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1

Therapy of Autoimmune Connective Tissue Diseases  

Microsoft Academic Search

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

Timothy M. Wright; Dana P. Ascherman

2

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

3

Hair disorders associated with autoimmune connective tissue diseases.  

PubMed

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

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

2014-10-01

4

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

5

Connective Tissue Disorders  

MedlinePLUS

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

6

Connective Tissue Ulcers  

PubMed Central

Connective tissue disorders (CTD), which are often also termed collagen vascular diseases, include a number of related inflammatory conditions. Some of these diseases include rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis (scleroderma), localized scleroderma (morphea variants localized to the skin), Sjogren’s syndrome, dermatomyositis, polymyositis, and mixed connective tissue disease. In addition to the systemic manifestations of these diseases, there are a number of cutaneous features that make these conditions recognizable on physical exam. Lower extremity ulcers and digital ulcers are an infrequent but disabling complication of long-standing connective tissue disease. The exact frequency with which these ulcers occur is not known, and the cause of the ulcerations is often multifactorial. Moreover, a challenging component of CTD ulcerations is that there are still no established guidelines for their diagnosis and treatment. The morbidity associated with these ulcerations and their underlying conditions is very substantial. Indeed, these less common but intractable ulcers represent a major medical and economic problem for patients, physicians and nurses, and even well organized multidisciplinary wound healing centers. PMID:23756459

Dabiri, Ganary; Falanga, Vincent

2013-01-01

7

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

8

Cutaneous mucinosis in mixed connective tissue disease.  

PubMed

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

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

2013-01-01

9

Cutaneous mucinosis in mixed connective tissue disease*  

PubMed Central

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

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

2013-01-01

10

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

PubMed

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

Cunningham, Madeleine W

2014-01-01

11

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

12

Heritable Disorders of Connective Tissue  

MedlinePLUS

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

13

Mechanisms of tissue injury in autoimmune liver diseases.  

PubMed

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

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

2014-09-01

14

What Are Heritable Disorders of Connective Tissue?  

MedlinePLUS

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

15

Pulmonary hypertension associated with connective tissue disease.  

PubMed

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

Fagan, Karen A; Badesch, David B

2002-01-01

16

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

17

Autoimmune hepatitis  

MedlinePLUS

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

18

Update on Management of Connective Tissue Panniculitides  

PubMed Central

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

Braunstein, Inbal; Werth, Victoria P.

2012-01-01

19

Pulmonary hypertension complicating connective tissue disease.  

PubMed

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

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

2013-10-01

20

The arthritis of mixed connective tissue disease.  

PubMed Central

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

Bennett, R M; O'Connell, D J

1978-01-01

21

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

22

Drug induction in connective tissue diseases.  

PubMed

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

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

2014-10-01

23

Chondroitin sulphate inhibits connective tissue mast cells  

PubMed Central

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

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

2000-01-01

24

Questions and Answers on Autoimmunity and Autoimmune Diseases  

MedlinePLUS

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

25

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

26

Connective Tissue Disorders and Smooth Muscle Disorders in Cardiology  

Microsoft Academic Search

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

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

27

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

28

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

29

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

PubMed

Silicon may be important for bone and connective tissue health. Higher concentrations of silicon are suggested to be associated with bone and the connective tissues, compared with the non-connective soft tissues. Moreover, in connective tissues it has been suggested that silicon levels may decrease with age based upon analyses of human aorta. These claims, however, have not been tested under controlled conditions. Here connective and non-connective tissues were collected and analysed for silicon levels from female Sprague-Dawley rats of different ages (namely, 3, 5, 8, 12, 26 and 43weeks; n=8-10 per age group), all maintained on the same feed source and drinking water, and kept in the same environment from weaning to adulthood. Tissues (696 samples) were digested in nitric acid and analysed by inductively coupled plasma optical emission spectrometry for total silicon content. Fasting serum samples were also collected, diluted and analysed for silicon. Higher concentrations of silicon (up to 50-fold) were found associated with bone and the connective tissues compared with the non-connective tissues. Although total silicon content increased with age in all tissues, the highest connective tissue silicon concentrations (up to 9.98?g/g wet weight) were found in young weanling rats, decreasing thereafter with age (by 2-6 fold). Fasting serum silicon concentrations reflected the pattern of connective tissue silicon concentrations and, both measures, when compared to collagen data from a prior experiment in Sprague-Dawley rats, mirrored type I collagen turnover with age. Our findings confirm the link between silicon and connective tissues and would imply that young growing rats have proportionally higher requirements for dietary silicon than mature adults, for bone and connective tissue development, although this was not formally investigated here. However, estimation of total body silicon content suggested that actual Si requirements may be substantially lower than previously estimated which could explain why absolute silicon deficiency is difficult to achieve but, when it is achieved in young growing animals, it results in stunted growth and abnormal development of bone and other connective tissues. PMID:25687224

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

2015-06-01

30

Association of anti-phospholipid antibodies with connective tissue diseases  

PubMed Central

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

Rai, Reena; Swetha, T.

2015-01-01

31

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

PubMed

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

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

2009-08-01

32

Detection of Connective Tissue Disorders from 4D Aortic MR  

E-print Network

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

33

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

34

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

35

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

36

[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

37

Electrical impedance along connective tissue planes associated with acupuncture meridians  

PubMed Central

Background Acupuncture points and meridians are commonly believed to possess unique electrical properties. The experimental support for this claim is limited given the technical and methodological shortcomings of prior studies. Recent studies indicate a correspondence between acupuncture meridians and connective tissue planes. We hypothesized that segments of acupuncture meridians that are associated with loose connective tissue planes (between muscles or between muscle and bone) visible by ultrasound have greater electrical conductance (less electrical impedance) than non-meridian, parallel control segments. Methods We used a four-electrode method to measure the electrical impedance along segments of the Pericardium and Spleen meridians and corresponding parallel control segments in 23 human subjects. Meridian segments were determined by palpation and proportional measurements. Connective tissue planes underlying those segments were imaged with an ultrasound scanner. Along each meridian segment, four gold-plated needles were inserted along a straight line and used as electrodes. A parallel series of four control needles were placed 0.8 cm medial to the meridian needles. For each set of four needles, a 3.3 kHz alternating (AC) constant amplitude current was introduced at three different amplitudes (20, 40, and 80 ?Amps) to the outer two needles, while the voltage was measured between the inner two needles. Tissue impedance between the two inner needles was calculated based on Ohm's law (ratio of voltage to current intensity). Results At the Pericardium location, mean tissue impedance was significantly lower at meridian segments (70.4 ± 5.7 ?) compared with control segments (75.0 ± 5.9 ?) (p = 0.0003). At the Spleen location, mean impedance for meridian (67.8 ± 6.8 ?) and control segments (68.5 ± 7.5 ?) were not significantly different (p = 0.70). Conclusion Tissue impedance was on average lower along the Pericardium meridian, but not along the Spleen meridian, compared with their respective controls. Ultrasound imaging of meridian and control segments suggested that contact of the needle with connective tissue may explain the decrease in electrical impedance noted at the Pericardium meridian. Further studies are needed to determine whether tissue impedance is lower in (1) connective tissue in general compared with muscle and (2) meridian-associated vs. non meridian-associated connective tissue. PMID:15882468

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

2005-01-01

38

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

PubMed

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

Solomon, Joshua J; Fischer, Aryeh

2013-12-25

39

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

40

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

41

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

42

Absorption of Hydrocortisone Acetate in Human Connective Tissue Using Phonophoresis  

PubMed Central

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

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

2011-01-01

43

A Framework for Modelling Connective Tissue Changes in VIIP Syndrome  

NASA Technical Reports Server (NTRS)

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

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

2014-01-01

44

Role of Connective Tissue Growth Factor in Cardiac Fibrosis  

Microsoft Academic Search

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

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

45

Neurologic manifestations of inherited disorders of connective tissue.  

PubMed

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

Debette, Stéphanie; Germain, Dominique P

2014-01-01

46

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

47

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

PubMed

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

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

1997-01-01

48

Coverage of gingival recession using tunnel connective tissue graft technique  

PubMed Central

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

Khuller, Nitin

2009-01-01

49

Connective tissue photodamage in the hairless mouse is partially reversible  

SciTech Connect

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

Kligman, L.H.

1987-03-01

50

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. PMID:25705389

Howard, Luke S.

2015-01-01

51

Autoimmune Inner Ear Disease (AIED)  

MedlinePLUS

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

52

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

PubMed Central

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

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

2013-01-01

53

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

PubMed

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

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

2014-01-01

54

Lipodermatosclerosis in patients with diffuse connective tissue diseases.  

PubMed

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

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

2006-07-01

55

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

PubMed

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

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

2012-12-01

56

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

PubMed Central

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

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

2015-01-01

57

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

Microsoft Academic Search

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

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

2009-01-01

58

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

PubMed

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

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

2014-11-01

59

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

60

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

61

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

PubMed

Reported mechanical properties of orbital connective tissue and fat have been too sparse to model strain-stress relationships underlying biomechanical interactions in strabismus. We performed rheological tests to develop a multi-mode upper convected Maxwell (UCM) model of these tissues under shear loading. From 20 fresh bovine orbits, 30 samples of connective tissue were taken from rectus pulley regions and 30 samples of fatty tissues from the posterior orbit. Additional samples were defatted to determine connective tissue weight proportion, which was verified histologically. Mechanical testing in shear employed a triborheometer to perform: strain sweeps at 0.5-2.0 Hz; shear stress relaxation with 1% strain; viscometry at 0.01-0.5 s(-1) strain rate; and shear oscillation at 1% strain. Average connective tissue weight proportion was 98% for predominantly connective tissue and 76% for fatty tissue. Connective tissue specimens reached a long-term relaxation modulus of 668 Pa after 1,500 s, while corresponding values for fatty tissue specimens were 290 Pa and 1,100 s. Shear stress magnitude for connective tissue exceeded that of fatty tissue by five-fold. Based on these data, we developed a multi-mode UCM model with variable viscosities and time constants, and a damped hyperelastic response that accurately described measured properties of both connective and fatty tissues. Model parameters differed significantly between the two tissues. Viscoelastic properties of predominantly connective orbital tissues under shear loading differ markedly from properties of orbital fat, but both are accurately reflected using UCM models. These viscoelastic models will facilitate realistic global modeling of EOM behavior in binocular alignment and strabismus. PMID:21207094

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

2011-12-01

62

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

63

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

64

Inhibition of rheumatoid arthritis by blocking connective tissue growth factor.  

PubMed

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

2014-11-18

65

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

66

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

67

Congenital complete heart block and maternal connective tissue disease.  

PubMed

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

Jayaprasad, N; Johnson, Francis; Venugopal, K

2006-09-20

68

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

69

Autoimmune Polyglandular Syndrome Type 1  

Microsoft Academic Search

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

Pärt Peterson

70

Understanding Autoimmune Diseases  

MedlinePLUS

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

71

Connective Tissue Growth Factor as a Mediator of Intraocular Fibrosis  

PubMed Central

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

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

2008-01-01

72

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

PubMed

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

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

1993-11-01

73

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

Microsoft Academic Search

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

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

2012-01-01

74

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-hydrostat; muscle; octopus; skeletal support The eight arms of octopuses are capable of a re- markable diversity

Kier, William M.

75

Expression of Connective Tissue Growth Factor in Intra-Abdominal Adhesions  

Microsoft Academic Search

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

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

2002-01-01

76

Carpal tunnel syndrome as a herald of autoimmune rheumatic disorders.  

