Tissue Integration of a Volume-Stable Collagen Matrix in an Experimental Soft Tissue Augmentation Model.

PubMed

Ferrantino, Luca; Bosshardt, Dieter; Nevins, Myron; Santoro, Giacomo; Simion, Massimo; Kim, David

Reducing the need for a connective tissue graft by using an efficacious biomaterial is an important task for dental professionals and patients. This experimental study aimed to test the soft tissue response to a volume-stable new collagen matrix. The device demonstrated good stability during six different time points ranging from 0 to 90 days of healing with no alteration of the wound-healing processes. The 90-day histologic specimen demonstrates eventual replacement of most of the matrix with new connective tissue fibers.

Micromechanics and constitutive modeling of connective soft tissues.

PubMed

Fallah, A; Ahmadian, M T; Firozbakhsh, K; Aghdam, M M

2016-07-01

In this paper, a micromechanical model for connective soft tissues based on the available histological evidences is developed. The proposed model constituents i.e. collagen fibers and ground matrix are considered as hyperelastic materials. The matrix material is assumed to be isotropic Neo-Hookean while the collagen fibers are considered to be transversely isotropic hyperelastic. In order to take into account the effects of tissue structure in lower scales on the macroscopic behavior of tissue, a strain energy density function (SEDF) is developed for collagen fibers based on tissue hierarchical structure. Macroscopic response and properties of tissue are obtained using the numerical homogenization method with the help of ABAQUS software. The periodic boundary conditions and the proposed constitutive models are implemented into ABAQUS using the DISP and the UMAT subroutines, respectively. The existence of the solution and stable material behavior of proposed constitutive model for collagen fibers are investigated based on the poly-convexity condition. Results of the presented micromechanics model for connective tissues are compared and validated with available experimental data. Effects of geometrical and material parameters variation at microscale on macroscopic mechanical behavior of tissues are investigated. The results show that decrease in collagen content of the connective tissues like the tendon due to diseases leads 20% more stretch than healthy tissue under the same load which can results in connective tissue malfunction and hypermobility in joints. Copyright © 2016 Elsevier Ltd. All rights reserved.

Connective tissue responses to some heavy metals. II. Lead: histology and ultrastructure.

PubMed Central

Ellender, G.; Ham, K. N.

1987-01-01

Lead loaded ion exchange resin beads implanted into the loose connective tissue of the rat pinna induced local lesions which differed widely from those of the control (sodium loaded) beads (Ellender & Ham 1987). These lesions were characterized by changes in the granulation tissue and the approximating connective tissue. Granulation tissue contained mononuclear phagocytes in various guises, and some cells with intranuclear inclusion bodies. The matrix of the granulation tissue contained collagen fibrils having a wide range of diameters suggestive of altered collagen biosynthesis. Foci of collagen mineralization occurred in zones of combined trauma and lead impregnation. Once mineralized they became enveloped by giant cells and epithelioid cells. Lead in damaged tissues is thought to modify the protective mechanism of calcification inhibition and the biosynthesis of the matrix. Images Fig. 6 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 PMID:3040063

A biomechanical model of agonist-initiated contraction in the asthmatic airway.

PubMed

Brook, B S; Peel, S E; Hall, I P; Politi, A Z; Sneyd, J; Bai, Y; Sanderson, M J; Jensen, O E

2010-01-31

This paper presents a modelling framework in which the local stress environment of airway smooth muscle (ASM) cells may be predicted and cellular responses to local stress may be investigated. We consider an elastic axisymmetric model of a layer of connective tissue and circumferential ASM fibres embedded in parenchymal tissue and model the active contractile force generated by ASM via a stress acting along the fibres. A constitutive law is proposed that accounts for active and passive material properties as well as the proportion of muscle to connective tissue. The model predicts significantly different contractile responses depending on the proportion of muscle to connective tissue in the remodelled airway. We find that radial and hoop-stress distributions in remodelled muscle layers are highly heterogenous with distinct regions of compression and tension. Such patterns of stress are likely to have important implications, from a mechano-transduction perspective, on contractility, short-term cytoskeletal adaptation and long-term airway remodelling in asthma. Copyright 2009 Elsevier B.V. All rights reserved.

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

PubMed Central

Krieg, Thomas; Abraham, David; Lafyatis, Robert

2007-01-01

Fibrosis, characterized by excessive extracellular matrix accumulation, is a common feature of many connective tissue diseases, notably scleroderma (systemic sclerosis). Experimental studies suggest that a complex network of intercellular interactions involving endothelial cells, epithelial cells, fibroblasts and immune cells, using an array of molecular mediators, drives the pathogenic events that lead to fibrosis. Transforming growth factor-β and endothelin-1, which are part of a cytokine hierarchy with connective tissue growth factor, are key mediators of fibrogenesis and are primarily responsible for the differentiation of fibroblasts toward a myofibroblast phenotype. The tight skin mouse (Tsk-1) model of cutaneous fibrosis suggests that numerous other genes may also be important. PMID:17767742

The lack of effect of oxytetracycline on responses to sympathetic nerve stimulation and catecholamines in vascular tissue.

PubMed Central

Kalsner, S

1976-01-01

The effects of oxytetracycline, an inhibitor of amine binding in connective tissue, on the responses of perfused rabbit ear arteries to sympathetic nerve stimulation and to intraluminally administered noradrenaline were examined. The contractions of aortic strips to catecholamines in the presence of oxytetracycline were also examined. Oxytetracycline (0.1 mM) had no discernable effect on the magnitude of constrictions, measured as reductions in flow, produced by either nerve stimulation (0.5-10 Hz) or noradrenaline (0.5-50 ng) in the ear artery. In addition, the time taken for vessels to recover towards control flow values after endogenously released or exogenously applied noradrenaline had acted was not increased by oxytetracycline. Oxytetracycline (0.1 mM) did not alter the position or shape of the concentration-response curve to noradrenaline nor did it enhance the amplitude of individual responses to catecholamines in aortic strips. It is concluded, contrary to the observations of Powis (1973), that oxytetracycline does not increase the magnitude or duration of responses to sympathetic nerve activation or to catecholamines and that binding to connective tissue is of no material consequence in terminating their action in vascular tissue. PMID:974389

In vivo investigation on connective tissue healing to polished surfaces with different surface wettability.

PubMed

Kloss, Frank R; Steinmüller-Nethl, Doris; Stigler, Robert G; Ennemoser, Thomas; Rasse, Michael; Hächl, Oliver

2011-07-01

Connective tissue in contact to transgingival/-dermal implants presents itself as tight scar formation. Although rough surfaces support the attachment they increase bacterial colonisation as well. In contrast to surface roughness, little is known about the influence of surface wettability on soft-tissue healing in vivo. We therefore investigated the influence of different surface wettabilities on connective tissue healing at polished implant surfaces in vivo. Three polished experimental groups (titanium, titanium coated with hydrophobic nano-crystalline diamond (H-NCD) and titanium coated with hydrophilic nano-crystalline diamond (O-NCD) were inserted into the subcutaneous connective tissue of the abdominal wall of 24 rats. Animals were sacrificed after 1 and 4 weeks resulting in eight specimen per group per time point. Specimen were subjected to histological evaluation (van Giesson's staining) and immunohistochemistry staining for proliferating cell nuclear antigen (PCNA), fibronectin and tumour necrosis factor-alpha (TNF-α). Histological evaluation revealed dense scar formation at the titanium and H-NCD surfaces. In contrast, the connective tissue was loose at the O-NCD surface with a significantly higher number of cells after 4 weeks. O-NCD demonstrated a strong expression of PCNA and fibronectin but a weak expression of TNF-α. In contrast, the PCNA and fibronectin expression was low at the titanium and H-NCD, with a strong signal of TNF-α at the H-NCD surface. Hydrophilicity influences the connective tissue healing at polished implant surfaces in vivo positively. The attachment of connective tissue and the number of cells in contact to the surface were increased. Moreover, the inflammatory response is decreased at the hydrophilic surface. © 2010 John Wiley & Sons A/S.

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

PubMed Central

Quigley, Harry A.; Cone, Frances E.

2013-01-01

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

Histology-specific therapy for advanced soft tissue sarcoma and benign connective tissue tumors.

PubMed

Silk, Ann W; Schuetze, Scott M

2012-09-01

Molecularly targeted agents have shown activity in soft tissue sarcoma (STS) and benign connective tissue tumors over the past ten years, but response rates differ by histologic subtype. The field of molecularly targeted agents in sarcoma is increasingly complex. Often, clinicians must rely on phase II data or even case series due to the rarity of these diseases. In subtypes with a clear role of specific factors in the pathophysiology of disease, such as giant cell tumor of the bone and diffuse-type tenosynovial giant cell tumor, it is reasonable to treat with newer targeted therapies, when available, in place of chemotherapy when systemic treatment is needed to control disease. In diseases without documented implication of a pathway in disease pathogenesis (e.g. soft tissue sarcoma and vascular endothelial growth factor), clear benefit from drug treatment should be established in randomized phase III trials before implementation into routine clinical practice. Histologic subtype will continue to emerge as a critical factor in treatment selection as we learn more about the molecular drivers of tumor growth and survival in different subtypes. Many of the drugs that have been recently developed affect tumor growth more than survival, therefore progression-free survival may be a more clinically relevant intermediate endpoint than objective response rate using Response Evaluation Criteria In Solid Tumors (RECIST) in early phase sarcoma trials. Because of the rarity of disease and increasing need for multidisciplinary management, patients with connective tissue tumors should be evaluated at a center with expertise in these diseases. Participation in clinical trials, when available, is highly encouraged.

Mechanisms of alveolar fibrosis after acute lung injury.

PubMed

Marinelli, W A; Henke, C A; Harmon, K R; Hertz, M I; Bitterman, P B

1990-12-01

In patients who die after severe acute lung injury, a dramatic fibroproliferative response occurs within the alveolar air space, interstitium, and microvessels. Profound shunt physiology, dead space ventilation, and pulmonary hypertension are the physiologic consequences of this fibroproliferative response. The anatomic pattern of the response is unique within each alveolar compartment. For example, the air space is obliterated by granulation tissue, with replicating mesenchymal cells, their connective tissue products, and an expanding network of intra-alveolar capillaries. In contrast, the vascular fibroproliferative response is dominated by mesenchymal cell replication and connective tissue deposition within the walls of microvessels. Despite the unique anatomic features of these fibroproliferative processes, the regulatory signals involved are likely to be similar. Although our current understanding of the signals regulating the fibroproliferative response to acute lung injury is limited, inferences can be made from in vitro studies of mesenchymal cell behavior and several better understood fibroproliferative processes, including wound healing and chronic fibrotic lung diseases. As clinicians, our future ability to enhance effective lung repair will likely utilize therapeutic strategies specifically targeted to the signals that regulate the fibroproliferative process within the alveolar microenvironment.

Lysophosphatidic acid signaling through its receptor initiates profibrotic epithelial cell fibroblast communication mediated by epithelial cell derived connective tissue growth factor.

PubMed

Sakai, Norihiko; Chun, Jerold; Duffield, Jeremy S; Lagares, David; Wada, Takashi; Luster, Andrew D; Tager, Andrew M

2017-03-01

The expansion of the fibroblast pool is a critical step in organ fibrosis, but the mechanisms driving expansion remain to be fully clarified. We previously showed that lysophosphatidic acid (LPA) signaling through its receptor LPA 1 expressed on fibroblasts directly induces the recruitment of these cells. Here we tested whether LPA-LPA 1 signaling drives fibroblast proliferation and activation during the development of renal fibrosis. LPA 1 -deficient (LPA 1 -/- ) or -sufficient (LPA 1 +/+ ) mice were crossed to mice with green fluorescent protein expression (GFP) driven by the type I procollagen promoter (Col-GFP) to identify fibroblasts. Unilateral ureteral obstruction-induced increases in renal collagen were significantly, though not completely, attenuated in LPA 1 -/- Col-GFP mice, as were the accumulations of both fibroblasts and myofibroblasts. Connective tissue growth factor was detected mainly in tubular epithelial cells, and its levels were suppressed in LPA 1 -/- Col-GFP mice. LPA-LPA 1 signaling directly induced connective tissue growth factor expression in primary proximal tubular epithelial cells, through a myocardin-related transcription factor-serum response factor pathway. Proximal tubular epithelial cell-derived connective tissue growth factor mediated renal fibroblast proliferation and myofibroblast differentiation. Administration of an inhibitor of myocardin-related transcription factor/serum response factor suppressed obstruction-induced renal fibrosis. Thus, targeting LPA-LPA 1 signaling and/or myocardin-related transcription factor/serum response factor-induced transcription could be promising therapeutic strategies for renal fibrosis. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Deregulated expression of connective tissue growth factor (CTGF/CCN2) is linked to poor outcome in human cancer.

PubMed

Wells, Julia E; Howlett, Meegan; Cole, Catherine H; Kees, Ursula R

2015-08-01

Connective tissue growth factor (CTGF/CCN2) has long been associated with human cancers. The role it plays in these neoplasms is diverse and tumour specific. Recurring patterns in clinical outcome, histological desmoplasia and mechanisms of action have been found. When CTGF is overexpressed compared to low-expressing normal tissue or is underexpressed compared to high-expressing normal tissue, the functional outcome favours tumour survival and disease progression. CTGF acts by altering proliferation, drug resistance, angiogenesis, adhesion and migration contributing to metastasis. The pattern of CTGF expression and tumour response helps to clarify the role of this matricellular protein across a multitude of human cancers. © 2014 UICC.

An open prospective single cohort multicenter study evaluating the novel, tapered, conical connection implants supporting single crowns in the anterior and premolar maxilla: interim 1-year results.

PubMed

Fügl, Alexander; Zechner, Werner; Pozzi, Alessandro; Heydecke, Guido; Mirzakhanian, Christine; Behneke, Nikolaus; Behneke, Alexandra; Baer, Russell A; Nölken, Robert; Gottesman, Edward; Colic, Snjezana

2017-07-01

The aim of this multicenter prospective clinical study was to evaluate anodized tapered implants with a conical connection and integrated platform shifting placed in the anterior and premolar maxilla. The study enrolled patients requiring single-tooth restorations in healed sites of maxillary anterior and premolar teeth. All implants were immediately temporized. Clinical and radiographic evaluations were conducted at implant insertion, 6 months, and 1 year. Outcome measures included bone remodeling, cumulative survival rate (CSR), success rate, soft-tissue health and esthetics, and patient satisfaction. Bone remodeling and pink esthetic score were analyzed using Wilcoxon signed-rank tests. CSR was calculated using life table analysis. Other soft-tissue outcomes were analyzed using sign tests. Out of 97 enrolled patients (102 implants), 87 patients (91 implants) completed the 1-year visit. Marginal bone remodeling was -0.85 ± 1.36 mm. After the expected initial bone loss, a mean bone gain of 0.11 ± 1.05 mm was observed between 6 months and 1 year. The CSR was 99.0%, and the cumulative success rate was 97.0%. Partial or full papilla was observed at 30.8% of sites at baseline, 87.2% at 6 months, and 90.5% at 1 year. Soft-tissue response, esthetics, and patient satisfaction all improved during the study period. Bone gain was observed following the expected initial bone loss, and soft-tissue outcomes improved suggesting favorable tissue response using anodized tapered conical connection implants. Rapid stabilization of bone remodeling and robust papilla regeneration indicate favorable tissue healing promoted by the conical connection, platform-shift design. clinicaltrials.gov NCT02175550.

[Systemic lupus erythematosus and pregnancy].

PubMed

Basheva, S; Nikolov, A; Stoilov, R; Stoilov, N

2012-01-01

Connective-tissue disorders, also referred to as collagen-vascular disorders, are characterized by autoantibody-mediated connective-tissue abnormalities. These are also called immune-complex diseases because many involve deposition of immune complexes in specific organ or tissue sites. Some of these disorders are characterized by sterile inflammation, especially of the skin, joints, blood vessels, and kidneys, and are referred to as rheumatic diseases. For inexplicable reasons, many rheumatic diseases primarily affect women. Another major category of connective-tissue diseases includes inherited disorders of bone, skin, cartilage, blood vessels. Examples include Marfan syndrome, osteogenesis imperfecta, and Ehlers-Danlos syndrome. Lupus erythematosus (LE) is the main and most important disease in the group of systemic connective tissue diseases. It is heterogeneous, multiple organs autoimmune inflammatory disease with complex pathogenesis, which is the result of interaction between the susceptible genes and environmental factors that lead to abnormal immune response. In this review will consider: its incidence, pathogenesis, clinical forms and clinical features and diagnosis set based on generally accepted clinical criteria developed by the American College of Rheumatology (ACR), the course of pregnancy in patients suffering from LE, the most common complications of LE during pregnancy and antiphospholipid syndrome as part of LE.

Role of Complement on Broken Surfaces After Trauma.

PubMed

Huber-Lang, Markus; Ignatius, Anita; Brenner, Rolf E

2015-01-01

Activation of both the complement and coagulation cascade after trauma and subsequent local and systemic inflammatory response represent a major scientific and clinical problem. After severe tissue injury and bone fracture, exposure of innate immunity to damaged cells and molecular debris is considered a main trigger of the posttraumatic danger response. However, the effects of cellular fragments (e.g., histones) on complement activation remain enigmatic. Furthermore, direct effects of "broken" bone and cartilage surfaces on the fluid phase response of complement and its interaction with key cells of connective tissues are still unknown. Here, we summarize data suggesting direct and indirect complement activation by extracellular and cellular danger associated molecular patterns. In addition, key complement components and the corresponding receptors (such as C3aR, C5aR) have been detected on "exposed surfaces" of the damaged regions. On a cellular level, multiple effects of complement activation products on osteoblasts, osteoclasts, chondrocytes and mesenchymal stem cells have been found.In conclusion, the complement system may be activated by trauma-altered surfaces and is crucially involved in connective tissue healing and posttraumatic systemic inflammatory response.

Multimodal OCT for complex assessment of tumors response to therapy

NASA Astrophysics Data System (ADS)

Sirotkina, Marina A.; Kiseleva, Elena B.; Gubarkova, Ekaterina V.; Matveev, Lev A.; Zaitsev, Vladimir Yu.; Matveyev, Alexander L.; Shirmanova, Marina V.; Sovetsky, Alexander A.; Moiseev, Alexander A.; Zagaynova, Elena V.; Vitkin, Alex; Gladkova, Natalia D.

2017-07-01

Multimodal OCT is a promising tool for monitoring of individual tumor response to antitumor therapies. The changes of tumor cells, connective tissue, microcirculation and stiffness can be estimated simultaneously in real time with high resolution.

Mutations in B3GALT6, which Encodes a Glycosaminoglycan Linker Region Enzyme, Cause a Spectrum of Skeletal and Connective Tissue Disorders

PubMed Central

Nakajima, Masahiro; Mizumoto, Shuji; Miyake, Noriko; Kogawa, Ryo; Iida, Aritoshi; Ito, Hironori; Kitoh, Hiroshi; Hirayama, Aya; Mitsubuchi, Hiroshi; Miyazaki, Osamu; Kosaki, Rika; Horikawa, Reiko; Lai, Angeline; Mendoza-Londono, Roberto; Dupuis, Lucie; Chitayat, David; Howard, Andrew; Leal, Gabriela F.; Cavalcanti, Denise; Tsurusaki, Yoshinori; Saitsu, Hirotomo; Watanabe, Shigehiko; Lausch, Ekkehart; Unger, Sheila; Bonafé, Luisa; Ohashi, Hirofumi; Superti-Furga, Andrea; Matsumoto, Naomichi; Sugahara, Kazuyuki; Nishimura, Gen; Ikegawa, Shiro

2013-01-01

Proteoglycans (PGs) are a major component of the extracellular matrix in many tissues and function as structural and regulatory molecules. PGs are composed of core proteins and glycosaminoglycan (GAG) side chains. The biosynthesis of GAGs starts with the linker region that consists of four sugar residues and is followed by repeating disaccharide units. By exome sequencing, we found that B3GALT6 encoding an enzyme involved in the biosynthesis of the GAG linker region is responsible for a severe skeletal dysplasia, spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMD-JL1). B3GALT6 loss-of-function mutations were found in individuals with SEMD-JL1 from seven families. In a subsequent candidate gene study based on the phenotypic similarity, we found that B3GALT6 is also responsible for a connective tissue disease, Ehlers-Danlos syndrome (progeroid form). Recessive loss-of-function mutations in B3GALT6 result in a spectrum of disorders affecting a broad range of skeletal and connective tissues characterized by lax skin, muscle hypotonia, joint dislocation, and spinal deformity. The pleiotropic phenotypes of the disorders indicate that B3GALT6 plays a critical role in a wide range of biological processes in various tissues, including skin, bone, cartilage, tendon, and ligament. PMID:23664117

Reconstruction of the forehead acoustic properties in an Indo-Pacific humpback dolphin (Sousa chinensis), with investigation on the responses of soft tissue sound velocity to temperature.

PubMed

Song, Zhongchang; Zhang, Yu; Berggren, Per; Wei, Chong

2017-02-01

Computed tomography (CT) imaging and ultrasound experimental measurements were combined to reconstruct the acoustic properties (density, velocity, and impedance) of the head from a deceased Indo-Pacific humpback dolphin (Sousa chinensis). The authors extracted 42 soft forehead tissue samples to estimate the sound velocity and density properties at room temperature, 25.0  °C. Hounsfield Units (HUs) of the samples were read from CT scans. Linear relationships between the tissues' HUs and velocity, and HUs and density were revealed through regression analyses. The distributions of the head acoustic properties at axial, coronal, and sagittal cross sections were reconstructed, suggesting that the forehead soft tissues were characterized by low-velocity in the melon, high-velocity in the muscle and connective tissues. Further, the sound velocities of melon, muscle, and connective tissue pieces were measured under different temperatures to investigate tissues' velocity response to temperature. The results demonstrated nonlinear relationships between tissues' sound velocity and temperature. This study represents a first attempt to provide general information on acoustic properties of this species. The results could provide meaningful information for understanding the species' bioacoustic characteristics and for further investigation on sound beam formation of the dolphin.

Neuroinflammatory Mechanisms of Connective Tissue Fibrosis: Targeting Neurogenic and Mast Cell Contributions

PubMed Central

Monument, Michael J.; Hart, David A.; Salo, Paul T.; Befus, A. Dean; Hildebrand, Kevin A.

2015-01-01

Significance: The pathogenesis of fibrogenic wound and connective tissue healing is complex and incompletely understood. Common observations across a vast array of human and animal models of fibroproliferative conditions suggest neuroinflammatory mechanisms are important upstream fibrogenic events. Recent Advances: As detailed in this review, mast cell hyperplasia is a common observation in fibrotic tissue. Recent investigations in human and preclinical models of hypertrophic wound healing and post-traumatic joint fibrosis provides evidence that fibrogenesis is governed by a maladaptive neuropeptide-mast cell-myofibroblast signaling pathway. Critical Issues: The blockade and manipulation of these factors is providing promising evidence that if timed correctly, the fibrogenic process can be appropriately regulated. Clinically, abnormal fibrogenic healing responses are not ubiquitous to all patients and the identification of those at-risk remains an area of priority. Future Directions: Ultimately, an integrated appreciation of the common pathobiology shared by many fibrogenic connective tissue conditions may provide a scientific framework to facilitate the development of novel antifibrotic prevention and treatment strategies. PMID:25785237

Tissue matrix arrays for high throughput screening and systems analysis of cell function

PubMed Central

Beachley, Vince Z.; Wolf, Matthew T.; Sadtler, Kaitlyn; Manda, Srikanth S.; Jacobs, Heather; Blatchley, Michael; Bader, Joel S.; Pandey, Akhilesh; Pardoll, Drew; Elisseeff, Jennifer H.

2015-01-01

Cell and protein arrays have demonstrated remarkable utility in the high-throughput evaluation of biological responses; however, they lack the complexity of native tissue and organs. Here, we describe tissue extracellular matrix (ECM) arrays for screening biological outputs and systems analysis. We spotted processed tissue ECM particles as two-dimensional arrays or incorporated them with cells to generate three-dimensional cell-matrix microtissue arrays. We then investigated the response of human stem, cancer, and immune cells to tissue ECM arrays originating from 11 different tissues, and validated the 2D and 3D arrays as representative of the in vivo microenvironment through quantitative analysis of tissue-specific cellular responses, including matrix production, adhesion and proliferation, and morphological changes following culture. The biological outputs correlated with tissue proteomics, and network analysis identified several proteins linked to cell function. Our methodology enables broad screening of ECMs to connect tissue-specific composition with biological activity, providing a new resource for biomaterials research and translation. PMID:26480475

Electrophysiology of connection current spikes.

PubMed

Fish, Raymond M; Geddes, Leslie A

2008-12-01

Connection to a 60-Hz or other voltage source can result in cardiac dysrhythmias, a startle reaction, muscle contractions, and a variety of other physiological responses. Such responses can lead to injury, especially if significant ventricular cardiac dysrhythmias occur, or if a person is working at some height above ground and falls as a result of a musculoskeletal response. Physiological reactions are known to relate to intensity and duration of current exposure. The connection current that flows is a function of the applied voltage at the instant of connection, and the electrical impedance encountered by the voltage source in contact with the skin or other body tissues. In this article we describe a rarely investigated phenomenon, namely a contact, or connection, current spike that is many times higher than the steady-state current. This current spike occurs when an electrical connection is made at a non-zero voltage time in a sine wave or other waveform. Such current spikes may occur when electronic or manual switching or connecting of conductors occurs in electronic instrumentation connected to a patient. These findings are relevant to medical devices and instrumentation and to electrical safety in general.

Lupus erythematosus and localized scleroderma coexistent at the same sites: a rare presentation of overlap syndrome of connective-tissue diseases.

PubMed

Pascucci, Anabella; Lynch, Peter J; Fazel, Nasim

2016-05-01

Overlap syndromes are known to occur with connective-tissue diseases (CTDs). Rarely, the overlap occurs at the same tissue site. We report the case of a patient with clinical and histopathologic findings consistent with the presence of discoid lupus erythematosus (DLE) and localized scleroderma within the same lesions. Based on our case and other reported cases in the literature, the following features are common in patients with an overlap of lupus erythematosus (LE) and localized scleroderma: predilection for young women, photodistributed lesions, DLE, linear morphology clinically, and positivity along the dermoepidermal junction on direct immunofluorescence. Most patients showed good response to antimalarials, topical steroids, or systemic steroids.

Mutations in B3GALT6, which encodes a glycosaminoglycan linker region enzyme, cause a spectrum of skeletal and connective tissue disorders.

PubMed

Nakajima, Masahiro; Mizumoto, Shuji; Miyake, Noriko; Kogawa, Ryo; Iida, Aritoshi; Ito, Hironori; Kitoh, Hiroshi; Hirayama, Aya; Mitsubuchi, Hiroshi; Miyazaki, Osamu; Kosaki, Rika; Horikawa, Reiko; Lai, Angeline; Mendoza-Londono, Roberto; Dupuis, Lucie; Chitayat, David; Howard, Andrew; Leal, Gabriela F; Cavalcanti, Denise; Tsurusaki, Yoshinori; Saitsu, Hirotomo; Watanabe, Shigehiko; Lausch, Ekkehart; Unger, Sheila; Bonafé, Luisa; Ohashi, Hirofumi; Superti-Furga, Andrea; Matsumoto, Naomichi; Sugahara, Kazuyuki; Nishimura, Gen; Ikegawa, Shiro

2013-06-06

Proteoglycans (PGs) are a major component of the extracellular matrix in many tissues and function as structural and regulatory molecules. PGs are composed of core proteins and glycosaminoglycan (GAG) side chains. The biosynthesis of GAGs starts with the linker region that consists of four sugar residues and is followed by repeating disaccharide units. By exome sequencing, we found that B3GALT6 encoding an enzyme involved in the biosynthesis of the GAG linker region is responsible for a severe skeletal dysplasia, spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMD-JL1). B3GALT6 loss-of-function mutations were found in individuals with SEMD-JL1 from seven families. In a subsequent candidate gene study based on the phenotypic similarity, we found that B3GALT6 is also responsible for a connective tissue disease, Ehlers-Danlos syndrome (progeroid form). Recessive loss-of-function mutations in B3GALT6 result in a spectrum of disorders affecting a broad range of skeletal and connective tissues characterized by lax skin, muscle hypotonia, joint dislocation, and spinal deformity. The pleiotropic phenotypes of the disorders indicate that B3GALT6 plays a critical role in a wide range of biological processes in various tissues, including skin, bone, cartilage, tendon, and ligament. Copyright © 2013 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Evaluation of the tissue reaction to fast endodontic cement (CER) and Angelus MTA.

PubMed

Gomes-Filho, João Eduardo; Rodrigues, Guilherme; Watanabe, Simone; Estrada Bernabé, Pedro Felício; Lodi, Carolina Simonett; Gomes, Alessandra Cristina; Faria, Max Doulgas; Domingos Dos Santos, Alailson; Silos Moraes, João Carlos

2009-10-01

A new cement (CER; Cimento Endodôntico Rápido or fast endodontic cement) has been developed to improve handling properties. It is a formulation that has Portland cement in gel. However, there had not yet been any study evaluating its biologic properties. The purpose of this study was to evaluate the rat subcutaneous tissue response to CER and Angelus MTA. The materials were placed in polyethylene tubes and implanted into dorsal connective tissue of Wistar rats for 7, 30, and 60 days. The specimens were prepared to be stained with hematoxylin-eosin or von Kossa or not stained for polarized light. The presence of inflammation, predominant cell type, calcification, and thickness of fibrous connective tissue were recorded. Scores were defined as follows: 0, none or few inflammatory cells, no reaction; 1, <25 cells, mild reaction; 2, 25-125 cells, moderate reaction; 3, >125 cells, severe reaction. Fibrous capsule was categorized as thin when thickness was <150 mum and thick at >150 mum. Necrosis and formation of calcification were both recorded. Both materials Angelus MTA and CER caused moderate reactions at 7 days, which decreased with time. The response was similar to the control at 30 and 60 days with Angelus MTA and CER, characterized by organized connective tissue and presence of some chronic inflammatory cells. Mineralization and granulations birefringent to polarized light were observed with both materials. It was possible to conclude that CER was biocompatible and stimulated mineralization.

LDR brachytherapy: can low dose rate hypersensitivity from the "inverse" dose rate effect cause excessive cell killing to peripherial connective tissues and organs?

PubMed

Leonard, B E; Lucas, A C

2009-02-01

Examined here are the possible effects of the "inverse" dose rate effect (IDRE) on low dose rate (LDR) brachytherapy. The hyper-radiosensitivity and induced radioresistance (HRS/IRR) effect benefits cell killing in radiotherapy, and IDRE and HRS/IRR seem to be generated from the same radioprotective mechanisms. We have computed the IDRE excess cell killing experienced in LDR brachytherapy using permanent seed implants. We conclude, firstly, that IDRE is a dose rate-dependent manifestation of HRS/IRR. Secondly, the presence of HRS/IRR or IDRE in a cell species or tissue must be determined by direct dose-response measurements. Thirdly, a reasonable estimate is that 50-80% of human adjoining connective and organ tissues experience IDRE from permanent implanted LDR brachytherapy. If IDRE occurs for tissues at point A for cervical cancer, the excess cell killing will be about a factor of 3.5-4.0 if the initial dose rate is 50-70 cGy h(-1). It is greater for adjacent tissues at lower dose rates and higher for lower initial dose rates at point A. Finally, higher post-treatment complications are observed in LDR brachytherapy, often for unknown reasons. Some of these are probably a result of IDRE excess cell killing. Measurements of IDRE need be performed for connective and adjacent organ tissues, i.e. bladder, rectum, urinary tract and small bowels. The measured dose rate-dependent dose responses should extended to <10 cGy h(-1) and involve multiple patients to detect patient variability. Results may suggest a preference for high dose rate brachytherapy or LDR brachytherapy without permanent retention of the implant seeds (hence the dose rates in peripheral tissues and organs remain above IDRE thresholds).

Hematopoietic stem cell origin of connective tissues.

PubMed

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

2010-07-01

Connective tissue consists of "connective tissue proper," which is further divided into loose and dense (fibrous) connective tissues and "specialized connective tissues." Specialized connective tissues consist of blood, adipose tissue, cartilage, and bone. In both loose and dense connective tissues, the principal cellular element is fibroblasts. It has been generally believed that all cellular elements of connective tissue, including fibroblasts, adipocytes, chondrocytes, and bone cells, are generated solely by mesenchymal stem cells. Recently, a number of studies, including those from our laboratory based on transplantation of single hematopoietic stem cells, strongly suggested a hematopoietic stem cell origin of these adult mesenchymal tissues. This review summarizes the experimental evidence for this new paradigm and discusses its translational implications. Copyright 2010 ISEH - Society for Hematology and Stem Cells. All rights reserved.

Breast reconstruction in the high risk patient with systemic connective tissue disease: a case series.

PubMed

Chin, K Y; Chalmers, C R; Bryson, A V; Weiler-Mithoff, E M

2013-01-01

The presence of severe underlying connective tissue disease may restrict the reconstructive options offered to a woman in the event of mastectomy. Putative concerns about reconstructive surgery include the effects of connective tissue disease and immunosuppression on wound healing and donor site morbidity, and increased risks of deranged clotting and thrombophilia after free tissue transfer. There is also the possibility of an unpredictable tissue reaction after oncological resection surgery and adjuvant radiotherapy. Here we present a review of the current sparse evidence regarding reconstructive breast surgery in this challenging group of patients. In addition we present a series of six consecutive patients with a spectrum of connective tissue disorders including combinations of longstanding Systemic Lupus Erythematosis (SLE), Rheumatoid arthritis and Raynaud's Disease who underwent successful post-mastectomy reconstruction with an extended autologous latissimus dorsi flap, along with subsequent successful correction of asymmetry and/or nipple reconstruction. There is a paucity of literature on this subject perhaps suggesting that surgeons are reluctant to offer reconstruction or that uptake is poor in this group. Complications related to radiotherapy and free tissue transfer in patients with severe CTD is less than may be expected. The most common complications experienced by our patients with CTD after extended ALD breast reconstruction were persistent donor site seroma, wound dehiscence and delayed haematoma formation, reflecting the abnormal inflammatory response and deranged haemostatic cascade common to connective tissue disease. However, all six patients made a full recovery from surgery without residual donor site morbidity and with an acceptable aesthetic breast reconstruction. Careful peri-operative management is crucial in this group of patients, but good outcomes are possible using a variety of reconstructive techniques. This is the first reported series of patients with severe connective tissue disease who have been managed with extended ALD breast reconstruction. The majority of complications relate to the donor site but the favourable outcomes demonstrate that the extended ALD flap remains a reliable reconstructive option for this group. Copyright © 2012 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Mixed Connective Tissue Disease

MedlinePlus

Mixed connective tissue disease Overview Mixed connective tissue disease has signs and symptoms of a combination of disorders — primarily lupus, scleroderma and polymyositis. For this reason, mixed connective tissue disease ...

A Framework for Modelling Connective Tissue Changes in VIIP Syndrome

NASA Technical Reports Server (NTRS)

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

2014-01-01

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

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

PubMed

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

2013-04-01

Mesenchymal cells are central to connective tissue homeostasis and are widely used for tissue-engineering applications. Dermal fibroblasts and adipose-derived stromal cells (ASCs) allow successful tissue reconstruction by the self-assembly approach of tissue engineering. This method leads to the production of multilayered tissues, devoid of exogenous biomaterials, that can be used as stromal compartments for skin or vesical reconstruction. These tissues are formed by combining cell sheets, generated through cell stimulation with ascorbic acid, which favours the cell-derived production/organization of matrix components. Since media motion can impact on cell behaviour, we investigated the effect of dynamic culture on mesenchymal cells during tissue reconstruction, using the self-assembly method. Tissues produced using ASCs in the presence of a wave-like movement were nearly twice thicker than under standard conditions, while no difference was observed for tissues produced from dermal fibroblasts. The increased matrix deposition was not correlated with an increased proliferation of ASCs, or by higher transcript levels of fibronectin or collagens I and III. A 30% increase of type V collagen mRNA was observed. Interestingly, tissues engineered from dermal fibroblasts featured a four-fold higher level of MMP-1 transcripts under dynamic conditions. Mechanical properties were similar for tissues reconstructed using dynamic or static conditions. Finally, cell sheets produced using ASCs under dynamic conditions could readily be manipulated, resulting in a 2 week reduction of the production time (from 5 to 3 weeks). Our results describe a distinctive property of ASCs' response to media motion, indicating that their culture under dynamic conditions leads to optimized tissue engineering. Copyright © 2011 John Wiley & Sons, Ltd.

