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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.

2013-01-01

3

Undifferentiated connective tissue diseases (UCTD): Simplified systemic autoimmune diseases  

Microsoft Academic Search

Conditions characterized by the presence of clinical and serological manifestations suggestive of systemic autoimmune diseases but not fulfilling the classification criteria for defined connective tissue disease (CTD) are common in clinical practice and are indicated as undifferentiated (U) CTDs. Although epidemiological data are not available in the literature, up to 50% of the patients with an undifferentiated CTD of less

Marta Mosca; Chiara Tani; Rosaria Talarico; Stefano Bombardieri

2011-01-01

4

Hematopoietic stem cell transplantation in children with autoimmune connective tissue diseases.  

PubMed

Autoimmune connective tissue diseases (ACTDs) are heterogeneous disorders associated with different manifestations, clinical course of disease and prognosis among patients. Although recent advances in understanding the pathogenesis have led to major progress in target-oriented therapy, they still remain incurable. Novel biological drugs, cellular therapy and hematopoietic stem cell transplantation (HSCT) are real hopes for treatment development in the future. The concept of both autologous and allogeneic HSCT in children with autoimmune diseases is developing energetically since 1996, when the first HSCT was performed. Nowadays, after 17 years of clinical experience, both types of HSCT remain attractive and powerful salvage methods of treatment. However, there are still many doubts and unclear issues, which need further investigation. In the present review, we provide an overview of the knowledge concerning actual data on HSCT in a pediatric group of patients with different ACTDs, focused on juvenile idiopathic arthritis, systemic lupus erythematosus and systemic sclerosis. PMID:24604327

Witkowska, Magdalena; Smolewska, Elzbieta; Smolewski, Piotr

2014-08-01

5

Toll-like receptors as therapeutic targets for autoimmune connective tissue diseases  

PubMed Central

Autoimmune connective tissue diseases (ACTDs) are a family of consistent systemic autoimmune inflammatory disorders, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc) and Sjögren’s syndrome (SS). Toll-like receptors (TLRs) are located on various cellular membranes and sense exogenous and endogenous danger-associated molecular patterns (DAMPs) and pathogen-associated molecular patterns (PAMPs), playing a critical role in innate immune responses. During the past decade, the investigation of TLRs in inflammation autoimmune diseases has been fruitful. In this report, we review the significant biochemical, physiological and pathological studies of the key functions of TLRs in ACTDs. Several proteins in the TLR signaling pathways (e.g., IKK-2 and MyD88) have been identified as potential therapeutic targets for the treatment of ACTDs. Antibodies, oligodeoxyribonucleotides (ODNs) and small molecular inhibitors (SMIs) have been tested to modulate TLR signaling. Some drug-like SMIs of TLR signaling, such as RDP58, ST2825, ML120B and PHA-408, have demonstrated remarkable potential, with promising safety and efficacy profiles, which should warrant further clinical investigation. Nonetheless, one should bear in mind that all TLRs exert both protective and pathogenic functions; the function of TLR4 in inflammatory bowel disease represents such an example. Therefore, an important aspect of TLR modulator development involves the identification of a balance between the suppression of disease-inducing inflammation, while retaining the beneficiary host immune response.

Li, Jing; Wang, Xiaohui; Zhang, Fengchun; Yin, Hang

2013-01-01

6

A rare case of systemic autoimmune disease with intricate features of systemic sclerosis, lupus, polymyositis and rheumatoid arthritis. Overlap syndrome or mixed connective tissue disease?  

PubMed

We report an unusual case of connective tissue disease characterized by the coexistence of signs, symptoms and immunological features of 4 defined autoimmune diseases: systemic lupus erythematosus (SLE), systemic sclerosis (SSc), polymyositis (PM) and rheumatoid arthritis (RA). A 53-year-old female was admitted in our clinic with massive polyserositis (pretamponade) as well as skin, joint, muscular lesions and altered general status. The problem we found was the difficulty of including this case in a known clinical entity; SSc/SLE/PM//RA overlap syndrome and mixed connective tissue disease were the two most plausible diagnoses. We discuss the particularities of these clinical and immunological associations and the appropriate therapeutic options used in this kind of patients. PMID:17932479

Radulescu, Dan; Pripon, Sprin; Ciovicescu, Felix; Constantea, Nicolae A

2007-01-01

7

Occurrence of organ-specific and systemic autoimmune diseases among the first- and second-degree relatives of Caucasian patients with connective tissue diseases: report of data obtained through direct patient interviews  

Microsoft Academic Search

Studies have demonstrated a familial aggregation of systemic and organ-specific autoimmune diseases. The aim of the present\\u000a survey was to obtain, by patient interviews, a preliminary estimate of the prevalence of systemic and organ-specific autoimmune\\u000a diseases among the first- and second-degree relatives of Caucasian patients with connective tissue diseases (CTD) or inflammatory\\u000a arthritis followed at our unit. Between June 2007

Marta Mosca; Linda Carli; Anna d’Ascanio; Chiara Tani; Rosaria Talarico; Chiara Baldini; Laura Bazzichi; Antonio Tavoni; Paola Migliorini; Stefano Bombardieri

2008-01-01

8

Carotid artery intima-media thickness in patients with autoimmune connective tissue diseases: a case-control study.  

PubMed

Patients with autoimmune rheumatic disorders have an increased incidence of cardiovascular (CV) events and mortality. Despite this being related to a high prevalence of the traditional CV risk factors, systemic inflammation has been postulated to be an independent CV risk factor, particularly in patients with rheumatoid arthritis (RA). However, data are still controversial. We designed a case-control study, in which patients with autoimmune rheumatic disorders were matched with age-, sex-matched controls. Prevalence of early atherosclerosis was assessed by carotid artery intima-media thickness (IMT) measurement. IMT values were considered normal (IMT ? 0.9 mm) or abnormal (IMT > 0.9). Multivariate analysis was performed to identify predictors of pathological IMT. Overall, 152 patients and 140 matched controls were enrolled. Prevalence of >0.9 mm IMT values did not significantly differ between patients with autoimmune rheumatic disorders and controls (61 vs. 69%, p = 0.1). In detail, a similar IMT distribution between the 69 RA patients and controls was observed. Cases with a CV risk factor showed a higher prevalence of pathological IMT as compared to those without any risk factor, both in patients (77.1 vs. 38.6%; p < 0.0001) and controls (84.6 vs. 25%; p < 0.0001). At multivariate analysis, age and presence of CV risk factors were found to be independent predictors of >0.9 mm IMT, while RA as well as any other considered rheumatic disease were not. Our data found a similar prevalence of preclinical arterial wall atherosclerotic damage in patients with autoimmune rheumatic diseases and matched controls. Presence of traditional CV risk factors and patient age remain the main factors involved in preclinical atherosclerosis in patients with autoimmune rheumatic disorders, including RA. PMID:22033794

Bruzzese, Vincenzo; Marrese, Cinzia; Zullo, Angelo; Hassan, Cesare; Ridola, Lorenzo; Izzo, Annamaria; Riccioni, Camillo

2013-12-01

9

Occurrence of organ-specific and systemic autoimmune diseases among the first- and second-degree relatives of Caucasian patients with connective tissue diseases: report of data obtained through direct patient interviews.  

PubMed

Studies have demonstrated a familial aggregation of systemic and organ-specific autoimmune diseases. The aim of the present survey was to obtain, by patient interviews, a preliminary estimate of the prevalence of systemic and organ-specific autoimmune diseases among the first- and second-degree relatives of Caucasian patients with connective tissue diseases (CTD) or inflammatory arthritis followed at our unit. Between June 2007 and January 2008, 626 patients and 85 controls (patients with osteoarthritis, osteoporosis, or fibromyalgia) were interviewed. Three hundred ten patients (50%) versus 21 controls (25%) were found to have at least one relative affected with an autoimmune condition (p < 0.0001). The most common conditions were organ-specific autoimmune diseases: 160 (34%) autoimmune thyroid (AT) disease, 112 (24%) psoriasis, 21 vitiligo, and 19 insulin-dependent diabetes mellitus. Systemic autoimmune diseases were reported in 126 relatives: rheumatoid arthritis (66 cases, 14%), 16 sacroileitis, and CTD (43 cases). A significant difference was observed in the prevalence of AT disease between the relatives of the patients and controls (3% versus 0.5%). In conclusion, these data confirm the high prevalence of autoimmune conditions, particularly of AT disease, among the relatives of patients. PMID:18509714

Mosca, Marta; Carli, Linda; d'Ascanio, Anna; Tani, Chiara; Talarico, Rosaria; Baldini, Chiara; Bazzichi, Laura; Tavoni, Antonio; Migliorini, Paola; Bombardieri, Stefano

2008-08-01

10

Connective tissue derived polypeptides  

US Patent & Trademark Office Database

The present invention relates to compositions comprising one or more connective tissue derived polypeptides having a molecular weight of less than 30,000 Da that are capable of tolerising individuals to antigenic components of cartilage and prevent the appearance of and/or treat symptoms of arthritis and other musculoskeletal degenerative conditions. The present invention provides methods for recovering polypeptides having a molecular weight of less than 30,000 Da from connective tissue and having anti-arthritic or anti-inflammatory activity. The present invention further relates to compositions comprising a polypeptide containing an NC4 domain of collagen type IX alpha 1 chain or fragment thereof, having a molecular weight of less than 30,000 Da, where the polypeptide is capable of tolerising individuals to antigenic components of cartilage, preventing the appearance of arthritic symptoms, and/or treating the symptoms of arthritis.

2011-04-05

11

Connective tissue tumors.  

PubMed

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

Zelger, Bernhard

2002-01-01

12

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.

Langridge, William

2014-01-01

13

Overlap connective tissue disease syndromes.  

PubMed

Overlap Syndromes (OSs) have been defined as entities satisfying classification criteria of at least two connective tissue diseases (CTDs) occurring at the same or at different times in the same patient. CTDs include systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), systemic sclerosis (SSc), polymyositis/dermatomyositis (PDM), and Sjögren syndrome (SS). Every combination between these disorders has been reported. In some OS a specific autoantibody has been indentified, supporting the hypothesis that these syndromes are not a mere association of two or more CTD in the same patient, but a well defined clinical entity with specific clinical characteristics. As an example, anti-t-RNA synthetase syndrome is characterized by the presence of anti-t-RNA synthetase antibodies. Notably, clinical manifestations observed in OS may be different from those observed in the single CTD. The treatment of OS is mainly based on the use of corticosteroids and immunosuppressants. Biologic drugs, i.e. anti-TNF? or anti-CD20 monoclonal antibodies, have been recently introduced as alternative treatments in refractory cases. Moreover, there are some concerns with the use of anti-TNF agents in patients with systemic autoimmune diseases due to the risk of triggering disease exacerbations. In this paper the most frequent OS are described with a special focus on the specific immunologic and clinical aspects. Furthermore, some personal data on anti-t-RNA synthetase syndrome and rhupus syndrome are reported. PMID:22743033

Iaccarino, Luca; Gatto, Mariele; Bettio, Silvano; Caso, Francesco; Rampudda, Mariaelisa; Zen, Margherita; Ghirardello, Anna; Punzi, Leonardo; Doria, Andrea

2013-01-01

14

Achalasia and thyroid disease: possible autoimmune connection?  

PubMed

Many cases have been published showing a co-existence of autoimmune thyroid diseases (AITDs) and other autoimmune diseases. About a quarter of patients with achalasia have a concurrent thyroid disease, most commonly associated with hypothyroidism. Although relatively rare, the association of achalasia and hyperthyroidism requires attention. The physiopathology of Grave's Disease (GD) involves B- and T-mediator lymphocytes, which have an affinity for known thyroid antigens: thyroglobulin, thyroid-peroxidase, and thyrotrophin receptor. Currently, however, the real physiopathogenesis of achalasia continues to be unknown. Some important findings are suggestive of an autoimmune mechanism: significant infiltration of the myoenteric plexus by monocytes, presence of the class II-Human Histocompatibility Complex DQwl antigen and antibodies to myoenteric neurons. The present case reports a patient who, despite testing negative for Chagas' disease, had achalasia, progressed to developing significant wasting and worsening of his quality of life, was later diagnosed with hyperthyroidism. After endoscopic esophageal dilatation and radioiodine ablation of the thyroid gland, there was great improvement in the patient clinical condition. PMID:23329193

Quidute, Ana Rosa P; Freitas, Eduardo Vasconcelos de; Lima, Tadeu Gonçalves de; Feitosa, Ana Márcia Lima; Santos, Joyce Paiva dos; Correia, José Walter

2012-12-01

15

[Prolactin in connective tissue diseases].  

PubMed

This paper presents interactions between prolactin (PRL) and the immune system. We describe the role of PRL in the pathogenesis of rheumatic diseases, particularly connective tissue diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary Sjögren's syndrome, systemic sclerosis, polymyalgia rheumatica, and seronegative arthritis. We present current opinion on the mechanisms responsible for hyperprolactinemia in SLE patients and the association between hyperprolactinemia and SLE activity and organ involvement. The role of dopamine receptor agonists in the treatment of connective tissue diseases is discussed. PMID:16715039

Parada-Turska, Jolanta; Targo?ska-Stepniak, Bozena; Majdan, Maria

2006-01-01

16

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.

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

2013-01-01

17

Significance of tissue specific and tissue non specific autoimmune reactions of Graves' disease.  

PubMed

The relationship between the many immunologic abnormalities demonstrated in the peripheral blood of patients with Graves' disease (GD) and the broad spectrum of clinical features with which patients may present has not yet been addressed in detail. In this review we examine the evidence to support the notion that GD could be considered a multi-system autoimmune disorder in which tissue damage is restricted to the thyroid gland, connective tissue of the skin and orbit, extra-ocular and other skeletal muscles and, possibly, the lacrimal glands. Apart from the well recognized reactions of autoantibodies and sensitized T lymphocytes with epitopes on the thyroid specific TSH receptor, thyroid peroxidase and thyroglobulin, in patients with hyperthyroidism, there is also good evidence for autoantibody and, to a lesser extent, T lymphocyte reactivity with several eye muscle, other skeletal muscle and connective tissue, antigens in patients with ophthalmopathy, systemic myopathy, dermopathy and acropachy. There is also some evidence for immunoreactivity against lacrimal gland antigens in patients with ophthalmopathy associated with other features of GD. There are, in addition, a variety of organ non-specific reactions in GD; antinuclear antibodies are detected in serum from about one-third of patients with hyperthyroidism and ophthalmopathy, while from 5% to 10% have antibodies reactive with several other ubiquitous tissue proteins. Cloned proteins which are autoantigenic in some patients with hyperthyroidism or Hashimoto's thyroiditis and ophthalmopathy include collagen XIII, nebulin, the calcium binding protein calmitine, and the Mac-II antigen. All antibodies reactive with eye muscle antigens, except the 64 kDa protein which is also expressed in the thyroid, cross react with the same, or a related, protein in other skeletal muscle. Future research should focus on the underlying mechanisms for this broad loss of tolerance to self antigens and the effect of environmental factors such as stress, radioiodine and viral infection of the thyroid gland and other target tissues, in precipitating disease. PMID:8828951

Kiljanski, J; Nebes, V; Wall, J R

1996-01-01

18

Zosteriform connective tissue nevus: a case report.  

PubMed

Zosteriform connective tissue nevus is a rare form of connective tissue hamartomas, which arises from cells of mesodermal origin. Despite similar clinical appearance of many connective tissue nevi, they can be differentiated histochemically and/or biochemically on the basis of the primary connective tissue element present. There are only 3 reported cases of zosteriform connective tissue nevi in the worldwide literature. We report a case occurring in a 25-year-old male with approximately 40 nodules and smaller papules distributed in a zosteriform fashion on the right lower lumbar region and upper gluteal region. The identification of the lesion by deep biopsy excluded the important differential diagnosis of segmental neurofibromatosis. PMID:17519633

Amjadi, Mahyar; Khorrami-Arani, Nivmand; Mashman, Gillian; Allen, Phillip W

2007-06-01

19

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

20

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.

Braunstein, Inbal; Werth, Victoria P.

2012-01-01

21

Some connective tissue disorders of the lung.  

PubMed Central

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

Turner-Warwick, M.

1988-01-01

22

Latest advances in connective tissue disorders  

PubMed Central

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

Rao, Vijay

2013-01-01

23

Effector and regulatory T cell subsets in autoimmunity and tissue inflammation  

PubMed Central

Many autoimmune diseases are driven by self-reactive T helper cells. Until recently, organ-specific autoimmune diseases were primarily associated with Th1 cells but not Th2 cells. However, the discovery of a number of new effector T cell subsets, like Th17 and Th9 cells, and regulatory T cells, like Tregs and Tr1 cells, has changed the way we view and understand autoimmunity at cellular and molecular levels. In recent years, IL-17 producing Th17 cells have emerged as major players in autoimmunity. The complicated relationship between Th1 and Th17 cells, as well as the intricate balance between Tregs and Th17 cells, provide a basis for understanding the immunological mechanisms that induce and regulate autoimmunity. Here, we give an overview of the interplay between different effector T cell subsets and regulatory T cell subsets, and how they contribute to the development of autoimmunity and tissue inflammation.

Jager, Anneli; Kuchroo, Vijay K.

2011-01-01

24

Cardiac abnormalities in mixed connective tissue disease.  

PubMed

Sixteen patients with mixed connective tissue disease (MCTD) were studied using noninvasive cardiovascular techniques. Cardiovascular abnormalities including pericarditis, asymmetric septal hypertrophy, and LV dilatation were found in 38 percent of the study group. Borderline ECG and echocardiographic abnormalities were present in 31 percent of the study group, and the remaining 31 percent were normal by all study techniques. MCTD patients have a high prevalence of cardiovascular abnormalities when studied noninvasively. The most common clinical abnormality is a steroid-responsive pericarditis, present in 25 percent of our series. PMID:6822098

Oetgen, W J; Mutter, M L; Lawless, O J; Davia, J E

1983-02-01

25

Viral connection between drug rashes and autoimmune diseases: How autoimmune responses are generated after resolution of drug rashes  

Microsoft Academic Search

Viral infections are most likely triggering factors of autoimmune diseases, although a single vial infection is not sufficient to cause clinically evident autoimmune diseases. Any disease that profoundly alters the immune system may cause perturbed viral infections, thereby rendering otherwise refractory patients susceptible to autoimmune diseases. In this regard, drug-induced hypersensitivity syndrome (DIHS), a drug rash characterized by sequential reactivations

Noriko Aota; Tetsuo Shiohara

2009-01-01

26

Fibroblast involvement in soft connective tissue calcification.  

PubMed

Soft connective tissue calcification is not a passive process, but the consequence of metabolic changes of local mesenchymal cells that, depending on both genetic and environmental factors, alter the balance between pro- and anti-calcifying pathways. While the role of smooth muscle cells and pericytes in ectopic calcifications has been widely investigated, the involvement of fibroblasts is still elusive. Fibroblasts isolated from the dermis of pseudoxanthoma elasticum (PXE) patients and of patients exhibiting PXE-like clinical and histopathological findings offer an attractive model to investigate the mechanisms leading to the precipitation of mineral deposits within elastic fibers and to explore the influence of the genetic background and of the extracellular environment on fibroblast-associated calcifications, thus improving the knowledge on the role of mesenchymal cells on pathologic mineralization. PMID:23467434

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

2013-01-01

27

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.

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

2013-01-01

28

[Marfan syndrome and related connective tissue disorders].  

PubMed

Marfan syndrome is an autosomal dominantly inherited connective tissue disorder with a prevalence of approximately 1:5000 people. Typical manifestations affect the cardiovascular system, eyes, skeleton, lungs, skin and dura mater. Most patients have a so-called marfanoid habitus with tall stature, long and narrow limbs, a long and narrow head shape and other skeletal abnormalities. Of particular medical importance are the possible complications such as severe scoliosis or pectus excavatum, spontaneous pneumothorax, retinal detachment, or an acute glaucoma evoked by lens luxation. However, the most dangerous complication is acute dissection of the ascending aorta, which is usually the result of a slowly progressive aortic dilatation. With the introduction of therapies the average life expectancy of previously just 32 years could be raised to above 60 years. PMID:24280605

Steindl, Katharina

2013-11-27

29

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.

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

2000-01-01

30

Association of bronchiolitis with connective tissue disorders.  

PubMed Central

Among 173 consecutive open lung biopsies, nine gave a histopathological diagnosis of bronchiolitis. Seven of these patients had some connective tissue disorder (CTD), six of whom are presented in this report; two had classical and one possible rheumatoid arthritis (RA), one ankylosing spondylitis, one scleroderma, and one developed classical RA four years after biopsy. Four of the patients were smokers, most suffered from breathlessness and cough. In terms of lung function three patients had obstruction, one both restriction and obstruction and three a decreased diffusion capacity. For control purposes peripheral lung tissue was studied histologically from 24 consecutive smoking patients without CTD who underwent a lobectomy for cancer. Intraluminal plugs and mucosal lymphoplasmocytic infiltration of the bronchiolar walls were more prevalent and abundant in the CTD patients than in the controls (p less than 0.02 and p less than 0.001 respectively). Two CTD patients also showed some obliterative bronchiolitis. Corticosteroids were effective in one out of four patients treated. One patient improved and the others did not show any progression during the follow up. The results suggest that smoking alone does not explain the lesions of the small airways found in CTD patients, and that bronchiolitis may be specifically associated with the basic disorder in such cases. Images

Hakala, M; Paakko, P; Sutinen, S; Huhti, E; Koivisto, O; Tarkka, M

1986-01-01

31

Connective tissue disorders in domestic animals.  

PubMed

Though soft tissue disorders have been recognized and described to some detail in several types of domestic animals and small mammals for some years, not much progress has been made in our understanding of the biochemical basis and pathogenesis of these diseases in animals. Ehlers-Danlos syndrome described in dogs already in 1943 and later in cats affects mainly skin in these animals. The involved skin is thin and hyperextensible with easily inflicted injuries resulting in hemorrhagic wounds and atrophic scars. Joint laxity and dislocation common in people are less frequently found in dogs. No systemic complications, such as organ rupture or cardiovascular problems which have devastating consequences in people have been described in cats and dogs. The diagnosis is based on clinical presentation and on light or electron microscopic features of disorganized and fragmented collagen fibrils. Several cases of bovine and ovine dermatosparaxis analogous to human Ehlers-Danlos syndrome type VIIC were found to be caused by mutations in the procollagen I N-proteinase (pnPI) or ADAMTS2 gene, though mutations in other sites are likely responsible for other types of dermatosparaxis. Cattle suffering from a form of Marfan syndrome were described to have aortic dilatation and aneurysm together with ocular abnormalities and skeletal involvement. As in people mutations at different sites of bovine FBN1 may be responsible for Marfan phenotype. Hereditary equine regional dermal asthenia (HERDA), or hyperelastosis cutis, has been recognized in several horse breeds as affecting primarily skin, and, occasionally, tendons. A mutation in cyclophilin B, a chaperon involved in proper folding of collagens, has been identified in some cases. Degenerative suspensory ligament desmitis (DSLD) affects primarily tendons and ligaments of certain horse breeds. New data from our laboratory showed excessive accumulation of proteoglycans in organs with high content of connective tissues. We have identified an abnormal form of decorin with altered biological activity in these proteoglycan deposits, and more recently changes in processing of aggrecan were found by us and other investigators.The naturally occurring diseases of soft tissues in domestic animals described here have a potential to serve as good models for analogous human diseases. This is the case particularly relevant to dogs as a half out of the more than 400 naturally occurring hereditary canine diseases has the potential to serve as a model for human disease. PMID:24443030

Halper, Jaroslava

2014-01-01

32

Should Graves' disease be considered a collagen disorder of the thyroid, skeletal muscle and connective tissue?  

PubMed

Graves' disease comprises hyperthyroidism, ophthalmopathy, pretibial myxedema and acropachy, which occur separately or in various combinations. We have used the indirect immunofluorescence test to investigate reactivity of sera from patients with autoimmune thyroid disorders with and without ophthalmopathy, with porcine extra ocular muscle (EOM) and control tissue substrates. Sera from 75% of patients with Graves' hyperthyroidism (GH) and ophthalmopathy, which we call thyroid-associated opthalmopathy (TAO), contained one or more antibodies reactive with EOM compared to 32% of those with GH without the eye disorder, 41% of patients with Hashimoto's thyroiditis (HT), and 16% of normals. Antibodies reactive with an EOM connective tissue antigen(s), seen as fluorescence of the interstitium and endomysium, were found in sera from 10% of patients with TAO and 16% of those with GH, but not from any patient with HT or normal subject. Similar patterns of connective tissue reactivity were also found in lacrimal gland, skeletal muscle, kidney and salivary gland. Antinuclear antibodies were detected in sera from 31% of patients with TAO, but from only 8% with HT, in no patient with GH and in only 3% of normal subjects. The most common pattern was a fine speckled fluorescence, found in 45% of sera, consistent with reactivity against the Sm antigen or nuclear RNP. The finding of a high prevalence of ANA and, less often, anti-connective tissue antibodies in patients with thyroid autoimmunity and ophthalmopathy, is consistent with Graves' disease being a "collagen-like disorder". The reason why inflammation and resulting tissue damage is limited to the thyroid, connective tissue of the skin and orbit, skeletal muscle and, possibly, the lacrimal gland, is unclear. One possibility is cross reaction of ANA with tissue specific membrane proteins in these sites. The extent of immunologic abnormalities, and the resulting clinical features, in patients with Graves' disease may reflect the severity of a putative defect in immune regulation. PMID:8750780

Kiljanski, J; Nebes, V; Stachura, I; Kennerdell, J S; Wall, J R

1995-12-01

33

An ultrastructural study of connective tissue in mollusc integument III  

Microsoft Academic Search

We studied structure and ultrastructure of the subepidermal connective tissue (SEC) of the integument of three cephalopods (Sepia officinalis, Octopus vulgaris and Loligo pealii). In all species, three distinct regions of the SEC were recognised: (a) an outer zone (OZ) that included the dermal–epidermal junction, and consisted of a thin layer of connective tissue containing muscles, (b) an extensive middle

A Bairati; M Comazzi; M Gioria

2003-01-01

34

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

Microsoft Academic Search

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

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

2005-01-01

35

Connective tissue massage in the treatment of fibromyalgia  

Microsoft Academic Search

The aim of this study was to investigate the effect of connective tissue massage in the treatment of individuals with fibromyalgia. The results of this random study of 48 individuals diagnosed with fibromyalgia (23 in the treatment group and 25 in the reference group) show that a series of 15 treatments with connective tissue massage conveys a pain relieving effect

Gunilla Brattberg

1999-01-01

36

Pectus Excavatum and Heritable Disorders of the Connective Tissue  

PubMed Central

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

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

2013-01-01

37

Intrapleural Corticosteroid Injection in Eosinophilic Pleural Effusion Associated with Undifferentiated Connective Tissue Disease  

PubMed Central

Eosinophilic pleural effusion (EPE) is defined as a pleural effusion that contains at least 10% eosinophils. EPE occurs due to a variety of causes such as blood or air in the pleural space, infection, malignancy, or an autoimmune disease. Undifferentiated connective tissue disease (UCTD) associated with eosinophilic pleural effusion is a rare condition generally characterized by the presence of the signs and symptoms but not fulfilling the existing classification criteria. We report a case involving a 67-year-old man with UCTD and EPE, who has been successfully treated with a single intrapleural corticosteroid injection.

Kim, Eunjung; Yang, Bokyung; Kim, Mihee; Kang, Jingu; Lee, Jiun

2013-01-01

38

Modified single incision technique to harvest subepithelial connective tissue graft  

PubMed Central

Dental therapy in general and periodontal therapy in particular is directed increasingly at the esthetic outcome for patients. Gingival recession is one of the most common esthetic concerns associated with periodontal tissues. Although various treatment modalities have been developed, subepithelial connective tissue grafting remains the most successful and predictable technique for treatment of gingival recession. Harvesting a connective tissue graft from the palate is many times not only traumatic, but also very painful for the patient. Use of single incision to harvest the subepithelial connective tissue graft is one of the least traumatic, but relatively difficult technique to accomplish. This article presents a modified single incision technique, which is not only less traumatic and painful, but comparatively simple to employ and master. Two new instruments have been introduced to make harvesting of the connective tissue graft easier.

Kumar, Ashish; Sood, Vishal; Masamatti, Sujata Surendra; Triveni, M. G.; Mehta, D. S.; Khatri, Manish; Agarwal, Vipin

2013-01-01

39

Connective tissue metabolism and gingival overgrowth.  

PubMed

Gingival overgrowth occurs mainly as a result of certain anti-seizure, immunosuppressive, or antihypertensive drug therapies. Excess gingival tissues impede oral function and are disfiguring. Effective oral hygiene is compromised in the presence of gingival overgrowth, and it is now recognized that this may have negative implications for the systemic health of affected patients. Recent studies indicate that cytokine balances are abnormal in drug-induced forms of gingival overgrowth. Data supporting molecular and cellular characteristics that distinguish different forms of gingival overgrowth are summarized, and aspects of gingival fibroblast extracellular matrix metabolism that are unique to gingival tissues and cells are reviewed. Abnormal cytokine balances derived principally from lymphocytes and macrophages, and unique aspects of gingival extracellular matrix metabolism, are elements of a working model presented to facilitate our gaining a better understanding of mechanisms and of the tissue specificity of gingival overgrowth. PMID:15187034

Trackman, P C; Kantarci, A

2004-01-01

40

Bioreactors for Connective Tissue Engineering: Design and Monitoring Innovations  

Microsoft Academic Search

The challenges for the tissue engineering of connective tissue lie in creating off-the-shelf tissue constructs which are capable\\u000a of providing organs for transplantation. These strategies aim to grow a complex tissue with the appropri ate mechanical integrity\\u000a necessary for functional load bearing. Monolayer culture systems lack correlation with the in vivo environment and the naturally\\u000a occur ring cell phenotypes. Part

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

2009-01-01

41

Perioperative Management of Patients with Connective Tissue Disease  

PubMed Central

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

Goodman, Susan M.; Figgie, Mark P.

2010-01-01

42

Analyses of immunosenescent markers in patients with autoimmune disease  

Microsoft Academic Search

The objective of this study was to evaluate the degree of immunosenescence in patients with autoimmune disease. T cell receptor excision circles (TREC) and the percentage of CD4+CD28null T cells were studied as markers of immunosenescence in 175 patients with chronic autoimmune arthritis, other connective tissue autoimmune diseases, multiple sclerosis and 60 healthy controls. In both the rheumatoid arthritis (RA)

Marielle Thewissen; Veerle Somers; Koen Venken; Loes Linsen; Pieter Van Paassen; Piet Geusens; Jan Damoiseaux; Piet Stinissen

2007-01-01

43

FIBROBLAST CYTOSKELETAL REMODELING CONTRIBUTES TO CONNECTIVE TISSUE TENSION  

PubMed Central

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

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

2011-01-01

44

Autoimmune priming, tissue attack and chronic inflammation - The three stages of rheumatoid arthritis.  

PubMed

Extensive genome-wide association studies have recently shed some light on the causes of chronic autoimmune diseases and have confirmed a central role of the adaptive immune system. Moreover, better diagnostics using disease-associated autoantibodies have been developed, and treatment has improved through the development of biologicals with precise molecular targets. Here, we use rheumatoid arthritis (RA) as a prototype for chronic autoimmune disease to propose that the pathogenesis of autoimmune diseases could be divided into three discrete stages. First, yet unknown environmental challenges seem to activate innate immunity thereby providing an adjuvant signal for the induction of adaptive immune responses that lead to the production of autoantibodies and determine the subsequent disease development. Second, a joint-specific inflammatory reaction occurs. This inflammatory reaction might be clinically diagnosed as the earliest signs of the disease. Third, inflammation is converted to a chronic process leading to tissue destruction and remodeling. In this review, we discuss the stages involved in RA pathogenesis and the experimental approaches, mainly involving animal models that can be used to investigate each disease stage. Although we focus on RA, it is possible that a similar stepwise development of disease also occurs in other chronic autoimmune settings such as multiple sclerosis (MS), type 1 diabetes, and systemic lupus erythematosus. PMID:24737176

Holmdahl, Rikard; Malmström, Vivianne; Burkhardt, Harald

2014-06-01

45

Autoimmune diseases  

Microsoft Academic Search

Experimental models of autoimmune disease have been used to dissect the mechanisms of disease pathogenesis in the corresponding\\u000a human diseases. This chapter will deal with experimental autoimmune encephalomyelitis (EAE) as a model for human multiple\\u000a sclerosis (MS) and experimental autoimmune diabetes (EAD) in the NOD mouse as a model for human diabetes. In the case of these\\u000a tissue-specific autoimmune diseases,

William J. Karpus

46

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.

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

2013-01-01

47

Multiple Unilateral Zosteriform Connective Tissue Nevi on the Trunk  

PubMed Central

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

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

2011-01-01

48

Skin Involvement in Systemic Autoimmune Diseases  

Microsoft Academic Search

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

Shadi Rashtak; Mark R. Pittelkow

2008-01-01

49

Conversion of discoid lupus erythematosus to mixed connective tissue disease.  

PubMed

The progression from discoid lupus erythematosus (DLE) to severe systemic lupus erythematosus (SLE) is rare. Two patients with DLE for five and 10 years eventually developed systemic involvement with clinical features of mixed connective tissue disease (MCTD). Both patients had high titer serum antibody to ribonucleoprotein (RNP) and epidermal nuclear staining on direct immunofluorescence of normal skin. Neither patient had renal disease but one patient developed pulmonary involvement. This observation suggests that patients with DLE and the Raynaud phenomenon may have a connective tissue disease subset characterized by anti-RNP, the immunologic marker for MCTC. PMID:881692

Gilliam, J N; Prystowsky, S D

1977-01-01

50

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.

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

2005-01-01

51

Propagation in cardiac tissue adjacent to connective tissue: two-dimensional modeling studies.  

PubMed

The conditions for activation transmission across a region of extracellular space was demonstrated in two-dimensional preparations with results consistent with those previously seen in the one-dimensional fiber studies. In addition, one sees changes in action potential morphology which occur in the tissue nearest the connective-tissue border as well as changes in conduction velocity along the border. These results hinge on an adequate representation of the connective-tissue region achieved by careful implementation of the boundary conditions in the intracellular and interstitial spaces and the expansion of the connective-tissue discretization to a "double-tier network" description. Through a series of simulations, a clear dependence on fiber orientation is illustrated in the efficacy to transmit activation. The collision of a front with an embedded connective-tissue region was also examined. The results revealed that fibers aligned normal to a planar stimulus would more greatly disrupt the advancement of a planar front. Such pronounced disruptions have been shown to be proarrhythmic in the literature. The increasing evidence of the ability of connective tissue to transmit activation has implications in understanding spread of activation through infarcted tissues and through the healthy ventricular wall in the presence of connective-tissue sheets. PMID:9919822

Street, A M; Plonsey, R

1999-01-01

52

CONNECTIVE TISSUE REPARATION IN THE LIVER DURING ACUTE RADIATION SICKNESS  

Microsoft Academic Search

An investigation was made to determine the course of the connective ; tissue reparation in the liver under the influence of total irradiation with ; great doses of roentgen rays. The experiments were carried out on 84 albino ; rats, 13 of them belonging to the control group (non-irradiated), and 30 animals ; irradiated with a dose of 400 roentgens,

Loogna

1961-01-01

53

Ultrastructural immunolocalization of lysyl oxidase in vascular connective tissue  

Microsoft Academic Search

The localization of lysyl oxidase was exam- ined in calf and rat aortic connective tissue at the ul- trastructural level using polyclonal chicken anti-lysyl oxidase and gold conjugated rabbit anti-chicken im- munoglobulin G to identify immunoreactive sites. Electron microscopy of calf aortic specimens revealed discrete gold deposits at the interface between ex- tracellular bundles of amorphous elastin and the microfibrils

Herbert M. Kagan; Charles A. Vaccaro; Rebecca E. Bronson; Shiow-Shih Tang; Jerome S. Brody

1986-01-01

54

A Rasch analysis for classification of systemic lupus erythematosus and mixed connective tissue disease.  

PubMed

The classification of rheumatic diseases is challenging because these diseases have protean and frequently overlapping clinical and laboratory manifestations. This problem is typified by the difficulty of classification and differentiation of two prototypic multi-system autoimmune diseases, Systemic Lupus Erythematosus (SLE) and Mixed Connective Tissue Disease (MCTD). The researchers submitted medical risk factor data represented by instrument or laboratory measures and physician judgments (12 key features for SLE) from 43 patients diagnosed with SLE and 12 key features for MCTD from 51 patients diagnosed with MCTD to the WINSTEPS Rasch analysis program. Using Rasch model parameterization, and fit and residuals analyses, the researchers identified separate dimensions for MCTD and SLE, thereby lending support to the position that MCTD is its own separate disease, distinct from SLE. PMID:18480510

Perkins, Kyle; Hoffman, Robert W; Bezruczko, Nikolaus

2008-01-01

55

The Expression and Distribution of S-100 Protein and CD83 in Thyroid Tissues of Autoimmune Thyroid Diseases  

Microsoft Academic Search

To investigate the expression and distribution of S-100 protein and CD83 in the thyroid tissues of autoimmune thyroid diseases (ATDs), and to study the role of the dendritic cells in the pathogenesis of ATDs, immunohistochemical staining was used on pathological tissues of 20 patients with Hashimoto's thyroiditis (HT) and 20 patients with Graves' disease (GD) to check the expression and

Wencan Xu; Shenren Chen; Jiexiong Huang; Zhichao Zheng; Linxing Chen; Wei Zhang

2004-01-01

56

Role of PTP? in the Destruction of Periodontal Connective Tissues  

PubMed Central

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

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

2013-01-01

57

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.

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

2011-01-01

58

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

PubMed Central

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

Strek, Mary E.

2013-01-01

59

[Descamative Interstitial Pneumonia in a patient with Undifferentiated Connective-Tissue Disease].  