PubMed Central

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

Pal, B

1997-01-01

77

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

78

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

79

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

80

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

PubMed Central

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

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

2009-01-01

81

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

PubMed

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

82

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

83

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

PubMed

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

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

1982-02-01

84

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

PubMed

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

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

2014-01-01

85

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

PubMed

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

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

2000-11-15

86

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

87

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

PubMed

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

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

1978-12-01

88

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

89

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

90

NEWS AND COMMENTARY Autoimmunity  

E-print Network

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

Cai, Long

91

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

Microsoft Academic Search

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

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

1995-01-01

92

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

93

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

94

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

95

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

PubMed

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

96

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

97

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

98

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

PubMed

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

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

2014-06-01

99

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

PubMed

We propose the progressive mechanical expansion of cell-derived tissue analogues as a novel, growth-based approach to in vitro tissue engineering. The prevailing approach to producing tissue in vitro is to culture cells in an exogenous "scaffold" that provides a basic structure and mechanical support. This necessarily pre-defines the final size of the implantable material, and specific signals must be provided to stimulate appropriate cell growth, differentiation and matrix formation. In contrast, surgical skin expansion, driven by increments of stretch, produces increasing quantities of tissue without trauma or inflammation. This suggests that connective tissue cells have the innate ability to produce growth in response to elevated tension. We posit that this capacity is maintained in vitro, and that order-of-magnitude growth may be similarly attained in self-assembling cultures of cells and their own extracellular matrix. The hypothesis that growth of connective tissue analogues can be induced by mechanical expansion in vitro may be divided into three components: (1) tension stimulates cell proliferation and extracellular matrix synthesis; (2) the corresponding volume increase will relax the tension imparted by a fixed displacement; (3) the repeated application of static stretch will produce sustained growth and a tissue structure adapted to the tensile loading. Connective tissues exist in a state of residual tension, which is actively maintained by resident cells such as fibroblasts. Studies in vitro and in vivo have demonstrated that cellular survival, reproduction, and matrix synthesis and degradation are regulated by the mechanical environment. Order-of-magnitude increases in both bone and skin volume have been achieved clinically through staged expansion protocols, demonstrating that tension-driven growth can be sustained over prolonged periods. Furthermore, cell-derived tissue analogues have demonstrated mechanically advantageous structural adaptation in response to applied loading. Together, these data suggest that a program of incremental stretch constitutes an appealing way to replicate tissue growth in cell culture, by harnessing the constituent cells' innate mechanical responsiveness. In addition to offering a platform to study the growth and structural adaptation of connective tissues, tension-driven growth presents a novel approach to in vitro tissue engineering. Because the supporting structure is secreted and organised by the cells themselves, growth is not restricted by a "scaffold" of fixed size. This also minimises potential adverse reactions to exogenous materials upon implantation. Most importantly, we posit that the growth induced by progressive stretch will allow substantial volumes of connective tissue to be produced from relatively small initial cell numbers. PMID:24755458

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

2014-07-01

100

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

PubMed Central

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

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

2006-01-01

101

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

PubMed Central

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

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

2007-01-01

102

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

DOEpatents

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

103

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

104

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

PubMed

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

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

2015-03-10

105

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

PubMed

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

Henderson, B

1983-01-01

106

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

PubMed Central

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

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

2013-01-01

107

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

108

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

109

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

110

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

111

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

Microsoft Academic Search

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

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

2010-01-01

112

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

113

Periostin Regulates Collagen Fibrillogenesis and the Biomechanical Properties of Connective Tissues  

PubMed Central

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

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

2012-01-01

114

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

115

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 lessoniana, the oval squid. Outer tunic fiber angle (the angle of a tunic collagen fiber relative to the long axis of the squid) decreased from 33.5° in newly hatched animals to 17.7° in the largest animals

Kier, William M.

116

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

117

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

PubMed

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

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

2007-06-01

118

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...

119

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

PubMed

Number of sclerotic glomeruli increases during the aging process. Consequently, majority of remained nonsclerosed glomeruli become hypertrophic and some of them sclerotic, too. The aim of this study was to quantify the size and connective tissue content of nonsclerosed glomeruli and to evaluate the percentage of hypertrophic ones in examined human cases during the aging. Material was right kidney's tissue of 30 cadavers obtained during routine autopsies. Cadavers were without previously diagnosed kidney disease, diabetes, hypertension, or any other systemic disease. Tissue specimens were routinely prepared for histological and morphometric analysis. Images of the histological slices were analyzed and captured under 400x magnification with digital camera. Further they were morphometrically and statistically analyzed with ImageJ and NCSS-PASS software. Multiple and linear regression of obtained morphometric parameters showed significant increase of glomerular connective tissue area and percentage. Cluster analysis showed the presence of two types of glomeruli. Second type was characterized with significantly larger size, connective tissue content, and significantly lower cellularity, in relation to the first type. Such glomeruli might be considered as hypertrophic. First type of glomeruli was predominant in younger cases, while second type of glomeruli was predominant in cases older than 55 years. PMID:22654637

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

2012-01-01

120

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

PubMed

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

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

2011-06-01

121

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

PubMed

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

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

2015-05-01

122

[Autoimmune thyroid disease and associated diseases].  

PubMed

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

Lapcevi?, Mirjana

2005-10-01

123

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

124

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

PubMed Central

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

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

2014-01-01

125

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

Microsoft Academic Search

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

F. Haghighati; M. Mousavi; N. Moslemi

2006-01-01

126

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

PubMed Central

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

Li, Qiaoli; Uitto, Jouni

2014-01-01

127

Autoimmune Retinopathies  

Microsoft Academic Search

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

Jennifer K. Hall; Nicholas J. Volpe

128

Autoimmune Autonomic Ganglionopathy  

MedlinePLUS

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

129

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

PubMed

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

Felekis, Vasilios A

2002-10-01

130

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

PubMed

Exogenous enzymes tenderize meat through proteolysis. Triceps brachii and Supraspinatus were randomly assigned to the seven enzyme treatments, papain, ficin, bromelain, homogenized fresh ginger, Bacillus subtilis protease, and two Aspergillus oryzae proteases or control to determine the extent of tenderization (Warner-Bratzler shear and sensory evaluation) and mode of action (myofibrillar or collagen degradation). Sensory evaluation showed improvement (P<0.0009) for tenderness and connective tissue component and all except ginger had a lower shear force than the control (P<0.003). Ginger produced more off-flavor than all other treatments (P<0.0001). Only papain increased soluble collagen (P<0.0001). Control samples were only significantly less than ficin for water soluble (P=0.0002) and A. oryzae concentrate for salt soluble proteins (P=0.0148). All enzyme treatments can increase tenderness via myofibrillar and collagenous protein degradation with no difference among high and low-connective tissue muscles. PMID:20416788

Sullivan, G A; Calkins, C R

2010-08-01

131

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

132

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

PubMed

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

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

2010-09-30

133

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

134

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

Microsoft Academic Search

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

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

1997-01-01

135

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

136

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

Microsoft Academic Search

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

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

2006-01-01

137

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

E-print Network

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

Percy, Mary Lou

1976-01-01

138

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

PubMed Central

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

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

2011-01-01

139

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

PubMed Central

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

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

1996-01-01

140

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

NASA Astrophysics Data System (ADS)

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

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

141

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

142

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

143

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

PubMed

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

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

2013-12-01

144

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

PubMed

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

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

2011-06-15

145

Reaction of rat connective tissue to mineral trioxide aggregate and diaket  

PubMed Central

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

2011-01-01

146

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

PubMed

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

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

2011-10-01

147

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

148

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

149

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

PubMed

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; Chen, Zhibin

2014-03-10

150

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

151

Autoimmune encephalopathies.  

PubMed

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

Leypoldt, Frank; Armangue, Thaís; Dalmau, Josep

2015-03-01

152

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

PubMed Central

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

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

2013-01-01

153

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

PubMed Central

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

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

2013-01-01

154

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

155

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

PubMed Central

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

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

2010-01-01

156

Autoimmune Retinopathy  

PubMed Central

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

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

2013-01-01

157

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

PubMed Central

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

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

2009-01-01

158

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

159

Connections  

MedlinePLUS

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

160

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

PubMed Central

A key factor that contributes to the regenerative ability of regeneration-competent animals such as the salamander is their use of innate positional cues that guide the regeneration process. The limbs of mammals has severe regenerative limitations, however the distal most portion of the terminal phalange is regeneration competent. This regenerative ability of the adult mouse digit is level dependent: amputation through the distal half of the terminal phalanx (P3) leads to successful regeneration, whereas amputation through a more proximal location, e.g. the subterminal phalangeal element (P2), fails to regenerate. Do the connective tissue cells of the mammalian digit play a role similar to that of the salamander limb in controlling the regenerative response? To begin to address this question, we isolated and cultured cells of the connective tissue surrounding the phalangeal bones of regeneration competent (P3) and incompetent (P2) levels. Despite their close proximity and localization, these cells show very distinctive profiles when characterized in vitro and in vivo. In vitro studies comparing their proliferation and position-specific interactions reveal that cells isolated from the P3 and P2 are both capable of organizing and differentiating epithelial progenitors, but with different outcomes. The difference in interactions are further characterized with three-dimension cultures, in which P3 regenerative cells are shown to lack a contractile response that is seen in other fibroblast cultures, including the P2 cultures. In in vivo engraftment studies, the difference between these two cell lines is made more apparent. While both P2 and P3 cells participated in the regeneration of the terminal phalanx, their survival and proliferative indices were distinct, thus suggesting a key difference in their ability to interact within a regeneration permissive environment. These studies are the first to demonstrate distinct positional characteristics of connective tissue cells that are associated with their regenerative capabilities. PMID:23349966

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

2013-01-01

161

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

162

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

PubMed

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

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

1991-02-01

163

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

164

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

PubMed

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

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

2015-04-01

165

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

PubMed

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

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

2002-03-01

166

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

PubMed

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

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

2011-01-01

167

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

168

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

PubMed

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

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

1996-01-01

169

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

PubMed

We performed thallium 201 muscle scans to assess muscular involvement in 40 patients with different connective tissue diseases (7 with dermatomyositis, 7 with systemic lupus erythematosus, 12 with progressive systemic scleroderma, 2 with calcinosis, Raynaud's phenomenon, esophageal involvement, sclerodactyly, and telangiectasia (CREST) syndrome, 3 with monomelic scleroderma, 6 with morphea, and 3 with Raynaud's disease). Only 12 of these patients complained of fatigability and/or myalgia. Electromyography was performed and serum levels of muscle enzymes were measured in all patients. Comparison of thallium 201 exercise recording with the other tests revealed that scan sensitivity is greater than electromyographic and serum muscle enzymes levels. Thallium 201 scans showed abnormal findings in 32 patients and revealed subclinical lesions in 18 patients, while electromyography findings were abnormal in 25 of these 32 patients. Serum enzyme levels were raised in only 8 patients. Thallium 201 scanning proved to be a useful guide for modifying therapy when laboratory data were conflicting. It was useful to evaluate treatment efficacy. Because our data indicate a 100% positive predictive value, we believe that thallium 201 scanning should be advised for severe systemic connective tissue diseases with discordant test results. PMID:3372758

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

1988-04-01

170

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

171

Clinical evaluation of subepithelial connective tissue graft and guided tissue regeneration for treatment of Miller’s class 1 gingival recession (comparative, split mouth, six months study)  

PubMed Central

Objectives: The present study aims to clinically compare and evaluate subepithelial connective tissue graft and the GTR based root coverage in treatment of Miller’s Class I gingival recession. Study Design: 30 patients with at least one pair of Miller’s Class I gingival recession were treated either with Subepithelial connective tissue graft (Group A) or Guided tissue regeneration (Group B). Clinical parameters monitored included recession RD, width of keratinized gingiva (KG), probing depth (PD), clinical attachment level (CAL), attached gingiva (AG), residual probing depth (RPD) and % of Root coverage(%RC). Measurements were taken at baseline, three months and six months. A standard surgical procedure was used for both Group A and Group B. Data were recorded and statistical analysis was done for both intergroup and intragroup. Results: At end of six months % RC obtained were 84.47% (Group A) and 81.67% (Group B). Both treatments resulted in statistically significant improvement in clinical parameters. When compared, no statistically significant difference was found between both groups except in RPD, where it was significantly greater in Group A. Conclusions: GTR technique has advantages over subepithelial connective tissue graft for shallow Miller’s Class I defects and this procedure can be used to avoid patient discomfort and reduce treatment time. Key words:Collagen membrane, comparative split mouth study, gingival recession, subepithelial connective tissue graft, guided tissue regeneration (GTR). PMID:25136420

Bhavsar, Neeta-V.; Dulani, Kirti; Trivedi, Rahul

2014-01-01

172

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

PubMed

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

Blomberg, R

1986-07-01

173

Autoimmune response in experimental hippocampal pathology  

Microsoft Academic Search

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

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

1986-01-01

174

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 ...