Undifferentiated Connective Tissue Disease

MedlinePlus

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

The immune complex CTA1-DD/IgG adjuvant specifically targets connective tissue mast cells through FcγRIIIA and augments anti-HPV immunity after nasal immunization.

PubMed

Fang, Y; Zhang, T; Lidell, L; Xu, X; Lycke, N; Xiang, Z

2013-11-01

We have previously reported that CTA1-DD/IgG immune complexes augment antibody responses in a mast cell-dependent manner following intranasal (IN) immunizations. However, from a safety perspective, mast cell activation could preclude clinical use. Therefore, we have extended these studies and demonstrate that CTA1-DD/IgG immune complexes administered IN did not trigger an anaphylactic reaction. Importantly, CTA1-DD/IgE immune complexes did not activate mast cells. Interestingly, only connective tissue, but not mucosal, mast cells could be activated by CTA1-DD/IgG immune complexes. This effect was mediated by FcγRIIIA, only expressed on connective tissue mast cells, and found in the nasal submucosa. FcγRIIIA-deficient mice had compromised responses to immunization adjuvanted by CTA1-DD/IgG. Proof-of-concept studies revealed that IN immunized mice with human papillomavirus (HPV) type 16 L1 virus-like particles (VLP) and CTA1-DD/IgG immune complexes demonstrated strong and sustained specific antibody titers in serum and vaginal secretions. From a mast cell perspective, CTA1-DD/IgG immune complexes appear to be safe and effective mucosal adjuvants.

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

PubMed

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

2015-06-01

Silicon may be important for bone and connective tissue health. Higher concentrations of silicon are suggested to be associated with bone and the connective tissues, compared with the non-connective soft tissues. Moreover, in connective tissues it has been suggested that silicon levels may decrease with age based upon analyses of human aorta. These claims, however, have not been tested under controlled conditions. Here connective and non-connective tissues were collected and analysed for silicon levels from female Sprague-Dawley rats of different ages (namely, 3, 5, 8, 12, 26 and 43 weeks; n=8-10 per age group), all maintained on the same feed source and drinking water, and kept in the same environment from weaning to adulthood. Tissues (696 samples) were digested in nitric acid and analysed by inductively coupled plasma optical emission spectrometry for total silicon content. Fasting serum samples were also collected, diluted and analysed for silicon. Higher concentrations of silicon (up to 50-fold) were found associated with bone and the connective tissues compared with the non-connective tissues. Although total silicon content increased with age in all tissues, the highest connective tissue silicon concentrations (up to 9.98 μg/g wet weight) were found in young weanling rats, decreasing thereafter with age (by 2-6 fold). Fasting serum silicon concentrations reflected the pattern of connective tissue silicon concentrations and, both measures, when compared to collagen data from a prior experiment in Sprague-Dawley rats, mirrored type I collagen turnover with age. Our findings confirm the link between silicon and connective tissues and would imply that young growing rats have proportionally higher requirements for dietary silicon than mature adults, for bone and connective tissue development, although this was not formally investigated here. However, estimation of total body silicon content suggested that actual Si requirements may be substantially lower than previously estimated which could explain why absolute silicon deficiency is difficult to achieve but, when it is achieved in young growing animals, it results in stunted growth and abnormal development of bone and other connective tissues. Copyright © 2015. Published by Elsevier Inc.

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

PubMed Central

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

2015-01-01

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

Connective tissue disease-associated pulmonary arterial hypertension

PubMed Central

Howard, Luke S.

2015-01-01

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

Radiotherapy in patients with connective tissue diseases.

PubMed

Giaj-Levra, Niccolò; Sciascia, Savino; Fiorentino, Alba; Fersino, Sergio; Mazzola, Rosario; Ricchetti, Francesco; Roccatello, Dario; Alongi, Filippo

2016-03-01

The decision to offer radiotherapy in patients with connective tissue diseases continues to be challenging. Radiotherapy might trigger the onset of connective tissue diseases by increasing the expression of self-antigens, diminishing regulatory T-cell activity, and activating effectors of innate immunity (dendritic cells) through Toll-like receptor-dependent mechanisms, all of which could potentially lead to breaks of immune tolerance. This potential risk has raised some debate among radiation oncologists about whether patients with connective tissue diseases can tolerate radiation as well as people without connective tissue diseases. Because the number of patients with cancer and connective tissue diseases needing radiotherapy will probably increase due to improvements in medical treatment and longer life expectancy, the issue of interactions between radiotherapy and connective tissue diseases needs to be clearer. In this Review, we discuss available data and evidence for patients with connective tissue diseases treated with radiotherapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

[Muscles and connective tissue: histology].

PubMed

Delage, J-P

2012-10-01

Here, we give some comments about the DVD movies "Muscle Attitudes" from Endovivo productions, the movies up lighting some loss in the attention given to studies on the connective tissue, and especially them into muscles. The main characteristics of the different components in the intra-muscular connective tissue (perimysium, endomysium, epimysium) are shown here with special references to their ordered architecture and special references to their spatial distributions. This connective tissue is abundant into the muscles and is in continuity with the muscles in vicinity, with their tendons and their sheath, sticking the whole on skin. This connective tissue has also very abundant connections on the muscles fibres. It is then assumed that the connective tissue sticks every organs or cells of the locomotion system. Considering the elastic properties of the collagen fibres which are the most abundant component of connective tissue, it is possible to up light a panel of connective tissue associated functions such as the transmission of muscle contractions or the regulation of protein and energetic muscles metabolism. Copyright © 2012. Published by Elsevier SAS.

Tissue response to aqueous drainage in a functioning Molteno implant.

PubMed Central

Loeffler, K U; Jay, J L

1988-01-01

The tissue reaction to a functioning Molteno implant has been studied by light microscopy and by scanning and transmission electron microscopy. The material was obtained from an aphakic 83-year-old human eye which required enucleation because of intractable bullous keratopathy, despite well controlled intraocular pressure. The tissue response around the silicone rubber tube was that of simple fibroblastic activity. Around the implant, however, there was fibrous tissue in which necrotic cell debris was prominent. No significant inflammation was observed in this tissue, but the choroid beneath the implant showed a focal inflammatory cell infiltrate. The morphology suggests that the tissue around all surfaces of the implant (450 mm2) is exposed to aqueous, which seems to have a toxic effect on the encapsulating connective tissue. The changes seen in the tissue exposed to draining aqueous are similar to those described in experimental studies of the effect of aqueous on cell growth in tissue culture. Images PMID:3342217

Resistance Training: Physiological Responses and Adaptations (Part 2 of 4).

ERIC Educational Resources Information Center

Fleck, Stephen J.; Kraerner, William J.

1988-01-01

Resistance training causes a variety of physiological reactions, including changes in muscle size, connective tissue size, and bone mineral content. This article summarizes data from a variety of studies and research. (JL)

Glucose impairs tamoxifen responsiveness modulating connective tissue growth factor in breast cancer cells.

PubMed

Ambrosio, Maria Rosaria; D'Esposito, Vittoria; Costa, Valerio; Liguoro, Domenico; Collina, Francesca; Cantile, Monica; Prevete, Nella; Passaro, Carmela; Mosca, Giusy; De Laurentiis, Michelino; Di Bonito, Maurizio; Botti, Gerardo; Franco, Renato; Beguinot, Francesco; Ciccodicola, Alfredo; Formisano, Pietro

2017-12-12

Type 2 diabetes and obesity are negative prognostic factors in patients with breast cancer (BC). We found that sensitivity to tamoxifen was reduced by 2-fold by 25 mM glucose (High Glucose; HG) compared to 5.5 mM glucose (Low Glucose; LG) in MCF7 BC cells. Shifting from HG to LG ameliorated MCF7 cell responsiveness to tamoxifen. RNA-Sequencing of MCF7 BC cells revealed that cell cycle-related genes were mainly affected by glucose. Connective Tissue Growth Factor (CTGF) was identified as a glucose-induced modulator of cell sensitivity to tamoxifen. Co-culturing MCF7 cells with human adipocytes exposed to HG, enhanced CTGF mRNA levels and reduced tamoxifen responsiveness of BC cells. Inhibition of adipocyte-released IL8 reverted these effects. Interestingly, CTGF immuno-detection in bioptic specimens from women with estrogen receptor positive (ER + ) BC correlated with hormone therapy resistance, distant metastases, reduced overall and disease-free survival. Thus, glucose affects tamoxifen responsiveness directly modulating CTGF in BC cells, and indirectly promoting IL8 release by adipocytes.

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

PubMed Central

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

2017-01-01

Skeletal muscles belong to the musculoskeletal system, which is composed of bone, tendon, ligament and irregular connective tissue, and closely associated with motor nerves and blood vessels. The intrinsic molecular signals regulating myogenesis have been extensively investigated. However, muscle development, homeostasis and regeneration require interactions with surrounding tissues and the cellular and molecular aspects of this dialogue have not been completely elucidated. During development and adult life, myogenic cells are closely associated with the different types of connective tissue. Connective tissues are defined as specialized (bone and cartilage), dense regular (tendon and ligament) and dense irregular connective tissue. The role of connective tissue in muscle morphogenesis has been investigated, thanks to the identification of transcription factors that characterize the different types of connective tissues. Here, we review the development of the various connective tissues in the context of the musculoskeletal system and highlight their important role in delivering information necessary for correct muscle morphogenesis, from the early step of myoblast differentiation to the late stage of muscle maturation. Interactions between muscle and connective tissue are also critical in the adult during muscle regeneration, as impairment of the regenerative potential after injury or in neuromuscular diseases results in the progressive replacement of the muscle mass by fibrotic tissue. We conclude that bi-directional communication between muscle and connective tissue is critical for a correct assembly of the musculoskeletal system during development as well as to maintain its homeostasis in the adult. PMID:28386539

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

PubMed

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

2017-01-01

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

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

PubMed

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

2010-12-15

Gingival cells of the oral connective tissue are exposed to complex mechanical forces during mastication, speech, tooth movement and orthodontic treatments. Especially during wound healing following surgical procedures, internal and external forces may occur, creating pressure upon the newly formed tissue. This clinical situation has to be considered when developing biomaterials to augment soft tissue in the oral cavity. In order to pre-evaluate a collagen sponge intended to serve as a substitute for autogenous connective tissue grafts (CTGs), a dynamic bioreactor system was developed. Pressure and shear forces can be applied in this bioreactor in addition to a constant medium perfusion to cell-material constructs. Three-dimensional volume changes and stiffness of the matrices were analyzed. In addition, cell responses such as cell vitality and extracellular matrix (ECM) production were investigated. The number of metabolic active cells constantly increased under fully dynamic culture conditions. The sponges remained elastic even after mechanical forces were applied for 14 days. Analysis of collagen type I and fibronectin revealed a statistically significant accumulation of these ECM molecules (P < 0.05-0.001) when compared to static cultures. An increased expression of tenascin-c, indicating tissue remodeling processes, was observed under dynamic conditions only. The results indicate that the tested in vitro cell culture system was able to mimic both the biological and mechanical environments of the clinical situation in a healing wound. © 2010 Wiley Periodicals, Inc.

Tissue types (image)

MedlinePlus

... are 4 basic types of tissue: connective tissue, epithelial tissue, muscle tissue, and nervous tissue. Connective tissue supports ... binds them together (bone, blood, and lymph tissues). Epithelial tissue provides a covering (skin, the linings of the ...

Elasticity Imaging of Polymeric Media

PubMed Central

Sridhar, Mallika; Liu, Jie; Insana, Michael F.

2009-01-01

Viscoelastic properties of soft tissues and hydropolymers depend on the strength of molecular bonding forces connecting the polymer matrix and surrounding fluids. The basis for diagnostic imaging is that disease processes alter molecular-scale bonding in ways that vary the measurable stiffness and viscosity of the tissues. This paper reviews linear viscoelastic theory as applied to gelatin hydrogels for the purpose of formulating approaches to molecular-scale interpretation of elasticity imaging in soft biological tissues. Comparing measurements acquired under different geometries, we investigate the limitations of viscoelastic parameters acquired under various imaging conditions. Quasistatic (step-and-hold and low-frequency harmonic) stimuli applied to gels during creep and stress relaxation experiments in confined and unconfined geometries reveal continuous, bimodal distributions of respondance times. Within the linear range of responses, gelatin will behave more like a solid or fluid depending on the stimulus magnitude. Gelatin can be described statistically from a few parameters of low-order rheological models that form the basis of viscoelastic imaging. Unbiased estimates of imaging parameters are obtained only if creep data are acquired for greater than twice the highest retardance time constant and any steady-state viscous response has been eliminated. Elastic strain and retardance time images are found to provide the best combination of contrast and signal strength in gelatin. Retardance times indicate average behavior of fast (1–10 s) fluid flows and slow (50–400 s) matrix restructuring in response to the mechanical stimulus. Insofar as gelatin mimics other polymers, such as soft biological tissues, elasticity imaging can provide unique insights into complex structural and biochemical features of connectives tissues affected by disease. PMID:17408331

Effect of aging on gastric mucosal defense mechanisms: ROS, apoptosis, angiogenesis, and sensory neurons.

PubMed

Kang, Jung Mook; Kim, Nayoung; Kim, Joo-Hyon; Oh, Euichaul; Lee, Bong-Yong; Lee, Byoung Hwan; Shin, Cheol Min; Park, Ji Hyun; Lee, Mi Kyoung; Nam, Ryoung Hee; Lee, Hee Eun; Lee, Hye Seung; Kim, Joo Sung; Jung, Hyun Chae; Song, In Sung

2010-11-01

Aging changes in the stomach lead to a decreased capacity for tissue repair in response to gastric acid. The aim of this study was to determine the mechanism associated with the increased susceptibility to injury of aging mucosa including reactive oxygen species (5), apoptosis, angiogenesis, and sensory neuron activity. Fischer 344 rats at four different ages (6, 31, 74 wk, and 2 yr of age) were studied. The connective tissue indicators [salt-soluble collagen and sulfated glycosaminoglycan (sGAG)], lipid hydroperoxide (LPO), myeloperoxidase (MPO), and hexosamine were assessed. We also evaluated the expression of early growth response-1 (Egr-1), phosphatase and tension homologue deleted on chromosome 10 (PTEN), caspase-9 (index of apoptosis), VEGF (index of angiogenesis), calcitonin gene-related peptide (CGRP, index of sensory neurons), and neuronal nitric oxide synthase (nNOS). The histological connective tissue area in the lower part of rat gastric mucosa increased with aging, with increase of salt-soluble collagen and sGAG. LPO and MPO in old rats were significantly greater than in the young rats, whereas hexosamine was significantly reduced. The old gastric mucosa had increased expression of Egr-1, PTEN, and caspase-9, whereas the VEGF, CGRP, and nNOS expression were significantly reduced. These results indicate that the lower part of rat gastric mucosa was found to be replaced by connective tissue with accumulation of oxidative products with aging. In addition, impairment of apoptosis, angiogenesis, and sensory neuron activity via the activation of Egr-1 and PTEN might increase the susceptibility of gastric mucosa to injury during aging.

Tumors: wounds that do not heal-redux.

PubMed

Dvorak, Harold F

2015-01-01

Similarities between tumors and the inflammatory response associated with wound healing have been recognized for more than 150 years and continue to intrigue. Some years ago, based on our then recent discovery of vascular permeability factor (VPF)/VEGF, I suggested that tumors behaved as wounds that do not heal. More particularly, I proposed that tumors co-opted the wound-healing response to induce the stroma they required for maintenance and growth. Work over the past few decades has supported this hypothesis and has put it on a firmer molecular basis. In outline, VPF/VEGF initiates a sequence of events in both tumors and wounds that includes the following: increased vascular permeability; extravasation of plasma, fibrinogen and other plasma proteins; activation of the clotting system outside the vascular system; deposition of an extravascular fibrin gel that serves as a provisional stroma and a favorable matrix for cell migration; induction of angiogenesis and arterio-venogenesis; subsequent degradation of fibrin and its replacement by "granulation tissue" (highly vascular connective tissue); and, finally, vascular resorption and collagen synthesis, resulting in the formation of dense fibrous connective tissue (called "scar tissue" in wounds and "desmoplasia" in cancer). A similar sequence of events also takes place in a variety of important inflammatory diseases that involve cellular immunity. ©2015 American Association for Cancer Research.

Effects of Weightlessness on Vestibular Development of Quail

NASA Technical Reports Server (NTRS)

Fritzsch, Bernd; Bruce, Laura L.

1997-01-01

The lack of gravity is known to alter vestibular responses in developing and adult vertebrates. One cause of these altered responses may be changes in the connections between the vestibular receptor and the brain. Therefore we propose to investigate the effects of gravity on the formations of connections between the gravity receptors of the ear and the brain in developing quail incubated in space beginning at an age before these connections are established (incubation day three) until near the time of hatching, when they are to some extent functional. This investigation will make use of a novel technique, the diffusion of a lipophilic dye, DiI, in fixed tissue. This technique can thus be used to analyze the connections in specimens fixed in orbit, thus eliminating changes due to the earth's gravity. The evaluation of the data will enable us to detect gross deviations from normal patterns as well as detailed quantitative deviations.

Functional tooth restoration by next-generation bio-hybrid implant as a bio-hybrid artificial organ replacement therapy

PubMed Central

Oshima, Masamitsu; Inoue, Kaoru; Nakajima, Kei; Tachikawa, Tetsuhiko; Yamazaki, Hiromichi; Isobe, Tomohide; Sugawara, Ayaka; Ogawa, Miho; Tanaka, Chie; Saito, Masahiro; Kasugai, Shohei; Takano-Yamamoto, Teruko; Inoue, Takashi; Tezuka, Katsunari; Kuboki, Takuo; Yamaguchi, Akira; Tsuji, Takashi

2014-01-01

Bio-hybrid artificial organs are an attractive concept to restore organ function through precise biological cooperation with surrounding tissues in vivo. However, in bio-hybrid artificial organs, an artificial organ with fibrous connective tissues, including muscles, tendons and ligaments, has not been developed. Here, we have enveloped with embryonic dental follicle tissue around a HA-coated dental implant, and transplanted into the lower first molar region of a murine tooth-loss model. We successfully developed a novel fibrous connected tooth implant using a HA-coated dental implant and dental follicle stem cells as a bio-hybrid organ. This bio-hybrid implant restored physiological functions, including bone remodelling, regeneration of severe bone-defect and responsiveness to noxious stimuli, through regeneration with periodontal tissues, such as periodontal ligament and cementum. Thus, this study represents the potential for a next-generation bio-hybrid implant for tooth loss as a future bio-hybrid artificial organ replacement therapy. PMID:25116435

Discrete quasi-linear viscoelastic damping analysis of connective tissues, and the biomechanics of stretching.

PubMed

Babaei, Behzad; Velasquez-Mao, Aaron J; Thomopoulos, Stavros; Elson, Elliot L; Abramowitch, Steven D; Genin, Guy M

2017-05-01

The time- and frequency-dependent properties of connective tissue define their physiological function, but are notoriously difficult to characterize. Well-established tools such as linear viscoelasticity and the Fung quasi-linear viscoelastic (QLV) model impose forms on responses that can mask true tissue behavior. Here, we applied a more general discrete quasi-linear viscoelastic (DQLV) model to identify the static and dynamic time- and frequency-dependent behavior of rabbit medial collateral ligaments. Unlike the Fung QLV approach, the DQLV approach revealed that energy dissipation is elevated at a loading period of ∼10s. The fitting algorithm was applied to the entire loading history on each specimen, enabling accurate estimation of the material's viscoelastic relaxation spectrum from data gathered from transient rather than only steady states. The application of the DQLV method to cyclically loading regimens has broad applicability for the characterization of biological tissues, and the results suggest a mechanistic basis for the stretching regimens most favored by athletic trainers. Copyright © 2017 Elsevier Ltd. All rights reserved.

Discrete quasi-linear viscoelastic damping analysis of connective tissues, and the biomechanics of stretching

PubMed Central

Babaei, Behzad; Velasquez-Mao, Aaron J.; Thomopoulos, Stavros; Elson, Elliot L.; Abramowitch, Steven D.; Genin, Guy M.

2017-01-01

The time- and frequency-dependent properties of connective tissue define their physiological function, but are notoriously difficult to characterize. Well-established tools such as linear viscoelasticity and the Fung quasi-linear viscoelastic (QLV) model impose forms on responses that can mask true tissue behavior. Here, we applied a more general discrete quasi-linear viscoelastic (DQLV) model to identify the static and dynamic time- and frequency-dependent behavior of rabbit medial collateral ligaments. Unlike the Fung QLV approach, the DQLV approach revealed that energy dissipation is elevated at a loading period of ~10 seconds. The fitting algorithm was applied to the entire loading history on each specimen, enabling accurate estimation of the material's viscoelastic relaxation spectrum from data gathered from transient rather than only steady states. The application of the DQLV method to cyclically loading regimens has broad applicability for the characterization of biological tissues, and the results suggest a mechanistic basis for the stretching regimens most favored by athletic trainers. PMID:28088071

Molecular, Cellular and Functional Events in Axonal Sprouting after Stroke

PubMed Central

Kathirvelu, Balachander; Schweppe, Catherine A; Nie, Esther H

2016-01-01

Stroke is the leading cause of adult disability. Yet there is a limited degree of recovery in this disease. One of the mechanisms of recovery is the formation of new connections in the brain and spinal cord after stroke: post-stroke axonal sprouting. Studies indicate that post-stroke axonal sprouting occurs in mice, rats, primates and humans. Inducing post-stroke axonal sprouting in specific connections enhances recovery; blocking axonal sprouting impairs recovery. Behavioral activity patterns after stroke modify the axonal sprouting response. A unique regenerative molecular program mediates this aspect of tissue repair in the CNS. The types of connections that are formed after stroke indicate three patterns of axonal sprouting after stroke: Reactive, Reparative and Unbounded Axonal Sprouting. These differ in mechanism, location, relationship to behavioral recovery and, importantly, in their prospect for therapeutic manipulation to enhance tissue repair. PMID:26874223

Tissue-Specific Analysis of Pharmacological Pathways.

PubMed

Hao, Yun; Quinnies, Kayla; Realubit, Ronald; Karan, Charles; Tatonetti, Nicholas P

2018-06-19

Understanding the downstream consequences of pharmacologically targeted proteins is essential to drug design. Current approaches investigate molecular effects under tissue-naïve assumptions. Many target proteins, however, have tissue-specific expression. A systematic study connecting drugs to target pathways in in vivo human tissues is needed. We introduced a data-driven method that integrates drug-target relationships with gene expression, protein-protein interaction, and pathway annotation data. We applied our method to four independent genomewide expression datasets and built 467,396 connections between 1,034 drugs and 954 pathways in 259 human tissues or cell lines. We validated our results using data from L1000 and Pharmacogenomics Knowledgebase (PharmGKB), and observed high precision and recall. We predicted and tested anticoagulant effects of 22 compounds experimentally that were previously unknown, and used clinical data to validate these effects retrospectively. Our systematic study provides a better understanding of the cellular response to drugs and can be applied to many research topics in systems pharmacology. © 2018 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

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

PubMed Central

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

2014-01-01

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

The diagnostic value of plasma N-terminal connective tissue growth factor levels in children with heart failure.

PubMed

Li, Gang; Song, Xueqing; Xia, Jiyi; Li, Jing; Jia, Peng; Chen, Pengyuan; Zhao, Jian; Liu, Bin

2017-01-01

The aim of this study was to assess the diagnostic value of plasma N-terminal connective tissue growth factor in children with heart failure. Methods and results Plasma N-terminal connective tissue growth factor was determined in 61 children, including 41 children with heart failure, 20 children without heart failure, and 30 healthy volunteers. The correlations between plasma N-terminal connective tissue growth factor levels and clinical parameters were investigated. Moreover, the diagnostic value of N-terminal connective tissue growth factor levels was evaluated. Compared with healthy volunteers and children without heart failure, plasma N-terminal connective tissue growth factor levels were significantly elevated in those with heart failure (p0.05), but it obviously improved the ability of diagnosing heart failure in children, as demonstrated by the integrated discrimination improvement (6.2%, p=0.013) and net re-classification improvement (13.2%, p=0.017) indices. Plasma N-terminal connective tissue growth factor is a promising diagnostic biomarker for heart failure in children.

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

PubMed Central

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

2013-01-01

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

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

PubMed

Stafeev, А А

2015-01-01

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

Qualitative assessment of connective tissue graft with epithelial component. A microsurgical periodontal plastic surgical technique for soft tissue esthetics.

PubMed

Rossi, Roberto; Pilloni, Andrea; Morales, Regina Santos

2009-01-01

Connective tissue grafts have been used successfully in the treatment of gingival recession. In the mid 80s and late 90s, the periodontal literature presented various techniques such as free gingival grafts, pedicle flaps, subepithelial connective tissue grafts, acellular dermal matrix grafts, and guided tissue regeneration to cover denuded root surfaces. Currently, connective tissue grafting is a reliable treatment for esthetic root coverage. This paper presents a qualitative assessment of a surgical technique that uses a connective tissue graft, including a portion of epithelium in the shape of the defect. This procedure enhances the healing of the covered root surface, increases the thickness of the soft tissue and improves esthetics. The criteria used for evaluation were: color, volume, texture, and blending. This evaluation demonstrated encouraging results from an esthetic viewpoint.

Scleroderma

MedlinePlus

... of diseases that cause abnormal growth of connective tissue. Connective tissue is the material inside your body that gives ... joints. Symptoms of scleroderma include Calcium deposits in connective tissues Raynaud's phenomenon, a narrowing of blood vessels in ...

Energy-Based Tissue Fusion for Sutureless Closure: Applications, Mechanisms, and Potential for Functional Recovery.

PubMed

Kramer, Eric A; Rentschler, Mark E

2018-06-04

As minimally invasive surgical techniques progress, the demand for efficient, reliable methods for vascular ligation and tissue closure becomes pronounced. The surgical advantages of energy-based vessel sealing exceed those of traditional, compression-based ligatures in procedures sensitive to duration, foreign bodies, and recovery time alike. Although the use of energy-based devices to seal or transect vasculature and connective tissue bundles is widespread, the breadth of heating strategies and energy dosimetry used across devices underscores an uncertainty as to the molecular nature of the sealing mechanism and induced tissue effect. Furthermore, energy-based techniques exhibit promise for the closure and functional repair of soft and connective tissues in the nervous, enteral, and dermal tissue domains. A constitutive theory of molecular bonding forces that arise in response to supraphysiological temperatures is required in order to optimize and progress the use of energy-based tissue fusion. While rapid tissue bonding has been suggested to arise from dehydration, dipole interactions, molecular cross-links, or the coagulation of cellular proteins, long-term functional tissue repair across fusion boundaries requires that the reaction to thermal damage be tailored to catalyze the onset of biological healing and remodeling. In this review, we compile and contrast findings from published thermal fusion research in an effort to encourage a molecular approach to characterization of the prevalent and promising energy-based tissue bond.

BONE REGENERATION AFTER DEMINERALIZED BONE MATRIX AND CASTOR OIL (RICINUS COMMUNIS) POLYURETHANE IMPLANTATION

PubMed Central

Leite, Fábio Renato Manzolli; Ramalho, Lizeti Toledo de Oliveira

2008-01-01

Innocuous biocompatible materials have been searched to repair or reconstruct bone defects. Their goal is to restore the function of live or dead tissues. This study compared connective tissue and bone reaction when exposed to demineralized bovine bone matrix and a polyurethane resin derived from castor bean (Ricinus communis). Forty-five rats were assigned to 3 groups of 15 animals (control, bovine bone and polyurethane). A cylindrical defect was created on mandible base and filled with bovine bone matrix and the polyurethane. Control group received no treatment. Analyses were performed after 15, 45 and 60 days (5 animals each). Histological analysis revealed connective tissue tolerance to bovine bone with local inflammatory response similar to that of the control group. After 15 days, all groups demonstrated similar outcomes, with mild inflammatory reaction, probably due to the surgical procedure rather than to the material. In the polymer group, after 60 days, scarce multinucleated cells could still be observed. In general, all groups showed good stability and osteogenic connective tissue with blood vessels into the surgical area. The results suggest biocompatibility of both materials, seen by their integration into rat mandible. Moreover, the polyurethane seems to be an alternative in bone reconstruction and it is an inexhaustible source of biomaterial. PMID:19089203

Blood Flow Changes in Subsynovial Connective Tissue on Contrast-Enhanced Ultrasonography in Patients With Carpal Tunnel Syndrome Before and After Surgical Decompression.

PubMed

Motomiya, Makoto; Funakoshi, Tadanao; Ishizaka, Kinya; Nishida, Mutsumi; Matsui, Yuichiro; Iwasaki, Norimasa

2017-11-24

Although qualitative alteration of the subsynovial connective tissue in the carpal tunnel is considered to be one of the most important factors in the pathophysiologic mechanisms of carpal tunnel syndrome (CTS), little information is available about the microcirculation in the subsynovial connective tissue in patients with CTS. The aims of this study were to use contrast-enhanced ultrasonography (US) to evaluate blood flow in the subsynovial connective tissue proximal to the carpal tunnel in patients with CTS before and after carpal tunnel release. The study included 15 volunteers and 12 patients with CTS. The blood flow in the subsynovial connective tissue and the median nerve was evaluated preoperatively and at 1, 2, and 3 months postoperatively using contrast-enhanced US. The blood flow in the subsynovial connective tissue was higher in the patients with CTS than in the volunteers. In the patients with CTS, there was a significant correlation between the blood flow in the subsynovial connective tissue and the median nerve (P = .01). The blood flow in both the subsynovial connective tissue and the median nerve increased markedly after carpal tunnel release. Our results suggest that increased blood flow in the subsynovial connective tissue may play a role in the alteration of the microcirculation within the median nerve related to the pathophysiologic mechanisms of CTS. The increase in the blood flow in the subsynovial connective tissue during the early postoperative period may contribute to the changes in intraneural circulation, and these changes may lead to neural recovery. © 2017 by the American Institute of Ultrasound in Medicine.

Pectus Excavatum and Heritable Disorders of the Connective Tissue

PubMed Central

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

2013-01-01

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. PMID:24198927

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

PubMed

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

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. Copyright© Ferrata Storti Foundation.

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

PubMed Central

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

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

Mechanical Tension Increases CCN2/CTGF Expression and Proliferation in Gingival Fibroblasts via a TGFβ-Dependent Mechanism

PubMed Central

Guo, Fen; Carter, David E.; Leask, Andrew

2011-01-01

Unlike skin, oral gingival do not scar in response to tissue injury. Fibroblasts, the cell type responsible for connective tissue repair and scarring, are exposed to mechanical tension during normal and pathological conditions including wound healing and fibrogenesis. Understanding how human gingival fibroblasts respond to mechanical tension is likely to yield valuable insights not only into gingival function but also into the molecular basis of scarless repair. CCN2/connective tissue growth factor is potently induced in fibroblasts during tissue repair and fibrogenesis. We subjected gingival fibroblasts to cyclical strain (up to 72 hours) using the Flexercell system and showed that CCN2 mRNA and protein was induced by strain. Strain caused the rapid activation of latent TGFβ, in a fashion that was reduced by blebbistatin and FAK/src inhibition, and the induction of endothelin (ET-1) mRNA and protein expression. Strain did not cause induction of α-smooth muscle actin or collagen type I mRNAs (proteins promoting scarring); but induced a cohort of pro-proliferative mRNAs and cell proliferation. Compared to dermal fibroblasts, gingival fibroblasts showed reduced ability to respond to TGFβ by inducing fibrogenic mRNAs; addition of ET-1 rescued this phenotype. Pharmacological inhibition of the TGFβ type I (ALK5) receptor, the endothelin A/B receptors and FAK/src significantly reduced the induction of CCN2 and pro-proliferative mRNAs and cell proliferation. Controlling TGFβ, ET-1 and FAK/src activity may be useful in controlling responses to mechanical strain in the gingiva and may be of value in controlling fibroproliferative conditions such as gingival hyperplasia; controlling ET-1 may be of benefit in controlling scarring in response to injury in the skin. PMID:21611193

Expression of collagen and related growth factors in rat tendon and skeletal muscle in response to specific contraction types

PubMed Central

Heinemeier, K M; Olesen, J L; Haddad, F; Langberg, H; Kjaer, M; Baldwin, K M; Schjerling, P

2007-01-01

Acute exercise induces collagen synthesis in both tendon and muscle, indicating an adaptive response in the connective tissue of the muscle–tendon unit. However, the mechanisms of this adaptation, potentially involving collagen-inducing growth factors (such as transforming growth factor-β-1 (TGF-β-1)), as well as enzymes related to collagen processing, are not clear. Furthermore, possible differential effects of specific contraction types on collagen regulation have not been investigated. Female Sprague–Dawley rats were subjected to 4 days of concentric, eccentric or isometric training (n = 7–9 per group) of the medial gastrocnemius, by stimulation of the sciatic nerve. RNA was extracted from medial gastrocnemius and Achilles tendon tissue 24 h after the last training bout, and mRNA levels for collagens I and III, TGF-β-1, connective tissue growth factor (CTGF), lysyl oxidase (LOX), metalloproteinases (MMP-2 and -9) and their inhibitors (TIMP-1 and 2) were measured by Northern blotting and/or real-time PCR. In tendon, expression of TGF-β-1 and collagens I and III (but not CTGF) increased in response to all types of training. Similarly, enzymes/factors involved in collagen processing were induced in tendon, especially LOX (up to 37-fold), which could indicate a loading-induced increase in cross-linking of tendon collagen. In skeletal muscle, a similar regulation of gene expression was observed, but in contrast to the tendon response, the effect of eccentric training was significantly greater than the effect of concentric training on the expression of several transcripts. In conclusion, the study supports an involvement of TGF-β-1 in loading-induced collagen synthesis in the muscle–tendon unit and importantly, it indicates that muscle tissue is more sensitive than tendon to the specific mechanical stimulus. PMID:17540706

Expression of collagen and related growth factors in rat tendon and skeletal muscle in response to specific contraction types.

PubMed

Heinemeier, K M; Olesen, J L; Haddad, F; Langberg, H; Kjaer, M; Baldwin, K M; Schjerling, P

2007-08-01

Acute exercise induces collagen synthesis in both tendon and muscle, indicating an adaptive response in the connective tissue of the muscle-tendon unit. However, the mechanisms of this adaptation, potentially involving collagen-inducing growth factors (such as transforming growth factor-beta-1 (TGF-beta-1)), as well as enzymes related to collagen processing, are not clear. Furthermore, possible differential effects of specific contraction types on collagen regulation have not been investigated. Female Sprague-Dawley rats were subjected to 4 days of concentric, eccentric or isometric training (n = 7-9 per group) of the medial gastrocnemius, by stimulation of the sciatic nerve. RNA was extracted from medial gastrocnemius and Achilles tendon tissue 24 h after the last training bout, and mRNA levels for collagens I and III, TGF-beta-1, connective tissue growth factor (CTGF), lysyl oxidase (LOX), metalloproteinases (MMP-2 and -9) and their inhibitors (TIMP-1 and 2) were measured by Northern blotting and/or real-time PCR. In tendon, expression of TGF-beta-1 and collagens I and III (but not CTGF) increased in response to all types of training. Similarly, enzymes/factors involved in collagen processing were induced in tendon, especially LOX (up to 37-fold), which could indicate a loading-induced increase in cross-linking of tendon collagen. In skeletal muscle, a similar regulation of gene expression was observed, but in contrast to the tendon response, the effect of eccentric training was significantly greater than the effect of concentric training on the expression of several transcripts. In conclusion, the study supports an involvement of TGF-beta-1 in loading-induced collagen synthesis in the muscle-tendon unit and importantly, it indicates that muscle tissue is more sensitive than tendon to the specific mechanical stimulus.

Genome-wide strategies identify downstream target genes of chick connective tissue-associated transcription factors.