PubMed

A 49 year-old Caucasian male, smoker (15 pack-year), had at the beginning of his disease an additive, symmetric polyarthritis, affecting predominantly the small joints of the hands, wrists, shoulders and tibiotarsal joints. The autoimmune study revealed ANA and anti-ribosomal P protein antibodies positivity. An undifferentiated connective tissue disease was diagnosed and treatment with deflazacort, naproxen and hydroxychloroquine was begun. Two years later, he starts exertional dyspnea, without other respiratory symptoms. A chest high-resolution computerized tomography scan was performed, evidencing diffuse "ground-glass" opacities. Respiratory functional study showed low diffusion capacity. The bronchoalveolar lavage (BAL) revealed a neutrophilic and eosinophilic (20%) alveolitis, which was not associated with peripheral blood eosinophilia. The definitive diagnosis was obtained by a surgical lung biopsy, which showed features consistent with Descamative Interstitial Pneumonia (DIP). This rare entity is referred as a smoke-related disease. The debate about an eventual association of DIP with autoimmune diseases and BAL eosinophilia is discussed by the authors based on the present clinical case features. PMID:24126429

Bastos, Helder N; Sampaio, Luzia; Mota, Patrícia; Cunha, Rui; Pardal, Joana; Moura, Conceiçăo Souto; Morais, António

2012-01-01

60

Silicone breast implants and connective tissue disease: no association  

Microsoft Academic Search

The association of silicone breast implants with connective tissue diseases (CTDs), including systemic sclerosis, systemic\\u000a lupus erythematosus, rheumatoid arthritis, and fibromyalgia, as well as a hypothesized new “atypical” disease, which does\\u000a not meet established diagnostic criteria for any known CTD, has been extensively studied. We have reviewed the epidemiologic\\u000a literature regarding an association between cosmetic breast implants and CTDs, with

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

2011-01-01

61

Carcinoma cells may modulate their supporting connective tissue.  

PubMed Central

The patterns of growth of two chemically-induced murine squamous cell carcinoma cell lines and their effect on a deep connective tissue graft bed were examined in syngeneic C57Bl/6 mice. The two cell lines displayed markedly different patterns of histo-differentiation but in vivo the poorly-differentiated line (FS) gave rise to tumours with much lower inocula than the well-differentiated cell line (A5). To evaluate the effect of the tumour cells on the graft bed a bioassay involving transplantation of epidermal sheets was used. Whereas the pretreatment of the deep connective tissue graft bed with the FS cell line facilitated the subsequent growth of the epidermal sheets, beds treated with the A5 cell line, lethally irradiated tumour cells or receiving no treatment failed to support continued growth of normal epidermis. We suggest that this ability of a carcinoma cell line to modify the connective tissue may facilitate the establishment of metastatic deposits. Images Fig. 1 Fig. 2 Fig. 3

Vincent, S. D.; Hill, M. W.

1986-01-01

62

Purpura fulminans in a patient with mixed connective tissue disease.  

PubMed

A 43-year-old lady was admitted to the intensive care unit with sepsis. She had a history of mixed connective tissue disease, Raynaud's syndrome and hypothyroidism. 2 days later, she developed a purpuric rash on her face and extremities with a livedoid background. Few days later, her distal fingers and toes became gangrenous which then had to be amputated. Laboratory investigations showed that she was coagulopathic and had multiple organ dysfunctions. Antiphospholipid antibodies were negative; however, protein C and antithrombin III levels were low. A skin biopsy showed fibrinoid necrosis in the vessel wall with microthrombi and red-cell extravasation. A diagnosis of purpura fulminans was made. PMID:23370948

Murad, Aizuri A; Jeffers, Michael; Tobin, Anne-Marie; Connolly, Maureen

2013-01-01

63

Serological profiles in the connective tissue diseases in Zimbabwean patients.  

PubMed Central

The serological profiles of 104 Zimbabwean patients with clinically diagnosed connective tissue diseases were determined. The prevalence of rheumatoid factor was less than would have been expected in other geographical groups, but the prevalence of antinuclear antibodies was similar. Despite considerable racial, socioeconomic, and genetic differences in our patient group compared with other previously published studies the specificity and sensitivity of antinuclear antibodies, notably to DNA and Sm, correlated well with clinical diagnoses. This study validates the use of these serological tests in the investigation of this group of patients.

Davis, P; Stein, M; Ley, H; Johnston, C

1989-01-01

64

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

PubMed

Musculoskeletal ultrasonography is now widely used by almost all rheumatologists thanks to an improvement in the quality of ultrasound unit and probe and to the systematic teaching of this imaging technique to the rheumatology fellows. Applications have broadened from the study of degenerative and mechanical diseases to inflammatory rheumatic diseases. Ultrasound is more sensitive than clinical examination. Power Doppler allows the direct visualisation of inflammation within the tissues. Finally, it is a prognostic tool helping the physician in the management of the disease. This review will focus on the value and applications of ultrasonography in the 2 most frequent rheumatic diseases: rheumatoid arthritis and spondyloarthritis. We will also give some recent data on the usefulness of this imaging technique in the study of musculoskeletal manifestations associated with connective tissue disease. PMID:24439720

Mérot, O; Le Goff, B

2014-08-01

65

Myoarchitecture and connective tissue in hearts with tricuspid atresia  

PubMed Central

Objective—To compare the atrial and ventricular myoarchitecture in the normal heart and the heart with tricuspid atresia, and to investigate changes in the three dimensional arrangement of collagen fibrils.?Methods—Blunt dissection and cell maceration with scanning electron microscopy were used to study the architecture of the atrial and ventricular musculature and the arrangement of collagen fibrils in three specimens with tricuspid atresia and six normal human hearts.?Results—There were significant modifications in the myoarchitecture of the right atrium and the left ventricle, both being noticeably hypertrophied. The middle layer of the ventricle in the abnormal hearts was thicker than in the normal hearts. The orientation of the superficial layer in the left ventricle in hearts with tricuspid atresia was irregular compared with the normal hearts. Scanning electron microscopy showed coarser endomysial sheaths and denser perimysial septa in hearts with tricuspid atresia than in normal hearts.?Conclusions—The overall architecture of the muscle fibres and its connective tissue matrix in hearts with tricuspid atresia differed from normal, probably reflecting modelling of the myocardium that is inherent to the malformation. This is in concordance with clinical observations showing deterioration in pump function of the dominant left ventricle from very early in life.?? Keywords: tricuspid atresia; congenital heart defects; connective tissue; fibrosis

Sanchez-Quintana, D; Climent, V; Ho, S; Anderson, R

1999-01-01

66

Connective Tissue Disease-associated Interstitial Lung Disease: A review  

PubMed Central

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

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

2012-01-01

67

The Repertoires of Peptides Presented by MHC-II in the Thymus and in Peripheral Tissue: A Clue for Autoimmunity?  

PubMed Central

T-cell tolerance to self-antigens is established in the thymus through the recognition by developing thymocytes of self-peptide-MHC complexes and induced and maintained in the periphery. Efficient negative selection of auto-reactive T cells in the thymus is dependent on the in situ expression of both ubiquitous and tissue-restricted self-antigens and on the presentation of derived peptides. Weak or inadequate intrathymic expression of self-antigens increases the risk to generate an autoimmune-prone T-cell repertoire. Indeed, even small changes of self-antigen expression in the thymus affect negative selection and increase the predisposition to autoimmunity. Together with other mechanisms, tolerance is maintained in the peripheral lymphoid organs via the recognition by mature T cells of a similar set of self-peptides in homeostatic conditions. However, non-lymphoid peripheral tissue, where organ-specific autoimmunity takes place, often have differential functional processes that may lead to the generation of epitopes that are absent or non-presented in the thymus. These putative differences between peptides presented by MHC molecules in the thymus and in peripheral tissues might be a major key to the initiation and maintenance of autoimmune conditions.

Collado, Javier A.; Guitart, Carolina; Ciudad, M. Teresa; Alvarez, Inaki; Jaraquemada, Dolores

2013-01-01

68

Cell-based and biomaterial approaches to connective tissue repair  

NASA Astrophysics Data System (ADS)

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

Stalling, Simone Suzette

69

Trigeminal sensory neuropathy and bilateral carpal tunnel syndrome: the initial manifestation of mixed connective tissue disease  

Microsoft Academic Search

A patient is described who devloped a bilateral carpal tunnel syndrome and a trigeminal sensory neuropathy as the initial manifestations of mixed connective tissue disease. Either condition can occur in other connective tissue diseases, but this combination has not been reported previously in mixed connective tissue disease, in which, however, trigeminal sensory neuropathy is frequently seen.

F M Vincent; R N Van Houzen

1980-01-01

70

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

Microsoft Academic Search

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

A. Bairati; M. Comazzi; M. Gioria

2001-01-01

71

Biological properties and regulation of IL-10 related cytokines and their contribution to autoimmune disease and tissue injury.  

PubMed

The IL-10 cytokine family has nine members, four of which are located in the IL10 cluster on chromosome 1q32. These cytokines are the immune regulatory cytokine IL-10 itself, and the IL-20 subfamily members IL-19, IL-20, and IL-24. IL-10 instructs innate and adaptive immune responses and limits pro-inflammatory responses in order to prevent tissue damage. The IL-20 subfamily members are involved in host defense mechanisms, particularly from epithelial cells and seem essential for tissue integrity. Dysregulation of IL-10 family cytokines results in inflammation and autoimmune disease. Here, we discuss cellular source, gene regulation, and receptor complexes of cytokines in the IL10 cluster and their contribution to autoimmune disease and tissue damage. PMID:22459704

Hofmann, S R; Rösen-Wolff, A; Tsokos, G C; Hedrich, C M

2012-05-01

72

Paraneoplastic syndromes with connective tissue involvement. "It's not always lupus!".  

PubMed

Paraneoplastic syndromes (PNS) are remote effects of cancer that are, by definition, caused neither by invasion of the tumor or its metastases nor by infection, ischemia, metabolic and nutritional deficits, surgery or other forms of tumor treatment. The purpose of the current review was to present the challenging elements of differential diagnosis in oncology, as they may represent the main clinical problem in a patient diagnosed with cancer, even though the complete knowledge of both their clinical aspects and pathogenesis remain quite poor. This review focuses on the paraneoplastic syndromes related to dermatology and rheumatology, as the most frequent manifestations come from connective tissues that might determine a patient to ask for consultation by a general practitioner. PMID:23033275

Timis, T; Berce, C; Duarte-Garcia, A; Petrushev, B; Cristea, V; Tomuleasa, C

2012-01-01

73

[Targeted therapies including monoclonal antibodies for connective tissue diseases].  

PubMed

Recent advance of targeted therapies including monoclonal antibodies and fusion proteins has allowed effective strategies in the treatment of rheumatoid arthritis. And now, TNF inhibitors are broadly used for rheumatoid arthritis and prevent the disease progression. Meanwhile, B cell targeted therapies and anti-interleukin-6 receptor antibody treatment are not only used for second line biological agents for rheumatoid arthritis, but also expected for the treatments of various autoimmune diseases. Recent year, some of novel small molecules, which inhibit the signal transduction of various surface receptors of immune cells, are in clinical trials. These drugs will be a breakthrough for the treatment of some autoimmune disorders. PMID:19280937

Hayashi, Taichi; Sumida, Takayuki

2009-03-01

74

Autoantibodies to human nuclear antigen(s)-HNA-in connective tissue diseases and other disorders.  

PubMed Central

Autoantibodies reacting with nuclear antigen(s) on human cells (HNA) with weak or without reactivity on nuclei of other species have been found by the indirect immunofluorescence technique used in routine tests for the diagnosis of autoimmune diseases. Precipitin lines were obtained by counterimmunoelectrophoresis (CIE) only when human lymphocyte extracts were used and not with rabbit thymus acetone powder. By comparison with reference sera, the autoantibodies directed to HNA were found to be different from SSA/Ro antibodies and did not give the fluorescence pattern of anti nuclear mitotic apparatus (NuMA) antibodies on HEp-2 cells. The prevalence of sera with anti-HNA antibodies not associated with other antinuclear antibodies (ANA) is low (about 0.7% of ANA found in routine assay). In association with ANA of other specificities, the prevalence of anti-HNA antibodies, demonstrated after absorption of sera with rat liver acetone powder, was higher (about 1% of ANA positive sera). By treatment with physicochemical agents and enzymes, the HNA was found to be a DNA (glyco)-protein complex extractable with saline solution, resistant to 56 degrees C for 6 h and stable at pH values ranging from 3 to 10. Anti-HNA antibodies were found in patients with mild connective tissue diseases, but also in idiopathic interstitial pneumonia and in chronic hepatitis. Images Fig. 2

Passaleva, A; Vannucci, F; Bonali, A; Iannello, G L; Massai, G; Ricci, M

1986-01-01

75

Evidence for thyrotropin receptor immunoreactivity in pretibial connective tissue from patients with thyroid-associated dermopathy  

Microsoft Academic Search

Pretibial myxedema (PTM), mainly characterized by the accumulation of glycosaminoglycans in the dermis and subcutaneous tissue, is an extrathyroidal manifestation of autoimmune Graves' disease (GD), almost always associated with Graves' ophthalmopathy (GO). The thyrotropin receptor (TSH- R) has been proposed as the common target antigen in GD, GO and PTM, with evidence for receptor transcripts and\\/or protein in these locations.

C Daumerie; M Ludgate; S Costagliola

2002-01-01

76

Characterisation of connective tissue from the hypertrophic skeletal muscle of myostatin null mice  

PubMed Central

Myostatin is a potent inhibitor of muscle development. Genetic deletion of myostatin in mice results in muscle mass increase, with muscles often weighing three times their normal values. Contracting muscle transfers tension to skeletal elements through an elaborate connective tissue network. Therefore, the connective tissue of skeletal muscle is an integral component of the contractile apparatus. Here we examine the connective tissue architecture in myostatin null muscle. We show that the hypertrophic muscle has decreased connective tissue content compared with wild-type muscle. Secondly, we show that the hypertrophic muscle fails to show the normal increase in muscle connective tissue content during ageing. Therefore, genetic deletion of myostatin results in an increase in contractile elements but a decrease in connective tissue content. We propose a model based on the contractile profile of muscle fibres that reconciles this apparent incompatible tissue composition phenotype.

Elashry, Mohamed I; Collins-Hooper, Henry; Vaiyapuri, Sakthivel; Patel, Ketan

2012-01-01

77

Epithelial-connective tissue boundary in the oral part of the human soft palate  

PubMed Central

The papillary layer of the oral part of the human soft palate was studied in 31 subjects of different age by means of histological, immunohistochemical and scanning electron microscopical methods. For scanning electron microscopy a new maceration method was introduced. Results determine epithelial thickness, height and density of connective tissue papillae and their 3-dimensional architecture inside the lining epithelium as well as the collagenous arrangement of the openings of the glandular ducts. The individual connective tissue papillae of the soft palate are compared with the connective tissue boundary on the other side of the oral cavity. The connective tissue plateaux carrying a variable number of connective tissue papillae were found to be the basic structural units of the papillary body. The function of the epithelial-connective tissue interface and the extracellular matrix arrangement in the lamina propria are discussed in order to promote the comparability of normal with pathologically altered human soft palates.

PAULSEN, FRIEDRICH; THALE, ANDREAS

1998-01-01

78

A Case of Hypertrophic Cranial Pachymeningitis Presenting with Scleritis in a Patient with Undifferentiated Connective Tissue Disease  

PubMed Central

Hypertrophic cranial pachymeningitis (HCP) is an uncommon disorder that causes a localized or diffuse thickening of the dura mater and has been reported to be infrequently associated with systemic autoimmune disorders such as Wegener's granulomatosis, rheumatoid arthritis, sarcoidosis, Behçet's disease, Sjögren syndrome, and temporal arteritis. Here, we report a case of HCP initially presented with scleritis and headache in a patient with undifferenciated connective tissue disease (UCTD). HCP was initially suspected on brain magnetic resonance imaging and defined pathologically on meningial biopsy. Immunologic studies showed the presence of anti-RNP antibody. After high dose corticosteroid therapy, the patient's symptoms and radiologic abnormalities of brain were improved. Our case suggested that HCP should be considered in the differential diagnosis of headache in a patient with UCTD presenting with scleritis.

Kim, Ji-Hyeon; Joo, Young-Bin; Kim, Jeana

2010-01-01

79

Silicone breast implants and connective tissue disease: no association.  

PubMed

The association of silicone breast implants with connective tissue diseases (CTDs), including systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, and fibromyalgia, as well as a hypothesized new "atypical" disease, which does not meet established diagnostic criteria for any known CTD, has been extensively studied. We have reviewed the epidemiologic literature regarding an association between cosmetic breast implants and CTDs, with particular emphasis on results drawn from the most recent investigations, many of which are large cohort studies with long-term follow-up, as well as on those studies that address some of the misinformation and historically widespread claims regarding an association between breast implants and CTDs. These claims have been unequivocally refuted by the remarkably consistent evidence from published studies, as well as numerous independent meta-analyses and critical reviews, which have demonstrated that cosmetic breast implants are not associated with a subsequent increased occurrence of individual CTDs or all CTDs combined, including fibromyalgia. Moreover, there is no credible evidence for the conjectured excess of "atypical" CTD among women with cosmetic breast implants, or of a rheumatic symptom profile unique to these women. No increased risk of CTDs is evident in women with extracapsular ruptures in two studies, which evaluated risk by implant rupture status, and no consistent association has been observed between silicone breast implants and a variety of serologic markers or autoantibodies. Thus, any claims that remain regarding an association between cosmetic breast implants and CTDs are not supported by the scientific literature but rather are a residual byproduct of the unprecedented large-scale product liability litigation in the USA. PMID:21369953

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

2011-05-01

80

Mechanical properties of orbital fat and its encapsulating connective tissue.  

PubMed

There is an increasing need to understand the mechanical properties of human orbital fat and its encapsulating connective tissue (OFCT), but such knowledge is not available in the current literature. The purpose of the present study is to examine the mechanical properties of the OFCT. From 5 pairs of 76- to 92-year-old Caucasian human eyes and 33 5- to 7-month-old porcine eyes, 5 human and 11 porcine OFCT samples were dissected at the posterior pole or adjacent to the pole in the vertical, horizontal, and radial directions. Sample dimensions were fixed or measured. Tensile tests were performed on the samples in body-temperature saline. The stress-strain relationship was first approximately linear and then became nonlinear. The linear, the neo-Hookean, and the Mooney-Rivlin constants are reported in Tables 1 and 2. No statistical difference was found among their properties in the different directions in either the human or the porcine samples. Statistical differences were found between the human and the porcine material constants in the horizontal and radial directions. Among our material models, only the Mooney-Rivlin model was able to capture the mechanical properties of the OFCT in large deformation properly. The Mooney-Rivlin model was especially adaptive to the human data. This is the first time the mechanical properties of the human and porcine OFCT have been examined in the literature. We believe our data will provide valuable information to others regarding designing implant biomaterials in orbital treatments and developing computer models to study orbital biomechanics. PMID:21744934

Chen, Kinon; Weiland, James D

2011-06-01

81

Autoimmunity in thyroid disease  

Microsoft Academic Search

The autoimmune thyroid diseases, Graves' disease and autoimmune hypothyroidism, represent the two ends of a disease spectrum where an immune response is directed against the thyroid gland. In Graves' disease, antibodies directed against the thyrotropin receptor (TSH-R) lead to the development of glandular overactivity, while in autoimmune hypothyroidism, cell-mediated and humoral thyroid injury leads to destruction of thyroid tissue and

Joanne Collins; Stephen Gough

2002-01-01

82

Tissue-resident exhausted effector memory CD8+ T cells accumulate in the retina during chronic experimental autoimmune uveoretinitis.  

PubMed

Experimental autoimmune uveoretinitis is a model for noninfectious posterior segment intraocular inflammation in humans. Although this disease is CD4(+) T cell dependent, in the persistent phase of disease CD8(+) T cells accumulate. We show that these are effector memory CD8(+) T cells that differ from their splenic counterparts with respect to surface expression of CD69, CD103, and Ly6C. These retinal effector memory CD8(+) T cells have limited cytotoxic effector function, are impaired in their ability to proliferate in response to Ag-specific stimulation, and upregulate programmed death 1 receptor. Treatment with fingolimod (FTY720) during the late phase of disease revealed that retinal CD8(+) T cells were tissue resident. Despite signs of exhaustion, these cells were functional, as their depletion resulted in an expansion of retinal CD4(+) T cells and CD11b(+) macrophages. These results demonstrate that, during chronic autoimmune inflammation, exhausted CD8(+) T cells become established in the local tissue. They are phenotypically distinct from peripheral CD8(+) T cells and provide local signals within the tissue by expression of inhibitory receptors such as programmed death 1 that limit persistent inflammation. PMID:24740509

Boldison, Joanne; Chu, Colin J; Copland, David A; Lait, Philippa J P; Khera, Tarnjit K; Dick, Andrew D; Nicholson, Lindsay B

2014-05-15

83

Tissue-Resident Exhausted Effector Memory CD8+ T Cells Accumulate in the Retina during Chronic Experimental Autoimmune Uveoretinitis  

PubMed Central

Experimental autoimmune uveoretinitis is a model for noninfectious posterior segment intraocular inflammation in humans. Although this disease is CD4+ T cell dependent, in the persistent phase of disease CD8+ T cells accumulate. We show that these are effector memory CD8+ T cells that differ from their splenic counterparts with respect to surface expression of CD69, CD103, and Ly6C. These retinal effector memory CD8+ T cells have limited cytotoxic effector function, are impaired in their ability to proliferate in response to Ag-specific stimulation, and upregulate programmed death 1 receptor. Treatment with fingolimod (FTY720) during the late phase of disease revealed that retinal CD8+ T cells were tissue resident. Despite signs of exhaustion, these cells were functional, as their depletion resulted in an expansion of retinal CD4+ T cells and CD11b+ macrophages. These results demonstrate that, during chronic autoimmune inflammation, exhausted CD8+ T cells become established in the local tissue. They are phenotypically distinct from peripheral CD8+ T cells and provide local signals within the tissue by expression of inhibitory receptors such as programmed death 1 that limit persistent inflammation.

Boldison, Joanne; Chu, Colin J.; Copland, David A.; Lait, Philippa J. P.; Khera, Tarnjit K.; Dick, Andrew D.

2014-01-01

84

Cardiac tamponade and pericardial disorders in connective tissue diseases: case report and literature review.  

PubMed Central

Pericardial disorders occurring in connective tissue diseases are not uncommon and may present as acute or chronic pericarditis with or without an effusion. In many instances, a diagnosis of pericardial involvement is not found until autopsy. Echocardiography and other currently employed radiographic techniques have enhanced the ability to make a diagnosis. Approximate frequencies of common connective tissue disorders with pericardial involvement include scleroderma (59%), systemic lupus erythematosus (44%), mixed connective tissue disease (30%), rheumatoid arthritis (24%), and polymyositis/dermatomyositis (11%). Cardiac tamponade or constriction is rare. This article describes a patient with clinical features consistent with mixed connective tissue disease that presented with a pericardial effusion and cardiac tamponade. In addition, a review of pericardial involvement in connective tissue diseases and the occurrence of cardiac tamponade or constriction is included.

Langley, R. L.; Treadwell, E. L.

1994-01-01

85

Autoimmune thyroid diseases and nonorgan?specific autoimmunity.  

PubMed

Autoimmune thyroid diseases (ATD), as the most common organ?specific autoimmune disorder, is frequently accompanied by other organ- and nonorgan?specific autoimmune diseases. Although the exact pathogenic mechanism of the coexistence of autoimmune disorders has not been clearly defined, genetic and environmental factors, immune defects, and hormonal changes, may play a key role in polyautoimmunity. The role of human leukocyte antigen (HLA) haplotypes, HLA-B8 and -DR3, in the overlapping of autoimmune disorders was well supported by higher frequency of these haplotypes in primary Sjögren's syndrome (PSS) and ATD. In addition, polymorphisms of the cytotoxic T lymphocytic antigen 4 gene have been reported to be associated with many autoimmune disorders especially those coexisting with ATD. Definite noncasual association of ATD has been clearly documented in patients with PSS, rheumatoid arthritis, and systemic lupus erythematosus. Possible association with ATD is also considered in systemic sclerosis and dermatomyositis. Many authors documented a significantly higher prevalence of antinuclear antibodies (ANAs) in ATD patients in comparison with controls; however, the clinical significance of ANAs in this group is still unknown. The presence of other non?organ?specific antibodies has not been convincingly demonstrated. On the other hand, the prevalence of antithyroid antibodies as well as ATD is higher in patients with systemic connective tissue disease compared with the general population. Basedon these data, there is no evidence for the utility of ANA testing in patients with ATD, but because of the high prevalence of ATD and antithyroid autoantibodies, it is clinically important to screen patients with autoimmune rheumatic disorders for the presence of thyroid autoimmunity. PMID:23222800

Lazúrová, Ivica; Benhatchi, Karim

2012-01-01

86

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

Microsoft Academic Search

Reported mechanical properties of orbital connective tissue and fat have been too sparse to model strain–stress relationships\\u000a underlying biomechanical interactions in strabismus. We performed rheological tests to develop a multi-mode upper convected\\u000a Maxwell (UCM) model of these tissues under shear loading. From 20 fresh bovine orbits, 30 samples of connective tissue were\\u000a taken from rectus pulley regions and 30 samples

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

87

Proteolytic Processing of Connective Tissue Growth Factor in Normal Ocular Tissues and during Corneal Wound Healing  

PubMed Central

Purpose. Connective tissue growth factor (CTGF) is a fibrogenic cytokine that is up-regulated by TGF-? and mediates most key fibrotic actions of TGF-?, including stimulation of synthesis of extracellular matrix and differentiation of fibroblasts into myofibroblasts. This study addresses the role of proteolytic processing of CTGF in human corneal fibroblasts (HCF) stimulated with TGF-?, normal ocular tissues and wounded corneas. Methods. Proteolytic processing of CTGF in HCF cultures, normal animal eyes, and excimer laser wounded rat corneas were examined by Western blot. The identity of a 21-kDa band was determined by tandem mass spectrometry, and possible alternative splice variants of CTGF were assessed by 5? Rapid Amplification of cDNA Ends (RACE). Results. HCF stimulated by TGF-? contained full length 38-kDa CTGF and fragments of 25, 21, 18, and 13 kDa, while conditioned medium contained full length 38- and a 21-kDa fragment of CTGF that contained the middle “hinge” region of CTGF. Fragmentation of recombinant CTGF incubated in HCF extracts was blocked by the aspartate protease inhibitor, pepstatin. Normal mouse, rat, and rabbit whole eyes and rabbit ocular tissues contained abundant amounts of C-terminal 25- and 21-kDa fragments and trace amounts of 38-kDa CTGF, although no alternative transcripts were detected. All forms of CTGF (38, 25, and 21 kDa) were detected during healing of excimer ablated rat corneas, peaking on day 11. Conclusions. Proteolytic processing of 38-kDa CTGF occurs during corneal wound healing, which may have important implications in regulation of corneal scar formation.

Robinson, Paulette M.; Smith, Tyler S.; Patel, Dilan; Dave, Meera; Lewin, Alfred S.; Pi, Liya; Scott, Edward W.; Tuli, Sonal S.; Schultz, Gregory S.

2012-01-01

88

Connective tissue growth factor expressed in rat alveolar bone regeneration sites after tooth extraction  

Microsoft Academic Search

Objective: To understand bone regeneration process after tooth extraction could be a clue to develop a new strategy for alveolar bone reconstruction. Recently, accumulated evidences support that connective tissue growth factor (CTGF) is implicated in tissue repair of many tissues. In this study, we investigated the spatial and temporal expression of CTGF in the rat tooth extraction sockets. Design: Five

Manabu Kanyama; Takuo Kuboki; Kentaro Akiyama; Kumiko Nawachi; Fabiora M Miyauchi; Hirofumi Yatani; Satoshi Kubota; Tohru Nakanishi; Masaharu Takigawa

2003-01-01

89

Stichopin-containing nerves and secretory cells specific to connective tissues of the sea cucumber.  

PubMed

Stichopin, a 17-amino acid peptide isolated from a sea cucumber, affects the stiffness change of the body-wall catch connective tissues and the contraction of the body-wall muscles. The localization of stichopin in sea cucumbers was studied by indirect immunohistochemistry using antiserum against stichopin. Double staining was performed with both stichopin antiserum and 1E11, the monoclonal antibody specific to echinoderm nerves. A stichopin-like immunoreactivity (stichopin-LI) was exclusively found in the connective tissues of various organs. Many fibres and cells with processes were stained by both the anti-stichopin antibody and 1E11. They were found in the body-wall dermis and the connective tissue layer of the cloacae and were suggested to be connective tissue-specific nerves. Oval cells with stichopin-LI (OCS) without processes were found in the body-wall dermis, the connective tissue sheath of the longitudinal body-wall muscles, the connective tissue layer of the tube feet and tentacles, and the connective tissue in the radial nerves separating the ectoneural part from the hyponeural part. Electron microscopic observations of the OCSs in the radial nerves showed that they were secretory cells. The OCSs were located either near the well-defined neural structures or near the water-filled cavities, such as the epineural sinus and the canals of the tube feet. The location near the water-filled cavities might suggest that stichopin was secreted into these cavities to function as a hormone. PMID:17623636

Tamori, Masaki; Saha, Apurba Kumar; Matsuno, Akira; Noskor, Sukumar Chandra; Koizumi, Osamu; Kobayakawa, Yoshitaka; Nakajima, Yoko; Motokawa, Tatsuo

2007-09-22

90

The cellular matrix: a feature of tensile bearing dense soft connective tissues.  

PubMed

The term connective tissue encompasses a diverse group of tissues that reside in different environments and must support a spectrum of mechanical functions. Although the extracellular matrix of these tissues is well described, the cellular architecture of these tissues and its relationship to tissue function has only recently become the focus of study. It now appears that tensile-bearing dense connective tissues may be a specific class of connective tissues that display a common cellular organization characterized by fusiform cells with cytoplasmic projections and gap junctions. These cells with their cellular projections are organised into a complex 3-dimensional network leading to a physically, chemically and electrically connected cellular matrix. The cellular matrix may play essential roles in extracellular matrix formation, maintenance and remodelling, mechanotransduction and during injury and healing. Thus, it is likely that it is the interaction of both the extracellular matrix and cellular matrix that provides the basis for tissue function. Restoration of both these matrices, as well as their interaction must be the goal of strategies to repair these connective tissues damaged by either injury or disease. PMID:11962757

Lo, I K; Chi, S; Ivie, T; Frank, C B; Rattner, J B

2002-04-01

91

Celiac disease and autoimmunity.  

PubMed

Celiac disease (CD) has a multifactorial etiology with complex genetics and frequently occurs in association with other autoimmune disorders. Even though triggered by a dietary antigen, it shows many autoimmune features, the most peculiar being the presence of high titers of anti-tissue transglutaminase 2 autoantibodies, produced in the small intestinal mucosa since the early stages of the disease. More than 60% of CD-associated susceptibility loci are shared with at least another autoimmune condition, suggesting common pathogenic mechanisms. In particular, recognition of peptides by HLA molecules, posttranslational modifications required for optimal peptide binding and immune mechanisms leading to tissue damage have been found in CD as well as in other autoimmune diseases. This review briefly summarizes the main autoimmune features of CD, underlining the similarities with other autoimmune disorders, in particular with type 1 diabetes mellitus. Furthermore, the role of gluten and microbiome in driving autoimmunity is discussed. PMID:24979198

Troncone, Riccardo; Discepolo, Valentina

2014-07-01

92

The role of endothelin in connective tissue diseases  

Microsoft Academic Search

Vascular dysregulation is centrally involved in the pathogenesis of diverse rheumatological diseases. The resulting pulmonary arterial hypertension as well as Raynaud's phenomenon may be accompanied by distinct tissue fibrosis. The pleiotropic cytokine endothelin may represent a link between these vascular and fibrotic processes, which are most evidently seen in systemic sclerosis. Among three closely related isoforms, endothelin-1 (ET-1) is the

M. Sticherling

2006-01-01

93

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.

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

94

Treatment of gingival recession with a modified "tunnel" technique and an acellular dermal connective tissue allograft.  

PubMed

The treatment of gingival recession through the creation of a "tunnel" beneath the buccal mucosa allows coronal repositioning the soft tissue with predictable root coverage and aesthetics. Vertical incisions on either side of this tunnel preparation enable placement of a connective tissue graft within the tunnel. The use of an acellular dermal connective tissue allograft permits grafting of multiple sites without the need for a donor tissue surgical site or additional visits. This article demonstrates a modified tunnel technique and a case presentation that incorporates this procedure. PMID:11301532

Mahn, D H

2001-01-01

95

Force Transmission in Wrinkled Membranes: A Numerical Tool to Study Connective Tissue Structures.  

National Technical Information Service (NTIS)

Experiments demonstrate that a quantitative prediction of force transmission in wrinkled and non-wrinkled membranes is possible with the developed numerical tool. Theoretical results for force transmission in collagenous connective tissue structures show ...

D. G. Roddeman

1988-01-01

96

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

97

Spontaneous aortic rupture early postpartum without trauma or connective tissue disorder.  

PubMed

Rupture of the thoracic aorta is a rare but recognized complication following pregnancy. The common causes of thoracic aortic rupture in the peripartum period are trauma, dissecting aneurysms and saccular aneurysms secondary to systemic connective tissue disease. We report a case of non-traumatic spontaneous aortic rupture in a patient without trauma or systemic connective tissue disease 1 day postpartum, which was successfully managed by surgical repair of the thoracic aorta. PMID:23242990

Menon, Ashvini; Bonser, Robert S

2013-06-01

98

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

99

Cytoskeletal remodeling of connective tissue fibroblasts in response to static stretch is dependent on matrix material properties  

PubMed Central

In areolar “loose” connective tissue, fibroblasts remodel their cytoskeleton within minutes in response to static stretch resulting in increased cell body cross-sectional area that relaxes the tissue to a lower state of resting tension. It remains unknown whether the loosely arranged collagen matrix, characteristic of areolar connective tissue, is required for this cytoskeletal response to occur. The purpose of this study was to evaluate cytoskeletal remodeling of fibroblasts in and dissociated from areolar and dense connective tissue in response to 2 hours of static stretch in both native tissue and collagen gels of varying crosslinking. Rheometric testing indicated that the areolar connective tissue had a lower dynamic modulus and was more viscous than the dense connective tissue. In response to stretch, cells within the more compliant areolar connective tissue adopted a large “sheet-like” morphology that was in contrast to the smaller dendritic morphology in the dense connective tissue. By adjusting the in vitro collagen crosslinking, and the resulting dynamic modulus, it was demonstrated that cells dissociated from dense connective tissue are capable of responding when seeded into a compliant matrix, while cells dissociated from areolar connective tissue can lose their ability to respond when their matrix becomes stiffer. This set of experiments indicated stretch-induced fibroblast expansion was dependent on the distinct matrix material properties of areolar connective tissues as opposed to the cells’ tissue of origin. These results also suggest that disease and pathological processes with increased crosslinks, such as diabetes and fibrosis, could impair fibroblast responsiveness in connective tissues.

Abbott, Rosalyn D; Koptiuch, Cathryn; Iatridis, James C; Howe, Alan K; Badger, Gary J; Langevin, Helene M

2012-01-01

100

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

PubMed

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

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

2013-04-01

101

An ultrastructural study of connective tissue in mollusc integument: I. Bivalvia  

Microsoft Academic Search

The ultrastructure of the subepidermal connective tissue (SEC) in different areas of the integument of the bivalves Callista chione, Pecten jacobaeus, Mytilus galloprovincialis and Ostrea edulis was studied by transmission electron microscopy. The main organisation of the SEC was broadly similar in all species: the SEC was connected to the epidermis by a basement membrane and merged directly with the

A. Bairati; M. Comazzi; M. Gioria

2000-01-01

102

Defective stromal remodeling and neutrophil extracellular traps in lymphoid tissues favor the transition from autoimmunity to lymphoma.  

PubMed

Altered expression of matricellular proteins can become pathogenic in the presence of persistent perturbations in tissue homeostasis. Here, we show that autoimmunity associated with Fas mutation was exacerbated and transitioned to lymphomagenesis in the absence of SPARC (secreted protein acidic rich in cysteine). The absence of SPARC resulted in defective collagen assembly, with uneven compartmentalization of lymphoid and myeloid populations within secondary lymphoid organs (SLO), and faulty delivery of inhibitory signals from the extracellular matrix. These conditions promoted aberrant interactions between neutrophil extracellular traps and CD5(+) B cells, which underwent malignant transformation due to defective apoptosis under the pressure of neutrophil-derived trophic factors and NF-?B activation. Furthermore, this model of defective stromal remodeling during lymphomagenesis correlates with human lymphomas arising in a SPARC-defective environment, which is prototypical of CD5(+) B-cell chronic lymphocytic leukemia (CLL). PMID:24189145

Sangaletti, Sabina; Tripodo, Claudio; Vitali, Caterina; Portararo, Paola; Guarnotta, Carla; Casalini, Patrizia; Cappetti, Barbara; Miotti, Silvia; Pinciroli, Patrizia; Fuligni, Fabio; Fais, Franco; Piccaluga, Pier Paolo; Colombo, Mario P

2014-01-01

103

Cartilage, bone, and intermandibular connective tissue in the Australian lungfish, Neoceratodus forsteri (Osteichthyes: Dipnoi).  

PubMed

The connective tissue that links the bones of the mandible in the Australian lungfish, Neoceratodus forsteri, has been described as an intermandibular cartilage, and as such has been considered important for phylogenetic analyses among lower vertebrates. However, light and electron microscopy of developing lungfish jaws demonstrates that the intermandibular tissue, like the connective tissue that links the bones of the upper jaw, contains fibroblasts and numerous bundles of collagen fibrils, extending from the trabeculae of the bones supporting the tooth plates. It differs significantly in structure and in staining reactions from the cartilage and the bone found in this species. In common with the cladistian Polypterus and with actinopterygians and some amphibians, lungfish have no intermandibular cartilage. The connective tissue linking the mandibular bones has no phylogenetic significance for systematic grouping of lungfish, as it is present in a range of different groups among lower vertebrates. PMID:23801584

Kemp, Anne

2013-10-01

104

Coexistence of five autoimmune diseases: diagnostic and therapeutic difficulties  

Microsoft Academic Search

We report the case of coexistence of five autoimmune diseases in a 36-year-old woman, who initially developed psoriasis. Several\\u000a years later, the patient was diagnosed with a mixed connective tissue disease and primary biliary cirrhosis (PBC). On admission\\u000a to the Department of Rheumatology and Connective Tissue Diseases, the patient fulfilled classification criteria of an overlap\\u000a syndrome systemic lupus erythematosus (SLE)

Ewa Wielosz; Maria Majdan; Iwona ?ychowska; Rados?aw Jeleniewicz

2008-01-01

105

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

Microsoft Academic Search

The Fas-Fas ligand (FasL) interaction is important for maintaining lymphocyte homeostasis by signaling for activation-induced cell death. Mice homozygous for the lpr or gld mutations do not express functional Fas or FasL, respectively, and spontaneously develop progressive autoimmune symptoms. Recent studies implicated expression of FasL on immunologically privileged tissues in protection from immune-mediated damage. Conversely, tissue expression of Fas may

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

106

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

107

TRPV1 Gates Tissue Access and Sustains Pathogenicity in Autoimmune Encephalitis  

PubMed Central

Multiple sclerosis (MS) is a chronic progressive, demyelinating condition whose therapeutic needs are unmet, and whose pathoetiology is elusive. We report that transient receptor potential vanilloid-1 (TRPV1) expressed in a major sensory neuron subset, controls severity and progression of experimental autoimmune encephalomyelitis (EAE) in mice and likely in primary progressive MS. TRPV1?/? B6 congenics are protected from EAE. Increased survival reflects reduced central nervous systems (CNS) infiltration, despite indistinguishable T cell autoreactivity and pathogenicity in the periphery of TRPV1-sufficient and -deficient mice. The TRPV1+ neurovascular complex defining the blood-CNS barriers promoted invasion of pathogenic lymphocytes without the contribution of TRPV1-dependent neuropeptides such as substance P. In MS patients, we found a selective risk-association of the missense rs877610 TRPV1 single nucleotide polymorphism (SNP) in primary progressive disease. Our findings indicate that TRPV1 is a critical disease modifier in EAE, and we identify a predictor of severe disease course and a novel target for MS therapy.

