateral ON (BON), and isolated monocular ON (ION). Demographic, clinical, and serum autoantibodies data were compared between them with and without SS involvement. Serum was drawn for antinuclear antibody (ANA), extractable nuclear antigen antibodies (SSA/SSB), rheumatoid factor (RF), anticardiolipin antibodies (ACA), and anti-double-stranded DNA antibody (A-ds DNA), anticardiolipin antibody (ACLs), anti-?2-glycoprotein I (?2-GPI) and Aquaporin-4 antibodies (AQP4-Ab). Spectral-domain optical coherence tomography (SD-OCT) was used to evaluate the atrophy of the optic nerve. Results 68 patients (35.79%) had abnormal autoantibodies, 26(13.68%) patients met diagnostic criteria for CTDs, including 15(7.89%) patients meeting the criteria for SS. Antibodies including SSA/SSB 23 (30.26%) (p1 and p 2<0.001) and AQP4–Ab10 (13.16%) (p1?=?0.044, p2?=?0.01) were significantly different in patients in the RON group when compared with those in the BON (P1?=?RON VS ION) and ION (p2?=?RON VS ION) groups. SS was more common in RON patients (p1?=?0.04, p2?=?0.028). There was no significant difference between SSA/SSB positive and negative patients in disease characteristics or severity. Similar results were obtained when SS was diagnosed in SSA/SSB positive patients. Conclusion RON and BON were more likely associated with abnormal autoantibodies; furthermore, AQP4 antibody, SSA/SSB and SS were more common in the RON patients. AQP4 antibodydetermination is crucial in RON patients who will develop NMO. However, when compared with other autoantibodies, SSA/SSB detected in patients was not significantly associated with disease characteristics or severity. PMID:24950188

Yi, Zuohuizi; Huang, Dehui; Wei, Shihui

2014-01-01

318

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

PubMed Central

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

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

319

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

PubMed Central

Background Broad-band UVA, long-wave UVA1 and PUVA treatment have been described as an alternative/adjunct therapeutic option in a number of inflammatory and malignant skin diseases. Nevertheless, controlled studies investigating the efficacy of UVA irradiation in connective tissue diseases and related disorders are rare. Methods Searching the PubMed database the current article systematically reviews established and innovative therapeutic approaches of broad-band UVA irradiation, UVA1 phototherapy and PUVA photochemotherapy in a variety of different connective tissue disorders. Results Potential pathways include immunomodulation of inflammation, induction of collagenases and initiation of apoptosis. Even though holding the risk of carcinogenesis, photoaging or UV-induced exacerbation, UVA phototherapy seems to exhibit a tolerable risk/benefit ratio at least in systemic sclerosis, localized scleroderma, extragenital lichen sclerosus et atrophicus, sclerodermoid graft-versus-host disease, lupus erythematosus and a number of sclerotic rarities. Conclusions Based on the data retrieved from the literature, therapeutic UVA exposure seems to be effective in connective tissue diseases and related disorders. However, more controlled investigations are needed in order to establish a clear-cut catalogue of indications. PMID:15380024

Breuckmann, Frank; Gambichler, Thilo; Altmeyer, Peter; Kreuter, Alexander

2004-01-01

320

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

PubMed Central

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

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

2013-01-01

321

TGF ?1 and PDGF AA override Collagen type I inhibition of proliferation in human liver connective tissue cells  

PubMed Central

Background A marked expansion of the connective tissue population and an abnormal deposition of extracellular matrix proteins are hallmarks of chronic and acute injuries to liver tissue. Liver connective tissue cells, also called stellate cells, derived from fibrotic liver have been thoroughly characterized and correspond phenotypically to myofibroblasts. They are thought to derive from fat-storing Ito cells in the perisinusoidal space and acquire a contractile phenotype when activated by tissue injury. In the last few years it has become evident that several peptide growth factors such as PDGF AA and TGF-? are involved in the development of fibrosis by modulating myofibroblast proliferation and collagen secretion. The fact that during the development of chronic fibrosis there is concomitant deposition of collagen, a known inhibitory factor, and sustained cell proliferation, raises the possibility that stellate cells from chronic liver fibrosis patients fail to respond to normal physiologic controls. Methods In this study we address whether cells from fibrotic liver patients respond to normal controls of proliferation. We compared cell proliferation of primary human liver connective tissue cells (LCTC) from patients with liver fibrosis and skin fibroblasts (SF) in the presence of collagens type I and IV; TGF-?, PDGF AA and combinations of collagen type I and TGF-? or PDGF AA. Results Our results indicate that despite displaying normal contact and collagen-induced inhibition of proliferation LCTC respond more vigorously to lower concentrations of PDGF AA. In addition, we show that collagen type I synergizes with growth factors to promote mitogenesis of LCTC but not SF. Conclusions The synergistic interaction of growth factors and extracellular matrix proteins may underlie the development of chronic liver fibrosis. PMID:15579200

Geremias, Alvaro T; Carvalho, Marcelo A; Borojevic, Radovan; Monteiro, Alvaro NA

2004-01-01

322

Fragile privileges: autoimmunity in brain and eye  

PubMed Central

Brain and eye tissues are subject to a reduced version of immune surveillance, which has evolved to protect the particularly sensitive tissues from accidental bystander damage created by regular inflammatory responses. Yet, there are autoimmune diseases in both organs. This review discusses the nature of immune reactivity in the healthy eye and brain tissues, and mechanisms that can overcome the protective barriers to create tissue specific disease. PMID:20818330

Wekerle, Hartmut; Sun, De-ming

2010-01-01

323

Perspectives on autoimmunity  

SciTech Connect

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.

Cohen, I.R.

1987-01-01

324

Autoimmune polyglandular syndromes  

Microsoft Academic Search

The autoimmune polyglandular syndromes—a group of syndromes comprising a combination of endocrine and nonendocrine autoimmune diseases—differ in their component diseases and in the immunologic features of their pathogenesis. One of the three main syndromes, type 1 autoimmune polyglandular syndrome (APS-1), has a unique pathogenic mechanism owing to mutations in the autoimmune regulator (AIRE) gene, which results in the loss of

Peter A. Gottlieb; Aaron W. Michels

2010-01-01

325

Natural killer cells in human autoimmune diseases  

PubMed Central

Natural killer (NK) cells have been implicated in tumour surveillance and in the early control of several microbial infections. In autoimmune disease their involvement in these processes has been evaluated in animal models, with conflicting results. Both a disease-controlling and a disease-promoting role have been suggested. In human autoimmune disease only a few studies, mainly descriptive, have demonstrated qualitative and quantitative modification of NK cells. These changes were observed on blood- or tissue-infiltrating NK cells. Taken together with our expanding knowledge of the genetical variability of NK cell receptors and NK cell physiology, these findings pave the way for the dissection of the role of NK cells in human autoimmune diseases. NK cells may be directly involved in these diseases through their potential autoreactivity or through their interaction with dendritic cells, macrophages or T lymphocytes, thereby inducing excessive inflammation or favouring the adaptive autoimmune response. Thus, NK cells may be implicated in the onset, the maintenance or the progression of autoimmune diseases. Some reports also suggest the involvement of NK cells in the treatment of human autoimmune disease by biotherapies. All these observations suggest that NK cells are involved in the complex processes of autoimmune diseases. Nevertheless, further careful analysis of NK cells at different steps of these diseases, in different tissues and through combined genetical and functional studies will contribute to a better understanding of their role in autoimmune diseases. This knowledge might allow the development of new therapeutic strategies based on NK cells for the treatment of some autoimmune diseases. PMID:21039469

Schleinitz, Nicolas; Vély, Frédéric; Harlé, Jean-Robert; Vivier, Eric

2010-01-01

326

On the connection between autoimmunity, tic disorders and obsessive-compulsive disorders: a meta-analysis on anti-streptolysin O titres.  

PubMed

Anti-streptolysin O (ASO) titration is useful in the context of autoimmune pathologies, including specific cases of tic and obsessive-compulsive disorders occurring after streptococcal infections. There is currently a lack of consensus on the use of ASO titres; therefore we performed a meta-analysis to systematise available data and clarify the role of ASO titres in the context of neuropsychiatric disorders. A meta-analysis was performed on ASO titration in neuropsychiatric patients, including tic disorders and obsessive-compulsive disorders. Included studies reported numbers of positive subjects, depending on a chosen threshold, or detailed ASO titrations. Three hundred and twenty nine studies were identified, of which 13 were eligible for meta-analysis. Due to limited available data, only tic disorders were evaluated. The odds ratio of finding an abnormal ASO titre in patients was 3.22 (95% C.I. 1.51-6.88) as compared to healthy controls and 16.14 (95% C.I. 8.11-32.11) as compared to non-psychiatric patients. Studies using different thresholds were generally concordant. ASO titres were also compared quantitatively, finding an overall difference of the means of 70.50 U/ml (95% C.I. 25.21-115.80) in favour of patients with tic disorders. Based on current evidence, tic disorders are associated with a significant increase in ASO titres, evident both in a threshold-level perspective and on a quantitative level. These results encourage the systematisation of ASO titration in the context of tic disorders. PMID:25091468

Pozzi, Marco; Pellegrino, Paolo; Carnovale, Carla; Perrone, Valentina; Antoniazzi, Stefania; Perrotta, Cristiana; Radice, Sonia; Clementi, Emilio

2014-12-01

327

Primer: epigenetics of autoimmunity  

Microsoft Academic Search

Interactions between environmental and genetic factors are proposed to explain why autoimmunity afflicts certain individuals and not others. Genes and genetic loci predisposing to autoimmunity are being identified, but theories as to how the environment contributes to autoimmunity still rely largely on examples such as drug-induced systemic lupus erythematosus (SLE) and epidemiologic evidence of occupational exposure, without clear mechanistic explanations

Bruce Richardson

2007-01-01

328

The study of cells and tissues Tissues 4 basic types  

E-print Network

Histology The study of cells and tissues #12;Tissues ­ 4 basic types epithelial connective muscular, alveolar, simple, complex #12;Connective Tissues Non-binding Connective Tissue blood/lymph Binding Connective Tissue loose connective tissue dense connective tissue cartilage bone #12;Non-binding Connective

Houde, Peter

329

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

E-print Network

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.

Gal deBotton; Tal Oren

2012-01-02

330

Role of Radiation-Induced Signaling Proteins in the Response of Vascular and Connective Tissues  

Microsoft Academic Search

\\u000a Over the years considerable effort has been made not only to quantify the tolerance of normal tissue to radiation, but also\\u000a to provide a baseline for radiotherapy at maximum biological effective doses. Normal tissue complications induced by ionizing\\u000a radiation differ depending on the target organ and cell types. Acute or early reactions are primarily characterized by rapidly\\u000a occurring changes within

H. P. Rodemann

331

The role of AIRE in human autoimmune disease  

Microsoft Academic Search

The autoimmune regulator (AIRE) gene encodes a transcription factor involved in the presentation of tissue-restricted antigens during T-cell development in the thymus. Mutations of this gene lead to type 1 autoimmune polyglandular syndrome (APS-1), also termed autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome, which is characterized by the clinical presentation of at least two of a triad of underlying disorders: Addison disease,

Eitan M. Akirav; Nancy H. Ruddle; Kevan C. Herold

2010-01-01

332

Vaccination and Autoimmunity—‘vaccinosis’: A Dangerous Liaison?  

Microsoft Academic Search

The question of a connection between vaccination and autoimmune illness (or phenomena) is surrounded by controversy. A heated debate is going on regarding the causality between vaccines, such as measles and anti-hepatits B virus (HBV), and multiple sclerosis (MS). Brain antibodies as well as clinical symptoms have been found in patients vaccinated against those diseases. Other autoimmune illnesses have been

Shoenfeld Y; Aron-Maor A

2000-01-01

333

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

PubMed

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

Halper, Jaroslava; Kjaer, Michael

2014-01-01

334

Sirolimus for Autoimmune Disease of Blood Cells  

ClinicalTrials.gov

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

2014-10-17

335

Morphometric analysis of cellular and vascular changes in gingival connective tissue in long-term insulin-dependent diabetes.  