175

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

PubMed

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

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

2005-10-01

176

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 ...

177

Plasmapheresis and Autoimmune Disease  

MedlinePLUS

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

178

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

PubMed

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

Baguma-Nibasheka, Mark; Kablar, Boris

2008-02-01

179

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

180

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

181

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

182

AntiInterferon Autoantibodies in Autoimmune Polyendocrinopathy Syndrome Type 1  

Microsoft Academic Search

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

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

2006-01-01

183

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

184

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

PubMed

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

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

2014-06-01

185

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

PubMed

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

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

2012-12-01

186

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

PubMed

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

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

1990-03-01

187

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

PubMed

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

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

2014-06-01

188

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

PubMed Central

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

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

2014-01-01

189

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

190

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

Microsoft Academic Search

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

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

2010-01-01

191

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

192

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

PubMed Central

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

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

2013-01-01

193

“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

194

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

PubMed Central

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

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

2013-01-01

195

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

PubMed

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

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

2007-03-21

196

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

PubMed Central

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

2015-01-01

197

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

198

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

199

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

200

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.

201

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

Microsoft Academic Search

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

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

2008-01-01

202

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

Microsoft Academic Search

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

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

2005-01-01

203

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

Microsoft Academic Search

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

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

2007-01-01

204

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

PubMed

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

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

2015-04-01

205

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

206

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

PubMed

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

Nechaeva, G I; Drokina, O V

2014-01-01

207

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

208

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

PubMed Central

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

2012-01-01

209

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

PubMed

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

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

1992-02-01

210

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

2015-01-01

211

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

PubMed Central

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

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

2014-01-01

212

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

213

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

PubMed Central

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

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

2008-01-01

214

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

PubMed

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

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

2007-11-01

215

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

PubMed

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

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

2008-08-01

216

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

PubMed Central

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

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

2007-01-01

217

Autoimmune hepatitis.  

PubMed

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

Mieli-Vergani, Giorgina; Vergani, Diego

2011-06-01

218

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

PubMed Central

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

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

2014-01-01

219

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

PubMed Central

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

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

2014-01-01

220

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

PubMed Central

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

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

2013-01-01

221

Exercise training in pulmonary arterial hypertension associated with connective tissue diseases  

PubMed Central

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

2012-01-01

222

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

PubMed Central

Connective tissue growth factor (CTGF/CCN2) is a member of the CCN family of secreted proteins that are believed to play an important role in the development of neoplasia. In particular, CTGF has been reported to play an important role in mammary tumorigenesis and to have prognostic value in female breast cancer (FBC). The aim of the present study was to investigate clinicopathologic correlations and prognostic value of CTGF in male breast cancer (MBC) and to compare these findings with FBC. For this, we studied CTGF protein expression by immunohistochemistry in 109 MBC cases and 75 FBC cases. In MBC, stromal CTGF expression was seen in the majority of the cases 78% (85/109) with high expression in 31/109 cases (28.4%), but expression in tumor cells was only seen in 9.2% (10/109) of cases. High stromal CTGF expression correlated with high grade and high proliferation index (>15%) assessed by MIB-1 immunohistochemical staining. CTGF expression in tumor epithelial cells did not correlate with any of the clinicopathologic features. In FBC, stromal CTGF expression positively correlated with mitotic count and tumor CTGF expression was associated with triple negative status of the tumor (p = 0.002). Neither stromal nor tumor epithelial cell CTGF expression had prognostic value in MBC and FBC. In conclusion, stromal CTGF expression was seen in a high percentage of MBC and was correlated with high grade and high proliferation index. In view of the important role of the microenvironment in cancer progression, this might suggest that stromal CTGF could be an interesting target for novel therapies and molecular imaging. However, the lack of association with prognosis warrants caution. The potential role of CTGF as a therapeutic target for triple negative FBC deserves to be further studied. PMID:25738829

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

2015-01-01

223

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

224

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

PubMed Central

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

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

2013-01-01

225

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

PubMed Central

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

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

2010-01-01

226

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

PubMed

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

Shukunami, Chisa; Oshima, Yusuke; Hiraki, Yuji

2005-07-29

227

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

228

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

229

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

230

Autoimmune Lymphoproliferative Syndrome (ALPS)  

MedlinePLUS

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

231

Toxicology of Autoimmune Diseases  

PubMed Central

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

Hultman, Per; Kono, Dwight H.

2010-01-01

232

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

PubMed

Echinoderms have catch connective tissues that change their stiffness as a result of nervous control. The coordination between catch connective tissue and muscles was studied in the spine joint of the sea urchin Diadema setosum. Spine joints are equipped with two kinds of effector: spine muscles and a kind of catch connective tissue, which is called the catch apparatus (CA). The former is responsible for spine movements and the latter for maintenance of spine posture. Diadema show a shadow reaction in which they wave spines when a shadow falls on them, which is a reflex involving the radial nerves. Dynamic mechanical tests were performed on the CA in a joint at which the muscles were severed so as not to interfere with the mechanical measurements. The joint was on a piece of the test that contained other spines and a radial nerve. Darkening of the preparation invoked softening of the CA and spine waving (the shadow reaction). Electrical stimulation of the radial nerve invoked a similar response. These responses were abolished after the nerve pathways from the radial nerve to spines had been cut. A touch applied to the CA stiffened it and the adjacent spines inclined toward the touched CA. A touch to the base of the adjacent spine softened the CA and the spines around the touched spine inclined towards it. The softening of the CA can be interpreted as a response that reduces the resistance of the ligaments to spine movements. Our results clearly show coordination between catch connective tissue and muscles through nerves. PMID:25740901

Motokawa, Tatsuo; Fuchigami, Yoshiro

2015-03-01

233

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

234

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

Microsoft Academic Search

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

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

235

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

Microsoft Academic Search

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

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

2004-01-01

236

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

237

Autoimmunity and primary biliary cirrhosis.  

PubMed

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

Mackay, I R

2000-08-01

238

[Systemic autoimmune disorders and pregnancy].  

PubMed

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

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

2011-10-23

239

Neonatal autoimmune diseases: a critical review.  

PubMed

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

Chang, Christopher

2012-05-01

240

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

PubMed Central

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

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

2012-01-01

241

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

PubMed Central

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

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

2015-01-01

242

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

243

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

244

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

245

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

PubMed Central

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

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

1994-01-01

246

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

PubMed

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

Usheva, L N; Frolova, L T

2000-01-01

247

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

248

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

PubMed Central

Purpose. To assess FGF-?, TGF-?, and COX2 expression and immunocompetent cells in the orbital tissue of patients with severe and mild Graves' orbitopathy. Patients and Methods. Orbital tissue was taken from 27 patients with GO: (1) severe GO (n = 18), the mean clinical activity score (CAS) being 8.5 (SD 2.5); and (2) mild GO (n = 9), the mean CAS being 2.2 (SD 0.8), and from 10 individuals undergoing blepharoplasty. The expression of CD4+, CD8+, CD20+, and CD68 and FGF-?, TGF-?, and COX2 in the orbital tissue was evaluated by immunohistochemical methods. Results. We demonstrated predominant CD4+ T cells in severe GO. CD68 expression was observed in the fibrous connective area of mild GO and was robust in severe GO, while the prominent TGF-? expression was seen in all GO. Increased FGF-? expression was observed in the fibroblasts and adipocytes of severe GO. No expression of COX2 was found in patients with GO. Conclusions. Macrophages and CD4 T lymphocytes are both engaged in the active/severe and long stage of inflammation in the orbital tissue. FGF-? and TGF-? expression may contribute to tissue remodeling, fibrosis, and perpetuation of inflammation in the orbital tissue of GO especially in severe GO. PMID:25309050

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

2014-01-01

249

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

PubMed

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

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

2006-11-01

250

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

PubMed

The 3D imaging of soft tissues in their native state is challenging, especially when high resolution is required. An X-ray-based microCT is, to date, the best choice for high resolution 3D imaging of soft tissues. However, since X-ray attenuation of soft tissues is very low, contrasting enhancement using different staining materials is needed. The staining procedure, which also usually involves tissue fixation, causes unwanted and to some extent unknown tissue alterations. Here, we demonstrate that a method that enables 3D imaging of soft tissues without fixing and staining using an X-ray-based bench-top microCT can be applied to a variety of different tissues. With the sample mounted in a custom-made loading device inside a humidity chamber, we obtained soft tissue contrast and generated 3D images of fresh, soft tissues with a resolution of 1 micron voxel size. We identified three critical conditions which make it possible to image soft tissues: humidified environment, mechanical stabilization of the sample and phase enhancement. We demonstrate the capability of the technique using different specimens: an intervertebral disc, the non-mineralized growth plate, stingray tessellated radials (calcified cartilage) and the collagenous network of the periodontal ligament. Since the scanned specimen is fresh an interesting advantage of this technique is the ability to scan a specimen under load and track the changes of the different structures. This method offers a unique opportunity for obtaining valuable insights into 3D structure-function relationships of soft tissues. PMID:24437605