PubMed

Orgeur, Mickael; Martens, Marvin; Leonte, Georgeta; Nassari, Sonya; Bonnin, Marie-Ange; Börno, Stefan T; Timmermann, Bernd; Hecht, Jochen; Duprez, Delphine; Stricker, Sigmar

2018-03-29

Connective tissues support organs and play crucial roles in development, homeostasis and fibrosis, yet our understanding of their formation is still limited. To gain insight into the molecular mechanisms of connective tissue specification, we selected five zinc-finger transcription factors - OSR1, OSR2, EGR1, KLF2 and KLF4 - based on their expression patterns and/or known involvement in connective tissue subtype differentiation. RNA-seq and ChIP-seq profiling of chick limb micromass cultures revealed a set of common genes regulated by all five transcription factors, which we describe as a connective tissue core expression set. This common core was enriched with genes associated with axon guidance and myofibroblast signature, including fibrosis-related genes. In addition, each transcription factor regulated a specific set of signalling molecules and extracellular matrix components. This suggests a concept whereby local molecular niches can be created by the expression of specific transcription factors impinging on the specification of local microenvironments. The regulatory network established here identifies common and distinct molecular signatures of limb connective tissue subtypes, provides novel insight into the signalling pathways governing connective tissue specification, and serves as a resource for connective tissue development. © 2018. Published by The Company of Biologists Ltd.

Elevated expression in situ of selectin and immunoglobulin superfamily type adhesion molecules in retroocular connective tissues from patients with Graves' ophthalmopathy.

PubMed Central

Heufelder, A E; Bahn, R S

1993-01-01

Activation of certain adhesion molecules within vascular endothelium and the surrounding extravascular space is a critical event in the recruitment and targeting of an inflammatory response or autoimmune attack to a particular tissue site. We have recently demonstrated that the adhesion of lymphocytes to cultured retroocular fibroblasts obtained from patients with Graves' ophthalmopathy (GO) is mediated predominantly by the interaction of lymphocyte function-associated antigen-1 (LFA-1), expressed on lymphocytes, with intercellular adhesion molecule-1 (ICAM-1), expressed by these cells following exposure to interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), IL-1 alpha or purified thyroid-stimulating immunoglobulins. We now report the expression and localization in situ of several adhesion molecules, ICAM-1, endothelial leucocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1), and LFA-3 in retroocular tissues derived from patients with severe GO (n = 4) and normal individuals (n = 3). Serial cryostat sections of tissue specimens were processed for immunoperoxidase staining using various MoAbs against ICAM-1, ELAM-1, VCAM-1 and LFA-3. In addition, consecutive sections were stained with MoAbs against LFA-1, CD45RO (UCHL-1)DR-human leucocyte antigen (HLA-DR), CD11b/CD18 (Mac-1), and CD11c/CD18 (p150,95). In GO-retroocular tissues, strong immunoreactivity for ICAM-1 and LFA-3 was detected in blood vessels (> 90%), in perimysial fibroblasts surrounding extraocular muscle fibres, and in connective tissue distinct from extraocular muscle. No ICAM-1 or LFA-3 immunoreactivity was present in extraocular muscle cells themselves. ICAM-1 and LFA-3 immunoreactivity in normal tissues was minimal or absent both in connective and muscle tissues. Vascular endothelium was strongly positive for ELAM-1 and VCAM-1 in GO-retroocular tissues, while VCAM-1 immunoreactivity was minimal (< 5% of blood vessels) and ELAM-1 immunoreactivity was generally absent in normal retroocular tissue. LFA-1-expressing, activated mononuclear cells and memory T lymphocytes (CD3+/CD45RO+) were only detected in GO-retrocular tissues, and were mainly localized around blood vessels and in areas of ICAM-1-expressing connective and perimysial tissue. HLA-DR expression was restricted to GO-tissue specimens, with strong immunoreactivity detected in blood vessels, macrophages and connective tissue and perimysial fibroblasts. No HLA-DR was detectable in extraocular muscle cells. In conclusion, infiltration of the orbit in GO by mononuclear cells, and their targeting within the orbit, may depend upon the coordinate expression of certain adhesion and MHC molecules.(ABSTRACT TRUNCATED AT 400 WORDS) Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 PMID:7680294

Endermologie New Aproach in the Medicine Treatment

NASA Astrophysics Data System (ADS)

Mezencevová, Viktória; Torok, Jozef; Czánová, Tatiana; Zajac, Ján

2017-10-01

Using the effect of mechanical forces affecting cellular response in the treatment of post-traumatic, postoperative, post-imlantation conditions through the application of Endermologie®- mechanotransduction represents a revolutionary solution in tissue-rehabilitation and positive target tissue influencing, with faster regeneration (1). Endermologie® is a noninvasive, painless, natural method of treatments of all connective tissue transformations, muscle and circulation pathologies. The aim of our study is investigation and explanation the mechanism of action by observing the physiological effects of Endermologie® based on human studies. The paper is focused on monitoring of possitive effect tissue regeneration using endermologie as a tools mechanostimulation improvements of systems integridy and health improvement.

Genetics Home Reference: arterial tortuosity syndrome

MedlinePlus

... tortuosity syndrome is a disorder that affects connective tissue. Connective tissue provides strength and flexibility to structures throughout the ... outside the circulatory system are caused by abnormal connective tissue in other parts of the body. These features ...

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

PubMed

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

2013-04-01

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

Molecular and physiological mechanisms regulating tissue reunion in incised plant tissues.

PubMed

Asahina, Masashi; Satoh, Shinobu

2015-05-01

Interactions among the functionally specialized organs of higher plants ensure that the plant body develops and functions properly in response to changing environmental conditions. When an incision or grafting procedure interrupts the original organ or tissue connection, cell division is induced and tissue reunion occurs to restore physiological connections. Such activities have long been observed in grafting techniques, which are advantageous not only for agriculture and horticulture but also for basic research. To understand how this healing process is controlled and how this process is initiated and regulated at the molecular level, physiological and molecular analyses of tissue reunion have been performed using incised hypocotyls of cucumber (Cucumis sativus) and tomato (Solanum lycopersicum) and incised flowering stems of Arabidopsis thaliana. Our results suggest that leaf gibberellin and microelements from the roots are required for tissue reunion in the cortex of the cucumber and tomato incised hypocotyls. In addition, the wound-inducible hormones ethylene and jasmonic acid contribute to the regulation of the tissue reunion process in the upper and lower parts, respectively, of incised Arabidopsis stems. Ethylene and jasmonic acid modulate the expression of ANAC071 and RAP2.6L, respectively, and auxin signaling via ARF6/8 is essential for the expression of these transcription factors. In this report, we discuss recent findings regarding molecular and physiological mechanisms of the graft union and the tissue reunion process in wounded tissues of plants.

Cell Connections by Tunneling Nanotubes: Effects of Mitochondrial Trafficking on Target Cell Metabolism, Homeostasis, and Response to Therapy

PubMed Central

2017-01-01

Intercellular communications play a major role in tissue homeostasis and responses to external cues. Novel structures for this communication have recently been described. These tunneling nanotubes (TNTs) consist of thin-extended membrane protrusions that connect cells together. TNTs allow the cell-to-cell transfer of various cellular components, including proteins, RNAs, viruses, and organelles, such as mitochondria. Mesenchymal stem cells (MSCs) are both naturally present and recruited to many different tissues where their interaction with resident cells via secreted factors has been largely documented. Their immunosuppressive and repairing capacities constitute the basis for many current clinical trials. MSCs recruited to the tumor microenvironment also play an important role in tumor progression and resistance to therapy. MSCs are now the focus of intense scrutiny due to their capacity to form TNTs and transfer mitochondria to target cells, either in normal physiological or in pathological conditions, leading to changes in cell energy metabolism and functions, as described in this review. PMID:28659978

Hyaluronan (HA) interacting proteins RHAMM and hyaluronidase impact prostate cancer cell behavior and invadopodia formation in 3D HA-based hydrogels.

PubMed

Gurski, Lisa A; Xu, Xian; Labrada, Lyana N; Nguyen, Ngoc T; Xiao, Longxi; van Golen, Kenneth L; Jia, Xinqiao; Farach-Carson, Mary C

2012-01-01

To study the individual functions of hyaluronan interacting proteins in prostate cancer (PCa) motility through connective tissues, we developed a novel three-dimensional (3D) hyaluronic acid (HA) hydrogel assay that provides a flexible, quantifiable, and physiologically relevant alternative to current methods. Invasion in this system reflects the prevalence of HA in connective tissues and its role in the promotion of cancer cell motility and tissue invasion, making the system ideal to study invasion through bone marrow or other HA-rich connective tissues. The bio-compatible cross-linking process we used allows for direct encapsulation of cancer cells within the gel where they adopt a distinct, cluster-like morphology. Metastatic PCa cells in these hydrogels develop fingerlike structures, "invadopodia", consistent with their invasive properties. The number of invadopodia, as well as cluster size, shape, and convergence, can provide a quantifiable measure of invasive potential. Among candidate hyaluronan interacting proteins that could be responsible for the behavior we observed, we found that culture in the HA hydrogel triggers invasive PCa cells to differentially express and localize receptor for hyaluronan mediated motility (RHAMM)/CD168 which, in the absence of CD44, appears to contribute to PCa motility and invasion by interacting with the HA hydrogel components. PCa cell invasion through the HA hydrogel also was found to depend on the activity of hyaluronidases. Studies shown here reveal that while hyaluronidase activity is necessary for invadopodia and inter-connecting cluster formation, activity alone is not sufficient for acquisition of invasiveness to occur. We therefore suggest that development of invasive behavior in 3D HA-based systems requires development of additional cellular features, such as activation of motility associated pathways that regulate formation of invadopodia. Thus, we report development of a 3D system amenable to dissection of biological processes associated with cancer cell motility through HA-rich connective tissues.

The Effect of Tissue Entrapment on Screw Loosening at the Implant/Abutment Interface of External- and Internal-Connection Implants: An In Vitro Study.

PubMed

Zeno, Helios A; Buitrago, Renan L; Sternberger, Sidney S; Patt, Marisa E; Tovar, Nick; Coelho, Paulo; Kurtz, Kenneth S; Tuminelli, Frank J

2016-04-01

To compare the removal of torque values of machined implant abutment connections (internal and external) with and without soft tissue entrapment using an in vitro model. Thirty external- and 30 internal-connection implants were embedded in urethane dimethacrylate. Porcine tissue was prepared and measured to thicknesses of 0.5 and 1.0 mm. Six groups (n = 10) were studied: External- and internal-connection implants with no tissue (control), 0.5, and 1.0 mm of tissue were entrapped at the implant/abutment interface. Abutments were inserted to 20 Ncm for all six groups. Insertion torque values were recorded using a digital torque gauge. All groups were then immersed in 1 M NaOH for 48 hours to dissolve tissue. Subsequent reverse torque measurements were recorded. Mean and standard deviation were determined for each group, and one-way ANOVA and Bonferroni test were used for statistical analysis. All 60 specimens achieved a 20-Ncm insertion torque, despite tissue entrapment. Reverse torque measurements for external connection displayed a statistically significant difference (p < 0.05) between all groups with mean reverse torque values for the control (13.71 ± 1.4 Ncm), 0.5 mm (7.83 ± 2.4 Ncm), and 1.0 mm tissue entrapment (2.29 ± 1.4 Ncm) groups. Some statistically significant differences (p < 0.05) were found between internal-connection groups. In all specimens, tissue did not completely dissolve after 48 hours. External-connection implants were significantly affected by tissue entrapment; the thicker the tissue, the lower the reverse torque values noted. Internal-connection implants were less affected by tissue entrapment. © 2015 by the American College of Prosthodontists.

An atlas of B-cell clonal distribution in the human body.

PubMed

Meng, Wenzhao; Zhang, Bochao; Schwartz, Gregory W; Rosenfeld, Aaron M; Ren, Daqiu; Thome, Joseph J C; Carpenter, Dustin J; Matsuoka, Nobuhide; Lerner, Harvey; Friedman, Amy L; Granot, Tomer; Farber, Donna L; Shlomchik, Mark J; Hershberg, Uri; Luning Prak, Eline T

2017-09-01

B-cell responses result in clonal expansion, and can occur in a variety of tissues. To define how B-cell clones are distributed in the body, we sequenced 933,427 B-cell clonal lineages and mapped them to eight different anatomic compartments in six human organ donors. We show that large B-cell clones partition into two broad networks-one spans the blood, bone marrow, spleen and lung, while the other is restricted to tissues within the gastrointestinal (GI) tract (jejunum, ileum and colon). Notably, GI tract clones display extensive sharing of sequence variants among different portions of the tract and have higher frequencies of somatic hypermutation, suggesting extensive and serial rounds of clonal expansion and selection. Our findings provide an anatomic atlas of B-cell clonal lineages, their properties and tissue connections. This resource serves as a foundation for studies of tissue-based immunity, including vaccine responses, infections, autoimmunity and cancer.

Small-Scale Fabrication of Biomimetic Structures for Periodontal Regeneration

PubMed Central

Green, David W.; Lee, Jung-Seok; Jung, Han-Sung

2016-01-01

The periodontium is the supporting tissues for the tooth organ and is vulnerable to destruction, arising from overpopulating pathogenic bacteria and spirochaetes. The presence of microbes together with host responses can destroy large parts of the periodontium sometimes leading tooth loss. Permanent tissue replacements are made possible with tissue engineering techniques. However, existing periodontal biomaterials cannot promote proper tissue architectures, necessary tissue volumes within the periodontal pocket and a “water-tight” barrier, to become clinically acceptable. New kinds of small-scale engineered biomaterials, with increasing biological complexity are needed to guide proper biomimetic regeneration of periodontal tissues. So the ability to make compound structures with small modules, filled with tissue components, is a promising design strategy for simulating the anatomical complexity of the periodotium attachment complexes along the tooth root and the abutment with the tooth collar. Anatomical structures such as, intima, adventitia, and special compartments such as the epithelial cell rests of Malassez or a stellate reticulum niche need to be engineered from the start of regeneration to produce proper periodontium replacement. It is our contention that the positioning of tissue components at the origin is also necessary to promote self-organizing cell–cell connections, cell–matrix connections. This leads to accelerated, synchronized and well-formed tissue architectures and anatomies. This strategy is a highly effective preparation for tackling periodontitis, periodontium tissue resorption, and to ultimately prevent tooth loss. Furthermore, such biomimetic tissue replacements will tackle problems associated with dental implant support and perimimplantitis. PMID:26903872

Interaction of Vascular Smooth Muscle Cells Under Low Shear Stress

NASA Technical Reports Server (NTRS)

Seidel, Charles L.

1998-01-01

The blood vessel wall consists of three cellular layers, an outer adventitial, a middle medial and an inner intimal layer. When the blood vessel forms in the embryo it begins as a tube composed of a single cell type called endothelial cells. Over time, other cells are recruited from the surrounding tissue to form additional layers on the outer surface of the endothelial tube. The cells that are recruited are called mesenchymal cells. Mesenchymal cells are responsible for the production of connective tissue that holds the blood vessel together and for developing into vascular smooth muscle cells that are responsible for regulating the diameter of the vessel (1) and therefore, blood flow. In a fully developed blood vessel, the endothelial cells make- up the majority of cells in the intimal layer while the mesenchymal cells make-up the majority of cells in the medial and adventitial layers. Within the medial layer of a mature vessel, cells are organized into multiple circular layers of alternating bands of connective tissue and cells. The cell layer is composed of a mixture of mesenchymal cells that have not developed into smooth muscle cells and fully developed smooth muscle cells (2). The assembly and organization of complex tissues is directed in part by a signaling system composed of proteins on the cell surface called adhesion molecules. Adhesion molecules enable cells to recognize each other as well as the composition of the connective tissue in which they reside (3). It was hypothesized that the different cell types that compose the vascular wall possess different adhesion molecules that enable them to recognize each other and through this recognition system, form the complex layered organization of the vascular wall. In other words, the layered organization is an intrinsic property of the cells. If this hypothesis is correct then the different cells that make up the vessel wall, when mixed together, should organize themselves into a layered structure resembling an intact blood vessel. Experiments described below were designed to test this hypothesis.

Initial Biochemical Characterization of Cells Derived from Human Periodontium and Their In vitro Response to Platelet-Derived Growth Factor, Epidermal Growth Factor and Transforming Growth Factor-Beta

DTIC Science & Technology

1988-05-01

Periodontal disease is characterized by a loss of connective tissue...obtained for bone cells and fibroblasts. • " S,. O. ipr’ 0 II. LITERATURE REVIEW A . Periodontal Regeneration Periodontal disease is characterized by a ...fracture are felt to involve a similar sequence of cellular events. Since periodontal disease also involves the loss of soft tissue structures, such

Effect of houttuynia cordata aetherolea on adiponectin and connective tissue growth factor in a rat model of diabetes mellitus.

PubMed

Wang, Hai-Ying; Bao, Jun-Lu

2012-03-01

To determine the effect of Houttuynia cordata Aetherolea on connective tissue growth factor and adiponectin in a rat model of diabetes mellitus (DM). DM was induced in rats using streptozotocin (STZ) and high glucose-lipid animal feed. Animals were then treated with Houttuynia cordata Aetherolea for 8 weeks. Changes in connective tissue growth factor and adiponectin levels in rats were observed. Connective tissue growth factor and adiponectin levels in rats with DM improved after Houttuynia cordata Aetherolea treatment. Houttuynia cordata Aetherolea had a positive effect on rats with DM by reducing levels of connective tissue growth factor and increasing adiponectin levels.

Use of collagen film as a dural substitute: preliminary animal studies.

PubMed

Collins, R L; Christiansen, D; Zazanis, G A; Silver, F H

1991-02-01

Cadaver grafts, laminated metallic materials, and synthetic fabrics have been evaluated as dural substitutes. Use of cadaver tissues is limited by fear of transmission of infectious disease while use of synthetic materials is associated with implant encapsulation and foreign body reactions. The purpose of this study is to evaluate the use of collagen film as a dural substitute. Collagen films prepared from bovine skin were used to replace the dura of rabbits and histological observations were made at 16, 28, 42, and 56 days postimplantation. Controls consisted of dura that was removed and then reattached. Control dura showed no signs of inflammation or adhesion to underlying tissue at 16 and 28 days postimplantation. By 56 days postimplantation, extensive connective tissue deposition was observed in close proximity to adjacent bone as well as pia arachnoid adhesions. Implanted collagen film behaved in a similar manner to control dura showing minimal inflammatory response at all time periods. At 56 days postimplantation collagen film appeared strongly infiltrated by connective tissue cells that deposited new collagen. The results of this study suggest that a reconstituted type I collagen film crosslinked with cyanamide acts as a temporary barrier preventing loss of fluid and adhesion formation. It is replaced after approximately 2 months with host collagen with limited inflammatory and fibrotic complications. Further studies are needed to completely characterize the new connective tissue formed as well as long-term biocompatibility and functioning of a reconstituted collagen dural substitute.

Vascularization after treatment of gingival recession defects with platelet-rich fibrin or connective tissue graft.

PubMed

Eren, Gülnihal; Kantarcı, Alpdoğan; Sculean, Anton; Atilla, Gül

2016-11-01

The aim of this study was to evaluate histologically the following treatment of bilateral localized gingival recessions with coronally advanced flap (CAF) combined with platelet-rich fibrin (PRF) or subepithelial connective tissue graft (SCTG). Tissue samples were harvested from 14 subjects either 1 or 6 months after the surgeries. The 2-mm punch biopsies were obtained from the mid-portion of the grafted sites. Neutral buffered formalin fixed, paraffin-embedded 5-μm thick tissue sections were stained with hematoxylin eosin and Masson's trichrome in order to analyze the collagen framework, epithelium thickness and rete-peg length. Multiple sequential sections were cut from paraffin-embedded blocks of tissue and immunohistochemically prepared for detection of vascular endothelial growth factor, CD31 and CD34, for the assessment of vascularization. Rete peg formation was significantly increased in the sites treated with PRF compared to the SCTG group after 6 months (p < 0.05). On the contrary, the number of vessels was increased in the SCTG group compared to the PRF group after 6 months (p < 0.05). No statistically significant differences were observed in the collagen density. Staining intensity of CD31 increased in submucosal area of PRF group than SCTG group after 1 month. Higher staining intensity of CD34 was observed in the submucosal area of PRF group compared with SCTG group after 6 months. The results of the present study suggest that in histological evaluation because of its biological compounds, PRF results earlier vessel formation and tissue maturation compared to connective tissue graft. PRF regulated the vascular response associated with an earlier wound healing.

Connective tissue diseases, multimorbidity and the ageing lung.

PubMed

Spagnolo, Paolo; Cordier, Jean-François; Cottin, Vincent

2016-05-01

Connective tissue diseases encompass a wide range of heterogeneous disorders characterised by immune-mediated chronic inflammation often leading to tissue damage, collagen deposition and possible loss of function of the target organ. Lung involvement is a common complication of connective tissue diseases. Depending on the underlying disease, various thoracic compartments can be involved but interstitial lung disease is a major contributor to morbidity and mortality. Interstitial lung disease, pulmonary hypertension or both are found most commonly in systemic sclerosis. In the elderly, the prevalence of connective tissue diseases continues to rise due to both longer life expectancy and more effective and better-tolerated treatments. In the geriatric population, connective tissue diseases are almost invariably accompanied by age-related comorbidities, and disease- and treatment-related complications, which contribute to the significant morbidity and mortality associated with these conditions, and complicate treatment decision-making. Connective tissue diseases in the elderly represent a growing concern for healthcare providers and an increasing burden of global health resources worldwide. A better understanding of the mechanisms involved in the regulation of the immune functions in the elderly and evidence-based guidelines specifically designed for this patient population are instrumental to improving the management of connective tissue diseases in elderly patients. Copyright ©ERS 2016.

Tendon and Ligament Regeneration and Repair: Clinical Relevance and Developmental Paradigm

PubMed Central

Tuan, Rocky S.

2014-01-01

Tendon and ligament (T/L) are dense connective tissues connecting bone to muscle and bone to bone, respectively. Similar to other musculoskeletal tissues, T/L arise from the somitic mesoderm, but they are derived from a recently discovered somitic compartment, the syndetome. The adjacent sclerotome and myotome provide inductive signals to the interposing syndetome, thereby upregulating the expression of the transcription factor Scleraxis, which in turn leads to further tenogenic and ligamentogenic differentiation. These advances in the understanding of T/L development have been sought to provide a knowledge base for improving the healing of T/L injuries, a common clinical challenge due to the intrinsically poor natural healing response. Specifically, the three most common tendon injuries involve tearing of the rotator cuff of the shoulder, the flexor tendon of the hand, and the Achilles tendon. At present, injuries to these tissues are treated by surgical repair and/or conservative approaches, including biophysical modalities such as physical rehabilitation and cryotherapy. Unfortunately, the healing tissue forms fibrovascular scar and possesses inferior mechanical and biochemical properties as compared to native T/L. Therefore, tissue engineers have sought to improve upon the natural healing response by augmenting the injured tissue with cells, scaffolds, bioactive agents, and mechanical stimulation. These strategies show promise, both in vitro and in vivo, for improving T/L healing. However, several challenges remain in restoring full T/L function following injury, including uncertainties over the optimal combination of these biological agents as well how to best deliver tissue engineered elements to the injury site. A greater understanding of the molecular mechanisms involved in T/L development and natural healing, coupled with the capability of producing complex biomaterials to deliver multiple growth factors with high spatiotemporal resolution and specificity, will allow tissue engineers to more closely recapitulate T/L morphogenesis, thereby offering future patients the prospect of T/L regeneration, as opposed to simple tissue repair. PMID:24078497

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

NASA Astrophysics Data System (ADS)

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

2016-09-01

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

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

NASA Astrophysics Data System (ADS)

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

2016-10-01

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

Cells of the connective tissue differentiate and migrate into pollen sacs

NASA Astrophysics Data System (ADS)

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

2002-01-01

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

Biocompatible magnetic core-shell nanocomposites for engineered magnetic tissues

NASA Astrophysics Data System (ADS)

Rodriguez-Arco, Laura; Rodriguez, Ismael A.; Carriel, Victor; Bonhome-Espinosa, Ana B.; Campos, Fernando; Kuzhir, Pavel; Duran, Juan D. G.; Lopez-Lopez, Modesto T.

2016-04-01

The inclusion of magnetic nanoparticles into biopolymer matrixes enables the preparation of magnetic field-responsive engineered tissues. Here we describe a synthetic route to prepare biocompatible core-shell nanostructures consisting of a polymeric core and a magnetic shell, which are used for this purpose. We show that using a core-shell architecture is doubly advantageous. First, gravitational settling for core-shell nanocomposites is slower because of the reduction of the composite average density connected to the light polymer core. Second, the magnetic response of core-shell nanocomposites can be tuned by changing the thickness of the magnetic layer. The incorporation of the composites into biopolymer hydrogels containing cells results in magnetic field-responsive engineered tissues whose mechanical properties can be controlled by external magnetic forces. Indeed, we obtain a significant increase of the viscoelastic moduli of the engineered tissues when exposed to an external magnetic field. Because the composites are functionalized with polyethylene glycol, the prepared bio-artificial tissue-like constructs also display excellent ex vivo cell viability and proliferation. When implanted in vivo, the engineered tissues show good biocompatibility and outstanding interaction with the host tissue. Actually, they only cause a localized transitory inflammatory reaction at the implantation site, without any effect on other organs. Altogether, our results suggest that the inclusion of magnetic core-shell nanocomposites into biomaterials would enable tissue engineering of artificial substitutes whose mechanical properties could be tuned to match those of the potential target tissue. In a wider perspective, the good biocompatibility and magnetic behavior of the composites could be beneficial for many other applications.The inclusion of magnetic nanoparticles into biopolymer matrixes enables the preparation of magnetic field-responsive engineered tissues. Here we describe a synthetic route to prepare biocompatible core-shell nanostructures consisting of a polymeric core and a magnetic shell, which are used for this purpose. We show that using a core-shell architecture is doubly advantageous. First, gravitational settling for core-shell nanocomposites is slower because of the reduction of the composite average density connected to the light polymer core. Second, the magnetic response of core-shell nanocomposites can be tuned by changing the thickness of the magnetic layer. The incorporation of the composites into biopolymer hydrogels containing cells results in magnetic field-responsive engineered tissues whose mechanical properties can be controlled by external magnetic forces. Indeed, we obtain a significant increase of the viscoelastic moduli of the engineered tissues when exposed to an external magnetic field. Because the composites are functionalized with polyethylene glycol, the prepared bio-artificial tissue-like constructs also display excellent ex vivo cell viability and proliferation. When implanted in vivo, the engineered tissues show good biocompatibility and outstanding interaction with the host tissue. Actually, they only cause a localized transitory inflammatory reaction at the implantation site, without any effect on other organs. Altogether, our results suggest that the inclusion of magnetic core-shell nanocomposites into biomaterials would enable tissue engineering of artificial substitutes whose mechanical properties could be tuned to match those of the potential target tissue. In a wider perspective, the good biocompatibility and magnetic behavior of the composites could be beneficial for many other applications. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00224b

Alveolar ridge augmentation by connective tissue grafting using a pouch method and modified connective tissue technique: A prospective study.

PubMed

Agarwal, Ashish; Gupta, Narinder Dev

2015-01-01

Localized alveolar ridge defect may create physiological and pathological problems. Developments in surgical techniques have made it simpler to change the configuration of a ridge to create a more aesthetic and more easily cleansable shape. The purpose of this study was to compare the efficacy of alveolar ridge augmentation using a subepithelial connective tissue graft in pouch and modified connective tissue graft technique. In this randomized, double blind, parallel and prospective study, 40 non-smoker individuals with 40 class III alveolar ridge defects in maxillary anterior were randomly divided in two groups. Group I received modified connective tissue graft, while group II were treated with subepithelial connective tissue graft in pouch technique. The defect size was measured in its horizontal and vertical dimension by utilizing a periodontal probe in a stone cast at base line, after 3 months, and 6 months post surgically. Analysis of variance and Bonferroni post-hoc test were used for statistical analysis. A two-tailed P < 0.05 was considered to be statistically significant. Mean values in horizontal width after 6 months were 4.70 ± 0.87 mm, and 4.05 ± 0.89 mm for group I and II, respectively. Regarding vertical heights, obtained mean values were 4.75 ± 0.97 mm and 3.70 ± 0.92 mm for group I and group II, respectively. Within the limitations of this study, connective tissue graft proposed significantly more improvement as compare to connective tissue graft in pouch.

Theory of Force Regulation by Nascent Adhesion Sites

PubMed Central

Bruinsma, Robijn

2005-01-01

The mechanical coupling of a cell with the extracellular matrix relies on adhesion sites, clusters of membrane-associated proteins that communicate forces generated along the F-Actin filaments of the cytoskeleton to connecting tissue. Nascent adhesion sites have been shown to regulate these forces in response to tissue rigidity. Force-regulation by substrate rigidity of adhesion sites with fixed area is not possible for stationary adhesion sites, according to elasticity theory. A simple model is presented to describe force regulation by dynamical adhesion sites. PMID:15849245

The Rationale for Joint Mobilization.

ERIC Educational Resources Information Center

Burkhardt, Sandy

This paper presents an overview of the functions of connective tissue and the mechanisms of joint injury and contracture formation in relation to therapeutic exercise. The components of connective tissue operation are explained, including fibroblasts, macrophages, plasma cells, and collagen. An examination of the histology of connective tissue as…

Visible hyperspectral imaging evaluating the cutaneous response to ultraviolet radiation

NASA Astrophysics Data System (ADS)

Ilias, Michail A.; Häggblad, Erik; Anderson, Chris; Salerud, E. Göran

2007-02-01

In vivo diagnostics of skin diseases as well as understanding of the skin biology constitute a field demanding characterization of physiological and anatomical parameters. Biomedical optics has been successfully used, to qualitatively and quantitatively estimate the microcirculatory conditions of superficial skin. Capillaroscopy, laser Doppler techniques and spectroscopy, all elucidate different aspects of microcirculation, e.g. capillary anatomy and distribution, tissue perfusion and hemoglobin oxygenation. We demonstrate the use of a diffuse reflectance hyperspectral imaging system for spatial and temporal characterization of tissue oxygenation, important to skin viability. The system comprises: light source, liquid crystal tunable filter, camera objective, CCD camera, and the decomposition of the spectral signature into relative amounts of oxy- and deoxygenized hemoglobin as well as melanin in every pixel resulting in tissue chromophore images. To validate the system, we used a phototesting model, creating a graded inflammatory response of a known geometry, in order to evaluate the ability to register spatially resolved reflectance spectra. The obtained results demonstrate the possibility to describe the UV inflammatory response by calculating the change in tissue oxygen level, intimately connected to a tissue's metabolism. Preliminary results on the estimation of melanin content are also presented.

Histopathologic criteria to confirm white-nose syndrome in bats

USGS Publications Warehouse

Meteyer, Carol U.; Buckles, Elizabeth L.; Blehert, David S.; Hicks, Alan C.; Green, David E.; Shearn-Bochsler, Valerie I.; Thomas, Nancy J.; Gargas, Andrea; Behr, Melissa

2009-01-01

White-nose syndrome (WNS) is a cutaneous fungal disease of hibernating bats associated with a novel Geomyces sp. fungus. Currently, confirmation of WNS requires histopathologic examination. Invasion of living tissue distinguishes this fungal infection from those caused by conventional transmissible dermatophytes. Although fungal hyphae penetrate the connective tissue of glabrous skin and muzzle, there is typically no cellular inflammatory response in hibernating bats. Preferred tissue samples to diagnose this fungal infection are rostral muzzle with nose and wing membrane fixed in 10% neutral buffered formalin. To optimize detection, the muzzle is trimmed longitudinally, the wing membrane is rolled, and multiple cross-sections are embedded to increase the surface area examined. Periodic acid-Schiff stain is essential to discriminate the nonpigmented fungal hyphae and conidia. Fungal hyphae form cup-like epidermal erosions and ulcers in the wing membrane and pinna with involvement of underlying connective tissue. In addition, fungal hyphae are present in hair follicles and in sebaceous and apocrine glands of the muzzle with invasion of tissue surrounding adnexa. Fungal hyphae in tissues are branching and septate, but the diameter and shape of the hyphae may vary from parallel walls measuring 2 ??m in diameter to irregular walls measuring 3-5 ??m in diameter. When present on short aerial hyphae, curved conidia are approximately 2.5 ??m wide and 7.5 ??m in curved length. Conidia have a more deeply basophilic center, and one or both ends are usually blunt. Although WNS is a disease of hibernating bats, severe wing damage due to fungal hyphae may be seen in bats that have recently emerged from hibernation. These recently emerged bats also have a robust suppurative inflammatory response.

Histopathologic criteria to confirm white-nose syndrome in bats.

PubMed

Meteyer, Carol Uphoff; Buckles, Elizabeth L; Blehert, David S; Hicks, Alan C; Green, D Earl; Shearn-Bochsler, Valerie; Thomas, Nancy J; Gargas, Andrea; Behr, Melissa J

2009-07-01

White-nose syndrome (WNS) is a cutaneous fungal disease of hibernating bats associated with a novel Geomyces sp. fungus. Currently, confirmation of WNS requires histopathologic examination. Invasion of living tissue distinguishes this fungal infection from those caused by conventional transmissible dermatophytes. Although fungal hyphae penetrate the connective tissue of glabrous skin and muzzle, there is typically no cellular inflammatory response in hibernating bats. Preferred tissue samples to diagnose this fungal infection are rostral muzzle with nose and wing membrane fixed in 10% neutral buffered formalin. To optimize detection, the muzzle is trimmed longitudinally, the wing membrane is rolled, and multiple cross-sections are embedded to increase the surface area examined. Periodic acid-Schiff stain is essential to discriminate the nonpigmented fungal hyphae and conidia. Fungal hyphae form cup-like epidermal erosions and ulcers in the wing membrane and pinna with involvement of underlying connective tissue. In addition, fungal hyphae are present in hair follicles and in sebaceous and apocrine glands of the muzzle with invasion of tissue surrounding adnexa. Fungal hyphae in tissues are branching and septate, but the diameter and shape of the hyphae may vary from parallel walls measuring 2 microm in diameter to irregular walls measuring 3-5 microm in diameter. When present on short aerial hyphae, curved conidia are approximately 2.5 microm wide and 7.5 microm in curved length. Conidia have a more deeply basophilic center, and one or both ends are usually blunt. Although WNS is a disease of hibernating bats, severe wing damage due to fungal hyphae may be seen in bats that have recently emerged from hibernation. These recently emerged bats also have a robust suppurative inflammatory response.

Measurement of the Mechanical Properties of Intact Collagen Fibrils

NASA Astrophysics Data System (ADS)

Mercedes, H.; Heim, A.; Matthews, W. G.; Koob, T.

2006-03-01

Motivated by the genetic disorder Ehlers-Danlos syndrome (EDS), in which proper collagen synthesis is interrupted, we are investigating the structural and mechanical properties of collagen fibrils. The fibrous glycoprotein collagen is the most abundant protein found in the human body and plays a key role in the extracellular matrix of the connective tissue, the properties of which are altered in EDS. We have selected as our model system the collagen fibrils of the sea cucumber dermis, a naturally mutable tissue. This system allows us to work with native fibrils which have their proteoglycan complement intact, something that is not possible with reconstituted mammalian collagen fibrils. Using atomic force microscopy, we measure, as a function of the concentration of divalent cations, the fibril diameter, its response to force loading, and the changes in its rigidity. Through these experiments, we will shed light on the mechanisms which control the properties of the sea cucumber dermis and hope to help explain the altered connective tissue extracellular matrix properties associated with EDS.

Imaging of connective tissue diseases of the head and neck

PubMed Central

2016-01-01

We review the imaging appearance of connective tissue diseases of the head and neck. Bilateral sialadenitis and dacryoadenitis are seen in Sjögren’s syndrome; ankylosis of the temporo-mandibular joint with sclerosis of the crico-arytenoid joint are reported in rheumatoid arthritis and lupus panniculitis with atypical infection are reported in patients with systemic lupus erythematosus. Relapsing polychondritis shows subglottic stenosis, prominent ear and saddle nose; progressive systemic sclerosis shows osteolysis of the mandible, fibrosis of the masseter muscle with calcinosis of the subcutaneous tissue and dermatomyositis/polymyositis shows condylar erosions and autoimmune thyroiditis. Vascular thrombosis is reported in antiphospholipid antibodies syndrome; cervical lymphadenopathy is seen in adult-onset Still’s disease, and neuropathy with thyroiditis reported in mixed connective tissue disorder. Imaging is important to detect associated malignancy with connective tissue disorders. Correlation of the imaging findings with demographic data and clinical findings are important for the diagnosis of connective tissue disorders. PMID:26988082

Cerebriform connective tissue nevus of lumbar.

PubMed

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

2015-02-01

Connective tissue nevi represents a kind of hamartoma, and coalescence of the lesions in a cerebriform mode in the lumbar region without Proteus syndrome is rarely seen. Here, we report a 26-year-old woman presenting with nodules and plaques in her left lumbar region of 26 years in duration. Histopathological examination and Masson-trichrome stain showed increased dermal collagen bundles in a haphazard array. The diagnosis of connective tissue nevi was made. This is the first case report on cerebriform connective tissue nevi without Proteus syndrome in the lumbar region. © 2014 Japanese Dermatological Association.