PubMed

This study examined cellular and vascular changes in gingival connective tissue samples by stereologic point-counting procedures and interactive digital analyzing systems in long-term insulin-dependent diabetes mellitus patients. Gingival connective tissue capillaries representing a clinically healthy sulcus with no evidence of periodontal disease at the site of biopsy were studied in 29 patients with diabetes. Based upon their long-term medical records, 19 were identified as having poorly controlled (PIDD) and 10 as controlled insulin-dependent diabetes mellitus (CIDD). Ten nondiabetic, age- and gender-matched individuals served as controls. Thirty-nine biopsies were processed for light microscopy, and the blood vessel area was analyzed using an interactive digital analyzing system; 9 gingival biopsies, 5 diabetic and 4 controls, were processed for morphometric electron microscopic analysis. For each individual, site-specific recordings were made for the plaque index, bleeding index, probing depth, loss of attachment, and radiographic loss of interproximal alveolar bone. No evident signs of periodontitis occurred at the biopsy sites. For each PIDD patient, respective volumetric and numeric densities of cellular components including fibroblasts, neutrophilic granulocytes, monocyte/macrophages, mast cells, lymphocytes, blast cells, and plasma cells were recorded in the inflamed connective tissue (ICT). Non-cellular components such as collagen fibers and blood vessels were also recorded. PIDD patients had elevated plasma cell levels relative to controls and they appeared also to have a decreased collagen fiber density. In addition, fibroblasts occupied less volume in the ICT of PIDD patients than in controls. PIDD patients had the largest mean area of cross-section of the blood vessels, but this difference was not statistically significant (P > or = 0.211; t-test). No specific characteristics of ICT or vascular changes were detectable in adult well-controlled long-term diabetics under similar plaque conditions. Swollen and proliferated endothelial cells were frequently found in PIDD patients and the mean distance from the lumen to the outer border of basement membrane was greater in the PIDD than in the controls (P < 0.001; t-test). Overall, our findings that cellular, vascular, and connective tissue changes indicative of increased catabolism rather than anabolism detected in gingiva are especially associated with poorly controlled long-term insulin-dependent diabetes. PMID:9444601

Seppälä, B; Sorsa, T; Ainamo, J

1997-12-01

336

Softenin, a Novel Protein That Softens the Connective Tissue of Sea Cucumbers through Inhibiting Interaction between Collagen Fibrils  

PubMed Central

The dermis in the holothurian body wall is a typical catch connective tissue or mutable collagenous tissue that shows rapid changes in stiffness. Some chemical factors that change the stiffness of the tissue were found in previous studies, but the molecular mechanisms of the changes are not yet fully understood. Detection of factors that change the stiffness by working directly on the extracellular matrix was vital to clarify the mechanisms of the change. We isolated from the body wall of the sea cucumber Stichopus chloronotus a novel protein, softenin, that softened the body-wall dermis. The apparent molecular mass was 20 kDa. The N-terminal sequence of 17 amino acids had low homology to that of known proteins. We performed sequential chemical and physical dissections of the dermis and tested the effects of softenin on each dissection stage by dynamic mechanical tests. Softenin softened Triton-treated dermis whose cells had been disrupted by detergent. The Triton-treated dermis was subjected to repetitive freeze-and-thawing to make Triton-Freeze-Thaw (TFT) dermis that was softer than the Triton-treated dermis, implying that some force-bearing structure had been disrupted by this treatment. TFT dermis was stiffened by tensilin, a stiffening protein of sea cucumbers. Softenin softened the tensilin-stiffened TFT dermis while it had no effect on the TFT dermis without tensilin treatment. We isolated collagen from the dermis. When tensilin was applied to the suspending solution of collagen fibrils, they made a large compact aggregate that was dissolved by the application of softenin or by repetitive freeze-and-thawing. These results strongly suggested that softenin decreased dermal stiffness through inhibiting cross-bridge formation between collagen fibrils; the formation was augmented by tensilin and the bridges were broken by the freeze-thaw treatment. Softenin is thus the first softener of catch connective tissue shown to work on the cross-bridges between extracellular materials. PMID:24454910

Takehana, Yasuhiro; Yamada, Akira; Tamori, Masaki; Motokawa, Tatsuo

2014-01-01

337

Softenin, a novel protein that softens the connective tissue of sea cucumbers through inhibiting interaction between collagen fibrils.  

PubMed

The dermis in the holothurian body wall is a typical catch connective tissue or mutable collagenous tissue that shows rapid changes in stiffness. Some chemical factors that change the stiffness of the tissue were found in previous studies, but the molecular mechanisms of the changes are not yet fully understood. Detection of factors that change the stiffness by working directly on the extracellular matrix was vital to clarify the mechanisms of the change. We isolated from the body wall of the sea cucumber Stichopus chloronotus a novel protein, softenin, that softened the body-wall dermis. The apparent molecular mass was 20 kDa. The N-terminal sequence of 17 amino acids had low homology to that of known proteins. We performed sequential chemical and physical dissections of the dermis and tested the effects of softenin on each dissection stage by dynamic mechanical tests. Softenin softened Triton-treated dermis whose cells had been disrupted by detergent. The Triton-treated dermis was subjected to repetitive freeze-and-thawing to make Triton-Freeze-Thaw (TFT) dermis that was softer than the Triton-treated dermis, implying that some force-bearing structure had been disrupted by this treatment. TFT dermis was stiffened by tensilin, a stiffening protein of sea cucumbers. Softenin softened the tensilin-stiffened TFT dermis while it had no effect on the TFT dermis without tensilin treatment. We isolated collagen from the dermis. When tensilin was applied to the suspending solution of collagen fibrils, they made a large compact aggregate that was dissolved by the application of softenin or by repetitive freeze-and-thawing. These results strongly suggested that softenin decreased dermal stiffness through inhibiting cross-bridge formation between collagen fibrils; the formation was augmented by tensilin and the bridges were broken by the freeze-thaw treatment. Softenin is thus the first softener of catch connective tissue shown to work on the cross-bridges between extracellular materials. PMID:24454910

Takehana, Yasuhiro; Yamada, Akira; Tamori, Masaki; Motokawa, Tatsuo

2014-01-01

338

Comparison of Characteristics of Connective Tissue Disease-Associated Interstitial Lung Diseases, Undifferentiated Connective Tissue Disease-Associated Interstitial Lung Diseases, and Idiopathic Pulmonary Fibrosis in Chinese Han Population: A Retrospective Study  

PubMed Central

Our study compared the prevalence and characteristics of patients with connective tissue disease-associated interstitial lung disease (CTD-ILD), undifferentiated connective tissue disease-associated interstitial lung disease (UCTD-ILD), or idiopathic pulmonary fibrosis (IPF) between January 2009 and December 2012 in West China Hospital, western China. Patients who met the criteria for ILD were included and were assigned to CTD-ILD, UCTD-ILD, or IPF group when they met the criteria for CTD, UCTD, or IPF, respectively. Clinical characteristics, laboratory tests, and high-resolution CT images were analyzed and compared among three groups. 203 patients were included, and all were Han nationality. CTD-ILD was identified in 31%, UCTD-ILD in 32%, and IPF in 37%. Gender and age differed among groups. Pulmonary symptoms were more common in IPF, while extrapulmonary symptoms were more common in CTD-ILD and UCTD-ILD group. Patients with CTD-ILD had more abnormal antibody tests than those of UCTD-ILD and IPF. Little significance was seen in HRCT images among three groups. A systematic evaluation of symptoms and serologic tests in patients with ILD can identify CTD-ILD, UCTD-ILD, and IPF. PMID:24171031

Pan, Lin; Liu, Yuan; Sun, Rongfei; Fan, Mingyu; Shi, Guixiu

2013-01-01

339

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

PubMed Central

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

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

2013-01-01

340

Immuno-Histochemical Studies of Connective Tissue: The Use of Contrasting Fluorescent Protein Tracers in the Comparison of two Antisera  

PubMed Central

Two fluorochromes of contrasting colour, fluorescein and lissamine rhodamine B200 have been used in an application of Coons's immuno-histochemical technique to a comparison of the reactions with their antigens in tissue sections of anti-human-glomerulus antisera and anti-human-synovium antisera. A uniform redistribution of labelled antibodies took place when tissue sections pre-treated with fluorescein labelled anti-glomerulus globulin were exposed to anti-glomerulus globulin labelled with lissamine rhodamine B200. In sections pre-treated with an anti-human-glomerulus conjugate and exposed to an anti-human-synovium conjugate labelled contrastingly, and vice versa, the redistribution of antibodies did not occur to the same extent in every situation. The findings can be explained by the hypothesis that there is a difference in the stability of union between certain connective tissue antigens and antibodies present in anti-glomerulus conjugates, on the one hand, and anti-synovium conjugates on the other. The results of these experiments and of others in which anti-glomerulus and anti-synovium conjugates labelled contrastingly were allowed to react with tissue sections simultaneously, indicate that splenic reticulin is antigenically dissimilar to fibrils in vascular adventitia. ImagesFIG. 1FIG. 2FIG. 3FIG. 4 PMID:14444205

Scott, D. G.

1960-01-01

341

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

SciTech Connect

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.

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

342

Connective Tissue Growth Factor Does Not Affect Transforming Growth Factor-Beta 1Induced Smad3 Phosphorylation and T Lymphocyte Proliferation Inhibition  

Microsoft Academic Search

Transforming growth factor-beta 1 (TGF-?1) is a key regulator of immune tolerance. TGF-?1 controls T lymphocte activation and is involved in the immunosuppressive function and generation of regulatory T lymphocytes. Connective tissue growth factor (CTGF) has an essential role in the formation of connective tissue and blood vessels. CTGF expression is induced by TGF-?1 in several cell types and CTGF

S. Kunzmann; A. Seher; B. W. Kramer; R. Schenk; N. Schütze; F. Jakob; W. Sebald; C. P. Speer

2008-01-01

343

Dynamics of connective-tissue localization during chronic Borrelia burgdorferi infection  

PubMed Central

The etiologic agent of Lyme disease, Borrelia burgdorferi, localizes preferentially in the extracellular matrix during persistence. In chronically infected laboratory mice, there is a direct association between B. burgdorferi and the proteoglycan decorin, which suggests that decorin has a role in defining protective niches for persistent spirochetes. In this study, the tissue colocalization of B. burgdorferi with decorin and the dynamics of borrelial decorin tropism were evaluated during chronic infection. Spirochetes were found to colocalize absolutely with decorin, but not collagen I in chronically infected immunocompetent C3H mice. Passive immunization of infected C3H-scid mice with B. burgdorferi-specific immune serum resulted in the localization of spirochetes in decorin-rich microenvironments, with clearance of spirochetes from decorin-poor microenvironments. In passively immunized C3H-scid mice, tissue spirochete burdens were initially reduced, but increased over time as the B. burgdorferi-specific antibody levels waned. Concurrent repopulation of the previously cleared decorin-poor microenvironments was observed with the rising tissue spirochete burden and declining antibody titer. These findings indicate that the specificity of B. burgdorferi tissue localization during chronic infection is determined by decorin, driven by the borrelia-specific antibody response, and fluctuates with the antibody response. PMID:23797360

Imai, Denise M; Feng, Sunlian; Hodzic, Emir; Barthold, Stephen W

2014-01-01

344

Chondromodulin-I and Tenomodulin: The Negative Control of Angiogenesis in Connective Tissue  

Microsoft Academic Search

The negative regulation of angiogenesis may provide a promising therapeutic target for a number of lifestyle-related diseases, as the switch to an angiogenic phenotype in many tissues represents a critical step during the progression of such disorders. Cartilage is avascular and shows resistance to vascular invasion from the surrounding well-vascularized mesenchyme. Using guanidine extracts of fetal bovine cartilage, we have