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

2014-01-01

251

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

PubMed

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

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

2014-01-01

252

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

PubMed Central

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

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

2014-01-01

253

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

254

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

PubMed

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

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

2015-05-01

255

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

256

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

PubMed

Augmentation of the mechanical properties of connective tissue using ultraviolet (UV) radiation-by targeting collagen cross-linking in the tissue at predetermined UV exposure time [Formula: see text] and wavelength [Formula: see text]-has been proposed as a therapeutic method for supporting the treatment for structural-related injuries and pathologies. However, the effects of [Formula: see text] and [Formula: see text] on the tissue elasticity, namely elastic modulus [Formula: see text] and modulus of resilience [Formula: see text], are not entirely clear. We present a thermomechanical framework to reconcile the [Formula: see text]- and [Formula: see text]-related effects on [Formula: see text] and [Formula: see text]. The framework addresses (1) an energy transfer model to describe the dependence of the absorbed UV photon energy, [Formula: see text], per unit mass of the tissue on [Formula: see text] and [Formula: see text], (2) an intervening thermodynamic shear-related parameter, [Formula: see text], to quantify the extent of UV-induced cross-linking in the tissue, (3) a threshold model for the [Formula: see text] versus [Formula: see text] relationship, characterized by   [Formula: see text]-the critical [Formula: see text] underpinning the association of [Formula: see text] with [Formula: see text]-and (4) the role of [Formula: see text] in the tissue elasticity. We hypothesized that [Formula: see text] regulates [Formula: see text] (UV-stiffening hypothesis) and [Formula: see text] (UV-resilience hypothesis). The framework was evaluated with the support from data derived from tensile testing on isolated ligament fascicles, treated with two levels of [Formula: see text] (365 and 254 nm) and three levels of [Formula: see text] (15, 30 and 60 min). Predictions from the energy transfer model corroborated the findings from a two-factor analysis of variance of the effects of [Formula: see text] and [Formula: see text] treatments. Student's t test revealed positive change in [Formula: see text] and [Formula: see text] with increases in [Formula: see text]-the findings lend support to the hypotheses, implicating the implicit dependence of UV-induced cross-links on [Formula: see text] and [Formula: see text] for directing tissue stiffness and resilience. From a practical perspective, the study is a step in the direction to establish a UV irradiation treatment protocol for effective control of exogenous cross-linking in connective tissues. PMID:24419559

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

2014-10-01

257

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

PubMed Central

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

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

2014-01-01

258

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

259

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

PubMed

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

Marafetti, Lucas E; Romeo, Horacio E

2014-11-15

260

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

PubMed

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

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

2014-01-01

261

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

262

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

PubMed

It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson's trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ?treated group. Similarly, PQ treatment of MRC?5 human lung fibroblast cells caused an increase in CTGF in a dose?dependent manner. Furthermore, the addition of CTGF to MRC?5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of ??smooth muscle actin (??SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ?induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury. PMID:25815693

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

2015-07-01

263

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

264

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

Microsoft Academic Search

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

Robin Jacquet; Jennifer Hillyer; William J. Landis

2005-01-01

265

Autoimmune effector memory T cells: the bad and the good  

PubMed Central

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

Devarajan, Priyadharshini; Chen, Zhibin

2014-01-01

266

Autoimmune primary ovarian insufficiency.  

PubMed

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

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

2014-01-01

267

NK Cell Autoreactivity and Autoimmune Diseases  

PubMed Central

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

Poggi, Alessandro; Zocchi, Maria Raffaella

2014-01-01

268

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

PubMed

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

Régent, Alexis; Mouthon, Luc

2009-05-01

269

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

PubMed Central

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

Castori, Marco

2012-01-01

270

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

PubMed Central

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

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

2005-01-01

271

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

272

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

273

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

PubMed Central

Young female athletes experience a higher incidence of ligament injuries than their male counterparts, females experience a higher incidence of joint hypermobility syndrome (a risk factor for osteoarthritis development), and post-menopausal females experience a higher prevalence of osteoarthritis than age-matched males. These observations indicate that fluctuating sex hormone levels in young females and loss of ovarian sex hormone production due to menopause likely contribute to observed sex differences in knee joint function and risk for loss of function. In studies of osteoarthritis, however, there is a general lack of appreciation for the heterogeneity of hormonal control in both women and men. Progress in this field is limited by the relatively few preclinical osteoarthritis models, and that most of the work with established models uses only male animals. To elucidate sex differences in osteoarthritis, it is important to examine sex hormone mechanisms in cells from knee tissues and the sexual dimorphism in the role of inflammation at the cell, tissue, and organ levels. There is a need to determine if the risk for loss of knee function and integrity in females is restricted to only the knee or if sex-specific changes in other tissues play a role. This paper discusses these gaps in knowledge and suggests remedies. PMID:23374322

2013-01-01

274

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

PubMed Central

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

2012-01-01

275

Human Cytomegalovirus and Autoimmune Disease  

PubMed Central

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

2014-01-01

276

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

277

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

278

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

279

Update in Endocrine Autoimmunity  

PubMed Central

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

Anderson, Mark S.

2008-01-01

280

Neuroendocrinology of autoimmunity  

Microsoft Academic Search

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

Michael Harbuz

2002-01-01

281

Progesterone and autoimmune disease.  

PubMed

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

Hughes, Grant C

2012-05-01

282

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

283

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

284

Ovarian autoimmune disease: clinical concepts and animal models.  

PubMed

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

2014-11-01

285

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

286

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. PMID:25685279

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

2015-01-01

287

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

PubMed

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

Emura, Shoichi; Okumura, Toshihiko; Chen, Huayue

2008-09-01

288

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

289

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

PubMed

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

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

1999-03-01

290

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

PubMed Central

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

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

2010-01-01

291

Autoimmune Thyroid Disorders  

PubMed Central

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

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

2013-01-01

292

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

PubMed Central

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

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

2013-01-01

293

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

294

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

PubMed

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

Mancano, Michael A

2014-03-01

295

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

296

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

PubMed Central

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

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

1984-01-01

297

Autoimmunity and the Gut  

PubMed Central

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

Campbell, Andrew W.

2014-01-01

298

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

299

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

300

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

PubMed Central

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

Jiang, Qiujie; Uitto, Jouni

2012-01-01

301

[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

302

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

PubMed Central

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

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

1994-01-01

303

Stress proteins, autoimmunity, and autoimmune disease.  

PubMed

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

Winfield, J B; Jarjour, W N

1991-01-01

304

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

Microsoft Academic Search

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

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

1999-01-01

305

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

306

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

307

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

308

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

Microsoft Academic Search

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

Peter Chin Wan Fung; Peter Chin; Wan Fung

2009-01-01

309

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

Microsoft Academic Search

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

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

1990-01-01

310

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

PubMed Central

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

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

2012-01-01

311

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

PubMed Central

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

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

1988-01-01

312

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

313

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

PubMed

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

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

2008-08-01

314

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

PubMed Central

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

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

2015-01-01

315

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

PubMed Central

Antiproliferative factor (APF) is a sialoglycopeptide elevated in the urine of patients with interstitial cystitis (IC)—a chronic, painful bladder disease of unknown etiology. APF inhibits the proliferation of normal bladder epithelial and T24 bladder carcinoma cells in vitro by binding to cytoskeleton-associated protein 4 (CKAP4) and altering the transcription of genes involved in proliferation, cellular adhesion, and tumorigenesis; however, specific molecular mechanisms and effector genes that control APF's antiproliferative effects are unknown. In this study, we found that there was a 7.5-fold up-regulation of connective tissue growth factor (CTGF/CCN2) expression in T24 bladder carcinoma cells treated with APF. Western blot revealed a dose-dependent increase in CCN2 protein levels, with secretion into the culture medium after APF treatment. CCN2 overexpression enhanced APF's antiproliferative activity, whereas CCN2 knockdown diminished APF-induced p53 expression. Using a luciferase reporter construct, we found that APF treatment resulted in fivefold activation of the CCN2 proximal promoter and, of importance, that small interfering RNA–mediated knockdown of CKAP4 inhibited CCN2 upregulation. In addition, we demonstrate that CKAP4 translocates to the nucleus and binds to the CCN2 proximal promoter in an APF-dependent manner, providing evidence that CCN2 regulation by APF involves CKAP4 nuclear translocation and binding to the CCN2 promoter. PMID:22438586

Matika, Christina A.; Wasilewski, Melissa; Arnott, John A.; Planey, Sonia Lobo

2012-01-01

316

Reconceiving autoimmunity: An overview.  

PubMed

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

Tauber, Alfred I

2014-05-29

317

Autoimmunity and asbestos exposure.  

PubMed

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

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

2014-01-01

318

Undifferentiated Connective Tissue Disease  

MedlinePLUS

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319

Epigenetics and Autoimmune Diseases  

PubMed Central

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

Quintero-Ronderos, Paula; Montoya-Ortiz, Gladis

2012-01-01

320

Inflammasomes and autoimmunity  

PubMed Central

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

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

2010-01-01

321

Inflammasomes and autoimmunity.  

PubMed

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

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

2011-02-01

322

Leukocyte trafficking in experimental autoimmune uveitis in vivo  

Microsoft Academic Search

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

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

1998-01-01

323

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

PubMed

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

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

2014-12-01

324

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

PubMed Central

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

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

2014-01-01

325

Stress and Autoimmune Thyroid Diseases  

Microsoft Academic Search

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

Marcello Bagnasco; Irene Bossert; Giampaola Pesce

2006-01-01

326

Autoimmune hemolytic anemia: From lab to bedside.  

PubMed

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

Chaudhary, R K; Das, Sudipta Sekhar

2014-01-01

327

Autoimmune hemolytic anemia: From lab to bedside  

PubMed Central

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

Chaudhary, R. K.; Das, Sudipta Sekhar

2014-01-01

328

Celiac Disease-Associated Autoimmune Endocrinopathies  

PubMed Central

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

Kumar, Vijay; Rajadhyaksha, Manoj; Wortsman, Jacobo

2001-01-01

329

Scurfy mice: A model for autoimmune disease  

SciTech Connect

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

Godfrey, V.L.

1993-01-01

330

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

PubMed

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

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

1998-05-01

331

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

PubMed Central

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

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

2010-01-01

332

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

PubMed

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

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

2014-06-01

333

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

PubMed

Cell transplantation is a promising strategy to promote CNS repair and has been studied for several decades with a focus on glial cells. Promising candidates include Schwann cells (SCs) and olfactory ensheathing cells (OECs). Both cell types are thought to be neural crest derived and share many properties in common, although OECs appear to be a better candidate for transplantation by evoking less astrogliosis. Using CNS mixed myelinating rat cultures plated on to a monolayer of astrocytes, we demonstrated that SCs, but not OECs, secrete a heat labile factor(s) that inhibits oligodendrocyte myelination. Comparative qRT-PCR and ELISA showed that SCs expressed higher levels of mRNA and protein for connective tissue growth factor (CTGF) than OECs. Anti-CTGF reversed the SCM-mediated effects on myelination. Both SCM and CTGF inhibited the differentiation of purified rat oligodendrocyte precursor cells (OPCs). Furthermore, pretreatment of astrocyte monolayers with SCM inhibited CNS myelination and led to transcriptional changes in the astrocyte, corresponding to upregulation of bone morphogenic protein 4 mRNA and CTGF mRNA (inhibitors of OPC differentiation) and the downregulation of insulin-like growth factor 2 mRNA (promoter of OPC differentiation). CTGF pretreatment of astrocytes increased their expression of CTGF, suggesting that this inhibitory factor can be positively regulated in astrocytes. These data provide evidence for the advantages of using OECs, and not mature SCs, for transplant-mediated repair and provide more evidence that they are a distinct and unique glial cell type. PMID:24259589

Lamond, Rebecca; Barnett, Susan C

2013-11-20

334

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

SciTech Connect

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

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

2008-03-10

335

MDSC in autoimmunity  

Microsoft Academic Search

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

James G. Cripps; James D. Gorham

2011-01-01

336

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

PubMed Central

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

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

2011-01-01

337

Internal Tissue Adhesive Approved  

MedlinePLUS

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

338

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

PubMed

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

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

2003-09-01

339

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

SciTech Connect

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

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

1980-12-01

340

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

Microsoft Academic Search

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

Xiaojun Ren; Guangju Guan; Gang Liu; Gaohong Liu

2009-01-01

341

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

PubMed

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

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

2012-01-01

342

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

Microsoft Academic Search

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

Marita Uusitalo; Tero Kivelfi; Ahti Tarkkanen

1994-01-01

343

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

Microsoft Academic Search

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

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

1998-01-01

344

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

Microsoft Academic Search

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

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

2008-01-01

345

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

PubMed

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

Estrela, C; Pesce, H F

1997-01-01

346

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

PubMed Central

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

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

2015-01-01

347

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

SciTech Connect

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

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

1993-07-01

348

Mechanisms of autoimmune liver disease.  