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

PubMed

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

2017-02-01

An organized layer of connective tissue coursing from aorta to esophagus was recently discovered in the mediastinum. The relations with other peri-esophageal fascias have not been described and it is unclear whether this layer can be visualized by non-invasive imaging. This study aimed to provide a comprehensive description of the peri-esophageal fascias and determine whether the connective tissue layer between aorta and esophagus can be visualized by magnetic resonance imaging (MRI). First, T2-weighted MRI scanning of the thoracic region of a human cadaver was performed, followed by histological examination of transverse sections of the peri-esophageal tissue between the thyroid gland and the diaphragm. Secondly, pretreatment motion-triggered MRI scans were prospectively obtained from 34 patients with esophageal cancer and independently assessed by two radiologists for the presence and location of the connective tissue layer coursing from aorta to esophagus. A layer of connective tissue coursing from the anterior aspect of the descending aorta to the left lateral aspect of the esophagus, with a thin extension coursing to the right pleural reflection, was visualized ex vivo in the cadaver on MR images, macroscopic tissue sections, and after histologic staining, as well as on in vivo MR images. The layer connecting esophagus and aorta was named 'aorto-esophageal ligament' and the layer connecting aorta to the right pleural reflection 'aorto-pleural ligament'. These connective tissue layers divides the posterior mediastinum in an anterior compartment containing the esophagus, (carinal) lymph nodes and vagus nerve, and a posterior compartment, containing the azygos vein, thoracic duct and occasionally lymph nodes. The anterior compartment was named 'peri-esophageal compartment' and the posterior compartment 'para-aortic compartment'. The connective tissue layers superior to the aortic arch and at the diaphragm corresponded with the currently available anatomic descriptions. This study confirms the existence of the previously described connective tissue layer coursing from aorta to esophagus, challenging the long-standing paradigm that no such structure exists. A comprehensive, detailed description of the peri-esophageal fascias is provided and, furthermore, it is shown that the connective tissue layer coursing from aorta to esophagus can be visualized in vivo by MRI. © 2016 Anatomical Society.

Echinococcus granulosus equinus: an ultrastructural study of murine tissue response to hydatid cysts.

PubMed

Richards, K S; Arme, C; Bridges, J F

1983-06-01

Peritoneal hydatids of Echinococcus granulosus equinus of 9 months standing in BALB/c mice occurred as free cysts or cysts within cyst masses. Both showed wide variation in size and in host tissue response, and all had a well-developed laminated layer separating the host tissue response from the germinal layer. In the smallest cyst-mass cysts the host tissue response was present as remnants of the initial cellular attack involving eosinophils. Slightly larger cyst-mass cysts possessed a primary macrophage invasion which phagocytosed the remnants of the initial attack and also, though to little effect, the laminated layer material. In the largest cyst-mass cysts a second macrophage invasion, of monocyte origin, had commenced and transformation stages of these cells to macrophages were observed. No fibroblasts surrounded individual cyst-mass cysts but they were present around the cyst mass, encapsulating it and possibly preventing further host cell invasion. Thus, the host tissue response around individual cyst-mass cysts remained 'preserved' at an early stage such as existed at the time of encapsulation. Small free cysts showed a primary macrophage invasion and transformation stages of cells of a secondary infiltration of peritoneal origin. Peripheral to the macrophages were fibroblasts demonstrating limited fibrinogenesis, and each cyst was surrounded by a layer of mesothelial cells. Large free cysts, also delimited by a mesothelial layer, possessed peripheral connective tissue, a deep fibrous layer and a monolayer of very compressed macrophages lying adjacent to the laminated layer. It is emphasized that an understanding of the host tissue response in cysts of different sizes and from different locations is an essential pre-requisite for the design of experimental studies.

Association between antinuclear antibody titers and connective tissue diseases in a Rheumatology Department.

PubMed

Menor Almagro, Raúl; Rodríguez Gutiérrez, Juan Francisco; Martín-Martínez, María Auxiliadora; Rodríguez Valls, María José; Aranda Valera, Concepción; de la Iglesia Salgado, José Luís

To determine the dilution titles at antinuclear antibodies (ANA) by indirect immunofluorescence observed in cell substrate HEp-2 and its association with the diagnosis of systemic connective tissue disease in ANA test requested by a Rheumatology Unit. Samples of patients attended for the first time in the rheumatology unit, without prior ANA test, between January 2010 and December 2012 were selected. The dilution titers, immunofluorescence patterns and antigen specificity were recorded. In January 2015 the diagnosis of the patients were evaluated and classified in systemic disease connective tissue (systemic lupus erythematosus, Sjögren's syndrome, systemic sclerosis, undifferentiated connective, antiphospholipid syndrome, mixed connective tissue and inflammatory myophaty) or not systemic disease connective tissue. A total of 1282 ANA tests requested by the Rheumatology Unit in subjects without previous study, 293 were positive, predominance of women (81.9%). Patients with systemic connective tissue disease were recorded 105, and 188 without systemic connective tissue disease. For 1/640 dilutions the positive predictive value in the connective was 73.3% compared to 26.6% of non-connective, and for values ≥1/1,280 85% versus 15% respectively. When performing the multivariate analysis we observed a positive association between 1/320 dilution OR 3.069 (95% CI: 1.237-7.614; P=.016), 1/640 OR 12.570 (95% CI: 3.659-43.187; P=.000) and ≥1/1,280 OR 42.136 (95% CI: 8.604-206.345; P=.000). These results show association titles dilution ≥1/320 in ANA's first test requested by a Rheumatology Unit with patients with systemic connective tissue disease. The VPP in these patients was higher than previous studies requested by other medical specialties. This may indicate the importance of application of the test in a targeted way. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

In vitro and in vivo assessment of oral autologous artificial connective tissue characteristics that influence its performance as a graft.

PubMed

Fontanilla, Marta Raquel; Espinosa, Lady Giovanna

2012-09-01

Several studies have evaluated proteins secreted by fibroblasts comprising skin substitutes, finding that they are secreted in combinations and concentrations that promote wound healing. However, assessment of proteins secreted by oral fibroblasts forming a part of oral substitutes is scarce. In our previous work, collagen type-I scaffolds (CSs) and autologous artificial connective tissue (AACT) were produced and implanted in rabbit oral lesions, evidencing that AACT outperforms CS. The present work determined the secreted factor profile of AACT in the time of grafting as well as that of the AACT embedded in the clot. It also evaluated the proliferation and viability of AACT fibroblasts to establish the dwell time of these cells in the grafted area. Finally, it assessed whether CS, AACT, and clot-embedded AACT increase fibroblast recruitment induced by a fibrin clot, because the cell migratory response has been associated with the wound-healing outcome. We found that some of the factors secreted by AACT fibroblasts are significantly different from those secreted by clot-embedded AACT fibroblasts. Also, that the profile of proteins secreted by AACT fibroblasts and clot-embedded AACT fibroblasts is different from already reported protein secretion profiles of other engineered tissues used in treating oral mucosa wounds. It was also found that AACT fibroblasts are viable when grafted and remain in the treated area for almost 2 weeks, and that the migratory response of fibroblasts to tissue-substitute stimulus is significantly less than the migratory response induced by the clot alone. Overall, data suggest that AACT secretion of proteins is modulated by three-dimensionality and environment factors. This bioactivity and the fact that AACT does not increase fibroblast migration can be held accountable for AACT's good performance as a graft.

Polymer fiber-based models of connective tissue repair and healing.

PubMed

Lee, Nancy M; Erisken, Cevat; Iskratsch, Thomas; Sheetz, Michael; Levine, William N; Lu, Helen H

2017-01-01

Physiologically relevant models of wound healing are essential for understanding the biology of connective tissue repair and healing. They can also be used to identify key cellular processes and matrix characteristics critical for the design of soft tissue grafts. Modeling the various stages of repair post tendon injury, polymer meshes of varying fiber diameter (nano-1 (390 nm) < nano-2 (740 nm) < micro (1420 nm)) were produced. Alignment was also introduced in the nano-2 group to model matrix undergoing biological healing rather than scar formation. The response of human tendon fibroblasts on these model substrates were evaluated over time as a function of fiber diameter and alignment. It was observed that the repair models of unaligned nanoscale fibers enhanced cell growth and collagen synthesis, while these outcomes were significantly reduced in the mature repair model consisting of unaligned micron-sized fibers. Organization of paxillin and actin on unaligned meshes was enhanced on micro- compared to nano-sized fibers, while the expression and activity of RhoA and Rac1 were greater on nanofibers. In contrast, aligned nanofibers promoted early cell organization, while reducing excessive cell growth and collagen production in the long term. These results show that the early-stage repair model of unaligned nanoscale fibers elicits a response characteristic of the proliferative phase of wound repair, while the more mature model consisting of unaligned micron-sized fibers is more representative of the remodeling phase by supporting cell organization while suppressing growth and biosynthesis. Interestingly, introduction of fiber alignment in the nanofiber model alters fibroblast response from repair to healing, implicating matrix alignment as a critical design factor for circumventing scar formation and promoting biological healing of soft tissue injuries. Copyright © 2016 Elsevier Ltd. All rights reserved.

Alveolar ridge augmentation by connective tissue grafting using a pouch method and modified connective tissue technique: A prospective study

PubMed Central

Agarwal, Ashish; Gupta, Narinder Dev

2015-01-01

Background: Localized alveolar ridge defect may create physiological and pathological problems. Developments in surgical techniques have made it simpler to change the configuration of a ridge to create a more aesthetic and more easily cleansable shape. The purpose of this study was to compare the efficacy of alveolar ridge augmentation using a subepithelial connective tissue graft in pouch and modified connective tissue graft technique. Materials and Methods: In this randomized, double blind, parallel and prospective study, 40 non-smoker individuals with 40 class III alveolar ridge defects in maxillary anterior were randomly divided in two groups. Group I received modified connective tissue graft, while group II were treated with subepithelial connective tissue graft in pouch technique. The defect size was measured in its horizontal and vertical dimension by utilizing a periodontal probe in a stone cast at base line, after 3 months, and 6 months post surgically. Analysis of variance and Bonferroni post-hoc test were used for statistical analysis. A two-tailed P < 0.05 was considered to be statistically significant. Results: Mean values in horizontal width after 6 months were 4.70 ± 0.87 mm, and 4.05 ± 0.89 mm for group I and II, respectively. Regarding vertical heights, obtained mean values were 4.75 ± 0.97 mm and 3.70 ± 0.92 mm for group I and group II, respectively. Conclusion: Within the limitations of this study, connective tissue graft proposed significantly more improvement as compare to connective tissue graft in pouch. PMID:26759591

[Nailfold capillaroscopy in the evaluation of Raynaud's phenomenon and undifferentiated connective tissue disease].

PubMed

Cortes, Sara; Clemente-Coelho, Paulo

2008-01-01

Microvascular abnormalities involved in the pathogenic mechanism of several connective tissue disorders can be detected by nailfold capillaroscopy. Evaluation of the interest of nailfold capillaroscopy results in patients with Raynaud s phenomenon or undifferentiated connective tissue disease and their correlation with diagnostic and therapeutical evolution. Selection of capillaroscopic and laboratory results of patients with the diagnosis of Raynaud s phenomenon (without defined connective tissue disease) or undifferentiated connective tissue disease. Evaluation of the present diagnosis and treatment comparing with the ones existed at the time of capillaroscopy performance. 80 patients were enrolled with an age of 51.4+/-14.3 years (mean+/-SD) 78 females (97.5%) with Raynaud s phenomenon and undifferentiated connective tissue disease 27 patients (33.8%); Raynaud s Phenomenon 46 patients (57.5%); undifferentiated connective tissue disease 7 patients (8.7%). The capillaroscopic results were normal 30 patients (37.5%); minor changes tortuosity enlargement 16 patients (20.0%) major changes 34 patients (42.5%) hemorrhages 25 patients (31.3%) megacapillaries 26 patients (32.5%) avascular areas 3 patients (3.8%). The introduction of new treatments after the capillaroscopy occurred in 32 patients (40.0%) and a new diagnosis was done in 39 patients (48.8%). Major changes in capillaroscopy correlated with the change of diagnosis and the introduction of a new treatment (p<0.0001). Nailfold capillaroscopy performed in patients with isolated Raynaud s phenomenon or undifferentiated connective tissue disease has a role in the prognostic evaluation related to the possibility of an evolution of the diagnosis or to the need of the introduction of new treatments.

Differential effect of subcutaneous abdominal and visceral adipose tissue on cardiometabolic risk.

PubMed

Sam, Susan

2018-03-09

Metabolic and cardiovascular diseases are increasing worldwide due to the rise in the obesity epidemic. The metabolic consequences of obesity vary by distribution of adipose tissue. Visceral and ectopic adipose accumulation are associated with adverse cardiometabolic consequences, while gluteal-femoral adipose accumulation are negatively associated with these adverse complications and subcutaneous abdominal adipose accumulation is more neutral in its associations. Gender, race and ethnic differences in adipose tissue distribution have been described and could account for the observed differences in risk for cardiometabolic disease. The mechanisms behind the differential impact of adipose tissue on cardiometabolic risk have started to be unraveled and include differences in adipocyte biology, inflammatory profile, connection to systemic circulation and most importantly the inability of the subcutaneous adipose tissue to expand in response to positive energy balance.

Connective tissue cells expressing fibro/adipogenic progenitor markers increase under chronic damage: relevance in fibroblast-myofibroblast differentiation and skeletal muscle fibrosis.

PubMed

Contreras, Osvaldo; Rebolledo, Daniela L; Oyarzún, Juan Esteban; Olguín, Hugo C; Brandan, Enrique

2016-06-01

Fibrosis occurs in skeletal muscle under various pathophysiological conditions such as Duchenne muscular dystrophy (DMD), a devastating disease characterized by fiber degeneration that results in progressive loss of muscle mass, weakness and increased extracellular matrix (ECM) accumulation. Fibrosis is also observed after skeletal muscle denervation and repeated cycles of damage followed by regeneration. The ECM is synthesized largely by fibroblasts in the muscle connective tissue under normal conditions. Myofibroblasts, cells that express α-smooth muscle actin (α-SMA), play a role in many tissues affected by fibrosis. In skeletal muscle, fibro/adipogenic progenitors (FAPs) that express cell-surface platelet-derived growth factor receptor-α (PDGFR-α) and the transcription factor Tcf4 seem to be responsible for connective tissue synthesis and are good candidates for the origin of myofibroblasts. We show that cells positive for Tcf4 and PDGFR-α are expressed in skeletal muscle under normal conditions and are increased in various skeletal muscles of mdx mice, a murine model for DMD, wild type muscle after sciatic denervation and muscle subjected to chronic damage. These cells co-label with the myofibroblast marker α-SMA in dystrophic muscle but not in normal tissue. The Tcf4-positive cells lie near macrophages mainly concentrated in dystrophic necrotic-regenerating foci. The close proximity of Tcf4-positive cells to inflammatory cells and their previously described role in muscle regeneration might reflect an active interaction between these cell types and growth factors, possibly resulting in a muscular regenerative or fibrotic condition.

Oral mucosa tissue response to titanium cover screws.

PubMed

Olmedo, Daniel G; Paparella, María L; Spielberg, Martín; Brandizzi, Daniel; Guglielmotti, María B; Cabrini, Rómulo L

2012-08-01

Titanium is the most widely used metal in dental implantology. The release of particles from metal structures into the biologic milieu may be the result of electrochemical processes (corrosion) and/or mechanical disruption during insertion, abutment connection, or removal of failing implants. The aim of the present study is to evaluate tissue response of human oral mucosa adjacent to titanium cover screws. One hundred fifty-three biopsies of the supra-implant oral mucosa adjacent to the cover screw of submerged dental implants were analyzed. Histologic studies were performed to analyze epithelial and connective tissue as well as the presence of metal particles, which were identified using microchemical analysis. Langerhans cells, macrophages, and T lymphocytes were studied using immunohistochemical techniques. The surface of the cover screws was evaluated by scanning electron microscopy (SEM). Forty-one percent of mucosa biopsies exhibited metal particles in different layers of the section thickness. Particle number and size varied greatly among specimens. Immunohistochemical study confirmed the presence of macrophages and T lymphocytes associated with the metal particles. Microchemical analysis revealed the presence of titanium in the particles. On SEM analysis, the surface of the screws exhibited depressions and irregularities. The biologic effects seen in the mucosa in contact with the cover screws might be associated with the presence of titanium or other elements, such as aluminum or vanadium. The potential long-term biologic effects of particles on soft tissues adjacent to metallic devices should be further investigated because these effects might affect the clinical outcome of the implant.

Neurovascular manifestations of connective-tissue diseases: A review

PubMed Central

Kim, Sarasa T; Lanzino, Giuseppe; Kallmes, David F

2016-01-01

Patients with connective tissue diseases are thought to be at a higher risk for a number of cerebrovascular diseases such as intracranial aneurysms, dissections, and acute ischemic strokes. In this report, we aim to understand the prevalence and occurrences of such neurovascular manifestations in four heritable connective tissue disorders: Marfan syndrome, Ehlers-Danlos syndrome, Neurofibromatosis Type 1, and Loeys-Dietz syndrome. We discuss the fact that although there are various case studies reporting neurovascular findings in these connective tissue diseases, there is a general lack of case-control and prospective studies investigating the true prevalence of these findings in these patient populations. Furthermore, the differences observed in the manifestations and histology of such disease pathologies encourages future multi-center registries and studies in better characterizing the pathophysiology, prevalence, and ideal treatment options of neurovascular lesions in patents with connective tissue diseases. PMID:27511817

Comparative anatomy of the dorsal hump in mature Pacific salmon.

PubMed

Susuki, Kenta; Ban, Masatoshi; Ichimura, Masaki; Kudo, Hideaki

2017-07-01

Mature male Pacific salmon (Genus Oncorhynchus) demonstrate prominent morphological changes, such as the development of a dorsal hump. The degree of dorsal hump formation depends on the species in Pacific salmon. It is generally accepted that mature males of sockeye (O. nerka) and pink (O. gorbuscha) salmon develop most pronounced dorsal humps. The internal structure of the dorsal hump in pink salmon has been confirmed in detail. In this study, the dorsal hump morphologies were analyzed in four Pacific salmon species inhabiting Japan, masu (O. masou), sockeye, chum (O. keta), and pink salmon. The internal structure of the dorsal humps also depended on the species; sockeye and pink salmon showed conspicuous development of connective tissue and growth of bone tissues in the dorsal tissues. Masu and chum salmon exhibited less-pronounced increases in connective tissues and bone growth. Hyaluronic acid was clearly detected in dorsal hump connective tissue by histochemistry, except for in masu salmon. The lipid content in dorsal hump connective tissue was richer in masu and chum salmon than in sockeye and pink salmon. These results revealed that the patterns of dorsal hump formation differed among species, and especially sockeye and pink salmon develop pronounced dorsal humps through both increases in the amount of connective tissue and the growth of bone tissues. In contrast, masu and chum salmon develop their dorsal humps by the growth of bone tissues, rather than the development of connective tissue. © 2017 Wiley Periodicals, Inc.

An Investigation of Voice Quality in Individuals with Inherited Elastin Gene Abnormalities

ERIC Educational Resources Information Center

Watts, Christopher R.; Awan, Shaheen N.; Marler, Jeffrey A.

2008-01-01

The human elastin gene (ELN) is responsible for the generation of elastic fibres in the extracellular matrix of connective tissue throughout the body, including the vocal folds. Individuals with Supravalvular aortic stenosis (SVAS) and Williams syndrome (WS) lack one normal ELN allele due to heterozygous ELN abnormalities, resulting in a…

Orthostatic intolerance and chronic fatigue syndrome associated with Ehlers-Danlos syndrome.

PubMed

Rowe, P C; Barron, D F; Calkins, H; Maumenee, I H; Tong, P Y; Geraghty, M T

1999-10-01

To report chronic fatigue syndrome (CFS) associated with both Ehlers-Danlos syndrome (EDS) and orthostatic intolerance. Case series of adolescents referred to a tertiary clinic for the evaluation of CFS. All subjects had 2-dimensional echocardiography, tests of orthostatic tolerance, and examinations by both a geneticist and an ophthalmologist. Twelve patients (11 female), median age 15.5 years, met diagnostic criteria for CFS and EDS, and all had either postural tachycardia or neurally mediated hypotension in response to orthostatic stress. Six had classical-type EDS and 6 had hypermobile-type EDS. Among patients with CFS and orthostatic intolerance, a subset also has EDS. We propose that the occurrence of these syndromes together can be attributed to the abnormal connective tissue in dependent blood vessels of those with EDS, which permits veins to distend excessively in response to ordinary hydrostatic pressures. This in turn leads to increased venous pooling and its hemodynamic and symptomatic consequences. These observations suggest that a careful search for hypermobility and connective tissue abnormalities should be part of the evaluation of patients with CFS and orthostatic intolerance syndromes.

Cone-Beam Computed Tomography Evaluation of Horizontal and Vertical Dimensional Changes in Buccal Peri-Implant Alveolar Bone and Soft Tissue: A 1-Year Prospective Clinical Study.

PubMed

Kaminaka, Akihiro; Nakano, Tamaki; Ono, Shinji; Kato, Tokinori; Yatani, Hirofumi

2015-10-01

This study evaluated changes in the horizontal and vertical dimensions of the buccal alveolar bone and soft tissue over a 1-year period following implant prosthesis. Thirty-three participants with no history of guided bone regeneration or soft tissue augmentation underwent dental implant placement with different types of connections. The dimensions of the buccal alveolar bone and soft tissue were evaluated immediately and at 1 year after prosthesis from reconstructions of cross-sectional cone-beam computed tomography images. The vertical and horizontal loss of buccal bone and soft tissue around implants with conical connections were lower than around those with external or internal connections. Statistically significant negative correlations were observed between initial horizontal bone thickness and changes in vertical bone and soft tissue height (p < .05), and between initial horizontal soft tissue thickness and the change in vertical soft tissue height (p < .05). Implants with a conical connection preserve peri-implant alveolar bone and soft tissue more effectively than other connection types. Furthermore, the initial buccal alveolar bone and soft tissue thickness around the implant platform may influence their vertical dimensional changes at 1 year after implant prosthesis. © 2014 Wiley Periodicals, Inc.

Asymmetric stem-cell divisions define the architecture of human oesophageal epithelium.

PubMed

Seery, J P; Watt, F M

2000-11-16

In spite of its clinical importance, little is known about the stem-cell compartment of the human oesophageal epithelium [1,2]. The epithelial basal layer consists of two distinct zones, one overlying the papillae of the supporting connective tissue (PBL) and the other covering the interpapillary zone (IBL) [3]. In examining the oesophageal basal layer, we found that proliferating cells were rare in the IBL and a high proportion of mitoses were asymmetrical, giving rise to one basal daughter and one suprabasal, differentiating daughter. In the PBL, mitoses were more frequent and predominantly symmetrical. The IBL was characterised by low expression of ?1 integrins and high expression of the beta2 laminin chain. By combining fluorescence-activated cell sorting (FACS) with in vitro clonal analysis, we obtained evidence that the IBL is enriched for stem cells. A normal oesophageal epithelium with asymmetric divisions was reconstituted on denuded oesophageal connective tissue. In contrast, asymmetric divisions were not sustained on skin connective tissue, and the epithelium formed resembled epidermis. We propose that stem cells located in the IBL give rise to differentiating daughters through asymmetric divisions in response to cues from the underlying basement membrane. Until now, stem-cell fate in stratified squamous epithelia was believed to be achieved largely through populational asymmetry [4-6].

Organism-Level Analysis of Vaccination Reveals Networks of Protection across Tissues.

PubMed

Kadoki, Motohiko; Patil, Ashwini; Thaiss, Cornelius C; Brooks, Donald J; Pandey, Surya; Deep, Deeksha; Alvarez, David; von Andrian, Ulrich H; Wagers, Amy J; Nakai, Kenta; Mikkelsen, Tarjei S; Soumillon, Magali; Chevrier, Nicolas

2017-10-05

A fundamental challenge in immunology is to decipher the principles governing immune responses at the whole-organism scale. Here, using a comparative infection model, we observe immune signal propagation within and between organs to obtain a dynamic map of immune processes at the organism level. We uncover two inter-organ mechanisms of protective immunity mediated by soluble and cellular factors. First, analyzing ligand-receptor connectivity across tissues reveals that type I IFNs trigger a whole-body antiviral state, protecting the host within hours after skin vaccination. Second, combining parabiosis, single-cell analyses, and gene knockouts, we uncover a multi-organ web of tissue-resident memory T cells that functionally adapt to their environment to stop viral spread across the organism. These results have implications for manipulating tissue-resident memory T cells through vaccination and open up new lines of inquiry for the analysis of immune responses at the organism level. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

Love, Ryan J; Jones, Kim S

2013-12-01

Connective tissue rapidly proliferates on and around biomaterials implanted in vivo, which impairs the function of the engineered tissues, biosensors, and devices. Glucocorticoids can be utilized to suppress tissue ingrowth, but can only be used for a limited time because they nonselectively arrest cell proliferation in the local environment. The present study examined use of a prolyl-4-hydroxylase inhibitor, 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (1,4-DPCA), to suppress connective tissue ingrowth in porous PLGA discs implanted in the peritoneal cavity for 28 days. The prolyl-4-hydroxylase inhibitor was found to be effective at inhibiting collagen deposition within and on the outer surface of the disc, and also limited connective tissue ingrowth, but not to the extent of glucocorticoid inhibition. Finally, it was discovered that 1,4-DPCA suppressed Scavenger Receptor A expression on a macrophage-like cell culture, which may account for the drug's ability to limit connective tissue ingrowth in vivo. Copyright © 2013 Wiley Periodicals, Inc., a Wiley Company.

Immediate placement and provisionalization of maxillary anterior single implant with guided bone regeneration, connective tissue graft, and coronally positioned flap procedures.

PubMed

Waki, Tomonori; Kan, Joseph Y K

2016-01-01

Immediate implant placement and provisionalization in the esthetic zone have been documented with success. The benefit of immediate implant placement and provisionalization is the preservation of papillary mucosa. However, in cases with osseous defects presenting on the facial bony plate, immediate implant placement procedures have resulted in facial gingival recession. Subepithelial connective tissue grafts for immediate implant placement and provisionalization procedures have been reported with a good esthetic outcome. Biotype conversion around implants with subepithelial connective tissue grafts have been advocated, and the resulting tissues appear to be more resistant to recession. The dimensions of peri-implant mucosa in a thick biotype were significantly greater than in a thin biotype. Connective tissue graft with coronally positioned flap procedures on natural teeth has also been documented with success. This article describes a technique combining immediate implant placement, provisionalization, guided bone regeneration (GBR), connective tissue graft, and a coronally positioned flap in order to achieve more stable peri-implant tissue in facial osseous defect situations.

Spatiotemporal Evolution of the Wound Repairing Process in a 3D Human Dermis Equivalent.

PubMed

Lombardi, Bernadette; Casale, Costantino; Imparato, Giorgia; Urciuolo, Francesco; Netti, Paolo Antonio

2017-07-01

Several skin equivalent models have been developed to investigate in vitro the re-epithelialization process occurring during wound healing. Although these models recapitulate closure dynamics of epithelial cells, they fail to capture how a wounded connective tissue rebuilds its 3D architecture until the evolution in a scar. Here, the in vitro tissue repair dynamics of a connective tissue is replicated by using a 3D human dermis equivalent (3D-HDE) model composed of fibroblasts embedded in their own extracellular matrix (ECM). After inducing a physical damage, 3D-HDE undergoes a series of cellular and extracellular events quite similar to those occurring in the native dermis. In particular, fibroblasts differentiation toward myofibroblasts phenotype and neosynthesis of hyaluronic acid, fibronectin, and collagen during the repair process are assessed. Moreover, tissue reorganization after physical damage is investigated by measuring the diameter of bundles and the orientation of fibers of the newly formed ECM network. Finally, the ultimate formation of a scar-like tissue as physiological consequence of the repair and closure process is demonstrated. Taking together, the results highlight that the presence of cell-assembled and responsive stromal components enables quantitative and qualitative in vitro evaluation of the processes involved in scarring during wound healing. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identifying the architecture of a supracellular actomyosin network that induces tissue folding

NASA Astrophysics Data System (ADS)

Yevick, Hannah; Stoop, Norbert; Dunkel, Jorn; Martin, Adam

During embryonic development, the establishment of correct tissue form ensures proper tissue function. Yet, how the thousands of cells within a tissue coordinate force production to sculpt tissue shape is poorly understood. One important tissue shape change is tissue folding where a cell sheet bends to form a closed tube. Drosophila (fruit fly) embryos undergo such a folding event, called ventral furrow formation. The ventral furrow is associated with a supracellular network of actin and myosin, where actin-myosin fibers assemble and connect between cells. It is not known how this tissue-wide network grows and connects over time, how reproducible it is between embryos, and what determines its architecture. Here, we used topological feature analysis to quantitatively and dynamically map the connections and architecture of this supracellular network across hundreds of cells in the folding tissue. We identified the importance of the cell unit in setting up the tissue-scale architecture of the network. Our mathematical framework allows us to explore stereotypic properties of the myosin network such that we can investigate the reproducibility of mechanical connections for a morphogenetic process. NIH F32.

Evaluation of In Vivo Wound Healing Activity of Bacopa monniera on Different Wound Model in Rats

PubMed Central

Murthy, S.; Gautam, M. K.; Goel, Shalini; Purohit, V.; Sharma, H.; Goel, R. K.

2013-01-01

Wound healing effects of 50% ethanol extract of dried whole plant of Bacopa monniera (BME) was studied on wound models in rats. BME (25 mg/kg) was administered orally, once daily for 10 days (incision and dead space wound models) or for 21 days or more (excision wound model) in rats. BME was studied for its in vitro antimicrobial and in vivo wound breaking strength, WBS (incision model), rate of contraction, period of epithelization, histology of skin (excision model), granulation tissue free radicals (nitric oxide and lipid peroxidation), antioxidants (catalase, superoxide dismutase, and reduced glutathione), acute inflammatory marker (myeloperoxidase), connective tissue markers (hydroxyproline, hexosamine, and hexuronic acid), and deep connective tissue histology (dead space wound). BME showed antimicrobial activity against skin pathogens, enhanced WBS, rate of contraction, skin collagen tissue formation, and early epithelization period with low scar area indicating enhanced healing. Healing effect was further substantiated by decreased free radicals and myeloperoxidase and enhanced antioxidants and connective tissue markers with histological evidence of more collagen formation in skin and deeper connective tissues. BME decreased myeloperoxidase and free radical generated tissue damage, promoting antioxidant status, faster collagen deposition, other connective tissue constituent formation, and antibacterial activity. PMID:23984424

Evaluation of in vivo wound healing activity of Bacopa monniera on different wound model in rats.

PubMed

Murthy, S; Gautam, M K; Goel, Shalini; Purohit, V; Sharma, H; Goel, R K

2013-01-01

Wound healing effects of 50% ethanol extract of dried whole plant of Bacopa monniera (BME) was studied on wound models in rats. BME (25 mg/kg) was administered orally, once daily for 10 days (incision and dead space wound models) or for 21 days or more (excision wound model) in rats. BME was studied for its in vitro antimicrobial and in vivo wound breaking strength, WBS (incision model), rate of contraction, period of epithelization, histology of skin (excision model), granulation tissue free radicals (nitric oxide and lipid peroxidation), antioxidants (catalase, superoxide dismutase, and reduced glutathione), acute inflammatory marker (myeloperoxidase), connective tissue markers (hydroxyproline, hexosamine, and hexuronic acid), and deep connective tissue histology (dead space wound). BME showed antimicrobial activity against skin pathogens, enhanced WBS, rate of contraction, skin collagen tissue formation, and early epithelization period with low scar area indicating enhanced healing. Healing effect was further substantiated by decreased free radicals and myeloperoxidase and enhanced antioxidants and connective tissue markers with histological evidence of more collagen formation in skin and deeper connective tissues. BME decreased myeloperoxidase and free radical generated tissue damage, promoting antioxidant status, faster collagen deposition, other connective tissue constituent formation, and antibacterial activity.

Immunohistochemical Analysis of Galectins-1, -3, and -7 in Periapical Granulomas, Radicular Cysts, and Residual Radicular Cysts.

PubMed

Brito, Lívia Natália Sales; de Lemos Almeida, Maria Manuela Rodrigues; de Souza, Lélia Batista; Alves, Pollianna Muniz; Nonaka, Cassiano Francisco Weege; Godoy, Gustavo Pina

2018-05-01

Galectins play important roles in immunoinflammatory responses, but their participation in the development of periapical lesions remains unclear. This study aimed to evaluate the expressions of galectins-1, -3, and -7 in periapical lesions, correlating them with the intensity of the inflammatory infiltrate and the pattern of the cystic epithelium. Twenty periapical granulomas (PGs), 20 radicular cysts (RCs), and 20 residual radicular cysts (RRCs) were submitted to immunohistochemistry using anti-galectin-1, -3, and -7 antibodies. The percentage of immunopositive cells in epithelial and connective tissues was determined. In connective tissue, PGs exhibited higher cytoplasmic/membrane expression of galectins-1 and -7 than RCs and RRCs (P < .05). There was higher nuclear expression of galectin-1 in PGs compared with RCs and RRCs (P < .05). The expression of galectins-1 and -7 in connective tissue was higher in lesions with grade III inflammation (P < .05). No significant differences in galectin-3 immunoexpression were observed for any of the parameters evaluated (P > .05). In the epithelial component, a higher nuclear expression of galectin-7 was detected in RRCs (P < .05), and a higher cytoplasmic/membrane expression of this protein was found in cysts with hyperplastic epithelium (P < .05). Positive correlations were observed between the nuclear and cytoplasmic/membrane expression of galectin-1 in connective tissue (P < .05) as well as between the nuclear and cytoplasmic/membrane expression of galectin-7 in epithelial tissue of cysts (P < .05). Galectins-1 and -7 may play important roles in the pathogenesis of PGs, RCs, and RRCs. On the other hand, the present results suggest only a minor involvement of galectin-3 in the development of these lesions. Copyright © 2018 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

[Pathogenesis of skin scleroderma--literature review].

PubMed

Wojas-Pelc, Anna; Lipko-Godlewska, Sylwia

2005-01-01

The pathogenesis of skin scleroderma (LS) is still unknown. Disturbances of vessels system, connective tissue metabolism and humoral and cellular immunological response is observed. Antinuclear antibodies are detected in 30-80% of patients with different types of skin scleroderma. They are present more often in patients with disseminated lesions and linear type of LS compared to morphoea au plaque. In our own analysis 28.5% of patients had also antibodies directed against Borrelia burgdorferi. It is believed that the injury of endothelial cells and proliferation in medial part of small vessels - which both lead to chronic ischemia - are the earliest disturbances observed in histopathological examination of the skin taken from systemic as well as from skin scleroderma patients. During last few years, there were some interesting reports concerning functional changes of endothelial cells which led to disturbances in tension of vessels smooth muscles. Free radicals - in genetically predispose people--can also provoke scleroderma lesions through their injury action on endothelial cells and stimulation of fibroblasts. In morphoea, the process of fibrosis begins around vessels. Deposition of connective tissue matrix is observed, especially collagen type I and III. This stimulation of fibroblasts as well as accumulation of connective tissue matrix are secondary to some stimulatory factors. These are: PDF, bFGF, TGFbeta and some cytokines. In morphoea patients serum levels of IL-1, IL-2, IL-4, IL-6 and IL-8 were elevated. In literature, levels and production of collagenases were decreased, although more authors say that tissue inhibitors of metalloproteinases are the main factor in fibrosis. The analysis of data tends to suspicion that enormous fibrosis observed in different types of scleroderma can be the result of increased production of collagen and other components of connective tissue as well as their incomplete degradation. Presented clinical and laboratory data show how many different factors influence etiopathogenesis of morphoea.