Chisa Shukunami; Yuji Hiraki

2007-01-01

345

Impact of Microbes on Autoimmune Diseases  

PubMed Central

Autoimmune and autoinflammatory diseases arise as a consequence of complex interactions of environmental factors with genetic traits. Although specific allelic variations cluster in predisposed individuals and promote the generation and/or expansion of autoreactive T and B lymphocytes, auto-immunity appears in various disease phenotypes and localizes to diverging tissues. Furthermore, the discovery that allelic variations within genes encoding components of the innate immune system drive self-reactive immune responses as well, led to the distinction of immune responses against host tissues into auto-immune and autoinflammatory diseases. In both categories of disorders, different pathogenic mechanisms and/or subsequent orders of tissue assaults may underlie the target cell specificity of the respective autoimmune attack. Furthermore, the transition from the initial tissue assault to the development of full-blown disease is likely driven by several factors. Thus, the development of specific forms of autoimmunity and autoinflammation reflects a multi-factorial process. The delineation of the specific factors involved in the pathogenic process is hampered by the fact that certain symptoms are assembled under the umbrella of a specific disease, although they might originate from diverging pathogenic pathways. These multi-factorial triggers and pathogenic pathways may also explain the inter-individual divergent courses and outcomes of diseases among humans. Here, we will discuss the impact of different environmental factors in general and microbial pathogens in particular on the regulation/ expression of genes encoded within susceptibility alleles, and its consequences on subsequent autoimmune and/or autoinflammatory tissue damage utilizing primarily the chronic cholestatic liver disease primary biliary cirrhosis as model. PMID:23417246

Danzer, Claudia

2014-01-01

346

Local implantation of autologous mononuclear cells from bone marrow and peripheral blood for treatment of ischaemic digits in patients with connective tissue diseases  

Microsoft Academic Search

Objective. CD34-positive bone marrow mononuclear cells (MNCs) have been successfully used for regeneration of small arteries in Buerger's disease. The objective of this study is to examine the angiogenetic potential of autologous MNCs from bone marrow and peripheral blood implanted into the ischaemic digits from patients with connective tissue diseases. Methods. Three patients with systemic sclerosis, two with mixed connective

Y. Kamata; Y. Takahashi; M. Iwamoto; K. Matsui; Y. Murakami; K. Muroi; U. Ikeda; K. Shimada; T. Yoshio; H. Okazaki; S. Minota

2007-01-01

347

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

Microsoft Academic Search

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

C. Andrew L. Bassett; Ingeborg Herrmann

1961-01-01

348

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

Microsoft Academic Search

Biologically tolerated biomaterials are the focus of intense research. In this work, we examined the biocompatibility of three-dimensional (3D) nonwovens of sericin-deprived, Bombyx mori silk fibroin (SF) in ?-sheet form implanted into the subcutaneous tissue of C57BL6 mice, using sham-operated mice as controls. Both groups of mice similarly healed with no residual problem. Macroarray analysis showed that an early (day

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

2005-01-01

349

Connective Tissue Disease-associated Pulmonary Arterial Hypertension in the Modern Treatment Era  

Microsoft Academic Search

Rationale: Pulmonary arterial hypertension in association with con- nective tissue disease (CTD-PAH) has historically had a poor prog- nosis, with a 1-year survival rate among patients with systemic sclerosis-associated pulmonary arterial hypertension (SSc-PAH) of 45%. However, more therapies have become available. Objectives: To investigate the survival and characteristics of all patients diagnosed with CTD-PAH in the U.K. pulmonary hyperten- sion

Robin Condliffe; David G. Kiely; Andrew J. Peacock; Paul A. Corris; J. Simon; R. Gibbs; Charlie A. Elliot; Martin Johnson; Julia DeSoyza; Chantal Torpy; Kim Goldsmith; Denise Hodgkins; Rodney J. Hughes; Joanna Pepke-Zaba; J. Gerry Coghlan

350

Ehlers-Danlos syndrome type VIII is clinically heterogeneous disorder associated primarily with periodontal disease, and variable connective tissue features.  

PubMed

Ehlers-Danlos syndrome (EDS) type VIII (periodontitis type) is a distinct form of EDS characterized by periodontal disease leading to precocious dental loss and a spectrum of joint and skin manifestations. EDS type VIII is transmitted in an autosomal dominant pattern; however, the mutated gene has not been identified. There are insufficient data on the spectrum of clinical manifestations and natural history of the disorder, and only a limited number of patients and pedigrees with this condition have been reported. We present a four-generation EDS type VIII kindred and show that EDS VIII is clinically variable and although some cases lack the associated skin and joint manifestations, microscopic evidence of collagen disorganization is detectable.We further propose that the diagnosis of EDS type VIII should be considered in familial forms of periodontitis, even when the associated skin and joint manifestations are unconvincing for the diagnosis of a connective tissue disorder. This novel observation highlights the uncertainty of using connective tissue signs in clinical practice to diagnose EDS type VIII. PMID:22739343

Reinstein, Eyal; DeLozier, Celia Dawn; Simon, Ziv; Bannykh, Serguei; Rimoin, David L; Curry, Cynthia J

2013-02-01

351

Vascular and connective tissue anomalies associated with X-linked periventricular heterotopia due to mutations in Filamin A.  

PubMed

Mutations conferring loss of function at the FLNA (encoding filamin A) locus lead to X-linked periventricular nodular heterotopia (XL-PH), with seizures constituting the most common clinical manifestation of this disorder in female heterozygotes. Vascular dilatation (mainly the aorta), joint hypermobility and variable skin findings are also associated anomalies, with some reports suggesting that this might represents a separate syndrome allelic to XL-PH, termed as Ehlers-Danlos syndrome-periventricular heterotopia variant (EDS-PH). Here, we report a cohort of 11 males and females with both hypomorphic and null mutations in FLNA that manifest a wide spectrum of connective tissue and vascular anomalies. The spectrum of cutaneous defects was broader than previously described and is inconsistent with a specific type of EDS. We also extend the range of vascular anomalies associated with XL-PH to included peripheral arterial dilatation and atresia. Based on these observations, we suggest that there is little molecular or clinical justification for considering EDS-PH as a separate entity from XL-PH, but instead propose that there is a spectrum of vascular and connective tissues anomalies associated with this condition for which all individuals with loss-of-function mutations in FLNA should be evaluated. In addition, since some patients with XL-PH can present primarily with a joint hypermobility syndrome, we propose that screening for cardiovascular manifestations should be offered to those patients when there are associated seizures or an X-linked pattern of inheritance. PMID:23032111

Reinstein, Eyal; Frentz, Sophia; Morgan, Tim; García-Mińaúr, Sixto; Leventer, Richard J; McGillivray, George; Pariani, Mitchel; van der Steen, Anthony; Pope, Michael; Holder-Espinasse, Muriel; Scott, Richard; Thompson, Elizabeth M; Robertson, Terry; Coppin, Brian; Siegel, Robert; Bret Zurita, Montserrat; Rodríguez, Jose I; Morales, Carmen; Rodrigues, Yuri; Arcas, Joaquín; Saggar, Anand; Horton, Margaret; Zackai, Elaine; Graham, John M; Rimoin, David L; Robertson, Stephen P

2013-05-01

352

Ehlers–Danlos syndrome type VIII is clinically heterogeneous disorder associated primarily with periodontal disease, and variable connective tissue features  

PubMed Central

Ehlers–Danlos syndrome (EDS) type VIII (periodontitis type) is a distinct form of EDS characterized by periodontal disease leading to precocious dental loss and a spectrum of joint and skin manifestations. EDS type VIII is transmitted in an autosomal dominant pattern; however, the mutated gene has not been identified. There are insufficient data on the spectrum of clinical manifestations and natural history of the disorder, and only a limited number of patients and pedigrees with this condition have been reported. We present a four-generation EDS type VIII kindred and show that EDS VIII is clinically variable and although some cases lack the associated skin and joint manifestations, microscopic evidence of collagen disorganization is detectable. We further propose that the diagnosis of EDS type VIII should be considered in familial forms of periodontitis, even when the associated skin and joint manifestations are unconvincing for the diagnosis of a connective tissue disorder. This novel observation highlights the uncertainty of using connective tissue signs in clinical practice to diagnose EDS type VIII. PMID:22739343

Reinstein, Eyal; DeLozier, Celia Dawn; Simon, Ziv; Bannykh, Serguei; Rimoin, David L; Curry, Cynthia J

2013-01-01

353

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

PubMed Central

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

Yu, Lilei; Zhou, Xiaohui; Yang, Kang

2014-01-01

354

Prostaglandin synthetase and prostacyclin synthetase in mature rat skeletal muscles: immunohistochemical localisation to arterioles, tendons and connective tissues.  

PubMed Central

Mature skeletal muscles produce appreciable quantities of prostacyclin (PGI2) and smaller amounts of PGF2 alpha and PGE2, but the sources of these prostaglandins within skeletal muscle are unknown. Monoclonal antibodies to prostaglandin synthetase and prostacyclin synthetase were used to determine which muscle cells produce prostaglandins. The antibody to prostacyclin synthetase stained the tendon, fascia, epimysium and the arteries leading to the muscles. The endothelia of arterioles were also stained in the tibialis anterior and cremaster but not in the soleus muscles. Only trace levels of immunoreactivity were observed with the antibody to prostaglandin synthetase in normal muscles. However, immunoreactivity was observed in the muscles of rats that had been pretreated with aspirin, a drug that inhibits and stabilises prostaglandin synthetase. In muscles of the aspirin-treated rats, all cell types that were stained by the antiprostacyclin synthetase also reacted weakly with the antibody to prostaglandin synthetase. In addition, some cells in the endomysium were strongly stained with the antiprostaglandin synthetase but not with the antiprostacyclin synthetase. We conclude that (1) at least one aspect of the regulation of blood flow in the microcirculation of slow muscles is different from that of fast muscles, (2) that the tendon and connective tissue is the major source of PGI2 in mature skeletal muscles, and (3) that the prostaglandin-dependent effects of insulin and some other stimuli on skeletal muscle may be mediated by the muscle's arterioles or connective tissue. Images Fig. 1 Fig. 2 Fig. 3 PMID:1810931

McLennan, I S; Macdonald, R E

1991-01-01

355

Migration of connective tissue-derived cells is mediated by ultra-low concentration gradient fields of EGF  

PubMed Central

The directed migration of cells towards chemical stimuli incorporates simultaneous changes in both the concentration of a chemotactic agent and its concentration gradient, each of which may influence cell migratory response. In this study, we utilized a microfluidic system to examine the interactions between Epidermal Growth Factor (EGF) concentration and EGF gradient in stimulating the chemotaxis of connective-tissue derived fibroblast cells. Cells seeded within microfluidic devices were exposed to concentration gradients established by EGF concentrations that matched or exceeded those required for maximum chemotactic responses seen in transfilter migration assays. The migration of individual cells within the device was measured optically after steady-state gradients had been experimentally established. Results illustrate that motility was maximal at EGF concentration gradients between .01- and 0.1-ng/(mL.mm) for all concentrations used. In contrast, the numbers of motile cells continually increased with increasing gradient steepness for all concentrations examined. Microfluidics-based experiments exposed cells to minute changes in EGF concentration and gradient that were in line with the acute EGFR phosphorylation measured. Correlation of experimental data with established mathematical models illustrated that the fibroblasts studied exhibit an unreported chemosensitivity to minute changes in EGF concentration, similar to that reported for highly motile cells, such as macrophages. Our results demonstrate that shallow chemotactic gradients, while previously unexplored, are necessary to induce the rate of directed cellular migration and the number of motile cells in the connective tissue-derived cells examined. PMID:21536028

Kong, Qingjun; Majeska, Robert J.; Vazquez, Maribel

2011-01-01

356

Vascular and connective tissue anomalies associated with X-linked periventricular heterotopia due to mutations in Filamin A  

PubMed Central

Mutations conferring loss of function at the FLNA (encoding filamin A) locus lead to X-linked periventricular nodular heterotopia (XL-PH), with seizures constituting the most common clinical manifestation of this disorder in female heterozygotes. Vascular dilatation (mainly the aorta), joint hypermobility and variable skin findings are also associated anomalies, with some reports suggesting that this might represents a separate syndrome allelic to XL-PH, termed as Ehlers-Danlos syndrome-periventricular heterotopia variant (EDS-PH). Here, we report a cohort of 11 males and females with both hypomorphic and null mutations in FLNA that manifest a wide spectrum of connective tissue and vascular anomalies. The spectrum of cutaneous defects was broader than previously described and is inconsistent with a specific type of EDS. We also extend the range of vascular anomalies associated with XL-PH to included peripheral arterial dilatation and atresia. Based on these observations, we suggest that there is little molecular or clinical justification for considering EDS-PH as a separate entity from XL-PH, but instead propose that there is a spectrum of vascular and connective tissues anomalies associated with this condition for which all individuals with loss-of-function mutations in FLNA should be evaluated. In addition, since some patients with XL-PH can present primarily with a joint hypermobility syndrome, we propose that screening for cardiovascular manifestations should be offered to those patients when there are associated seizures or an X-linked pattern of inheritance. PMID:23032111

Reinstein, Eyal; Frentz, Sophia; Morgan, Tim; García-Mińaúr, Sixto; Leventer, Richard J; McGillivray, George; Pariani, Mitchel; van der Steen, Anthony; Pope, Michael; Holder-Espinasse, Muriel; Scott, Richard; Thompson, Elizabeth M; Robertson, Terry; Coppin, Brian; Siegel, Robert; Bret Zurita, Montserrat; Rodríguez, Jose I; Morales, Carmen; Rodrigues, Yuri; Arcas, Joaquín; Saggar, Anand; Horton, Margaret; Zackai, Elaine; Graham, John M; Rimoin, David L; Robertson, Stephen P

2013-01-01

357

Increased connective tissue attachment to silicone implants by a water vapor plasma treatment.  