PubMed

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

Baier, Julia L C; Mattner, Jochen

2014-11-01

349

[Autoimmune hemolytic anemia].  

PubMed

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

Marmont, A; Zanella, A

2000-10-01

350

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

PubMed

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

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

2009-08-01

351

Etiopathogenesis of insulin autoimmunity.  

PubMed

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

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

2012-01-01

352

Leptin in autoimmune diseases.  

PubMed

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

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

2015-01-01

353

Epilepsy in systemic autoimmune disorders.  

PubMed

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

Valencia, Ignacio

2014-09-01

354

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

PubMed

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

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

2014-01-01

355

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

E-print Network

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

Demas, Greg

356

Targeting dendritic cell function during systemic autoimmunity to restore tolerance.  

PubMed

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

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

2014-01-01

357

Targeting Dendritic Cell Function during Systemic Autoimmunity to Restore Tolerance  

PubMed Central

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

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

2014-01-01

358

The Dopaminergic System in Autoimmune Diseases  

PubMed Central

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

Pacheco, Rodrigo; Contreras, Francisco; Zouali, Moncef

2014-01-01

359

Fueling Autoimmunity: Type I Interferon in Autoimmune Diseases  

PubMed Central

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

Di Domizio, Jeremy; Cao, Wei

2013-01-01

360

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

PubMed Central

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

Elphick, Maurice R.

2012-01-01

361

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

PubMed Central

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

Grand-Pierre, Alix E; Schurgers, Leon J

2011-01-01

362

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

Microsoft Academic Search

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

Andres Hilfiker; Cornelia Kasper; Ralf Hass; Axel Haverich

2011-01-01

363

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

PubMed

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

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

2014-11-01

364

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

Microsoft Academic Search

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

T. Nishimura; A. Hattori; K. Takahashi

2010-01-01

365

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

PubMed Central

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

Giordano, Chiara; Kleiven, Svein

2014-01-01

366

Spontaneous activation of RNA-sensing pathways in autoimmune disease  

PubMed Central

Multiple intracellular RNA sensing innate immune pathways have been linked to autoimmune disease. RNA-related ligands taken up by the endocytic pathway activate TLRs, and affect primarily immune cells. This type of activation is enhanced by nucleic acid-specific antibodies and induces an inflammatory program. In contrast, spontaneous activation of cytoplasmic RNA sensing pathways target mostly non-hematopoietic tissues and their effect on autoimmune disease is secondary to the release of interferon in the circulation. The fact that pathologies result from spontaneous activation of innate pathways implies that endogenous RNA ligands that might be sensed as pathogenic are commonly found in both immune and non-immune cells. PMID:24455767

Crampton, Steve P; Bolland, Silvia

2013-01-01

367

Ionizing radiation and autoimmunity: Induction of autoimmune disease in mice by high dose fractionated total lymphoid irradiation and its prevention by inoculating normal T cells  

SciTech Connect

Ionizing radiation can functionally alter the immune system and break self-tolerance. High dose (42.5 Gy), fractionated (2.5 Gy 17 times) total lymphoid irradiation (TLI) on mice caused various organ-specific autoimmune diseases, such as gastritis, thyroiditis, and orchitis, depending on the radiation dosages, the extent of lymphoid irradiation, and the genetic background of the mouse strains. Radiation-induced tissue damage is not the primary cause of the autoimmune disease because irradiation of the target organs alone failed to elicit the autoimmunity and shielding of the organs from irradiation was unable to prevent it. In contrast, irradiation of both the thymus and the peripheral lymphoid organs/tissues was required for efficient induction of autoimmune disease by TLI. TLI eliminated the majority of mature thymocytes and the peripheral T cells for 1 mo, and inoculation of spleen cell, thymocyte, or bone marrow cell suspensions (prepared from syngeneic nonirradiated mice) within 2 wk after TLI effectively prevented the autoimmune development. Depletion of T cells from the inocula abrogated the preventive activity. CD4[sup +] T cells mediated the autoimmune prevention but CD8[sup +] T cells did not. CD4[sup +] T cells also appeared to mediate the TLI-induced autoimmune disease because CD4[sup +] T cells from disease-bearing TLI mice adoptively transferred the autoimmune disease to syngeneic naive mice. Taken together, these results indicate that high dose, fractionated ionizing radiation on the lymphoid organs/tissues can cause autoimmune disease by affecting the T cell immune system, rather than the target self-Ags, presumably by altering T cell-dependent control of self-reactive T cells. 62 refs., 9 figs., 2 tabs.

Sakaguchi, N.; Sakaguchi, S. (Stanford Univ. School of Medicine, CA (United States) Scripps Research Institute, La Jolla, CA (United States) PRESTO, JRDC, Institute of Phical and Chemical Research, Tsukuba, Ibaraki (Japan)); Miyai, K. (Univ. of California, San Diego, LA Jolla, CA (United States))

1992-11-01

368

Academic and molecular matrices: A study of the transformations of connective tissue research at the University of Manchester (1947–1996)?  

PubMed Central

This paper explores the different identities adopted by connective tissue research at the University of Manchester during the second half of the 20th century. By looking at the long-term redefinition of a research programme, it sheds new light on the interactions between different and conflicting levels in the study of biomedicine, such as the local and the global, or the medical and the biological. It also addresses the gap in the literature between the first biomedical complexes after World War II and the emergence of biotechnology. Connective tissue research in Manchester emerged as a field focused on new treatments for rheumatic diseases. During the 1950s and 60s, it absorbed a number of laboratory techniques from biology, namely cell culture and electron microscopy. The transformations in scientific policy during the late 70s and the migration of Manchester researchers to the US led them to adopt recombinant DNA methods, which were borrowed from human genetics. This resulted in the emergence of cell matrix biology, a new field which had one of its reference centres in Manchester. The Manchester story shows the potential of detailed and chronologically wide local studies of patterns of work to understand the mechanisms by which new biomedical tools and institutions interact with long-standing problems and existing affiliations. PMID:21486662

García-Sancho, Miguel

2011-01-01

369

Connective tissue disease related interstitial lung diseases and idiopathic pulmonary fibrosis: provisional core sets of domains and instruments for use in clinical trials  

PubMed Central

Rationale Clinical trial design in interstitial lung diseases (ILDs) has been hampered by lack of consensus on appropriate outcome measures for reliably assessing treatment response. In the setting of connective tissue diseases (CTDs), some measures of ILD disease activity and severity may be confounded by non-pulmonary comorbidities. Methods The Connective Tissue Disease associated Interstitial Lung Disease (CTD-ILD) working group of Outcome Measures in Rheumatology—a non-profit international organisation dedicated to consensus methodology in identification of outcome measures—conducted a series of investigations which included a Delphi process including >248 ILD medical experts as well as patient focus groups culminating in a nominal group panel of ILD experts and patients. The goal was to define and develop a consensus on the status of outcome measure candidates for use in randomised controlled trials in CTD-ILD and idiopathic pulmonary fibrosis (IPF). Results A core set comprising specific measures in the domains of lung physiology, lung imaging, survival, dyspnoea, cough and health-related quality of life is proposed as appropriate for consideration for use in a hypothetical 1-year multicentre clinical trial for either CTD-ILD or IPF. As many widely used instruments were found to lack full validation, an agenda for future research is proposed. Conclusion Identification of consensus preliminary domains and instruments to measure them was attained and is a major advance anticipated to facilitate multicentre RCTs in the field. PMID:24368713

Saketkoo, Lesley Ann; Mittoo, Shikha; Huscher, Dörte; Khanna, Dinesh; Dellaripa, Paul F; Distler, Oliver; Flaherty, Kevin R; Frankel, Sid; Oddis, Chester V; Denton, Christopher P; Fischer, Aryeh; Kowal-Bielecka, Otylia M; LeSage, Daphne; Merkel, Peter A; Phillips, Kristine; Pittrow, David; Swigris, Jeffrey; Antoniou, Katerina; Baughman, Robert P; Castelino, Flavia V; Christmann, Romy B; Christopher-Stine, Lisa; Collard, Harold R; Cottin, Vincent; Danoff, Sonye; Highland, Kristin B; Hummers, Laura; Shah, Ami A; Kim, Dong Soon; Lynch, David A; Miller, Frederick W; Proudman, Susanna M; Richeldi, Luca; Ryu, Jay H; Sandorfi, Nora; Sarver, Catherine; Wells, Athol U; Strand, Vibeke; Matteson, Eric L; Brown, Kevin K; Seibold, James R

2014-01-01

370

Three-Dimensional Aspects of the Lingual Papillae and Their Connective Tissue Cores in the Tongue of Rats: A Scanning Electron Microscope Study  

PubMed Central

The aim of the present study was to describe the tridimensional morphological characteristics of the lingual papillae and their connective tissue cores (CTCs) in Sprague Dawley rats. Four types of papillae were reported on the dorsal surface. Filiform papillae were distributed on the tongue surface and after epithelial maceration a conic and multifilamentary shape of the CTCs was revealed. Fungiform papillae were reported on the rostral and middle regions covered by a squamous epithelium. After the removal of the epithelium, the shape of a volcano with the taste orifice at its top was noted. Foliate papillae were composed of five pairs of epithelial folds situated on the lateral-caudal margin of the tongue. After the removal of the epithelium, they were shown to be limited by thin laminar projections. The vallate papilla with an oval shape was present in the caudal region and delimited by an incomplete groove. The morphological characteristics of the lingual papillae of Sprague Dowley rats, three-dimensional SEM images, and the types of papillae on the dorsal surface were similar to those reported previously in other rodent mammals. The maceration technique revealed the details of extracellular matrix with varied shapes form of connective tissue cores. PMID:25436229

Reginato, Gabriela de Souza; Watanabe, Ii-sei; Ciena, Adriano Polican

2014-01-01

371

Adult Stem Cell Therapy for Autoimmune Disease  

PubMed Central

Many studies of autologous hematopoietic stem cell transplantation (HSCT) and allogeneic HSCT have been conducted for autoimmune disease in various animal models. Because of the substantial risk of morbidity and mortality associated with allogeneic bone marrow transplantation, autologous transplants justified trying this approach in patient with severe autoimmune disease who were refractory to current treatments. Remission was achieved in some of the patients and some of them relapsed. Recently, many in vitro studies have reported that mesenchymal stem cells (MSC) have immunomodulatory properties and immunosuppressive effects on MHC-mismatched lymphocytes proliferation by inhibiting naďve, memory and activated T cells, B cell, NK cells and dendritic cells. In addition, adipose tissue-derived MSC (AT-MSC) are becoming an alternative source of MSC for therapeutic applications because adipose tissues are abundant, easily accessible, easily obtainable with little patient discomfort and large amounts of AT-MSC can be easily obtained. A large body of in vitro research has shown that AT-MSC have same or similar immunomodulatory effects with bone marrow derived MSC. Drawing on this finding, the increasing numbers of researchers have turned on their attention to preclinical studies on AT-MSC. As this new path of research evolves with subsequent reports, MSC would make a significant contribution to stem cell therapy or combination therapy for ameliorating symptoms and curing autoimmune disease. By searching and studying the appropriate therapeutic gene, the therapeutic gene transfected stem cell therapy will be able to acquire the synergy effect and the combined advantage of gene therapy and stem cell therapy. PMID:24855531

Choi, Eun Wha

2009-01-01

372

Mineralization of the connective tissue: a complex molecular process leading to age-related loss of function.  