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

PubMed Central

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

2014-01-01

Background and aims. Connective tissue grafts with and without periosteum is used in regenerative treatments of bone and has demonstrated successful outcomes in previous investigations. The aim of present study was to evaluate the effectiveness of connective tissue graft with and without periosteum in regeneration of intrabony defects. Materials and methods. In this single-blind randomized split-mouth clinical trial, 15 pairs of intrabony defects in 15 patients with moderate to advanced periodontitis were treated by periosteal connective tissue graft + ABBM (test group) or non-periosteal connective tissue graft + ABBM (control group). Probing pocket depth, clinical attachment level, free gingival margin position, bone crestal position, crest defect depth and defect depth to stent were measured at baseline and after six months by surgical re-entry. Data was analyzed by Student’s t-test and paired t-tests (α=0.05). Results. Changes in clinical parameters after 6 months in the test and control groups were as follows: mean of PPD reduction: 3.1±0.6 (P<0.0001); 2.5±1.0 mm (P<0.0001), CAL gain: 2.3±0.9 (P<0.0001); 2.2±1.0 mm (P<0.0001), bone fill: 2.2±0.7 mm (P<0.0001); 2.2±0.7 mm (P<0.0001), respectively. No significant differences in the position of free gingival margin were observed during 6 months compared to baseline in both groups. Conclusion. Combinations of periosteal connective tissue graft + ABBM and non-periosteal connective tissue graft + ABBM were similarly effective in treating intrabony defects without any favor for any group. Connective tissue and perio-steum can be equally effective in regeneration of intrabony defects. PMID:25587379

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

PubMed

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

2016-07-01

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

Transforming growth factor-β (TGF-β) expression is increased in the subsynovial connective tissues of patients with idiopathic carpal tunnel syndrome.

PubMed

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

2014-01-01

Non-inflammatory fibrosis of the subsynovial connective tissue (SSCT) is a hallmark of carpal tunnel syndrome (CTS). The etiology of this finding and its relationship to the development of CTS remain poorly understood. Recent studies have found that transforming growth factor-β (TGF-β) plays a central role in fibrosis. The purpose of this study was to investigate the expression of TGF-β and connective tissue growth factor (CTGF), a downstream mediator of TGF-β, in the pathogenesis of CTS. We compared SSCT specimens from 26 idiopathic CTS patients with specimens from 10 human cadaver controls with no previous diagnosis of CTS. Immunohistochemistry was performed to determine levels TGF-β1, CTGF, collagen 1(Col1) and collagen 3 (Col3) expression. TGF-β1 (p < 0.01), CTGF (p < 0.01), and Col3 (p < 0.01) were increased in SSCT of CTS patients compared with control tissue. In addition, a strong positive correlation was found between TGF-β1 and CTGF, (R(2) = 0.80, p < 0.01) and a moderate positive correlation between Col3 and TGF-β1 (R(2) = 0.49, p < 0.01). These finding suggest that there is an increased expression of TGF-β and CTGF, a TGF-β regulated protein, and that this TGF-β activation may be responsible for SSCT fibrosis in CTS patients. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Morphology of the lingual papillae in the fishing cat.

PubMed

Emura, Shoichi; Okumura, Toshihiko; Chen, Huayue

2014-01-01

We examined the dorsal lingual surface of an adult fishing cat (Prionailurus viverrinus) by scanning electron microscopy. The filiform papillae on the lingual apex had several pointed processes. The connective tissue core of the filiform papillae resembleda a well in shape. The filiform papillae on the anterior part of the lingual body were large and cylindrical in shape. The connective tissue core of the filiform papillae consisted of a large conical papilla. The filiform papillae on the central part of the lingual body were large and conical. The connective tissue core of the filiform papillae consisted of a large main process and some secondary processes. The connective tissue core of the fungiform papillae did not have processes. The vallate papillae were surrounded by a groove and a pad. The top of the connective tissue core of the vallate papillae had a rough surface with no spines.

Connective Tissue Disorders and Cardiovascular Complications: The indomitable role of Transforming Growth Factor-beta signaling

PubMed Central

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

2015-01-01

Marfan Syndrome (MFS) and Loeys-Dietz Syndrome (LDS) represent heritable connective tissue disorders that cosegregate with a similar pattern of cardiovascular defects (thoracic aortic aneurysm, mitral valve prolapse/regurgitation, and aortic 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-β) 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-β signaling pathway, heritable connective tissue syndromes related to TGF-β receptor (TGFBR) mutations, and discuss the pathogenic contribution of TGF-β to these syndromes with a primary focus on the cardiovascular system. PMID:24443024

Collagenous Extracellular Matrix Biomaterials for Tissue Engineering: Lessons from the Common Sea Urchin Tissue.

PubMed

Goh, Kheng Lim; Holmes, David F

2017-04-25

Scaffolds for tissue engineering application may be made from a collagenous extracellular matrix (ECM) of connective tissues because the ECM can mimic the functions of the target tissue. The primary sources of collagenous ECM material are calf skin and bone. However, these sources are associated with the risk of having bovine spongiform encephalopathy or transmissible spongiform encephalopathy. Alternative sources for collagenous ECM materials may be derived from livestock, e.g., pigs, and from marine animals, e.g., sea urchins. Collagenous ECM of the sea urchin possesses structural features and mechanical properties that are similar to those of mammalian ones. However, even more intriguing is that some tissues such as the ligamentous catch apparatus can exhibit mutability, namely rapid reversible changes in the tissue mechanical properties. These tissues are known as mutable collagenous tissues (MCTs). The mutability of these tissues has been the subject of on-going investigations, covering the biochemistry, structural biology and mechanical properties of the collagenous components. Recent studies point to a nerve-control system for regulating the ECM macromolecules that are involved in the sliding action of collagen fibrils in the MCT. This review discusses the key attributes of the structure and function of the ECM of the sea urchin ligaments that are related to the fibril-fibril sliding action-the focus is on the respective components within the hierarchical architecture of the tissue. In this context, structure refers to size, shape and separation distance of the ECM components while function is associated with mechanical properties e.g., strength and stiffness. For simplicity, the components that address the different length scale from the largest to the smallest are as follows: collagen fibres, collagen fibrils, interfibrillar matrix and collagen molecules. Application of recent theories of stress transfer and fracture mechanisms in fibre reinforced composites to a wide variety of collagen reinforcing (non-mutable) connective tissue, has allowed us to draw general conclusions concerning the mechanical response of the MCT at specific mechanical states, namely the stiff and complaint states. The intent of this review is to provide the latest insights, as well as identify technical challenges and opportunities, that may be useful for developing methods for effective mechanical support when adapting decellularised connective tissues from the sea urchin for tissue engineering or for the design of a synthetic analogue.

Collagenous Extracellular Matrix Biomaterials for Tissue Engineering: Lessons from the Common Sea Urchin Tissue

PubMed Central

Goh, Kheng Lim; Holmes, David F.

2017-01-01

Scaffolds for tissue engineering application may be made from a collagenous extracellular matrix (ECM) of connective tissues because the ECM can mimic the functions of the target tissue. The primary sources of collagenous ECM material are calf skin and bone. However, these sources are associated with the risk of having bovine spongiform encephalopathy or transmissible spongiform encephalopathy. Alternative sources for collagenous ECM materials may be derived from livestock, e.g., pigs, and from marine animals, e.g., sea urchins. Collagenous ECM of the sea urchin possesses structural features and mechanical properties that are similar to those of mammalian ones. However, even more intriguing is that some tissues such as the ligamentous catch apparatus can exhibit mutability, namely rapid reversible changes in the tissue mechanical properties. These tissues are known as mutable collagenous tissues (MCTs). The mutability of these tissues has been the subject of on-going investigations, covering the biochemistry, structural biology and mechanical properties of the collagenous components. Recent studies point to a nerve-control system for regulating the ECM macromolecules that are involved in the sliding action of collagen fibrils in the MCT. This review discusses the key attributes of the structure and function of the ECM of the sea urchin ligaments that are related to the fibril-fibril sliding action—the focus is on the respective components within the hierarchical architecture of the tissue. In this context, structure refers to size, shape and separation distance of the ECM components while function is associated with mechanical properties e.g., strength and stiffness. For simplicity, the components that address the different length scale from the largest to the smallest are as follows: collagen fibres, collagen fibrils, interfibrillar matrix and collagen molecules. Application of recent theories of stress transfer and fracture mechanisms in fibre reinforced composites to a wide variety of collagen reinforcing (non-mutable) connective tissue, has allowed us to draw general conclusions concerning the mechanical response of the MCT at specific mechanical states, namely the stiff and complaint states. The intent of this review is to provide the latest insights, as well as identify technical challenges and opportunities, that may be useful for developing methods for effective mechanical support when adapting decellularised connective tissues from the sea urchin for tissue engineering or for the design of a synthetic analogue. PMID:28441344

Chronic tissue response to untethered microelectrode implants in the rat brain and spinal cord

NASA Astrophysics Data System (ADS)

Ersen, Ali; Elkabes, Stella; Freedman, David S.; Sahin, Mesut

2015-02-01

Objective. Microelectrodes implanted in the central nervous system (CNS) often fail in long term implants due to the immunological tissue response caused by tethering forces of the connecting wires. In addition to the tethering effect, there is a mechanical stress that occurs at the device-tissue interface simply because the microelectrode is a rigid body floating in soft tissue and it cannot reshape itself to comply with changes in the surrounding tissue. In the current study we evaluated the scar tissue formation to tetherless devices with two significantly different geometries in the rat brain and spinal cord in order to investigate the effects of device geometry. Approach. One of the implant geometries resembled the wireless, floating microstimulators that we are currently developing in our laboratory and the other was a (shank only) Michigan probe for comparison. Both electrodes were implanted into either the cervical spinal cord or the motor cortices, one on each side. Main results. The most pronounced astroglial and microglial reactions occurred within 20 μm from the device and decreased sharply at larger distances. Both cell types displayed the morphology of non-activated cells past the 100 μm perimeter. Even though the aspect ratios of the implants were different, the astroglial and microglial responses to both microelectrode types were very mild in the brain, stronger and yet limited in the spinal cord. Significance. These observations confirm previous reports and further suggest that tethering may be responsible for most of the tissue response in chronic implants and that the electrode size has a smaller contribution with floating electrodes. The electrode size may be playing primarily an amplifying role to the tethering forces in the brain whereas the size itself may induce chronic response in the spinal cord where the movement of surrounding tissues is more significant.

[CLINICAL CHARACTERISTICS OF CONGENITAL HEART DISEASES ASSOCIATED WITH CONNECTIVE TISSUE DISPLASIA AT CHILDREN LIVING IN EAST REGION OF KAZAKHSTAN].

PubMed

Madiyeva, M; Rymbayeva, T

2017-11-01

The frequency of the combination of congenital heart defects (CHD) and connective tissue dysplasia remains poorly understood. And connective tissue dysplasia enhance severity the clinical of CHD. The aim of the study was to conduct a clinical and laboratory analysis of combinations of congenital heart defects and connective tissue dysplasia in children of Semey and to determine the risk for the development of these pathologies. The object of the study is the children of Semey (East Kazakhstan) aged 1-14 with congenital heart defects (CHD), with connective tissue dysplasia, healthy children and their mothers. Definition complex clinical and laboratory studies in children with CHD and connective tissue dysplasia, and their mothers. In children with CHD, the frequency of external and visceral signs of dysplasia was high. In 88.1% of cases in children with CHD was diagnosed 2-3 degrees of dysplasia. Was found difference in the microelement composition of blood serum and of hemostasis in children with CHD were expressed by hypofibrinogenemia, hypocalcemia, hypomagnesemia. Excess of the frequency of signs of dysplasia in mothers over the control group to consider dysplasia as a factor that influences the clinical of CHD.

Connective tissue fibroblasts and Tcf4 regulate myogenesis

PubMed Central

Mathew, Sam J.; Hansen, Jody M.; Merrell, Allyson J.; Murphy, Malea M.; Lawson, Jennifer A.; Hutcheson, David A.; Hansen, Mark S.; Angus-Hill, Melinda; Kardon, Gabrielle

2011-01-01

Muscle and its connective tissue are intimately linked in the embryo and in the adult, suggesting that interactions between these tissues are crucial for their development. However, the study of muscle connective tissue has been hindered by the lack of molecular markers and genetic reagents to label connective tissue fibroblasts. Here, we show that the transcription factor Tcf4 (transcription factor 7-like 2; Tcf7l2) is strongly expressed in connective tissue fibroblasts and that Tcf4GFPCre mice allow genetic manipulation of these fibroblasts. Using this new reagent, we find that connective tissue fibroblasts critically regulate two aspects of myogenesis: muscle fiber type development and maturation. Fibroblasts promote (via Tcf4-dependent signals) slow myogenesis by stimulating the expression of slow myosin heavy chain. Also, fibroblasts promote the switch from fetal to adult muscle by repressing (via Tcf4-dependent signals) the expression of developmental embryonic myosin and promoting (via a Tcf4-independent mechanism) the formation of large multinucleate myofibers. In addition, our analysis of Tcf4 function unexpectedly reveals a novel mechanism of intrinsic regulation of muscle fiber type development. Unlike other intrinsic regulators of fiber type, low levels of Tcf4 in myogenic cells promote both slow and fast myogenesis, thereby promoting overall maturation of muscle fiber type. Thus, we have identified novel extrinsic and intrinsic mechanisms regulating myogenesis. Most significantly, our data demonstrate for the first time that connective tissue is important not only for adult muscle structure and function, but is a vital component of the niche within which muscle progenitors reside and is a critical regulator of myogenesis. PMID:21177349

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

PubMed Central

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

2009-01-01

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

Functional Attachment of Soft Tissues to Bone: Development, Healing, and Tissue Engineering

PubMed Central

Lu, Helen H.; Thomopoulos, Stavros

2014-01-01

Connective tissues such as tendons or ligaments attach to bone across a multitissue interface with spatial gradients in composition, structure, and mechanical properties. These gradients minimize stress concentrations and mediate load transfer between the soft and hard tissues. Given the high incidence of tendon and ligament injuries and the lack of integrative solutions for their repair, interface regeneration remains a significant clinical challenge. This review begins with a description of the developmental processes and the resultant structure-function relationships that translate into the functional grading necessary for stress transfer between soft tissue and bone. It then discusses the interface healing response, with a focus on the influence of mechanical loading and the role of cell-cell interactions. The review continues with a description of current efforts in interface tissue engineering, highlighting key strategies for the regeneration of the soft tissue–to-bone interface, and concludes with a summary of challenges and future directions. PMID:23642244

Information generation and processing systems that regulate periodontal structure and function.

PubMed

Bartold, P Mark; McCulloch, Christopher A

2013-10-01

The periodontium is a very dynamic organ that responds rapidly to mechanical and chemical stimuli. It is very complex in that it is composed of two hard tissues (cementum and bone) and two soft connective tissues (periodontal ligament and gingiva). Together these tissues are defined by the molecules expressed by the resident periodontal cells in each compartment and this determines not only the structure and function of the periodontium but also how it responds to infection and inflammation. The biological activity of these molecules is tightly regulated in time and space to preserve tissue homeostasis, influence inflammatory responses and participate in tissue regeneration. In this issue of Periodontology 2000 we explore new experimental approaches and data sets which help to understand the molecules and cells that regulate tissue form and structure in health, disease and regeneration. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

miR-133b Regulation of Connective Tissue Growth Factor

PubMed Central

Gjymishka, Altin; Pi, Liya; Oh, Seh-Hoon; Jorgensen, Marda; Liu, Chen; Protopapadakis, Yianni; Patel, Ashnee; Petersen, Bryon E.

2017-01-01

miRNAs are involved in liver regeneration, and their expression is dysregulated in hepatocellular carcinoma (HCC). Connective tissue growth factor (CTGF), a direct target of miR-133b, is crucial in the ductular reaction (DR)/oval cell (OC) response for generating new hepatocyte lineages during liver injury in the context of hepatotoxin-inhibited hepatocyte proliferation. Herein, we investigate whether miR-133b regulation of CTGF influences HCC cell proliferation and migration, and DR/OC response. We analyzed miR-133b expression and found it to be down-regulated in HCC patient samples and induced in the rat DR/OC activation model of 2-acetylaminofluorene with partial hepatectomy. Furthermore, overexpression of miR-133b via adenoviral system in vitro led to decreased CTGF expression and reduced proliferation and Transwell migration of both HepG2 HCC cells and WBF-344 rat OCs. In vivo, overexpression of miR-133b in DR/OC activation models of 2-acetylaminofluorene with partial hepatectomy in rats, and 3,5-diethoxycarbonyl-1,4-dihydrocollidine in mice, led to down-regulation of CTGF expression and OC proliferation. Collectively, these results show that miR-133b regulation of CTGF is a novel mechanism critical for the proliferation and migration of HCC cells and OC response. PMID:26945106

Connective Tissue Characteristics around Healing Abutments of Different Geometries: New Methodological Technique under Circularly Polarized Light.

PubMed

Delgado-Ruiz, Rafael Arcesio; Calvo-Guirado, Jose Luis; Abboud, Marcus; Ramirez-Fernandez, Maria Piedad; Maté-Sánchez de Val, José Eduardo; Negri, Bruno; Gomez-Moreno, Gerardo; Markovic, Aleksa

2015-08-01

To describe contact, thickness, density, and orientation of connective tissue fibers around healing abutments of different geometries by means of a new method using coordinates. Following the bilateral extraction of mandibular premolars (P2, P3, and P4) from six fox hound dogs and a 2-month healing period, 36 titanium implants were inserted, onto which two groups of healing abutments of different geometry were screwed: Group A (concave abutments) and Group B (wider healing abutment). After 3 months the animals were sacrificed and samples extracted containing each implant and surrounding soft and hard tissues. Histological analysis was performed without decalcifying the samples by means of circularly polarized light under optical microscope and a system of vertical and horizontal coordinates across all the connective tissue in an area delimited by the implant/abutment, epithelium, and bone tissue. In no case had the connective tissue formed a connection to the healing abutment/implant in the internal zone; a space of 35 ± 10 μm separated the connective tissue fibers from the healing abutment surface. The total thickness of connective tissue in the horizontal direction was significantly greater in the medial zone in Group B than in Group A (p < .05). The orientation of the fibers varied according to the coordinate area so that internal coordinates showed a higher percentage of parallel fibers in Group A (p < .05) and a higher percentage of oblique fibers in Group B (p < .05); medial coordinates showed more oblique fibers (p < .05); and the area of external coordinates showed the highest percentage of perpendicular fibers (p < .05). The fiber density was higher in the basal and medial areas (p < .05). Abutment geometry influences the orientation of collagen fibers; therefore, an abutment with a profile wider than the implant platform favors oblique and perpendicular orientation of collagen fibers and greater connective tissue thickness. © 2013 Wiley Periodicals, Inc.

[50 years of connective tissue research: from the French Connective Tissue Club to the French Society of Extracellular Matrix Biology].

PubMed

Maquart, François-Xavier; Borel, Jacques-Paul

2012-01-01

The history of connective tissue research began in the late 18th century. However, it is only 50 years later that the concept of connective tissue was shaped. It took another fifty years before biochemical knowledge of extracellular matrix macromolecules began to emerge in the first half of the 20th century. In 1962, thanks to Ladislas and Barbara Robert, back from the US, the first society called "French Connective Tissue Club" was created in Paris. The first board was constituted of Albert Delaunay, Suzanne Bazin and Ladislas Robert. Very quickly, under the influence of these pioneers, national and international meetings were organized and, in 1967, a "Federation of the European Connective Tissue Clubs" was created at the initiative of Ladislas Robert (Paris) and John Scott (Manchester). It spread rapidly to the major European nations. In 1982 the transformation of "Clubs" in "Societies" occurred, a name more in line with the requirements of the time. In 2008, the "French Connective Tissue Society" became the "French Society of Extracellular Matrix Biology" ("Société Française de Biologie de la Matrice Extracellulaire", SFBMEc), to better highlight the importance of the extracellular matrix in the biology of living organisms. The SFBMEc's mission today is to promote and develop scientific exchanges between academic, industrial, and hospital laboratories involved in research on the extracellular matrix. SFBMEc organizes or subsidizes scientific meetings and awards scholarships to Ph.D. students or post-docs to participate in international conferences. It includes 200 to 250 members from different disciplines, developing strong interactions between scientists, clinicians and pathologists. It is present all around the French territory in many research laboratories. During these last 50 years, the extraordinary advances made possible by the development of new investigation techniques, in particular molecular biology, cell and tissue imaging, molecular modeling, etc., have permitted a considerable increase of the knowledge in the field of connective tissue. © Société de Biologie, 2012.

Emergent cell and tissue dynamics from subcellular modeling of active biomechanical processes

NASA Astrophysics Data System (ADS)

Sandersius, S. A.; Weijer, C. J.; Newman, T. J.

2011-08-01

Cells and the tissues they form are not passive material bodies. Cells change their behavior in response to external biochemical and biomechanical cues. Behavioral changes, such as morphological deformation, proliferation and migration, are striking in many multicellular processes such as morphogenesis, wound healing and cancer progression. Cell-based modeling of these phenomena requires algorithms that can capture active cell behavior and their emergent tissue-level phenotypes. In this paper, we report on extensions of the subcellular element model to model active biomechanical subcellular processes. These processes lead to emergent cell and tissue level phenotypes at larger scales, including (i) adaptive shape deformations in cells responding to slow stretching, (ii) viscous flow of embryonic tissues, and (iii) streaming patterns of chemotactic cells in epithelial-like sheets. In each case, we connect our simulation results to recent experiments.

Gene expression profile of the fibrotic response in the peritoneal cavity.

PubMed

Le, S J; Gongora, M; Zhang, B; Grimmond, S; Campbell, G R; Campbell, J H; Rolfe, B E

2010-01-01

The cellular response to materials implanted in the peritoneal cavity has been utilised to produce tissue for grafting to hollow smooth muscle organs (blood vessels, bladder, uterus and vas deferens). To gain insight into the regulatory mechanisms involved in encapsulation of a foreign object, and subsequent differentiation of encapsulating cells, the present study used microarray technology and real-time RT-PCR to identify the temporal changes in gene expression associated with tissue development. Immunohistochemical analysis showed that 3-7 days post-implantation of foreign objects (cubes of boiled egg white) into rats, they were encapsulated by tissue comprised primarily of haemopoietic (CD45(+)) cells, mainly macrophages (CD68(+), CCR1(+)). By day 14, tissue capsule cells no longer expressed CD68, but were positive for myofibroblast markers alpha-smooth muscle (SM) actin and SM22. In accordance with these results, gene expression data showed that early capsule (days 3-7) development was dominated by the expression of monocyte/macrophage-specific genes (CD14, CSF-1, CSF-1R, MCP-1) and pro-inflammatory mediators such as transforming growth factor (TGF-beta). As tissue capsule development progressed (days 14-21), myofibroblast-associated and pro-fibrotic genes (associated with TGF-beta and Wnt/beta-catenin signalling pathways, including Wnt 4, TGFbetaRII, connective tissue growth factor (CTGF), SMADs-1, -2, -4 and collagen-1 subunits) were significantly up-regulated. The up-regulation of genes associated with Cardiovascular and Skeletal and Muscular System Development at later time-points suggests the capacity of cells within the tissue capsule for further differentiation to smooth muscle, and possibly other cell types. The identification of key regulatory pathways and molecules associated with the fibrotic response to implanted materials has important applications not only for optimising tissue engineering strategies, but also to control deleterious fibrotic responses.

STRETCHING IMPACTS INFLAMMATION RESOLUTION IN CONNECTIVE TISSUE

PubMed Central

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

2016-01-01

Acute inflammation is accompanied from its outset by the release of specialized pro-resolving mediators (SPMs), including resolvins, that orchestrate the resolution of local inflammation. We showed earlier that, in rats with subcutaneous inflammation of the back induced by carrageenan, stretching for 10 minutes twice daily reduced inflammation and improved pain, two weeks after carrageenan injection. In this study, we hypothesized that stretching of connective tissue activates local pro-resolving mechanisms within the tissue in the acute phase of inflammation. In rats injected with carrageenan and randomized to stretch vs. no stretch for 48 hours, stretching reduced inflammatory lesion thickness and neutrophil count, and increased resolvin (RvD1) concentrations within lesions. Furthermore, subcutaneous resolvin injection mimicked the effect of stretching. In ex vivo experiments, stretching of connective tissue reduced the migration of neutrophils and increased tissue RvD1 concentration. These results demonstrate a direct mechanical impact of stretching on inflammation-regulation mechanisms within connective tissue. PMID:26588184

Impact of Oral Commensal Bacteria on Degradation of Periodontal Connective Tissue in Mice.

PubMed

Irie, Koichiro; Tomofuji, Takaaki; Ekuni, Daisuke; Morita, Manabu; Shimazaki, Yoshihiro; Darveau, Richard P

2015-07-01

Innate and adaptive immunosurveillance mechanisms in response to the normal commensal bacteria can affect periodontal innate defense status. However, it is still unclear how commensal bacteria contribute to the inflammatory responses of junctional epithelium (JE) and periodontal connective tissue (PCT). The aim of the present study is to investigate the contribution of commensal bacteria on inflammatory responses in JE and PCT in mice. The periodontal tissue of germ-free (GF) and specific-pathogen-free (SPF) mice were compared at age 11 to 12 weeks (n = 6 per group). In this study, the number of neutrophils and expression of intercellular adhesion molecule (ICAM)-1, fibroblast growth factor receptor (FGFR)-1, matrix metalloproteinase (MMP)-1, and MMP-8 within the JE and the PCT are evaluated. The collagen density was also determined in PCT stained with picrosirius red (PSR). PSR staining combined with or without polarized light microscopy has been used to assess the organization and maturation of collagen matrix. In the present findings, the area of JE in SPF mice was significantly greater than that in GF mice (P <0.05). In addition, the JE and PCT in SPF mice showed greater migration of neutrophils and higher expression of ICAM-1, FGFR-1, MMP-1, and MMP-8 than those in GF mice (P <0.05). Furthermore, the density of collagen in PCT in SPF mice was lower compared to GF mice (P <0.05). These results indicate that commensal bacteria induced a low-grade inflammatory state in JE and that such conditions may contribute to degradation of collagen in PCT in mice.

Quantitative morphology in canine cutaneous soft tissue sarcomas.

PubMed

Simeonov, R; Ananiev, J; Gulubova, M

2015-12-01

Stained cytological specimens from 24 dogs with spontaneous soft tissue sarcomas [fibrosarcoma (n = 8), liposarcoma (n = 8) and haemangiopericytoma (n = 8)], and 24 dogs with reactive connective tissue lesions [granulation tissue (n = 12) and dermal fibrosis (n = 12)] were analysed by computer-assisted nuclear morphometry. The studied morphometric parameters were: mean nuclear area (MNA; µm(2)), mean nuclear perimeter (MNP; µm), mean nuclear diameter (MND mean; µm), minimum nuclear diameter (Dmin; µm) and maximum nuclear diameter (Dmax; µm). The study aimed to evaluate (1) possibility for quantitative differentiation of soft tissue sarcomas from reactive connective tissue lesions and (2) by using cytomorphometry, to differentiate the various histopathological soft tissue sarcomas subtypes in dogs. The mean values of all nuclear cytomorphometric parameters (except for Dmax) were statistically significantly higher in reactive connective tissue processes than in soft tissue sarcomas. At the same time, however, there were no considerable differences among the different sarcoma subtypes. The results demonstrated that the quantitative differentiation of reactive connective tissue processes from soft tissue sarcomas in dogs is possible, but the same was not true for the different canine soft tissue sarcoma subtypes. Further investigations on this topic are necessary for thorough explication of the role of quantitative morphology in the diagnostics of mesenchymal neoplasms and tumour-like fibrous lesions in dogs. © 2014 John Wiley & Sons Ltd.

Vascular Ehlers-Danlos Syndrome Presenting as a Pulsatile Neck Mass: a Case Report and Review of Literature.

PubMed

Maraj, Bharat; Harding-Theobald, Emily; Karaki, Fatima

2018-04-26

Ehlers-Danlos syndrome refers to a spectrum of connective tissue disorders typically caused by mutations in genes responsible for the synthesis of collagen. Patients with Ehlers-Danlos syndrome often exhibit hyperflexibility of joints, increased skin elasticity, and tissue fragility. Vascular Ehlers-Danlos (vEDS) is a subtype of Ehlers-Danlos syndrome with a predilection to involve blood vessels. As such, it often manifests as vascular aneurysms and vessel rupture leading to hemorrhage. There are few reports describing primary prevention of aneurysms in the setting of undiagnosed, suspected vEDS. We present a case of a 30-year-old woman who presents with a pulsatile neck mass found to have multiple arterial aneurysms on imaging, hyperflexibility, and characteristic facial features consistent with vEDS. As described in this case, management of a suspected connective tissue disorder is a multidisciplinary approach including vascular surgery, medical therapy, and genetic testing to confirm the diagnosis. We review literature regarding the care of patients with vascular Ehlers-Danlos as it might pertain to hospitalized patients.

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

PubMed

Hanser, Thomas; Khoury, Fouad

2016-01-01

This study evaluated volume stability after alveolar ridge contouring with free connective tissue grafts at implant placement in single-tooth gaps. A total of 52 single-tooth gaps with labial volume deficiencies in the maxilla (incisors, canines, and premolars) were consecutively treated with implants and concomitant free palatal connective tissue grafts in 46 patients between 2006 and 2009. Implants had to be covered with at least 2 mm peri-implant local bone after insertion. At implant placement, a free connective tissue graft from the palate was fixed inside a labial split-thickness flap to form an existing concave buccal alveolar ridge contour due to tissue volume deficiency into a convex shape. Standardized volumetric measurements of the labial alveolar contour using a template were evaluated before connective tissue grafting and at 2 weeks, 1 year, and 5 years after implantprosthetic incorporation. Tissue volume had increased significantly (P < .05) in all six reference points representing the outer alveolar soft tissue contour of the implant before connective tissue grafting to baseline (2 weeks after implant-prosthetic incorporation). Statistically, 50% of the reference points (P > .05) kept their volume from baseline to 1 year after prosthetic incorporation and from baseline to 5 years after prosthetic incorporation, respectively, whereas reference points located within the area of the implant sulcus showed a significant (P < .05) decrease in volume. Clinically, 5 years after prosthetic incorporation the originally concave buccal alveolar contour was still convex in all implants, leading to a continuous favorable anatomical shape and improved esthetic situation. Intraoral radiographs confirmed osseointegration and stable peri-implant parameters with a survival rate of 100% after a follow-up of approximately 5 years. Implant placement with concomitant free connective tissue grafting appears to be an appropriate long-term means to contour preexisting buccal alveolar volume deficiencies in single implants.

Expression of connective tissue growth factor is a prognostic marker for patients with intrahepatic cholangiocarcinoma.

PubMed

Gardini, A; Corti, B; Fiorentino, M; Altimari, A; Ercolani, G; Grazi, G L; Pinna, A D; Grigioni, W F; D'Errico Grigioni, A

2005-04-01

Connective tissue growth factor is a member of the 'CCN' protein family. Consistent with its profibrotic properties, it is over-expressed in several human epithelial malignancies. We have retrospectively evaluated by immunohistochemistry the presence of connective tissue growth factor in archival tissues from 55 resected intrahepatic cholangiocarcinomas and compared its expression to the main pathological parameters, disease free and overall survival. Tumours were scored as high and low/absent expressers (> or =50%, 0-50% cells, respectively). Thirty-three of 55 cholangiocarcinomas (60%) were high and 22 (40%) low expressers. No significant correlation was found between connective tissue growth factor and tumour grade, tumour location, vascular and perineural invasion. Eighteen of 22 (82%) low/absent expressers and 12/33 (36%) high expressers had recurrence of disease (P=0.001). Low/absent expressers showed a poor disease free and overall survival compared with the higher expressers (P<0.001). Vascular invasion was related to tumour recurrence (P=0.025) and to decreased disease free survival (P<0.05). During proportional hazard regression analysis, only connective tissue growth factor was found to influence disease free survival (P=0.01). Expression of connective tissue growth factor is an independent prognostic indicator of both tumour recurrence and overall survival for intrahepatic cholangiocarcinoma patients regardless of tumour location, tumour grade, vascular and perineural invasion.

Elastic Response of Crimped Collagen Fibrils

NASA Technical Reports Server (NTRS)

Freed, Alan D.; Doehring, Todd C.

2005-01-01

A physiologic constitutive expression is presented in algorithmic format for the elastic response of wavy collagen fibrils found in soft connective tissues. The model is based on the observation that crimped fibrils have a three-dimensional structure at the micrometer scale that we approximate as a helical spring. The symmetry of this waveform allows the force/displacement relationship derived from Castigliano's theorem to be solved in closed form. Model predictions are in good agreement with experimental observations for mitral-valve chordae tendineae

[The gastrointestinal tract microbiom in connective tissue diseases].

PubMed

Krajewska-Włodarczyk, Magdalena

Factors such as genetics, the environment, infections, and the human body microbiota, mainly gastrointestinal tract microbiota may play a role in the pathogenesis of autoimmune disorders. There is an increasing evidence that suggest an association between gastrointestinal tract dysbiosis, and in particular gut dysbiosis, and connective tissue diseases but it still remains unclear whether alterations in the microbiome are a pathogenic cause or an effect of autoimmune disease. Given the strong variability and abundance of microbes living in close relation with human host, it becomes a difficult task to define what should be considered the normal or the favorable microbiome. Further studies are needed to establish how the human microbiome contributes to disease susceptibility, and to characterize the role of microbial diversity in the pathogenesis of connective tissue diseases and their clinical manifestations. The identification of dysbiosis specific for certain connective tissue diseases may help in the development of an individualized management for each patient. This review aims to summarize current data on the role of the gastrointestinal tract microbiome in connective tissue diseases.

A theoretical approach of the relationships between collagen content, collagen cross-links and meat tenderness.

PubMed

Lepetit, J

2007-05-01

This work concerns the relationship between meat tenderness and the rubber-like properties, i.e. pressure and elastic modulus, that endomysium and perimysium connective tissues develop when meat has been heated to a temperature above which collagen contracts. For rest length meats with similar intramuscular connective tissue morphology, and which are at the same ageing state and pH, the elastic modulus of the collagenous fraction of connective tissues is approximately proportional to the total number of collagen cross-links present per volume of meat. Calculations from various published experiments concerned with the effect on tenderness of muscle type, animal age, type, and sex from different species show that this modulus follows most of the variations of meat toughness. Moreover, the proportionality between the increase in this elastic modulus and the increase in meat toughness approaches unity in situations where toughness mainly depends on connective tissues. This work demonstrates the decisive role of rubber-like properties of connective tissues in meat tenderness variations.

The Architecture of the Connective Tissue in the Musculoskeletal System—An Often Overlooked Functional Parameter as to Proprioception in the Locomotor Apparatus

PubMed Central

van der Wal, Jaap

2009-01-01

The architecture of the connective tissue, including structures such as fasciae, sheaths, and membranes, is more important for understanding functional meaning than is more traditional anatomy, whose anatomical dissection method neglects and denies the continuity of the connective tissue as integrating matrix of the body. The connective tissue anatomy and architecture exhibits two functional tendencies that are present in all areas of the body in different ways and relationships. In body cavities, the “disconnecting” quality of shaping space enables mobility; between organs and body parts, the “connecting” dimension enables functional mechanical interactions. In the musculoskeletal system, those two features of the connective tissue are also present. They cannot be found by the usual analytic dissection procedures. An architectural description is necessary. This article uses such a methodologic approach and gives such a description for the lateral elbow region. The result is an alternative architectural view of the anatomic substrate involved in the transmission and conveyance of forces over synovial joints. An architectural description of the muscular and connective tissue organized in series with each other to enable the transmission of forces over these dynamic entities is more appropriate than is the classical concept of “passive” force-guiding structures such as ligaments organized in parallel to actively force-transmitting structures such as muscles with tendons. The discrimination between so-called joint receptors and muscle receptors is an artificial distinction when function is considered. Mechanoreceptors, also the so-called muscle receptors, are arranged in the context of force circumstances—that is, of the architecture of muscle and connective tissue rather than of the classical anatomic structures such as muscle, capsules, and ligaments. In the lateral cubital region of the rat, a spectrum of mechanosensitive substrate occurs at the transitional areas between regular dense connective tissue layers and the muscle fascicles organized in series with them. This substrate exhibits features of type and location of the mechanosensitive nerve terminals that usually are considered characteristic for “joint receptors” as well as for “muscle receptors.” The receptors for proprioception are concentrated in those areas where tensile stresses are conveyed over the elbow joint. Structures cannot be divided into either joint receptors or muscle receptors when muscular and collagenous connective tissue structures function in series to maintain joint integrity and stability. In vivo, those connective tissue structures are strained during movements of the skeletal parts, those movements in turn being induced and led by tension in muscular tissue. In principle, because of the architecture, receptors can also be stimulated by changes in muscle tension without skeletal movement, or by skeletal movement without change in muscle tension. A mutual relationship exists between structure (and function) of the mechanoreceptors and the architecture of the muscular and regular dense connective tissue. Both are instrumental in the coding of proprioceptive information to the central nervous system. PMID:21589740

Understanding the effect of pulsed electric fields on thermostability of connective tissue isolated from beef pectoralis muscle using a model system.