PubMed

Polydimethylsiloxane (PDMS) is the most common type of silicone polymer for the fabrication of implantable medical devices. Because of its inherent hydrophobic nature, the PDMS surface does not readily promote cellular adhesion, which leads to diverse clinical issues. Previously, we reported a simple water vapor plasma treatment of PDMS surfaces that resulted in stable long-term wettability and excellent in vitro cell compatibility. In this work, we report investigation of the in vivo local responses to PDMS implants treated by water vapor plasma using a subcutaneous rat model. The local tissue responses were assessed after 2 and 4 weeks of implantation by means of macroscopic and histomorphometric analysis. After 2 weeks of implantation, the plasma-treated implants elicited the formation of fibrous tissue capsules that were significantly thinner, more adherent, and vascularized than the control counterparts. The improved cell adhesion was correlated with an increased amount of cells attached to the implant surface after retrieval. There was no difference in the inflammatory response between untreated and treated samples. This study provides a rational approach to optimize the long-term performance of silicone implants, which is likely to have a significant impact in clinical applications demanding enhanced tissue integration of the implants. PMID:22767530

Jensen, C; Gurevich, L; Patriciu, A; Struijk, J J; Zachar, V; Pennisi, C P

2012-12-01

358

Ocular Antigens IV: A Comparative Study of the Localisation of Immunogenic Determinants of Ocular Structural Glycoproteins in Connective Tissues of Various Organs  

Microsoft Academic Search

Antisera against the structural glycoproteins isolated from bovine lens capsule (anti-LSGP), sclera (anti-SSGP) and corneal stroma (anti-CSGP) have been tested on tissues of joint, spleen, pancreas, skin, tendon, heart valve, kidney and cartilage by means of the indirect immunofluorescence technique. Anti-LSGP stains basement membranes and reticular structures in all tissues. Anti-CSGP and anti-SSGP stain all collagenous and reticular connective tissues

J. J. J. M. van der Eerden; R. M. Broekhuyse

1973-01-01

359

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

NASA Technical Reports Server (NTRS)

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.

Globus, R. K.; Moursi, A.; Zimmerman, D.; Lull, J.; Damsky, C.

1995-01-01

360

Immunogenicity of influenza H1N1 vaccination in mixed connective tissue disease: effect of disease and therapy  

PubMed Central

OBJECTIVE: To assess the potential acute effects regarding the immunogenicity and safety of non-adjuvanted influenza A H1N1/2009 vaccine in patients with mixed connective tissue disease and healthy controls. METHODS: Sixty-nine mixed connective tissue disease patients that were confirmed by Kasukawa's classification criteria and 69 age- and gender-matched controls participated in the study; the participants were vaccinated with the non-adjuvanted influenza A/California/7/2009 (H1N1) virus-like strain. The percentages of seroprotection, seroconversion, geometric mean titer and factor increase in the geometric mean titer were calculated. The patients were clinically evaluated, and blood samples were collected pre- and 21 days post-vaccination to evaluate C-reactive protein, muscle enzymes and autoantibodies. Anti-H1N1 titers were determined using an influenza hemagglutination inhibition assay. ClinicalTrials.gov: NCT01151644. RESULTS: Before vaccination, no difference was observed regarding the seroprotection rates (p?=?1.0) and geometric mean titer (p?=?0.83) between the patients and controls. After vaccination, seroprotection (75.4% vs. 71%, p?=?0.7), seroconversion (68.1% vs. 65.2%, p?=?1.00) and factor increase in the geometric mean titer (10.0 vs. 8.0, p?=?0.40) were similar in the two groups. Further evaluation of seroconversion in patients with and without current or previous history of muscle disease (p?=?0.20), skin ulcers (p?=?0.48), lupus-like cutaneous disease (p?=?0.74), secondary Sjögren syndrome (p?=?0.78), scleroderma-pattern in the nailfold capillaroscopy (p?=?1.0), lymphopenia ?1000/mm3 on two or more occasions (p?=?1.0), hypergammaglobulinemia ?1.6 g/d (p?=?0.60), pulmonary hypertension (p?=?1.0) and pulmonary fibrosis (p?=?0.80) revealed comparable rates. Seroconversion rates were also similar in patients with and without immunosuppressants. Disease parameters, such as C-reactive protein (p?=?0.94), aldolase (p?=?0.73), creatine phosphokinase (p?=?0.40) and ribonucleoprotein antibody levels (p?=?0.98), remained largely unchanged pre and post-vaccination. No severe side effects were reported. CONCLUSIONS: The non-adjuvanted influenza A/H1N1 vaccination immune response in mixed connective tissue disease patients is adequate and does not depend on the disease manifestations and therapy. PMID:23525305

Miossi, Renata; Fuller, Ricardo; Moraes, Júlio C. B.; Ribeiro, Ana Cristina M.; Saad, Carla G. S.; Aikawa, Nadia E.; Miraglia, Joăo L; Ishida, Maria A; Bonfá, Eloisa; Caleiro, M Teresa C.

2013-01-01

361

Autoimmune markers in children with chronic pancreatitis  

PubMed Central

Introduction In the last decade we can observe a gradual increase in the incidence of autoimmune diseases. The aetiology of chronic pancreatitis (CP) in children is varied and includes gene mutations, anatomic anomalies and others. The reported paediatric experience with chronic CP is scarce and little is known about the role of autoimmune pancreatitis (AIP). Aim To assess the frequency of autoimmune markers in children with CP. Material and methods One hundred and twenty-nine children hospitalised between 2005 and 2012 at the Department of Gastroenterology, The Children's Memorial Health Institute, were examined for the presence of AIP; the level of IgG4 was determined, and tests for anti-tissue antibodies (ANA, ASMA, AMA, ANCA, AHA) were conducted. Clinical data were recorded and analysed. Results Anti-tissue antibodies were detected in 75/129 children (58%), and 24/68 patients (35.3%) showed an increased IgG4 level. Based on the International Association of Pancreatology criteria, a suspicion of AIP was raised in 6 patients (4.6%). We found gene mutations predisposing to CP in 32/75 (42.6%) patients with autoimmune markers. In 16/75 children (21.3%), anatomic anomalies were found. There was no difference in the severity of the disease and clinical course between children with evidence of autoimmune process and patients without autoimmune markers (p = NS). Conclusions In children with CP, similarly to adults, there is a high frequency of biochemical markers of autoimmunity. It is worth remembering that AIP can occur in children. PMID:25097710

Cukrowska, Bo?ena; Kierku?, Jaros?aw; Ry?ko, Józef

2014-01-01

362

Molecular Diagnosis in Autoimmune Skin Blistering Conditions  

PubMed Central

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

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

2014-01-01

363

Autoimmune polyendocrine syndromes.  

PubMed

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

Cutolo, Maurizio

2014-02-01

364

Autoimmunity: Alopecia Areata  

Microsoft Academic Search

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

Maria Hordinsky; Marna Ericson

2004-01-01

365

Cell damage and autoimmunity: a critical appraisal.  

PubMed

In April 2007, an international Colloquium bridging scientific and clinical disciplines was held to discuss the role of cellular and tissue damage in the initiation, development and persistence of autoimmune disease. Five potential etiologic and pathophysiologic processes fundamental to autoimmune disease (i.e. inflammation, infection, apoptosis, environmental exposure and genetics) were the focus of the presentations and integrative discussions at the Colloquium. The information presented on these topics is condensed in this review. Inflammation has close clinico-pathologic associations with autoimmunity, but future analyses will require better definition and metrics of inflammation, particularly for the earliest cellular and molecular components dependent on recruitment of elements of innate immunity. Although infection may be associated with increased levels of autoantibodies, most infections and virtually all vaccinations in humans lack well-established links to autoimmune diseases. Further application of well-designed, long-term epidemiologic and population-based studies is urgently needed to relate antecedent exposures with later occurring stigmata of autoimmunity with a goal of discerning potentially susceptible individuals or subpopulations. Suspect infections requiring closer interrogation include EB virus (SLE and other diseases), HCV (autoimmune hepatitis), beta hemolytic streptococci (rheumatic carditis) and Helicobacter pylori (autoimmune gastritis) among others. And even if a micro-organism was to be incriminated, mechanisms of initiation/perpetuation of autoimmunity continue to challenge investigators. Plausible mechanisms include potentiation and diversion of innate immunity; exposure or spillage of intracellular autoantigens; or provision of autoantigenic mimics. Integrity of apoptosis as a critical safeguard against autoimmunity was discussed in the contexts of over-reactivity causing autoantigens to gain enhanced exposure to the immune system, or under-reactivity producing insufficient elimination of autoreactive clones of lymphocytes. Although environmental agents are widely believed to serve as necessary "triggers" of autoimmune disease in genetically predisposed individuals, only a few such agents (mainly drugs and some nutrients) have been clearly identified and their mechanism of action defined. Finally an essential genetic foundation underlies all these hazards for autoimmunity in the form of risk-associated polymorphisms in immunoregulatory genes. They may be predictive of future or impending disease. PMID:18194728

Mackay, Ian R; Leskovsek, Natasha V; Rose, Noel R

2008-01-01

366

Using T-Cells for Transplantation and Autoimmune Therapy  

Cancer.gov

Transplant complications and autoimmune diseases are primarily caused by T-cell immune responses against normal host tissue or transplanted tissues. Current treatment for these disorders is often not effective, and is typically associated with significant side effects, including global immune suppression. Researchers at NCI's Experimental Transplantation and Immunology Branch have developed a cellular therapy to treat graft-vs.-host disease (GVHD) that results from hematopoetic transplant and other autoimmune disorders.

367

Autoimmune lymphoproliferative syndrome.  

PubMed

Autoimmune lymphoproliferative syndrome arises early in childhood in people who inherit mutations in genes that mediate lymphocyte apoptosis, or programmed cell death. In the immune system, antigen-induced lymphocyte apoptosis maintains immune homeostasis by limiting lymphocyte accumulation and minimizing reactions against self-antigens. In autoimmune lymphoproliferative syndrome, defective lymphocyte apoptosis manifests as chronic, nonmalignant adenopathy and splenomegaly; the expansion of an unusual population of CD4-CD8- T cells; and the development of autoimmune disease. Most cases of autoimmune lymphoproliferative syndrome involve heterozygous mutations in the lymphocyte surface protein Fas (CD95, Apo1) that impair a major apoptotic pathway. Prospective evaluations of patients and their families have revealed an ever-expanding spectrum of autoimmune lymphoproliferative syndrome and its major complications. PMID:12819469

Sneller, Michael C; Dale, Janet K; Straus, Stephen E

2003-07-01

368

Dextrose-Induced Subsynovial Connective Tissue Fibrosis in the Rabbit Carpal Tunnel: A Potential Model to Study Carpal Tunnel Syndrome?  