Paltser, Geoffrey; Liu, Xue Jun; Yantha, Jason; Winer, Shawn; Tsui, Hubert; Wu, Ping; Maezawa, Yuko; Cahill, Lindsay S; Laliberte, Christine L; Ramagopalan, Sreeram V; DeLuca, Gabriele C; Sadovnick, A Dessa; Astsaturov, Igor; Ebers, George C; Henkelman, R Mark; Salter, Michael W; Dosch, H-Michael

2013-01-01

108

TRPV1 gates tissue access and sustains pathogenicity in autoimmune encephalitis.  

PubMed

Multiple sclerosis (MS) is a chronic progressive, demyelinating condition whose therapeutic needs are unmet, and whose pathoetiology is elusive. We report that transient receptor potential vanilloid-1 (TRPV1) expressed in a major sensory neuron subset, controls severity and progression of experimental autoimmune encephalomyelitis (EAE) in mice and likely in primary progressive MS. TRPV1-/- B6 congenics are protected from EAE. Increased survival reflects reduced central nervous systems (CNS) infiltration, despite indistinguishable T cell autoreactivity and pathogenicity in the periphery of TRPV1-sufficient and -deficient mice. The TRPV1+ neurovascular complex defining the blood-CNS barriers promoted invasion of pathogenic lymphocytes without the contribution of TRPV1-dependent neuropeptides such as substance P. In MS patients, we found a selective risk-association of the missense rs877610 TRPV1 single nucleotide polymorphism (SNP) in primary progressive disease. Our findings indicate that TRPV1 is a critical disease modifier in EAE, and we identify a predictor of severe disease course and a novel target for MS therapy. PMID:23689362

Paltser, Geoffrey; Liu, Xue Jun; Yantha, Jason; Winer, Shawn; Tsui, Hubert; Wu, Ping; Maezawa, Yuko; Cahill, Lindsay S; Laliberté, Christine L; Ramagopalan, Sreeram V; DeLuca, Gabriele C; Sadovnick, A Dessa; Astsaturov, Igor; Ebers, George C; Henkelman, R Mark; Salter, Michael W; Dosch, H-Michael

2013-01-01

109

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

PubMed Central

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

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

2009-01-01

110

Epitope mapping of the U1 small nuclear ribonucleoprotein particle in patients with systemic lupus erythematosus and mixed connective tissue disease  

PubMed Central

Systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) are autoimmune illnesses characterized by the presence of high titers of autoantibodies directed against a wide range of ‘self ’ antigens. Proteins of the U1 small nuclear ribonucleoprotein particle (U1 snRNP) are among the most immunogenic molecules in patients with SLE and MCTD. The recent release of a crystallized U1 snRNP provides a unique opportunity to evaluate the effects of tertiary and quaternary structures on autoantigenicity within the U1 snRNP. In the present study, an epitope map was created using the U1 snRNP crystal structure. A total of 15 peptides were tested in a cohort of 68 patients with SLE, 29 with MCTD and 26 healthy individuals and mapped onto the U1 snRNP structure. Antigenic sites were detected in a variety of structures and appear to include RNA binding domains, but mostly exclude regions necessary for protein–protein interactions. These data suggest that while some autoantibodies may target U1 snRNP proteins as monomers or apoptosis-induced, protease-digested fragments, others may recognize epitopes on assembled protein subcomplexes of the U1 snRNP. Although nearly all of the peptides are strong predictors of autoimmune illness, none were successful at distinguishing between SLE and MCTD. The antigenicity of some peptides significantly correlated with several clinical symptoms. This investigation implicitly highlights the complexities of autoimmune epitopes, and autoimmune illnesses in general, and demonstrates the variability of antigens in patient populations, all of which contribute to difficult clinical diagnoses.

Somarelli, JA; Mesa, A; Rodriguez, R; Avellan, R; Martinez, L; Zang, YJ; Greidinger, EL; Herrera, RJ

2014-01-01

111

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

PubMed Central

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

Boueiz, Adel; Hassoun, Paul M.

2014-01-01

112

Epithelial and connective tissue cell CTGF/CCN2 expression in gingival fibrosis.  

PubMed

Gingival overgrowth 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. The present study has investigated the hypothesis that CTGF/CCN2 is expressed in human gingival fibromatosis tissues and contributes to this form of non-drug-induced gingival overgrowth. Histopathology/immunohistochemistry studies showed 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 polymerase chain reaction (PCR) analyses of RNA extracted from drug-induced gingival overgrowth tissues for CTGF/CCN2 were fully consistent with these findings. Finally, normal primary gingival epithelial cell cultures were analysed for basal and transforming growth factor beta1 (TGF-beta1) or lysophosphatidic acid-stimulated CTGF/CCN2 expression at protein and RNA levels. These data indicate that fibrotic human gingival tissues express CTGF/CCN2 in both the epithelium and connective tissues; that cultured gingival epithelial cells express CTGF/CCN2; and that 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, A; Black, S A; Xydas, C E; Murawel, P; Uchida, Y; Yucekal-Tuncer, B; Atilla, G; Emingil, G; Uzel, M I; Lee, A; Firatli, E; Sheff, M; Hasturk, H; Van Dyke, T E; Trackman, P C

2006-09-01

113

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.

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

114

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

115

Bone and soft connective tissue response to porous acrylic implants. A histokinetic study.  

PubMed

The ingrowth kinetics of soft and hard tissues near pre-polymerized and in-situ-polymerized large pore, in-situ-polymerized small pore and solid acrylic implants were investigated. Empty cavities served as controls. Aqueous sodium carboxymethyl cellulose (CMC) gel was dispersed in bone cement to create interconnected porosity. After periods of insertion from 2 days up to 26 weeks in frontal and parietal bones in pigs, tissue blocks containing implants were embedded in JB4 and studied by light microscopy. After the disappearance of the CMC-gel, at first only cells invaded the large pore implants but necrotized when at some distance from the implant surface. Later, when blood vessels grew into the pores, accompanying vital fibrous connective tissue was observed. Finally, all pores were filled with connective tissue. Surrounding bone was first resorbed, starting at day 7, creating a soft tissue interface. A zone of bone deposition, starting deep in the remaining bone at day 2, moved towards the implant, thereby bridging the soft tissue interface. At 6 weeks bone grew into the pores, thus anchoring the implant. Continuing deposition of bone around the implant provided a so-called lamina dura effect with all implants. Qualitatively similar tissue kinetics were observed around solid and pre-polymerized large pore implants, evidently in the case of solid implants without tissue ingrowth. Into the small pore implants only superficial soft or hard tissue ingrowth was seen because of the too small interconnections. PMID:3164321

van Mullem, P J; de Wijn, J R

1988-04-01

116

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

117

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

PubMed Central

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

Rinehart, James F.

1951-01-01

118

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.

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

2011-01-01

119

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

PubMed

Catch connective tissue of echinoderms at rest (in the standard state) either stiffens or softens in response to different kinds of stimulation. The energy consumption associated with the changes was estimated by measurement of the oxygen consumption rate (VO(2)) in three types of connective tissues-echinoid catch apparatus (CA), holothuroid body-wall dermis (HD), and asteroid body-wall dermis (AD). Mechanical stimulation by repetitive compression (10%-15% strain), which increased viscosity measured by creep tests, was employed for inducing the stiff state. Noradrenaline (10(-3) mol l(-1)), which decreased viscosity of CA, and static 80% compressive strain, which decreased viscosity of HD, were used to induce the soft state in the respective tissues. The VO(2) (in ?l/g/h) values of the standard state were 2.91 (CA), 1.41 (HD), and 0.56 (AD), which were less than 1/4 of the VO(2) of the resting body-wall muscle of the starfish. The VO(2) of the stiff state was about 1.5 times greater than that of the standard state in all types of connective tissues. The VO(2) of the soft state was 3.4 (CA)-9.1 (HD) times greater than that of the standard state. The economical nature of catch connective tissue in posture maintenance is discussed. PMID:22589405

Motokawa, Tatsuo; Sato, Eriko; Umeyama, Kenichi

2012-04-01

120

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

PubMed Central

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

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

2009-01-01

121

A microstructural model for the tensile constitutive and failure behavior of soft skeletal connective tissues.  

PubMed

We propose a microstructural model for the uniaxial tensile constitutive and failure behavior of soft skeletal connective tissues. The model characterizes the tissues as two-phase composites consisting of collagen fibers embedded in ground substance. Nonlinear toe region behavior in the stress versus strain curve results from the straightening of crimped fibers and from fiber reorientation. Subsequent linear behavior results from fiber stretching affected by fiber volume fraction, collagen type, crosslink density, and fiber orientation. Finally, the tissue fails when fibers successively rupture at their ultimate tensile strain. We apply the model to tendon, meniscus, and articular cartilage. The model provides a consistent approach to modeling the tensile behavior of a wide range of soft skeletal connective tissues. PMID:9675681

Wren, T A; Carter, D R

1998-02-01

122

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

PubMed Central

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

2014-01-01

123

Functional role of periostin in development and wound repair: implications for connective tissue disease  

Microsoft Academic Search

Integrity of the extracellular matrix (ECM) is essential for maintaining the normal structure and function of connective tissues.\\u000a ECM is secreted locally by cells and organized into a complex meshwork providing physical support to cells, tissues, and organs.\\u000a Initially thought to act only as a scaffold, the ECM is now known to provide a myriad of signals to cells regulating

Douglas W. Hamilton

2008-01-01

124

Genetic diseases of connective tissues: cellular and extracellular effects of ECM mutations.  

PubMed

Tissue-specific extracellular matrices (ECMs) are crucial for normal development and tissue function, and mutations in ECM genes result in a wide range of serious inherited connective tissue disorders. Mutations cause ECM dysfunction by combinations of two mechanisms. First, secretion of the mutated ECM components can be reduced by mutations affecting synthesis or by structural mutations causing cellular retention and/or degradation. Second, secretion of mutant protein can disturb crucial ECM interactions, structure and stability. Moreover, recent experiments suggest that endoplasmic reticulum (ER) stress, caused by mutant misfolded ECM proteins, contributes to the molecular pathology. Targeting ER stress might offer a new therapeutic strategy. PMID:19204719

Bateman, John F; Boot-Handford, Raymond P; Lamandé, Shireen R

2009-03-01

125

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

Microsoft Academic Search

BACKGROUND: In humans, connective tissue forms a complex, interconnected network throughout the body that may have mechanosensory, regulatory and signaling functions. Understanding these potentially important phenomena requires non-invasive measurements of collagen network structure that can be performed in live animals or humans. The goal of this study was to show that ultrasound can be used to quantify dynamic changes in

Helene M Langevin; Donna M Rizzo; James R Fox; Gary J Badger; Junru Wu; Elisa E Konofagou; Debbie Stevens-Tuttle; Nicole A Bouffard; Martin H Krag

2007-01-01

126

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

PubMed

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). Control and HDP samples were obtained immediately post-treatment and after 14days of aging for SEM and Warner-Bratzler shear force (WBSF) analysis. Immediately post-treatment, HDP treated samples exhibited lower (P<0.01) WBSF than did controls. After aging, HDP-PC samples had lower (P<0.01) WBSF than that of aged controls. SEM analysis indicated that HDP-PC treatment disrupted the integrity of the collagen fibril network of the endomysium in both the non-aged and aged samples. Aging effects on the intramuscular connective tissue were observed in the HDP-PC and control samples. Both WBSF and connective tissue changes were greater in the HDP-PC than in the HDP-CU treated samples. Data suggest that shockwave alterations to connective tissue contribute to the meat tenderization of HDP. PMID:23803280

Zuckerman, H; Bowker, B C; Eastridge, J S; Solomon, M B

2013-11-01

127

Intraneural Connective Tissue Proliferation of the Median Nerve in the Carpal Tunnel,  

National Technical Information Service (NTIS)

In order to evaluate the proliferation of the intraneural connective tissue and its intrinsic vasculature, segments were taken from the median nerve from the distal fourth of the right forearm and the carpal tunnel area in 23 embalmed human cadavers. The ...

W. A. Castelli F. G. Evans R. Diaz-Perez T. J. Armstrong

1988-01-01

128

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

129

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

Microsoft Academic Search

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

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

1996-01-01

130

MECHANICAL DIVERSITY OF CONNECTIVE TISSUE OF THE BODY WALL OF SEA ANEMONES  

Microsoft Academic Search

SUMMARY Techniques for analysing polymer mechanics were used to describe quantitatively the time-dependent mechanical properties of the body-wall connective tissue (mesogloea) and to indicate macromolecular mechanisms responsible for the mechanical behaviour of two species of sea anemones, Metridium senile and Anthopleura xanthogrammica. 1. The mesogloea of M. senile is more extensible and less resilient than that of A. xanthogrammica when

M. A. R. KOEHL

1977-01-01

131

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

Microsoft Academic Search

AIMS\\/BACKGROUND: The connective tissue system of the levator palpebrae superioris muscle (LPS) consists of the septa surrounding its muscle sheath, the superior transverse ligament (STL) commonly referred to as 'Whitnall's ligament' and the common sheath which is the fascia between the LPS and the superior rectus muscle (SRM). The anterior band-like component of the common sheath is called transverse superior

A Ettl; S Priglinger; J Kramer; L Koornneef

1996-01-01

132

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

133

Elevated Dietary Magnesium Prevents Connective Tissue Mineralization in a Mouse Model of Pseudoxanthoma Elasticum (Abcc6?\\/?)  

Microsoft Academic Search

Pseudoxanthoma elasticum (PXE) is an autosomal recessive multisystem disorder characterized by ectopic connective tissue mineralization, with clinical manifestations primarily in the skin, eyes, and cardiovascular system. There is considerable, both intra- and interfamilial, variability in the spectrum of phenotypic presentation. Previous studies have suggested that mineral content of the diet may modify the severity of the clinical phenotype in PXE.

Jennifer LaRusso; Qiaoli Li; Qiujie Jiang; Jouni Uitto

2009-01-01

134

Spine fusion using allograft bone matrix enriched in bone marrow cells and connective tissue progenitors  

Microsoft Academic Search

Purpose of study: Marrow-derived connective tissue progenitor cells (CTPs) can be rapidly concentrated in the operating room using bone matrix as an affinity column. We hypothesized that increasing the concentration of CTPs in a graft site using this method would significantly improve the efficacy of an allograft matrix using an established canine spine fusion model.Methods used: Twelve male beagle dogs

Hidetake Takigami; Yoichi Matsukura; Cynthia Boehm; Anthony Valdevit

2002-01-01

135

Adult Bone Marrow-Derived Stem Cells in Muscle Connective Tissue and Satellite Cell Niches  

PubMed Central

Skeletal muscle includes satellite cells, which reside beneath the muscle fiber basal lamina and mainly represent committed myogenic precursor cells, and multipotent stem cells of unknown origin that are present in muscle connective tissue, express the stem cell markers Sca-1 and CD34, and can differentiate into different cell types. We tracked bone marrow (BM)-derived stem cells in both muscle connective tissue and satellite cell niches of irradiated mice transplanted with green fluorescent protein (GFP)-expressing BM cells. An increasing number of GFP+ mononucleated cells, located both inside and outside of the muscle fiber basal lamina, were observed 1, 3, and 6 months after transplantation. Sublaminal cells expressed unambiguous satellite cell markers (M-cadherin, Pax7, NCAM) and fused into scattered GFP+ muscle fibers. In muscle connective tissue there were GFP+ cells located close to blood vessels that expressed the ScaI or CD34 stem-cell antigens. The rate of settlement of extra- and intralaminal compartments by BM-derived cells was compatible with the view that extralaminal cells constitute a reservoir of satellite cells. We conclude that both muscle satellite cells and stem cell marker-expressing cells located in muscle connective tissue can derive from BM in adulthood.

Dreyfus, Patrick A.; Chretien, Fabrice; Chazaud, Benedicte; Kirova, Youlia; Caramelle, Philippe; Garcia, Luis; Butler-Browne, Gillian; Gherardi, Romain K.

2004-01-01

136

Subcutaneous Connective Tissue Reaction to Methacrylate Resin–based and Zinc Oxide and Eugenol Sealers  

Microsoft Academic Search

IntroductionAn evaluation was made of the connective tissue reaction in rats after subcutaneous implantation of methacrylate resin-based sealers (EndoREZ [Ultradent Products, Inc, South Jordan, UT] with a polymerization accelerator and RealSeal [Sybron Dental Specialties, Orange, CA]) and Pulp Canal Sealer (Sybron Dental Specialties), a zinc oxide and eugenol-based sealer used as the control.

Osvaldo Zmener; Cornelis H. Pameijer; Gabriel A. Kokubu; Daniel R. Grana

2010-01-01

137

A small angle light scattering device for planar connective tissue microstructural analysis.  

PubMed

The planar fibrous connective tissues of the body are composed of a dense extracellular network of collagen and elastin fibers embedded in a ground matrix, and thus can be thought of as biocomposites. Thus, the quantification of fiber architecture is an important step in developing an understanding of the mechanics of planar tissues in health and disease. We have used small angle light scattering (SALS) to map the gross fiber orientation of several soft membrane connective tissues. However, the device and analysis methods used in these studies required extensive manual intervention and were unsuitable for large-scale fiber architectural mapping studies. We have developed an improved SALS device that allows for rapid data acquisition, automated high spatial resolution specimen positioning, and new analysis methods suitable for large-scale mapping studies. Extensive validation experiments revealed that the SALS device can accurately measure fiber orientation for up to a tissue thickness of at least 500 microns to an angular resolution of approximately 1 degree and a spatial resolution of +/-254 microns. To demonstrate the new device's capabilities, structural measurements from porcine aortic valve leaflets are presented. Results indicate that the new SALS device provides an accurate method for rapid quantification of the gross fiber structure of planar connective tissues. PMID:9236980

Sacks, M S; Smith, D B; Hiester, E D

1997-01-01

138

Connective tissues--possible implications of the temporal changes for the aging process.  

PubMed

Two of the "old" mono-cause theories of aging have temporal changes in the connective tissues, especially those in collagen, as main events. The crosslinking of collagen is stable under physiological conditions shortly after the formation of fibrils and the additional physico-chemical stability attained later on probably does not influence the physiological functions of the tissues significantly. The temporal changes in collagen seen as increased thermal stability, decreased solubility and increased mechanical stiffness are discussed in relation to the underlying structural changes. It is concluded that the increased stability of the collagen (mainly type I) in the locomotive system and skin are not "true" aging phenomena. It is possible that the changes in the connective tissues of the lungs and kidneys contribute to the decrease of function with age. The "normal" increase of stiffness of type I collagen may contibute to the increased compliance and residual volume of the aging lung. Our present knowledge of the structure and function of collagens and ground substances in various basement membranes does not permit an evaluation of the role of connective tissues in the age changes in the alveolo--capillary complex, the glomeruli and the exchange between tissues and capillaries in general. PMID:374896

Viidik, A

1979-02-01

139

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

140

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

PubMed Central

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

2009-01-01

141

Connections.  

ERIC Educational Resources Information Center

Provides an annotated list of resources dealing with the theme of various types of connections. Includes Web sites, CD-ROMs/software, videos, books, and additional resources with appropriate grade levels and subject disciplines indicated in most cases. Sidebars include toys that connect, connecting with nature, it's a small world-satellites,…

Online-Offline, 2000

2000-01-01

142

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

NASA Astrophysics Data System (ADS)

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

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

143

Retention mechanism of imidazoles in connective tissue. I. Binding to elastin.  

PubMed

To elucidate the retention mechanism of drugs with imidazole moiety in the connective tissue, the retention form and site of [2-14C]imidazole and 2-methyl[2-14C]imidazole were studied after intravenous administration to rats (3 micromol/kg body weight). The aorta, which is representative of the connective tissue, retained considerable radioactivity after dosing for both the imidazoles. It was observed that most of the aortic radioactivity came from the irreversibly bound fraction with elastin and that this was in close agreement with the microautoradiographic observation that showed that the retention of radioactivity occurred near the elastic fiber in the aorta. Pretreatment of rats with SKF525-A significantly increased the irreversible binding of radioactivity from the imidazoles in aorta, whereas neither phenobarbital nor 3-methylcholanthrene increased the binding. Regarding the urinary metabolite profile, the excretion of intact form significantly increased by SKF525-A pretreatment for imidazole, and an increasing tendency was also observed for 2-methylimidazole. However, no in vitro irreversible binding of imidazoles to aortic tissue was observed after incubating at physiological pH and temperature. These findings indicate that the retention of drugs with imidazole moiety in the connective tissue is largely attributable to irreversible binding between the imidazole moiety and elastin, and that the binding may be mediated through cytochrome P450-independent biotransformation. PMID:8971133

Ohta, K; Yamaguchi, J I; Akimoto, M; Fukushima, K; Suwa, T; Awazu, S

1996-12-01

144

Connective Tissue Reaction to White and Gray MTA Mixed With Distilled Water or Chlorhexidine in Rats  

PubMed Central

INTRODUCTION: The purpose of this study was to compare the histocompatibility of white (WMTA) and gray (GMTA) mineral trioxide aggregate mixed with 0.12% chlorhexidine (CHX) and distilled water (DW) in subcutaneous connective tissues of rats. MATERIALS AND METHODS: The freshly mixed WMTA and GMTA with CHX or DW were inserted in polyethylene tubes and implanted into dorsal subcutaneous connective tissue of 50 Wistar Albino rats; tissue biopsies were collected and were then examined histologically 7, 15, 30, 60 and 90 days after the implantation procedure. The histology results were scored from 1-4; score 4 was considered as the worst finding. Data were analyzed using one-way ANOVA tests. RESULTS: All experimented materials were tolerated well by the connective tissues after 90-day evaluation, except for the WMTA/CHX group that had significantly more mean inflammatory scores (P<0.001). There was a statistically significant difference in the mean inflammation grades between experimental groups in each interval (P<0.001). After 90 days, GMTA/CHX group had the lowest inflammatory score. CONCLUSION: Although adding CHX to WMTA produces significantly higher inflammatory response, it seems a suitable substitute for DW in combination with GMTA. Further research is necessary to recommend this mixture for clinical use.

Yavari, Hamid Reza; Shahi, Shahriar; Rahimi, Saeed; Shakouie, Sahar; Roshangar, Leila; Mesgari Abassi, Mehran; Sattari Khavas, Sahar

2009-01-01

145

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

PubMed

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

Bairati, A; Comazzi, M; Gioria, M

2001-10-01

146

Relationships between Values of Antibodies to Several Connective Tissue Disease Autoantigens and Pulmonary Function in a Japanese General Population: The Takahata Study  

PubMed Central

Background Accumulating evidence suggests the involvement of an autoimmune mechanism in the pathogenesis of respiratory dysfunction. The aim of this study was to investigate the relationship between pulmonary function and serum antibodies to several connective tissue disease autoantigens (ACTDA) levels, which has not been investigated in a general population. Methods Blood sampling and spirometry were performed for subjects (n = 3,257) aged ?40 years who participated in a community-based annual health check in Takahata, Japan, from 2004 to 2006. ACTDA was measured by enzyme immunoassay, and subjects with ACTDA values ?20 were defined as positive. Results In males, there were significant inverse relationships between logarithmically transformed ACTDA values and spirometric parameters, including % predicted values for forced expiratory volume in 1 s (FEV1) and maximal midexpiratory flow (MMF) as well as FEV1/forced vital capacity (FVC). Multiple linear regression analysis revealed that except for the relationship between ACTDA and FEV1/FVC, these relationships were still significant after adjustment for Brinkman index (a measure of inhaled cigarette consumption). The prevalence of positive ACTDA was greater in male never-smokers with mixed ventilation disorders and relatively severe airflow obstruction (% predicted FEV1 below the median value). Conclusions Autoimmunity may be involved in the mechanism of impaired pulmonary function in the general population.

Nakano, Hiroshi; Shibata, Yoko; Inoue, Sumito; Igarashi, Akira; Yamauchi, Keiko; Abe, Shuichi; Sato, Masamichi; Aida, Yasuko; Nunomiya, Keiko; Kimura, Tomomi; Nemoto, Takako; Watanabe, Tetsu; Konta, Tsuneo; Ueno, Yoshiyuki; Kato, Takeo; Kayama, Takamasa; Kubota, Isao

2013-01-01

147

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

PubMed

Echinoderms and sponges share a unique feature that helps them face predators and other environmental pressures. They both possess collagenous tissues with adaptable viscoelastic properties. In terms of morphology these structures are typical connective tissues containing collagen fibrils, fibroblast- and fibroclast-like cells, as well as unusual components such as, in echinoderms, neurosecretory-like cells that receive motor innervation. The mechanisms underpinning the adaptability of these tissues are not completely understood. Biomechanical changes can lead to an abrupt increase in stiffness (increasing protection against predation) or to the detachment of body parts (in response to a predator or to adverse environmental conditions) that are regenerated. Apart from these advantages, the responsiveness of echinoderm and sponge collagenous tissues to ionic composition and temperature makes them potentially vulnerable to global environmental changes. PMID:24008006

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

2014-02-01

148

An ultrastructural study of connective tissue in mollusc integument: I. Bivalvia.  

PubMed

The ultrastructure of the subepidermal connective tissue (SEC) in different areas of the integument of the bivalves Callista chione, Pecten jacobaeus, Mytilus galloprovincialis and Ostrea edulis was studied by transmission electron microscopy. The main organisation of the SEC was broadly similar in all species: the SEC was connected to the epidermis by a basement membrane and merged directly with the deeper connective tissue surrounding muscles. The SEC was not differentiated into layers like the papillary and reticular dermis of mammals, however, the architecture, thickness and shape of the basement membrane varied from species to species, as well as within species (in the foot, central or marginal zones of the mantle). The ultrastructure of the lamina densa was broadly similar to that in mammals: although basotubules and double pegs were absent, proteoglycans and rod-like units homologous to 'double tracks' were always abundant. A zone similar to the lamina lucida was irregularly present and was shot thorough with small protrusions of the lamina densa that connected with the epithelial hemidesmosomes or focal adhesions. Nevertheless zones were observed where the lamina densa fuse directly to the epithelial plasmamembrane. This variability of connection may be related to the various types of epidermal cell. A lamina fibroreticularis was not recognized since anchoring fibrils and microfibrils were not present; lamina densa protrusions into the extracellular matrix (ECM) of SEC characterize the connection between basement membrane and SEC. Collagen fibrils were small and of constant diameter and were never organised into fibres. Anchoring devices - similar to the anchoring plaques of mammalian dermis - were abundant and scattered between SEC collagen fibrils. The orange-pink pigmentation of C. chione seems due to electron-dense granules embedded within the connective ECM. PMID:11201282

Bairati, A; Comazzi, M; Gioria, M

2000-10-01

149

Connections  

NSF Publications Database

Title : NSF 94-74 Connections Type : General Publication NSF Org: MPS Date : November 29, 1994 File : nsf9474 CONNECTIONS Investments for the 21st Century THE ULTIMATE KNOWLEDGE INDUSTRY A PUBLICATION FOR THE DIRECTORATE OF MATHEMATICAL AND PHYSICAL SCIENCES OF THE NATIONAL SCIENCE FOUNDATION Introducing Connections The process of creating fundamental new knowledge is exciting and rewarding in itself. The Mathematical and Physical Sciences Directorate supports a wide array of research and ...

150

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.

Li, Qiaoli; Uitto, Jouni

2014-01-01

151

Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis.  

PubMed

Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell contact and indirectly through the secretion of cytokines and growth factors. We report that connective tissue growth factor (Ctgf, also known as Ccn2) is highly expressed in murine bone marrow stromal cells. In contrast, connective tissue growth factor is barely detectable in unfractionated adult bone marrow cells. While connective tissue growth factor has been implicated in hematopoietic malignancies, and is known to play critical roles in skeletogenesis and regulation of bone marrow stromal cells, its role in hematopoiesis has not been described. Here we demonstrate that the absence of connective tissue growth factor in mice results in impaired hematopoiesis. Using a chimeric fetal liver transplantation model, we show that absence of connective tissue growth factor has an impact on B-cell development, in particular from pro-B to more mature stages, which is linked to a requirement for connective tissue growth factor in bone marrow stromal cells. Using in vitro culture systems, we demonstrate that connective tissue growth factor potentiates B-cell proliferation and promotes pro-B to pre-B differentiation in the presence of interleukin-7. This study provides a better understanding of the functions of connective tissue growth factor within the bone marrow, showing the dual regulatory role of the growth factor in skeletogenesis and in stage-specific B lymphopoiesis. PMID:24727816

Cheung, Laurence C; Strickland, Deborah H; Howlett, Meegan; Ford, Jette; Charles, Adrian K; Lyons, Karen M; Brigstock, David R; Goldschmeding, Roel; Cole, Catherine H; Alexander, Warren S; Kees, Ursula R

2014-07-01

152

Connective tissue growth factor is expressed in bone marrow stromal cells and promotes interleukin-7-dependent B lymphopoiesis  

PubMed Central

Hematopoiesis occurs in a complex bone marrow microenvironment in which bone marrow stromal cells provide critical support to the process through direct cell contact and indirectly through the secretion of cytokines and growth factors. We report that connective tissue growth factor (Ctgf, also known as Ccn2) is highly expressed in murine bone marrow stromal cells. In contrast, connective tissue growth factor is barely detectable in unfractionated adult bone marrow cells. While connective tissue growth factor has been implicated in hematopoietic malignancies, and is known to play critical roles in skeletogenesis and regulation of bone marrow stromal cells, its role in hematopoiesis has not been described. Here we demonstrate that the absence of connective tissue growth factor in mice results in impaired hematopoiesis. Using a chimeric fetal liver transplantation model, we show that absence of connective tissue growth factor has an impact on B-cell development, in particular from pro-B to more mature stages, which is linked to a requirement for connective tissue growth factor in bone marrow stromal cells. Using in vitro culture systems, we demonstrate that connective tissue growth factor potentiates B-cell proliferation and promotes pro-B to pre-B differentiation in the presence of interleukin-7. This study provides a better understanding of the functions of connective tissue growth factor within the bone marrow, showing the dual regulatory role of the growth factor in skeletogenesis and in stage-specific B lymphopoiesis.

Cheung, Laurence C.; Strickland, Deborah H.; Howlett, Meegan; Ford, Jette; Charles, Adrian K.; Lyons, Karen M.; Brigstock, David R.; Goldschmeding, Roel; Cole, Catherine H.; Alexander, Warren S.; Kees, Ursula R.

2014-01-01

153

A Comparative Study of the Biocompatibility of Three Root-end Filling Materials in Rat Connective Tissue  

Microsoft Academic Search

The purpose of this study was to compare the biocompatibility of amalgam, gray MTA and white MTA in the connective tissue of rats. We used 45 Sprague-Dawley rats in this study. The rats were divided into three groups. Root end filling materials were placed in polyethylene tubes and inserted into the rats’ connective tissue through incisions. The rats were sacrificed

Shahriar Shahi; Saeed Rahimi; Mehrdad Lotfi; HamidReza Yavari; AliReza Gaderian

2006-01-01

154

Specialized connective tissue: bone, the structural framework of the upper extremity.  

PubMed

Bone is a connective tissue containing cells, fibers, and ground substance. There are many functions in the body in which the bone participates, such as storing minerals, providing internal support, protecting vital organs, enabling movement, and providing attachment sites for muscles and tendons. Bone is unique because its collagen framework absorbs energy, whereas the mineral encased within the matrix allows bone to resist deformation. This article provides an overview of the structure and function of bone tissue from a macroscopic to microscopic level and discusses the physiological processes contributing to upper extremity bone health. It concludes by discussing common conditions influencing upper extremity bone health. PMID:22047807

Weatherholt, Alyssa M; Fuchs, Robyn K; Warden, Stuart J

2012-01-01

155

Influence of ionic environment of the stress relaxation behavior of an invertebrate connective tissue.  

PubMed

The rheological properties of an invertebrate connective tissue were measured in three different ionic environments. Short-term stress relaxation tests were conducted on sections of holothurian (Echinodermata) body wall immersed in isotonic monovalent and divalent salt solutions and deionized water. Using a reduced modulus format, the viscoelastic behavior over the experimental time scale was described by a two term Maxwell equation with empirically determined spring constants and relaxation times. In addition, equilibrium relaxation moduli (Ge) were estimated from the empirical relationship of Chasset and Thirion (1965, in Physics of Non Crystalline Solids, ed. Prins, North Holland). The experiments indicated that both relaxation times and equilibrium moduli decreased in the presence of monovalent and divalent inorganic ions whereby the effect of the Na+ was greater than that of the Ca++. The present findings are compared with those reported for vertebrate connective tissue. PMID:6736052

Greenberg, A R; Eylers, J P

1984-01-01

156

Genetic dissection of marfan syndrome and related connective tissue disorders: an update 2012.  

PubMed

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

2012-08-01

157

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

PubMed Central

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 understanding and identifying the effector cells, the proinflammatory and profibrotic mediators, and the pathways involved in the pathogenesis of CTD-ILD. Serum biomarkers may provide new insights as risk factors for pulmonary fibrosis and as measures of disease progression. Despite these recent advances, the management of patients with CTD-ILD remains suboptimal. Further studies are therefore urgently needed to better understand these conditions, and to develop effective therapeutic interventions.

2010-01-01

158

The effect of muscle actions on the level of connective tissue damage.  

PubMed

The aim of this study was to compare the effect of concentric with eccentric muscle actions on the resulting level of damage to connective tissues by urinary concentration of hydroxyproline. Twenty-one male volunteers were divided into control group (CG), experimental concentric group (ECG), and experimental eccentric group (EEG). The measures of hydroxyproline were performed at three times: pretest, fourth week, and posttest. Biceps curl and chest press exercises also were performed with three sets of 10 repetitions two times per week for both experimental groups. Analysis of variance (ANOVA) showed a significant difference between pretest of the CG and pretest of the ECG (p = 0.002), and between pretest and posttest for the EEG (p = 0.029). Therefore, this study concluded that the level of damage to the connective tissue is greater when exercises involving eccentric muscle actions are performed. The continuity of training, however might reduce this damage. PMID:21988268

Nogueira, Antonio de C; Vale, Rodrigo G S; Gomes, André L M; Dantas, Estélio H M

2011-10-01

159

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.

Hoffjan, S.

2012-01-01

160

Dimensional changes during early healing after a subepithelial connective tissue graft procedure.  

PubMed

Background: The subepithelial connective tissue graft (CTG) is a popular means to treat gingival recession and augment keratinized tissue. Studies exist that examine long-term outcomes of this procedure; however, changes in tissue dimensions during early healing (0 to 21 days postoperatively) are unknown. The aim of this study is to examine bucco-lingual tissue dimension (gingival tissue thickness [GT]) changes during early CTG healing using a non-invasive technique. Methods: Thirteen patients who had treatment planned for CTG on a single tooth were recruited for the study. Using a customized acrylic stent, GT was measured preoperatively, at surgery completion, and at 3, 7, 14, and 21 days postoperatively. CTG was performed using an envelope technique. GT changes were analyzed by repeated-measures analysis of variance. Results: All CTG procedures were considered successful with no postoperative complications. GT increased 1.5 mm immediately after surgery (baseline) compared to the preoperative measurement. GT increased on average 96%, 47%, and 2% compared to baseline at days 3, 7, and 14, respectively. Day 3 and day 7 measurements were significantly different from baseline (P <0.001). At day 21, GT decreased 15% compared to baseline, with an average increase of 1.29 mm from preoperative measurements. Conclusions: The early postoperative healing of CTGs used for root coverage exhibits a significant but transient increase in bucco-lingual tissue dimension. The observed increase in bucco-lingual tissue dimension subsides by the end of the second postoperative week. PMID:24215201

Rotenberg, Shaun A; Tatakis, Dimitris N

2014-07-01

161

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

PubMed

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

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

2011-08-23

162

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

PubMed Central

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

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

2011-01-01

163

Characterizing the mechanical contribution of fiber angular distribution in connective tissue: comparison of two modeling approaches  

Microsoft Academic Search

Modeling of connective tissues often includes collagen fibers explicitly as one of the components. These fibers can be oriented\\u000a in many directions; therefore, several studies have considered statistical distributions to describe the fiber arrangement.\\u000a One approach to formulate a constitutive framework for distributed fibers is to express the mechanical parameters, such as\\u000a strain energy and stresses, in terms of angular

Daniel H. Cortes; Spencer P. Lake; Jennifer A. Kadlowec; Louis J. Soslowsky; Dawn M. Elliott

2010-01-01

164

Effect of thermal process on connective tissue from jumbo squid ( Dosidicus gigas) mantle  

Microsoft Academic Search

The effect of two thermal treatments (fast freezing at ?40°C and vapor cooking at 100°C) on connective tissue extract (CTE) from jumbo squid (Dosidicus gigas) was investigated. Samples of CTE frozen at ?40°C were taken at 0, 3, 5 and 12min. Also CTE was cooked at 100°C and samples were taken at 0, 1, 2.5 and 5min. Light microscopic observations

Adriana Zulema Valencia-Pérez; Miriam Hiessu García-Morales; José Luis Cárdenas-López; José Ronaldo Herrera-Urbina; Ofelia Rouzaud-Sández; Josafat Marina Ezquerra-Brauer

2008-01-01

165

Undifferentiated Connective Tissue Disease-Associated Interstitial Lung Disease: Changes in Lung Function  

Microsoft Academic Search

Undifferentiated connective tissue disease (UCTD) is a distinct clinical entity that may be accompanied by interstitial lung\\u000a disease (ILD). The natural history of UCTD-ILD is unknown. We hypothesized that patients with UCTD-ILD would be more likely\\u000a to have improvement in lung function than those with idiopathic pulmonary fibrosis (IPF) during longitudinal follow-up. We\\u000a identified subjects enrolled in the UCSF ILD

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

2010-01-01

166

Cell-mediated immunity against connective tissue in experimental pulmonary fibrosis  

Microsoft Academic Search

Cell-mediated immunity against an extract of homologous normal lung connective tissue was determined in vitro in spleen cells\\u000a from CD1 mice with bleomycin-induced pulmonary fibrosis. Blastoid transformation and macrophage migration inhibitory factor\\u000a (MIF) were measured at intervals in spleen lymphocytes for a total of seven weeks after the initiation of the fibrogenic process.\\u000a MIF production was evident from the third

R. E. Carvajal; R. González; M. Selman

1982-01-01

167

Connective tissue growth factor: Potential role in glomerulosclerosis and tubulointerstitial fibrosis  

Microsoft Academic Search

Connective tissue growth factor: Potential role in glomerulosclerosis and tubulointerstitial fibrosis. Transforming growth factor beta (TGF-?) is a pivotal driver of glomerulosclerosis and tubulointerstitial fibrosis in renal diseases. Because TGF-? also plays important anti-inflammatory and antiproliferative roles in mammalian systems, there has been a recent drive to elucidate downstream mediators of TGF-?'s pro-fibrotic effects with the ultimate goal of developing

Sunil Gupta; Michael R. Clarkson; Joseph Duggan; Hugh R. Brady

2000-01-01

168

Potential Risk Factors for Undifferentiated Connective Tissue Disease among Women: Implanted Medical Devices  

Microsoft Academic Search

A case-control study was conducted among 205 women in Michigan and Ohio who were diagnosed with undifferentiated connective tissue disease (UCTD) to investigate the significance of self-reported past exposures to implanted silicone-containing or non-silicone-containing medical devices. The 205 UCTD cases were compared with 2,095 controls who were sampled by random digit dialing. When silicone-containing devices, including shunts and catheters, were

Timothy J. Laing; David Schottenfeld; James V. Lacey; Brenda W. Gillespie; David H. Garabrant; Brenda C. Cooper; Steven G. Heeringa; Kirsten H. Alcser; Maureen D. Mayes

169

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

Microsoft Academic Search

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

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

1993-01-01

170

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

Microsoft Academic Search

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

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

2007-01-01

171

Antifibrillarin Autoantibodies Present in Systemic Sclerosis and Other Connective Tissue Diseases Interact with Similar Epitopes  

Microsoft Academic Search

Summary Autoantibodies specific against fibrillarin, a 34-kD nucleolar protein associated with U3-snRNP, are present in patients with systemic sclerosis (SSc). To understand the mechanisms involved in the induction of these autoantibodies, we prepared a series of human fibrillarin recombinant proteins covering the entire molecule and analyzed their interaction with the autoantibodies present in various connective tissue diseases. Our results showed

Kuppuswamy N. Kasturi; Akira Hatakeyama; Harry Spier; Constantin A. Bon

1995-01-01

172

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

PubMed

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

2010-01-01

173

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

174

A nonphosphaturic mesenchymal tumor mixed connective tissue variant of the sacrum.  