PubMed

Alahakoon, A U; Oey, I; Silcock, P; Bremer, P

2017-10-01

Brisket is a low value/tough meat cut that contains a large amount of connective tissue. Conversion of collagen into gelatin during heating reduces the toughness of the connective tissue however this conversion is slow at low cooking temperatures (around 60°C). The objective of this project was to determine the ability of pulsed electric field (PEF) processing to reduce the thermal stability of connective tissue. To achieve this, a novel model system was designed in which connective tissue obtained from beef deep pectotalis muscle (brisket) was exposed to PEF at combinations of electric field strength (1.0 and 1.5kV/cm) and specific energy (50 and 100kJ/kg) within an agar matrix at electrical conductivities representing the electrical conductivity found in brisket. Differential scanning calorimetry showed that PEF treatment significantly (p<0.05) decreased the denaturation temperature of connective tissue compared to untreated samples. Increasing electric field strength and the specific energy increased the Ringer soluble collagen fraction. PEF treated samples showed higher solubilization compared to the untreated samples at both 60°C and 70°C in heat solubility test. SEM examination of PEF treated (at 1.5kV/cm and 100kJ/kg) and untreated samples revealed that PEF appeared to increase the porosity of the connective tissue structure. These finding suggest that PEF processing is a technology that could be used to improve the tenderness and decrease the cooking time of collagen rich, meat cuts. Copyright © 2017 Elsevier Ltd. All rights reserved.

The serum levels of connective tissue growth factor in patients with systemic lupus erythematosus and lupus nephritis.

PubMed

Wang, F-M; Yu, F; Tan, Y; Liu, G; Zhao, M-H

2014-06-01

The expression of connective tissue growth factor mRNA in human kidneys may serve as an early marker for lupus nephritis progression. Therefore, we speculated that connective tissue growth factor may be involved in the pathogenesis of systemic lupus erythematosus and lupus nephritis. In this study, we set out to investigate the associations between serum connective tissue growth factor levels and clinicopathological features of patients with systemic lupus erythematosus and lupus nephritis. Serum samples from patients with non-renal systemic lupus erythematosus, renal biopsy-proven lupus nephritis and healthy control subjects were detected by enzyme-linked immunosorbent assay for serum connective tissue growth factor levels. The associations between connective tissue growth factor levels and clinicopathological features of the patients were further analysed. The levels of serum connective tissue growth factor in patients with non-renal systemic lupus erythematosus and lupus nephritis were both significantly higher than those in the normal control group (34.14 ± 12.17 ng/ml vs. 22.8 ± 3.0 ng/ml, p<0.001; 44.1 ± 46.8 ng/ml vs. 22.8 ± 3.0 ng/ml, p = 0.035, respectively). There was no significant difference of the serum connective tissue growth factor levels between non-renal systemic lupus erythematosus and lupus nephritis group (34.14 ± 12.17 ng/ml vs. 44.1 ± 46.8 ng/ml, p = 0.183). Serum connective tissue growth factor levels were significantly higher in lupus nephritis patients with the following clinical manifestations, including anaemia (51.3 ± 51.4 ng/ml vs. 23.4 ± 9.7 ng/ml, p<0.001) and acute renal failure (85.5 ± 75.0 ng/ml vs. 31.2 ± 21.8 ng/ml, p = 0.002). Serum connective tissue growth factor levels in class IV were significantly higher than that in class II, III and V (57.6 ± 57.5 ng/ml vs. 18.7 ± 6.4 ng/ml, p = 0.019; 57.6 ± 57.5 ng/ml vs. 25.2 ± 14.9 ng/ml, p = 0.006; 57.6 ± 57.5 ng/ml vs. 30.5 ± 21.3 ng/ml, p = 0.017, respectively). Serum connective tissue growth factor levels were significantly higher in those with both active/chronic lesions than those in those with active lesions only in either class IV (84.9 ± 69.6 ng/ml vs. 40.0 ± 40.2 ng/ml, p = 0.001) or in combination of class III and IV lupus nephritis (63.3 ± 63.4 ng/ml vs. 38.3 ± 37.9 ng/ml, p = 0.035, respectively). Serum connective tissue growth factor levels were negatively associated with estimated glomerular filtration rate (r = -0.46, p<0.001) and positively associated with interstitial inflammation (r = 0.309, p = 0.002) and interstitial fibrosis (r = 0.287, p = 0.004). Serum connective tissue growth factor level was a risk factor for doubling of serum creatinine in lupus nephritis (p<0.001, hazard ratio = 1.015, 95% confidence intervals 1.008-1.022) in univariate analysis. Serum connective tissue growth factor levels were significantly higher in lupus and correlated with chronic renal interstitial injury and doubling of serum creatinine in patients with lupus nephritis. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Applications and Emerging Trends of Hyaluronic Acid in Tissue Engineering, as a Dermal Filler, and in Osteoarthritis Treatment

PubMed Central

Fakhari, Amir; Berkland, Cory

2013-01-01

Hyaluronic acid (HA) is a naturally occurring biodegradable polymer with a variety of applications in medicine including scaffolding for tissue engineering, dermatological fillers, and viscosupplementation for osteoarthritis treatment. HA is available in most connective tissues in body fluids such as synovial fluid and the vitreous humor of the eye. HA is responsible for several structural properties of tissues as a component of extracellular matrix (ECM) and is involved in cellular signaling. Degradation of HA is a step-wise process that can occur via enzymatic or non-enzymatic reactions. A reduction in HA mass or molecular weight via degradation or slowing of synthesis affects physical and chemical properties such as tissue volume, viscosity, and elasticity. This review addresses the distribution, turnover, and tissue-specific properties of HA. This information is used as context for considering recent products and strategies for modifying the viscoelastic properties of HA in tissue engineering, as a dermal filler, and in osteoarthritis treatment. PMID:23507088

Gingival Fibroblasts Display Reduced Adhesion and Spreading on Extracellular Matrix: A Possible Basis for Scarless Tissue Repair?

PubMed Central

Guo, Fen; Carter, David E.; Mukhopadhyay, Anuradha; Leask, Andrew

2011-01-01

Unlike skin, oral gingiva do not scar in response to injury. The basis of this difference is likely to be revealed by comparing the responses of dermal and gingival fibroblasts to fibrogenic stimuli. Previously, we showed that, compared to dermal fibroblasts, gingival fibroblasts are less responsive to the potent pro-fibrotic cytokine TGFβ, due to a reduced production of endothelin-1 (ET-1). In this report, we show that, compared to dermal fibroblasts, human gingival fibroblasts show reduced expression of pro-adhesive mRNAs and proteins including integrins α2 and α4 and focal adhesion kinase (FAK). Consistent with these observations, gingival fibroblasts are less able to adhere to and spread on both fibronectin and type I collagen. Moreover, the enhanced production of ET-1 mRNA and protein in dermal fibroblasts is reduced by the FAK/src inhibitor PP2. Given our previous observations suggesting that fibrotic fibroblasts display elevated adhesive properties, our data suggest that scarring potential may be based, at least in part, on differences in adhesive properties among fibroblasts resident in connective tissue. Controlling adhesive properties may be of benefit in controlling scarring in response to tissue injury. PMID:22073262

Pathways connecting telomeres and p53 in senescence, apoptosis, and cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Artandi, Steven E.; Attardi, Laura D.

2005-06-10

The ends of eukaryotic chromosomes are protected by specialized structures termed telomeres that serve in part to prevent the chromosome end from activating a DNA damage response. However, this important function for telomeres in chromosome end protection can be lost as telomeres shorten with cell division in culture or in self-renewing tissues with advancing age. Impaired telomere function leads to induction of a DNA damage response and activation of the tumor suppressor protein p53. p53 serves a critical role in enforcing both senescence and apoptotic responses to dysfunctional telomeres. Loss of p53 creates a permissive environment in which critically shortmore » telomeres are inappropriately joined to generate chromosomal end-to-end fusions. These fused chromosomes result in cycles of chromosome fusion-bridge-breakage, which can fuel cancer initiation, especially in epithelial tissues, by facilitating changes in gene copy number.« less

Optic Nerve Head Biomechanics in Aging and Disease

PubMed Central

Downs, J. Crawford

2015-01-01

This nontechnical review is focused upon educating the reader on optic nerve head biomechanics in both aging and disease along two main themes: what is known about how mechanical forces and the resulting deformations are distributed in the posterior pole and ONH (biomechanics) and what is known about how the living system responds to those deformations (mechanobiology). We focus on how ONH responds to IOP elevations as a structural system, insofar as the acute mechanical response of the lamina cribrosa is confounded with the responses of the peripapillary sclera, prelaminar neural tissues, and retrolaminar optic nerve. We discuss the biomechanical basis for IOP-driven changes in connective tissues, blood flow, and cellular responses. We use glaucoma as the primary framework to present the important aspects of ONH biomechanics in aging and disease, as ONH biomechanics, aging, and the posterior pole extracellular matrix (ECM) are thought to be centrally involved in glaucoma susceptibility, onset and progression. PMID:25819451

Polypropylene Surgical Mesh Coated with Extracellular Matrix Mitigates the Host Foreign Body Response

PubMed Central

Wolf, Matthew T.; Carruthers, Christopher A.; Dearth, Christopher L.; Crapo, Peter M.; Huber, Alexander; Burnsed, Olivia A.; Londono, Ricardo; Johnson, Scott A.; Daly, Kerry A.; Stahl, Elizabeth C.; Freund, John M.; Medberry, Christopher J.; Carey, Lisa E.; Nieponice, Alejandro; Amoroso, Nicholas J.; Badylak, Stephen F.

2013-01-01

Surgical mesh devices composed of synthetic materials are commonly used for ventral hernia repair. These materials provide robust mechanical strength and are quickly incorporated into host tissue; factors which contribute to reduced hernia recurrence rates. However, such mesh devices cause a foreign body response with the associated complications of fibrosis and patient discomfort. In contrast, surgical mesh devices composed of naturally occurring extracellular matrix (ECM) are associated with constructive tissue remodeling, but lack the mechanical strength of synthetic materials. A method for applying a porcine dermal ECM hydrogel coating to a polypropylene mesh is described herein with the associated effects upon the host tissue response and biaxial mechanical behavior. Uncoated and ECM coated heavy-weight BARD™ Mesh were compared to the light-weight ULTRAPRO™ and BARD™ Soft Mesh devices in a rat partial thickness abdominal defect overlay model. The ECM coated mesh attenuated the pro-inflammatory response compared to all other devices, with a reduced cell accumulation and fewer foreign body giant cells. The ECM coating degraded by 35 days, and was replaced with loose connective tissue compared to the dense collagenous tissue associated with the uncoated polypropylene mesh device. Biaxial mechanical characterization showed that all of the mesh devices were of similar isotropic stiffness. Upon explantation, the light-weight mesh devices were more compliant than the coated or uncoated heavy-weight devices. The present study shows that an ECM coating alters the default host response to a polypropylene mesh, but not the mechanical properties in an acute in vivo abdominal repair model. PMID:23873846

Human Periodontal Cells Demonstrate Osteoblast-Like and Fibroblast-Like Characteristics in Tissue Culture

DTIC Science & Technology

1989-05-05

gingiva and periodontal ligament emphasizes similarities between the connective tissues of gingiva and periodontal ligament. Possible regeneration of...Clinicians and researchers gradually realized the importance of periodontal ligament granulation tissue in periodontal regeneration (Melcher, 1976...isolated osseous defects. The guided tissue regeneration technique uses membrane filters to isolate healing periodontal defects from gingival connective

Increased expression of Interleukin-13 and connective tissue growth factor, and their potential roles during foreign body encapsulation of subcutaneous implants.

PubMed

Ward, W Kenneth; Li, Allen G; Siddiqui, Yasmin; Federiuk, Isaac F; Wang, Xiao-Jing

2008-01-01

The purpose of this study was to better understand whether interleukin-13 (IL-13) and connective tissue growth factor (CTGF) are highly expressed during foreign body encapsulation of subcutaneous devices. Mock biosensors were implanted into rats for three lengths of time (7-, 21- and 48-55 days) to address different stages of the foreign body response. Using quantitative real-time PCR and immunofluorescence, the expression of IL13, CTGF, collagen 1, decorin and fibronectin were measured in this tissue. IL-13, a product of Th2 cells, was highly expressed at all time points, with greatest expression at day 21. The IL-13 expression was paralleled by increased presence of T-cells at all time points. CTGF was also found to be more highly expressed in foreign body tissue than in controls. Collagen and decorin were highly expressed at the middle and later stages. Given the increased expression of IL-13 and CTGF in foreign body tissue, and their roles in other fibrotic disorders, these cytokines may well contribute to the formation of the foreign body capsule. Since the peak gene expression of IL-13 occurred later than the previously-reported TGFbeta expression peak, IL-13 is probably not the major stimulus to TGFbeta expression during foreign body encapsulation and may contribute to fibrosis independently.

Mast cells are present in the choroid of the normal eye in most vertebrate classes.

PubMed

McMenamin, Paul Gerard; Polla, Emily

2013-07-01

Mast cells are bone marrow-derived tissue-homing leukocytes, which have traditionally been regarded as effector cells in allergic disorders, responses against parasites, and regulation of blood flow, but a broader perspective of their functional heterogeneity, such as immunomodulation, angiogenesis, tissue repair, and remodeling after injury, is now emerging. The persistence of mast cells in connective tissues throughout the evolution of vertebrates is evidence of strong selective pressure suggesting that these cells must have multiple beneficial and important roles in normal homeostasis. While mast cells are present within the uveal tract of eutherian mammals, there is little known about their presence in the choroid of other vertebrate classes. Eye tissues from a range of vertebrate species (fish, amphibian, reptiles, birds, marsupials, monotreme, and eutherian mammals) were investigated. Tissues were fixed in either 2% glutaraldehyde, 2% paraformaldehyde or a mixture of both and processed for resin embedding. Semi-thin sections of the retina and choroid were cut and stained with toluidine blue. Mast cells were identified in the choroid of all classes of vertebrates investigated except sharks. Their morphology, location, and staining characteristics were remarkably similar from teleost fish through to eutherian mammals and bore close morphological resemblance to mammalian connective tissue mast cells. The similar morphology and distribution of mast cells in the choroid of all vertebrate classes studied suggest a basic physiological function that has been retained since the evolution of the vertebrate eye. © 2013 American College of Veterinary Ophthalmologists.

An update of neurological manifestations of vasculitides and connective tissue diseases: a literature review

PubMed Central

Bougea, Anastasia; Anagnostou, Evangelos; Spandideas, Nikolaos; Triantafyllou, Nikolaos; Kararizou, Evangelia

2015-01-01

Vasculitides comprise a heterogeneous group of autoimmune disorders, occurring as primary or secondary to a broad variety of systemic infectious, malignant or connective tissue diseases. The latter occur more often but their pathogenic mechanisms have not been fully established. Frequent and varied central and peripheral nervous system complications occur in vasculitides and connective tissue diseases. In many cases, the neurological disorders have an atypical clinical course or even an early onset, and the healthcare professionals should be aware of them. The purpose of this brief review was to give an update of the main neurological disorders of common vasculitis and connective tissue diseases, aiming at accurate diagnosis and management, with an emphasis on pathophysiologic mechanisms. PMID:26313435

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

PubMed Central

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

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-β 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-β signaling pathways. The Slc39a13-KO mouse represents a novel animal model linking zinc metabolism, BMP/TGF-β signaling and connective tissue dysfunction. PMID:18985159

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

PubMed

Sanjana, Faria; Chaudhry, Hans; Findley, Thomas

2017-01-01

Altered connective tissue structure has been identified in adults with chronic low back pain (LBP). A self-care treatment for managing LBP is the MELT method. The MELT method is a hands-off, self-treatment that is said to alleviate chronic pain, release tension and restore mobility, utilizing specialized soft treatments balls, soft body roller and techniques mimicking manual therapy. The objective of this study was to determine whether thickness of thoracolumbar connective tissue and biomechanical and viscoelastic properties of myofascial tissue in the low back region change in subjects with chronic LBP as a result of MELT. This study was designed using a quasi experimental pre-post- design that analyzed data from subjects who performed MELT. Using ultrasound imaging and an algorithm developed in MATLAB, thickness of thoracolumbar connective tissue was analyzed in 22 subjects. A hand-held digital palpation device, called the MyotonPRO, was used to assess biomechanical properties such as stiffness, elasticity, tone and mechanical stress relaxation time of the thoracolumbar myofascial tissue. A forward bending test assessing flexibility and pain scale was added to see if MELT affected subjects with chronic LBP. A significant decrease in connective tissue thickness and pain was observed in participants. Significant increase in flexibility was also recorded. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tension, cell shape and triple-junction angle anisotropy in the Drosophila germband

NASA Astrophysics Data System (ADS)

Lacy, Monica; Hutson, M. Shane; Meyer, Christian; McDonald, Xena

In the field of tissue mechanics, the embryonic development of Drosophila melanogaster offers many opportunities for study. One of Drosophila's most crucial morphogenetic stages is the retraction of an epithelial tissue called the germband. During retraction, the segments of the retracting germband, as well as the individual germband cells, elongate in response to forces from a connected tissue, the amnioserosa. Modeling of this elongation, based on tissue responses to laser wounding, has plotted the internal germband tension against the external amnioserosa stress, creating a phase space to determine points and regions corresponding to stable elongation. Although the resulting fits indicate a necessary opposition of internal and external forces, they are inconclusive regarding the exact balance. We will present results testing the model predictions by measuring cell shapes and the correlations between cell-edge directions and triple-junction angles. These measures resolve the ambiguity in pinpointing the internal-external force balance for each germband segment. Research was supported by NIH Grant Numbers 1R01GM099107 and 1R21AR068933.

Scaffold architecture and fibrin gels promote meniscal cell proliferation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pawelec, K. M., E-mail: pawelec.km@gmail.com, E-mail: jw626@cam.ac.uk; Best, S. M.; Cameron, R. E.

2015-01-01

Stability of the knee relies on the meniscus, a complex connective tissue with poor healing ability. Current meniscal tissue engineering is inadequate, as the signals for increasing meniscal cell proliferation have not been established. In this study, collagen scaffold structure, isotropic or aligned, and fibrin gel addition were tested. Metabolic activity was promoted by fibrin addition. Cellular proliferation, however, was significantly increased by both aligned architectures and fibrin addition. None of the constructs impaired collagen type I production or triggered adverse inflammatory responses. It was demonstrated that both fibrin gel addition and optimized scaffold architecture effectively promote meniscal cell proliferation.

Testing Current and Developing Novel Therapies for NF1-Mutant Sarcomas in a Genetically Engineered Mouse Model

DTIC Science & Technology

2015-04-01

Patients with Neurofibromatosis type 1 (NF1) are at increased risk for developing malignant tumors of the connective tissue called soft-tissue sarcomas...mouse model, MPNST, Neurofibromatosis , NF1 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE...9 9. Appendices……………………………………………………………9 4   1. INTRODUCTION: Patients with Neurofibromatosis type 1 (NF1) are at increased risk for

A long-distance fluid transport pathway within fibrous connective tissues in patients with ankle edema.

PubMed

Li, Hongyi; Yang, Chongqing; Lu, Kuiyuan; Zhang, Liyang; Yang, Jiefu; Wang, Fang; Liu, Dongge; Cui, Di; Sun, Mingjun; Pang, Jianxin; Dai, Luru; Han, Dong; Liao, Fulong

2016-10-05

Although the microcirculatory dysfunctions of edema formation are well documented, the draining pattern of dermal edema lacks information. This study was to assess the potential drainage pathways of the interstitial fluid in patients with ankle edema using the anatomical and histological methods. Four amputees of lower leg participated in this study. Fluorescent imaging agent was injected into lateral ankle dermis in one volunteered patient before the amputation and three lower legs after the amputation. Physiologically in the volunteer or enhanced by cyclical compression on three amputated limbs, several fluorescent longitudinal pathways from ankle dermis to the broken end of the amputated legs were subsequently visualized and studied using histological methods, laser confocal microscopy and electron microscopy methods respectively. Interestingly, the fluorescent pathways confirmed to be fibrous connective tissues and the presence of two types: those of the cutaneous pathway (located in dermis or the interlobular septum among adipose tissues within the hypodermis) and those of the perivascular pathway (located in connective tissues surrounding the veins and the arteries). The intrinsic three-dimensional architecture of each fluorescent pathway was the longitudinally running and interconnected fibril bundles, upon which, an interfacial transport pathway within connective tissues was visualized by fluorescein. The current anatomical data suggested that a unique long-distance transport pathway composed of oriented fibrous connective tissues might play a pathophysiological role in draining dermal edema besides vascular circulations and provide novel understandings of general fibrous connective tissues in life science.

Ultrastructure of periprosthetic Dacron knee ligament tissue. Two cases of ruptured anterior cruciate ligament reconstruction.

PubMed

Salvi, M; Velluti, C; Misasi, M; Bartolozzi, P; Quacci, D; Dell'Orbo, C

1991-04-01

Light- and electron-microscopic investigations were performed on two failed Dacron ligaments that had been removed from 2 patients shortly after failure of the implant 2-3 years after reconstruction of the anterior cruciate ligament. Two different cell populations and matrices were correlated with closeness to the Dacron threads. Fibroblasts surrounded by connective tissue with collagen fibrils were located far from the Dacron threads. Roundish cells, appearing to be myofibroblasts surrounded by a more lax connective tissue and elastic fibers, were found close to the Dacron threads. The presence of myofibroblasts and the matrix differentiation could be attributed to the different mechanical forces acting on the Dacron and on the connective tissue because of their different coefficients of elasticity. The sparse occurrence of inflammatory cells in the synovial membrane and in the connective tissue surrounding the Dacron supports the biologic inertness of this artificial material. However, the repair tissue was not structured to resist tension stresses.

Sensory Innervation of the Nonspecialized Connective Tissues in the Low Back of the Rat

PubMed Central

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

2011-01-01

Chronic musculoskeletal pain, including low back pain, is a worldwide debilitating condition; however, the mechanisms that underlie its development remain poorly understood. Pathological neuroplastic changes in the sensory innervation of connective tissue may contribute to the development of nonspecific chronic low back pain. Progress in understanding such potentially important abnormalities is hampered by limited knowledge of connective tissue's normal sensory innervation. The goal of this study was to evaluate and quantify the sensory nerve fibers terminating within the nonspecialized connective tissues in the low back of the rat. With 3-dimensional reconstructions of thick (30–80 μm) tissue sections we have for the first time conclusively identified sensory nerve fiber terminations within the collagen matrix of connective tissue in the low back. Using dye labeling techniques with Fast Blue, presumptive dorsal root ganglia cells that innervate the low back were identified. Of the Fast Blue-labeled cells, 60–88% also expressed calcitonin gene-related peptide (CGRP) immunoreactivity. Based on the immunolabeling with CGRP and the approximate size of these nerve fibers (≤2 μm) we hypothesize that they are Aδ or C fibers and thus may play a role in the development of chronic pain. PMID:21411968

Three dimensional microstructural network of elastin, collagen, and cells in Achilles tendons.

PubMed

Pang, Xin; Wu, Jian-Ping; Allison, Garry T; Xu, Jiake; Rubenson, Jonas; Zheng, Ming-Hao; Lloyd, David G; Gardiner, Bruce; Wang, Allan; Kirk, Thomas Brett

2017-06-01

Similar to most biological tissues, the biomechanical, and functional characteristics of the Achilles tendon are closely related to its composition and microstructure. It is commonly reported that type I collagen is the predominant component of tendons and is mainly responsible for the tissue's function. Although elastin has been found in varying proportions in other connective tissues, previous studies report that tendons contain very small quantities of elastin. However, the morphology and the microstructural relationship among the elastic fibres, collagen, and cells in tendon tissue have not been well examined. We hypothesize the elastic fibres, as another fibrillar component in the extracellular matrix, have a unique role in mechanical function and microstructural arrangement in Achilles tendons. It has been shown that elastic fibres present a close connection with the tenocytes. The close relationship of the three components has been revealed as a distinct, integrated and complex microstructural network. Notably, a "spiral" structure within fibril bundles in Achilles tendons was observed in some samples in specialized regions. This study substantiates the hierarchical system of the spatial microstructure of tendon, including the mapping of collagen, elastin and tenocytes, with 3-dimensional confocal images. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:1203-1214, 2017. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Micromechanical response of articular cartilage to tensile load measured using nonlinear microscopy.

PubMed

Bell, J S; Christmas, J; Mansfield, J C; Everson, R M; Winlove, C P

2014-06-01

Articular cartilage (AC) is a highly anisotropic biomaterial, and its complex mechanical properties have been a topic of intense investigation for over 60 years. Recent advances in the field of nonlinear optics allow the individual constituents of AC to be imaged in living tissue without the need for exogenous contrast agents. Combining mechanical testing with nonlinear microscopy provides a wealth of information about microscopic responses to load. This work investigates the inhomogeneous distribution of strain in loaded AC by tracking the movement and morphological changes of individual chondrocytes using point pattern matching and Bayesian modeling. This information can be used to inform models of mechanotransduction and pathogenesis, and is readily extendable to various other connective tissues. Copyright © 2014 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Micromechanical modeling of rate-dependent behavior of Connective tissues.

PubMed

Fallah, A; Ahmadian, M T; Firozbakhsh, K; Aghdam, M M

2017-03-07

In this paper, a constitutive and micromechanical model for prediction of rate-dependent behavior of connective tissues (CTs) is presented. Connective tissues are considered as nonlinear viscoelastic material. The rate-dependent behavior of CTs is incorporated into model using the well-known quasi-linear viscoelasticity (QLV) theory. A planar wavy representative volume element (RVE) is considered based on the tissue microstructure histological evidences. The presented model parameters are identified based on the available experiments in the literature. The presented constitutive model introduced to ABAQUS by means of UMAT subroutine. Results show that, monotonic uniaxial test predictions of the presented model at different strain rates for rat tail tendon (RTT) and human patellar tendon (HPT) are in good agreement with experimental data. Results of incremental stress-relaxation test are also presented to investigate both instantaneous and viscoelastic behavior of connective tissues. Copyright © 2017 Elsevier Ltd. All rights reserved.

The effect of interleukin-8 and granulocyte macrophage colony stimulating factor on the response of neutrophils to formyl methionyl leucyl phenylalanine.

PubMed

Mikami, M; Llewellyn-Jones, C G; Stockley, R A

1998-08-14

Neutrophils isolated from patients with chronic bronchitis and emphysema have been shown to have enhanced responses to formyl peptides when assessed in vitro compared to age, sex matched controls. It is currently unclear whether the observed differences are due to a 'priming' effect by a second agent in vivo, or whether this is a primary difference in the neutrophils. We have studied the effects of interleukin-8, which is thought to be one of the major pro-inflammatory cytokines in chronic lung disease and granulocyte macrophage colony stimulating factor (GMCSF), in order to assess their effects on neutrophil chemotaxis and connective tissue degradation. In addition, we have assessed the effect of preincubation of these agents with neutrophils for 30 min followed by stimulation with F-Met-Leu-Phe (FMLP) to investigate any possible 'priming' effect that may be relevant to our clinical data. We report suppression of neutrophil chemotaxis to FMLP following incubation of the neutrophils with both IL-8 and GMCSF. However, we have observed an additive effect of IL-8 and FMLP for neutrophil degranulation leading to fibronectin degradation. The results suggest that IL-8 does not 'prime' neutrophils for subsequent FMLP stimulation as observed in vivo. Although the results for GMCSF were similar for the chemotactic response, the agent also had a synergistic effect on connective tissue degradation. However, it is concluded that neither agent could explain the enhanced neutrophil responses seen in our patients.

Hypericin-mediated selective photomodification of connective tissues

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hovhannisyan, V., E-mail: hovv@phys.ntu.edu.tw; Guo, H. W.; Chen, Y. F., E-mail: yfchen@phys.ntu.edu.tw

2014-12-29

Controllable modification of biological molecules and supramolecular components of connective tissue are important for biophysical and biomedical applications. Through the use of second harmonic generation imaging, two-photon fluorescence microscopy, and spectrofluorimetry, we found that hypericin, a natural pigment, induces photosensitized destruction of collagen fibers but does not affect elastic fibers and lipids in chicken tendon, skin, and blood vessels. We demonstrated the dynamics and efficiency of collagen photomodification and investigated mechanisms of this processes. Our results suggest that hypericin–mediated photoprocesses in biological tissues may be useful in biomedical applications that require selective modification of connective tissues.

Agminated Fibroblastic Conective Tissue Nevus: A New Clinical Presentation.

PubMed

Downey, Camila; Requena, Luis; Bagué, Silvia; Sánchez Martínez, Miquel Ángel; Lloreta, Josep; Baselga, Eulalia

2016-07-01

Connective tissue nevi are benign hamartomatous lesions in which one or several of the components of the dermis (collagen, elastin, glicosaminoglycans) show predominance or depletion. Recently, de Feraudy et al broadened the spectrum of connective tissue nevus, describing fibroblastic connective tissue nevus (FCTN), which is characterized by proliferation of CD34(+) cells of fibroblastic and myofibroblastic lineage. Only solitary papules and nodules have been described. We present the first case of FCTN with multiple agminated lesions on the leg of an infant and the difficulties encountered in the differential diagnosis with dermatofibrosarcoma protuberans. © 2016 Wiley Periodicals, Inc.

Validation of color Doppler sonography for evaluating relative displacement between the flexor tendon and subsynovial connective tissue.

PubMed

Tat, Jimmy; Kociolek, Aaron M; Keir, Peter J

2015-04-01

A common pathologic finding in carpal tunnel syndrome is fibrosis and thickening of the subsynovial connective tissue. This finding suggests an etiology of excessive shear forces, with relative longitudinal displacement between the flexor tendon and adjacent subsynovial connective tissue. The purpose of this study was to validate color Doppler sonography for measurement of tendon displacement over time. Eight unmatched fresh frozen cadaver arms were used to evaluate color Doppler sonography for measurement of tendon displacement. The middle flexor digitorum superficialis tendon was moved through a physiologic excursion of 20 mm at 3 different tendon velocities (50, 100, and 150 mm/s). We found that color Doppler sonography provided accurate measurement of tendon displacement, with absolute errors of -0.05 mm (50 mm/s), -1.24 mm (100 mm/s), and -2.36 mm (150 mm/s) on average throughout the tendon excursion range. Evaluating relative displacement between the tendon and subsynovial connective tissue during finger flexion-extension movements also offered insight into the gliding mechanism of the subsynovial connective tissue. During flexion, we observed a curvilinear increase in relative displacement, with greater differential motion at the end range of displacement, likely due to the sequential stretch of the fibrils between successive layers of the subsynovial connective tissue. In extension, there was a linear return in relative displacement, suggesting a different unloading mechanism characterized by uniform relaxation of fibrils. We demonstrated the validity of color Doppler displacement for use in the evaluation of relative motion. Color Doppler sonography is useful in our understanding of the behavior of the subsynovial connective tissue during tendon excursion, which may elucidate the role of finger motion in the etiology of shear injury. © 2015 by the American Institute of Ultrasound in Medicine.

Secular trends of pregnancies in women with inflammatory connective tissue disease.

PubMed

Wallenius, Marianne; Salvesen, Kjell Å; Daltveit, Anne K; Skomsvoll, Johan F

2015-11-01

This study examined secular trends in reproductive outcome in women with inflammatory connective tissue disease compared with reference deliveries from the general population. Historical cohort study based on data registered in the Medical Birth Register of Norway from 1967 to 2009. The study included singleton births in women recorded with connective tissue disease (n = 851) and reference deliveries from the general population (n = 2 437 110). Births were stratified in four periods, 1967-1979, 1980-1989, 1990-1999 and 2000-2009. Associations between connective tissue disease and maternal and perinatal outcomes by decade were assessed in logistic regression analyses and adjusted for maternal age at delivery and parity. In the 1970s, around 2.7 deliveries/year were registered for women with connective tissue disease (0.004% of all deliveries). This increased to 42 deliveries/year (0.07% of all deliveries) after 2000. Adjusted odds ratios (aOR) for cesarean section were 5.0 (95% CI 2.1-11.9) in the first and 1.8 (95% CI 1.4-2.3) in the last period. For preterm delivery the aOR decreased from 4.9 (95% CI 2.1-11.4) to 3.1 (95% CI 2.3-4.2) and the aOR for birthweight <2500 g changed from 7.3 (95% CI 3.3-16.3) to 4.1 (95% CI 3.0-5.6). An increasing number of births were observed over time among women with connective tissue disease. Adverse pregnancy outcomes were more common among women with connective tissue disease but risks have decreased over time. © 2015 Nordic Federation of Societies of Obstetrics and Gynecology.

[Mixed connective tissue disease: prevalence and clinical characteristics in African black, study of 7 cases in Gabon and review of the literature].

PubMed

Missounga, Landry; Ba, Josaphat Iba; Nseng Nseng Ondo, Ingrid Rosalie; Nziengui Madjinou, Maria Ines Carine; Malekou, Doris; Mouendou Mouloungui, Emeline Gracia; Nzengue, Emmanuel Ecke; Boguikouma, Jean Bruno; Kombila, Moussavou

2017-01-01

The literature reports that mixed connective tissue disease seems more frequent in the black population and among Asians. This study aims to determine the prevalence of mixed connective tissue disease (MCTD) among connective tissue disorders and all rheumatologic pathologies in a hospital population in Gabon as well as to describe the clinical features of this disease. We conducted a retrospective study by reviewing the medical records of patients treated for mixed connective tissue disease (Kasukawa criteria) and other entities of connective tissue disorders (ACR criteria) in the Division of Rheumatology at the University Hospital in Libreville between January 2010 and December 2015. For each case of MCTD the parameters studied were articular and extra-articular manifestations, anti-U1RNP antibodies levels, patient's evolution. Over a period of 6 years, data were collected by medical records of 7 patients out of 6050 patients and 67 cases of connective tissue disorders, reflecting a prevalence of 0.11% and 10.44% respectively. the 7 patients were women (100%), with an average age of 39.5 years. Articular manifestations included: polyarthritis, myalgias, chubby fingers and Raynaud's phenomenon in 87.5%, 87.5%, 28.6% and 14% respectively. The 7 patients had high anti-U1RNP antibodies levels, ranging between 5 and 35N (N≤ 7 IU). A case of death due to pulmonary arterial hypertension (PAH) was certified. This is the largest case series of MCTD reported in Black Africa. The disease seems to be rare among the black Africans; the reason could be genetic. The demographic and clinical aspects appear similar to those in Caucasians, Asians and Blacks except for a low frequency of Raynaud?s phenomenon among Blacks.

Maturation State and Matrix Microstructure Regulate Interstitial Cell Migration in Dense Connective Tissues.

PubMed

Qu, Feini; Li, Qing; Wang, Xiao; Cao, Xuan; Zgonis, Miltiadis H; Esterhai, John L; Shenoy, Vivek B; Han, Lin; Mauck, Robert L

2018-02-19

Few regenerative approaches exist for the treatment of injuries to adult dense connective tissues. Compared to fetal tissues, adult connective tissues are hypocellular and show limited healing after injury. We hypothesized that robust repair can occur in fetal tissues with an immature extracellular matrix (ECM) that is conducive to cell migration, and that this process fails in adults due to the biophysical barriers imposed by the mature ECM. Using the knee meniscus as a platform, we evaluated the evolving micromechanics and microstructure of fetal and adult tissues, and interrogated the interstitial migratory capacity of adult meniscal cells through fetal and adult tissue microenvironments with or without partial enzymatic digestion. To integrate our findings, a computational model was implemented to determine how changing biophysical parameters impact cell migration through these dense networks. Our results show that the micromechanics and microstructure of the adult meniscus ECM sterically hinder cell mobility, and that modulation of these ECM attributes via an exogenous matrix-degrading enzyme permits migration through this otherwise impenetrable network. By addressing the inherent limitations to repair imposed by the mature ECM, these studies may define new clinical strategies to promote repair of damaged dense connective tissues in adults.

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

PubMed

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

2016-01-01

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

Nematode infection in liver of the fish Gymnotus inaequilabiatus (Gymnotiformes: Gymnotidae) from the Pantanal Region in Brazil: pathobiology and inflammatory response.