PubMed Central

In this pilot study, hypertonic dextrose solution was used to induce fibrosis of the subsynovial connective tissue (SSCT) and create an animal model of potential use in the study of carpal tunnel syndrome (CTS). The SSCT of the carpal tunnel in 15 New Zealand white rabbits were injected with 0.05 ml of 10% dextrose solution in 1 paw and 0.05 ml of saline in the contralateral paw, to serve as a control. The animals were killed at 1, 2, 4, 8, or 12 weeks. While the saline side showed minimal changes at any time period, the hypertonic dextrose side showed progressive noninflammatory SSCT fibrosis, with vascular proliferation and thickening of collagen bundles. Demyelination of the median nerve developed at 12 weeks after the injection on the dextrose side. These findings are similar to the progression of pathology noted in humans with CTS. PMID:18780118

Oh, Sangho; Ettema, Anke M.; Zhao, Chunfeng; Zobitz, Mark E.; Wold, Lester E.; An, Kai-Nan

2007-01-01

369

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

PubMed Central

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

Quigley, Harry A.; Cone, Frances E.

2013-01-01

370

Autoimmunity in Coxsackievirus B3 induced myocarditis: role of estrogen in suppressing autoimmunity  

PubMed Central

SUMMARY Picornaviruses are small, non-enveloped, single stranded, positive sense RNA viruses which cause multiple diseases including myocarditis/dilated cardiomyopathy, type 1 diabetes, encephalitis, myositis, orchitis and hepatitis. Although picornaviruses directly kill cells, tissue injury primarily results from autoimmunity to self antigens. Viruses induce autoimmunity by: aborting deletion of self-reactive T cells during T cell ontogeny; reversing anergy of peripheral autoimmune T cells; eliminating T regulatory cells; stimulating self-reactive T cells through antigenic mimicry or cryptic epitopes; and acting as an adjuvant for self molecules released during virus infection. Most autoimmune diseases (SLE, rheumatoid arthritis, Grave’s disease) predominate in females, but diseases associated with picornavirus infections predominate in males. T regulatory cells are activated in infected females because of the combined effects of estrogen and innate immunity. PMID:20963181

2010-01-01

371

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

NASA Technical Reports Server (NTRS)

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.

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

1980-01-01

372

The Zinc Transporter SLC39A13/ZIP13 Is Required for Connective Tissue Development; Its Involvement in BMP/TGF-? Signaling Pathways  

PubMed Central

Background Zinc (Zn) is an essential trace element and it is abundant in connective tissues, however biological roles of Zn and its transporters in those tissues and cells remain unknown. Methodology/Principal Findings Here we report that mice deficient in Zn transporter Slc39a13/Zip13 show changes in bone, teeth and connective tissue reminiscent of the clinical spectrum of human Ehlers-Danlos syndrome (EDS). The Slc39a13 knockout (Slc39a13-KO) mice show defects in the maturation of osteoblasts, chondrocytes, odontoblasts, and fibroblasts. In the corresponding tissues and cells, impairment in bone morphogenic protein (BMP) and TGF-? signaling were observed. Homozygosity for a SLC39A13 loss of function mutation was detected in sibs affected by a unique variant of EDS that recapitulates the phenotype observed in Slc39a13-KO mice. Conclusions/Significance Hence, our results reveal a crucial role of SLC39A13/ZIP13 in connective tissue development at least in part due to its involvement in the BMP/TGF-? signaling pathways. The Slc39a13-KO mouse represents a novel animal model linking zinc metabolism, BMP/TGF-? signaling and connective tissue dysfunction. PMID:18985159

Shimoda, Shinji; Mishima, Kenji; Higashiyama, Hiroyuki; Idaira, Yayoi; Asada, Yoshinobu; Kitamura, Hiroshi; Yamasaki, Satoru; Hojyo, Shintaro; Nakayama, Manabu; Ohara, Osamu; Koseki, Haruhiko; dos Santos, Heloisa G.; Bonafe, Luisa; Ha-Vinh, Russia; Zankl, Andreas; Unger, Sheila; Kraenzlin, Marius E.; Beckmann, Jacques S.; Saito, Ichiro; Rivolta, Carlo; Ikegawa, Shiro; Superti-Furga, Andrea; Hirano, Toshio

2008-01-01

373

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

NASA Technical Reports Server (NTRS)

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.

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

374

Autoimmune Cholangitis: A Variant Syndrome of Autoimmune Hepatitis  

PubMed Central

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

Sharma, Brij; Raina, Sujeet; Sharma, Rajesh

2014-01-01

375

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

PubMed Central

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

2014-01-01

376

BMP9 inhibits the bone metastasis of breast cancer cells by downregulating CCN2 (connective tissue growth factor, CTGF) expression.  

PubMed

Bone morphogenetic proteins (BMPs), which belong to the transforming growth factor-? superfamily, regulate a wide range of cellular responses including cell proliferation, differentiation, adhesion, migration, and apoptosis. BMP9, the latest BMP to be discovered, is reportedly expressed in a variety of human carcinoma cell lines, but the role of BMP9 in breast cancer has not been fully clarified. In a previous study, BMP9 was found to inhibit the growth, migration, and invasiveness of MDA-MB-231 breast cancer cells. In the current study, the effect of BMP9 on the bone metastasis of breast cancer cells was investigated. After absent or low expression of BMP9 was detected in the MDA-MB-231 breast cancer cells and breast non-tumor adjacent tissues using Western blot and immunohistochemistry, In our previous study, BMP9 could inhibit the proliferation and invasiveness of breast cancer cells MDA-MB-231 in vitro and in vivo. This paper shows that BMP9 inhibit the bone metastasis of breast cancer cells by activating the BMP/Smad signaling pathway and downregulating connective tissue growth factor (CTGF); however, when CTGF expression was maintained, the inhibitory effect of BMP9 on the MDA-MB-231 cells was abolished. Together, these observations indicate that BMP9 is an important mediator of breast cancer bone metastasis and a potential therapeutic target for treating this deadly disease. PMID:24413988

Ren, Wei; Sun, Xiaoxiao; Wang, Ke; Feng, Honglei; Liu, Yuehong; Fei, Chang; Wan, Shaoheng; Wang, Wei; Luo, Jinyong; Shi, Qiong; Tang, Min; Zuo, Guowei; Weng, Yaguang; He, Tongchuan; Zhang, Yan

2014-03-01

377

MicroRNAs in Autoimmune Diseases  

PubMed Central

Autoimmune diseases (ADs) are featured by body's immune responses being directed towards its own specific target organs or multiple organ systems, causing persistent inflammation and consequent tissue damage. miRNAs are small noncoding RNAs in a size of approximately 22?nt that play important regulatory roles in many organisms by cleavage or translational inhibition of targeted mRNAs. Many miRNAs are reported to be differentially expressed in ADs and may play a pivotal role in regulating immune responses and autoimmunity. In this review, current research progress in the miRNAs in ADs was elucidated. PMID:24991561

Qu, Zigang; Li, Wenhui; Fu, Baoquan

2014-01-01

378

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

PubMed

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 weeks) 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 histopathological sections and by chemical assay of calcium and phosphate. Abcc6(-/-) mice on experimental diet 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

Jiang, Qiujie; Uitto, Jouni

2012-09-01

379

Connective Tissue Growth Factor reporter mice label a subpopulation of mesenchymal progenitor cells that reside in the trabecular bone region.  

PubMed

Few gene markers selectively identify mesenchymal progenitor cells inside the bone marrow. We have investigated a cell population located in the mouse bone marrow labeled by Connective Tissue Growth Factor reporter expression (CTGF-EGFP). Bone marrow flushed from CTGF reporter mice yielded an EGFP+ stromal cell population. Interestingly, the percentage of stromal cells retaining CTGF reporter expression decreased with age in vivo and was half the frequency in females compared to males. In culture, CTGF reporter expression and endogenous CTGF expression marked the same cell types as those labeled using Twist2-Cre and Osterix-Cre fate mapping approaches, which previously had been shown to identify mesenchymal progenitors in vitro. Consistent with this past work, sorted CTGF+ cells displayed an ability to differentiate into osteoblasts, chondrocytes, and adipocytes in vitro and into osteoblast, adipocyte, and stromal cell lineages after transplantation into a parietal bone defect. In vivo examination of CTGF reporter expression in bone tissue sections revealed that it marked cells highly localized to the trabecular bone region and was not expressed in the perichondrium or periosteum. Mesenchymal cells retaining high CTGF reporter expression were adjacent to, but distinct from mature osteoblasts lining bone surfaces and endothelial cells forming the vascular sinuses. Comparison of CTGF and Osterix reporter expression in bone tissue sections indicated an inverse correlation between the strength of CTGF expression and osteoblast maturation. Down-regulation of CTGF reporter expression also occurred during in vitro osteogenic differentiation. Collectively, our studies indicate that CTGF reporter mice selectively identify a subpopulation of bone marrow mesenchymal progenitor cells that reside in the trabecular bone region. PMID:25464947

Wang, Wen; Strecker, Sara; Liu, Yaling; Wang, Liping; Assanah, Fayekah; Smith, Spenser; Maye, Peter

2015-02-01

380

Ovarian autoimmune disease: clinical concepts and animal models  

PubMed Central

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

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

2014-01-01

381

Type 1 diabetes and polyglandular autoimmune syndrome: A review  

PubMed Central

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.

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

2015-01-01

382

Type 1 diabetes and polyglandular autoimmune syndrome: A review.  

PubMed

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

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

2015-02-15

383

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

PubMed

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

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

2014-01-01

384

Autoimmunity in Immunodeficiency  

PubMed Central

Primary immunodeficiencies (PID) comprise a diverse group of clinical disorders with varied genetic defects. Paradoxically, a substantial proportion of PID patients develop autoimmune phenomena in addition to having increased susceptibility to infections from their impaired immunity. Although much of our understanding comes from data gathered through experimental models, there are several well-characterized PID that have improved our knowledge of the pathways that drive autoimmunity. The goals of this review will be to discuss these immunodeficiencies and to review the literature with respect to the proposed mechanisms for autoimmunity within each put forth to date. PMID:23591608

Todoric, Krista; Koontz, Jessica B.; Mattox, Daniel; Tarrant, Teresa K.

2013-01-01

385

Commensal microbiota influence systemic autoimmune responses.  

PubMed

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

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

386

Inhibition of Connective Tissue Growth Factor (CTGF\\/CCN2) Expression Decreases the Survival and Myogenic Differentiation of Human Rhabdomyosarcoma Cells  

Microsoft Academic Search

Connective tissue growth factor (CTGF\\/CCN2), a cysteine-rich protein of the CCN (Cyr61, CTGF, Nov) family of genes, emerged from a microar- ray screen of genes expressed by human rhabdomyosarcoma cells. Rhab- domyosarcoma is a soft tissue sarcoma of childhood deriving from skeletal muscle cells. In this study, we investigated the role of CTGF in rhabdomy- osarcoma. Human rhabdomyosarcoma cells of

Stefania Croci; Lorena Landuzzi; Annalisa Astolfi; Giordano Nicoletti; Angelo Rosolen; Francesca Sartori; Matilde Y. Follo; Noelynn Oliver; Carla De Giovanni; Patrizia Nanni; Pier-Luigi Lollini

2004-01-01

387

Nanomedicine in autoimmunity.  

PubMed

The application of nanotechnology to the diagnosis and therapy of human diseases is already a reality and is causing a real revolution in how we design new therapies and vaccines. In this review we focus on the applications of nanotechnology in the field of autoimmunity. First, we review scenarios in which iron oxide nanoparticles have been used in the diagnosis of autoimmune diseases, mostly through magnetic resonance imaging (MRI), both in animal models and patients. Second, we discuss the potential of nanoparticles as an immunotherapeutic platform for autoimmune diseases, for now exclusively in pre-clinical models. Finally, we discuss the potential of this field to generate the 'perfect drug' with the capacity to report on its therapeutic efficacy in real time, that is, the birth of theranostics in autoimmunity. PMID:24406504

Clemente-Casares, Xavier; Santamaria, Pere

2014-01-01

388

Immune aging and autoimmunity  

PubMed Central

Age is an important risk for autoimmunity, and many autoimmune diseases preferentially occur in the second half of adulthood when immune competence has declined and thymic T cell generation has ceased. Many tolerance checkpoints have to fail for an autoimmune disease to develop, and several of those are susceptible to the immune aging process. Homeostatic T cell proliferation which is mainly responsible for T cell replenishment during adulthood can lead to the selection of T cells with increased affinity to self- or neoantigens and enhanced growth and survival properties. These cells can acquire a memory-like phenotype, in particular under lymphopenic conditions. Accumulation of end-differentiated effector T cells, either specific for self-antigen or for latent viruses, have a low activation threshold due to the expression of signaling and regulatory molecules and generate an inflammatory environment with their ability to be cytotoxic and to produce excessive amounts of cytokines and thereby inducing or amplifying autoimmune responses. PMID:22466672

Weyand, Cornelia M.