PubMed

Tumor-induced or oncogenic osteomalacia is a rare paraneoplastic syndrome characterized by overproduction of fibroblast growth factor-23 as a phosphaturic agent and renal phosphate wasting. A range of predominantly mesenchymal neoplasms have been associated with tumor-induced osteomalacia and classified as phosphaturic mesenchymal tumor mixed connective tissues. However, phosphaturic mesenchymal tumor mixed connective tissues could be nonphosphaturic in the first stage of the disease, either because the tumors are resected early in the clinical course or because the patient's osteomalacia was attributed to another cause. This article presents a case of a 42-year-old woman with a 2-year history of low back and right leg pain. Laboratory examinations including serum and urine calcium and phosphorous were within normal values. Imaging of the lumbar spine and pelvis showed an osteolytic lesion occupying the right sacral wing. Histology was unclear. Reverse-transcription polymerase chain reaction analysis for fibroblast growth factor-23 was positive and confirmed the diagnosis of phosphaturic mesenchymal tumor mixed connective tissues. Preoperative selective arterial embolization and complete intralesional excision, bone grafting, and instrumented fusion from L4 to L5 to the iliac wings bilaterally was performed. Postoperative recovery was uneventful. Neurological deficits were not observed. A lumbopelvic corset was applied for 3 months. At 12 months, the patient was asymptomatic. Serum and urine values of calcium and phosphorous were normal throughout the follow-up evaluation. PMID:21053876

Mavrogenis, Andreas F; Sakellariou, Vasileios I; Soultanis, Konstantinos; Mahera, Helen; Korres, Demetrios S; Papagelopoulos, Panayiotis J

2010-11-01

175

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

PubMed Central

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

Latuskiewicz-Potemska, Joanna; Biernacka-Zielinska, Malgorzata; Stanczyk, Jerzy; Smolewska, Elzbieta

2013-01-01

176

MDSC in Autoimmunity  

PubMed Central

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 contrast to the proposed deleterious role of MDSC in cancer - where these cells likely inhibit tumor immunity - in the context of autoimmunity, MDSC have the potential to suppress the autoimmune response, thereby limiting tissue injury. A logical corollary of this hypothesis is that a failure of endogenous MDSC to appropriately control autoimmune T cell responses in vivo may actually contribute to the pathogenesis of autoimmune disease.

Cripps, James G.; Gorham, James D.

2011-01-01

177

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.

178

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

179

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.

2011-01-01

180

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

181

Fibroblastic Differentiation of Human Mesenchymal Stem Cells using Connective Tissue Growth Factor  

PubMed Central

The present study was designed to explore an ex vivo culturing protocol for fibroblastic differentiation of human mesenchymal stem cells (hMSCs) using connective tissue growth factor (CTGF). Fibroblastic differentiation from stem cells is of widespread significance in the engineering of virtually all tissues including tendons, ligaments, periodontal ligament, cranial sutures and as interstitial filler of all organs. The treatment with 100 ng/ml of recombinant human CTGF and 50 ?g/ml ascorbic acids on monolayer cultured hMSCs showed significant increases in type I collagen and tenascin-C (Tn-C) contents by 2 and 4 wks. In addition, CTGF-treated hMSCs failed to show osteogenic or chondrogenic differentiation. The present data show that CTGF is an effective induction factor for fibroblastic differentiation of hMSCs. These findings have implications for engineering fibrous tissue by providing the initial evidence of a reproducible protocol for fibroblastic differentiation of hMSCs.

Lee, Chang H.; Moioli, Eduardo K.; Mao, Jeremy J.

2010-01-01

182

Autoimmune neutropenia.  

PubMed

Autoimmune neutropenia (AIN) is a rare entity caused by antibodies directed against neutrophil-specific antigens. It includes primary and secondary autoimmune neutropenia. Acute autoimmune neutropenia can be related to drug-induced mechanism or viral infections. Chronic autoimmune neutropenias occur in the context of autoimmune diseases, hematological malignancies, such as large granular lymphocyte leukemia, primary immune deficiency syndromes or solid tumors. The therapeutic management depends on the etiology. Granulocyte growth factor is the main therapeutic option, raising the question of their long-term utilization safety. Corticosteroids or immunosuppressive therapy are indicated in infection-related AIN or in case of symptomatic autoimmune disease or LGL leukemia. PMID:24680423

Autrel-Moignet, Aline; Lamy, Thierry

2014-04-01

183

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.

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

2012-01-01

184

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.

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

2013-01-01

185

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.

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

186

Differences in infrared spectroscopic data of connective tissues in transflectance and transmittance modes.  

PubMed

Fourier transform infrared imaging spectroscopy (FT-IRIS) has been used extensively to characterize the composition and orientation of macromolecules in thin tissue sections. Earlier and current studies of normal and polarized FT-IRIS data have primarily used tissues sectioned onto infrared transmissive substrates, such as salt windows. Recently, the use of low-emissivity ("low-e") substrates has become of great interest because of their low cost and favorable infrared optical properties. However, data are collected in transflectance mode when using low-e slides and in transmittance mode using salt windows. In the current study we investigated the comparability of these two modes for assessment of the composition of connective tissues. FT-IRIS data were obtained in transflectance and transmittance modes from serial sections of cartilage, bone and tendon, and from a standard polymer, polymethylmethacrylate. Both non-polarized and polarized FTIR data differed in absorbance, and in some cases peak position, between transflectance and transmittance modes. However, the FT-IRIS analysis of the collagen fibril orientation in cartilage resulted in the expected zonal arrangement of fibrils in both transmittance and transflectance. We conclude that numerical comparison of FT-IRIS-derived parameters of tissue composition should account for substrate type and data collection mode, while analysis of overall tissue architecture may be more invariant between modes. PMID:23663670

Hanifi, Arash; McGoverin, Cushla; Ou, Ya-Ting; Safadi, Fayez; Spencer, Richard G; Pleshko, Nancy

2013-05-24

187

Connective tissue biomatrix: its isolation and utilization for long- term cultures of normal rat hepatocytes  

PubMed Central

A new procedure is introduced for the isolation of connective tissue fibers, called biomatrix, containing a significant portion of the extracellular matrix (basement membrane components and components of the ground substance). Biomatrix isolated from normal rat liver contains >90% of the tissue's collagens and all of the known collagen types, including types I and III and basement membrane collagens. The purified collagenous fibers are associated with noncollagenous acidic proteins (including fibronectins and possibly small amounts of glycosaminoglycans). Procedures are also described for preparing tissue culture substrates with these fibers by either smearing tissue culture dishes with frozen sections or by shredding the biomatrix into small fibrils with a homogenizer. The biomatrix as a substrate has a remarkable ability to sustain normal rat hepatocytes long-term in culture. The hepatocytes, which on tissue culture plastic or on type I collagen gels do not survive more than a few weeks, have been maintained for more than 5 mo in vitro when cultured on biomatrix. These cells cultured on rat liver biomatrix show increased attachment and survival efficiencies, long-term survival (months) and retention of some hepatocyte-specific functions.

1980-01-01

188

Differences in infrared spectroscopic data of connective tissues in transflectance and transmittance modes  

PubMed Central

Fourier transform infrared imaging spectroscopy (FT-IRIS) has been used extensively to characterize the composition and orientation of macromolecules in thin tissue sections. Earlier and current studies of normal and polarized FT-IRIS data have primarily used tissues sectioned onto infrared transmissive substrates, such as salt windows. Recently, the use of low-emissivity (“low-e”) substrates has become of great interest because of their low cost and favourable infrared optical properties. However, data is collected in transflectance mode when using low-e slides and in transmittance mode using salt windows. In the current study we investigated the comparability of these two modes for assessment of the composition of connective tissues. FT-IRIS data were obtained in transflectance and transmittance modes from serial sections of cartilage, bone and tendon, and from a standard polymer, polymethylmethacrylate. Both non-polarized and polarized FTIR data differed in absorbance, and in some cases peak position, between transflectance and transmittance modes. However, the FT-IRIS analysis of the collagen fibril orientation in cartilage resulted in the expected zonal arrangement of fibrils in both transmittance and transflectance. We conclude that numerical comparison of FT-IRIS-derived parameters of tissue composition should account for substrate type and data collection mode, while analysis of overall tissue architecture may be more invariant between modes.

Hanifi, Arash; McGoverin, Cushla; Ou, Ya-Ting; Safadi, Fayez; Spencer, Richard; Pleshko, Nancy

2013-01-01

189

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.

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

2009-01-01

190

Structure and function of the mammalian fibrillin gene family: implications for human connective tissue diseases.  

PubMed

Fibrillins and latent transforming growth factor ? binding proteins (LTBPs) are components of the extracellular matrix of connective tissue. While fibrillins are integral to the 10nm microfibrils, and often associated with elastin, all family members are likely to have an additional role in regulating the bioavailability of transforming growth factor ? (TGB?). Both fibrillins and LTBPs are large glycoproteins, containing a series of calcium binding epidermal growth factor domains as well as a number of copies of a unique 8 cysteine domain found only in this protein superfamily. There are three mammalian fibrillins and four LTBPs. Fibrillin monomers link head to tail in microfibrils which can then form two and three dimensional structures. In some tissues elastin is recruited to the fibrillin microfibrils to provide elasticity to the tissue. LTBPs are part of the TGB? large latent complex which sequesters TGB? in the extracellular matrix. Fibrillin-1 appears to bind to LTBPs to assist in this process and is thus involved in regulating the bioavailability of TGB?. Mutation of fibrillin genes results in connective tissue phenotypes which reflect both the increased level of active TGB? and the structural failure of the extracellular matrix due to the absence or abnormality of fibrillin protein. Fibrillinopathies include Marfan syndrome, familial ectopia lentis, familial thoracic aneurysm (mutations of FBN1) and congenital contractural arachnodactyly (mutation of FBN2). There are no diseases currently associated with mutation of FBN3 in humans, and this gene is no longer active in rodents. Expression patterns of fibrillin genes are consistent with their role in extracellular matrix structure of connective tissue. FBN1 expression is high in most cell types of mesenchymal origin, particularly bone. Human and mouse FBN2 expression is high in fetal cells and has more restricted expression in mesenchymal cell types postnatally. FBN3 is expressed early in development (embryonic and fetal tissues) in humans. The fibrillins are thus important in maintaining the structure and integrity of the extracellular matrix and, in combination with their sequence family members the LTBPs, also contribute to the regulation of the TGF? family of major growth factors. PMID:22921888

Davis, Margaret R; Summers, Kim M

2012-12-01

191

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.

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

2010-01-01

192

An ultrastructural study of connective tissue in mollusc integument III. Cephalopoda.  

PubMed

We studied structure and ultrastructure of the subepidermal connective tissue (SEC) of the integument of three cephalopods (Sepia officinalis, Octopus vulgaris and Loligo pealii). In all species, three distinct regions of the SEC were recognised: (a) an outer zone (OZ) that included the dermal-epidermal junction, and consisted of a thin layer of connective tissue containing muscles, (b) an extensive middle zone (MZ) containing a compact network of collagen fibres and numerous cells, (c) an inner zone (IZ) of loose connective tissue that merged with muscular fascia. This arrangement differs from that in bivalves and gastropods and recalls vertebrate integument. The dermal-epidermal junction of cephalopods differed from that of bivalves, gastropods and mammals in that the epidermal cells did not possess hemidesmosomes, and their intermediate filaments terminated directly in the plasmamembrane. The thick (120-500 nm) basal membrane (BM) had a superficial zone containing a regular array of granules; a lamina densa composed of a compact network of small filaments and granules; and an IZ distinguished by expansions of granular material protruding into underlying structures. Collagen fibres contained fibroblast-derived cytoplasmic thread, running through their centres and were surrounded by granular material that joins them to adjacent fibres. The collagen fibrils were of medium diameter (30-80 nm) had the typical ultrastructure of fibrillar collagens, and were surrounded by abundant interfibrillar material. The hypodermis was loose, with a network of small bundles of collagen fibrils. Cephalopod integument appears to represent a major evolutionary step distinguishing this class of molluscs. PMID:12798125

Bairati, A; Comazzi, M; Gioria, M

2003-06-01

193

Low yield of genetic testing for known vascular connective tissue disorders in patients with fibromuscular dysplasia.  

PubMed

Patients with fibromuscular dysplasia (FMD) may have clinical features consistent with Mendelian vascular connective tissue disorders. The yield of genetic testing for these disorders among patients with FMD has not been determined. A total of 216 consecutive patients with FMD were identified. Clinical characteristics were collected and genetic test results reviewed for abnormalities in the following genes: transforming growth factor-? receptor 1 and 2 (TGF?R1 and TGF?R2), collagen 3A1, fibrillin-1, smooth muscle ?-actin 2, and SMAD3. A total of 63 patients (63/216; 29.2%) were referred for genetic counseling with testing performed in 35 (35/63; 55.6%). The percentage of patients with a history of arterial or aortic dissection, history of aortic aneurysm, systemic features of a connective tissue disorder, and a family history of sudden death was significantly larger in the group that underwent genetic testing (62.9% vs 18.2%, p < 0.001; 8.6% vs 1.7%, p = 0.02; 51.4% vs 17.1%, p < 0.001; and 42.9% vs 22.7%, p = 0.04, respectively). Two patients were found to have distinct variants in the TGF?R1 gene (c.611 C>T, p.Thr204lle and c.1285 T>C, p.Tyr429His). The yield of genetic testing for vascular connective tissue disorders was low in a high-risk subset of FMD patients. However, two patients with a similar phenotype had novel and distinct variants in the TGF?R1 gene, a finding which merits further investigation. PMID:23064905

Poloskey, Stacey L; Kim, Esther Sh; Sanghani, Ruchi; Al-Quthami, Adeeb H; Arscott, Patricia; Moran, Rocio; Rigelsky, Christina M; Gornik, Heather L

2012-12-01

194

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

PubMed

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

195

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.

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

2013-01-01

196

Different biochemical composition of connective tissue in continent and stress incontinent women.  

PubMed

The collagen content in biopsies from skin and ligamentum rotundum of 7 women with a long history of stress incontinence was compared with that of continent controls. The collagen was extracted with 0.5 M acetic acid, followed by digestion with pepsin and quantitated as hydroxyproline. The skin of stress incontinent women contained 40% less collagen than that of continent women. The findings for ligamentum rotundum were similar. These results suggest a deteriorated connective tissue in stress-incontinent women and cast new light on the etiology of the disease. PMID:3425248

Ulmsten, U; Ekman, G; Giertz, G; Malmström, A

1987-01-01

197

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.

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

2012-01-01

198

Decorin gene expression in the differentiation of the skeletal connective tissues of the developing limb.  

PubMed

Tendons and cartilages are connective tissues of essential importance in the musculoskeletal system. During digit development, cartilage and tendon primordia develop from the undifferentiated mesenchymal cells originated in the lateral plate mesoderm. The specification of these tissues begins with the establishment of cellular aggregates, which prefigure the tendons and phalanges. Transforming growth factor beta proteins (TGF?s) are the inductive signals responsible not only for the initiation of chondrogenesis and tenogenesis during digit formation, but also for joint specification. An early role of this family of secreted proteins during these processes is to promote mesenchymal cell precursors condensation. Here we show that Decorin presents an overlapping pattern of expression with TGF?2 in joint and tendon blastemas of the embryonic digits. Furthermore, Decorin expression is induced by TGF? signaling, and DECORIN promotes aggregation of digit mesenchymal cell precursors. In addition, we provide gene expression studies suggesting that Cadherin-11 may function as an effector of Decorin in this experimental model. PMID:24769017

Lorda-Diez, Carlos I; García-Porrero, Juan A; Hurlé, Juan M; Montero, Juan A

2014-05-01

199

The muscular force transmission system: role of the intramuscular connective tissue.  

PubMed

The objective of this review is to analyze in detail the microscopic structure and relations among muscular fibers, endomysium, perimysium, epimysium and deep fasciae. In particular, the multilayer organization and the collagen fiber orientation of these elements are reported. The endomysium, perimysium, epimysium and deep fasciae have not just a role of containment, limiting the expansion of the muscle with the disposition in concentric layers of the collagen tissue, but are fundamental elements for the transmission of muscular force, each one with a specific role. From this review it appears that the muscular fibers should not be studied as isolated elements, but as a complex inseparable from their fibrous components. The force expressed by a muscle depends not only on its anatomical structure, but also the angle at which its fibers are attached to the intramuscular connective tissue and the relation with the epimysium and deep fasciae. PMID:23294690

Turrina, Andrea; Martínez-González, Miguel Antonio; Stecco, Carla

2013-01-01

200

Progranulin antibodies in autoimmune diseases.  

PubMed

Systemic vasculitides constitute a heterogeneous group of diseases. Autoimmunity mediated by B lymphocytes and their humoral effector mechanisms play a major role in ANCA-associated vasculitis (AAV) as well as in non-ANCA associated primary systemic vasculitides and in the different types of autoimmune connective tissue disorders and rheumatoid arthritis. In order to detect autoantibodies in systemic vasculitides, we screened protein macroarrays of human cDNA expression libraries with sera from patients with ANCA-associated and ANCA-negative primary systemic vasculitides. This approach led to the identification of antibodies against progranulin, a 88 kDA secreted glycoprotein with strong anti-inflammatory activity in the course of disease of giant-cell arteritis/polymyalgia rheumatica (14/65), Takayasu's arteritis (4/13), classical panarteritis nodosa (4/10), Behcet's disease (2/6) and in the course of disease in granulomatosis with polyangiitis (31/75), Churg-Strauss syndrome (7/23) and in microscopic polyangiitis (7/19). In extended screenings the progranulin antibodies were also detected in other autoimmune diseases such as systemic lupus erythematosus (39/91) and rheumatoid arthritis (16/44). Progranulin antibodies were detected only in 1 of 97 healthy controls. Anti-progranulin positive patients with systemic vasculitides, systemic lupus erythematosus or rheumatoid arthritis had significant lower progranulin plasma levels, indicating a neutralizing effect. In light of the anti-inflammatory effects of progranulin, progranulin antibodies might exert pro-inflammatory effects thus contributing to the pathogenesis of the respective autoimmune diseases and might serve as a marker for disease activity. This hypothesis is supported by the fact that a positive progranulin antibody status was associated with active disease in granulomatosis with polyangiitis. PMID:23149338

Thurner, Lorenz; Preuss, Klaus-Dieter; Fadle, Natalie; Regitz, Evi; Klemm, Philipp; Zaks, Marina; Kemele, Maria; Hasenfus, Andrea; Csernok, Elena; Gross, Wolfgang L; Pasquali, Jean-Louis; Martin, Thierry; Bohle, Rainer Maria; Pfreundschuh, Michael

2013-05-01

201

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

PubMed

Life-long regular endurance exercise is known to counteract the deterioration of cardiovascular and metabolic function and overall mortality. Yet it remains unknown if life-long regular endurance exercise can influence the connective tissue accumulation of advanced glycation endproducts (AGEs) that is associated with aging and lifestyle-related diseases. We therefore examined two groups of healthy elderly men: 15 master athletes (64?±?4 years) who had been engaged in life-long endurance running and 12 old untrained (66?±?4 years) together with two groups of healthy young men; ten young athletes matched for running distance (26?±?4 years), and 12 young untrained (24?±?3 years). AGE cross-links (pentosidine) of the patellar tendon were measured biochemically, and in the skin, it was assessed by a fluorometric method. In addition, we determined mechanical properties and microstructure of the patellar tendon. Life-long regular endurance runners (master athletes) had a 21 % lower AGE cross-link density compared to old untrained. Furthermore, both master athletes and young athletes displayed a thicker patellar tendon. These cross-sectional data suggest that life-long regular endurance running can partly counteract the aging process in connective tissue by reducing age-related accumulation of AGEs. This may not only benefit skin and tendon but also other long-lived protein tissues in the body. Furthermore, it appears that endurance running yields tendon tissue hypertrophy that may serve to lower the stress on the tendon and thereby reduce the risk of injury. PMID:24997017

Couppé, Christian; Svensson, René B; Grosset, Jean-Francois; Kovanen, Vuokko; Nielsen, Rie H; Olsen, Morten R; Larsen, Jytte O; Praet, Stephan F E; Skovgaard, Dorthe; Hansen, Mette; Aagaard, Per; Kjaer, Michael; Magnusson, S Peter

2014-08-01

202

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

PubMed

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

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

2012-07-01

203

Targeted Ablation of the Abcc6 Gene Results in Ectopic Mineralization of Connective Tissues  

PubMed Central

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

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

2005-01-01

204

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.

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

205

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

206

Gender and Ocular Manifestations of Connective Tissue Diseases and Systemic Vasculitides  

PubMed Central

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

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

2014-01-01

207

[The influence of paracetamol on the parameters of connective tissue metabolism during experimental osteoarthrosis].  

PubMed

We present results of the biochemical investigation of changes in the metabolism and accumulation of articular cartilage matrix macromolecules and the inflammatory tests in experimental animals with corticosteroidal dystrophy of connective tissues after the therapy by paracetamol in low doses, which corresponded to a standard mean therapeutic dose MTD= 40 mg/kg, 1/2 MTD = 20 mg/kg, 1/4 MTD = 10 mg/kg, and 1/8 MTD = 5 mg/kg, in comparison to the effect of glucosamine hydrochloride treatment in a dose of 50 mg/kg. It is established that paracetamol in low doses exhibits a moderate chondroprotective effect and stimulates the articular cartilage reparative regeneration under conditions of corticostereoidal dystrophy of connective tissues. The most pronounced chondroprotective effect of paracetamol was observed in doses of 1/4 MTD and 1/8 MTD (10 and 5 mg/kg, respectively), but not in the case of MTD. At the same time, the antiinflammatory properties of paracetamol in all doses were insufficiently pronounced. PMID:19928578

Tuliakov, V A; Zupanets, I A

2009-01-01

208

Functional Connectivity in Islets of Langerhans from Mouse Pancreas Tissue Slices  

PubMed Central

We propose a network representation of electrically coupled beta cells in islets of Langerhans. Beta cells are functionally connected on the basis of correlations between calcium dynamics of individual cells, obtained by means of confocal laser-scanning calcium imaging in islets from acute mouse pancreas tissue slices. Obtained functional networks are analyzed in the light of known structural and physiological properties of islets. Focusing on the temporal evolution of the network under stimulation with glucose, we show that the dynamics are more correlated under stimulation than under non-stimulated conditions and that the highest overall correlation, largely independent of Euclidean distances between cells, is observed in the activation and deactivation phases when cells are driven by the external stimulus. Moreover, we find that the range of interactions in networks during activity shows a clear dependence on the Euclidean distance, lending support to previous observations that beta cells are synchronized via calcium waves spreading throughout islets. Most interestingly, the functional connectivity patterns between beta cells exhibit small-world properties, suggesting that beta cells do not form a homogeneous geometric network but are connected in a functionally more efficient way. Presented results provide support for the existing knowledge of beta cell physiology from a network perspective and shed important new light on the functional organization of beta cell syncitia whose structural topology is probably not as trivial as believed so far.

Stozer, Andraz; Gosak, Marko; Dolensek, Jurij; Perc, Matjaz; Marhl, Marko; Rupnik, Marjan Slak; Korosak, Dean

2013-01-01

209

Regulation of Connective Tissue Growth Factor Gene Expression and Fibrosis in Human Heart Failure  

PubMed Central

Background Heart failure (HF) is associated with excessive extracellular matrix (ECM) deposition and abnormal ECM degradation leading to cardiac fibrosis. Connective Tissue Growth Factor (CTGF) modulates ECM production during inflammatory tissue injury, but available data on CTGF gene expression in failing human heart and its response to mechanical unloading are limited. Methods and Results LV tissue from patients undergoing cardiac transplantation for ischemic (ICM; n=20) and dilated (DCM; n=20) cardiomyopathies, and from nonfailing (NF; n=20) donor hearts were examined. Paired samples (n=15) from patients undergoing LV assist device (LVAD) implantation as “bridge to transplant” (34-1145 days) were also analyzed. There was more interstitial fibrosis in both ICM and DCM compared to NF hearts. Hydroxyproline concentration was also significantly increased in DCM relative to NF samples. The expression of CTGF,TGFB1, COL1-A1, COL3-A1, MMP2 and MMP9 mRNAs in ICM and DCM were also significantly elevated as compared to NF controls. Although TGFB1, CTGF, COL1-A1, and COL3-A1 mRNA levels were reduced by unloading, there was only a modest reduction in tissue fibrosis and no difference in protein-bound hydroxyproline concentration between pre- and post-LVAD tissue samples. The persistent fibrosis may be related to a concomitant reduction in MMP9 mRNA and protein levels following unloading. Conclusions CTGF may be a key regulator of fibrosis during maladaptive remodeling and progression to HF. Although mechanical unloading normalizes most genotypic and functional abnormalities, its effect on ECM remodeling during HF is incomplete.

Koshman, Yevgeniya E.; Patel, Nilamkumar; Chu, Miensheng; Iyengar, Rekha; Kim, Taehoon; Ersahin, Cagatay; Lewis, William; Heroux, Alain; Samarel, Allen M.

2013-01-01

210

CCN2 (Connective Tissue Growth Factor) Promotes Fibroblast Adhesion to Fibronectin  

PubMed Central

In vivo, CCN2 (connective tissue growth factor) promotes angiogenesis, osteogenesis, tissue repair, and fibrosis, through largely unknown mechanisms. In vitro, CCN2 promotes cell adhesion in a variety of systems via integrins and heparin sulfate proteoglycans (HSPGs). However, the physiological relevance of CCN2-mediated cell adhesion is unknown. Here, we find that HSPGs and the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase cascade are required for adult human dermal fibroblasts to adhere to CCN2. Endogenous CCN2 directly binds fibronectin and the fibronectin receptors integrins ?4 ?1 and ?5 and syndecan 4. Using Ccn2-/- mouse embryonic fibroblasts, we show that loss of endogenous CCN2 results in impaired spreading on fibronectin, delayed ?-smooth muscle actin stress fiber formation, and reduced ERK and focal adhesion kinase phosphorylation. These results suggest that a physiological role of CCN2 is to potentiate the ability of fibroblasts to spread on fibronectin, which may be important in modulating fibroblast adhesion to the provisional matrix during tissue development and wound healing. These results are consistent with the notion that a principal function of CCN2 is to modulate receptor/ligand interactions in vivo.

Chen, Yunliang; Abraham, David J.; Shi-wen, Xu; Pearson, Jeremy D.; Black, Carol M.; Lyons, Karen M.; Leask, Andrew

2004-01-01

211

Photobleaching as a tool to measure the local strain field in fibrous membranes of connective tissues.  

PubMed

Connective tissues are complex structures which contain collagen and elastin fibers. These fiber-based structures have a great influence on material mechanical properties and need to be studied at the microscopic scale. Several microscopy techniques have been developed in order to image such microstructures; among them are two-photon excited fluorescence microscopy and second harmonic generation. These observations have been coupled with mechanical characterization to link microstructural kinematics to macroscopic material parameter evolution. In this study, we present a new approach to measure local strain in soft biological tissues using a side-effect of fluorescence microscopy: photobleaching. Controlling the loss of fluorescence induced by photobleaching, we create a pattern on our sample that we can monitor during mechanical loading. The image analysis allows three-dimensional displacements of the patterns at various loading levels to be computed. Then, local strain distribution is derived using the finite element discretization on a four-node element mesh created from our photobleached pattern. Photobleaching tests on a human liver capsule have revealed that this technique is non-destructive and does not have any impact on mechanical properties. This method is likely to have other applications in biological material studies, considering that all collagen-elastin fiber-based biological tissues possess autofluorescence properties and thus can be photobleached. PMID:24568925

Jayyosi, C; Fargier, G; Coret, M; Bruyčre-Garnier, K

2014-06-01

212

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

PubMed Central

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

2012-01-01

213

Epidermal nuclear immunoglobulin deposits in some connective tissue diseases: correlation with ENA antibodies.  

PubMed Central

In-vivo nuclear deposits of IgG were demonstrated by direct immunofluorescence in epidermal cells of normal skin from 6 patients with serum antibodies to an RNase-sensitive extractable nuclear antigen (ENA). Addition of complement to the skin sections showed that C3 could bind to epidermal cells with IgG deposits. A skin biopsy from a patient with polymyositis and serum antibodies to ENA, but without nuclear IgG deposits, showed nuclear binding of C3 after addition of complement to the skin sections. The clinical diagnoses of patients with immunofluorescent staining of epidermal cells were mixed connective tissue disease (MCTD) 4 cases, systemic lupus erythematosus (SLE) 2 cases, and polymyositis 1 case. No epidermal nuclear IgG deposits could be demonstrated in 5 cases of SLE, 2 cases of MCTD, one case of polymyositis, or 15 cases of rheumatoid arthritis without antibodies to ENA. Images

Andersen, I; Andersen, P; Elling, P; Graudal, H

1983-01-01

214

Spontaneous Esophageal Perforation in a Patient with Mixed Connective Tissue Disease  

PubMed Central

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

Lyman, David

2011-01-01

215

The connective tissue component of the caprine arthritis-encephalitis syndrome.  

PubMed Central

The gross and microscopic connective tissue lesions in 12 goats with caprine arthritis-encephalitis (CAE) are described, including those from which a virus (CAEV) was isolated. Lesions were most often associated with synovial-lined structures including joints, tendon sheaths, and bursae, and were typified by synovial cell proliferations, subsynovial mononuclear cell infiltration, the presence of fibrin, fibrinous concretions, necrosis, and mineralization. Extrasynovial lesions were located in kidneys, vessels, and brain. The inflammatory infiltrates in these organs were predominantly mononuclear. Amyloid was also found in liver, spleen, and kidney. Microbiologic techniques failed to demonstrate any bacteria, mycoplasma, or chlamydia in the lesions. Images Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 1 Figure 2 Figure 3 Figure 4

Crawford, T. B.; Adams, D. S.; Sande, R. D.; Gorham, J. R.; Henson, J. B.

1980-01-01

216

Antinuclear antibodies and their detection methods in diagnosis of connective tissue diseases: a journey revisited  

PubMed Central

It has been more than 50 years since antinuclear antibodies were first discovered and found to be associated with connective tissue diseases. Since then different methods have been described and used for their detection or confirmation. For many decades immunofluorescent antinuclear antibody test has been the "gold standard" in the diagnosis of these disorders. However to increase the sensitivity and specificity of antinuclear antibody detection further approaches were explored. Today a battery of newer techniques are available some of which are now considered better and are competing with the older methods. This article provides an overview on advancement in antinuclear antibody detection methods, their future prospects, advantages, disadvantages and guidelines for use of these tests.

Kumar, Yashwant; Bhatia, Alka; Minz, Ranjana Walker

2009-01-01

217

Successful treatment with tacrolimus in a case of lung-dominant connective tissue disease.  

PubMed

A 49-year-old man with dyspnea was found to have reticular opacities and ground-glass attenuation with traction bronchiectasis or bronchiolectasis on computed tomography. The patient met the criteria for lung-dominant connective tissue disease (LD-CTD) and histopathologically exhibited a chronic fibrotic interstitial pneumonia illustrating framework of a usual interstitial pneumonia-like pattern. Due to worsening of the disease, therapy was initiated with corticosteroids in combination with cyclosporine A. However, treatment with these drugs was ineffective. Pirfenidone and intravenous cyclophosphamide therapy also proved ineffective. The cyclosporine A was therefore switched to tacrolimus, and the patient's disease improved, allowing for a reduction in the dose of the corticosteroids. Our experience in this case suggests that treatment with tacrolimus might be useful for treating refractory LD-CTD even when histopathologically chronic fibrotic interstitial pneumonia is evident. PMID:23448773

Okamoto, Masaki; Fujimoto, Kiminori; Nakamura, Masayuki; Yoshida, Tsukasa; Idemoto, Akiko; Kitasato, Yasuhiko; Kawayama, Tomotaka; Fukuoka, Junya; Ichiki, Masao; Hoshino, Tomoaki

2013-01-01

218

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

219

Ceramide inhibits connective tissue growth factor expression by human retinal pigment epithelial cells.  

PubMed

Connective tissue growth factor (CTGF) is known to be involved in retinal fibrotic disorders. We used human retinal pigment epithelial cells (HRPE), which play critical roles in retinal fibrosis, to examine the expression of CTGF and its regulation by ceramide and TGF-?. Real-time PCR analysis showed downregulation of CTGF mRNA by C2 ceramide and upregulation by TGF-?. C2 ceramide also inhibited constitutive and TGF-?-enhanced CTGF secretion by HRPE cells. Predominant secretion (>80% of total) of CTGF from the apical side was observed in highly polarized HRPE cells. Fumonosin, an inhibitor of ceramide synthesis, stimulated CTGF secretion while 4HPR, an activator of ceramide synthesis, downregulated CTGF secretion. Based on these results demonstrating ceramide regulation of CTGF secretion by HRPE, we suggest that ceramide may have therapeutic potential for the treatment of retinal fibrotic diseases by inhibiting CTGF production. PMID:24758915

Sonoda, Shozo; Nagineni, Chandrasekharam N; Kitamura, Mizuki; Spee, Christine; Kannan, Ram; Hinton, David R

2014-08-01

220

Developmental Changes in the Connective Tissues of the Porcine Recurrent Laryngeal Nerve  

PubMed Central

The recurrent laryngeal nerve (RLN) branches from the vagus cranial nerve to innervate structures important for voicing and swallowing. Damage to this nerve, commonly associated with surgery or idiopathic etiologies that largely occur with aging, results in impaired voicing and swallowing. Sunderland proposed a model of peripheral nerve damage whereby a nerve’s ability to resist damage from stretch and compression is determined by the quantity and composition of its epineurial connective tissues. Thus, it would be expected that epineurium differs depending upon the forces imposed on a nerve within its anatomical setting. The purpose of this study was to investigate RLN epineurium quantity and composition with development. A porcine model (piglet vs. juvenile) was used because of the similarity between porcine and human laryngeal innervation, anatomy, and function. The entire RLN was excised bilaterally, and stereological methods were used to quantify the composition of epineurial connective tissues. Compared to the piglet, the juvenile pig RLN was double in diameter. While the piglet had no differences in the percent of epineurial collagen and adipose between proximal and distal segments of both sides of the RLN, the juvenile pig had a greater percent of collagen in the proximal segment of both sides of the RLN and a greater percent of adipose in the distal segment of the left RLN compared to the proximal segment. In addition, unlike the piglet, the juvenile pig had a greater number of fascicles in the proximal than distal segment of the RLN, regardless of nerve side. These findings are consistent with predicted patterns associated with the different anatomical settings of the left and right RLN, show that the RLN changes with age, and support Sunderland’s model.

Campbell, Ellen O.; Samlan, Robin A.; McMullen, Nathaniel T.; Cook, Sarah; Smiley-Jewell, Suzette; Barkmeier-Kraemer, Julie

2013-01-01

221

Human histologic evaluation of root coverage obtained with connective tissue graft over a compomer restoration.  

PubMed

This investigation was designed to evaluate the histologic healing pattern of two Miller Class III recession defects associated with noncarious cervical lesions (NCCLs) treated with a connective tissue graft (CTG) and coronally advance flap (CAF). One patient presenting with two teeth predetermined to be surgically extracted was enrolled and consented to treatment. One month after phase I treatment, a full-thickness flap was reflected and the NCCLs treated with a compomer restoration; at the same time, a CTG was harvested from the palate and positioned over the compomer restoration. The flap was then coronally repositioned. After 4 months of healing, an en bloc biopsy extraction of the two teeth was executed. The teeth were analyzed histologically to assess the periodontal wound healing. A long junctional epithelial attachment was noted throughout the major portion of the restored surface. Only minimal signs of connective adhesion and new bone formation could be seen in the apical portion of the restored area, without signs of root resorption or ankylosis. This report provides evidence that the presence of a compomer restoration allowed the formation of a long juctional epithelium after CTG and CAF treatment. PMID:24396839

Comuzzi, Luca; Mazzocco, Fabio; Stefani, Riccardo; Gobbato, Luca; Fornea, Edoardo; Stellini, Edoardo; Iezzi, Giovanna; Piattelli, Adriano

2014-01-01

222

[Autoimmune hepatitis and autoimmune cholangitis].  