PubMed

Sayyaf Dezfuli, Bahram; Fernandes, Carlos E; Galindo, Gizela M; Castaldelli, Giuseppe; Manera, Maurizio; DePasquale, Joseph A; Lorenzoni, Massimo; Bertin, Sara; Giari, Luisa

2016-08-30

A survey on endoparasitic helminths from freshwater fishes in the Pantanal Region (Mato Grosso do Sul, Brazil) revealed the occurrence of third-larval stage of the nematode Brevimulticaecum sp. (Heterocheilidae) in most organs of Gymnotus inaequilabiatus (Gymnotidae) also known by the local name tuvira. The aim of the present study was to examine Brevimulticaecum sp.-infected tuvira liver at the ultrastructural level and clarify the nature of granulomas and the cellular elements involved in the immune response to nematode larvae. Thirty-eight adult specimens of tuvira from Porto Morrinho, were acquired in January and March 2016. Infected and uninfected liver tissues were fixed and prepared for histological and ultrastructure investigations. The prevalence of infection of tuvira liver by the nematode larvae was 95 %, with an intensity of infection ranging from 4 to 343 larvae (mean ± SD: 55.31 ± 73.94 larvae per liver). In livers with high numbers of nematode larvae, almost entire hepatic tissue was occupied by the parasites. Hepatocytes showed slight to mild degenerative changes and accumulation of pigments. Parasite larvae were surrounded by round to oval granulomas, the result of focal host tissue response to the infection. Each granuloma was typically formed by three concentric layers: an outer layer of fibrous connective tissue with thin elongated fibroblasts; a middle layer of mast cells entrapped in a thin fibroblast-connective mesh; and an inner layer of densely packed epithelioid cells, displaying numerous desmosomes between each other. Numerous macrophage aggregates occurred in the granulomas and in the parenchyma. Our results in tuvira showed that the larvae were efficiently sequestered within the granulomas, most of the inflammatory components were confined within the thickness of the granuloma, and the parenchyma was relatively free of immune cells and without fibrosis. Presumably this focal encapsulation of the parasites permits uninfected portions of liver to maintain its functions and allows the survival of the host.

Acoustic properties of healthy and reconstructed cleft lip

NASA Astrophysics Data System (ADS)

Thijssen, Johan M.; van Hees, Nancy J.; Weijers, Gert G.; Huyskens, Rinske W.; Nillesen, Maartje; Katsaros, Christos; de Korte, Chris L.

2006-03-01

The feasibility of echographic imaging of the tissues in healthy lip and in reconstructed cleft lip and estimating the dimensions and the normalized echo level of these tissues is investigated. Echographic images of the upper lip were made with commercial medical ultrasound equipment, using a linear array transducer (7-11 MHz bandwidth) and a non-contact gel coupling. Tissue dimensions were measured by means of software calipers. Echo levels were calibrated and corrected for beam characteristics, gel path and tissue attenuation by using a tissue-mimicking phantom. At central position of philtrum, mean thickness (and standard deviation) of lip loose connective tissue layer, orbicularis oris muscle and dense connective layer was 4.0 (sd 0.1) mm, 2.3 (sd 0.7) mm, 2.2 (sd 0.7) mm, respectively, in healthy lip at rest. Mean (sd) echo level of muscle and dense connective tissue layer with respect to echo level of lip loose connective tissue layer was in relaxed condition: - 19.3 (sd 0.6) dB and - 10.7 (sd 4.0) dB, respectively. Echo level of loose connective tissue layer was +25.6 (sd 4.2) dB relative to phantom echo level obtained in the focus of the transducer. Color mode echo images were calculated, after adaptive filtering of the images, which show the tissues in separate colors and highlight the details of healthy lip and reconstructed cleft lip. Quantitative assessment of thickness and echo level of various lip tissues is feasible after proper calibration of the echographic equipment. Diagnostic potentials of the developed quantitative echographic techniques for non-invasive evaluation of the outcome of cleft lip reconstruction are promising.

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

PubMed

Li, Qiaoli; Jiang, Qiujie; Uitto, Jouni

2014-01-01

Ectopic mineralization of connective tissues is a complex process leading to deposition of calcium phosphate complexes in the extracellular matrix, particularly affecting the skin and the arterial blood vessels and common in age-associated disorders. A number of initiating and contributing metabolic and environmental factors are linked to aberrant mineralization in these diseases, making the identification of precise pathomechanistic pathways exceedingly difficult. However, there has been significant recent progress in understanding the ectopic mineralization processes through study of heritable single-gene disorders, which have allowed identification of discrete pathways and contributing factors leading to aberrant connective tissue mineralization. These studies have provided support for the concept of an intricate mineralization/anti-mineralization network present in peripheral connective tissues, providing a perspective to development of pharmacologic approaches to limit the phenotypic consequences of ectopic mineralization. This overview summarizes the current knowledge of ectopic heritable mineralization disorders, with accompanying animal models, focusing on pseudoxanthoma elasticum and generalized arterial calcification of infancy, two autosomal recessive diseases manifesting with extensive connective tissue mineralization in the skin and the cardiovascular system. © 2013.

[Pulmonary involvement in connective tissue disease].

PubMed

Bartosiewicz, Małgorzata

2016-01-01

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

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

PubMed Central

Li, Qiaoli; Jiang, Qiujie; Uitto, Jouni

2013-01-01

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

Polarization spectrometry diagnostic of cervical pathological states of endometriosis

NASA Astrophysics Data System (ADS)

Yermolenko, S. B.; Peresunko, O. P.; Burkovets, D. N.

2018-01-01

The purpose of the study was to determine the histochemical and laser criteria for diagnosis of background, precancerous and endometrial cancer by the state of the cervical canal wall. The given data on the state of connective tissue in the endocervix can distinguish three differential prognostic possibilities: - prediction of the condition of the connective tissue of the endocervix of the normal endometrium without the possibility of differentiating the phases of the ovarian cycle; - prediction of the endocervix endotracheal connective tissue state of the endometrium as a separate process; - prediction for the condition of the connective tissue of the endocervix of the processes of expressed proliferation of the typical (glandular hyperplasia and glandular polyps) or atypical (adenocarcinoma) glandular first endometrial epithelial differentiation without the possibility of these processes among them. The stroke-scrape of the epithelium of the cervical canal (endocervix) allows the condition of the connective tissue to diagnose the processes of pronounced proliferation of the typical (hyperplasia, polyp) and atypical (adenocarcinoma) epithelium of the endometrium without the possibility of differentiating these processes among themselves.

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

NASA Technical Reports Server (NTRS)

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

1995-01-01

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

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

PubMed

Henderson, B

1983-01-01

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

Central nervous system tissue heterotopia of the nose: case report and review of the literature

PubMed Central

Altissimi, G; Ascani, S; Falcetti, S; Cazzato, C; Bravi, I

2009-01-01

Summary The Authors present a case of heterotopic central nervous system tissue observed in an 81-year-old male in the form of an ethmoidal polyp. A review of the literature indicates that this is a rare condition characterised by a connective tissue lesion with astrocytic and oligodendrocytic glial cells, which may be located outside the nasal pyramid in some cases and inside the nasal cavity in others. The most important diagnostic aspect involves differentiating these from meningoencephalocele, which maintains an anatomical connection with central nervous system tissue. Contrast-enhanced imaging is essential for diagnosis, as in cases of heterotopic central nervous system tissue, it will demonstrate that there are no connections with intra-cranial tissue. Endoscopic excision is the treatment of choice. PMID:20161881

A novel chemically modified curcumin reduces inflammation-mediated connective tissue breakdown in a rat model of diabetes: periodontal and systemic effects.

PubMed

Elburki, M S; Moore, D D; Terezakis, N G; Zhang, Y; Lee, H-M; Johnson, F; Golub, L M

2017-04-01

Periodontal disease is the most common chronic inflammatory disease known to mankind (and the major cause of tooth loss in the adult population) and has also been linked to various systemic diseases, particularly diabetes mellitus. Based on the literature linking periodontal disease with diabetes in a "bidirectional manner", the objectives of the current study were to determine: (i) the effect of a model of periodontitis, complicated by diabetes, on mechanisms of tissue breakdown including bone loss; and (ii) the response of the combination of this local and systemic phenotype to a novel pleiotropic matrix metalloproteinase inhibitor, chemically modified curcumin (CMC) 2.24. Diabetes was induced in adult male rats by intravenous injection of streptozotocin (nondiabetic rats served as controls), and Escherichia coli endotoxin (lipopolysaccharide) was repeatedly injected into the gingiva to induce periodontitis. CMC 2.24 was administered by oral gavage (30 mg/kg) daily; untreated diabetic rats received vehicle alone. After 3 wk of treatment, the rats were killed, and gingiva, jaws, tibia and skin were collected. The maxillary jaws and tibia were dissected and radiographed. The gingival tissues of each experimental group (n = 6 rats/group) were pooled, extracted, partially purified and, together with individual skin samples, analyzed for matrix metalloproteinase (MMP)-2 and MMP-9 by gelatin zymography; MMP-8 was analyzed in gingival and skin tissue extracts, and in serum, by western blotting. The levels of three bone-resorptive cytokines [interleukin (IL)-1β, IL-6 and tumor necrosis factor-α], were measured in gingival tissue extracts and serum by ELISA. Systemic administration of CMC 2.24 to diabetic rats with endotoxin-induced periodontitis significantly inhibited alveolar bone loss and attenuated the severity of local and systemic inflammation. Moreover, this novel tri-ketonic phenylaminocarbonyl curcumin (CMC 2.24) appeared to reduce the pathologically excessive levels of inducible MMPs to near-normal levels, but appeared to have no significant effect on the constitutive MMPs required for physiologic connective tissue turnover. In addition to the beneficial effects on periodontal disease, induced both locally and systemically, CMC 2.24 also favorably affected extra-oral connective tissues, skin and skeletal bone. This study supports our hypothesis that CMC 2.24 is a potential therapeutic pleiotropic MMP inhibitor, with both intracellular and extracellular effects, which reduces local and systemic inflammation and prevents hyperglycemia- and bacteria-induced connective tissue destruction. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

PubMed

Kasten, Robert; Pfirrmann, Gudrun; Voigtländer, Volker

2005-08-01

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

Heart Valve Biomechanics and Underlying Mechanobiology

PubMed Central

Ayoub, Salma; Ferrari, Giovanni; Gorman, Robert C.; Gorman, Joseph H.; Schoen, Frederick J.; Sacks, Michael S.

2017-01-01

Heart valves control unidirectional blood flow within the heart during the cardiac cycle. They have a remarkable ability to withstand the demanding mechanical environment of the heart, achieving lifetime durability by processes involving the ongoing remodeling of the extracellular matrix. The focus of this review is on heart valve functional physiology, with insights into the link between disease-induced alterations in valve geometry, tissue stress, and the subsequent cell mechanobiological responses and tissue remodeling. We begin with an overview of the fundamentals of heart valve physiology and the characteristics and functions of valve interstitial cells (VICs). We then provide an overview of current experimental and computational approaches that connect VIC mechanobiological response to organ- and tissue-level deformations and improve our understanding of the underlying functional physiology of heart valves. We conclude with a summary of future trends and offer an outlook for the future of heart valve mechanobiology, specifically, multiscale modeling approaches, and the potential directions and possible challenges of research development. PMID:27783858

Connective tissue graft as a biological barrier for guided tissue regeneration in intrabony defects: a histological study in dogs.

PubMed

Ribeiro, Fernando Salimon; Pontes, Ana Emília Farias; Zuza, Elizangela Partata; da Silva, Vanessa Camila; Lia, Raphael Carlos Comelli; Marcantonio Junior, Elcio

2015-06-01

The use of the autogenous periosteal graft as biological barrier has been proposed for periodontal regeneration. The aim of this study was to evaluate the histometric findings of the subepithelial connective tissue graft as barrier in intrabony defects compared to a bioabsorbable membrane. Three-walled intrabony defects were created surgically in the mesial aspect of the right and left maxillary canines in five healthy mongrel dogs. The defects were chronified, and two types of barriers were randomly carried out for guided tissue regeneration in a split-mouth design: the test group with a subepithelial connective tissue graft and the control group with a bioabsorbable membrane. The specimens were processed for histometric analyses of the epithelium (E), connective tissue (CT), newly formed cementum (NC), new bone (NB), and total newly formed tissues (NFT). The test side showed smaller mean of NC (3.6 ± 1.2), NB (2.1 ± 0.7), and NFT (7.7 ± 0.8) than the control group (NC 7.3 ± 0.5; NB 5.3 ± 1.3; NFT 10.1 ± 2.2; P < 0.05). No statistically significant differences were verified for E (test 3.1 ± 2.0; control 2.8 ± 2.1; P > 0.05) and CT (test 2.5 ± 1.1; control 2.0 ± 0.5; P > 0.05) between groups. The bioabsorbable membrane was more effective in maintaining the space for periodontal regeneration than periosteal connective graft when used as barrier. The bioabsorbable membrane showed more favorable regenerative results in intrabony defects in dogs than the subepithelial connective tissue graft as biological barrier.

[Morphological characteristics of kidneys connective tissue of mature fetuses and newborns from mothers, whose pregnancy was complicated by preeclampsia of varying degrees of severity].

PubMed

Sorokina, Iryna V; Myroshnychenko, Mykhailo S; Kapustnyk, Nataliia V; Khramova, Tetyana O; Dehtiarova, Oksana V; Danylchenko, Svitlana I

2018-01-01

Introduction: The kidneys connective tissue condition in the antenatal period affects the formation of tissues and it changes with the development of various general pathological processes in this organ. The aim of the study was to identify the morphological features of kidneys connective tissue of fetuses and newborns from mothers whose pregnancy was complicated by preeclampsia of varying degrees of severity. Materials and methods: The material of the study was the tissue of kidneys of mature fetuses and newborns from mothers with physiological pregnancy (28 cases), as well as from mothers whose pregnancy was complicated by preeclampsia of varying degrees of severity (78 cases). Immunohistochemical study was performed by an indirect Coons method according to M. Brosman's technique using monoclonal antibodies to collagen type I, III and IV. Results: The kidneys connective tissue of fetuses and newborns developing under the maternal preeclampsia conditions is characterized by the qualitative and quantitative changes that indicate the development of sclerotic processes in this organ, the severity of which increase with the age and with the increase of the maternal preeclampsia severity. Qualitative changes are characterized by an increase of the fibrous component, thickening of the bundles of connective tissue fibers, and a decrease in the distance between them. Quantitative changes are characterized by a pronounced predominance of collagen fibers over elastic fibers, almost total absence in some field of view elastic fibers and the violation of the content of collagen type I, III and IV. Conclusion: Maternal preeclampsia underlies the development of qualitative and quantitative changes in kidneys connective tissue of fetuses and newborns, which as a result will lead to disruption of the functions of these organs in such children.

Connective Tissue Growth Factor Domain 4 Amplifies Fibrotic Kidney Disease through Activation of LDL Receptor-Related Protein 6.

PubMed

Johnson, Bryce G; Ren, Shuyu; Karaca, Gamze; Gomez, Ivan G; Fligny, Cécile; Smith, Benjamin; Ergun, Ayla; Locke, George; Gao, Benbo; Hayes, Sebastian; MacDonnell, Scott; Duffield, Jeremy S

2017-06-01

Connective tissue growth factor (CTGF), a matrix-associated protein with four distinct cytokine binding domains, has roles in vasculogenesis, wound healing responses, and fibrogenesis and is upregulated in fibroblasts and myofibroblasts in disease. Here, we investigated the role of CTGF in fibrogenic cells. In mice, tissue-specific inducible overexpression of CTGF by kidney pericytes and fibroblasts had no bearing on nephrogenesis or kidney homeostasis but exacerbated inflammation and fibrosis after ureteral obstruction. These effects required the WNT receptor LDL receptor-related protein 6 (LRP6). Additionally, pericytes isolated from these mice became hypermigratory and hyperproliferative on overexpression of CTGF. CTGF is cleaved in vivo into distinct domains. Treatment with recombinant domain 1, 1+2 (N terminus), or 4 (C terminus) independently activated myofibroblast differentiation and wound healing responses in cultured pericytes, but domain 4 showed the broadest profibrotic activity. Domain 4 exhibited low-affinity binding to LRP6 in in vitro binding assays, and inhibition of LRP6 or critical signaling cascades downstream of LRP6, including JNK and WNT/ β -catenin, inhibited the biologic activity of domain 4. Administration of blocking antibodies specifically against CTGF domain 4 or recombinant Dickkopf-related protein-1, an endogenous inhibitor of LRP6, effectively inhibited inflammation and fibrosis associated with ureteral obstruction in vivo Therefore, domain 4 of CTGF and the WNT signaling pathway are important new targets in fibrosis. Copyright © 2017 by the American Society of Nephrology.

Stromal cell-based immunotherapy in transplantation.

PubMed

Charles, Ronald; Lu, Lina; Qian, Shiguang; Fung, John J

2011-12-01

Organs are composed of parenchymal cells that characterize organ function and nonparenchymal cells that are composed of cells in transit, as well as tissue connective tissue, also referred to as tissue stromal cells. It was originally thought that these tissue stromal cells provided only structural and functional support for parenchymal cells and were relatively inert. However, we have come to realize that tissue stromal cells, not restricted to in the thymus and lymphoid organs, also play an active role in modulating the immune system and its response to antigens. The recognition of these elements and the elucidation of their mechanisms of action have provided valuable insight into peripheral immune regulation. Extrapolation of these principles may allow us to utilize their potential for clinical application. In this article, we will summarize a number of tissue stromal elements/cell types that have been shown to induce hyporesponsiveness to transplants. We will also discuss the mechanisms by which these stromal cells create a tolerogenic environment, which in turn results in long-term allograft survival.

Keloids and Hypertrophic Scars

MedlinePlus

... to the skin both skin cells and connective tissue cells (fibroblasts) begin multiplying to repair the damage. A scar is made up of 'connective tissue', gristle-like fibers deposited in the skin by ...

Wavelet analysis in two-dimensional tomography

NASA Astrophysics Data System (ADS)

Burkovets, Dimitry N.

2002-02-01

The diagnostic possibilities of wavelet-analysis of coherent images of connective tissue in its pathological changes diagnostics. The effectiveness of polarization selection in obtaining wavelet-coefficients' images is also shown. The wavelet structures, characterizing the process of skin psoriasis, bone-tissue osteoporosis have been analyzed. The histological sections of physiological normal and pathologically changed samples of connective tissue of human skin and spongy bone tissue have been analyzed.

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

PubMed Central

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

2014-01-01

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

Comparative morphology of changeable skin papillae in octopus and cuttlefish.

PubMed

Allen, Justine J; Bell, George R R; Kuzirian, Alan M; Velankar, Sachin S; Hanlon, Roger T

2014-04-01

A major component of cephalopod adaptive camouflage behavior has rarely been studied: their ability to change the three-dimensionality of their skin by morphing their malleable dermal papillae. Recent work has established that simple, conical papillae in cuttlefish (Sepia officinalis) function as muscular hydrostats; that is, the muscles that extend a papilla also provide its structural support. We used brightfield and scanning electron microscopy to investigate and compare the functional morphology of nine types of papillae of different shapes, sizes and complexity in six species: S. officinalis small dorsal papillae, Octopus vulgaris small dorsal and ventral eye papillae, Macrotritopus defilippi dorsal eye papillae, Abdopus aculeatus major mantle papillae, O. bimaculoides arm, minor mantle, and dorsal eye papillae, and S. apama face ridge papillae. Most papillae have two sets of muscles responsible for extension: circular dermal erector muscles arranged in a concentric pattern to lift the papilla away from the body surface and horizontal dermal erector muscles to pull the papilla's perimeter toward its core and determine shape. A third set of muscles, retractors, appears to be responsible for pulling a papilla's apex down toward the body surface while stretching out its base. Connective tissue infiltrated with mucopolysaccharides assists with structural support. S. apama face ridge papillae are different: the contraction of erector muscles perpendicular to the ridge causes overlying tissues to buckle. In this case, mucopolysaccharide-rich connective tissue provides structural support. These six species possess changeable papillae that are diverse in size and shape, yet with one exception they share somewhat similar functional morphologies. Future research on papilla morphology, biomechanics and neural control in the many unexamined species of octopus and cuttlefish may uncover new principles of actuation in soft, flexible tissue.

Washington View: Not a Snapshot of Public Opinion but an Album

ERIC Educational Resources Information Center

Ferguson, Maria

2015-01-01

The columnist weighs in on the most recent PDK/Gallup poll. The real value of the poll, the author says, comes from looking at each response and then thinking about the connective tissue between and among them. The poll's 47-year history adds yet another layer of rich context. Uniquely, the poll provides not a snapshot of public opinion, rather an…

A left cerebellar pathway mediates language in prematurely-born young adults

PubMed Central

Constable, R. Todd; Vohr, Betty R.; Scheinost, Dustin; Benjamin, Jennifer R.; Fulbright, Robert K.; Lacadie, Cheryl; Schneider, Karen C.; Katz, Karol H.; Zhang, Heping; Papademetris, Xenophon; Ment, Laura R.

2012-01-01

Preterm (PT) subjects are at risk for developmental delay, and task-based studies suggest that developmental disorders may be due to alterations in neural connectivity. Since emerging data imply the importance of right cerebellar function for language acquisition in typical development, we hypothesized that PT subjects would have alternate areas of cerebellar connectivity, and that these areas would be responsible for differences in cognitive outcomes between PT subjects and term controls at age 20 years. Nineteen PT and 19 term control young adults were prospectively studied using resting-state functional MRI (fMRI) to create voxel-based contrast maps reflecting the functional connectivity of each tissue element in the grey matter through analysis of the intrinsic connectivity contrast degree (ICC-d). Left cerebellar ICC-d differences between subjects identified a region of interest that was used for subsequent seed-based connectivity analyses. Subjects underwent standardized language testing, and correlations with cognitive outcomes were assessed. There were no differences in gender, hand preference, maternal education, age at study, or Peabody Picture Vocabulary Test (PPVT) scores. Functional connectivity (FcMRI) demonstrated increased tissue connectivity in the biventer, simple and quadrangular lobules of the L cerebellum (p<0.05) in PTs compared to term controls; seed-based analyses from these regions demonstrated alterations in connectivity from L cerebellum to both R and L inferior frontal gyri (IFG) in PTs compared to term controls. For PTs but not term controls, there were significant positive correlations between these connections and PPVT scores (R IFG: r=0.555, p=0.01; L IFG: r=0.454, p=0.05), as well as Verbal Comprehension Index (VCI) scores (R IFG: r=0.472, p=0.04). These data suggest the presence of a left cerebellar language circuit in PT subjects at young adulthood. These findings may represent either a delay in maturation or the engagement of alternative neural pathways for language in the developing PT brain. PMID:22982585

Marfan Syndrome

MedlinePlus

Marfan syndrome is a disorder that affects connective tissue. Connective tissues are proteins that support skin, bones, blood vessels, ... A problem with the fibrillin gene causes Marfan syndrome. Marfan syndrome can be mild to severe, and ...

Uterine Prolapse

MedlinePlus

... during bowel movements Family history of weakness in connective tissue Being Hispanic or white Complications Uterine prolapse is ... You might experience: Anterior prolapse (cystocele). Weakness of connective tissue separating the bladder and vagina may cause the ...

In vivo response to starch-based scaffolds designed for bone tissue engineering applications.

PubMed

Salgado, A J; Coutinho, O P; Reis, R L; Davies, J E

2007-03-15

Our purpose was to evaluate the in vivo endosseous response to three starch-based scaffolds implanted in rats (n = 54). We implanted the three scaffold groups; a 50/50 (wt %) blend of corn starch and ethylene-vinyl alcohol (SEVA-C), the same composition coated with a biomimetic calcium phosphate (Ca-P) layer (SEVA-C/CaP), and a 50/50 (wt %) blend of corn starch and cellulose acetate (SCA), all produced by extrusion with blowing agents, into distal femurs proximal to the epiphyseal plate, for 1, 3, or 6 weeks. Our results showed that at 1 week considerable reparative bone formed around all scaffold groups, although the bone was separated from the scaffold by an intervening soft tissue interfacial zone that comprised two distinct compartments: the surface of the scaffold was occupied by multinucleate giant cells and the compartment between these cells and the surrounding bone was occupied by a streaming fibrous-like tissue. The extracellular matrix of the latter was continuous with the extracellular bone matrix itself, labeled positively for osteocalcin and appeared mineralized by back-scattered electron imaging. All three scaffolds showed a similar tissue response, with the soft tissue interface diminishing with time. No bone contact was observed with SEVA-C at any time point, only transitory bone contact was observed with SEVA-C/CaP at 3 weeks, but SCA exhibited direct bone contact at 6 weeks where 56.23 +/- 6.46% of the scaffold surface was occupied by bone. We conclude that all materials exhibited a favorable bony response and that the rapidly forming initial "connective tissue" seen around all scaffolds was a very early form of bone formation.

The contribution of the sclera and lamina cribrosa to the pathogenesis of glaucoma: Diagnostic and treatment implications.

PubMed

Quigley, Harry A

2015-01-01

Glaucoma, the second most common cause of world blindness, results from loss of retinal ganglion cells (RGC). RGC die as a consequence of injury to their axons, as they pass through the transition between the environment within the eye and that of the retrobulbar optic nerve, as they course to central visual centers. At the optic nerve head (ONH), axonal transport becomes abnormal, at least in part due to the effect of strain induced by intraocular pressure (IOP) on the sclera and ONH. Animal glaucoma models provide the ability to study how alterations in ocular connective tissues affect this pathological process. New therapeutic interventions are being investigated to mitigate glaucoma blindness by modifying the remodeling of ocular tissues in glaucoma. Some genetically altered mice are resistant to glaucoma damage, while treatment of the sclera with cross-linking agents makes experimental mouse glaucoma damage worse. Inhibition of transforming growth factor β activity is strikingly protective. Treatments that alter the response of ocular connective tissues to IOP may be effective in protecting those with glaucoma from vision loss. © 2015 Elsevier B.V. All rights reserved.

Deformation micromechanisms of collagen fibrils under uniaxial tension

PubMed Central

Tang, Yuye; Ballarini, Roberto; Buehler, Markus J.; Eppell, Steven J.

2010-01-01

Collagen, an essential building block of connective tissues, possesses useful mechanical properties due to its hierarchical structure. However, little is known about the mechanical properties of collagen fibril, an intermediate structure between the collagen molecule and connective tissue. Here, we report the results of systematic molecular dynamics simulations to probe the mechanical response of initially unflawed finite size collagen fibrils subjected to uniaxial tension. The observed deformation mechanisms, associated with rupture and sliding of tropocollagen molecules, are strongly influenced by fibril length, width and cross-linking density. Fibrils containing more than approximately 10 molecules along their length and across their width behave as representative volume elements and exhibit brittle fracture. Shorter fibrils experience a more graceful ductile-like failure. An analytical model is constructed and the results of the molecular modelling are used to find curve-fitted expressions for yield stress, yield strain and fracture strain as functions of fibril structural parameters. Our results for the first time elucidate the size dependence of mechanical failure properties of collagen fibrils. The associated molecular deformation mechanisms allow the full power of traditional material and structural engineering theory to be applied to our understanding of the normal and pathological mechanical behaviours of collagenous tissues under load. PMID:19897533

Necrotic and inflammatory changes in metal-on-metal resurfacing hip arthroplasties

PubMed Central

2009-01-01

Background Necrosis and inflammation in peri-implant soft tissues have been described in failed second-generation metal-on-metal (MoM) resurfacing hip arthroplasties and in the pseudotumors associated with these implants. The precise frequency and significance of these tissue changes is unknown. Method We analyzed morphological and immunophenotypic changes in the periprosthetic soft tissues and femoral heads of 52 revised MoM arthroplasties (fracture in 21, pseudotumor in 13, component loosening in 9, and other causes in 9 cases). Results Substantial necrosis was observed in the periprosthetic connective tissue in 28 of the cases, including all pseudotumors, and 5 cases of component loosening. A heavy, diffuse inflammatory cell infiltrate composed mainly of HLA-DR+/CD14+/CD68+ macrophages and CD3+ T cells was seen in 45 of the cases. Perivascular lymphoid aggregates composed of CD3+ cells and CD20+ B cells were noted in 27 of the cases, but they were not seen in all cases of component loosening or pseudotumors. Plasma cells were noted in 30 cases. Macrophage granulomas were noted in 6 cases of component loosening. In the bone marrow of the femoral head, a macrophage and T cell response was seen in 31 of the cases; lymphoid aggregates were noted in 19 of the cases and discrete granulomas in 1 case. Interpretation Our findings indicate that there is a spectrum of necrotic and inflammatory changes in response to the deposition of cobalt-chrome (Co-Cr) wear particles in periprosthetic tissues. Areas of extensive coagulative necrosis and a macrophage and T lymphocyte response occur in implant failure and pseudotumors, in which there is also granuloma formation. The pathogenesis of these changes is uncertain but it may involve both a cytotoxic response and a delayed hypersensitivity (type IV) response to Co-Cr particles. PMID:19995315

Isolation, separation, and characterization of epithelial and connective cells from rat palate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Terranova, Victor Paul

1979-01-01

Epithelial and connective tissue cells were isolated from rat palate by sequential collagenase, hyaluronidase and trypsin digestion of the extracellular matrix. Differences between the two populations were noted with respect to total cell protein, total cell water, proline uptake and incorporation, percent collagen synthesized, effects of parathyroid hormone, metabolism of D-valine and cell density. Basal epithelial cells were subsequently separated from the heterogeneous epithelial cell population on shallow linear density gradients by velocity centrifugation. The type of collagen synthesized by the basal epithelial cells was compared to the type of collagen synthesized by the connective tissue cells by means ofmore » labeled amino acid incorporation ratios. Cells isolated from the epithelial and connective tissue were compared. From these studies it can be concluded that epithelial and connective tissue cells can be isolated from rat palate as viable and distinct populations with respect to the biochemical parameters examined. Furthermore, subpopulations can be separated and biochemically characterized.« less

Rod-Shaped Neural Units for Aligned 3D Neural Network Connection.

PubMed

Kato-Negishi, Midori; Onoe, Hiroaki; Ito, Akane; Takeuchi, Shoji

2017-08-01

This paper proposes neural tissue units with aligned nerve fibers (called rod-shaped neural units) that connect neural networks with aligned neurons. To make the proposed units, 3D fiber-shaped neural tissues covered with a calcium alginate hydrogel layer are prepared with a microfluidic system and are cut in an accurate and reproducible manner. These units have aligned nerve fibers inside the hydrogel layer and connectable points on both ends. By connecting the units with a poly(dimethylsiloxane) guide, 3D neural tissues can be constructed and maintained for more than two weeks of culture. In addition, neural networks can be formed between the different neural units via synaptic connections. Experimental results indicate that the proposed rod-shaped neural units are effective tools for the construction of spatially complex connections with aligned nerve fibers in vitro. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Heritable Disorders of Connective Tissue

MedlinePlus

... skin. Epidermolysis bullosa affects the skin, causing blisters. Marfan syndrome can affect the heart, blood vessels, lungs, eyes, ... Disorders of Connective Tissue, Questions and Answers about Marfan Syndrome, Questions and Answers about Marfan Syndrome, Easy-to- ...

Soft tissue wound healing around teeth and dental implants.

PubMed

Sculean, Anton; Gruber, Reinhard; Bosshardt, Dieter D

2014-04-01

To provide an overview on the biology and soft tissue wound healing around teeth and dental implants. This narrative review focuses on cell biology and histology of soft tissue wounds around natural teeth and dental implants. The available data indicate that: (a) Oral wounds follow a similar pattern. (b) The tissue specificities of the gingival, alveolar and palatal mucosa appear to be innately and not necessarily functionally determined. (c) The granulation tissue originating from the periodontal ligament or from connective tissue originally covered by keratinized epithelium has the potential to induce keratinization. However, it also appears that deep palatal connective tissue may not have the same potential to induce keratinization as the palatal connective tissue originating from an immediately subepithelial area. (d) Epithelial healing following non-surgical and surgical periodontal therapy appears to be completed after a period of 7–14 days. Structural integrity of a maturing wound between a denuded root surface and a soft tissue flap is achieved at approximately 14-days post-surgery. (e) The formation of the biological width and maturation of the barrier function around transmucosal implants requires 6–8 weeks of healing. (f) The established peri-implant soft connective tissue resembles a scar tissue in composition, fibre orientation, and vasculature. (g) The peri-implant junctional epithelium may reach a greater final length under certain conditions such as implants placed into fresh extraction sockets versus conventional implant procedures in healed sites. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

PubMed

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

2014-05-01

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

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

PubMed Central

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

2014-01-01

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

Motivations, concerns, and experiences of women who donate normal breast tissue.

PubMed

Doherty, Eileen F; MacGeorge, Erina L; Gillig, Traci; Clare, Susan E

2015-01-01

The Susan G. Komen for the Cure Tissue Bank at the IU Simon Cancer Center (KTB) was established in 2007 with funding from Susan G. Komen for the Cure to provide scientists with a resource for normal breast tissue. To date, nearly 3,500 women have donated their healthy breast tissue to the bank, but little is known about their perspectives. This study was designed to examine their motivations, concerns, and experiences. We conducted brief interviews with donors (n = 221) to investigate their donation-related motivations, concerns, and experiences. Donor responses were coded and quantitatively analyzed (descriptive statistics and χ(2)). The most frequent motivation to donate (48% of donors) was personal connection to a breast cancer patient/survivor. A majority of donors (60%) were unconcerned about donation before the event; reported concerns included pain, fear, and dislike of surgical procedures. The most frequent positive experiences were minimal pain and positive behavior by KTB staff and volunteers. A majority of donors (61%) reported no negative experience, but reported negative experiences included the biopsy machine and anesthetic. Younger donors (ages 18-24) reported more concerns and negative experiences than older donors (25+). Donors of healthy breast tissue are motivated by survivor connections and the ability to help by donating. Their concerns and experiences are relatively positive and consistent with undergoing a minor surgical procedure. Younger donors have more concerns and negative experiences. Findings from this study can inform recruitment campaigns and donation procedures for banking of healthy tissue. ©2014 American Association for Cancer Research.

TRAP-Positive Multinucleated Giant Cells Are Foreign Body Giant Cells Rather Than Osteoclasts: Results From a Split-Mouth Study in Humans.

PubMed

Lorenz, Jonas; Kubesch, Alica; Korzinskas, Tadas; Barbeck, Mike; Landes, Constantin; Sader, Robert A; Kirkpatrick, Charles J; Ghanaati, Shahram

2015-12-01

This study compared the material-specific tissue response to the synthetic, hydroxyapatite-based bone substitute material NanoBone (NB) with that of the xenogeneic, bovine-based bone substitute material Bio-Oss (BO). The sinus cavities of 14 human patients were augmented with NB and BO in a split-mouth design. Six months after augmentation, bone biopsies were extracted for histological and histomorphometric investigation prior to dental implant insertion. The following were evaluated: the cellular inflammatory pattern, the induction of multinucleated giant cells, vascularization, the relative amounts of newly formed bone, connective tissue, and the remaining bone substitute material. NB granules were well integrated in the peri-implant tissue and were surrounded by newly formed bone tissue. Multinucleated giant cells were visible on the surfaces of the remaining granules. BO granules were integrated into the newly formed bone tissue, which originated from active osteoblasts on their surface. Histomorphometric analysis showed a significantly higher number of multinucleated giant cells and blood vessels in the NB group compared to the BO group. No statistical differences were observed in regard to connective tissue, remaining bone substitute, and newly formed bone. The results of this study highlight the different cellular reactions to synthetic and xenogeneic bone substitute materials. The significantly higher number of multinucleated giant cells within the NB implantation bed seems to have no effect on its biodegradation. Accordingly, the multinucleated giant cells observed within the NB implantation bed have characteristics more similar to those of foreign body giant cells than to those of osteoclasts.

ECSIT links TLR and BMP signaling in FOP connective tissue progenitor cells.

PubMed

Wang, Haitao; Behrens, Edward M; Pignolo, Robert J; Kaplan, Frederick S

2018-04-01

Clinical and laboratory observations strongly suggest that the innate immune system induces flare-ups in the setting of dysregulated bone morphogenetic protein (BMP) signaling in fibrodysplasia ossificans progressiva (FOP). In order to investigate the signaling substrates of this hypothesis, we examined toll-like receptor (TLR) activation and bone morphogenetic protein (BMP) signaling in connective tissue progenitor cells (CTPCs) from FOP patients and unaffected individuals. We found that inflammatory stimuli broadly activate TLR expression in FOP CTPCs and that TLR3/TLR4 signaling amplifies BMP pathway signaling through both ligand dependent and independent mechanisms. Importantly, Evolutionarily Conserved Signaling Intermediate in the Toll Pathway (ECSIT) integrates TLR injury signaling with dysregulated BMP pathway signaling in FOP CTPCs. These findings provide novel insight into the cell autonomous integration of injury signals from the innate immune system with dysregulated response signals from the BMP signaling pathway and provide new exploratory targets for therapeutic approaches to blocking the induction and amplification of FOP lesions. Copyright © 2018 Elsevier Inc. All rights reserved.