2014-01-01

389

[Necrotizing autoimmune myopathy].  

PubMed

Idiopathic inflammatory myopathies are systemic autoimmune diseases characterized by symmetrical proximal muscle weakness. One of them is the subgroup of necrotizing autoimmune myopathy, which has recently been recognized as a separate entity. In addition to the typical symmetrical muscle weakness, it is characterized by very high creatine kinase levels, myopathic triad in the electromyography, and myocyte necrosis without significant inflammation. The paper aims to review this rare entity, which has to be diagnosed and treated quickly in every case. PMID:22985665

Bodoki, Levente; Vincze, Melinda; Hortobágyi, Tibor; Griger, Zoltán; Cseri, Karolina; Sz?ll?si, Lászlóné; Dankó, Katalin

2012-09-23

390

Viral triggers for autoimmunity  

PubMed Central

In this review we want to consider some of the requirements for autoimmune disease to develop and how this may be reproduced in animal models. Besides a genetic predisposition, environmental triggering factors seem to play a central role in the etiology of many autoimmune diseases. In theory, a structural similarity or identity between the host and an invading pathogen might cause the immune system of the host to react not only to the pathogen but also to self-components. However, in order for such a process of molecular mimicry to induce autoimmunity the mechanisms of maintaining tolerance or ignorance to the self-components need to be circumvented. Subsequently, in order to advance autoimmunity to overt autoimmune disease the frequency and avidity of autoaggressive lymphocytes has to be of sufficient magnitude. Intuitively, one would assume that tolerance might be stronger to identical structures than to structures that just share a certain degree of similarity. Self-reactive lymphocytes with high-avidity are more likely to be deleted or functionally silenced by central and/or peripheral tolerance mechanisms. Thus, perfect mimicry between identical structures might fail in inducing autoimmunity because of efficient tolerance mechanisms. In contrast, imperfect mimicry between similar but not identical structures might on one hand circumvent tolerance but on the other hand result in the generation of lymphocytes with only low- to intermediate avidity. Here we examine animal models that use the concept of molecular mimicry as a potential mechanism for inducing or accelerating autoimmunity. We focus on the RIP-LCMV model for type 1 diabetes and the novel cytochrome P450 2D6 (CYP2D6) model for autoimmune hepatitis, which use either identical or similar triggering and target antigens. PMID:19716269

Christen, Urs; Hintermann, Edith; Holdener, Martin; von Herrath, Matthias G.

2009-01-01

391

Histomorphometrical and clinical study of connective tissue around titanium dental implants with porous surfaces in a canine model.  

PubMed

Connective tissue (CT) reactions and collagen fiber orientation were evaluated on titanium implants with porous surfaces made by a laser method. Three groups in which the diameters of pores were 10 ± 5 µm, 40 ± 5 µm, and 70 ± 5 µm were involved in this test, together with a machined group as control. A total of 24 implants were randomly placed in mandibles after 3 months of premolars and the first molar extraction in beagle dogs. All the implants were firmly anchored in the bone after 3-month insertion. Histological sections showed that the gingival tissue was attached tightly to implant surface and there was no significant difference in inflammatory cell invasion and probing depth among all groups (p > 0.05). Histomorphometric analysis demonstrated that no significant difference in total CT length was observed among four groups (p > 0.05), however, the gingival recession in the 40 ± 5 µm and 70 ± 5 µm porous groups was less than in the 10 ± 5 µm porous group and control group (p < 0.05). Collagen fibers at the inner zone of the CT around the 40 ± 5 µm and 70 ± 5 µm porous implants aligned mostly in an oblique orientation, while there was a mainly parallel fiber direction around the 10 ± 5 µm porous and control implants. It was noted that some fibroblasts and fibers in the 70 ± 5 µm porous group was inserted into the pores of implant surface, indicating that pores of a proper size on the implant surface could induce the insertion of CT and prevent gingival recession. PMID:22210806

Zhao, Bao Hong; Cui, Fu Zhai; Liu, Yang; Deng, Chun Fu

2013-02-01

392

Vaccines and autoimmunity.  

PubMed

Vaccines have eradicated or controlled many infectious diseases, saving each year millions of lives and quality of life of many other millions of people. In spite of the success of vaccines over the last two centuries, parents (and also some health care workers) gloss over the devastating consequences of diseases, which are now avoided thanks to vaccines, and direct their attention to possible negative effects of immunization. Three immunological objections are raised: vaccines cause antigenic overload, natural immunity is safer and better than vaccine-induced immunity, and vaccines induce autoimmunity. The last point is examined in this review. Theoretically, vaccines could trigger autoimmunity by means of cytokine production, anti-idiotypic network, expression of human histocompatibility leukocyte antigens, modification of surface antigens and induction of novel antigens, molecular mimicry, bystander activation, epitope spreading, and polyclonal activation of B cells. There is strong evidence that none of these mechanisms is really effective in causing autoimmune diseases. Vaccines are not a source of autoimmune diseases. By contrast, absolute evidence exists that infectious agents can trigger autoimmune mechanisms and that they do cause autoimmune diseases. PMID:23755743

De Martino, M; Chiappini, E; Galli, L

2013-01-01

393

The epigenetics of autoimmunity.  

PubMed

The etiology of autoimmune diseases remains largely unknown. Concordance rates in monozygotic twins are lower than 50% while genome-wide association studies propose numerous significant associations representing only a minority of patients. These lines of evidence strongly support other complementary mechanisms involved in the regulation of genes expression ultimately causing overt autoimmunity. Alterations in the post-translational modification of histones and DNA methylation are the two major epigenetic mechanisms that may potentially cause a breakdown of immune tolerance and the perpetuation of autoimmune diseases. In recent years, several studies both in clinical settings and experimental models proposed that the epigenome may hold the key to a better understanding of autoimmunity initiation and perpetuation. More specifically, data support the impact of epigenetic changes in systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis and other autoimmune diseases, in some cases based on mechanistical observations. We herein discuss what we currently know and what we expect will come in the next future. Ultimately, epigenetic treatments already being used in oncology may soon prove beneficial also in autoimmune diseases. PMID:21278766

Meda, Francesca; Folci, Marco; Baccarelli, Andrea; Selmi, Carlo

2011-05-01

394

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

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

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

1978-01-01

395

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

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.

T. Sminia

1972-01-01

396

Bosentan treatment for pulmonary arterial hypertension related to connective tissue disease: a subgroup analysis of the pivotal clinical trials and their open-label extensions  

Microsoft Academic Search

Background: Endothelin-1 is considered to be a central pathogenic factor in connective tissue diseases (CTDs) such as systemic sclerosis (SSc), leading to vasoconstriction, fibrosis, hypertrophy and inflammation. A frequent complication of CTD is pulmonary arterial hypertension (PAH), which has a major effect on functioning and quality of life, and is associated with a particularly poor prognosis.Objective: To present a subgroup

C P Denton; M Humbert; L Rubin; C M Black

2006-01-01

397

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

PubMed

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

Raman, Maya; Mathew, Saleena

2014-08-01

398

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

PubMed

We observed the morphology of the lingual papillae (filiform, conical, fungiform, and vallate papillae, and lateral organ) and their connective tissue cores (CTCs) in the American mink (Neovison vison) using light and scanning electron microscopy. Filiform papillae were distributed on the apex linguae and rostral regions of the corpus linguae. Conical papillae were distributed over the caudal region and absent in the radix linguae. Numerous ridges were present in the radix linguae. Four to six vallate papillae were situated at the border between the corpus and radix linguae. Instead of foliate papillae, a pair of lateral organs was situated on the caudal edge of the corpus. The epithelial surface of each filiform papilla consisted of a single main process and 10-12 accessory processes. Notably, filiform papillae in the apex linguae exhibited morphological variation, and some were dome-like and lacked processes. In contrast, filiform papillae on the rostral part were not variable, were extended to a sharp tip, were associated with an eosinophilic stratum corneum, and lacked nuclei. The CTCs of the filiform papillae consisted of a main core and slender accessory cores surrounding a concavity. Those in the apex linguae were similar in appearance and consisted of main and adjacent accessory cores. The fungiform papillae had a dome-like epithelial surface and their CTCs were columnar, with upper concavities and flanges. The simplified lingual morphology of the American mink, particularly in the filiform papillae in the apex linguae, may be influenced by its diet and semiaquatic lifestyle. PMID:24832902

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

2014-05-01

399

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

PubMed Central

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

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

2012-01-01

400

Finite Element Model of Subsynovial Connective Tissue Deformation due to Tendon Excursion in the Human Carpal Tunnel  

PubMed Central

Carpal Tunnel Syndrome (CTS) is a nerve entrapment disease which has been extensively studied by the engineering and medical community. Although the direct cause is unknown, in vivo and in vitro medical research has shown that tendon excursion creates micro tears in the subsynovial connective tissue (SSCT) surrounding the tendon in the carpal tunnel. One proposed mechanism for the SSCT injury is shearing which is believed to cause fibrosis of the SSCT. Few studies have reported quantitative observations of SSCT response to mechanical loading. Our proposed model is a 2-D section that consists of an FDS tendon, interstitial SSCT and adjacent stationary tendons. We believe that developing this model will allow the most complete quantitative observations of SSCT response to mechanical loading reported thus far. Boundary conditions were applied to the FEA model to simulate single finger flexion. A velocity was applied to the FDS tendon in the model to match loading conditions of the documented cadaver wrist kinematics studies. The cadaveric and FEA displacement results were compared to investigate the magnitude of stiffness required for the SSCT section of the model. The relative motions between the model and cadavers matched more closely than the absolute displacements. Since cadaveric models do not allow identification of the SSCT layers, an FEA model will help determine the displacement and stress experienced by each SSCT layer. Thus, we believe this conceptual model is a first step in understanding how the SSCT layers are recruited during tendon excursion. PMID:20887993

Henderson, Jacqueline; Thoreson, Andrew; Yoshii, Yuichi; Zhao, Kristin D.; Amadio, Peter C.; An, Kai-Nan

2010-01-01

401

Connective Tissue Growth Factor (CTGF) Inactivation Leads to Defects in Islet Cell Lineage Allocation and ?-Cell Proliferation during Embryogenesis  

PubMed Central

The factors necessary for normal pancreatic islet morphogenesis have not been well characterized. Here we report that connective tissue growth factor (CTGF) is involved in the establishment of normal islet endocrine cell ratio and architecture. CTGF is a secreted protein known to modulate several growth factor-signaling pathways including TGF-?, BMP, and Wnt. Although its role in pancreatic diseases such as pancreatitis and pancreatic cancer are well documented, a role for CTGF in normal pancreas development and function has heretofore not been examined. Using a lacZ-tagged CTGF allele, we describe for the first time the expression pattern of CTGF in the developing pancreas and the requirement of CTGF for normal islet morphogenesis and embryonic ?-cell proliferation. CTGF is highly expressed in pancreatic ductal epithelium and vascular endothelium, as well as at lower levels in developing insulin+ cells, but becomes down-regulated in ?-cells soon after birth. Pancreata from CTGF null embryos have an increase in glucagon+ cells with a concomitant decrease in insulin+ cells, and show defects in islet morphogenesis. Loss of CTGF also results in a dramatic decrease in ?-cell proliferation at late gestation. Unlike CTGF null embryos, CTGF heterozygotes survive past birth and exhibit a range of islet phenotypes, including an intermingling of islet cell types, increased number of glucagon+ cells, and ?-cell hypertrophy. PMID:19131512

Crawford, Laura A.; Guney, Michelle A.; Oh, Young Ah; DeYoung, R. Andrea; Valenzuela, David M.; Murphy, Andrew J.; Yancopoulos, George D.; Lyons, Karen M.; Brigstock, David R.; Economides, Aris; Gannon, Maureen

2009-01-01

402

Pneumocystis jirovecii pneumonia in mycophenolate mofetil-treated patients with connective tissue disease: analysis of 17 cases.  