PubMed

Autoimmune liver diseases encompass autoimmune hepatitis, primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) as lesions of the biliary tract. The term autoimmune cholangitis has not been generally accepted, so it remains an entitiy waiting for precise definition. AIH is a chronic progressive necroinflammatory liver disease mostly occuring in female individuals and leading to ultimate autodestruction of the liver if not treated. Histopathology of the liver reflects the gerneral understanding of the underlying immune especially self reactive CD4 + T-helper cells mediated mechanisms in destruction of liver cells displaying a typical but by no means pathognomonic histopathological pattern. Since there are no specific and generally valid tests the diagnosis should be confirmed by a scoring system including histopathology. Variants of autoimmune hepatitis cover seronegative cases, acute onset autoimmune hepatitis and autoimmune hepatitis with centrilobular necrosis. Differential diagnosis of autoimmune hepatitis includes drug induced chronic hepatitis that may mimick autoimmune hepatitis by clinical course and serology. Histopathology may give helpful hints for the correct diagnosis. Autoimmune lesions of the biliary tract are PBC in the first line. The target antigen of the autoimmune response has been identified, natural history of the diseases is well known and histopathology is pathognomonic in about a third of the cases. In clinical practice liver biopsy is taken to exclude other etiologies when AMA is present in the serum, staging the disease at first diagnosis and to establish diagnosis in cases of AMA negativity. The autoimmune nature of PSC has been discussed in the literature ever since the first description and the answer in not settled yet. Histopathology is relevant for the diagnosis in excluding other etiologies and confirming the diagnosis of small duct PSC. The term autoimmune cholangitis has been used to designate AMA-negative PBC, however, based on research experience and the clinical data it should be reserved to the overlap syndrome of AIH and PSC in children that seem to make up a disease entitiy of its own. PMID:18035685

Dienes, H P

2005-01-01

223

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

224

Elevated aqueous humour tissue inhibitor of matrix metalloproteinase-1 and connective tissue growth factor in pseudoexfoliation syndrome  

PubMed Central

Background/aims: Pseudoexfoliation syndrome (PXF) was recently found to be associated with increased expression of transforming growth factor ?1 (TGF?1) in the aqueous humour. As concern has been raised regarding anti-TGF? therapy, which can potentially disrupt the maintenance of anterior chamber asso-ciated immune deviation, the authors explored the levels of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9), and connective tissue growth factor (CTGF) in aqueous humour to determine if these may represent alternative therapeutic targets. Methods: Aqueous humour samples were collected from patients who underwent routine cataract surgery. All patients were categorised into three main groups—PXF, uveitis, and control. The PXF group was further subcategorised into three grades based on the density of the exfoliative material observed on biomicroscopy, as well as the presence or absence of glaucoma. TIMP-1, MMP-9, and CTGF levels were measured using specific enzyme immunoassays (ELISA). Results: Eyes with PXF had significantly higher aqueous humour TIMP-1 concentration (n?=?56, mean (SE), 9.76 (1.10) ng/ml) compared with controls (n?=?112, 5.73 (0.43) ng/ml, p<0.01). Similarly, the CTGF level in PXF eyes (n?=?36, 4.38 (0.65) ng/ml) was higher than controls (n?=?29, 2.35 (0.46) ng/ml, p<0.05). Further, the CTGF concentration in the PXF glaucoma group is significantly higher compared with PXF eyes without glaucoma (6.03 (1.09) ng/ml v 2.73 (0.45) ng/ml, p<0.01). The MMP-9 levels were low and below detection limit in all PXF and control samples with no statistical difference between groups. Conclusion: A raised TIMP-1 level and a low MMP-9 level in aqueous humour of PXF eyes may imply a downregulation in proteolytic activity. The increased CTGF concentration supports the proposed fibrotic pathology of PXF. Regulation of MMP/TIMP expression and anti-CTGF therapy may offer potential therapeutic avenues for controlling PXF associated ocular morbidity.

Ho, S L; Dogar, G F; Wang, J; Crean, J; Wu, Q D; Oliver, N; Weitz, S; Murray, A; Cleary, P E; O'Brien, C

2005-01-01

225

Characterizing the mechanical contribution of fiber angular distribution in connective tissue: comparison of two modeling approaches  

PubMed Central

Modeling of connective tissues often includes collagen fibers explicitly as one of the components. These fibers can be oriented in many directions; therefore, several studies have considered statistical distributions to describe the fiber arrangement. One approach to formulate a constitutive framework for distributed fibers is to express the mechanical parameters, such as strain energy and stresses, in terms of angular integrals. These integrals represent the addition of the contribution of infinitesimal fractions of fibers oriented in a given direction. This approach leads to accurate results; however, it requires lengthy calculations. Recently, the use of generalized structure tensors has been proposed to represent the angular distribution in the constitutive equations of the fibers. Although this formulation is much simpler and fewer calculations are required, such structure tensors can only be used when all the fibers are in tension and the angular distribution is small. However, the amount of error introduced in these cases of non-tensile fiber loading and large angular distributions have not been quantified. Therefore, the objective of this study is to determine the range of values of angular distribution for which acceptable differences (less than 10%) between these two formulations are obtained. It was found, analytically and numerically, that both formulations are equivalent for planar distributions under equal-biaxial stretch. The comparison also showed, for other loading conditions, that the differences decrease when the fiber distribution is very small. Differences of less than 10% were usually obtained when the fiber distribution was very low (? ? 0.03; ? ranges between 0 and 1/3, for aligned and isotropic distributed fibers, respectively). This range of angular distribution greatly limits the types of tissue that can be accurately analyzed using generalized structure tensors. It is expected that the results from this study guide the selection of a proper approach to analyze a particular tissue under a particular loading condition.

Cortes, Daniel H.; Lake, Spencer P.; Kadlowec, Jennifer A.; Soslowsky, Louis J.

2010-01-01

226

Dynamic vibration cooperates with connective tissue growth factor to modulate stem cell behaviors.  

PubMed

Vocal fold disorders affect 3-9% of the U.S. population. Tissue engineering offers an alternative strategy for vocal fold repair. Successful engineering of vocal fold tissues requires a strategic combination of therapeutic cells, biomimetic scaffolds, and physiologically relevant mechanical and biochemical factors. Specifically, we aim to create a vocal fold-like microenvironment to coax stem cells to adopt the phenotype of vocal fold fibroblasts (VFFs). Herein, high frequency vibratory stimulations and soluble connective tissue growth factor (CTGF) were sequentially introduced to mesenchymal stem cells (MSCs) cultured on a poly(?-caprolactone) (PCL)-derived microfibrous scaffold for a total of 6 days. The initial 3-day vibratory culture resulted in an increased production of hyaluronic acids (HA), tenascin-C (TNC), decorin (DCN), and matrix metalloproteinase-1 (MMP1). The subsequent 3-day CTGF treatment further enhanced the cellular production of TNC and DCN, whereas CTGF treatment alone without the vibratory preconditioning significantly promoted the synthesis of collagen I (Col 1) and sulfated glycosaminoglycans (sGAGs). The highest level of MMP1, TNC, Col III, and DCN production was found for cells being exposed to the combined vibration and CTGF treatment. Noteworthy, the vibration and CTGF elicited a differential stimulatory effect on elastin (ELN), HA synthase 1 (HAS1), and fibroblast-specific protein-1 (FSP-1). The mitogenic activity of CTGF was only elicited in naďve cells without the vibratory preconditioning. The combined treatment had profound, but opposite effects on mitogen-activated protein kinase (MAPK) pathways, Erk1/2 and p38, and the Erk1/2 pathway was critical for the observed mechano-biochemical responses. Collectively, vibratory stresses and CTGF signals cooperatively coaxed MSCs toward a VFF-like phenotype and accelerated the synthesis and remodeling of vocal fold matrices. PMID:24456068

Tong, Zhixiang; Zerdoum, Aidan B; Duncan, Randall L; Jia, Xinqiao

2014-07-01

227

Autoimmune Diseases  

MedlinePLUS

... of the body. No one is sure what causes autoimmune diseases. They do tend to run in families. Women - ... a low fever. The classic sign of an autoimmune disease is inflammation, which can cause redness, heat, pain and swelling. The diseases may ...

228

Assessment of T Regulatory Cells and Expanded Profiling of Autoantibodies May Offer Novel Biomarkers for the Clinical Management of Systemic Sclerosis and Undifferentiated Connective Tissue Disease  

PubMed Central

In order to identify disease biomarkers for the clinical and therapeutic management of autoimmune diseases such as systemic sclerosis (SSc) and undifferentiated connective tissue disease (UCTD), we have explored the setting of peripheral T regulatory (T reg) cells and assessed an expanded profile of autoantibodies in patients with SSc, including either limited (lcSSc) or diffuse (dcSSc) disease, and in patients presenting with clinical signs and symptoms of UCTD. A large panel of serum antibodies directed towards nuclear, nucleolar, and cytoplasmic antigens, including well-recognized molecules as well as less frequently tested antigens, was assessed in order to determine whether different antibody profiles might be associated with distinct clinical settings. Beside the well-recognized association between lcSSc and anti-centromeric or dcSSC and anti-topoisomerase-I antibodies, we found a significative association between dcSSc and anti-SRP or anti-PL-7/12 antibodies. In addition, two distinct groups emerged on the basis of anti-RNP or anti-PM-Scl 75/100 antibody production among UCTD patients. The levels of T reg cells were significantly lower in patients with SSc as compared to patients with UCTD or to healthy controls; in patients with lcSSc, T reg cells were inversely correlated to disease duration, suggesting that their levels may represent a marker of disease progression.

Cordiali-Fei, Paola; Mussi, Anna; D'Agosto, Giovanna; Trento, Elisabetta; Bordignon, Valentina; Trincone, Silvana; Vento, Antonella; Sperduti, Isabella; Cristaudo, Antonio; Ensoli, Fabrizio

2013-01-01

229

Telomere Dysfunction, Autoimmunity and Aging  

PubMed Central

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

Hohensinner, Philipp J.; Goronzy, Jorg J.; Weyand, Cornelia M.

2011-01-01

230

Interproximal Papillae Reconstruction around Implant Using Subepithelial Connective Tissue Graft in Maxillary Anterior Region: A Case Series  

PubMed Central

ABSTRACT Objectives The present study was undertaken to evaluate the effectiveness of interproximal papillae reconstruction around early loaded single implant using subepithelial connective tissue graft in maxillary anterior region. Material and Methods Ten systemically healthy patients (mean age = 29.3 [SD 7.9] years) in need of dental implants in maxillary anterior region were included in the study. Interproximal papillae reconstruction around single implant using subepithelial connective tissue graft was applied. The donor palatal tissue was harvested by a "trap door approach". Subepithelial connective tissue graft was inserted in the pouch created on mesial and distal site of implant. Clinical and radiographic parameters were recorded around the each implant, including papillary height and papillary gingival contour, at baseline, 3 and 6 months after operation. Results The mesial papilla height was increased by 1.9 (SD 0.87) mm, P = 0.005 at 3 month and maintained at 1.5 (SD 0.97) mm, P = 0.007 at 6 months. The distal papilla height was increased by 2 (SD 0.66) mm, P = 0.004 at 3 month and maintained at 1.2 (SD 0.78) mm, P = 0.010 at 6 months. Assessment of papilla contour index showed 90% aesthetic success both for mesial and distal papilla at 6 months. Conclusions It can be concluded that subepithelial connective tissue graft may be used to successfully augment the gingival papillae adjacent to single tooth implant restoration.

Gupta, Satish; Williams, Cecil

2012-01-01

231

Characterization of Connective Tissue Disease-Associated Pulmonary Arterial Hypertension From REVEAL  

PubMed Central

Background: REVEAL (the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management) is the largest US cohort of patients with pulmonary arterial hypertension (PAH) confirmed by right-sided heart catheterization (RHC), providing a more comprehensive subgroup characterization than previously possible. We used REVEAL to analyze the clinical features of patients with connective tissue disease-associated PAH (CTD-APAH). Methods: All newly and previously diagnosed patients with World Health Organization (WHO) group 1 PAH meeting RHC criteria at 54 US centers were consecutively enrolled. Cross-sectional and 1-year mortality and hospitalization analyses from time of enrollment compared CTD-APAH to idiopathic disease and systemic sclerosis (SSc) to systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), and rheumatoid arthritis (RA). Results: Compared with patients with idiopathic disease (n = 1,251), patients with CTD-APAH (n = 641) had better hemodynamics and favorable right ventricular echocardiographic findings but a higher prevalence of pericardial effusions, lower 6-min walk distance (300.5 ± 118.0 vs 329.4 ± 134.7 m, P = .01), higher B-type natriuretic peptide (BNP) levels (432.8 ± 789.1 vs 245.6 ± 427.2 pg/mL, P < .0001), and lower diffusing capacity of carbon monoxide (Dlco) (44.9% ± 18.0% vs 63.6% ± 22.1% predicted, P < .0001). One-year survival and freedom from hospitalization were lower in the CTD-APAH group (86% vs 93%, P < .0001; 67% vs 73%, P = .03). Compared with patients with SSc-APAH (n = 399), those with other CTDs (SLE, n = 110; MCTD, n = 52; RA, n = 28) had similar hemodynamics; however, patients with SSc-APAH had the highest BNP levels (552.2 ± 977.8 pg/mL), lowest Dlco (41.2% ± 16.3% predicted), and poorest 1-year survival (82% vs 94% in SLE-APAH, 88% in MCTD-APAH, and 96% in RA-APAH). Conclusions: Patients with SSc-APAH demonstrate a unique phenotype with the highest BNP levels, lowest Dlco, and poorest survival of all CTD-APAH subgroups. Trial registry: ClinicalTrials.gov; No.: NCT00370214; URL: clinicaltrials.gov

Liu, Juliana; Parsons, Lori; Hassoun, Paul M.; McGoon, Michael; Badesch, David B.; Miller, Dave P.; Nicolls, Mark R.; Zamanian, Roham T.

2010-01-01

232

Changes in the activity of connective tissue matrix enzymes in the metabolic syndrome  

PubMed Central

Introduction Early atherosclerotic changes in the endothelium associated with metabolic syndrome are generated with the participation of inflammatory cells, cytokines and enzymes of the extracellular matrix. The study is aimed at a comparison between the activity of inflammatory agents, tumour necrosis factor ? (TNF-?) and the enzymes of the connective tissue matrix in the blood of healthy female patients as well as those suffering from the metabolic syndrome. Material and methods The examination included 35 women with metabolic syndrome (MS). The control group (C) comprised 35 healthy women. Lipidogram, C-reactive protein level (CRP), fasting glucose level (FGL), matrix metalloproteinase (MMP)-8 and -9 activity, tissue inhibitor of metalloproteinase-1 (TIMP-1) and TNF-? levels in blood were determined. Results As compared with the control group, the level of inflammatory factors and the activity of extracellular matrix enzymes in the metabolic syndrome were statistically higher (p < 0.05) and concerned the following parameters: TNF-? (pg/ml): MS 6.59 ±3.18, C 4.78 ±2.91; CRP (mg/dl): MS 2.18 ±2.04, C 1,26 ±1.35; TIMP-1 (ng/ml): MS 265.5 ±2.9, C 205.4 ±72.6; MMP-9 (ng/ml): MS 198.2 ±138.6, C 138.6 ±116.1. Statistically significant correlations were also found between TIMP-1 and the following factors: BMI (R = 0.400, p < 0.001), waist/hip ratio (WHR) (R = 0.278, p < 0.05), waistline (R = 0.417, p < 0.001), FGL (R = 0.290, p < 0.05), HDL cholesterol (R = –0.253, p < 0.05) and triglycerides (R = 0.269, p < 0.05).There were positive correlations of MMP-9 with FGL (R = 0.446, p < 0.001) and waistline (R = 0.260, p < 0.05); MMP-8 with FGL (R = 0.308, p < 0.05); and CRP with BMI (R = 0.370, p < 0.01), WHR (R = 0.325, p < 0.01) and waistline (R = 0.368, p < 0.01). Conclusions Metabolic syndrome is connected with higher activity of cytokines (TNF-?), inflammatory markers (CRP) and matrix enzymes (MMP-9, MMP-8, TIMP-1).

Mieczkowska, Jolanta; Mosiewicz, Jerzy; Barud, Wojciech; Kwasniewski, Wojciech

2011-01-01

233

Connective tissue growth factor causes EMT-like cell fate changes in vivo and in vitro  

PubMed Central

Summary Connective tissue growth factor (CTGF) plays an important role in the pathogenesis of chronic fibrotic diseases. However, the mechanism by which paracrine effects of CTGF control the cell fate of neighboring epithelial cells is not known. In this study, we investigated the paracrine effects of CTGF overexpressed in fibroblasts of Col1a2-CTGF transgenic mice on epithelial cells of skin and lung. The skin and lungs of Col1a2-CTGF transgenic mice were examined for phenotypic markers of epithelial activation and differentiation and stimulation of signal transduction pathways. In addition to an expansion of the dermal compartment in Col1a2-CTGF transgenic mice, the epidermis was characterized by focal hyperplasia, and basal cells stained positive for ?SMA, Snail, S100A4 and Sox9, indicating that these cells had undergone a change in their genetic program. Activation of phosphorylated p38 and phosphorylated Erk1/2 was observed in the granular and cornified layers of the skin. Lung fibrosis was associated with a marked increase in cells co-expressing epithelial and mesenchymal markers in the lesional and unaffected lung tissue of Col1a2-CTGF mice. In epithelial cells treated with TGF?, CTGF-specific siRNA-mediated knockdown suppressed Snail, Sox9, S100A4 protein levels and restored E-cadherin levels. Both adenoviral expression of CTGF in epithelial cells and treatment with recombinant CTGF induced EMT-like morphological changes and expression of ?-SMA. Our in vivo and in vitro data supports the notion that CTGF expression in mesenchymal cells in the skin and lungs can cause changes in the differentiation program of adjacent epithelial cells. We speculate that these changes might contribute to fibrogenesis.

Sonnylal, Sonali; Xu, Shiwen; Jones, Helen; Tam, Angela; Sreeram, Vivek R.; Ponticos, Markella; Norman, Jill; Agrawal, Pankaj; Abraham, David; de Crombrugghe, Benoit

2013-01-01

234

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.

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

2014-01-01

235

Connective tissue growth factor causes EMT-like cell fate changes in vivo and in vitro.  

PubMed

Connective tissue growth factor (CTGF) plays an important role in the pathogenesis of chronic fibrotic diseases. However, the mechanism by which paracrine effects of CTGF control the cell fate of neighboring epithelial cells is not known. In this study, we investigated the paracrine effects of CTGF overexpressed in fibroblasts of Col1a2-CTGF transgenic mice on epithelial cells of skin and lung. The skin and lungs of Col1a2-CTGF transgenic mice were examined for phenotypic markers of epithelial activation and differentiation and stimulation of signal transduction pathways. In addition to an expansion of the dermal compartment in Col1a2-CTGF transgenic mice, the epidermis was characterized by focal hyperplasia, and basal cells stained positive for ?SMA, Snail, S100A4 and Sox9, indicating that these cells had undergone a change in their genetic program. Activation of phosphorylated p38 and phosphorylated Erk1/2 was observed in the granular and cornified layers of the skin. Lung fibrosis was associated with a marked increase in cells co-expressing epithelial and mesenchymal markers in the lesional and unaffected lung tissue of Col1a2-CTGF mice. In epithelial cells treated with TGF?, CTGF-specific siRNA-mediated knockdown suppressed Snail, Sox9, S100A4 protein levels and restored E-cadherin levels. Both adenoviral expression of CTGF in epithelial cells and treatment with recombinant CTGF induced EMT-like morphological changes and expression of ?-SMA. Our in vivo and in vitro data supports the notion that CTGF expression in mesenchymal cells in the skin and lungs can cause changes in the differentiation program of adjacent epithelial cells. We speculate that these changes might contribute to fibrogenesis. PMID:23525012

Sonnylal, Sonali; Xu, Shiwen; Jones, Helen; Tam, Angela; Sreeram, Vivek R; Ponticos, Markella; Norman, Jill; Agrawal, Pankaj; Abraham, David; de Crombrugghe, Benoit

2013-05-15

236

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

PubMed

Connective tissue attachment to a mesh structure incorporated on the surface of oral implants and extra-oral endosseous craniofacial implants (EOECI) was investigated. Two types of implants were prepared: TI and TI-Mesh. TI was composed of an upper and a lower component, both comprised of a titanium cylinder, which could be connected using a titanium screw. The composition of the TIMesh was similar, but the lower cylinder had a lateral groove that was covered with a titanium mesh. In animal experiments performed using rat calvaria, the lower component was first implanted and was left submerged for 3 weeks, then the upper component was mounted percutaneously. After an additional 2 weeks, each implant and the surrounding tissues were harvested and evaluated. Histological observations revealed collagen fibers originating from surrounding hypodermal tissues anchored to the mesh structures of the TI-Mesh whereas no such collagen fibers were observed around TI. Significantly greater values of the attachment strength, the thickness of the dermal tissue, the thickness of hypodermal tissue, and the attachment lengths were observed in TI-Mesh than those of TI. Thus connective tissue attachment with collagen fibers anchored to the mesh was achieved by incorporating mesh structures into the percutaneously placed implants. PMID:24658962

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

2014-01-01

237

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

PubMed Central

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

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

2013-01-01

238

Silymarin decreases connective tissue growth factor to improve liver fibrosis in rats treated with carbon tetrachloride.  

PubMed

Silymarin is an herbal product showing potential as protection against hepatic disorders. In an attempt to develop the agent for the treatment of hepatic fibrosis, we screened the effects of silymarin on a rat model of hepatic fibrosis induced by carbon tetrachloride (CCl?). Intraperitoneal administration of CCl? to rats for 8?weeks not only increased the plasma levels of glutamic oxaloacetic transaminase (GOT) and glutamic pyruvic transaminase (GPT) but also induced a marked increase in the formation of hepatic fibrosis. Moreover, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were also reduced in the liver of rats treated with CCl?. Oral administration of silymarin (200?mg/kg, three times daily), in parallel, decreased the plasma levels of GOT and GPT. Furthermore, in addition to the improvement of hepatic fibrosis, the hepatic levels of hydroxyproline and connective tissue growth factor (CTGF) were both markedly decreased by silymarin. Silymarin also elevated the activities of SOD and GPx in liver isolated from CCl?-treated rats. The results suggest that oral administration of silymarin protects against CCl?-induced hepatic fibrosis in rats, likely due to the decrease in fibrotic parameters such as CTGF. PMID:22933420

Tzeng, Jann-Inn; Chen, Mei-Fen; Chung, Hsien-Hui; Cheng, Juei-Tang

2013-07-01

239

The Skeletal Site-Specific Role of Connective Tissue Growth Factor in Prenatal Osteogenesis  

PubMed Central

Background Connective tissue growth factor (CTGF/CCN2) is a matricellular protein that is highly expressed during bone development. Mice with global CTGF ablation (knockout, KO) have multiple skeletal dysmorphisms and perinatal lethality. A quantitative analysis of the bone phenotype has not been conducted. Results We demonstrated skeletal site-specific changes in growth plate organization, bone microarchitecture, and shape and gene expression levels in CTGF KO compared with wild-type mice. Growth plate malformations included reduced proliferation zone and increased hypertrophic zone lengths. Appendicular skeletal sites demonstrated decreased metaphyseal trabecular bone, while having increased mid-diaphyseal bone and osteogenic expression markers. Axial skeletal analysis showed decreased bone in caudal vertebral bodies, mandibles, and parietal bones in CTGF KO mice, with decreased expression of osteogenic markers. Analysis of skull phenotypes demonstrated global and regional differences in CTGF KO skull shape resulting from allometric (size-based) and nonallometric shape changes. Localized differences in skull morphology included increased skull width and decreased skull length. Dysregulation of the transforming growth factor-?-CTGF axis coupled with unique morphologic traits provides a potential mechanistic explanation for the skull phenotype. Conclusions We present novel data on a skeletal phenotype in CTGF KO mice, in which ablation of CTGF causes site-specific aberrations in bone formation.

Lambi, Alex G.; Pankratz, Talia L.; Mundy, Christina; Gannon, Maureen; Barbe, Mary F.; Richtsmeier, Joan T.; Popoff, Steven N.

2013-01-01

240

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.

Fernandez Perez, 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

241

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

PubMed

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

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

2010-11-15

242

PLGA nanofiber-coated silk microfibrous scaffold for connective tissue engineering.  

PubMed

A modified degumming technique, involving boiling in 0.25% Na2CO3 with addition of 1% sodium dodecyl sulphate and intermittent ultrasonic agitation, was developed for knitted silk scaffolds. Sericin was efficiently removed, while mechanical and structural properties of native silk fibroin were preserved. Biocompatible and mechanically robust hybrid nano-microscaffolds were fabricated by coating these degummed silk scaffolds with an intervening adhesive layer of silk solution followed by electrospun poly-lactic-co-glycolic acid (PLGA) nanofibers. Cell proliferation on the hybrid silk scaffolds was improved by seeding cells on both surfaces of the flat scaffolds. Rolling up and continued culture of the cell-seeded hybrid scaffolds yielded cylindrical constructs that permitted cell proliferation, extracellular matrix deposition, and generated ligament/tendon graft analogs. Although PLGA-based hybrid scaffolds have earlier been proposed for dense connective tissue engineering, rapid biodegradation of PLGA was a drawback. In contrast, the underlying strong and slowly-degrading microfibrous silk scaffold used in this study ensured that the hybrid scaffold maintained adequate mechanical properties for longer periods, which is vital for continued support to the injured ligament/tendon throughout its healing period. PMID:20665681

Sahoo, Sambit; Toh, Siew Lok; Goh, James Cho Hong

2010-10-01

243

Human immunodeficiency virus-related connective tissue diseases: a Zimbabwean perspective.  

PubMed

Our clinical experience with patients in Zimbabwe suggests that an arthropathy may be a feature of HIV disease. This takes two forms: the first is a reactive arthropathy usually affecting the large, lower limb joints with no other clinical features of a connective tissue disease. The second form is seen in association with features of complete or incomplete Reiter's syndrome with involvement of large and small peripheral joints (having an asymmetric distribution). Although this arthropathy may been seen in association with HIV positive asymptomatic disease and often is the reason for first presentation at hospital, the majority of our patients have clinical features of persistent generalized lymphadenopathy, plus or minus features of constitutional illness (such as fever, weight loss, and diarrhea). A small percentage of our patients have arthropathy in association with secondary systemic infection. Other locomotor conditions have been observed, although their numbers are too small to determine whether or not they truly are related to HIV disease. In Zimbabwe there is no association between the development of HIV-associated arthropathy and the presence of HLA-B27. PMID:2041891

Davis, P; Stein, M

1991-02-01

244

Palatal harvesting technique modification for better control of the connective tissue graft dimensions.  

PubMed

Subepithelial connective tissue graft (SCTG) has been extensively used for a variety of clinical applications. However, the surgical procedure may not allow control of graft thickness. The purpose of this case series is to illustrate a modification to the single incision palatal harvesting technique in order to control the SCTG thickness without increasing patient discomfort. Fifty cases from thirty systemically and periodontally healthy patients with at least one multiple gingival recession were treated with coronally advanced flaps combined with a SCTG. The palatal area served as the donor site, from where a single perpendicular incision was made to obtain a full thickness flap. Next, 1-2 mm of the flap was elevated and dissected to obtain a partial thickness flap. The graft remained attached to the full-partial thickness flap. After determining the desired SCTG thickness, the graft was harvested from the palatal flap. The patients healed uneventfully at 7 days postoperatively and primary closure was obtained for all palatal donor sites. The SCTG length and width varied depending on the needs of each case, but the SCTG thickness was well controlled with only 0.24 mm standard deviation. The suggested modification granted control of the SCTG dimensions and achieved complete wound closure within a week. PMID:24474350

Reino, Danilo Maeda; Novaes, Arthur Belém; Grisi, Márcio Fernando de Moraes; Maia, Luciana Prado; de Souza, Sérgio Luis Scombatti

2013-01-01

245

The Mechanical Properties of the Rabbit Carpal Tunnel Subsynovial Connective Tissue  

PubMed Central

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

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

2008-01-01

246

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.

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

2012-01-01

247

The Response of the Rabbit Subsynovial Connective Tissue to a Stress-Relaxation Test  

PubMed Central

The subsynovial connective tissue (SSCT) in the carpal tunnel may play a role in the etiology of carpal tunnel syndrome (CTS), yet the material properties of the SSCT remain unclear. Thus, we investigated the mechanical response of the SSCT in a rabbit model. Twenty-four rabbit cadaver paws were used for mechanical testing; two paws were used for scanning electron microscopy (SEM) imaging. After testing normal tendon excursion, the divided third digit flexor digitorum superficialis (FDS) tendon was pulled to displacements of 2, 3.5, 5, or 8 mm, maintained at that position until force decay, and then the process was repeated. Normal excursion of the FDS averaged 4.8 mm. The ratio of the second peak force to the first peak force in the 2 mm group was 0.98 (SD = 0.16), which was significantly higher than the other groups (3.5 mm: 0.74, 5 mm, 0.63, and 8 mm: 0.59; p < 0.05). SEM showed ruptured fibrils in the displaced specimen. The declining force ratio with displacements >2 mm suggests damage to the SSCT within the physiological tendon excursion. These data may be useful in understanding SSCT mechanics in CTS, which is associated with SSCT fibrosis.

Morizaki, Yutaka; Vanhees, Matthias; Thoreson, Andrew R.; Larson, Dirk; Zhao, Chunfeng; An, Kai-Nan; Amadio, Peter C.

2014-01-01

248

The Effect of Displacement on the Mechanical Properties of Human Cadaver Subsynovial Connective Tissue  

PubMed Central

The subsynovial connective tissue (SSCT) in the carpal tunnel may participate in the origin of carpal tunnel syndrome (CTS), yet material properties of the SSCT have not been well-characterized. We investigated the response of the SSCT to repeated ramp stretch tests. Eight human cadaver wrists were used. The physiological excursion of the flexor digitorum superficialis of the third digit (FDS 3) was measured, starting from a neutral position to maximal flexion of the metacarpophalangeal and proximal interphalangeal joints. The FDS 3 tendon was pulled to 40, 60, 90, and 120% of the physiological excursion. Two ‘ramp stretch’ cycles were performed at every excursion level, except for 120% of excursion, where 3 cycles were performed. The ratio of energy absorbed between the second (E2) and first (E1) ramp-stretch was 0.94 (Std. Dev. = 0.07) for 60%, 0.84 (Std. Dev. = 0.11) for 90%, and 0.68 (Std. Dev. = 0.11) for 120% of the physiological excursion. A significant decrease occurred in energy absorbed after the first ramp-stretch cycle at 90% and 120% of the physiological excursion, which was not seen at 60%. Our data are consistent with a stepwise damage occurring in the SSCT. Furthermore, the damage seems to initiate within the physiological range of tendon excursion. This finding may be important in understanding the pathophysiology of conditions that are associated with SSCT pathology, such as carpal tunnel syndrome.

Vanhees, Matthias; Morizaki, Yutaka; Thoreson, Andrew R.; Larson, Dirk; Zhao, Chunfeng; An, Kai-Nan; Amadio, Peter C.

2012-01-01

249

The immune system which adversely alter thyroid functions: a review on the concept of autoimmunity.  

PubMed

The immune system protect individual from many pathogens exists within our environment and in human body, by destroying them through molecular and cellular mechanism of B and T cells of immune system. Autoimmunity is an adverse relation of immune system against non- foreign substances leaving behind either alters the normal function or destroying the tissue involved. Autoimmunity occur in genetically predispose persons with familial connections. The autoimmunity to the thyroid gland mainly consists of Hashimato thyroiditis and Grave's disease, the two end of spectrum in thyroid function of hypo and hyperactivity, respectively. The thyroid stimulating hormone receptor, thyroglobuline, enzymes of thyroid hormones synthesis are targeted by autoantibodies and cell- mediated reactions. The aim of this review is to explore the studies reported on the autoimmunity to the thyroid gland. PMID:21850926

Mansourian, Azad Reza

2010-08-15

250

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

Microsoft Academic Search

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

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

2007-01-01

251

Anticardiolipin Antibodies Are Associated with Pulmonary Hypertension in Patients with Mixed Connective Tissue Disease or Systemic Lupus Erythematosus  

Microsoft Academic Search

Anticardiolipin antibodies (aCL) were studied in relation to pulmonary hypertension (PH) in 22 patients with mixed connective tissue disease (MCTD) or systemic lupus erythematosus (SLE). The mean pulmonary arterial pressure (mPAP) values were similar in the 12 MCTD and 10 SLE patients: 26 ± 11 and 25 ± 11 mm Hg, respectively. However, the frequency of PH was higher in

Masayuki Miyata; Kyoji Suzuki; Fumitaka Sakuma; Hiroshi Watanabe; Shunji Kaise; Tomoe Nishimaki; Reiji Kasukawa

1993-01-01

252

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

Microsoft Academic Search

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

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

1998-01-01

253

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

254

Quantitative genetic variation in CD19 expression correlates with autoimmunity.  

PubMed

Signaling thresholds influence the balance between humoral immunity and autoimmunity. Cell surface CD19 regulates intrinsic and Ag receptor-induced B lymphocyte signaling thresholds, and transgenic mice that overexpress CD19 by 3-fold generate spontaneous autoantibodies in a genetic background not associated with autoimmunity. To quantify the extent that genetically determined differences in expression of a single cell surface molecule can influence autoantibody production, we have assessed autoimmunity in a C57BL/6-transgenic mouse line with subtle 15-29% increases in CD19 cell surface expression (CD19 transgenic). Antinuclear Abs, especially anti-spindle pole Abs, rheumatoid factor, and autoantibodies for ssDNA, dsDNA, and histone were produced in these transgenic mice, but not littermate controls. This demonstrates that small changes in CD19 expression can induce autoantibody production. Remarkably, similar changes in CD19 expression were found on B cells from patients with systemic sclerosis, a multisystem disorder of connective tissue with autoantibody production. CD19 density on blood B cells from systemic sclerosis patients was significantly ( approximately 20%) higher compared with normal individuals, whereas CD20, CD22, and CD40 expression were normal. These results suggest that modest changes in the expression or function of regulatory molecules such as CD19 may shift the balance between tolerance and immunity to autoimmunity. Thereby autoimmune disease may result from a collection of subtle multigenic alterations that could include incremental density changes in cell surface signaling molecules. PMID:11086109

Sato, S; Hasegawa, M; Fujimoto, M; Tedder, T F; Takehara, K

2000-12-01

255

Adjuvants and autoimmunity.  

PubMed

Some adjuvants may exert adverse effects upon injection or, on the other hand, may not trigger a full immunological reaction. The mechanisms underlying adjuvant adverse effects are under renewed scrutiny because of the enormous implications for vaccine development. In the search for new and safer adjuvants, several new adjuvants were developed by pharmaceutical companies utilizing new immunological and chemical innovations. The ability of the immune system to recognize molecules that are broadly shared by pathogens is, in part, due to the presence of special immune receptors called toll-like receptors (TLRs) that are expressed on leukocyte membranes. The very fact that TLR activation leads to adaptive immune responses to foreign entities explains why so many adjuvants used today in vaccinations are developed to mimic TLR ligands. Alongside their supportive role, adjuvants were found to inflict by themselves an illness of autoimmune nature, defined as 'the adjuvant diseases'. The debatable question of silicone as an adjuvant and connective tissue diseases, as well as the Gulf War syndrome and macrophagic myofaciitis which followed multiple injections of aluminium-based vaccines, are presented here. Owing to the adverse effects exerted by adjuvants, there is no doubt that safer adjuvants need to be developed and incorporated into future vaccines. Other needs in light of new vaccine technologies are adjuvants suitable for use with mucosally delivered vaccines, DNA vaccines, cancer and autoimmunity vaccines. In particular, there is demand for safe and non-toxic adjuvants able to stimulate cellular (Th1) immunity. More adjuvants were approved to date besides alum for human vaccines, including MF59 in some viral vaccines, MPL, AS04, AS01B and AS02A against viral and parasitic infections, virosomes for HBV, HPV and HAV, and cholera toxin for cholera. Perhaps future adjuvants occupying other putative receptors will be employed to bypass the TLR signaling pathway completely in order to circumvent common side effects of adjuvant-activated TLRs such as local inflammation and the general malaise felt because of the costly whole-body immune response to antigen. PMID:19880572

Israeli, E; Agmon-Levin, N; Blank, M; Shoenfeld, Y

2009-11-01

256

The role of infections in autoimmune disease  

PubMed Central

Autoimmunity occurs when the immune system recognizes and attacks host tissue. In addition to genetic factors, environmental triggers (in particular viruses, bacteria and other infectious pathogens) are thought to play a major role in the development of autoimmune diseases. In this review, we (i) describe the ways in which an infectious agent can initiate or exacerbate autoimmunity; (ii) discuss the evidence linking certain infectious agents to autoimmune diseases in humans; and (iii) describe the animal models used to study the link between infection and autoimmunity.

Ercolini, A M; Miller, S D

2009-01-01

257

Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells.  

PubMed Central

Although commonly used to control a variety of inflammatory diseases, the mechanism of action of a low dose of methotrexate remains a mystery. Methotrexate accumulates intracellularly where it may interfere with purine metabolism. Therefore, we determined whether a 48-hr pretreatment with methotrexate affected adenosine release from [14C]adenine-labeled human fibroblasts and umbilical vein endothelial cells. Methotrexate significantly increased adenosine release by fibroblasts from 4 +/- 1% to 31 +/- 6% of total purine released (EC50, 1 nM) and by endothelial cells from 24 +/- 4% to 42 +/- 7%. Methotrexate-enhanced adenosine release from fibroblasts was further increased to 51 +/- 4% (EC50, 6 nM) and from endothelial cells was increased to 58 +/- 5% of total purine released by exposure to stimulated (fMet-Leu-Phe at 0.1 microM) neutrophils. The effect of methotrexate on adenosine release was not due to cytotoxicity since cells treated with maximal concentrations of methotrexate took up [14C]adenine and released 14C-labeled purine (a measure of cell injury) in a manner identical to control cells. Methotrexate treatment of fibroblasts dramatically inhibited adherence to fibroblasts by both unstimulated neutrophils (IC50, 9 nM) and stimulated neutrophils (IC50, 13 nM). Methotrexate treatment inhibited neutrophil adherence by enhancing adenosine release from fibroblasts since digestion of extracellular adenosine by added adenosine deaminase completely abrogated the effect of methotrexate on neutrophil adherence without, itself, affecting adherence. One hypothesis that explains the effect of methotrexate on adenosine release is that, by inhibition of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase, methotrexate induces the accumulation of AICAR, the nucleoside precursor of which (5-aminoimidazole-4-carboxamide ribonucleoside referred to hereafter as acadesine) has previously been shown to cause adenosine release from ischemic cardiac tissue. We found that acadesine also promotes adenosine release from and inhibits neutrophil adherence to connective tissue cells. The observation that the antiinflammatory actions of methotrexate are due to the capacity of methotrexate to induce adenosine release may form the basis for the development of an additional class of antiinflammatory drugs.