PubMed

Age-related metastatic mineralization of soft tissues has been considered a passive and spontaneous process. Recent data have demonstrated that calcium salt deposition in soft tissues could be a highly regulated process. Although calcification occurs in any tissue type, vascular calcification has been of particular interest due to association with atherosclerosis, chronic kidney disease (CKD), and osteoporosis. Different mechanisms underlying calcium apatite accumulation are explored with these age-related disorders. In the case of atherosclerotic plaques, oxy-lipids trigger release of the pro-inflammatory cytokines and inflammation that activate calcification processes in aorta intimae. In CKD patients, renal failure alters the balance between calcium and phosphate levels usually regulated by fibroblast growth factor-23 (FGF23), Klotho, and vitamin D, and vascular smooth muscle cells (VSMCs) begin to explore an osteoblastosteoblast-like phenotype. Calcification could affect extracellular matrix along with VSMCs. Collagen is a major component of extracellular matrix and its modifications accumulate with age. The formation of cross-links between collagen fibers is regulated by the action of lysine hydroxylases and lysyl oxidase and could occur spontaneously. Oxidation-induced advanced glycation end products (AGEs) are a major type of spontaneous cross-links that accelerate with age and may result in tissue stiffness, problems with recycling, and potential accumulation of calcium apatite. Applying strategies for clearing the AGEs proposed by de Grey may be more difficult in the highly mineralized extracellular matrix. We performed bioinformatic analysis of the molecular pathways underlying calcification in atherosclerotic and CKD patients, signaling pathways of collagen cross-links formation, and bone mineralization, and we propose new potential targets and review drugs for calcification treatment. PMID:23902273

Shindyapina, Anastasia V; Mkrtchyan, Garik V; Gneteeva, Tatiana; Buiucli, Sveatoslav; Tancowny, B; Kulka, M; Aliper, Alexander; Zhavoronkov, Alexander

2014-04-01

373

Annual cycle of expression of connective tissue polypeptide markers in the mantle of the mussel Mytilus galloprovincialis  

Microsoft Academic Search

We suggest that gonad development in the mantle tissue of the bivalve molluscMytilus galloprovincialis Lmk. is an example of epithelial\\/mesenchymal interactions (i.e. soma\\/germline interactions) and morphogenesis in the adult state. According to this concept, the aim of the present study was to use biochemical and immunochemical methods for identifying and characterizing the mantle cell polypeptide markers whose expression is seasonally

A. T. Mikhailov; M. Torrado; J. Méndez; M. J. López

1996-01-01

374

Controlled Compaction with Ruthenium-catalyzed Photochemical Cross-linking of Fibrin-based Engineered Connective Tissue  

PubMed Central

Tissue engineering utilizing fibrin gel as a scaffold has the advantage of creating a completely biological replacement. Cells seeded in a fibrin gel can induce fibril alignment by traction forces when subjected to appropriate mechanical constraints. While gel compaction is key to successful tissue fabrication, excessive compaction can result due to low gel stiffness. This study investigated using ruthenium-catalyzed photo-cross-linking as a method to increase gel stiffness in order to minimize over-compaction. Cross-links between the abundant tyrosine molecules that comprise fibrin were created upon exposure to blue light. Cross-linking was effective in increasing the stiffness of the fibrin gel by 93% with no adverse effects on cell viability. Long-term culture of cross-linked tubular constructs revealed no detrimental effects on cell proliferation or collagen deposition due to cross-linking. After 4 weeks of cyclic distension, the cross-linked samples were more than twice as long as non-cross-linked controls, with similar cell and collagen contents. However, the cross-linked samples required a longer incubation period to achieve a UTS and modulus comparable to controls. This study shows that photo-cross-linking is an attractive option to stiffen the initial fibrin gel and thereby reduce cell-induced compaction, which can allow for longer incubation periods and thus more tissue growth without compaction below a useful size. PMID:19782397

Syedain, Zeeshan H.; Bjork, Jason; Sando, Lillian; Tranquillo, Robert T.

2009-01-01

375

Age-associated differences in triceps surae muscle composition and strength – an MRI-based cross-sectional comparison of contractile, adipose and connective tissue  

PubMed Central

Background In human skeletal muscles, the aging process causes a decrease of contractile and a concomitant increase of intramuscular adipose (IMAT) and connective (IMCT) tissues. The accumulation of non-contractile tissues may contribute to the significant loss of intrinsic muscle strength typically observed at older age but their in vivo quantification is challenging. The purpose of this study was to establish MR imaging-based methods to quantify the relative amounts of IMCT, IMAT and contractile tissues in young and older human cohorts, and investigate their roles in determining age-associated changes in skeletal muscle strength. Methods Five young (31.6?±?7.0 yrs) and five older (83.4?±?3.2 yrs) Japanese women were subject to a detailed MR imaging protocol, including Fast Gradient Echo, Quantitative Fat/Water (IDEAL) and Ultra-short Echo Time (UTE) sequences, to determine contractile muscle tissue and IMAT within the entire Triceps Surae complex, and IMCT within both heads of the Gastrocnemius muscle. Specific force was calculated as the ratio of isometric plantarflexor force and the physiological cross-sectional area of the Triceps Surae complex. Results In the older cohort, total Triceps Surae volume was smaller by 17.5%, while the relative amounts of Triceps Surae IMAT and Gastrocnemius IMCT were larger by 55.1% and 48.9%, respectively. Differences of 38.6% and 42.1% in plantarflexor force and specific force were observed. After subtraction of IMAT and IMCT from total muscle volume, differences in intrinsic strength decreased to 29.6%. Conclusions Our data establishes that aging causes significant changes in skeletal muscle composition, with marked increases in non-contractile tissues. Such quantification of the remodeling process is likely to be of functional and clinical importance in elucidating the causes of the disproportionate age-associated decrease of force compared to that of muscle volume. PMID:24939372

2014-01-01

376

Autoimmune Thyroid Diseases in Children  

PubMed Central

The two major autoimmune thyroid diseases (ATDs) include Graves' disease (GD) and autoimmune thyroiditis (AT); both of which are characterized by infiltration of the thyroid by T and B cells reactive to thyroid antigens, by the production of thyroid autoantibodies and by abnormal thyroid function (hyperthyroidism in GD and hypothyroidism in AT). While the exact etiology of thyroid autoimmunity is not known, it is believed to develop when a combination of genetic susceptibility and environmental encounters leads to breakdown of tolerance. It is important to recognize thyroid dysfunction at an early stage by maintaining an appropriate index of suspicion. PMID:21209713

Cappa, Marco; Bizzarri, Carla; Crea, Francesca

2011-01-01

377

Rheumatic symptoms in autoimmune thyroiditis.  

PubMed

Autoimmune thyroiditis (ATD) is generally regarded as a classic example of single organ autoimmunity with a high association with endocrine thyroid disorders. However, it is closely associated with several autoimmune diseases including rheumatologic syndromes and has long been known to have several rheumatic manifestations particularly in association with hypothyroidism. More recently, it has also been implicated in rheumatologic syndromes in the absence of hypothyroidism or subclinical hypothyroidism. There is also an emerging body of evidence that ATD is highly linked to chronic generalized pain syndromes including fibromyalgia. This review examines the rheumatic symptoms of ATD described in the current literature and discusses the clinical relevance of ATD in general rheumatology. PMID:25618571

Tagoe, Clement E

2015-02-01

378

Pivotal Roles of GM-CSF in Autoimmunity and Inflammation  

PubMed Central

Granulocyte macrophage-colony stimulating factor (GM-CSF) is a hematopoietic growth factor, which stimulates the proliferation of granulocytes and macrophages from bone marrow precursor cells. In autoimmune and inflammatory diseases, Th17 cells have been considered as strong inducers of tissue inflammation. However, recent evidence indicates that GM-CSF has prominent proinflammatory functions and that this growth factor (not IL-17) is critical for the pathogenicity of CD4+ T cells. Therefore, the mechanism of GM-CSF-producing CD4+ T cell differentiation and the role of GM-CSF in the development of autoimmune and inflammatory diseases are gaining increasing attention. This review summarizes the latest knowledge of GM-CSF and its relationship with autoimmune and inflammatory diseases. The potential therapies targeting GM-CSF as well as their possible side effects have also been addressed in this review.

Shiomi, Aoi; Usui, Takashi

2015-01-01

379

Model connective-tissue systems. A study of polyion–mobile ion and of excluded-volume interactions of proteoglycans  

PubMed Central

The osmotic pressure of solutions of sulphated proteoglycans isolated from the intervertebral discs of animals of various ages was determined. The behaviour of the solutions in salt-added systems was investigated in terms of the Donnan distribution of the mobile ions. It is evident that this effect is the dominating factor in explaining the observed nonidealities. Although marked variations in the compositions of the proteoglycan, with regard to their chondroitin sulphate and keratan sulphate content and hence charge content, occur with increasing age of parent tissue, the osmotic activities of the various preparations are very similar. This is explained by the `fixation' of the counterions in such a way as to counteract any change in the charge content of the polyion; an `osmotic buffering' effect. The swelling behaviour of gelatin gels containing the proteoglycan preparations has been measured. In all cases pressures in excess of the sum of the osmotic pressures of the individual components are observed. However, the magnitude of the excess decreases with increasing age of the parent tissue. It is suggested that the age changes, as reflected by a decrease in water content of the gel system, are not the result of changes in the osmotic properties of the individual components but rather reflect changes in the entropic interaction of the proteoglycan with the gelatin matrix. The relevance of this observation to the situation in vivo is discussed. PMID:4282705

Comper, Wayne D.; Preston, Barry N.

1974-01-01

380

Retroviruses and autoimmune rheumatic diseases.  