PubMed

The association of Pneumocystis jirovecii pneumonia (PJP) with connective tissue disease (CTD) and mycophenolate mofetil's (MMF) potent activity against PJP have been separately reported. Until now, there have been no papers describing the occurrence of PJP following MMF treatment in CTD patients. The objective of this study was to describe the clinical features, risk factors, outcomes of PJP in patients with CTD and investigates the effects of MMF on the occurrence of PJP in China. In this retrospective cohort study, we performed a chart review, analyzing clinical features, treatment, and outcomes of PJP in patients with CTD in a single hospital. A total of 17 cases met the inclusion criteria of having PJP and a CTD diagnosis: systemic lupus erythematosus; polymyositis; dermatomyositis; rheumatoid arthritis; Wegener's granulomatosis; and microscopic polyangiitis. Sixteen patients were treated with glucocorticoids (GCs) plus immunosuppressive drugs. Only one patient had GCs without immunosuppressive drugs. Ten subjects (62.5 %) received MMF (1-1.5 g/day), and all ten had lymphopenia. The mortality rates of MMF and non-MMF patients were 50 and 14 %, respectively. This study is the first report of PJP following MMF plus GC treatment in patients with CTD. CTD itself may be a risk factor for PJP. When CTD patients receiving MMF therapy have low lymphocyte counts and/or CD4 lymphocyte counts <250/µL, we should be care of occurrence of PJP. PMID:24948376

Zhang, Yongfeng; Zheng, Yi

2014-12-01

403

Expression and clinical significance of connective tissue growth factor in advanced head and neck squamous cell cancer.  

PubMed

Connective tissue growth factor (CTGF) has been reported to play critical roles in the tumorigenesis of several human malignancies. This study was performed to evaluate CTGF protein expression in head and neck squamous cell carcinoma (HNSCC). Surgical specimens from 76 primary HNSCC were obtained with written informed consents and the expression level of CTGF was immunohistochemically evaluated. The cytoplasmic immunoreactivity of CTGF in cancer cells was semiquantitatively classified into low and high expression. Among all 76 cases with or without neoadjuvant therapy, low CTGF showed significantly longer (P = 0.0282) overall survival (OS), but not disease-free survival (DFS) than high CTGF. Although low CTGF in patients with stage I, II and III did not result in any significant difference of the OS and DFS, stage IV HNSCC patients with low CTGF showed significantly longer OS (P = 0.032) and DFS (P = 0.0107) than those with high CTGF. These differences in stage IV cases were also confirmed using multivariate analyses. These results suggest that low CTGF in stage IV HNSCC is an independent prognostic factor, despite with or without neoadjuvant therapy. PMID:24700237

Kikuchi, Ryoko; Kikuchi, Yoshihiro; Tsuda, Hitoshi; Maekawa, Hitoshi; Kozaki, Ken-Ichi; Imoto, Issei; Tamai, Seiichi; Shiotani, Akihiro; Iwaya, Keiichi; Sakamoto, Masaru; Sekiya, Takao; Matsubara, Osamu

2014-07-01

404

[Autoimmune thrombocitopenic purpura in pregnancy].  

PubMed

The author deals with haematologists' and obstetricians' current views on acquired ATP in children and adults, characterised by a transient, acute or chronic decrease in platelets count (<50.109/l) due to premature destruction by the reticuloendothelial system. The most common questions arising in connection with this disease are: what is autoimmune thrombocytopenic purpura; is there any correlation between pregnancy and ATP; what are its symptoms; does pregnancy itself affect the autoimmune disease. If is of utter importance for women with ATP to be aware of the risks these symptoms pose both on the health of the mother and the foetus. Obstetricians and gynaecologists seldom object to pregnancy in women with ATP. Nevertheless, it is essential to point out that additional monitoring and therapy are needed. There is no medical evidence that supports the notion of terminating pregnancy due to ATP. Assessment is made only by an obstetrician, haematologist and pediatrician working in close collaboration. This collaborative work must be present throughout the whole pregnancy, delivery and puerperium. The treatment necessary for women with ATP aims to establish platelet count over 50.000 ppm when approaching the end of pregnancy, preferably between 80.000 ppm - 100.000 ppm taking into account vagina or surgical delivery as well as the administration of anaesthetic. Delivery management must be decided entirely on obstetrics consideration, but not on ATP ones. Pregnant women with ATP must be monitored and treated with caution by a highly specialised medical team. PMID:20225496

Christova, R; Lisichkov, T; Chernev, T

2009-01-01

405

Anti Tumor Immunity Can Be Uncoupled From Autoimmunity Following Hsp70-Mediated Inflammatory Killing Of Normal Pancreas1  

PubMed Central

We have a long term interest in the connectivity between autoimmunity and tumor rejection. However, outside of the melanocyte/melanoma paradigm, little is known about whether autoimmune responses to normal tissue can induce rejection of tumors of the same histological type. Here, we induced direct, pathogen-like cytotoxicity to the normal pancreas in association with the immune adjuvant hsp70. In sharp contrast to our studies with a similar approach for the treatment of prostate cancer, inflammatory killing of the normal pancreas induced a Th-1-like, anti-self response to pancreatic antigens which was rapidly suppressed by a concomitant suppressive regulatory T cell (Treg) response. Interestingly, even when Treg cells were depleted, the Th-1-like response was insufficient to induce significant ongoing autoimmunity. However, the Th-1-like response to antigens expressed in the pancreas at the time of damage was sufficient to induce rejection of tumors expressing either a foreign (ova) antigen, or fully syngeneic tumor antigens (on PancO2 tumor cells), provided that Treg were depleted prior to inflammatory killing of the normal pancreas. Taken together, these data indicate that profound differences exist between the immunoprotective mechanisms in place between different tissues (pancreas and prostate) in their response to pathogen-like damage. Moreover, they also show that, although multiple layers of immunological safeguards are in place to prevent the development of severe autoimmune consequences in the pancreas (in contrast to the prostate), tumor rejection responses can still be de-coupled from pathological autoimmune responses in vivo, which may provide novel insights into the immunotherapeutic treatment of pancreatic cancer. PMID:19738045

Kottke, Timothy; Pulido, Jose; Thompson, Jill; Sanchez-Perez, Luis; Chong, Heung; Calderwood, Stuart K.; Selby, Peter; Harrington, Kevin; Melcher, Alan; Vile, Richard

2009-01-01

406

Autoimmunity induced by syngeneic splenocyte membranes carrying irreversibly adsorbed paramyxovirus.  

PubMed Central

Newcastle disease virus was adsorbed to a membrane fraction prepared from splenocytes, and the resulting preparation was injected into syngeneic C3H mice. Complement fixing and cytotoxic antibodies reactive with syngeneic tissue and intact cells developed, and some mice died with autoimmune disease characterized by wasting, severe kidney damage, and loss of lymphoid tissue as described previously for animals receiving the membrane fraction of a syngeneic lymphoma in which Newcastle disease virus had grown. Similar experiments were done with L929 mouse fibroblasts and allogeneic spleen membrane fractions. With syngeneic spleen tissue and L929 fibroblasts, serological evidence of autoimmunity appeared after several injections, but deaths from autoimmunity were considerably delayed unless Freund's complete adjuvant was given with the antigen. The results suggest that antigen modification occurs after adsorption of the paramyxovirus to normal tissue as well as lymphoma cell membranes. PMID:7380556

Eaton, M D

1980-01-01

407

Tenascin-Y: a protein of novel domain structure is secreted by differentiated fibroblasts of muscle connective tissue  

PubMed Central

Tenascin-Y was identified in chicken as a novel member of the tenascin (TN) family of ECM proteins. Like TN-C, TN-R, and TN-X, TN-Y is a multidomain protein consisting of heptad repeats, epidermal growth factor-like repeats, fibronectin type III-like (FNIII) domains and a domain homologous to fibrinogen. In contrast to all other known TNs, the series of FNIII domains is interrupted by a novel domain, rich in serines (S) and prolines (P) that occur as repeated S-P-X-motifs, where X stands for any amino acid. Interestingly, the TN-Y-type FNIII domains are 70-100% identical with respect to their DNA sequence. Different TN- Y variants are created by alternative splicing of FNIII domains. Although, based on sequence comparisons TN-Y is most similar to mammalian TN-X, these molecules are not species homologues. TN-Y is predominantly expressed in embryonic and adult chicken heart and skeletal muscle and, to a lower extent, also in several non-muscular tissues. Two major transcripts of approximately 6.5 and 9.5 kb are differentially expressed during heart and skeletal muscle development and are also present in the adult. Anti-TN-Y antibodies recognize a approximately 400-kD double band and a approximately 300-kD form of TN- Y on immunoblots of chicken heart extracts. In situ hybridization and immunofluorescence analysis of aortic smooth muscle, heart, and skeletal muscle revealed that TN-Y is mainly expressed and secreted by cells within muscle-associated connective tissue. Cultured primary muscle fibroblasts released a approximately 220-kD doublet and a approximately 170-kD single TN-Y variant only when cultured in 10% horse serum but not in medium containing 10% fetal calf serum. All TN-Y variants isolated bind to heparin under physiologically relevant conditions that may indicate an important function retained in all tenascins. PMID:8830777

1996-01-01

408

Plasma CCN2/connective tissue growth factor is associated with right ventricular dysfunction in patients with neuroendocrine tumors  

PubMed Central

Background Carcinoid heart disease, a known complication of neuroendocrine tumors, is characterized by right heart fibrotic lesions. Carcinoid heart disease has traditionally been defined by the degree of valvular involvement. Right ventricular (RV) dysfunction due to mural involvement may also be a manifestation. Connective tissue growth factor (CCN2) is elevated in many fibrotic disorders. Its role in carcinoid heart disease is unknown. We sought to investigate the relationship between plasma CCN2 and valvular and mural involvement in carcinoid heart disease. Methods Echocardiography was performed in 69 patients with neuroendocrine tumors. RV function was assessed using tissue Doppler analysis of myocardial systolic strain. Plasma CCN2 was analyzed using an enzyme-linked immunosorbent assay. Mann-Whitney U, Kruskal-Wallis, Chi-squared and Fisher's exact tests were used to compare groups where appropriate. Linear regression was used to evaluate correlation. Results Mean strain was -21% ± 5. Thirty-three patients had reduced RV function (strain > -20%, mean -16% ± 3). Of these, 8 had no or minimal tricuspid and/or pulmonary regurgitation (TR/PR). Thirty-six patients had normal or mildly reduced RV function (strain ? -20%, mean -25% ± 3). There was a significant inverse correlation between RV function and plasma CCN2 levels (r = 0.47, p < 0.001). Patients with reduced RV function had higher plasma CCN2 levels than those with normal or mildly reduced RV function (p < 0.001). Plasma CCN2 ? 77 ?g/L was an independent predictor of reduced RV function (odds ratio 15.36 [95% CI 4.15;56.86]) and had 88% sensitivity and 69% specificity for its detection (p < 0.001). Plasma CCN2 was elevated in patients with mild or greater TR/PR compared to those with no or minimal TR/PR (p = 0.008), with the highest levels seen in moderate to severe TR/PR (p = 0.03). Conclusions Elevated plasma CCN2 levels are associated with RV dysfunction and valvular regurgitation in NET patients. CCN2 may play a role in neuroendocrine tumor-related cardiac fibrosis and may serve as a marker of its earliest stages. PMID:20053285

2010-01-01

409

Occurrence of HSV-1-induced pneumonitis in patients under standard immunosuppressive therapy for rheumatic, vasculitic, and connective tissue disease  