Cronstein, B N; Eberle, M A; Gruber, H E; Levin, R I

1991-01-01

258

Silicone Gel Enhances the Development of Autoimmune Disease in New Zealand Black Mice but Fails To Induce It in BALB\\/cAnPt Mice  

Microsoft Academic Search

Anecdotal evidence links silicone gel breast implants with the development of autoimmune connective tissue disease in women. To investigate whether silicone gel is capable of directly inducing and\\/or enhancing the development of autoimmune disease, female BALB\\/cAnPt (BALB\\/c) and New Zealand Black (NZB) mice were injected subcutaneously with silicone gel, pristane, a nonmetabolizable substance that can cause plasmacytomas in BALB\\/c and

Kimberly Weir

1998-01-01

259

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.

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

2014-01-01

260

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.

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

261

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

PubMed

Exposure of rodents to angiotensin II (AngII) is a common model of fibrosis. We have previously shown that cellular infiltration of bone marrow-derived progenitor cells (fibrocytes) occurs before deposition of extracellular matrix and is associated with the production of connective tissue growth factor (CTGF). In the present study, we characterized the role of CTGF in promoting fibrocyte accumulation and regulation after AngII exposure. In animals exposed to AngII using osmotic minipumps (2.0 ?g/kg per min), myocardial CTGF mRNA peaked at 6 hours (21-fold; P < 0.01), whereas transforming growth factor-? (TGF-?) peaked at 3 days (fivefold; P < 0.05) compared with saline control. Early CTGF expression occurred before fibrocyte migration (1 day) into the myocardium or ECM deposition (3 days). CTGF protein expression was evident by day 3 of AngII exposure and seemed to be localized to resident cells. Isolated cardiomyocytes and microvascular endothelial cells responded to AngII with increased CTGF production (2.1-fold and 2.8-fold, respectively; P < 0.05), which was abolished with the addition of anti-TGF-? neutralizing antibody. The effect of CTGF on isolated fibrocytes suggested a role in fibrocyte proliferation (twofold; P < 0.05) and collagen production (2.3-fold; P < 0.05). In summary, we provide strong evidence that AngII exposure first resulted in Smad2-dependent production of CTGF by resident cells (6 hours), well before the accumulation of fibrocytes or TGF-? mRNA up-regulation. In addition, CTGF contributes to fibrocyte proliferation in the myocardium and enhances fibrocyte differentiation into a myofibroblast phenotype responsible for ECM deposition. PMID:23287510

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

2013-03-01

262

Caspase-3-mediated secretion of connective tissue growth factor by apoptotic endothelial cells promotes fibrosis.  

PubMed

Apoptosis of endothelial cells (ECs) is an early pathogenic event in various fibrotic diseases. In this study, we evaluated whether paracrine mediators produced by apoptotic ECs play direct roles in fibrogenesis. C3H mice injected subcutaneously with serum-free medium conditioned by apoptotic ECs (SSC) showed increased skin thickness and heightened protein levels of alpha-smooth-muscle actin (alphaSMA), vimentin and collagen I as compared with mice injected with medium conditioned by non-apoptotic ECs. Fibroblasts exposed to SSC in vitro showed cardinal features of myofibroblast differentiation with increased stress fiber formation and expression of alphaSMA. Caspase-3 silencing in ECs prevented the release of mediators favoring myofibroblast differentiation. To identify the fibrogenic factor(s) released by ECs, the protein contents of media conditioned by either apoptotic or non-apoptotic ECs were compared using SDS-PAGE-liquid chromatography (LC)-tandem mass spectrometry (MS/MS) and two-dimensional LC-MS/MS. Connective tissue growth factor (CTGF) was the only fibrogenic protein found increased in SSC. Pan-caspase inhibition with ZVAD-FMK or caspase-3 silencing in ECs confirmed that CTGF was released downstream of caspase-3 activation. The fibrogenic signaling signatures of SSC and CTGF on fibroblasts in vitro were similarly Pyk2-, Src-family kinases- and PI3K dependent, but TGF-beta-independent. CTGF-immunodepleted SSC failed to induce myofibroblast differentiation in vitro and skin fibrosis in vivo. These results identify caspase-3 activation in ECs as a novel inducer of CTGF release and fibrogenesis. PMID:19730442

Laplante, P; Sirois, I; Raymond, M-A; Kokta, V; Béliveau, A; Prat, A; Pshezhetsky, A V; Hébert, M-J

2010-02-01

263

High glucose upregulates connective tissue growth factor expression in human vascular smooth muscle cells  

PubMed Central

Background Connective tissue growth factor (CTGF) is a potent profibrotic factor, which is implicated in fibroblast proliferation, angiogenesis and extracellular matrix (ECM) synthesis. It is a downstream mediator of some of the effects of transforming growth factor ? (TGF?) and is potentially induced by hyperglycemia in human renal mesangial cells. However, whether high glucose could induce the CTGF expression in vascular smooth muscle cells (VSMCs) remains unknown. Therefore, this study was designed to test whether high glucose could regulate CTGF expression in human VSMC. The effect of modulating CTGF expression on VSMC proliferation and migration was further investigated. Results Expression of CTGF mRNA was up-regulated as early as 6 hours in cultured human VSMCs after exposed to high glucose condition, followed by ECM components (collagen type I and fibronectin) accumulation. The upregulation of CTGF mRNA appears to be TGF?-dependent since anti-TGF? antibody blocks the effect of high glucose on CTGF gene expression. A small interference RNA (siRNA) targeting CTGF mRNA (CTGF-siRNA) effectively suppressed CTGF up-regulation stimulated by high glucose up to 79% inhibition. As a consequence of decreased expression of CTGF gene, the deposition of ECM proteins in the VSMC was also declined. Moreover, CTGF-siRNA expressing vector partially inhibited the high glucose-induced VSMC proliferation and migration. Conclusion Our data suggest that in the development of macrovascular complications in diabetes, CTGF might be an important factor involved in the patho-physiological responses to high glucose in human VSMCs. In addition, the modulatory effects of CTGF-siRNA during this process suggest that specific targeting CTGF by RNA interference could be useful in preventing intimal hyperplasia in diabetic macrovascular complications.

Liu, Xiaojing; Luo, Fengming; Pan, Kejian; Wu, Wenchao; Chen, Huaiqing

2007-01-01

264

FoxO Proteins Mediate Hypoxic Induction of Connective Tissue Growth Factor in Endothelial Cells*  

PubMed Central

Hypoxia, a driving force in neovascularization, promotes alterations in gene expression mediated by hypoxia-inducible factor (HIF)-1?. Connective tissue growth factor (CTGF, CCN2) is a modulator of endothelial cell growth and migration, but its regulation by hypoxia is poorly understood. Therefore, we analyzed signaling pathways involved in the regulation of CTGF by hypoxia in endothelial cells. Exposure to low oxygen tension or treatment with the hypoxia-mimetic dimethyloxalyl glycine (DMOG) stabilized HIF-1? and up-regulated CTGF in human umbilical vein endothelial cells and in a murine microvascular endothelial cell line. Induction of CTGF correlated with a HIF-dependent increase in protein and mRNA levels, and nuclear accumulation of the transcription factor FoxO3a. By contrast, gene expression and cellular localization of FoxO1 were not significantly altered by hypoxia. Expression of CTGF was strongly reduced by siRNA silencing of FoxO1 or FoxO3a. Furthermore, nuclear exclusion of FoxO1/3a transcription factors by inhibition of serine/threonine protein phosphatases by okadaic acid inhibited CTGF expression, providing evidence for both FoxO proteins as regulators of CTGF expression. The DMOG-stimulated induction of CTGF was further increased when endothelial cells were co-incubated with transforming growth factor-?, an activator of Smad signaling. Activation of RhoA-Rho kinase signaling by the microtubule-disrupting drug combretastatin A4 also enhanced the DMOG-induced CTGF expression, thus placing CTGF induction by hypoxia in a network of interacting signaling pathways. Our findings provide evidence that FoxO1, hypoxia-stimulated expression of FoxO3a and its nuclear accumulation are required for the induction of CTGF by hypoxia in endothelial cells.

Samarin, Jana; Wessel, Julia; Cicha, Iwona; Kroening, Sven; Warnecke, Christina; Goppelt-Struebe, Margarete

2010-01-01

265

FoxO proteins mediate hypoxic induction of connective tissue growth factor in endothelial cells.  

PubMed

Hypoxia, a driving force in neovascularization, promotes alterations in gene expression mediated by hypoxia-inducible factor (HIF)-1alpha. Connective tissue growth factor (CTGF, CCN2) is a modulator of endothelial cell growth and migration, but its regulation by hypoxia is poorly understood. Therefore, we analyzed signaling pathways involved in the regulation of CTGF by hypoxia in endothelial cells. Exposure to low oxygen tension or treatment with the hypoxia-mimetic dimethyloxalyl glycine (DMOG) stabilized HIF-1alpha and up-regulated CTGF in human umbilical vein endothelial cells and in a murine microvascular endothelial cell line. Induction of CTGF correlated with a HIF-dependent increase in protein and mRNA levels, and nuclear accumulation of the transcription factor FoxO3a. By contrast, gene expression and cellular localization of FoxO1 were not significantly altered by hypoxia. Expression of CTGF was strongly reduced by siRNA silencing of FoxO1 or FoxO3a. Furthermore, nuclear exclusion of FoxO1/3a transcription factors by inhibition of serine/threonine protein phosphatases by okadaic acid inhibited CTGF expression, providing evidence for both FoxO proteins as regulators of CTGF expression. The DMOG-stimulated induction of CTGF was further increased when endothelial cells were co-incubated with transforming growth factor-beta, an activator of Smad signaling. Activation of RhoA-Rho kinase signaling by the microtubule-disrupting drug combretastatin A4 also enhanced the DMOG-induced CTGF expression, thus placing CTGF induction by hypoxia in a network of interacting signaling pathways. Our findings provide evidence that FoxO1, hypoxia-stimulated expression of FoxO3a and its nuclear accumulation are required for the induction of CTGF by hypoxia in endothelial cells. PMID:20018872

Samarin, Jana; Wessel, Julia; Cicha, Iwona; Kroening, Sven; Warnecke, Christina; Goppelt-Struebe, Margarete

2010-02-12

266

Connective tissue growth factor is a target of notch signaling in cells of the osteoblastic lineage.  

PubMed

Connective tissue growth factor (Ctgf) or CCN2 is a protein synthesized by osteoblasts necessary for skeletal homeostasis, although its overexpression inhibits osteogenic signals and bone formation. Ctgf is induced by bone morphogenetic proteins, transforming growth factor ? and Wnt; and in the present studies, we explored whether Notch regulated Ctgf expression in osteoblasts. We employed Rosa(Notch) mice, where the Notch intracellular domain (NICD) is expressed following the excision of a STOP cassette, placed between the Rosa26 promoter and NICD. Notch was activated by transduction of adenoviral vectors expressing Cre recombinase (Ad-CMV-Cre). Notch induced Ctgf mRNA levels in a time dependent manner and increased Ctgf heterogeneous nuclear RNA. Notch also destabilized Ctgf mRNA shortening its half-life from 13h to 3h. The effect of Notch on Ctgf expression was lost following Rbpj? downregulation, demonstrating that it was mediated by Notch canonical signaling. However, downregulation of the classic Notch target genes Hes1, Hey1 and Hey2 did not modify the effect of Notch on Ctgf expression. Wild type osteoblasts exposed to immobilized Delta-like 1 displayed enhanced Notch signaling and increased Ctgf expression. In addition to the effects of Notch in vitro, Notch induced Ctgf in vivo, and calvariae and femurs from Rosa(Notch) mice mated with transgenics expressing the Cre recombinase in cells of the osteoblastic lineage exhibited increased expression of Ctgf. In conclusion, Ctgf is a target of Notch canonical signaling in osteoblasts, and may act in concert with Notch to regulate skeletal homeostasis. PMID:24792956

Canalis, Ernesto; Zanotti, Stefano; Smerdel-Ramoya, Anna

2014-07-01

267

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

PubMed

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- 1b (IL-1b), 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-1b 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-1b 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

2014-04-01

268

Alfacalcidol treatment restores derailed immune-regulation in patients with undifferentiated connective tissue disease.  

PubMed

Vitamin D deficiency may contribute to pathological changes in the number and function of CD4+ T helper cell subsets (CD4+Th1, CD4+Th17, CD4+CD25(bright)Foxp3-natural regulatory T cells-nTreg) in patients with undifferentiated connective tissue disease (UCTD). The aim of the present study was to evaluate, whether alfacalcidol could restore immune-regulatory changes in patients with UCTD. We assessed the optimal dose of alfacalcidol that could normalize the elevated levels of IFN-? expressed by the CD4+Th1 cells and the IL-17 expressed by Th17 cells. Furthermore alfacalcidol decreased the Th1 and Th17 related cytokine levels, repaired the nTreg/Th7 balance, and restored the functional activity of nTreg cells. Twenty one UCTD patients with Vitamin D deficiency (<30 ng/ml) were administered with three different daily doses of alfacalcidol. Seven patients were supplemented with 0.5 ?g/day, 7 patients with 1.0 ?g/day, and 7 patients with 1.5 ?g/day alfacalcidol treatment during 5 weeks. Our results indicated that 1.0 ?g/day alfacalcidol during 5 weeks was the optimal therapeutic regime to increase the vitamin D levels, repair the nTreg/Th17 balance and raise the capacity of nTreg cells to suppress the proliferation of autologous CD4+CD25- cells. 1.5 ?g daily dose alfacalcidol was not more effective than the 1.0 ?g/day treatment. In this study we described that vitamin D deficiency can contribute to the complex immune-regulatory abnormalities in patients with UCTD and vitamin D substitution therapy can improve the fine balance of pro- and anti-inflammatory processes in the disease. PMID:20868777

Zold, Eva; Szodoray, Peter; Nakken, Britt; Barath, Sandor; Kappelmayer, Janos; Csathy, Laszlo; Hajas, Agota; Sipka, Sandor; Gyimesi, Edit; Gaal, Janos; Barta, Zsolt; Hallay, Judit; Szegedi, Gyula; Bodolay, Edit

2011-01-01

269

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

270

NK Cells in Autoimmune Disease  

Microsoft Academic Search

The role of NK cells in autoimmunity has not been extensively studied. Speaking for a disease-promoting role for NK cells\\u000a in autoimmune diseases are recent results suggesting that IFN-? production by NK cells may help adaptive immune responses\\u000a diverge in the direction of a Th1 response. NK cells may also be involved in direct killing of tissue cells, which could

S. Johansson; H. Hall; L. Berg; P. Höglund

271

Expression stability of commonly used reference genes in canine articular connective tissues  

Microsoft Academic Search

BACKGROUND: The quantification of gene expression in tissue samples requires the use of reference genes to normalise transcript numbers between different samples. Reference gene stability may vary between different tissues, and between the same tissue in different disease states. We evaluated the stability of 9 reference genes commonly used in human gene expression studies. Real-time reverse transcription PCR and a

Duncan Ayers; Dylan N Clements; Fiona Salway; Philip JR Day

2007-01-01

272

[Thyroid autoimmunity].  

PubMed

This review of human autoimmune thyroid disease (AITD) focuses mainly on the epidemiology and pathophysiology of this very common disorder, although some specific clinical situations are discussed. One peculiarity of AITD is the existence of two contrasting phenotypes: hypothyroid thyroiditis and hyperthyroid Graves' disease. Graves' disease is characterized by the presence of anti-TSH receptor antibodies capable of activating the TSH receptor, leading to thyroid hypertrophy and hyperfunction. In contrast, autoimmune thyroiditis progresses slowly, through necrosis/apoptosis of thyroid cells and their functional impairment. Other forms of autoimmune thyroiditis such as postpartum thyroiditis and silent thyroiditis are also described. The aim of this non exhaustive review is to provide the interested reader with basic information required for further investigation. PMID:24672979

Orgiazzi, Jacques

2013-01-01

273

[Autoimmune hypophysitis].  

PubMed

Autoimmune hypophysitis (AH) - often referred to as lymphocytic hypophysitis - is a rare disease that affects the pituitary gland and causes inflammation. The disease enlarges the pituitary gland and the clinical presentations are lack of pituitary function and headaches. AH is mostly seen in women during pregnancy or postpartum, but also occurs in males and children. AH is often associated with other autoimmune diseases, most frequently with Hashimoto's thyroiditis. The symptoms are caused by enlargement of the pituitary gland and disturbances of the hormone function. Treatment is either immunosuppressive treatment or surgery. PMID:20412729

Krarup, Therese; Hagen, Claus

2010-03-15

274

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

PubMed Central

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. Images Fig. 3 Fig. 4 Fig. 5

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

1991-01-01

275

Connective tissue growth factor (CTGF/CCN2) is negatively regulated during neuron-glioblastoma interaction.  

PubMed

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

Romăo, Luciana F; Mendes, Fabio A; Feitosa, Natalia M; Faria, Jane Cristina O; Coelho-Aguiar, Juliana M; de Souza, Jorge Marcondes; Moura Neto, Vivaldo; Abreu, José Garcia

2013-01-01

276

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

PubMed Central

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

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

2013-01-01

277

Lower Urinary Connective Tissue Growth Factor Levels and Incident CKD Stage 3 in the General Population  

PubMed Central

Background Connective tissue growth factor (CTGF) is involved in the development and progression of kidney diseases including diabetic nephropathy and kidney fibrosis, but may also play a role in mesangial repair following injury. It is unknown whether, in the general population, urinary CTGF levels are associated with reduction of estimated glomerular filtration rate (eGFR) to less than 60 ml/min/1.73m2 (ie, development of chronic kidney disease [CKD] stage 3). Study Design Nested case-control. Setting & Participants 100 cases of incident CKD stage 3 and 100 age-and sex-matched controls in the Framingham Heart Study (FHS); 141 cases and 135 age-, sexand race-matched controls in the Atherosclerosis Risk in Communities (ARIC) Study. Controls had eGFR ?60 ml/min/1.73m2 at follow-up in both studies. Predictors Urinary CTGF concentrations. Outcomes Incident CKD stage 3, defined as eGFR <60 ml/min/1.73m2. Measurements Stored urine samples from Framingham Heart Study and ARIC were measured for CTGF. Covariates were obtained from Framingham Heart Study and ARIC participant examinations. Results In Framingham Heart Study, the median baseline urinary CTGF concentration was lower among cases (1.35 ng/mL) than controls (2.35 ng/mL; paired t-test P<0.0001). The multivariable-adjusted OR for incident CKD stage 3 was 0.33 (95% confidence interval [CI] 0.17–0.64; P<0.001) per 1-standard deviation increase in log urinary CTGF after adjustment for CKD risk factors, baseline eGFR and baseline log urinary albumin-creatinine ratio, with similar results among participants without diabetes (n=184). Results were not materially different when urinary CTGF was indexed to urinary creatinine (multivariable-adjusted OR, 0.34; 95% CI, 0.21–0.56; P<0.001). A similar, but non-significant, trend of risk of incident CKD stage 3 with lower baseline urinary CTGF concentration was observed in an independent case-control study conducted in the ARIC Study, with the strongest results observed among participants free of diabetes. This inverse relationship was robust in meta-analysis of both the overall and diabetes-free groups. Limitations Observational study; causality cannot be inferred. Conclusions Lower urinary CTGF concentrations precede the onset of CKD stage 3 in the general population. Further work is required to fully characterize how CTGF influences risk of CKD.

Seaghdha, Conall M. O'; Hwang, Shih-Jen; Bhavsar, Nrupen A.; Kottgen, Anna; Coresh, Josef; Astor, Brad C.; Fox, Caroline S.

2011-01-01

278

Ontogenetic changes in fibrous connective tissue organization in the oval squid, Sepioteuthis lessoniana Lesson, 1830.  

PubMed

Ontogenetic changes in the organization and volume fraction of collagenous connective tissues were examined in the mantle of 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 degrees in newly hatched animals to 17.7 degrees in the largest animals studied. The arrangement of intramuscular collagen fiber systems 1 (IM-1) and 2 (IM-2) also changed significantly during ontogeny. Because of the oblique trajectory of the IM-1 collagen fibers, two fiber angles were needed to describe their organization: (1) IM-1(SAG), the angle of an IM-1 collagen fiber relative to the squid's long axis when viewed from a sagittal plane and (2) IM-1(TAN), the angle of an IM-1 collagen fiber relative to the squid's long axis when viewed from a plane tangential to the outer curvature of the mantle. The sagittal component (IM-1(SAG)) of the IM-1 collagen fiber angle was lowest in hatchling squid (32.7 degrees ) and increased exponentially during growth to 43 degrees in squid with a dorsal mantle length (DML) of 15 mm. In squid larger than 15 mm DML, IM-1(SAG) fiber angle did not change. The tangential component (IM-1(TAN)) of IM-1 collagen fiber angle was highest in hatchling squid (39 degrees ) and decreased to 32 degrees in the largest squid examined. IM-2 collagen fiber angle (the angle of an IM-2 collagen fiber relative to the outer surface of the mantle) was lowest in hatchling squid (34.6 degrees ) and increased exponentially to about 50 degrees in 15-mm DML animals. In squid larger than 15 mm DML, IM-2 fiber angle increased slightly with size. The volume fraction of collagen in IM-1 and IM-2 increased 68 and 36 times, respectively, during growth. The ontogenetic changes in the organization of collagen fibers in the outer tunic, IM-1, and IM-2 may lead to ontogenetic differences in the kinematics of mantle movement and in elastic energy storage during jet locomotion. PMID:11687386

Thompson, J T; Kier, W M

2001-10-01

279

Pulmonary arterial hypertension associated with connective tissue disease: meta-analysis of clinical trials  

PubMed Central

Objectives Few studies have focused on pulmonary arterial hypertension (PAH) associated with connective tissue diseases (CTDs). The optimal treatment for CTD-PAH has yet to be established. Design Meta-analysis of the data from evaluations of treatment for PAH generally (19 studies) and CTD-PAH specifically (nine studies) to compare the effects of pulmonary vasodilative PAH agents. MEDLINE, EMBASE and BIOSIS were searched. English-language full-text articles published between January 1990 and August 2012 were eligible. Setting International. Participants Patients with PAH generally (n=3073) and CTD-PAH specifically (n=678). Primary outcome measure Exercise capacity (6?min walk distance, 6?MWD). Results Patients with PAH (all forms) had mean age 32–55?years (women, 61–87%); CTD-PAH patients had mean age 45–55?years (women, 74–95%). Overall estimate of mean change in 6?MWD from baseline (95% CI) for the active treatment group versus the control group in all patients with PAH was 34.6?m (27.4–41.9?m). Pooled mean differences from the results for patients receiving placebo by subgroup of patients receiving phosphodiesterase (PDE)-5 inhibitors, endothelin receptor antagonists (ERAs) and prostacyclin (PGI2) analogues were 22.4–45.5, 39.5–44.2 and 12.4–64.9?m, respectively. Overall estimate of mean difference between changes in 6?MWD in patients with CTD-PAH was 34.2?m (23.3–45.0?m). Pooled mean differences by subgroup of patients receiving PDE-5 inhibitors, ERAs and PGI2 analogues in patients with CTD-PAH were 37.0–47.1, 14.1–21.7 and 21.0–108.0?m, respectively. ERAs were less effective in patients with CTD-PAH than all-form patients with PAH: 14.1?m (?4.4–32.6?m) vs 39.5?m (19.5–59.6?m) for bosentan and 21.7?m (2.2–41.3?m) vs 44.2?m (30.2–58.2?m) for ambrisentan. Conclusions All three types of PAH agent are effective. However, ERAs may be a less effective choice against CTD-PAH; further studies are needed. Limitations include the limited number of studies for some agents and for patients with CTD-PAH.

Kuwana, Masataka; Watanabe, Hiroshi; Matsuoka, Nobushige; Sugiyama, Naonobu

2013-01-01

280

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

PubMed Central

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

Yi, Zuohuizi; Huang, Dehui; Wei, Shihui

2014-01-01

281

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.

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

2013-01-01

282

Mixed connective tissue disease. A clinical, histologic, and immunofluorescence study of eight cases.  

PubMed

A study of the cutaneous eruptions of eight patients with mixed connective tissue disease (MCTD) was performed to better characterize its dermatopathology and to explore a role for the membrane attack complex of complement C5b-9 in lesional pathogenesis. Nine lesional skin biopsies were obtained from eight patients with MCTD and analyzed by conventional light microscopy. Direct immunofluorescence (IF) and indirect IF using a monoclonal antibody to C5b-9 were applied in six and five cases respectively. The biopsied cutaneous eruptions were characterized clinically as photo-distributed erythematosus annular and/or papulosquamous lesions mimnicking subacute cutaneous lupus erythematosus (SCLE) in five of eight patients as an ill-defined, telangiectatic, scaly patch on the face in one patient, palpable purpura in one patient, and dorsal hand blisters resembling porphyria cutanea tarda (PCT) in another. With the exception of the latter two patients, the histology appeared similar, comprising a cell poor and/or lichenoid interface dermatitis with suprabasilar exocytosis around necrotic keratinocytes in the absence of deep periadnexal or perivascular extension or conspicuous follicular plugging, a pattern similar to that of SCLE. However, the lesions differed from SCLE by virtue of vasculopathic alterations comprising vascular ectasia, hypovascularity, and/or luminal thrombosis confined to the superficial vascular plexus and a sclerodermoid tissue reaction, the latter seen in two cases. One biopsy showed a pustular leukocytoclastic vasculitis (LCV). In another case, a biopsied hand blister demonstrated a PCT-like appearance histologically, namely, pauci-inflammatory subepithelial blister formation with hyalinization of dermal papillae capillaries accompanied by an LCV. There was nuclear keratinocyte decoration with IgG and C5b-9 in all cases studied, accompanied by a positive lupus band test in two cases and homogenous deposition of immunoreactants along the dermoepidermal junction and within vessels in the PCT-like eruption. Granular vascular decoration with immunoreactants including C5b-9 was seen in two LCV cases and in two biopsies from rashes clinically mimicking SCLE. Although the epidermal pathology of MCTD mimicks that of SCLE, a concomitant vasculopathy paralleling that seen in skin lesions of dermatomyositis distinquishes the dermatopathology of MCTD from that of SCLE. Corroborating the role of microangiopathy in the pathogenesis of the skin lesions of MCTD was the demonstration of C5b-9 in blood vessels. The deposition of C5b-9 in keratinocytes may explain the pattern Of IgG decoration of keratinocytes; the formation of plasmalemmal pores may permit binding of immunoglobulin to antigens in the nucleus and/or cytosol. The C 5b-9 complex may be the effector mechanism of epithelial and/or endothelial cell injury in MCTD or may serve to augment the effects of antibody-dependent cellular cytotoxicity. PMID:9185904

Magro, C M; Crowson, A N; Regauer, S

1997-06-01

283

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

Microsoft Academic Search

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

David R. Brigstock

2002-01-01

284

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

285

Widespread vasculopathy with hemolytic uremic syndrome, perimyocarditis and cystic pancreatitis in a young woman with mixed connective tissue disease  

Microsoft Academic Search

A 15-year-old girl had severe Raynaud's phenomenon and arthralgias. A high ANA-IF titer was found and undifferentiated connective tissue disease was diagnosed. After 7 years of moderately flaring disease the patient deteriorated and presented with congestive heart failure, pleuropericardial effusion, hemolytic uremic syndrome, proteinuria and moderate hypertension. Autoantibodies against DNA, Sm-protein, and very high titers against U1RNP were detected. Therapy

J. Braun; J. Sieper; A. Schwarz; F. Hiepe; T. Lenz; F. Keller; H. Herbst; A. Distler

1993-01-01

286

Efficacy of connective tissue massage and Mc Mennell joint manipulation in the rehabilitative treatment of the hands in systemic sclerosis  

Microsoft Academic Search

Rehabilitation may contribute to the management of systemic sclerosis (SSc) dealing with disabilities due to hand involvement.\\u000a The aim of this study is to evaluate the efficacy of a rehabilitation programme based on the combination of connective tissue\\u000a massage and Mc Mennell joint manipulation specifically conceived for SSc patients’ hands. Forty SSc patients were enrolled:\\u000a 20 (interventional group) were treated

Susanna Maddali Bongi; Angela Del Rosso; Felice Galluccio; Fabrizio Sigismondi; Irene Miniati; M. Letizia Conforti; Francesca Nacci; Marco Matucci Cerinic

2009-01-01

287

Effect of Cyclosporine and Sirolimus on the Expression of Connective Tissue Growth Factor in Rat Experimental Chronic Nephrotoxicity  

Microsoft Academic Search

Background\\/Aims: Connective tissue growth factor (CTGF) is a pro-fibrotic growth factor that acts downstream of transforming growth factor (TGF)-?. However, CTGF regulation remains unknown. We tried to determine the effect of two commonly used immunosuppressants, cyclosporine (CsA) and sirolimus (SRL), on CTGF expression in a model of chronic nephrotoxicity. Methods: Adult Sprague-Dawley rats kept on a low-salt diet were treated

Fuad S. Shihab; William M. Bennett; Hong Yi; Takeshi F. Andoh

2006-01-01

288

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

Microsoft Academic Search

In this pilot study, hypertonic dextrose solution was used to induce fibrosis of the subsynovial connective tissue (SSCT)\\u000a and create an animal model of potential use in the study of carpal tunnel syndrome (CTS). The SSCT of the carpal tunnel in\\u000a 15 New Zealand white rabbits were injected with 0.05 ml of 10% dextrose solution in 1 paw and 0.05 ml of

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

2008-01-01

289

Serum proteins and paraproteins in women with silicone implants and connective tissue disease: a case–control study  

Microsoft Academic Search

Prior studies have suggested abnormalities of serum proteins, including paraproteins, in women with silicone implants but did not control for the presence of connective-tissue disease (CTD). This retrospective case–control study, performed in tertiary-care academic centers, assessed possible alterations of serum proteins, including paraproteins, in such a population. Seventy-four women with silicone implants who subsequently developed CTD, and 74 age-matched and

Gyorgy Csako; Rene Costello; Ejaz A Shamim; Terrance P O'Hanlon; Anthony Tran; Daniel J Clauw; H James Williams; Frederick W Miller

2007-01-01

290

[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

291

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

PubMed Central

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

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

2004-01-01

292

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

Microsoft Academic Search

BackgroundZinc (Zn) is an essential trace element and it is abundant in connective tissues, however biological roles of Zn and its transporters in those tissues and cells remain unknown.Methodology\\/Principal FindingsHere we report that mice deficient in Zn transporter Slc39a13\\/Zip13 show changes in bone, teeth and connective tissue reminiscent of the clinical spectrum of human Ehlers-Danlos syndrome (EDS). The Slc39a13 knockout

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

2008-01-01

293

Preliminary observations on differences in the Raman spectra of cancerous and noncancerous cells and connective tissue of human skin  

NASA Astrophysics Data System (ADS)

A less invasive method of reliably detecting skin cancers is required. Raman spectroscopy is just one of several spectroscopic methods that look promising, but are not yet sufficiently reliable. More information is needed on how and why the Raman spectra of cancerous skin tissue is different from its normal counterpart. We have used confocal micro-Raman spectroscopy with a spatial resolution of about a micron to obtain spectra of unstained thin sections of human skin. We found that there were clear differences in the Raman spectra between cancerous and non-cancerous tissue both in cells and in the connective tissue. The DNA contribution to the spectra was generally stronger in malignant cells than normal ones. In regions of the dermis far away from the tumor one obtains the usual collagen spectra of normal skin, but adjacent to the tumor the spectra no longer appeared to be those of native collagen.

Short, Michael A.; Lui, Harvey; McLean, David I.; Zeng, Haishan; Alajlan, Abdulmajeed; Chen, Michael X.

2005-04-01

294

Chemically-defined medium for growth and differentiation of mixed epithelial and connective tissues in organ culture.  

PubMed

The effect on tissue differentiation and growth in vitro of certain of the factors implicated in collagen synthesis (ascorbic acid, alpha-ketoglutarate and oxygen) and the influence of hydrocortisone was studied using organ cultures of fetal mouse mandible as a mixed epithelial and connective tissue system. Using serum-free Waymouth's MB 752/1 chemically-defined medium, addition of high levels of ascorbic acid (300mug per ml), hydrocortisone (1mug per ml) and oxygen (95%) enhanced differentiation in a number of tissues, in particular skin and appendages, tooth germs and bone, while osteoid and dentine production were noticeable promoted. It is suggested that an essential aspect of media design for organ culture involves the incorporaation of collagen-promoting factors to the in vitro enviornment particularly with regard to the controlling role implicated for collagen in a variety of biological processess. PMID:986366

Hodges, G M; Melcher, A H

1976-06-01

295

Practical Modeling Concepts for Connective Tissue Stem Cell and Progenitor Compartment Kinetics  

PubMed Central

Stem cell activation and development is central to skeletal development, maintenance, and repair, as it is for all tissues. However, an integrated model of stem cell proliferation, differentiation, and transit between functional compartments has yet to evolve. In this paper, the authors review current concepts in stem cell biology and progenitor cell growth and differentiation kinetics in the context of bone formation. A cell-based modeling strategy is developed and offered as a tool for conceptual and quantitative exploration of the key kinetic variables and possible organizational hierarchies in bone tissue development and remodeling, as well as in tissue engineering strategies for bone repair.

2003-01-01

296

Myxobolus cuneus n. sp. (Myxosporea) infecting the connective tissue of Piaractus mesopotamicus (Pisces: Characidae) in Brazil: histopathology and ultrastructure.  

PubMed

The characteristics of Myxobolus cuneus n. sp. and its relationship to the host Piaractus mesopotamicus are described based on light and electron microscopy and histological observations. Polysporic plasmodia measuring 20 microm to 2.1 mm in size were found in 63.3 % of the P. mesopotamicus examined. The parasite was found in the gall bladder, urinary bladder, gills, spleen, fins, head surface, liver and heart. Generative cells and disporoblastic pansporoblasts occurred along the periphery of the plasmodia, and mature spores were found in the internal region. The mature spores had a pear shaped body in frontal view, with a total length of 10.0 +/- 0.6 microm and a width of 5.1 +/- 0.3 microm (mean +/- SD). The spore wall was smooth with sutural folds. The polar capsules were elongated, were pear shaped, and equal in size (length 5.7 +/- 03 microm; width 1.7 +/- 0.2 microm), with the anterior ends close to each other. The polar filaments were tightly coiled in 8-9 turns perpendicular to the axis of the capsule. The plasmodia were always found in connective tissue (wall of the arterioles of the gill filaments, serous capsule of the gall bladder, middle layer and subepithelial connective tissue of the urinary bladder, connective tissue between the rays of the fins, subcutaneous tissue of the head surface and fibrous capsule spleen). The parasite caused important damage in the gills, where development occurred in the wall of gill filament arterioles; a mild macrophage infiltrate was also observed. In advanced developmental stages, the plasmodia caused deformation of the arteriole structure, with a reduction and, in some cases, obstruction of the lumen. The parasite was found throughout the period studied and its prevalence was unaffected by host size, season or water properties. PMID:16800122

Adriano, E A; Arana, S; Cordeiro, N S

2006-06-01

297

Autoimmune hypophysitis.  

PubMed

Autoimmune (lymphocytic) hypophysitis is a rare disease that should be considered in the differential diagnosis of any nonsecreting pituitary mass, especially when occurring during pregnancy or postpartum. We have analyzed 370 articles published from January 1962 to October 2004 and identified a total of 379 patients with primary lymphocytic hypophysitis. The present review synthesizes the clinical and research data reported in this body of scientific literature. PMID:15634713

Caturegli, Patrizio; Newschaffer, Craig; Olivi, Alessandro; Pomper, Martin G; Burger, Peter C; Rose, Noel R

2005-08-01

298

[Molecular mechanisms of neuronal connective tissue genesis during the course of cerebral cortex development].  

PubMed

The cerebral cortex constitutes one of the most complex structures in our brain. In correlation with its elaborate functions, it is characterized by the great complexity of its neuronal connections, but the mechanisms responsible for the generation of these connections remain poorly known. We have recently initiated the characterization of a new multigenic family of axon guidance factors, the ephrin/Eph gene family, during the development of neuronal connections in the mouse cortex. Combining expression studies, in vitro guidance essays, and in vivo analysis of mutant mice, enabled us to demonstrate the critical role of ephrin/Eph genes in the development of cortical networks. Mutant mice for ephrin/Eph genes display a topographic distortion of their cortical somatosensory map, as well as ectopic projections from the motor thalamus to the somatosensory cortex. The identification of factors like ephrins, capable to (re)specify the pattern of neuronal connections, has implications for our understanding of pathological brain development (epilepsy, abnormal movements, psychiatric diseases), and in the perspective of the rational design of cell therapies of neurodegenerative diseases. PMID:15366735

Vanderhaeghen, P

2004-01-01

299

Thyroid autoimmunity.  

PubMed

This overview of the thyroid autoimmunity in human presents the various facets of a very common pathology. Focus is rather on fundamental than clinical aspects, although some specific clinical situations are discussed. Epidemiology, pathophysiology and pathology of AITD are detailed. One of the peculiarities of AITD is that they express two opposed phenotypes, hypothyroid thyroiditis and hyperthyroid Graves' disease. The latter is characterised by the presence of a unique type of autoantibodies, the anti-TSH receptor antibodies. Those are capable to activate the TSH receptor leading to the gland hypertrophy and hyperfunction. On the contrary, the autoimmune thyroiditis processus progressively and slowly tends to the necrosis/apoptosis of thyroid cells and their functional impairment. Other forms of autoimmune thyroiditis, postpartum thyroiditis and silent thyroiditis are also described. This review, which is not exhaustive, aims at providing a wide scope on the AITD, a basis from which the interested reader or the specialist will be able to find routes towards deeper knowledge. PMID:23164679

Orgiazzi, Jacques

2012-12-01

300

Efficacy of connective tissue massage and Mc Mennell joint manipulation in the rehabilitative treatment of the hands in systemic sclerosis.  