PubMed Central

In autoimmune rheumatic diseases, retroviruses have been repeatedly discussed as important etiologic factors. However, despite a considerable amount of indirect evidence that retroviruses might indeed be involved in triggering or perpetuating autoimmune rheumatic diseases, clear cut direct evidence is still missing. Studies on arthropathies associated with HIV-1 or HTLV-1 infection as well as new experimental animal models like the Tax transgene mice and new data from the MLR/lpr mouse model might help to answer the questions how and by what mechanisms retroviral infection may lead to autoimmune rheumatic diseases. From data obtained in the MLR/lpr mouse it seems obvious that a potential link of retroviruses, apoptosis and autogenes to autoimmune diseases opens exciting new approaches to the study of rheumatic disease pathogenesis. PMID:7923867

Kalden, J R; Gay, S

1994-01-01

381

American Autoimmune Related Diseases Association  

MedlinePLUS

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382

Associated Autoimmunity in Addison's Disease  

Microsoft Academic Search

As the last extensive series of patients with Addison's disease and coincident autoimmune phenomena were published approximately two decades ago, we studied the cause of the disease, the prevalence of autoimmune disorders and the frequency of occurrence of autoantibodies in 91 patients (31 men and 60 women, mean age 45.3-years-old, range 12–77) with Addison's disease.The cause of Addison's disease in

Pierre M. J. Zelissen; Egbert J. E. G. Bast; Ronald J. M. Croughs

1995-01-01

383

Autoimmune neutropenia preceding Helicobacter pylori-negative MALT lymphoma with nodal dissemination  

PubMed Central

Autoimmune neutropenia (AIN), resulting from granulocyte-specific autoantibodies, is much less frequent than other autoimmune hematologic disorders including autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). These autoimmune disorders may precede, synchronize, or follow collagen disorders, viral infections, and lymphoid neoplasms. Herein we present the first case of AIN in association with Helicobacter pylori-negative mucosa-associated lymphoid tissue (MALT) lymphoma with nodal dissemination. In our case, AIN, accompanied by ITP, occurred prior to the clinical manifestation of lymphoma. AIN and ITP were well managed afterwards, but they relapsed in accordance with the recurrence of lymphoma. The administration of prednisolone at 0.5 mg/kg daily alleviated the cytopenias within a week. In general, combination chemotherapy is performed for the treatment of lymphoma-associated autoimmune hematologic disorders and indeed seems to be effective. Our case indicates that corticosteroid monotherapy may be effective for lymphoma-associated AIN especially when AIN precedes the onset of lymphoma. PMID:25337296

Harada, Saori; Yamazaki, Sho; Nakamura, Fumihiko; Morita, Ken; Yoshimi, Akihide; Shinozaki-Ushiku, Aya; Fukayama, Masashi; Kurokawa, Mineo

2014-01-01

384

Autoimmune neutropenia preceding Helicobacter pylori-negative MALT lymphoma with nodal dissemination.  

PubMed

Autoimmune neutropenia (AIN), resulting from granulocyte-specific autoantibodies, is much less frequent than other autoimmune hematologic disorders including autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP). These autoimmune disorders may precede, synchronize, or follow collagen disorders, viral infections, and lymphoid neoplasms. Herein we present the first case of AIN in association with Helicobacter pylori-negative mucosa-associated lymphoid tissue (MALT) lymphoma with nodal dissemination. In our case, AIN, accompanied by ITP, occurred prior to the clinical manifestation of lymphoma. AIN and ITP were well managed afterwards, but they relapsed in accordance with the recurrence of lymphoma. The administration of prednisolone at 0.5 mg/kg daily alleviated the cytopenias within a week. In general, combination chemotherapy is performed for the treatment of lymphoma-associated autoimmune hematologic disorders and indeed seems to be effective. Our case indicates that corticosteroid monotherapy may be effective for lymphoma-associated AIN especially when AIN precedes the onset of lymphoma. PMID:25337296

Harada, Saori; Yamazaki, Sho; Nakamura, Fumihiko; Morita, Ken; Yoshimi, Akihide; Shinozaki-Ushiku, Aya; Fukayama, Masashi; Kurokawa, Mineo

2014-01-01

385

T-cell Responses to Myelin Antigens in Multiple Sclerosis; Relevance of the Predominant Autoimmune Reactivity to Myelin Oligodendrocyte Glycoprotein  

Microsoft Academic Search

Until recently, the search for the ‘culprit’ autoantigen towards which deleterious autoimmunity is directed in multiple sclerosis (MS) centered mostly on myelin basic protein (MBP) and proteolipid (PLP), the two most abundant protein components of central nervous system (CNS) myelin, the target tissue for the autoimmune attack in MS. Although such research has yielded important data, furthering our understanding of

Nicole Kerlero de Rosbo; Avraham Ben-Nun

1998-01-01

386

Optimum temperature in juvenile salmonids: connecting subcellular indicators to tissue function and whole-organism thermal optimum.  

PubMed

Temperature affects processes at all levels of biological organization, but it is unclear whether processes at different levels have similar thermal optima (T(opt)). Here, we compare the T(opt) for aerobic scope, a whole-organism measure of performance, with both the Arrhenius breakpoint temperature for maximum heart rate (HR-ABT), a measure of tissue level performance, and the temperature at which AMP-activated protein kinase (AMPK) is phosphorylated in the heart, an indicator of an increase in dependence on anaerobic energy metabolism at the cellular level in juvenile rainbow trout Oncorhynchus mykiss. The T(opt) for aerobic scope was 19°C, with aerobic scope being maintained at ?90% of maximum (termed a "T(opt) window") from 16.5° to 20.5°C. HR-ABT occurred at [Formula: see text], while the profile of AMPK phosphorylation started to change from baseline at 19°C, suggesting that these processes have similar thermal sensitivities as a fish is warmed to T(opt). The effects of temperature on AMPK phosphorylation were also measured in coho salmon Oncorhynchus kisutch hearts and compared with previously published values for HR-ABT and aerobic scope T(opt). AMPK phosphorylation in coho hearts began to change at temperatures above 17°C, which again is comparable with the published T(opt) for aerobic scope (17°C) and HR-ABT ([Formula: see text]) in these individuals. Thus, the thermal sensitivity of these subcellular, tissue, and whole-organism functions are highly correlated in both rainbow trout and coho salmon and may depend on each other. PMID:23434784

Anttila, Katja; Casselman, Matthew T; Schulte, Patricia M; Farrell, Anthony P

2013-01-01

387

Oral pamidronate prevents high-dose glucocorticoid-induced lumbar spine bone loss in premenopausal connective tissue disease (mainly lupus) patients.  

PubMed

Glucocorticoid (GC)-induced osteoporosis contributes to chronic damage in patients suffering from connective tissue diseases (CTD) such as systemic lupus erythematosus (SLE). In this study, performed in an highly selected cohort of premenopausal female CTD (mostly lupus) patients, given high-dose GC therapy for severe disease, we show that lumbar spine bone loss can be averted by treatment with oral disodium pamidronate combined with calcium salts and vitamin D3 supplements and not by calcium salts and vitamin D3 supplements alone. We stress the need for optimal GC-induced bone loss prevention therapy in premenopausal patients, a too often neglected issue in patients whose survival has dramatically improved over the last decades. PMID:16130506

Nzeusseu Toukap, A; Depresseux, G; Devogelaer, J-P; Houssiau, F A

2005-01-01

388

Diagnosis of autoimmune pancreatitis  

PubMed Central

Autoimmune pancreatitis (AIP) is a distinct form of chronic pancreatitis that is increasingly being reported. The presentation and clinical image findings of AIP sometimes resemble those of several pancreatic malignancies, but the therapeutic strategy differs appreciably. Therefore, accurate diagnosis is necessary for cases of AIP. To date, AIP is classified into two distinct subtypes from the viewpoints of etiology, serum markers, histology, other organ involvements, and frequency of relapse: type 1 is related to IgG4 (lymphoplasmacytic sclerosing pancreatitis) and type 2 is related to a granulocytic epithelial lesion (idiopathic duct-centric chronic pancreatitis). Both types of AIP are characterized by focal or diffuse pancreatic enlargement accompanied with a narrowing of the main pancreatic duct, and both show dramatic responses to corticosteroid. Unlike type 2, type 1 is characteristically associated with increasing levels of serum IgG4 and positive serum autoantibodies, abundant infiltration of IgG4-positive plasmacytes, frequent extrapancreatic lesions, and relapse. These findings have led several countries to propose diagnostic criteria for AIP, which consist of essentially similar diagnostic items; however, several differences exist for each country, mainly due to differences in the definition of AIP and the modalities used to diagnose this disease. An attempt to unite the diagnostic criteria worldwide was made with the publication in 2011 of the international consensus diagnostic criteria for AIP, established at the 2010 Congress of the International Association of Pancreatology (IAP). PMID:25469024

Matsubayashi, Hiroyuki; Kakushima, Naomi; Takizawa, Kohei; Tanaka, Masaki; Imai, Kenichiro; Hotta, Kinichi; Ono, Hiroyuki

2014-01-01

389

Defective Initiation of Glycosaminoglycan Synthesis due to B3GALT6 Mutations Causes a Pleiotropic Ehlers-Danlos-Syndrome-like Connective Tissue Disorder  

PubMed Central

Proteoglycans are important components of cell plasma membranes and extracellular matrices of connective tissues. They consist of glycosaminoglycan chains attached to a core protein via a tetrasaccharide linkage, whereby the addition of the third residue is catalyzed by galactosyltransferase II (?3GalT6), encoded by B3GALT6. Homozygosity mapping and candidate gene sequence analysis in three independent families, presenting a severe autosomal-recessive connective tissue disorder characterized by skin fragility, delayed wound healing, joint hyperlaxity and contractures, muscle hypotonia, intellectual disability, and a spondyloepimetaphyseal dysplasia with bone fragility and severe kyphoscoliosis, identified biallelic B3GALT6 mutations, including homozygous missense mutations in family 1 (c.619G>C [p.Asp207His]) and family 3 (c.649G>A [p.Gly217Ser]) and compound heterozygous mutations in family 2 (c.323_344del [p.Ala108Glyfs?163], c.619G>C [p.Asp207His]). The phenotype overlaps with several recessive Ehlers-Danlos variants and spondyloepimetaphyseal dysplasia with joint hyperlaxity. Affected individuals’ fibroblasts exhibited a large decrease in ability to prime glycosaminoglycan synthesis together with impaired glycanation of the small chondroitin/dermatan sulfate proteoglycan decorin, confirming ?3GalT6 loss of function. Dermal electron microcopy disclosed abnormalities in collagen fibril organization, in line with the important regulatory role of decorin in this process. A strong reduction in heparan sulfate level was also observed, indicating that ?3GalT6 deficiency alters synthesis of both main types of glycosaminoglycans. In vitro wound healing assay revealed a significant delay in fibroblasts from two index individuals, pointing to a role for glycosaminoglycan defect in impaired wound repair in vivo. Our study emphasizes a crucial role for ?3GalT6 in multiple major developmental and pathophysiological processes. PMID:23664118

Malfait, Fransiska; Kariminejad, Ariana; Van Damme, Tim; Gauche, Caroline; Syx, Delfien; Merhi-Soussi, Faten; Gulberti, Sandrine; Symoens, Sofie; Vanhauwaert, Suzanne; Willaert, Andy; Bozorgmehr, Bita; Kariminejad, Mohamad Hasan; Ebrahimiadib, Nazanin; Hausser, Ingrid; Huysseune, Ann; Fournel-Gigleux, Sylvie; De Paepe, Anne

2013-01-01

390

Defective initiation of glycosaminoglycan synthesis due to B3GALT6 mutations causes a pleiotropic Ehlers-Danlos-syndrome-like connective tissue disorder.  