PubMed Central

Background Herpes simplex virus type-1 (HSV-1) has been described to cause respiratory tract infections in critically ill patients or in individuals that are immunocompromised. It is a continuing matter of debate under which circumstances HSV-1 is a relevant pathogen for pneumonitis. While its role during critical illness has been investigated by prospective interventional studies, comparatively little systematic data is available on the role of HSV-1 for pneumonitis in outpatients with autoimmune disease under a maintenance regimen of immunosuppression. Methods We retrospectively reviewed the charts of ~1400 patients with rheumatoid arthritis, vasculitis, and systemic lupus erythematosus (SLE) that were followed at the outpatient clinic of a German University hospital during the years 2000–2007. Episodes of admission to a ward resulting in the diagnosis of pneumonia/pneumonitis were identified, and the type of pneumonia and clinical features retrospectively studied. Results 63 patients with rheumatoid arthritis, vasculitis, or SLE were admitted to a ward and diagnosed to have pneumonia/pneumonitis. Using bronchoscopy a total of 6 cases of pulmonary infection associated with HSV-1 in the lower respiratory tract were identified. Among those, 2 cases suggested a causative role of HSV-1 as the sole agent causing pneumonitis that proved clinically responsive to antiviral treatment. In the remaining 4 cases HSV-1 appeared as a bystander of bacterial infection. Maintenance therapy with leflunomide, which inhibits HSV-1 assembly in vitro, was associated with a milder course of pneumonitis in one patient. Detection of HSV-1 was associated with stronger immunosuppressive regimens and vasculitic disease. Conclusion The present study analyzed the frequency and hallmarks of cases of HSV-1 associated pneumonitis that occurred in a comparatively large cohort of patients with rheumatologic autoimmune diseases. In an area of controversy, this study provides further evidence that HSV-1 causes isolated pneumonitis in the immunocompromised. The study may provide an estimate on the frequency of relevant HSV-1 infection and bacterial agents in outpatients with autoimmune disease. PMID:19450259

Witt, Matthias N; Braun, Gerald S; Ihrler, Stephan; Schmid, Holger

2009-01-01

410

Expression changes and novel interaction partners of talin 1 in effector cells of autoimmune uveitis.  

PubMed

Autoimmune uveitis is characterized by crossing of blood-retinal barrier (BRB) by autoaggressive immune cells. Equine recurrent uveitis (ERU) is a valuable spontaneous model for autoimmune uveitis and analyses of differentially expressed proteins in ERU unraveled changed protein clusters in target tissues and immune system. Healthy eyes are devoid of leukocytes. In ERU, however, leukocytes enter the inner eye and subsequently destroy it. Molecular mechanisms enabling cell migration through BRB still remain elusive. Previously, we detected decreased talin 1 expression in blood-derived granulocytes of ERU cases, linking the innate immune system to ERU. Because changes in leukocyte protein expression pattern may play a role in pathological abnormalities leading to migration ability, we aimed at identifying interactors of talin 1 in leukocytes with immunoprecipitation, followed by LC-MS/MS for candidate identification. This enabled us to identify CD90 (Thy1) as novel interactor of talin 1 besides several other interactors. In blood-derived granulocytes from healthy individuals, CD90 was highly abundant and significantly reduced in ERU, especially in effector cells. Connection between talin 1 and CD90 and their expression differences in inflammation is an interesting novel finding allowing deeper insight into immune response of innate immune system and granulocyte migration ability in this organ-specific autoimmune disease. PMID:24144192

Degroote, Roxane L; Hauck, Stefanie M; Treutlein, Gudrun; Amann, Barbara; Fröhlich, Kristina J H; Kremmer, Elisabeth; Merl, Juliane; Stangassinger, Manfred; Ueffing, Marius; Deeg, Cornelia A

2013-12-01

411

Rare variants in the TREX1 gene and susceptibility to autoimmune diseases.  

PubMed

TREX1 (DNase III) is an exonuclease involved in response to oxidative stress and apoptosis. Heterozygous mutations in TREX1 were previously observed in patients with systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS). We performed a mutational analysis of the TREX1 gene on three autoimmune diseases: SLE (210 patients) and SS (58 patients), to confirm a TREX1 involvement in the Italian population, and systemic sclerosis (SSc, 150 patients) because it shares similarities with SLE (presence of antinuclear antibodies and connective tissue damage). We observed 7 variations; two of these are novel nonsynonymous variants (p.Glu198Lys and p.Met232Val). They were detected in one SS and in one SSc patient, respectively, and in none of the 200 healthy controls typed in this study and of the 1712 published controls. In silico analysis predicts a possibly damaging role on protein function for both variants. The other 5 variations are synonymous and only one of them is novel (p.Pro48Pro). This study contributes to the demonstration that TREX1 is involved in autoimmune diseases and proposes that the spectrum of involved autoimmune diseases can be broader and includes SSc. We do not confirm a role of TREX1 variants in SLE. PMID:24224166

Barizzone, Nadia; Monti, Sara; Mellone, Simona; Godi, Michela; Marchini, Maurizio; Scorza, Raffaella; Danieli, Maria G; D'Alfonso, Sandra

2013-01-01

412

Vaccination and autoimmunity-'vaccinosis': a dangerous liaison?  

PubMed

The question of a connection between vaccination and autoimmune illness (or phenomena) is surrounded by controversy. A heated debate is going on regarding the causality between vaccines, such as measles and anti-hepatitis B virus (HBV), and multiple sclerosis (MS). Brain antibodies as well as clinical symptoms have been found in patients vaccinated against those diseases. Other autoimmune illnesses have been associated with vaccinations. Tetanus toxoid, influenza vaccines, polio vaccine, and others, have been related to phenomena ranging from autoantibodies production to full-blown illness (such as rheumatoid arthritis (RA)). Conflicting data exists regarding also the connection between autism and vaccination with measles vaccine. So far only one controlled study of an experimental animal model has been published, in which the possible causal relation between vaccines and autoimmune findings has been examined: in healthy puppies immunized with a variety of commonly given vaccines, a variety of autoantibodies have been documented but no frank autoimmune illness was recorded. The findings could also represent a polyclonal activation (adjuvant reaction). The mechanism (or mechanisms) of autoimmune reactions following immunization has not yet been elucidated. One of the possibilities is molecular mimicry; when a structural similarity exists between some viral antigen (or other component of the vaccine) and a self-antigen. This similarity may be the trigger to the autoimmune reaction. Other possible mechanisms are discussed. Even though the data regarding the relation between vaccination and autoimmune disease is conflicting, it seems that some autoimmune phenomena are clearly related to immunization (e.g. Guillain-Barre syndrome). The issue of the risk of vaccination remains a philosophical one, since to date the advantages of this policy have not been refuted, while the risk for autoimmune disease has not been irrevocably proved. We discuss the pros and cons of this issue (although the temporal relationship (i.e. always 2-3 months following immunization) is impressive). PMID:10648110

Shoenfeld, Y; Aron-Maor, A

2000-02-01

413

Cellular Targeting in Autoimmunity  

PubMed Central

Many biologic agents that were first approved for the treatment of malignancies are now being actively investigated and used in a variety of autoimmune diseases such as rheumatoid arthritis (RA), antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis, systemic lupus erythematosus (SLE), and Sjogren’s syndrome. The relatively recent advance of selective immune targeting has significantly changed the management of autoimmune disorders, and in part, can be attributed to the progress made in understanding effector cell function and their signaling pathways. In this review, we will discuss the recent FDA approved biologic therapies that directly target immune cells as well as the most promising investigational drugs affecting immune cell function and signaling for the treatment of autoimmune disease. PMID:23054625

Rogers, Jennifer L.; Serafin, Donald S.; Timoshchenko, Roman G.; Tarrant, Teresa K.

2012-01-01

414

Autoimmune autonomic ganglionopathy.  

PubMed

Autoimmune autonomic ganglionopathy is an idiopathic acquired disorder of the autonomic nervous system associated with antibodies to the ganglionic nicotinic acetylcholine receptor found in sympathetic, parasympathetic and enteric ganglia. Symptoms and signs reflect diffuse impairment of autonomic functions. Prominent features are gastrointestinal dysmotility, orthostatic hypotension, and tonic pupils. Typical cases have a subacute onset (less than 3 months to maximum symptoms), are monophasic, and may show partial improvement over the course of several months. Other cases have a slowly progressive course which can resemble degenerative forms of autonomic failure. Treatment for milder cases is supportive care for symptom management. Anecdotally, plasma exchange, intravenous immunoglobulin, corticosteroids or immunosuppression have been used successfully to treat more severe cases. Autoimmune autonomic ganglionopathy represents one of a small group of autoimmune neuromuscular disorders that are caused by antibodies against ion channels. PMID:19349706

Winston, Nicole; Vernino, Steven

2009-01-01

415

Pioglitazone inhibits connective tissue growth factor expression in advanced atherosclerotic plaques in low-density lipoprotein receptor-deficient mice.  

PubMed

Connective tissue growth factor (CTGF) is expressed in atherosclerotic plaques. It is generally recognized that CTGF contributes to atherosclerosis by stimulating vascular smooth muscle cell (VSMC) proliferation and extracellular matrix production during the development of atherosclerosis. Recent studies indicate that CTGF may also contribute to plaque destabilization as it induces apoptosis and stimulates MMP-2 expression in VSMCs. Thiazolidinediones (TZDs), a new class of insulin sensitizing drugs for type 2 diabetes, inhibit atherosclerosis. However, their effect on CTGF expression in atherosclerotic plaques remains unknown. In this study, male LDL receptor-deficient mice were fed high-fat diet for 4 months to induce the formation of atherosclerotic plaques and then given the high-fat diet with or without pioglitazone for the next 3 months. At the end of the 7-month study, CTGF expression in aortic atherosclerotic lesions was examined. Results showed that CTGF expression was increased in mice fed the high-fat diet by seven-fold as compared to that in mice fed normal chow, but the treatment with pioglitazone significantly inhibited the high-fat diet-induced CTGF expression. To verify these in vivo observations, in vitro studies using human aortic SMC were conducted. Quantitative real-time PCR and Western blot showed that pioglitazone inhibited TGF-beta-stimulated CTGF expression. In conclusion, the present study has demonstrated that pioglitazone inhibits CTGF expression in mouse advanced atherosclerotic plaques and in cultured human SMCs, and hence unveiled a possible mechanism potentially involved in the inhibition of atherosclerosis by TZD. PMID:16901490

Game, Bryan A; He, Lin; Jarido, Veronica; Nareika, Alena; Jaffa, Ayad A; Lopes-Virella, Maria F; Huang, Yan

2007-05-01

416

TAZ promotes epithelial to mesenchymal transition via the upregulation of connective tissue growth factor expression in neuroblastoma cells.  

PubMed

Neuroblastoma (NB) is a neuroendocrine cancer that occurs most commonly in infants and young children. The Hippo signaling pathway regulates cell proliferation and apoptosis, and its primary downstream effectors are TAZ and yes?associated protein 1 (YAP). The effect of TAZ on the metastatic progression of neuroblastoma and the underlying mechanisms involved remain elusive. In the current study, it was determined by western blot analysis that the migratory and invasive properties of SK?N?BE(2) human neuroblastoma cells are associated with high expression levels of TAZ. Repressed expression of TAZ in SK?N?BE(2) cells was shown to result in a reduction in aggressiveness of the cell line, by Transwell migration and invasion assay. In contrast, overexpression of TAZ in SK?N?SH human neuroblastoma cells was shown by Transwell migration and invasion assays, and western blot analysis, to result in epithelial?mesenchymal transition (EMT) and increased invasiveness. Mechanistically, the overexpression of TAZ was demonstrated to upregulate the expression levels of connective tissue growth factor (CTGF), by western blot analysis and chromatin immunoprecipitation assay, while the knockdown of TAZ downregulated it. Furthermore, TAZ was shown by luciferase assay to induce CTGF expression by modulating the activation of the TGF??/Smad3 signaling pathway. In conclusion, the present study is, to the best of our knowledge, the first to demonstrate that the overexpression of TAZ induces EMT, increasing the invasive abilities of neuroblastoma cells. This suggests that TAZ may serve as a potential target in the development of novel therapies for the treatment of neuroblastoma. PMID:25354978

Wang, Qiang; Xu, Zhilin; An, Qun; Jiang, Dapeng; Wang, Long; Liang, Bingxue; Li, Zhaozhu

2015-02-01

417