PubMed

Rehabilitation may contribute to the management of systemic sclerosis (SSc) dealing with disabilities due to hand involvement. The aim of this study is to evaluate the efficacy of a rehabilitation programme based on the combination of connective tissue massage and Mc Mennell joint manipulation specifically conceived for SSc patients' hands. Forty SSc patients were enrolled: 20 (interventional group) were treated for a 9-week period (twice a week, 1 h per session) with a combination of connective tissue massage, Mc Mennell joint manipulation and home exercise programme, and 20 (control group) were assigned only to home exercise programme. Patients of both groups were assessed at baseline (T0), after 9 week (T1) and at a 9 weeks follow-up (T2). They were evaluated for quality of life by SF-36 and Health Assessment Questionnaire (HAQ), hands involvement by Hand Mobility in Scleroderma (HAMIS) test, Cochin hand functional disability scale and the measurements of ROM. In the interventional group, fist closure, HAMIS test and Cochin hand functional disability scale improved at the end of the treatment (p < 0.0001) as well as HAQ, Physical Synthetic Index (PSI) and Mental Synthetic Index (MSI) of SF-36 scores (HAQ and PSI, p < 0.0001; MSI, p < 0.001). In the control group, the programme of home daily exercises improved only fist closure at the end of the treatment (p < 0.0001). The combination of connective tissue massage, Mc Mennell joint manipulation and home exercise programme is effective in the rehabilitative treatment of SSc hands. This combined treatment may lead to an improvement of hand function and quality of life. PMID:19554274

Bongi, Susanna Maddali; Del Rosso, Angela; Galluccio, Felice; Sigismondi, Fabrizio; Miniati, Irene; Conforti, M Letizia; Nacci, Francesca; Cerinic, Marco Matucci

2009-10-01

301

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

Microsoft Academic Search

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

Chisa Shukunami; Yuji Hiraki

2007-01-01

302

Proliferative Diseases of Hemocytes, Endothelial Cells, and Connective Tissue Cells in Mollusks.  

National Technical Information Service (NTIS)

Probable neoplasia involving the hematopoietic or reticular tissues have been found in oysters (C. virginica, C. gigas, and O. lurida) and mussels (M. edulis). The disorders are rare (0.02% in crassostreids from both U.S. coasts, but epizootic (12%) in os...

C. A. Farley A. K. Sparks

1970-01-01

303

Molecular species of collagen in the intramuscular connective tissues of the marine crab, Scylla serrata  

Microsoft Academic Search

Type V like collagens are widely distributed in marine invertebrates, particularly crustaceans and molluscs. We have been investigating the nature of collagens in the muscular tissues of crustaceans. The presence of type V like homotrimeric collagen in prawn muscle was noted before. We report here a comparative analysis of collagens purified from the pepsin digest of abdominal and pereiopod muscle

Pitchumani Sivakumar; Lonchin Suguna; Gowri Chandrakasan

2000-01-01

304

Changing the gingival color discrepancy induced by pigmented root using subepithelial connective tissue graft: a case report.  

PubMed

Metallic alloys can suffer corrosion, and metallic posts and cores used for restorative procedures may develop a blue-gray pigmentation in root dentin, which in turn changes the color of gingival tissues. Removing posts and cores may lead to root fracture, and bleaching agents have a limited effect on staining from alloy corrosion. Surgical techniques for correcting undesirable esthetic deficiencies have been investigated in the literature. This article describes the case of a patient with gingival discoloration caused by root pigmentation in the maxillary area. A subepithelial connective graft harvested from the palate was used to treat the gingival color discrepancy. PMID:24784518

Sirolli, Marcelo; Martos, Josue; Sukekava, Flavia; Pannuti, Claudio Mendes; Cesar-Neto, Joao Batista

2014-01-01

305

[Pulmonary arterial hypertension: a flavor of autoimmunity].  

PubMed

It is admitted that autoimmunity results from a combination of risks such as genetic background, environmental triggers, and stochastic events. Pulmonary arterial hypertension (PAH) shares with the so-called prototypic autoimmune diseases, genetic risk factors, female predominance and sex hormone influence, association with other chronic inflammatory and autoimmune diseases, defects in regulatory T cells function, and presence of autoantibodies. Case reports have been published indicating the beneficial effect of some immunosuppressive and anti-inflammatory therapies in PAH, supporting the potential role of immune mechanisms in the pathophysiology of the disease. In this review, we discuss the current knowledge on autoimmune mechanisms operating in PAH, especially mounting a local autoimmune response inside the pulmonary tissue, namely pulmonary lymphoid neogenesis. A better understanding of the role of autoimmunity in pulmonary vascular remodelling may help develop targeted immunomodulatory strategies in PAH. PMID:23859515

Perros, Frédéric; Humbert, Marc; Cohen-Kaminsky, Sylvia

2013-01-01

306

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

307

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

PubMed Central

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

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

2013-01-01

308

Treatment of Gingival Recessions Associated to Cervical Abrasion Lesions with Subepithelial Connective Tissue Graft: A Case Report  

PubMed Central

Extensive gingival recessions associated with cervical abrasions are common among the population. Several different surgical and/or restorative therapies have been proposed to correct these lesions. This manuscript reports the treatment of multiple gingival recessions associated to cervical abrasions. The procedure involved the utilization of subepithelial connective tissue graft (SCTG) combined with coronally advanced flap onto a previously restored root surface. At the postoperative follow-up visits, the success of the restorative/surgical approach was confirmed by the absence of bleeding to probing and periodontal pockets as well as presence of gingival tissue with normal color, texture and contouring. After 18 months of follow-up, the clinical conditions are stable with satisfactory root coverage and periodontal health. An excellent esthetical outcome was achieved and the patient is satisfied with case resolution.

Deliberador, Tatiana M.; Bosco, Alvaro F.; Martins, Thiago M.; Nagata, Maria J. H.

2009-01-01

309

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

PubMed Central

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

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

2014-01-01

310

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

311

Safety of high-dose intravenous immunoglobulin in systemic autoimmune diseases  

Microsoft Academic Search

It is reported that the usage of high-dose intravenous immunoglobulin (HD-IVIG) in systemic autoimmune iseases is associated\\u000a with various adverse events in a wide range of severity. We aimed to investigate the frequency and profile of adverse events\\u000a in a group of patients with diffuse connective tissue diseases and Wegener’s granulomatosis (WG) who were administrated HD-IVIG\\u000a for different indications. We

Fatih Tufan; Sevil Kamali; Burak Erer; Ahmet Gul; Murat Inanc; Lale Ocal; Meral Konice; Orhan Aral

2007-01-01

312

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.

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

2013-01-01

313

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.

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

314

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

PubMed

Conventional sports training emphasizes adequate training of muscle fibres, of cardiovascular conditioning and/or neuromuscular coordination. Most sports-associated overload injuries however occur within elements of the body wide fascial net, which are then loaded beyond their prepared capacity. This tensional network of fibrous tissues includes dense sheets such as muscle envelopes, aponeuroses, as well as specific local adaptations, such as ligaments or tendons. Fibroblasts continually but slowly adapt the morphology of these tissues to repeatedly applied challenging loading stimulations. Principles of a fascia oriented training approach are introduced. These include utilization of elastic recoil, preparatory counter movement, slow and dynamic stretching, as well as rehydration practices and proprioceptive refinement. Such training should be practiced once or twice a week in order to yield in a more resilient fascial body suit within a time frame of 6-24 months. Some practical examples of fascia oriented exercises are presented. PMID:23294691

Schleip, Robert; Müller, Divo Gitta

2013-01-01

315

Autoimmune thyrotoxicosis: diagnostic challenges.  

PubMed

Autoimmune thyrotoxicosis or Graves' disease (GD) is the most common cause of hyperthyroidism in the United States (full text available online: http://education.amjmed.com/pp1/249). GD occurs more often in women (ratio 5:1) and has a population prevalence of 1-2%. A genetic determinant to the susceptibility to GD is suspected because of familial clustering of the disease, a high sibling recurrence risk, and the familial occurrence of thyroid autoantibodies. GD is a systemic autoimmune thyroid disorder characterized by the infiltration of immune effector cells and thyroid-antigen-specific T cells into the thyroid and thyroid stimulating hormone receptor (TSHR) expressing tissues, i.e. orbit, skin, with the production of autoantibodies to well-defined thyroidal antigens. Stimulatory autoantibodies in GD activate the TSHR leading to thyroid hyperplasia and unregulated thyroid hormone production and secretion. Diagnosis of GD is straightforward in a patient with a diffusely enlarged, heterogeneous, hypervascular (increased Doppler flow on neck ultrasound) thyroid gland, associated orbitopathy, biochemically confirmed thyrotoxicosis, positive TSHR autoantibodies, and often a family history of autoimmune disorders. PMID:22938935

Ponto, Katharina A; Kahaly, George J

2012-09-01

316

Hair loss in autoimmune systemic diseases.  

PubMed

Hair loss is commonly seen in autoimmune diseases. In pemphigus, although scalp involvement is common, hair loss is rarely reported. In classical bullous pemphigoid, alopecia is not reported while it is described in the Brusting-Perry variant of bullous pemphigoid and in epidermolysis bullosa acquisita. In these two diseases alopecia is cicatricial. In connective tissue diseases, in lupus erythematosus (LE) hair loss is frequent; in particular in LE there are two types of alopecia: non scarring and scarring alopecia. The non scarring form is a finding of acute systemic LE and the scarring form develops when a typical discoid lesion is located on the scalp. In dermatomyositis alopecia is usually non scarring and generalized. In scleroderma, alopecia is associated with en coupe de sabre morphea. PMID:24566567

Parodi, A; Cozzani, E

2014-02-01

317

Connecting incremental shear modulus and Poisson's ratio of lung tissue with morphology and rheology of microstructure.  

PubMed

The width and curvature of the collagen and elastin fiber bundles in the human pulmonary interalveolar septa and alveolar mouths are measured. The data, together with the known mechanical properties of collagen and elastin fibers, are used to derive the incremental elastic moduli of the lung tissue. The constitutive equation for small incremental stress and strain superposed on a homeostatic inflated lung is linear and isotropic, and characterized by two material constants. PMID:2605333

Fung, Y C

1989-01-01

318

Gangliosides and autoimmune diabetes.  

PubMed

Gangliosides are sialic acid-containing glycolipids which are formed by a hydrophobic portion, the ceramide, and a hydrophilic part, i.e. the oligosaccharide chain. First described in neural tissue, several studies have shown that gangliosides are almost ubiquitous molecules expressed in all vertebrate tissues. Within cells, gangliosides are usually associated with plasma membranes, where they can act as receptors for a variety of molecules and have been shown to take part in cell-to-cell interaction and in signal transduction. In addition, gangliosides are expressed in cytosol membranes like those of secretory granules of some endocrine cells (adrenal medulla, pancreatic islets). As far as the role of gangliosides in diseases is concerned, there are some cases in which an aberrant ganglioside expression plays a crucial role in the disease pathogenetic process. These diseases include two major forms of ganglioside storage, namely GM2-gangliosidosis (Tay-Sachs and its beta-hexosaminidase deficiency) and GM1-gangliosidosis (beta-galactosidase deficiency), where the most prominent pathological characteristic is the lysosomal ganglioside accumulation in neurons. Other inflammatory or degenerative diseases both within and outside the nervous system have been shown to be associated with an altered pattern of ganglioside expression in the target organ. Since monoclonal antibodies have been discovered and used in immunology, a large variety of ganglioside antigens has been described both as blood group antigens and as tumour-related antigens. Several studies have also indicated that gangliosides can act not only as antigens, but also as autoantigens. As a matter of fact, auto-antibodies to gangliosides, detected by immunostaining methods performed directly on TLC plates or by ELISA, have been described in several autoimmune disorders such as Guillain-Barré syndrome, multiple sclerosis, lupus erythematosus, Hashimoto's thyroiditis and, last but not least, insulin-dependent (type 1) diabetes mellitus. This last disease is caused by the autoimmune destruction of insulin-producing pancreatic islet cells in genetically predisposed individuals. Autoantibodies and T lymphocytes directed towards multiple islet autoantigens have been detected in the circulation, well before the clinical onset of the disease, in a prodromal phase during which pancreatic islet beta-cells are presumably destroyed. Among the target autoantigens, some are of protein nature but others are acidic glycolipids such as sulphatides158 and the gangliosides GT3, GD3 and especially GM2-1. This last component is specifically expressed in pancreatic islets and has been shown to represent a target of IgG autoantibodies highly associated with diabetes development in first-degree relatives of type 1 diabetic individuals. In addition, the GM2-1 ganglioside appears to be one of the antigens recognized by cytoplasmic ICA, a heterogeneous group of antibodies which specifically react with islets on pancreatic frozen sections. In conclusion, studies performed in the last decade have clearly indicated that gangliosides represent a heterogeneous class of molecules that are involved in several cellular processes that are of crucial importance in physiological as well as in pathological conditions. Interestingly, these molecules, despite their small size, have been shown to represent not only important antigens in tumour immunology but are also able to elicit a specific autoimmune response, thus representing important autoantigens in some autoimmune disorders. It is of interest that, in addition to neurological autoimmune disorders where autoimmunity to gangliosides is frequent and usually of considerable magnitude, an autoimmune response to this class of molecules has been observed in autoimmune diabetes. (ABSTRACT TRUNCATED) PMID:9307889

Misasi, R; Dionisi, S; Farilla, L; Carabba, B; Lenti, L; Di Mario, U; Dotta, F

1997-09-01

319

CD22 and autoimmune disease.  

PubMed

CD22 is a 140-kDa member of the Siglec family of cell surface proteins that is expressed by most mature B-cell lineages. As a co-receptor of the B-cell receptor (BCR), it is known to contribute to the sensitive control of the B-cell response to antigen. Cross-linking of CD22 and the BCR by antigen triggers the phosphorylation of CD22, which leads to activation of signaling molecules such as phosphatases. Signal transduction pathways involving CD22 have been explored in a number of mouse models, some of which have provided evidence that in the absence of functional CD22, B cells have a "hyperactivated" phenotype, and suggest that loss of CD22 function could contribute to the pathogenesis of autoimmune diseases. Modulating CD22 activity has therefore been suggested as a possible therapeutic approach to such diseases. For example, the novel CD22-targeting monoclonal antibody epratuzumab is currently under investigation as a treatment for the connective tissue disorder systemic lupus erythematosus (SLE). PMID:23083346

Dörner, Thomas; Shock, Anthony; Smith, Kenneth G C

2012-10-01

320

Vaccines for Autoimmune and Infectious Disease.  

National Technical Information Service (NTIS)

The present invention provides HLA-restricted antigens as vaccines for treating or preventing autoimmune diseases or conditions, transplant rejection or vasculitis in a patient. In particular aspects, there is provided Pr3, a myeloid tissue-restricted pro...

J. Molldrem

2004-01-01

321

Tumor necrosis factor-alpha in synovial fluid and plasma from patients with chronic connective tissue disease and its relation to temporomandibular joint pain  

Microsoft Academic Search

Purpose: The purpose of this study was to determine the level of tumor necrosis factor-alpha (TNF-?) in the temporomandibular joint (TMJ) synovial fluid (SF-TNF-?) and blood plasma (P-TNF-?) of patients with chronic inflammatory connective tissue disease and investigate its relation to TMJ pain, hyperalgesia, and allodynia.Patients and Methods: Twenty-four patients with a diagnosis of chronic inflammatory connective tissue disease and

Silvi Nordahl; Per Alstergren; Sigvard Kopp

2000-01-01

322

The U1-snRNP complex: structural properties relating to autoimmune pathogenesis in rheumatic diseases  

PubMed Central

Summary The U1 small nuclear ribonucleoprotein particle (snRNP) is a target of autoreactive B cells and T cells in several rheumatic diseases including systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD). We propose that inherent structural properties of this autoantigen complex, including common RNA-binding motifs, B and T-cell epitopes, and a unique stimulatory RNA molecule, underlie its susceptibility as a target of the autoimmune response. Immune mechanisms that may contribute to overall U1-snRNP immunogenicity include epitope spreading through B and T-cell interactions, apoptosis-induced modifications, and Toll-like receptor (TLR) activation through stimulation by U1-snRNA. We conclude that understanding the interactions between U1-snRNP and the immune system will provide insights into why certain patients develop anti-U1-snRNP autoimmunity, and more importantly how to effectively target therapies against this autoimmune response.

Kattah, Nicole H.; Kattah, Michael G.; Utz, Paul J.

2011-01-01

323

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.

Castori, Marco

2012-01-01

324

Muscle degeneration in neuraminidase 1-deficient mice results from infiltration of the muscle fibers by expanded connective tissue.  

PubMed

Neuraminidase 1 (NEU1) regulates the catabolism of sialoglycoconjugates in lysosomes. Congenital NEU1 deficiency in children is the basis of sialidosis, a severe neurosomatic disorder in which patients experience a broad spectrum of clinical manifestations varying in the age of onset and severity. Osteoskeletal deformities and muscle hypotonia have been described in patients with sialidosis. Here we present the first comprehensive analysis of the skeletal muscle pathology associated with loss of Neu1 function in mice. In this animal model, skeletal muscles showed an expansion of the epimysial and perimysial spaces, associated with proliferation of fibroblast-like cells and abnormal deposition of collagens. Muscle fibers located adjacent to the expanded connective tissue underwent extensive invagination of their sarcolemma, which resulted in the infiltration of the fibers by fibroblast-like cells and extracellular matrix, and in their progressive cytosolic fragmentation. Both the expanded connective tissue and the juxtaposed infiltrated muscle fibers were strongly positive for lysosomal markers and displayed increased proteolytic activity of lysosomal cathepsins and metalloproteinases. These combined features could lead to abnormal remodeling of the extracellular matrix that could be responsible for sarcolemmal invagination and progressive muscle fiber degeneration, ultimately resulting in an overt atrophic phenotype. This unique pattern of muscle damage, which has never been described in any myopathy, might explain the neuromuscular manifestations reported in patients with the type II severe form of sialidosis. More broadly, these findings point to a potential role of NEU1 in cell proliferation and extracellular matrix remodeling. PMID:20388541

Zanoteli, Edmar; van de Vlekkert, Diantha; Bonten, Erik J; Hu, Huimin; Mann, Linda; Gomero, Elida M; Harris, A John; Ghersi, Giulio; d'Azzo, Alessandra

2010-01-01

325

Muscle Degeneration in Neuramindase 1 Deficient Mice Results from Infiltration of the Muscle Fibers by Expanded Connective Tissue  

PubMed Central

SUMMARY Neuraminidase 1 (NEU1) regulates the catabolism of sialoglycoconjugates in lysosomes. Congenital NEU1 deficiency in children is the basis of sialidosis, a severe neurosomatic disorder in which patients experience a broad spectrum of clinical manifestations varying in the age of onset and severity. Osteoskeletal deformities and muscle hypotonia have been described in patients with sialidosis. Here we present the first comprehensive analysis of the skeletal muscle pathology associated with loss of Neu1 function in mice. In this animal model, skeletal muscles showed an expansion of the epimysial and perimysial spaces, associated with proliferation of fibroblast-like cells and abnormal deposition of collagens. Muscle fibers located adjacent to the expanded connective tissue underwent extensive invagination of their sarcolemma, which resulted in the infiltration of the fibers by fibroblast-like cells and extracellular matrix, and in their progressive cytosolic fragmentation. Both the expanded connective tissue and the juxtaposed infiltrated muscle fibers were strongly positive for lysosomal markers, and displayed increased proteolytic activity of lysosomal cathepsins and metalloproteinases. These combined features could lead to abnormal remodeling of the extracellular matrix that could be responsible for sarcolemmal invagination and progressive muscle fiber degeneration, ultimately resulting in an overt atrophic phenotype. This unique pattern of muscle damage, which has never been described in any myopathy, might explain the neuromuscular manifestations reported in patients with the type II severe form of sialidosis. More broadly, these findings point to a potential role of NEU1 in cell proliferation and extracellular matrix remodeling.

Zanoteli, Edmar; van de Vlekkert, Diantha; Bonten, Erik J.; Hu, Huimin; Mann, Linda; Gomero, Elida M.; Harris, A. John; Ghersi, Giulio; d'Azzo, Alessandra

2010-01-01

326

Passive mechanical properties of rat abdominal wall muscles suggest an important role of the extracellular connective tissue matrix.  

PubMed

Abdominal wall muscles have a unique morphology suggesting a complex role in generating and transferring force to the spinal column. Studying passive mechanical properties of these muscles may provide insights into their ability to transfer force among structures. Biopsies from rectus abdominis (RA), external oblique (EO), internal oblique (IO), and transverse abdominis (TrA) were harvested from male Sprague-Dawley rats, and single muscle fibers and fiber bundles (4-8 fibers ensheathed in their connective tissue matrix) were isolated and mechanically stretched in a passive state. Slack sarcomere lengths were measured and elastic moduli were calculated from stress-strain data. Titin molecular mass was also measured from single muscle fibers. No significant differences were found among the four abdominal wall muscles in terms of slack sarcomere length or elastic modulus. Interestingly, across all four muscles, slack sarcomere lengths were quite long in individual muscle fibers (>2.4 µm), and demonstrated a significantly longer slack length in comparison to fiber bundles (p < 0.0001). Also, the extracellular connective tissue matrix provided a stiffening effect and enhanced the resistance to lengthening at long muscle lengths. Titin molecular mass was significantly less in TrA compared to each of the other three muscles (p < 0.0009), but this difference did not correspond to hypothesized differences in stiffness. PMID:22267257

Brown, Stephen H M; Carr, John Austin; Ward, Samuel R; Lieber, Richard L

2012-08-01

327

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

PubMed Central

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

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

2011-01-01

328

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

PubMed Central

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

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

2013-01-01

329

[Autoimmune pancreatitis].  

PubMed

Autoimmune pancreatitis is a relatively rare form of chronic pancreatitis which is characterized by a lymphoplasmatic infiltrate with a storiform fibrosis and often goes along with painless jaundice and discrete discomfort of the upper abdomen. Clinically we distinguish between two subtypes, which differ in terms of their histology, clinical picture and prognosis. Type 1 autoimmune pancreatitis is the pancreatic manifestation of the IgG4-associated syndrome which also involves other organs. About one third of the patients can only be diagnosed after either histological prove or a successful steroid trail. Type 2 is IgG4-negative with the histological picture of an idiopathic duct centric pancreatitis and is to higher degree associated with inflammatory bowel disease. A definitive diagnosis can only be made using biopsy. Usually both forms show response to steroid treatment, but in type 1 up to 50?% of the patients might develop a relapse. The biggest challenge and most important differential diagnosis remains the discrimination of AIP from pancreatic cancer, because also AIP can cause mass of the pancreatic head, lymphadenopathy and ductal obstruction. This article summarizes recent advances on epidemiology, clinical presentation, diagnostic strategy, therapy and differential diagnosis in this relatively unknown disease. PMID:24193862

Beyer, G; Menzel, J; Krüger, P-C; Ribback, S; Lerch, M M; Mayerle, J

2013-11-01

330

Controlling the Fibroblastic Differentiation of Mesenchymal Stem Cells Via the Combination of Fibrous Scaffolds and Connective Tissue Growth Factor  

PubMed Central

Controlled differentiation of multi-potent mesenchymal stem cells (MSCs) into vocal fold-specific, fibroblast-like cells in vitro is an attractive strategy for vocal fold repair and regeneration. The goal of the current study was to define experimental parameters that can be used to control the initial fibroblastic differentiation of MSCs in vitro. To this end, connective tissue growth factor (CTGF) and micro-structured, fibrous scaffolds based on poly(glycerol sebacate) (PGS) and poly(?-caprolactone) (PCL) were used to create a three-dimensional, connective tissue-like microenvironment. MSCs readily attached to and elongated along the microfibers, adopting a spindle-shaped morphology during the initial 3 days of preculture in an MSC maintenance medium. The cell-laden scaffolds were subsequently cultivated in a conditioned medium containing CTGF and ascorbic acids for up to 21 days. Cell morphology, proliferation, and differentiation were analyzed collectively by quantitative PCR analyses, and biochemical and immunocytochemical assays. F-actin staining showed that MSCs maintained their fibroblastic morphology during the 3 weeks of culture. The addition of CTGF to the constructs resulted in an enhanced cell proliferation, elevated expression of fibroblast-specific protein-1, and decreased expression of mesenchymal surface epitopes without markedly triggering chondrogenesis, osteogenesis, adipogenesis, or apoptosis. At the mRNA level, CTGF supplement resulted in a decreased expression of collagen I and tissue inhibitor of metalloproteinase 1, but an increased expression of decorin and hyaluronic acid synthesase 3. At the protein level, collagen I, collagen III, sulfated glycosaminoglycan, and elastin productivity was higher in the conditioned PGS-PCL culture than in the normal culture. These findings collectively demonstrate that the fibrous mesh, when combined with defined biochemical cues, is capable of fostering MSC fibroblastic differentiation in vitro.

Tong, Zhixiang; Sant, Shilpa

2011-01-01

331

Large leg ulcers due to autoimmune diseases  

PubMed Central

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

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

2011-01-01

332

Connective tissue growth factor—a novel mediator of angiotensin II-stimulated cardiac fibroblast activation in heart failure in rats  

Microsoft Academic Search

The pathophysiologic mechanisms of myocardial remodeling in heart failure (HF) remain poorly understood. Using differential mRNA display of myocardial tissue from rats with ischemic HF vs. controls we identified robust myocardial induction of the mRNA encoding connective tissue growth factor (CTGF). The aim of this study was to investigate the sites of synthesis and the mechanisms of induction of CTGF

Mohammed Shakil Ahmed; Erik Řie; Leif Erik Vinge; Arne Yndestad; Geir Řystein Andersen; Yvonne Andersson; Toril Attramadal; Hĺvard Attramadal

2004-01-01

333

Viruses, cytokines, antigens, and autoimmunity.  

PubMed Central

To explain the pathogenesis of autoimmunity, we hypothesize that following an infection the immune response spreads to tissue-specific autoantigens in genetically predisposed individuals eventually determining progression to disease. Molecular mimicry between viral and self antigens could, in some instances, initiate autoimmunity. Local elicitation of inflammatory cytokines following infection probably plays a pivotal role in determining loss of functional tolerance to self autoantigens and the destructive activation of autoreactive cells. We also describe the potential role of interleukin 10, a powerful B-cell activator, in increasing the efficiency of epitope recognition, that could well be crucial to the progression toward disease.

Gianani, R; Sarvetnick, N

1996-01-01

334

Antigenic properties of a non-collagenous reticulin component of normal connective tissue  

PubMed Central

Rabbit antisera raised against a saline-insoluble non-collagenous reticulin component (NCRC) of pig and human kidney gave immunofluorescent staining of basement membranes, stroma of liver and kidney and newly formed blood vessels in pig, rat and human tissue. The staining patterns closely resembled those reported for anti-reticulin antibodies, and both species-specific and species-shared determinants could be distinguished. Although the antisera reacted least with rat glomeruli in cryostat sections, rabbit immunoglobulin localized persistently but harmlessly in the renal glomeruli of rats given the antisera intravenously. Absorption with NCRC of sera from patients with gluten-sensitive enteropathy in most cases removed the anti-reticulin antibody characteristic of this group of diseases. ImagesFIG. 1FIG. 2FIG. 3FIG. 4FIG. 5

Pras, M.; Johnson, G. D.; Holborow, E. J.; Glynn, L. E.

1974-01-01

335

Regaud Lecture, Granada 1994. Tumors of the connective and supporting tissues.  

PubMed

There has been a continuous acceleration of medical/scientific inquiry and of actual improvements in management of patients with neoplasms of the mesenchymal tissues over the last four decades. The number of publications in this field has increased from 1140 in 1970 and then to 1700 in 1990. Important advances discussed over this period include: establishment of sarcoma teams in major oncology centers; staging systems for both soft tissue and osseous sarcomas; demonstration of genetic determinants in the development of, at least, some of the sarcomas; the revolutionary change in quality of diagnostic imaging by the introduction of CT and MRI; use of immunohistochemistry in diagnostic pathology; the drastic gains in survival of patients with osteogenic sarcoma, Ewing's sarcoma and rhabdomyosarcoma due to the efficacy of multi-drug and multi-cycle chemotherapy protocols; major advances in surgical techniques which have made limb salvage practical; cell lines derived from human sarcomas have been shown to have in vitro radiation sensitivity comparable to that of cell lines from epithelial tumors; the combination of conservative surgery and moderate doses of radiation yields local control and survival results equivalent to that of radical surgery with a much improved functional and cosmetic outcome; intra-operative electron beam radiation therapy improves the outcome of patients with retroperitoneal sarcomas when given after grossly complete resection combined with external beam radiation therapy (pre- or postoperatively); radiation is a highly effective alternative to extensive surgery for desmoid tumors; local control of giant cell tumors by modern radiation techniques is approximately 80% and the incidence of radiation induced tumors at 10 years is approximately 3%; to decrease the incidence of radiation induced sarcoma, resection has replaced radiation in the management of selected patients with primary Ewing's sarcoma when the response to chemotherapy has been excellent and the morbidity/functional decrement consequent upon the surgery judged reasonable; proton beam radiation therapy has been accepted as being superior to conventional external beam radiation therapy for chondrosarcoma and chordoma of the skull base; and attempts to utilize brachytherapy for sarcomas of the spine/sacrum appear to offer promise. Projected advances in the coming two decades includes:Designation of sarcoma type on genetic characterization; molecular genetics will provide prognostic information as to probability of distant metastasis, response to chemotherapeutic agents and radiation; important further reductions in the radiation treatment volume due to the many technical developments entering, or soon to enter the clinic; non-invasive assessment of the response to chemotherapy; much increased appreciation of the late sequella of treatment, both radiation and chemotherapy. PMID:7597217

Suit, H

1995-02-01

336

Unexpected targets and triggers of autoimmunity.  

PubMed

Recent findings indicate that the role of Th17 cells in the pathogenesis of tissue inflammation and autoimmunity has become rather complicated. While interleukin-17 (IL-17) producing CD4(+) T cells are found frequently within the peripheral target tissue during the course of autoimmune disease, these cells may contribute to or protect from inflammation. Accumulating reports have revealed the existence of both pathogenic and non-pathogenic Th17 cells. These Th17 subsets produce the signature cytokines IL-17A and IL-17F yet have distinct and divergent roles in inducing autoimmune tissue inflammation. Comparative genomic sequence analyses between the pathogenic and non-pathogenic Th17 cells have exposed unexpected and extensive population heterogeneity within the Th17 subset. Here we review some of the unexpected factors that may drive pathogenic divergence. Understanding the functional consequences of Th17 cell diversity may allow for the selection of more precise targets for intervention in autoimmune and inflammatory diseases. PMID:24789684

Lee, Youjin; Collins, Mary; Kuchroo, Vijay K

2014-07-01

337

Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells  

SciTech Connect

Although commonly used to control a variety of inflammatory diseases, the mechanism of action of a low dose of methotrexate remains a mystery. Methotrexate accumulates intracellularly where it may interfere with purine metabolism. Therefore, the authors determined whether a 48-hr pretreatment with methotrexate affected adenosine release from ({sup 14}C)adenine-labeled human fibroblasts and umbilical vein endothelial cells. Methotrexate significantly increased adenosine release by fibroblasts. The effect of methotrexate on adenosine release was not due to cytotoxicity since cells treated with maximal concentrations of methotrexate took up ({sup 14}C)adenine and released {sup 14}C-labeled purine (a measure of cell injury) in a manner identical to control cells. Methotrexate treatment of fibroblasts dramatically inhibited adherence to fibroblasts by both unstimulated neutrophils and stimulated neutrophils. One hypothesis that explains the effect of methotrexate on adenosine release is that, by inhibition of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) transformylase, methotrexate induces the accumulation of AICAR, the nucleoside precursor of which has previously been shown to cause adenosine release from ischemic cardiac tissue. The observation that the antiinflammatory actions of methotrexate are due to the capacity of methotrexate to induce adenosine release may form the basis for the development of an additional class of antiinflammatory drugs.

Cronstein, B.N.; Eberle, M.A.; Levin, R.I. (New York Univ. Medical Center, New York (United States)); Gruber, H.E. (Gensia Pharmaceuticals, Inc., San Diego, CA (United States))

1991-03-15

338

A heart-adipose tissue connection in the regulation of energy metabolism.  

PubMed

Almost 20 years ago, the protein encoded by the ob locus in mice was identified as an adipocyte-secreted hormone, now termed leptin, which functions as a peripheral signal to communicate the organism's energy reserve--and thereby protects against starvation due to insufficient caloric resources. Additional peripheral factors have since been identified that coordinate interorgan crosstalk to manage energy resources. The heart is included in this network through its regulated release of natriuretic peptides A and B--cardiac hormones originally identified as important in blood pressure control. Emerging evidence that natriuretic peptide receptors are expressed in adipose tissue, and that circulating levels of these peptides are decreased in animals and humans with obesity, could imply that natriuretic peptides are also involved in the regulation of energy metabolism. The natriuretic peptides stimulate triglyceride lipolysis in adipocytes, a process also regulated by the sympathetic nervous system. In addition, these two pathways promote uncoupling of mitochondrial respiration and thermogenesis in brown adipocytes. This Review focuses on the roles of the natriuretic peptides and the sympathetic nervous system in regulating adipocyte metabolism. The potential for manipulating the natriuretic peptide pathway to increase energy expenditure in obesity and manage the complications of cardiometabolic disease is also discussed. PMID:24296515

Collins, Sheila

2014-03-01

339

Phosphaturic mesenchymal tumor, mixed connective tissue variant, of the mandible: Report of a case and review of the literature  

PubMed Central

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome that results in renal phosphate wasting with hypophosphatemia. In most cases, the underlying cause of TIO is a small mesenchymal neoplasm that is often difficult to detect, resulting in delayed diagnosis. One such neoplasm is the phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT), an unusual entity with unique morphologic and biochemical features. The majority of these tumors are found at appendicular sites with only rare cases reported in the jaws. We describe a PMTMCT involving the mandible in a patient with a protracted history of osteomalacia. A review of the current literature is provided with emphasis on the clinical and histologic features, etiopathogenesis, and management of PMTMCT in the setting of TIO.

Woo, Victoria L.; Landesberg, Regina; Imel, Erik A.; Singer, Steven R.; Folpe, Andrew L.; Econs, Michael J.; Kim, Taeyun; Harik, Lara R.; Jacobs, Thomas P.

2009-01-01

340

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

PubMed Central

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

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

2007-01-01

341

Regulation of lysyl oxidase, collagen, and connective tissue growth factor by TGF-beta1 and detection in human gingiva.  

PubMed

Gingival overgrowth is characterized by excess extracellular matrix accumulation and elevated levels of cytokines, including transforming growth factor-beta1 (TGF-beta1). The functional relationships between altered cytokine levels and extracellular matrix accumulation have not been extensively investigated in gingival cells and tissues. Lysyl oxidase catalyzes the final known enzymatic step required for cross-linking collagen and elastin in the synthesis of a functional extracellular matrix. This study investigated the regulation by TGF-beta1 of lysyl oxidase and its collagen and elastin substrates in early passage human gingival fibroblasts. In addition, TGF-beta1 regulation of connective tissue growth factor (CTGF) was assessed in human gingival cells and tissues. The results show that TGF-beta1 increases lysyl oxidase enzyme activity and mRNA levels for lysyl oxidase and alpha-1-type I collagen, but not elastin, in a dose- and time-dependent manner. Maximal stimulation of lysyl oxidase activity and mRNA levels for both lysyl oxidase and collagen occurs after 48 hours of treatment of gingival fibroblastic cells with 400 pM of TGF-beta1. This study shows for the first time that CTGF mRNA and protein are strongly and rapidly induced by TGF-beta1 in human gingival fibroblasts. Exogenous addition of 1 to 50 ng/ml CTGF to gingival fibroblasts stimulates production of lysyl oxidase enzyme activity up to 1.5-fold after 48 hours, and 50 ng/ml CTGF stimulated insoluble collagen accumulation 1.5- to 2.0-fold after 4, 11, and 18 days of treatment. It is interesting to note that the addition of CTGF-blocking antibodies in the presence of TGF-beta did not block TGF-beta stimulation of collagen mRNA levels. Thus, although CTGF itself contributes to increased insoluble collagenous extracellular matrix accumulation, CTGF does not mediate all of the effects of TGF-beta1 on stimulation of collagen mRNA levels in human gingival fibroblasts. Immunohistochemistry studies of gingival overgrowth tissue samples indicate for the first time detectable levels of CTGF protein in Dilantin-induced hyperplasia tissues also positive for TGF-beta1. CTGF was not found in TGF-beta1-negative samples. In addition, extracellular lysyl oxidase protein was detected in vivo. Taken together, these studies support mostly independent roles for TGF-beta1 and CTGF in stimulating collagenous extracellular matrix accumulation in human gingival fibroblasts and tissues. PMID:10616214

Hong, H H; Uzel, M I; Duan, C; Sheff, M C; Trackman, P C

1999-12-01

342

Autoimmune Cytopenias In Common Variable Immunodeficiency  

PubMed Central

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

Podjasek, Jenna C.; Abraham, Roshini S.

2012-01-01

343

Autoimmune encephalitis.  

PubMed

It is now accepted that there are antibody-mediated diseases of both the peripheral and central nervous systems. Myasthenia gravis remains the prototype autoimmune disease of the neuromuscular junction, but subsequent studies have revealed antibodies to other peripheral and autonomic targets. In the 1990s, antibodies to voltage-gated potassium channel complexes were identified in acquired neuromyotonia, a condition caused by peripheral nerve hyperexcitatibility that leads to muscle fasciulations, muscle cramps and pain. Somewhat surprisingly, the same antibodies were identified in relatively acute-onset central nervous system disorders such as Morvan's syndrome and limbic encephalitis. It turned out that the potassium channel antibodies were mainly directed at other proteins that are complexed with the channels in situ, such as LGI1 and CASPR2. These proteins help localise (CASPR2) and modify (LGI1) potassium channel function, and the antibodies bind to extracellular epitopes and are pathogenic in vitro. Tumours can be found in a proportion of each of these conditions, but the proportion varies from <10% to around 50%. Thymomas are the most common. In 2007, antibodies to NMDA receptors (NR1 principally) were identified and subsequently found quite commonly in younger patients, often women and small children, who have a very complicated form of encephalitis that results in psychiatric and movement disorders. Ovarian teratomas are common in the adult females but rare in children. Other antibodies have now been discovered, each one directed at a specific receptor or ion-channel related associated protein, although so far the associated diseases are fairly rare. Antibodies to glycine receptors are associated with a form of stiff person plus, usually termed progressive encephalomyelitis with rigidity and myoclonus (PERM), a condition which is well described in the literature and can be life threatening. Now it is recognised in more patients with a greater breadth of clinical symptoms. Each of these diseases shows a very good respond to immunotherapies such as steroids, plasma exchange, intravenous immunoglobulins. If the response is poor, second line therapies such as rituximab and/or cylclophosphamide are tried. Some require longer term immunosuppression with azathioprine or mycophenolate. Altogether there is a growing field of immunotherapy-responsive neurological diseases which need to be recognised by the clinicians and treated appropriately. There are now many neurological presentations in which the possibility of an autoimmune disease needs to be considered, and this is beginning to apply to those that are less clearly "organic". PMID:25009325

Vincent, Angela

2014-08-01

344

CCN2, CONNECTIVE TISSUE GROWTH FACTOR, STIMULATES COLLAGEN DEPOSITION BY GINGIVAL FIBROBLASTS VIA MODULE 3 AND ?6- AND ?1 INTEGRINS  

PubMed Central

CCN2, (connective tissue growth factor, CTGF) is a matricellular factor associated with fibrosis that plays an important role in the production and maintenance of fibrotic lesions. Increased collagen deposition and accumulation is a common feature of fibrotic tissues. The mechanisms by which CCN2 /CTGF contributes to fibrosis are not well understood. Previous studies suggest that CTGF exerts some of its biological effects at least in part by integrin binding, though this mechanism has not been previously shown to contribute to fibrosis. Utilizing full length CCN2/CTGF, CCN2/CTGF fragments, and integrin neutralizing antibodies, we provide evidence that the effects of CCN2/CTGF to stimulate extracellular matrix deposition by gingival fibroblasts are mediated by the C-terminal half of CCN2/CTGF, and by ?6 and ?1 integrins. In addition, a synthetic peptide corresponding to a region of CCN2/CTGF domain 3 that binds ?6?1 inhibits the collagen deposition assay. These studies employed a new and relatively rapid assay for CCN2/CTGF-stimulated collagen deposition based on Sirius Red staining of cell layers. Data obtained support a pathway in which CCN2/CTGF could bind to ?6?1 integrin and stimulate collagen deposition. These findings provide new experimental methodologies applicable to uncovering the mechanism and signal transduction pathways of CCN2/CTGF mediated collagen deposition, and may provide insights into potential therapeutic strategies to treat gingival fibrosis and other fibrotic conditions.