PubMed

Proteoglycans are important components of cell plasma membranes and extracellular matrices of connective tissues. They consist of glycosaminoglycan chains attached to a core protein via a tetrasaccharide linkage, whereby the addition of the third residue is catalyzed by galactosyltransferase II (?3GalT6), encoded by B3GALT6. Homozygosity mapping and candidate gene sequence analysis in three independent families, presenting a severe autosomal-recessive connective tissue disorder characterized by skin fragility, delayed wound healing, joint hyperlaxity and contractures, muscle hypotonia, intellectual disability, and a spondyloepimetaphyseal dysplasia with bone fragility and severe kyphoscoliosis, identified biallelic B3GALT6 mutations, including homozygous missense mutations in family 1 (c.619G>C [p.Asp207His]) and family 3 (c.649G>A [p.Gly217Ser]) and compound heterozygous mutations in family 2 (c.323_344del [p.Ala108Glyfs(?)163], c.619G>C [p.Asp207His]). The phenotype overlaps with several recessive Ehlers-Danlos variants and spondyloepimetaphyseal dysplasia with joint hyperlaxity. Affected individuals' fibroblasts exhibited a large decrease in ability to prime glycosaminoglycan synthesis together with impaired glycanation of the small chondroitin/dermatan sulfate proteoglycan decorin, confirming ?3GalT6 loss of function. Dermal electron microcopy disclosed abnormalities in collagen fibril organization, in line with the important regulatory role of decorin in this process. A strong reduction in heparan sulfate level was also observed, indicating that ?3GalT6 deficiency alters synthesis of both main types of glycosaminoglycans. In vitro wound healing assay revealed a significant delay in fibroblasts from two index individuals, pointing to a role for glycosaminoglycan defect in impaired wound repair in vivo. Our study emphasizes a crucial role for ?3GalT6 in multiple major developmental and pathophysiological processes. PMID:23664118

Malfait, Fransiska; Kariminejad, Ariana; Van Damme, Tim; Gauche, Caroline; Syx, Delfien; Merhi-Soussi, Faten; Gulberti, Sandrine; Symoens, Sofie; Vanhauwaert, Suzanne; Willaert, Andy; Bozorgmehr, Bita; Kariminejad, Mohamad Hasan; Ebrahimiadib, Nazanin; Hausser, Ingrid; Huysseune, Ann; Fournel-Gigleux, Sylvie; De Paepe, Anne

2013-06-01

391

In situ localization of two fibrillar collagens in two compact connective tissues by immunoelectron microscopy after cryotechnical processing.  

PubMed

Two fibrillar collagens, the worm cuticular collagen and the vertebrate Type I fish scale collagen, both organized in a compact tissue, were localized by immunogold electron microscopy in resin sections after freeze-fixation and freeze-substitution. Identification of these two fibrillar collagens failed with the use of postembedding labelling after conventional electron microscopic processing. Positive labeling of the Type I collagen was observed in sections of fish scales freeze-fixed by either slam-freezing or high-pressure freezing, freeze-substituted in acetone with or without osmium tetroxide, and embedded in LR White. The worm cuticular collagen was detected in sections of cuticle that were freeze-fixed, freeze-substituted (necessarily with osmium tetroxide added to acetone), and embedded in either LR White or Epon. It was also detected in specimens pre-fixed by aldehydes before freeze-fixation. The Type I fish scale collagen appears to be more sensitive than the fibrillar cuticular collagen of worms to the procedures employed for postembedding immunoelectron microscopy. Our results have shown that freeze-fixation and freeze-substitution preserved the antigenicity of the fibrillar collagens organized in a compact three-dimensional network, whereas immunolabeling failed after conventional electron microscopic procedures. These cryostabilization techniques appear to be of value to improve the immunolocalization of collagens. PMID:9010476

Nicolas, G; Gaill, F; Zylberberg, L

1997-01-01

392

Immune-Neuroendocrine Interactions and Autoimmune Diseases  

PubMed Central

The relationship between immune-neuroendocrine system is firmly established. The messengers of this connection are hormones, neuropeptides, neurotransmitters and cytokines. The immune-neuroendocrine system have the capacity to synthesize and release these molecules, which, in turn, can stimulate or suppress the activity of immune or neuroendocrine cells by binding to receptors. In fact, hormones, neuropeptides and neurotransmitters participate in innate and adaptive immune response.Autoimmune rheumatic diseases (ARD) are characterized by aberrant production of pro-inflammatory cytokines, which are a potent activator of the HPA axis. In consequence, high levels of pro-inflammatory hormones such as estrogens and prolactin, and low levels of glucocorticoids, an anti-inflammatory hormone, have been described in the active phase of ARD. In addition, high levels of pro-inflammatory hormones and cytokines have also been frequently detected in organ involvement of patients with ARD, suggesting an abnormal local neuroendocrine immune interaction. There is evidence that hormonal changes may appear before the symptomatic phase of the disease. Therefore, it is possible that a pro-inflammatory hormone favors the rupture of tolerance, which is a key feature of autoimmune diseases. The interactions between the immune-neuroendocrine system have a major impact on our understanding of the pathogenic mechanisms, diagnosis and therapy of ARD. PMID:17162354

Jara, Luis J.; Navarro, Carmen; Medina, Gabriela; Vera-Lastra, Olga; Blanco, Francisco

2006-01-01

393

Type 1 diabetes and autoimmunity.  

PubMed

Type 1 diabetes (T1D) is an organ-specific autoimmune disease caused by the autoimmune response against pancreatic ? cells. T1D is often complicated with other autoimmune diseases, and anti-islet autoantibodies precede the clinical onset of disease. The most common coexisting organ-specific autoimmune disease in patients with T1D is autoimmune thyroid disease, and its frequency is estimated at > 90% among patients with T1D and autoimmune diseases. The prevalence of anti-thyroid antibodies in children with T1D at disease onset is about 20% and is particularly common in girls. Furthermore, patients with anti-thyroid antibodies are 18 times more likely to develop thyroid disease than patients without anti-thyroid antibodies. Therefore, for early detection of autoimmune thyroid disease in children with T1D, measurement of anti-thyroid antibodies and TSH at T1D onset and in yearly intervals after the age of 12 yr is recommended. Anti-islet autoantibodies are predictive and diagnostic markers for T1D. The most frequently detected autoantibodies in Japanese patients are GAD autoantibodies (~80%) followed by IA-2 autoantibodies (~60%), insulin autoantibodies (~55%) and ZnT8 autoantibodies (~50%). In a combined analysis, 94% of Japanese patients with T1D can be defined as having type 1A diabetes. Furthermore, autoantibodies to ZnT8 and IA-2 are associated with childhood-onset and acute-onset patients. Thus, it is important to develop a diagnostic strategy for patients with type 1A diabetes in consideration of the age or mode of disease onset. PMID:25374439

Kawasaki, Eiji

2014-10-01

394

Type 1 Diabetes and Autoimmunity  

PubMed Central

Abstract. Type 1 diabetes (T1D) is an organ-specific autoimmune disease caused by the autoimmune response against pancreatic ? cells. T1D is often complicated with other autoimmune diseases, and anti-islet autoantibodies precede the clinical onset of disease. The most common coexisting organ-specific autoimmune disease in patients with T1D is autoimmune thyroid disease, and its frequency is estimated at > 90% among patients with T1D and autoimmune diseases. The prevalence of anti-thyroid antibodies in children with T1D at disease onset is about 20% and is particularly common in girls. Furthermore, patients with anti-thyroid antibodies are 18 times more likely to develop thyroid disease than patients without anti-thyroid antibodies. Therefore, for early detection of autoimmune thyroid disease in children with T1D, measurement of anti-thyroid antibodies and TSH at T1D onset and in yearly intervals after the age of 12 yr is recommended. Anti-islet autoantibodies are predictive and diagnostic markers for T1D. The most frequently detected autoantibodies in Japanese patients are GAD autoantibodies (~80%) followed by IA-2 autoantibodies (~60%), insulin autoantibodies (~55%) and ZnT8 autoantibodies (~50%). In a combined analysis, 94% of Japanese patients with T1D can be defined as having type 1A diabetes. Furthermore, autoantibodies to ZnT8 and IA-2 are associated with childhood-onset and acute-onset patients. Thus, it is important to develop a diagnostic strategy for patients with type 1A diabetes in consideration of the age or mode of disease onset. PMID:25374439

Kawasaki, Eiji

2014-01-01

395

Celiac sprue: a unique autoimmune disorder  

PubMed Central

Celiac sprue (CS) is a gluten-sensitive enteropathy with many autoimmune features. CS involves multiple organs through immune and nonimmune processes, and is frequently associated with other autoimmune disorders. This article reviews the co-occurrence of CS with autoimmune disorders of the cutaneous, nervous, endocrine, musculoskeletal, gastrointestinal and cardiovascular systems. The types of autoimmune disorders associated with CS and the prevalence of CS in other autoimmune disorders are also discussed. A brief review of the literature on the potential mechanisms behind these associations and the therapeutic effects of a gluten-free diet for autoimmune comorbidities in CS is also provided. PMID:20477645

Rashtak, Shadi; Marietta, Eric V; Murray, Joseph A

2011-01-01

396

Evaluation of root coverage with and without connective tissue graft for the treatment of single maxillary gingival recession using an image analysis system: a randomized controlled clinical trial.  

PubMed

The aim of this prospective randomized clinical study was to evaluate, by means of an image analysis system, the efficacy of two different surgical procedures for the treatment of Miller Class I and II maxillary gingival recession. Patients treated for maxillary gingival recession were recruited and randomly divided into two groups: patients who received a coronally advanced flap with connective tissue graft (CAF + CTG) or CAF alone. Outcome parameters included complete root coverage, recession reduction, and keratinized tissue amount. Twenty-five patients completed the 12-month follow-up period. Patients in the CAF + CTG group showed a better primary outcome- gingival recession at 12 months-than CAF patients (P = .0001). Gingival recession at 12 months had a median of 0.5 (interquartile range [IQR] 0.5 to 0.6) in the CAF + CTG group and a median of 1.0 (IQR 0.9 to 1.1) in the CAF group. CAF + CTG and CAF groups had similar complete root coverage at 6 and 12 months. Recession and keratinized tissue width significantly decreased over time (P < .0001), with no effect of treatment or of treatment over time. Buccal probing depth had similar values over time (P = .28) and in the two groups (P = .52). Buccal clinical attachment level had similar values in the two groups (P = .87); moreover, mesial and distal clinical attachment levels did not show any variation over time (P = .88 and P = .68, respectively). By means of a computerized image analysis system better outcomes in terms of recession reduction after 12 months of follow-up were measured for maxillary gingival recessions treated with CAF and CTG. Adjunctive application of a CTG under a CAF increased the probability of achieving complete root coverage in maxillary Miller Class I and II defects (61.5% versus 83.3%; P = .38). Both treatments were equally effective in providing a consistent reduction of the baseline recession. PMID:25738345

Lops, Diego; Gobbato, Luca; Nart, Jose; Guazzo, Riccardo; Ho, Daniel K; Bressan, Eriberto

2015-01-01

397

Autoimmune pancreatitis can develop into chronic pancreatitis  

PubMed Central

Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung’s and Santorini’s ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct. PMID:24884922

2014-01-01

398

Murine Genotype Influences the Specificity, Magnitude and Persistence of Murine Mercury-Induced Autoimmunity  

Microsoft Academic Search

Genetic factors are major contributors in determining the susceptibility to systemic autoimmune diseases. We studied the influence of genotype on systemic autoimmunity by treating female mice of the H-2sstrains SJL\\/N, SJL\\/J, A.SW, and B10.S with mercuric chloride (HgCl2) for 10 weeks and then following autoantibody and tissue immune deposits during the subsequent 12 months. All strains developed antinucleolar antibodies (ANoA)

Per Hultman; Shannon J. Turley; Sverker Eneström; Ulf Lindh; Michael K. Pollard

1996-01-01

399