Heng, Edwin C. K.; Huang, Yuanyi; Black, Samuel A.; Trackman, Philip C.

2006-01-01

345

Decorin Interacts with Connective Tissue Growth Factor (CTGF)/CCN2 by LRR12 Inhibiting Its Biological Activity*  

PubMed Central

Fibrotic disorders are the end point of many chronic diseases in different tissues, where an accumulation of the extracellular matrix occurs, mainly because of the action of the connective tissue growth factor (CTGF/CCN2). Little is known about how this growth factor activity is regulated. We found that decorin null myoblasts are more sensitive to CTGF than wild type myoblasts, as evaluated by the accumulation of fibronectin or collagen III. Decorin added exogenously negatively regulated CTGF pro-fibrotic activity and the induction of actin stress fibers. Using co-immunoprecipitation and in vitro interaction assays, decorin and CTGF were shown to interact in a saturable manner with a Kd of 4.4 nm. This interaction requires the core protein of decorin. Experiments using the deletion mutant decorin indicated that the leucine-rich repeats (LRR) 10–12 are important for the interaction with CTGF and the negative regulation of the cytokine activity, moreover, a peptide derived from the LRR12 was able to inhibit CTGF-decorin complex formation and CTGF activity. Finally, we showed that CTGF specifically induced the synthesis of decorin, suggesting a mechanism of autoregulation. These results suggest that decorin interacts with CTGF and regulates its biological activity.

Vial, Cecilia; Gutierrez, Jaime; Santander, Cristian; Cabrera, Daniel; Brandan, Enrique

2011-01-01

346

The Effects of Hypertonic Dextrose Injection on Connective Tissue and Nerve Conduction through the Rabbit Carpal Tunnel  

PubMed Central

Objective To investigate the effects of hypertonic dextrose injection on the subsynovial connective tissue (SSCT) in a rabbit model. We hypothesized that dextrose injection would induce proliferation of the SSCT, hinder median nerve conduction, and alter SSCT mechanical properties similar to what is observed in patients with carpal tunnel syndrome (CTS). Design Randomized, controlled prospective study. Setting Not applicable. Participants New Zealand white rabbits (N=28) weighing 4.0 to 4.5kg. Intervention One fore paw was randomly injected with 0.1ml of 10% dextrose solution. The contralateral paw was injected with a similar amount of 0.9% saline solution as a control. Animals were sacrificed at 12 weeks after injection. Main Outcome Measures Animals were evaluated by electrophysiology (EP), mechanical testing, and histology. EP was evaluated by distal motor latency and amplitude. Shear force was evaluated when the middle digit flexor digitorum superficialis tendon was pulled out from the carpal tunnel. The ultimate tensile load and the energy absorption were also measured. Tissue for histology was evaluated qualitatively. Results EP demonstrated significant prolongation of distal motor latency. The energy absorption and stiffness were also significantly increased in the dextrose group. Histologically, the dextrose group showed thickening of the collagen bundles and vascular proliferation within the SSCT compared to the saline group. Conclusions These results are consistent with the findings in CTS patients and suggest that hypertonic dextrose injection has the potential to create a novel animal model in which to study the evolution of CTS.

Yoshii, Yuichi; Zhao, Chunfeng; Schmelzer, James D.; Low, Phillip A.; An, Kai-Nan; Amadio, Peter C.

2009-01-01

347

Autoimmune disorders  

MedlinePLUS

... healthy body tissues and antigens is unknown. One theory is that some microorganisms (such as bacteria or ... Pernicious anemia Reactive arthritis Rheumatoid arthritis Sjogren syndrome Systemic lupus erythematosus Type I diabetes

348

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

PubMed Central

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

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

2008-01-01

349

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.

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

2013-01-01

350

Transcriptional landscapes of emerging autoimmunity: transient aberrations in the targeted tissue's extracellular milieu precede immune responses in Sj?gren's syndrome  

PubMed Central

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

2013-01-01

351

Vitamin D Status and Bone and Connective Tissue Turnover in Brown Bears (Ursus arctos) during Hibernation and the Active State  

PubMed Central

Background Extended physical inactivity causes disuse osteoporosis in humans. In contrast, brown bears (Ursus arctos) are highly immobilised for half of the year during hibernation without signs of bone loss and therefore may serve as a model for prevention of osteoporosis. Aim To study 25-hydroxy-vitamin D (25OHD) levels and bone turnover markers in brown bears during the hibernating state in winter and during the active state in summer. We measured vitamin D subtypes (D2 and D3), calcitropic hormones (parathyroid hormone [PTH], 1,25-dihydroxy-vitamin D [1,25(OH)2D]) and bone turnover parameters (osteocalcin, ICTP, CTX-I), PTH, serum calcium and PIIINP. Material and Methods We drew blood from seven immobilised wild brown bears during hibernation in February and in the same bears while active in June. Results Serum 25-hydroxy-cholecalciferol (25OHD3) was significantly higher in the summer than in the winter (22.8±4.6 vs. 8.8±2.1 nmol/l, two tailed p - 2p?=?0.02), whereas 25-hydroxy-ergocalciferol (25OHD2) was higher in winter (54.2±8.3 vs. 18.7±1.7 nmol/l, 2p<0.01). Total serum calcium and PTH levels did not differ between winter and summer. Activated 1,25(OH)2D demonstrated a statistically insignificant trend towards higher summer levels. Osteocalcin levels were higher in summer than winter, whereas other markers of bone turnover (ICTP and CTX-I) were unchanged. Serum PIIINP, which is a marker of connective tissue and to some degree muscle turnover, was significantly higher during summer than during winter. Conclusions Dramatic changes were documented in the vitamin D3/D2 ratio and in markers of bone and connective tissue turnover in brown bears between hibernation and the active state. Because hibernating brown bears do not develop disuse osteoporosis, despite extensive physical inactivity we suggest that they may serve as a model for the prevention of this disease.

Vestergaard, Peter; St?en, Ole-Gunnar; Swenson, Jon E.; Mosekilde, Leif; Heickendorff, Lene; Frobert, Ole

2011-01-01

352

Characterization of cell-associated and soluble forms of connective tissue growth factor (CTGF) produced by fibroblast cells in vitro.  

PubMed

Connective tissue growth factor (CTGF) is a mitogenic and chemotactic factor for cultured fibroblasts that has been implicated in wound healing, fibrotic disorders and uterine function. Although the primary translational products of the mouse, human and pig CTGF (mCTGF, hCTGF, pCTGF) genes are predicted to be secreted and of approximate M(r) 38,000, 10 kDa biologically active forms of pCTGF have recently been described. In this report, we show that human foreskin fibroblasts (HFFs) and mouse connective tissue fibroblasts contained 2.4 kb CTGF transcripts, stained positively with an anti-CTGF[81-94] peptide antiserum, and produced a 38 kDa protein that was immunoprecipitated by an anti-CTGF[247-260] peptide antiserum. While 38 kDa CTGF was readily detected in cell lysates, it was non- or barely detectable in conditioned medium. 38 kDa CTGF remained cell-associated for at least 5 days after synthesis and was not releasable by treatment of the cells with trypsin, heparin, 1 M NaCl or low pH. Purification of CTGF from human or mouse fibroblast conditioned medium resulted in the isolation of 10-12 kDa CTGF proteins that were heparin-binding, bioactive, and reactive with anti-CTGF[247-260] on Western blots. Whereas 10 kDa CTGF stimulated DNA synthesis in 3T3 cells to the same extent as platelet-derived growth factor (PDGF)-AA, -AB, or -BB, it did not compete with 125I-PDGF-BB for binding to alpha alpha, alpha beta or beta beta PDGF receptors (PDGF-R), did not stimulate tyrosine phosphorylation of PDGF-alpha-R or -beta-R, and was not antagonized by a neutralizing PDGF-R-alpha antiserum. These data show that, in cultured fibroblasts, 38 kDa CTGF is principally cell-associated whereas low mass forms of CTGF are soluble and biologically active. They further demonstrate that, contrary to the previously proposed properties of 38 kDa CTGF, 10 kDa CTGF does not bind to PDGF-R and stimulates Balb/c 3T3 cell mitosis via a PDGF-R-independent mechanism. PMID:9570041

Steffen, C L; Ball-Mirth, D K; Harding, P A; Bhattacharyya, N; Pillai, S; Brigstock, D R

1998-01-01

353

Granzyme B cleavage of autoantigens in autoimmunity  

Microsoft Academic Search

The systemic autoimmune diseases are a complex group of disorders characterized by elaboration of high titer autoantibodies and immune-mediated damage of tissues. Two striking features of autoimmune rheumatic diseases are their self-sustaining nature and capacity for autoamplification, exemplified by disease flares. These features suggest the presence of a feed-forward cycle in disease propagation, in which immune effector pathways drive the

E Darrah; A Rosen

2010-01-01

354

A Mouse Strain Where Basal Connective Tissue Growth Factor Gene Expression Can Be Switched from Low to High  

PubMed Central

Connective tissue growth factor (CTGF) is a signaling molecule that primarily functions in extracellular matrix maintenance and repair. Increased Ctgf expression is associated with fibrosis in chronic organ injury. Studying the role of CTGF in fibrotic disease in vivo, however, has been hampered by perinatal lethality of the Ctgf null mice as well as the limited scope of previous mouse models of Ctgf overproduction. Here, we devised a new approach and engineered a single mutant mouse strain where the endogenous Ctgf-3? untranslated region (3?UTR) was replaced with a cassette containing two 3?UTR sequences arranged in tandem. The modified Ctgf allele uses a 3?UTR from the mouse FBJ osteosarcoma oncogene (c-Fos) and produces an unstable mRNA, resulting in 60% of normal Ctgf expression (Lo allele). Upon Cre-expression, excision of the c-Fos-3?UTR creates a transcript utilizing the more stable bovine growth hormone (bGH) 3?UTR, resulting in increased Ctgf expression (Hi allele). Using the Ctgf Lo and Hi mutants, and crosses to a Ctgf knockout or Cre-expressing mice, we have generated a series of strains with a 30-fold range of Ctgf expression. Mice with the lowest Ctgf expression, 30% of normal, appear healthy, while a global nine-fold overexpression of Ctgf causes abnormalities, including developmental delay and craniofacial defects, and embryonic death at E10-12. Overexpression of Ctgf by tamoxifen-inducible Cre in the postnatal life, on the other hand, is compatible with life. The Ctgf Lo-Hi mutant mice should prove useful in further understanding the function of CTGF in fibrotic diseases. Additionally, this method can be used for the production of mouse lines with quantitative variations in other genes, particularly with genes that are broadly expressed, have distinct functions in different tissues, or where altered gene expression is not compatible with normal development.

Doherty, Heather E.; Kim, Hyung-Suk; Hiller, Sylvia; Sulik, Kathleen K.; Maeda, Nobuyo

2010-01-01

355

Assembly of the Prothrombinase Complex on the Surface of Human Foreskin Fibroblasts: Implications for Connective Tissue Growth Factor  

PubMed Central

Activated factor X (FXa) and thrombin can up-regulate gene expression of connective tissue growth factor (CTGF/CCN2) on fibroblasts. Since tissue factor (TF) is expressed on these cells, we hypothesized that they may assemble the prothrombinase complex leading to CTGF/CCN2 upregulation. In addition, the effect of thrombospondin-1 (TSP1) on this reaction was evaluated. Human foreskin fibroblasts were incubated with purified factor VII (FVII), factor X (FX), factor V (FV), prothrombin and calcium in the presence and absence of TSP1. Generation of FXa and of thrombin were assessed using chromogenic substrates. SMAD pathway phosphorylation was detected via Western-blot analysis. Pre-incubation of fibroblasts with FVII led to its auto-activation by cell-surface expressed TF, which in turn in the presence of FX, FVa, prothrombin and calcium led to FXa (9.7 ± 0.8 nM) and thrombin (7.9 ± 0.04 U/mL × 10-3) generation. Addition of TSP1 significantly enhanced thrombin (23.3 ± 0.7 U/mL × 10-3) but not FXa (8.5 ± 0.6 nM) generation. FXa and thrombin generation leads to upregulation of CTGF/CCN2. TSP1 alone upregulated CTGF/CCN2, an effect mediated via activation of transforming growth factor beta (TGF?) as showed by phosphorylation of the SMAD pathway an event blunted by using a TGF? receptor I inhibitor (TGF?RI). FXa- and thrombin-induced upregulation of CTGF/CCN2 was not blocked by TGF?RI. In summary, assembly of the prothrombinase complex occurs on fibroblast’s surface leading to serine proteases generation, an event enhanced by TSP1 and associated with CTGF/CCN2 upregulation. These mechanisms may play an important role in human diseases associated with fibrosis.

Rico, Mario C.; Rough, James J.; Manns, Joanne M.; Carpio-Cano, Fabiola Del; Safadi, Fayez F.; Kunapuli, Satya P.; Cadena, Raul A DeLa

2011-01-01

356

Inhibition of connective tissue growth factor suppresses hepatic stellate cell activation in vitro and prevents liver fibrosis in vivo.  

PubMed

Activation of hepatic stellate cells (HSC) represents a critical event in fibrosis, and connective tissue growth factor (CTGF) plays a profibrotic activity and a key factor in the pathogenesis of tissue fibrosis. The current study aimed to determine whether lentivirus-mediated short hairpin RNA (shRNA)-targeted CTGF downregulates the CTGF expression and furthermore whether it suppresses the activation and proliferation of HSC in vitro and prevents liver fibrosis in vivo. HSC-T6 cells were treated with recombinant lentivirus carrying CTGF siRNA. Real-time PCR, Western blotting, MTT, and flow cytometry were performed to investigate the activation and proliferation of HSC-T6 cells in response to CTGF silence. CCl4-induced rats were received lentivirus containing CTGF siRNA by intraportal vein injection. Levels of liver fibrosis were assessed by biochemical and histopathologic examinations. Recombinant lentivirus containing CTGF siRNA could effectively and specifically downregulate the expression of CTGF in both HSC-T6 cells and CCl4-induced rats with liver fibrosis. Blockade of CTGF resulted in significant inhibition of HSC activation and proliferation with decrease in TIMPs, MMP2, MMP9, and collagen I, as well as increase in cells in S phase. Silencing CTGF expression with siRNA prevented liver fibrosis in CCl4-induced rat model. These findings indicated that CTGF plays a key role in the pathogenesis of liver fibrosis and lentiviral-mediated CTGF siRNA has the potential to be an effective treatment for liver fibrosis. PMID:23456538

Hao, Chunqiu; Xie, Yumei; Peng, Meijuan; Ma, Li; Zhou, Yun; Zhang, Yan; Kang, Wenzhen; Wang, Jiuping; Bai, Xuefan; Wang, Pingzhong; Jia, Zhansheng

2014-05-01

357

Response of bone marrow derived connective tissue progenitor cell morphology and proliferation on geometrically modulated microtextured substrates  

PubMed Central

Varying geometry and layout of microposts on a cell culture substrate provides an effective technique for applying mechanical stimuli to living cells. In the current study, the optimal geometry and arrangement of microposts on the polydimethylsiloxane (PDMS) surfaces to enhance cell growth behavior were investigated. Human bone marrow derived connective tissue progenitor cells were cultured on PDMS substrates comprising unpatterned smooth surfaces and cylindrical post microtextures that were 10 µm in diameter, 4 heights (5, 10, 20 and 40 µm) and 3 pitches (10, 20, and 40 µm). With the same 10 µm diameter, post heights ranging from 5 to 40 µm resulted in a more than 535000 fold range of rigidity from 0.011 nNµm?1 (40 µm height) up to 5888 nNµm?1(5 µm height). Even though shorter microposts result in higher effective stiffness, decreasing post heights below the optimal value, 5 µm height micropost in this study decreased cell growth behavior. The maximum number of cells was observed on the post microtextures with 20 µm height and 10 µm inter-space, which exhibited a 675% increase relative to the smooth surfaces. The cells on all heights of post microtextures with 10 µm and 20 µm inter-spaces exhibited highly contoured morphology. Elucidating the cellular response to various external geometry cues enables us to better predict and control cellular behavior. In addition, knowledge of cell response to surface stimuli could lead to the incorporation of specific size post microtextures into surfaces of implants to achieve surface-textured scaffold materials for tissue engineering applications.

Kim, Eun Jung; Fleischman, Aaron J.; Muschler, George F.; Roy, Shuvo

2013-01-01

358

The lack of compound 48\\/80-induced contraction in isolated trachea of mast cell-deficient Ws\\/Ws rats in vitro: the role of connective tissue mast cells  

Microsoft Academic Search

In the rat trachea, two types of mast cells have been identified, connective tissue mast cells and mucosal mast cells. Their different characteristics may account for their different biological functions. The role of connective tissue mast cells in tracheal contraction as one feature of the immediate reaction of asthma was studied in vitro in isolated trachea, using tissue derived from

Zullies Ikawati; Mototaka Hayashi; Masato Nose; Kazutaka Maeyama

2000-01-01

359

Sustained autoimmune mechanisms in dermatomyositis.  

PubMed

Dermatomyositis is an autoimmune disease predominantly affecting skin and muscle. Its poorly understood pathogenesis is increasingly being linked to the overproduction of type 1 interferon-inducible gene transcripts and proteins. Mechanisms have been identified by which chronic sustained accumulation of these proteins might occur and thereby injure tissue in dermatomyositis. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. PMID:24687932

Greenberg, Steven A

2014-07-01

360

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

361

Contraction potency of hypertrophic scar-derived fibroblasts in a connective tissue model: in vitro analysis of wound contraction.  

PubMed

Many investigators have reported that collagen gel contraction reflects the mechanism of wound contraction. By using a connective tissue model (CTM) of collagen gel lattice, we analyzed the contraction potency of fibroblasts that had been obtained from hypertrophic scar, normal skin, and normal oral mucosa. We then tried to analyze the mechanism of CTM contraction by immunofluorescent microscopic and transmission electron microscopic examinations. Hypertrophic scar-derived fibroblasts in CTM possessed the greatest contraction potency and the shortest lag time when compared with those of normal skin and normal oral mucosa-derived CTMs. It became clear that the initial contractive degree of CTM was closely related to morphological changes of fibroblast cells into bipolar and elongated shapes. Hypertrophic scar-derived fibroblasts elongated their processes faster, and their intracellular actin filaments were more numerous than those of normal fibroblasts. We believe that the hypertrophic scar-derived CTM is a useful pathological model for the research of wound contraction and hypertrophic scar formation. PMID:8748348

Tsai, C; Hata, K; Torii, S; Matsuyama, M; Ueda, M

1995-12-01

362

Transgenic reporter mice as tools for studies of transplantability and connectivity of dopamine neuron precursors in fetal tissue grafts.  

PubMed

Cell therapy for Parkinson's disease (PD) is based on the idea that new midbrain dopamine (mDA) neurons, implanted directly into the brain of the patient, can structurally and functionally replace those lost to the disease. Clinical trials have provided proof-of-principle that the grafted mDA neurons can survive and function after implantation in order to provide sustained improvement in motor function for some patients. Nonetheless, there are a number of issues limiting the application of this approach as mainstream therapy, including: the use of human fetal tissue as the only safe and reliable source of transplantable mDA neurons, and variability in the therapeutic outcome. Here we review recent progress in this area from investigations using rodent models of PD, paying particular attention to the use of transgenic reporter mice as tools for neural transplantation studies. Cell type-specific expression of reporter genes, such as green fluorescent protein, affords valuable technical advantages in transplantation experiments, such as the ability to selectively isolate specific cell fractions from mixed populations prior to grafting, and the unambiguous visualization of graft-derived dopamine neuron fiber patterns after transplantation. The results from these investigations have given new insights into the transplantability of mDA precursors as well as their connectivity after grafting and have interesting implications for the development of stem cell based approaches for the treatment of PD. PMID:19660649

Thompson, Lachlan H; Björklund, Anders

2009-01-01

363

Stimulation of connective tissue-type mast cell proliferation by crosslinking of cell-bound IgE  

PubMed Central

Crosslinking of cell-bound IgE on mouse connective tissue-type mast cells (CTMC) by multivalent antigen or anti-IgE antibody induced clonal growth of CTMC in methylcellulose culture containing IL-3. Continuous presence of antigen, IgE antibody, and IL-3 in culture was required for extensive proliferation of CTMC. Optimal concentrations of antigen and anti-IgE antibody for proliferation of sensitized CTMC approximately corresponded to those for maximal histamine release from the cells, and it was observed that most dividing cells stimulated by antigen had pericellular degranulation halos in culture. Experiments of both single cell culture and serum free culture provided evidence for a direct effect of antigen stimulation on proliferation of CTMC. Neither accessory cells nor some factors in FCS were required for the clonal growth of CTMC in our culture condition. Compound 48/80, a direct stimulator of CTMC, also triggered histamine release from CTMC but failed to support their proliferation. These results suggest that stimulation of CTMC via IgE receptors not only triggers the release of chemical mediators from the cells but induces clonal growth of CTMC in the presence of IL-3. Our data indicate the possibility that antigen stimulation may play another role in the proliferation of CTMC.

1989-01-01

364

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

PubMed

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

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

2014-05-01

365

CCN2 (Connective Tissue Growth Factor) is essential for extracellular matrix production and integrin signaling in chondrocytes  

PubMed Central

The matricellular protein CCN2 (Connective Tissue Growth Factor; CTGF) is an essential mediator of ECM composition, as revealed through analysis of Ccn2 deficient mice. These die at birth due to complications arising from impaired endochondral ossification. However, the mechanism(s) by which CCN2 mediates its effects in cartilage are unclear. We investigated these mechanisms using Ccn2?/? chondrocytes. Expression of type II collagen and aggrecan were decreased in Ccn2?/? chondrocytes, confirming a defect in ECM production. Ccn2?/? chondrocytes also exhibited impaired DNA synthesis and reduced adhesion to fibronectin. This latter defect is associated with decreased expression of ?5 integrin. Moreover, CCN2 can bind to integrin ?5?1 in chondrocytes and can stimulate increased expression of integrin ?5. Consistent with an essential role for CCN2 as a ligand for integrins, immunofluorescence and Western blot analysis revealed that levels of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK)1/2 phosphorylation were reduced in Ccn2?/? chondrocytes. These findings argue that CCN2 exerts major effects in chondrocytes through its ability to (1) regulate ECM production and integrin ?5 expression, (2) engage integrins and (3) activate integrin-mediated signaling pathways.

Nishida, Takashi; Kawaki, Harumi; Baxter, Ruth M.; DeYoung, R. Andrea; Takigawa, Masaharu

2007-01-01

366

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.

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

367

Elevated expression of connective tissue growth factor, osteopontin and increased collagen content in human ascending thoracic aortic aneurysms.  

PubMed

Little is known about the molecular mechanisms of ascending thoracic aortic aneurysms (ATAAs). Abnormal extracellular matrix changes and variations of vascular smooth muscle cells (VSMCs) have been implicated in abdominal aortic aneurysm formation. Our objective was to investigate the alterations of collagen, stimulators of collagen synthesis and synthetic VSMCs in patients with ATAA. Surgical samples from ATAA were taken from 20 patients, and 18 control aortas were obtained during coronary artery bypass surgery. All aortic wall specimens were fixed for histology and immunohistochemistry for collagen, connective tissue growth factor (CTGF) and osteopontin. Realtime polymerase chain reaction was used to determine their mRNA expression. Histology and semi- quantitative analysis demonstrated that protein levels of collagen, CTGF and osteopontin significantly increased by 1.9-, 1.4- and 2.2-fold, respectively (P< 0.01 for all) in the ATAA group than in the control group. Similar results were shown in mRNA levels of type laland Illal collagen, CTGF and osteopontin. The protein levels of CTGF and osteopontin were positively correlated with aortic diameter (r= 0.67, r= 0.73; P< 0.01 for both). In conclusion, overexpression of aortic CTGF and synthetic VSMCs marker (osteopontin), which is likely to be responsible for elevated aortic collagen content, may provide a potential mechanism for aneurysmal enlargement. PMID:23508392

Meng, Y H; Tian, C; Liu, L; Wang, L; Chang, Q

2014-02-01

368

Smell and autoimmunity: a comprehensive review.  

PubMed

The sense of smell is an ancient sensory modality vital for sampling and perceiving the chemical composition of surrounding environments. Olfaction involves a pathway of biochemical and electrophysiological processes, which allows the conversion of molecular information into sensations. Disturbances in the olfactory function have been investigated mainly in neurological/neurodegenerative disorders such as Alzheimer's and Parkinson's diseases; impaired sense of smell has been associated with depressed mood. Only recently, smell capability was tested in other diseases, particularly autoimmune diseases. Shoenfeld and colleagues opened this chapter showing that patients affected with systemic lupus erythematosus (SLE) have disturbances in their olfactory functions and revealed its association with neuropsychiatric manifestations of the disease. This evidence was confirmed in experimental models and replicated in other SLE populations. The connection between autoimmunity and the sense of smell was lately emphasized by studies on patients with Sjögren's syndrome and in patients with other autoimmune/immune-mediated diseases, such as polydermatomyositis, recurrent spontaneous abortion, and hereditary angioedema. Genetic susceptibility and hormonal and environmental factors may play a role in these conditions. Olfactory receptor gene clusters are located in proximity to key locus of susceptibility for autoimmune diseases such as the major histocompatibility complex, suggesting not only a physic linkage, but a functional association. Nonetheless, gender- and hormone-mediated effects are fundamental in the development of autoimmune diseases. The different connections between smell and autoimmunity, genes and hormones may suggest that this is another tessera of a mosaic which is waiting the answer of Oedipus. PMID:23233263

Perricone, Carlo; Shoenfeld, Netta; Agmon-Levin, Nancy; de Carolis, Caterina; Perricone, Roberto; Shoenfeld, Yehuda

2013-08-01

369

HIV and autoimmunity  

Microsoft Academic Search

The association of immune dysfunction in patients with human immunodeficiency virus (HIV) infection and AIDS and the development of autoimmune diseases is intriguing. Yet, the spectrum of reported autoimmune phenomena in these patients is increasing. An infectious trigger for immune activation is one of the postulated mechanisms and derives from molecular mimicry. During frank loss of immunocompetence, autoimmune diseases that

Gisele Zandman-Goddard; Yehuda Shoenfeld

2002-01-01

370

High glucose and hyperinsulinemia stimulate connective tissue growth factor expression: A potential mechanism involved in progression to fibrosis in nonalcoholic steatohepatitis  

Microsoft Academic Search

Nonalcoholic steatohepatitis (NASH) may progress to liver fibrosis and cirrhosis. Mechanisms directly involved in the development of fibrosis have been poorly investigated. Because connective tissue growth factor (CTGF) is an intermediate key molecule involved in the pathogenesis of fibrosing chronic liver diseases and is potentially induced by hyperglycemia, the aims of this study were to (1) study the expression of

Valerie Paradis; Gabriel Perlemuter; Franck Bonvoust; Delphine Dargere; Beatrice Parfait; Michel Vidaud; Marc Conti; Stephane Huet; Nathalie Ba; Catherine Buffet; Pierre Bedossa

2001-01-01

371

B cell depletion for autoimmune diseases in paediatric patients.  

PubMed

Data on B cell depletion therapy in severe autoimmune diseases in paediatric patients are very limited. We conducted a retrospective cohort study and recruited patients who were treated with rituximab (RTX) and followed up for at least 6 months through the German societies of paediatric rheumatology and nephrology. The aim was to describe the spectrum of autoimmune disorders for which RTX was used and to describe the applied therapeutic regimens, the observed efficacy, as well as potential immunological side effects. The need to develop standard treatment guidelines for future trials should be discussed. Sixty-five patients were included. Nineteen patients suffered from systemic lupus erythematosus, 13 from vasculitic disorders, 12 from hematological autoimmune diseases, 5 from mixed connective tissue disorders, 4 from juvenile idiopathic arthritis, and 9 had other autoimmune diseases. Adverse, infusion-related events were reported in 12/65 (18%) patients. Considering laboratory and clinical parameters, 13 patients (22%) were in complete remission, 31 (52%) were in partial remission, 6 (10%) were unchanged and 10 (17%) had progressed after 6 months. In 46% of the patients, the steroid dose could be more than halved. IgG, IgM and IgA decreased from normal levels prior to RTX therapy to below normal levels at 6 months in 2/22 (9%), 10/21 (48%), and 4/22 (18%) patients, respectively. Immunoglobulin deficiency or prolonged CD20 depletion was reported in eight patients after an observation period longer than 12 months. RTX therapy led to a perceivable reduction in disease activity. However, long-term immunological alterations may occur in more than 10% of the patients. Guidelines and protocols for off-label therapy are desirable to document reasonable follow-up data. Controlled prospective studies for RTX therapies in children with standardised therapeutic and diagnostic protocols are urgently needed. PMID:21120559

Jansson, Annette F; Sengler, Claudia; Kuemmerle-Deschner, Jasmin; Gruhn, Bernd; Kranz, A Birgitta; Lehmann, Hartwig; Kleinert, Daniela; Pape, Lars; Girschick, Hermann J; Foeldvari, Ivan; Haffner, Dieter; Haas, Johannes P; Moebius, Dagmar; Foell, Dirk; Peitz, Joachim; Grote, Veit

2011-01-01

372

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

Microsoft Academic Search

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

Shoenfeld Y; Aron-Maor A

2000-01-01

373

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

374

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.

2014-01-01

375

Quantitative analysis of 17 amino acids in the connective tissue of patients with pelvic organ prolapse using capillary electrophoresis-tandem mass spectrometry.  

PubMed

The simultaneous determination of 17 amino acids in connective tissue using capillary electrophoresis is described in this study. Separation was carried out on a fused silica capillary column (80 cm x 50 mm i.d.) with 1M formic acid as the running electrolyte. The detection was conducted on a mass spectrometer by selective reaction monitoring (SRM) mode via an electrospray ionization source. Tissue samples were prepared by reduction and acid hydrolysis to extract amino acids; over 84.3% recovery was seen for all compounds. The method allowed for sensitive, reproducible, and reliable quantification, and all 17 amino acids were separated using this method. Good linearity over the investigated concentration ranges was observed, with values of R higher than 0.993 for all the analytes. Precision and accuracy examined at three concentration levels ranged from 0.2% to 19.5% and 84.1% to 120.0%, respectively. Matrix effects were also tested and ranged from -9.1% to 15.4%. The validated method was applied to the quantitation of 17 amino acids in pelvic connective tissue of pelvic organ prolapsed patients. Methionine, glutamine, and histidine were significantly higher in the experimental patients compared to the controls. This suggests that changes in the amino acid concentrations within the connective tissue could be a factor in the genesis of pelvic organ prolapse. Therefore, this method is potentially applicable for amino acid analysis in tissue, providing a more complete understanding of pelvic organ prolapse. PMID:18339589

Shama, Naz; Bai, Sang Wook; Chung, Bong Chul; Jung, Byung Hwa

2008-04-01

376

Granzyme B cleavage of autoantigens in autoimmunity.  

PubMed

The systemic autoimmune diseases are a complex group of disorders characterized by elaboration of high titer autoantibodies and immune-mediated damage of tissues. Two striking features of autoimmune rheumatic diseases are their self-sustaining nature and capacity for autoamplification, exemplified by disease flares. These features suggest the presence of a feed-forward cycle in disease propagation, in which immune effector pathways drive the generation/release of autoantigens, which in turn fuel the immune response. There is a growing awareness that structural modification during cytotoxic granule-induced cell death is a frequent and striking feature of autoantigens, and may be an important principle driving disease. This review focuses on granzyme B (GrB)-mediated cleavage of autoantigens including (i) features of GrB cleavage sites within autoantigens, (ii) co-location of cleavage sites with autoimmune epitopes, and (iii) GrB sensitivity of autoantigens in disease-relevant target tissue. The mechanisms whereby GrB-induced changes in autoantigen structure may contribute to the initiation and propagation of autoimmunity are reviewed and reveal that GrB has the potential to create or destroy autoimmune epitopes. As there remains no direct evidence showing a causal function for GrB cleavage of antigens in the generation of autoimmunity, this review highlights important outstanding questions about the function of GrB in autoantigen selection. PMID:20075942

Darrah, E; Rosen, A

2010-04-01

377

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

378

Correlation between Local Stress and Strain and Lamina Cribrosa Connective Tissue Volume Fraction in Normal Monkey Eyes  

PubMed Central

Purpose. To investigate the biomechanical response to IOP elevation of normal monkey eyes using eye-specific, three-dimensional (3-D) finite element (FE) models of the ONH that incorporate lamina cribrosa (LC) microarchitectural information. Methods. A serial sectioning and episcopic imaging technique was used to reconstruct the ONH and peripapillary sclera of four pairs of eyes fixed at 10 mm Hg. FE models were generated with local LC material properties representing the connective tissue volume fraction (CTVF) and predominant LC beam orientation and used to simulate an increase in IOP from 10 to 45 mm Hg. An LC material stiffness constant was varied to assess its influence on biomechanical response. Results. Strains and stresses within contralateral eyes were remarkably similar in both magnitude and distribution. Strain correlated inversely, and nonlinearly, with CTVF (median, r 2 = 0.73), with tensile strains largest in the temporal region. Stress correlated linearly with CTVF (median r2 = 0.63), with the central and superior regions bearing the highest stresses. Net average LC displacement was either posterior or anterior, depending on whether the laminar material properties were compliant or stiff. Conclusions. The results show that contralateral eyes exhibit similar mechanical behavior and suggest that local mechanical stress and strain within the LC are correlate highly with local laminar CTVF. These simulations emphasize the importance of developing both high-resolution imaging of the LC microarchitecture and next-generation, deep-scanning OCT techniques to clarify the relationships between IOP-related LC displacement and CTVF-related stress and strain in the LC. Such imaging may predict sites of IOP-related damage in glaucoma.

Roberts, Michael D.; Liang, Yi; Sigal, Ian A.; Grimm, Jonathan; Reynaud, Juan; Bellezza, Anthony; Burgoyne, Claude F.

2010-01-01

379

Connective tissue growth factor reacts as an IL-6/STAT3-regulated hepatic negative acute phase protein  

PubMed Central

AIM: To investigate the mechanisms involved in a possible modulator role of interleukin (IL)-6 signalling on CYR61-CTGF-NOV (CCN) 2/connective tissue growth factor (CTGF) expression in hepatocytes (PC) and to look for a relation between serum concentrations of these two parameters in patients with acute inflammation. METHODS: Expression of CCN2/CTGF, p-STAT3, p-Smad3/1 and p-Smad2 was examined in primary freshly isolated rat or cryo-preserved human PC exposed to various stimuli by Western blotting, electrophoretic mobility shift assay (EMSA), reporter-gene-assays and reverse-transcriptase polymerase chain reaction. RESULTS: IL-6 strongly down-regulated CCN2/CTGF protein and mRNA expression in PC, enhanceable by extracellular presence of the soluble IL-6 receptor gp80, and supported by an inverse relation between IL-6 and CCN2/CTGF concentrations in patients’ sera. The inhibition of TGF?1 driven CCN2/CTGF expression by IL-6 did not involve a modulation of Smad2 (and Smad1/3) signalling. However, the STAT3 SH2 domain binding peptide, a selective inhibitor of STAT3 DNA binding activity, counteracted the inhibitory effect of IL-6 on CCN2/CTGF expression much more pronounced than pyrrolidine-dithiocarbamate, an inhibitor primarily of STAT3 phosphorylation. An EMSA confirmed STAT3 binding to the proposed proximal STAT binding site in the CCN2/CTGF promoter. CONCLUSION: CCN2/CTGF is identified as a hepatocellular negative acute phase protein which is down-regulated by IL-6 via the STAT3 pathway through interaction on the DNA binding level.

Gressner, Olav A; Peredniene, Ieva; Gressner, Axel M

2011-01-01

380

Relationship of one form of human histamine-releasing factor to connective tissue activating peptide-III.  

PubMed Central

We have previously reported purification of three forms of histamine-releasing factors (HRFs) from mixtures of streptokinase-streptodornase stimulated human mononuclear cells and platelets with apparent molecular masses of 10-12, 15-17, and 40-41 kD (1989. J. Clin. Invest. 83:1204-1210). We have also prepared mouse MAbs against the 10-12-kD HRF (1989. J. Allergy Clin. Immunol. 83:281). Affinity-purified 10-12-kD HRF appears as a broad band upon polyacrylamide gel electrophoresis in the presence of SDS. We determined the NH2-terminal amino acid sequence of the top and bottom halves of this broad band. Sequence analysis revealed striking homology between this HRF and connective tissue activating peptide-III (CTAP-III), a platelet-derived 8-10-kD protein known to cause mitogenesis and extracellular matrix formation in fibroblast cultures. 19 of 21 NH2-terminal residues in the top half of the HRF band were identical to the NH2-terminal sequence of CTAP-III. 20 of 21 NH2-terminal residues in the bottom half were identical to the NH2-terminal sequence of neutrophil-activating peptide-2, which is derived from CTAP-III by proteolytic cleavage between residues 15 and 16. Purified CTAP-III also released histamine from basophils. Rabbit antiserum raised against either native or recombinant CTAP-III recognized affinity-purified HRF in immunodot blot assays, and MAb against HRF recognized CTAP-III in both dot blot and microtiter plate based immunoassays. These data demonstrate the first structural, functional, and immunologic relationship between one form of human HRF and a previously described cell product. Images

Baeza, M L; Reddigari, S R; Kornfeld, D; Ramani, N; Smith, E M; Hossler, P A; Fischer, T; Castor, C W; Gorevic, P G; Kaplan, A P

1990-01-01