The role of adipokines in chronic inflammation

PubMed Central

Mancuso, Peter

2016-01-01

Adipose tissue has traditionally been defined as connective tissue that stores excess calories in the form of triacylglycerol. However, the physiologic functions attributed to adipose tissue are expanding, and it is now well established that adipose tissue is an endocrine gland. Among the endocrine factors elaborated by adipose tissue are the adipokines; hormones, similar in structure to cytokines, produced by adipose tissue in response to changes in adipocyte triacylglycerol storage and local and systemic inflammation. They inform the host regarding long-term energy storage and have a profound influence on reproductive function, blood pressure regulation, energy homeostasis, the immune response, and many other physiologic processes. The adipokines possess pro- and anti-inflammatory properties and play a critical role in integrating systemic metabolism with immune function. In calorie restriction and starvation, proinflammatory adipokines decline and anti-inflammatory adipokines increase, which informs the host of energy deficits and contributes to the suppression of immune function. In individuals with normal metabolic status, there is a balance of pro- and anti-inflammatory adipokines. This balance shifts to favor proinflammatory mediators as adipose tissue expands during the development of obesity. As a consequence, the proinflammatory status of adipose tissue contributes to a chronic low-grade state of inflammation and metabolic disorders associated with obesity. These disturbances are associated with an increased risk of metabolic disease, type 2 diabetes, cardiovascular disease, and many other pathological conditions. This review focuses on the impact of energy homeostasis on the adipokines in immune function. PMID:27529061

Implant-Abutment Contact Surfaces and Microgap Measurements of Different Implant Connections Under 3-Dimensional X-Ray Microtomography.

PubMed

Scarano, Antonio; Valbonetti, Luca; Degidi, Marco; Pecci, Raffaella; Piattelli, Adriano; de Oliveira, P S; Perrotti, Vittoria

2016-10-01

The presence of a microgap between implant and abutment could produce a bacterial reservoir which could interfere with the long-term health of the periimplant tissues. The aim of this article was to evaluate, by x-ray 3-dimensional microtomography, implant-abutment contact surfaces and microgaps at the implant-abutment interface in different types of implant-abutment connections. A total of 40 implants were used in this in vitro study. Ten implants presented a screw-retained internal hexagon abutment (group I), 10 had a Morse Cone taper internal connection (group II), 10 another type of Morse Cone taper internal connection (group III), and 10 had a screwed trilobed connection (group IV). In both types of Morse Cone internal connections, there was no detectable separation at the implant-abutment in the area of the conical connection, and there was an absolute congruity without any microgaps between abutment and implant. No line was visible separating the implant and the abutment. On the contrary, in the screwed abutment implants, numerous gaps and voids were present. The results of this study support the hypothesis that different types of implant-abutment joints are responsible for the observed differences in bacterial penetration.

[The effect of neoplastic disease and systemic disease of connective tissue on the occurrence of dehiscence laparotomy].

PubMed

Paunović, Milorad

2013-01-01

Dehiscence after laparotomy is one of the major complications of laparotomy. This is a partial or complete wound with disruption and evisceratio abdominal organs and require urgent reintervention. The aim of this study was to determine the impact of neoplastic disease and systemic disease of connective tissue on the occurrence of dehiscence laparotomy. A prospective study were included 612 patients operated at the Clinic for General Surgery in Nis in the period from January 2009 to December 2010. The effect of neoplastic disease and the presence of systemic disease of connective tissue on the occurrence of dehiscence laparotomy. Results are displayed numerically and in percentages. Of the total 24 patients with dehiscence laparotomy, 15 patients were male or 62.5% and 9 female patients, or 37.5%. There was a statistically significant association between dehiscence laparotomy and neoplastic diseases (c2 = 42,196; p < 0.01). There was no statistically significant association between dehiscence laparo-tomy and systemic disease of connective tissue (c2 = 0,028; p > 0.05). In patients with neoplastic diseases dehis-cence laparotomy is common, and in patients suffering from systemic disease of connective tissue dehiscence laparotomy occurs less frequently.

The versatile subepithelial connective tissue graft: a literature update.

PubMed

Karthikeyan, B V; Khanna, Divya; Chowdhary, Kamedh Yashawant; Prabhuji, M Lv

2016-01-01

Harmony between hard and soft tissue morphologies is essential for form, function, and a good esthetic outlook. Replacement grafts for correction of soft tissue defects around the teeth have become important to periodontal plastic and implant surgical procedures. Among a multitude of surgical techniques and graft materials reported in literature, the subepithelial connective tissue graft (SCTG) has gained wide popularity and acceptance. The purpose of this article is to acquaint clinicians with the current understanding of the versatile SCTG. Key factors associated with graft harvesting as well as applications, limitations, and complications of SCTGs are discussed. This connective tissue has shown excellent short- and long-term stability, is easily available, and is economical to use. The SCTG should be considered as an alternative in all periodontal reconstruction surgeries.

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

DOEpatents

Schwarz, Richard I.

2002-08-13

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

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kubota, Jun; Tsunemura, Mami; Amano, Shigeko

1997-05-15

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

An Actomyosin-Arf-GEF Negative Feedback Loop for Tissue Elongation under Stress.

PubMed

West, Junior J; Zulueta-Coarasa, Teresa; Maier, Janna A; Lee, Donghoon M; Bruce, Ashley E E; Fernandez-Gonzalez, Rodrigo; Harris, Tony J C

2017-08-07

In response to a pulling force, a material can elongate, hold fast, or fracture. During animal development, multi-cellular contraction of one region often stretches neighboring tissue. Such local contraction occurs by induced actomyosin activity, but molecular mechanisms are unknown for regulating the physical properties of connected tissue for elongation under stress. We show that cytohesins, and their Arf small G protein guanine nucleotide exchange activity, are required for tissues to elongate under stress during both Drosophila dorsal closure (DC) and zebrafish epiboly. In Drosophila, protein localization, laser ablation, and genetic interaction studies indicate that the cytohesin Steppke reduces tissue tension by inhibiting actomyosin activity at adherens junctions. Without Steppke, embryogenesis fails, with epidermal distortions and tears resulting from myosin misregulation. Remarkably, actomyosin network assembly is necessary and sufficient for local Steppke accumulation, where live imaging shows Steppke recruitment within minutes. This rapid negative feedback loop provides a molecular mechanism for attenuating the main tension generator of animal tissues. Such attenuation relaxes tissues and allows orderly elongation under stress. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

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

2008-04-01

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

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

PubMed

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

2017-07-01

In a series of previous publications we have proposed a framework for conceptualizing the optic nerve head (ONH) as a biomechanical structure. That framework proposes important roles for intraocular pressure (IOP), IOP-related stress and strain, cerebrospinal fluid pressure (CSFp), systemic and ocular determinants of blood flow, inflammation, auto-immunity, genetics, and other non-IOP related risk factors in the physiology of ONH aging and the pathophysiology of glaucomatous damage to the ONH. The present report summarizes 20 years of technique development and study results pertinent to the characterization of ONH connective tissue deformation and remodeling in the unilateral monkey experimental glaucoma (EG) model. In it we propose that the defining pathophysiology of a glaucomatous optic neuropathy involves deformation, remodeling, and mechanical failure of the ONH connective tissues. We view this as an active process, driven by astrocyte, microglial, fibroblast and oligodendrocyte mechanobiology. These cells, and the connective tissue phenomena they propagate, have primary and secondary effects on retinal ganglion cell (RGC) axon, laminar beam and retrolaminar capillary homeostasis that may initially be "protective" but eventually lead to RGC axonal injury, repair and/or cell death. The primary goal of this report is to summarize our 3D histomorphometric and optical coherence tomography (OCT)-based evidence for the early onset and progression of ONH connective tissue deformation and remodeling in monkey EG. A second goal is to explain the importance of including ONH connective tissue processes in characterizing the phenotype of a glaucomatous optic neuropathy in all species. A third goal is to summarize our current efforts to move from ONH morphology to the cell biology of connective tissue remodeling and axonal insult early in the disease. A final goal is to facilitate the translation of our findings and ideas into neuroprotective interventions that target these ONH phenomena for therapeutic effect. Copyright © 2017 Elsevier Ltd. All rights reserved.

Treatment of gingival recession defects with xenogenic collagen matrix: a histologic report.

PubMed

Camelo, Marcelo; Nevins, Myron; Nevins, Marc L; Schupbach, Peter; Kim, David M

2012-04-01

The connective tissue graft (CTG) in conjunction with a coronally advanced flap is still regarded as the gold standard treatment for gingival recession defects. Increased surgical morbidity as well as limited tissue availability continues to spur interest in alternatives to the CTG. The current case report examines a porcine-derived, double-layer collagen matrix as an alternative to the CTG in managing Miller Class I and II recession defects. A long junctional epithelial attachment as well as connective tissue adhesion were noted when collagen matrix was used in conjunction with a coronally advanced flap in recession treatment protocols. The results suggest that it is possible to obtain root coverage without harvesting connective tissue.

Modelling of Soft Connective Tissues to Investigate Female Pelvic Floor Dysfunctions.

PubMed

Bhattarai, Aroj; Staat, Manfred

2018-01-01

After menopause, decreased levels of estrogen and progesterone remodel the collagen of the soft tissues thereby reducing their stiffness. Stress urinary incontinence is associated with involuntary urine leakage due to pathological movement of the pelvic organs resulting from lax suspension system, fasciae, and ligaments. This study compares the changes in the orientation and position of the female pelvic organs due to weakened fasciae, ligaments, and their combined laxity. A mixture theory weighted by respective volume fraction of elastin-collagen fibre compound (5%), adipose tissue (85%), and smooth muscle (5%) is adopted to characterize the mechanical behaviour of the fascia. The load carrying response (other than the functional response to the pelvic organs) of each fascia component, pelvic organs, muscles, and ligaments are assumed to be isotropic, hyperelastic, and incompressible. Finite element simulations are conducted during Valsalva manoeuvre with weakened tissues modelled by reduced tissue stiffness. A significant dislocation of the urethrovesical junction is observed due to weakness of the fascia (13.89 mm) compared to the ligaments (5.47 mm). The dynamics of the pelvic floor observed in this study during Valsalva manoeuvre is associated with urethral-bladder hypermobility, greater levator plate angulation, and positive Q-tip test which are observed in incontinent females.

Modelling of Soft Connective Tissues to Investigate Female Pelvic Floor Dysfunctions

PubMed Central

2018-01-01

After menopause, decreased levels of estrogen and progesterone remodel the collagen of the soft tissues thereby reducing their stiffness. Stress urinary incontinence is associated with involuntary urine leakage due to pathological movement of the pelvic organs resulting from lax suspension system, fasciae, and ligaments. This study compares the changes in the orientation and position of the female pelvic organs due to weakened fasciae, ligaments, and their combined laxity. A mixture theory weighted by respective volume fraction of elastin-collagen fibre compound (5%), adipose tissue (85%), and smooth muscle (5%) is adopted to characterize the mechanical behaviour of the fascia. The load carrying response (other than the functional response to the pelvic organs) of each fascia component, pelvic organs, muscles, and ligaments are assumed to be isotropic, hyperelastic, and incompressible. Finite element simulations are conducted during Valsalva manoeuvre with weakened tissues modelled by reduced tissue stiffness. A significant dislocation of the urethrovesical junction is observed due to weakness of the fascia (13.89 mm) compared to the ligaments (5.47 mm). The dynamics of the pelvic floor observed in this study during Valsalva manoeuvre is associated with urethral-bladder hypermobility, greater levator plate angulation, and positive Q-tip test which are observed in incontinent females. PMID:29568322

Genetically Engineered Autologous Cells for Antiangiogenic Therapy of Breast Cancer

DTIC Science & Technology

2004-07-01

consisted of a large, fragmented avascular center surrounded by a thin band of vascularized matrix material, itself covered by a capsule of connective tissue...contained dead cells that showed features of coagulation necrosis . The minimal inflammatory response consisted of neutrophils scattered within the...vascularize most likely contributed to the death (coagulation necrosis ) of implanted MSCs localized in the implant core and to the fragmentation of the

Tumors: Wounds that do not heal--Redux

PubMed Central

Dvorak, Harold F.

2014-01-01

Similarities between tumors and the inflammatory response associated with wound healing have been recognized for more than 150 years and continue to intrigue. Some years ago, based on our then recent discovery of vascular permeability factor (VPF)/vascular endothelial growth factor (VEGF), I suggested that tumors behaved as wounds that do not heal. More particularly, I proposed that tumors co-opted the wound healing response in order to induce the stroma they required for maintenance and growth. Work over the past few decades has supported this hypothesis and has put it on a firmer molecular basis. In outline, VPF/VEGF initiates a sequence of events in both tumors and wounds that includes the following: increased vascular permeability; extravasation of plasma, fibrinogen and other plasma proteins; activation of the clotting system outside the vascular system; deposition of an extravascular fibrin gel which serves as a provisional stroma and a favorable matrix for cell migration; induction of angiogenesis and arterio-venogenesis; subsequent degradation of fibrin and its replacement by “granulation tissue” (highly vascular connective tissue); and, finally, vascular resorption and collagen synthesis, resulting in the formation of dense fibrous connective tissue (called “scar tissue” in wounds and “desmoplasia” in cancer). A similar sequence of events also takes place in a variety of important inflammatory diseases that involve cellular immunity. PMID:25568067

Development of Clinical Trial Assessments for the Study of Interstitial Lung Disease in Patients who have Connective Tissue Diseases-Methodological Considerations.

PubMed

Huscher, Dörte; Saketkoo, Lesley Ann; Pittrow, David; Khanna, Dinesh

2010-05-01

This review article discusses the proposed methodology that will be utilized to develop core set items for connective tissue disease-associated interstitial lung disease (CTD-ILD). CTD-ILD remain an important enigma in clinical medicine. No consensus exists on measurement of disease activity or what constitutes a significant response to therapeutic interventions. Lack of appropriate measures inhibit effective drug development and hamper regulatory evaluation of candidate therapies.An interdisciplinary and international Steering Committee (SC) will oversee the execution of a 3-tier Delphi exercise involving experts in CTD and ILD. In parallel to the Delphi, qualitative information will be gathered from patients with ILD using focus groups. These data will subsequently be used to construct surveys to collect quantitative response from patients with ILD. The final Delphi and Patient Perspective results are to be scrutinized by SC and specialty sub-groups (including patient advocates) for truth, discrimination and feasibility - the OMERACT filters. Through application of Nominal Group technique, a core set of outcome measures will be proposed. Subsequent exercises will evaluate the applicability of a proposed core set to the unique issues posed by individual CTDs in addition to guidelines on screening, prognostication and damage scoring.

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

PubMed

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

2017-05-01

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

Development of Vibrational Culture Model Mimicking Vocal Fold Tissues.

PubMed

Kim, Dongjoo; Lim, Jae-Yol; Kwon, Soonjo

2016-10-01

The vocal folds (VFs) are connective tissues with complex matrix structures that provide the required mechanical properties for voice generation. VF injury leads to changes in tissue structure and properties, resulting in reduced voice quality. However, injury-induced biochemical changes and repair in scarred VF tissues have not been well characterized to date. To treat scarred VFs, it is essential to understand how physiological characteristics of VFs tissue change in response to external perturbation. In this study, we designed a simple vibrational culture model to mimic vibratory microenvironments observed in vivo. This model consists of a flexible culture plate, three linear actuators, a stereo splitter, and a function generator. Human vocal fold fibroblast (hVFF) monolayers were established on the flexible membrane, to which normal phonatory vibrations were delivered from linear actuators and a function generator. The hVFF monolayers were exposed to the vibrational stresses at a frequency of 205 Hz for 2, 6, and 10 h with maximum displacement of 47.1 μm, followed by a 6 h rest. We then observed the changes in cell morphology, cell viability, and gene expression related to extracellular matrix components. In our dynamic culture device mimicking normal phonatory frequencies, cell proliferation increased and expression of hyaluronic acid synthase 2 was downregulated in response to vibrational stresses. The results presented herein will be useful for evaluating cellular responses following VF injuries in the presence or absence of vibrational stresses.

Phosphaturic mesenchymal tumour-mixed connective tissue variant without oncogenic osteomalacia.

PubMed

Winters, R; Bihlmeyer, S; McCahill, L; Cooper, K

2009-08-01

Phosphaturic mesenchymal tumour-mixed connective tissue variant is a rare tumour classically associated with oncogenic osteomalacia. This report describes two patients with this distinct tumour type but with no evidence of the paraneoplastic syndrome.

Parvovirus B19 infection in an adult presenting with connective tissue disease-like symptoms: a report of the clinical and histological findings.

PubMed

Liles, J E; Shalin, S C; White, B A; Trigg, L B; Kaley, J R

2017-06-15

Parvovirus B19 infections in adults are usually associated with nonspecific and mild symptoms. However, cases presenting with a lupus-like syndrome have been described, leading to the hypothesis that parvovirus infection can induce connective tissue disease. Various histopathologic features of cutaneous manifestations of parvovirus have been reported, including features which overlap with those of connective tissue disease. Herein, we discuss an unusual case of Parvovirus  B19 infection in a middle-aged woman. The biopsy results showed granulomatous vasculitis and were consistent with the previously described superantigen id reaction. This case demonstrates that infectious causes should be considered in the differential diagnosis for granulomatous vasculitis and clinicopathologic correlation is required for accurate diagnosis. We also provide a review of the literature highlighting the possible role of parvovirus in induction of a connective tissue disease-like presentation.

WE-DE-202-00: Connecting Radiation Physics with Computational Biology

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

Radiation therapy for the treatment of cancer has been established as a highly precise and effective way to eradicate a localized region of diseased tissue. To achieve further significant gains in the therapeutic ratio, we need to move towards biologically optimized treatment planning. To achieve this goal, we need to understand how the radiation-type dependent patterns of induced energy depositions within the cell (physics) connect via molecular, cellular and tissue reactions to treatment outcome such as tumor control and undesirable effects on normal tissue. Several computational biology approaches have been developed connecting physics to biology. Monte Carlo simulations are themore » most accurate method to calculate physical dose distributions at the nanometer scale, however simulations at the DNA scale are slow and repair processes are generally not simulated. Alternative models that rely on the random formation of individual DNA lesions within one or two turns of the DNA have been shown to reproduce the clusters of DNA lesions, including single strand breaks (SSBs), double strand breaks (DSBs) without the need for detailed track structure simulations. Efficient computational simulations of initial DNA damage induction facilitate computational modeling of DNA repair and other molecular and cellular processes. Mechanistic, multiscale models provide a useful conceptual framework to test biological hypotheses and help connect fundamental information about track structure and dosimetry at the sub-cellular level to dose-response effects on larger scales. In this symposium we will learn about the current state of the art of computational approaches estimating radiation damage at the cellular and sub-cellular scale. How can understanding the physics interactions at the DNA level be used to predict biological outcome? We will discuss if and how such calculations are relevant to advance our understanding of radiation damage and its repair, or, if the underlying biological processes are too complex for a mechanistic approach. Can computer simulations be used to guide future biological research? We will debate the feasibility of explaining biology from a physicists’ perspective. Learning Objectives: Understand the potential applications and limitations of computational methods for dose-response modeling at the molecular, cellular and tissue levels Learn about mechanism of action underlying the induction, repair and biological processing of damage to DNA and other constituents Understand how effects and processes at one biological scale impact on biological processes and outcomes on other scales J. Schuemann, NCI/NIH grantsS. McMahon, Funding: European Commission FP7 (grant EC FP7 MC-IOF-623630)« less

WE-DE-202-01: Connecting Nanoscale Physics to Initial DNA Damage Through Track Structure Simulations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schuemann, J.

Radiation therapy for the treatment of cancer has been established as a highly precise and effective way to eradicate a localized region of diseased tissue. To achieve further significant gains in the therapeutic ratio, we need to move towards biologically optimized treatment planning. To achieve this goal, we need to understand how the radiation-type dependent patterns of induced energy depositions within the cell (physics) connect via molecular, cellular and tissue reactions to treatment outcome such as tumor control and undesirable effects on normal tissue. Several computational biology approaches have been developed connecting physics to biology. Monte Carlo simulations are themore » most accurate method to calculate physical dose distributions at the nanometer scale, however simulations at the DNA scale are slow and repair processes are generally not simulated. Alternative models that rely on the random formation of individual DNA lesions within one or two turns of the DNA have been shown to reproduce the clusters of DNA lesions, including single strand breaks (SSBs), double strand breaks (DSBs) without the need for detailed track structure simulations. Efficient computational simulations of initial DNA damage induction facilitate computational modeling of DNA repair and other molecular and cellular processes. Mechanistic, multiscale models provide a useful conceptual framework to test biological hypotheses and help connect fundamental information about track structure and dosimetry at the sub-cellular level to dose-response effects on larger scales. In this symposium we will learn about the current state of the art of computational approaches estimating radiation damage at the cellular and sub-cellular scale. How can understanding the physics interactions at the DNA level be used to predict biological outcome? We will discuss if and how such calculations are relevant to advance our understanding of radiation damage and its repair, or, if the underlying biological processes are too complex for a mechanistic approach. Can computer simulations be used to guide future biological research? We will debate the feasibility of explaining biology from a physicists’ perspective. Learning Objectives: Understand the potential applications and limitations of computational methods for dose-response modeling at the molecular, cellular and tissue levels Learn about mechanism of action underlying the induction, repair and biological processing of damage to DNA and other constituents Understand how effects and processes at one biological scale impact on biological processes and outcomes on other scales J. Schuemann, NCI/NIH grantsS. McMahon, Funding: European Commission FP7 (grant EC FP7 MC-IOF-623630)« less

THE LOCALIZATION OF HOMOLGOUS PLASMA PROTEINS IN THE TISSUES OF YOUNG HUMAN BEINGS AS DEMONSTRATED WITH FLUORESCENT ANTIBODIES

PubMed Central

Gitlin, David; Landing, Benjamin H.; Whipple, Ann

1953-01-01

Employing fluorescent antibodies for the detection of homologous plasma proteins in tissue sections, the distribution of plasma albumin, γ-globulin, β-lipoprotein, β1-metal-combining globulin, and fibrinogen has been studied in the tissues of infants and children. Plasma albumin, γ-globulin, and β1-metal-combining globulin were found in many cells and particularly cell nuclei, connective tissues and interstitial spaces, lymphatics, and blood vessels. β-Lipoprotein was found mostly in the nuclei of all cell types while fibrinogen was restricted largely to the lymphatic and vascular channels, connective tissues and the interstitial spaces. The widespread distribution of these plasma proteins in cells and connective tissues indicates the magnitude of the extravascular plasma protein pool which is in equilibrium with circulating plasma. Unfortunately, these results do not permit accurate localization of the sites of production of these plasma proteins, but do give some idea of their intimate relationship to the tissues. PMID:13022871

Bone tissue formation in extraction sockets from sites with advanced periodontal disease: a histomorphometric study in humans.

PubMed

Ahn, Jae-Jin; Shin, Hong-In

2008-01-01

To investigate postextraction bone formation over time in both diseased and healthy sockets. Core specimens of healing tissues following tooth extraction were obtained at the time of implant placement in patients treated between October 2005 and December 2007. A disease group and a control group were classified according to socket examination at the time of extraction. The biopsy specimens were analyzed histomorphometrically to measure the dimensional changes among 3 tissue types: epithelial layer, connective tissue area, and new bone tissue area. Fifty-five specimens from sites of previously advanced periodontal disease from 45 patients were included in the disease group. Another 12 specimens of previously healthy extraction sockets were collected from 12 different patients as a control. The postextraction period of the disease group varied from 2 to 42 weeks. In the disease group, connective tissue occupied most of the socket during the first 4 weeks. New bone area progressively replaced the connective tissue area after the first 4 weeks. The area proportion of new bone tissue exceeded that of connective tissue by 14 weeks. After 20 weeks, most extraction sockets in the disease group demonstrated continuous new bone formation. The control group exhibited almost complete socket healing after 10 weeks, with no more new bone formation after 20 weeks. Osseous regeneration in the diseased sockets developed more slowly than in the disease-free sockets. After 16 weeks, new bone area exceeded 50% of the total newly regenerated tissue in the sockets with severe periodontal destruction. In the control group, after 8 weeks, new bone area exceeded 50% of the total tissue.

Optic nerve head biomechanics in aging and disease.

PubMed

Downs, J Crawford

2015-04-01

This nontechnical review is focused upon educating the reader on optic nerve head biomechanics in both aging and disease along two main themes: what is known about how mechanical forces and the resulting deformations are distributed in the posterior pole and ONH (biomechanics) and what is known about how the living system responds to those deformations (mechanobiology). We focus on how ONH responds to IOP elevations as a structural system, insofar as the acute mechanical response of the lamina cribrosa is confounded with the responses of the peripapillary sclera, prelaminar neural tissues, and retrolaminar optic nerve. We discuss the biomechanical basis for IOP-driven changes in connective tissues, blood flow, and cellular responses. We use glaucoma as the primary framework to present the important aspects of ONH biomechanics in aging and disease, as ONH biomechanics, aging, and the posterior pole extracellular matrix (ECM) are thought to be centrally involved in glaucoma susceptibility, onset and progression. Copyright © 2015 Elsevier Ltd. All rights reserved.

Spontaneous coronary artery dissection and its association with heritable connective tissue disorders.

PubMed

Henkin, Stanislav; Negrotto, Sara M; Tweet, Marysia S; Kirmani, Salman; Deyle, David R; Gulati, Rajiv; Olson, Timothy M; Hayes, Sharonne N

2016-06-01

Spontaneous coronary artery dissection (SCAD) is an under-recognised but important cause of myocardial infarction and sudden cardiac death. We sought to determine the role of medical and molecular genetic screening for connective tissue disorders in patients with SCAD. We performed a single-centre retrospective descriptive analysis of patients with spontaneous coronary artery disease who had undergone medical genetics evaluation 1984-2014 (n=116). The presence or absence of traits suggestive of heritable connective tissue disease was extracted. Genetic testing for connective tissue disorders and/or aortopathies, if performed, is also reported. Of the 116 patients (mean age 44.2 years, 94.8% women and 41.4% with non-coronary fibromuscular dysplasia (FMD)), 59 patients underwent genetic testing, of whom 3 (5.1%) received a diagnosis of connective tissue disorder: a 50-year-old man with Marfan syndrome; a 43-year-old woman with vascular Ehlers-Danlos syndrome and FMD; and a 45-year-old woman with vascular Ehlers-Danlos syndrome. An additional 12 patients (20.3%) had variants of unknown significance, none of which was thought to be a definite disease-causing mutation based on in silico analyses. Only a minority of patients with SCAD who undergo genetic evaluation have a likely pathogenic mutation identified on gene panel testing. Even fewer exhibit clinical features of connective tissue disorder. These findings underscore the need for further studies to elucidate the molecular mechanisms of SCAD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Effect of Tissucol on connective tissue matrix during wound healing: an immunohistochemical study in rat skin.

PubMed

Romanos, G E; Strub, J R

1998-03-05

Fibrin sealants are very useful in different surgical fields. Fixation of free gingival grafts, root coverage procedures, and other techniques increasing connective tissue attachment may be associated with the application of Tissucol in periodontology. The aim of this study was to evaluate the influence of the fibrin sealant in the extracellular matrix, as well as alterations of the connective tissue matrix during wound-healing processes. In the back dermis of 15 Net male rats, Tissucol was implanted after intraperitoneal anesthesia. The implant material was placed in subcutaneous pockets (2 cm in length) which were sutured with interproximal sutures (test and control pockets). At 4, 7, 14, 21, and 28 days after surgery, biopsies of the healed and surrounding tissues were taken, frozen in liquid nitrogen, and examined histologically and immunohistochemically with antibodies against collagen types I, III, IV, V, VI, and VII. The findings showed thick and thin collagen type I and III fibers, respectively, with different orientations localized around the implant material. An increased amount of blood vessels and capillaries (their basement membranes containing collagen type IV) was observed during wound healing which may be associated with the implantation of the sealant. Collagen type V fibers were localized from the first days to the 4th postoperative week and, without any inflammatory reaction (according to histologic staining), formed a fibrillar extracellular matrix with high collagenase resistance. Collagen type VI showed a microfibrillar pattern of distribution, and collagen type VII was localized in the dermo epidermo junction and very deep in the connective tissue in the form of anchoring fibers (only in the test group) during the 4 postoperative weeks of healing. The data showed that Tissucol is a biocompatible component which cannot produce any extensive inflammatory reaction in the matrix. New blood vessel formation, an epithelial-connective tissue interface with high stability, as well as matrix alterations with high resistance in the proteolytic enzymes (i.e., collagenases) can be induced in the connective tissue after use of a fibrin sealant. All of these characteristics may be of great importance in connective tissue healing in periodontal surgical procedures.

Microgravity Stress: Bone and Connective Tissue.

PubMed

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

2016-03-15

The major alterations in bone and the dense connective tissues in humans and animals exposed to microgravity illustrate the dependency of these tissues' function on normal gravitational loading. Whether these alterations depend solely on the reduced mechanical loading of zero g or are compounded by fluid shifts, altered tissue blood flow, radiation exposure, and altered nutritional status is not yet well defined. Changes in the dense connective tissues and intervertebral disks are generally smaller in magnitude but occur more rapidly than those in mineralized bone with transitions to 0 g and during recovery once back to the loading provided by 1 g conditions. However, joint injuries are projected to occur much more often than the more catastrophic bone fracture during exploration class missions, so protecting the integrity of both tissues is important. This review focuses on the research performed over the last 20 years in humans and animals exposed to actual spaceflight, as well as on knowledge gained from pertinent ground-based models such as bed rest in humans and hindlimb unloading in rodents. Significant progress has been made in our understanding of the mechanisms for alterations in bone and connective tissues with exposure to microgravity, but intriguing questions remain to be solved, particularly with reference to biomedical risks associated with prolonged exploration missions. Copyright © 2016 John Wiley & Sons, Inc.

Polydopamine deposition with anodic oxidation for better connective tissue attachment to transmucosal implants.

PubMed

Teng, F; Chen, H; Xu, Y; Liu, Y; Ou, G

2018-04-01

Nowadays, most designs for the transmucosal surface of implants are machined-smooth. However, connective tissue adhered to the smooth surface of an implant has poor mechanical resistance, which can render separation of tissue from the implant interface and induce epithelial downgrowth. Modification of the transmucosal surface of implants, which can help form a good seal of connective tissue, is therefore desired. We hypothesized that anodic oxidation (AO) and polydopamine (PD) deposition could be used to enhance the attachment between an implant and peri-implant connective tissue. We tested this hypothesis in the mandibles of Beagle dogs. AO and PD were used to modify the transmucosal region of transmucosal implants (implant neck). The surface microstructure, surface roughness and elemental composition were investigated in vitro. L929 mouse fibroblasts were cultured to test the effect of PD on cell adhesion. Six Beagle dogs were used for the in vivo experiment (n = 6 dogs per group). Three months after building the edentulous animal model, four groups of implants (control, AO, PD and AO + PD) were inserted. After 4 months of healing, samples were harvested for histometric analyses. The surfaces of anodized implant necks were overlaid with densely distributed pores, 2-7 μm in size. On the PD-modified surfaces, N1s, the chemical bond of nitrogen in PD, was detected using X-ray photoelectron spectroscopy. L929 developed pseudopods more quickly on the PD-modified surfaces than on the surfaces of the control group. The in vivo experiment showed a longer connective tissue seal and a more coronally located peri-implant soft-tissue attachment in the AO + PD group than in the control group (P < .05). The modification of AO + PD on the implant neck yielded better attachment between the implant and peri-implant connective tissue. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Exostosis following a subepithelial connective tissue graft.

PubMed

Corsair, A J; Iacono, V J; Moss, S S

2001-04-01

This case report describes the formation of an unusual unaesthetic gingival enlargement during a five year post operative period subsequent to a subepithelial connective tissue graft placed facial to teeth #4 and #6. Histological assessment of the enlarged tissue indicated that it consisted of viable bone and marrow. The exostosis was reduced with rotary instruments and acceptable soft tissue aesthetics were created using a carbon dioxide laser for gingivoplasty. Possible causes for this unusual enlargement are discussed.

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

PubMed

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

2016-08-01

For 3-dimensional (3D) imaging of a tissue, 3 methodological steps are essential and their successful application depends on specific characteristics of the type of tissue. The steps are 1° clearing of the opaque tissue to render it transparent for microscopy, 2° fluorescence labeling of the tissues and 3° 3D imaging. In the past decades, new methodologies were introduced for the clearing steps with their specific advantages and disadvantages. Most clearing techniques have been applied to the central nervous system and other organs that contain relatively low amounts of connective tissue including extracellular matrix. However, tissues that contain large amounts of extracellular matrix such as dermis in skin or gingiva are difficult to clear. The present survey lists methodologies that are available for clearing of tissues for 3D imaging. We report here that the BABB method using a mixture of benzyl alcohol and benzyl benzoate and iDISCO using dibenzylether (DBE) are the most successful methods for clearing connective tissue-rich gingiva and dermis of skin for 3D histochemistry and imaging of fluorescence using light-sheet microscopy. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

Prevaccination with SRL172 (heat-killed Mycobacterium vaccae) inhibits experimental periodontal disease in Wistar rats

PubMed Central

Breivik, T; Rook, G A W

2000-01-01

Periodontal disease is a bacterial dental plaque-induced destructive inflammatory condition of the tooth-supporting tissues, which is thought to be mediated by T lymphocytes secreting T helper 2 (Th2) cytokines, resulting in recruitment of high numbers of antibody-producing B lymphocytes/plasma cells as well as polymorphonuclear leucocytes (PMN) secreting tissue-destructive components, such at matrix metalloproteinases and reactive oxygen metabolites into the gingival connective tissues. One treatment strategy may be to down-regulate the Th2 response to those dental plaque microorganisms which induce the destructive inflammatory response. In this study we have examined the effects of a potent down-regulator of Th2 responses on ligature-induced periodontal disease in an experimental rat model. A single s.c. injection into Wistar rats of 0·1 or 1 mg of SRL172, a preparation of heat-killed Mycobacterium vaccae (NCTC 11659), 13 days before application of the ligature, significantly reduced the subsequent destruction of the tooth-supporting tissues, as measured by loss of periodontal attachment fibres (P < 0·001) and bone (P < 0·002). This protective effect occurred not only on the experimental (ligatured) side but also on the control unligatured side. SRL172 has undergone extensive toxicological studies and safety assessments in humans, and it is suggested that it may provide a safe and novel therapeutic approach to periodontal disease. PMID:10844524

Connective tissue ulcers.

PubMed

Dabiri, Ganary; Falanga, Vincent

2013-11-01

Connective tissue disorders (CTD), which are often also termed collagen vascular diseases, include a number of related inflammatory conditions. Some of these diseases include rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis (scleroderma), localized scleroderma (morphea variants localized to the skin), Sjogren's syndrome, dermatomyositis, polymyositis, and mixed connective tissue disease. In addition to the systemic manifestations of these diseases, there are a number of cutaneous features that make these conditions recognizable on physical exam. Lower extremity ulcers and digital ulcers are an infrequent but disabling complication of long-standing connective tissue disease. The exact frequency with which these ulcers occur is not known, and the cause of the ulcerations is often multifactorial. Moreover, a challenging component of CTD ulcerations is that there are still no established guidelines for their diagnosis and treatment. The morbidity associated with these ulcerations and their underlying conditions is very substantial. Indeed, these less common but intractable ulcers represent a major medical and economic problem for patients, physicians and nurses, and even well organized multidisciplinary wound healing centers. Copyright © 2013 Tissue Viability Society. Published by Elsevier Ltd. All rights reserved.

Outcomes of sympathectomy and vascular bypass for digital ischaemia in connective tissue disorders.

PubMed

Shammas, R L; Hwang, B H; Levin, L S; Richard, M J; Ruch, D S; Mithani, S K

2017-10-01

All patients (36 hands) with connective tissue disorders who underwent periarterial sympathectomy of the hand alone or in conjunction with vascular bypass at our institution between 1995-2013 were reviewed. The durable resolution of ulcers was significantly higher in patients treated by periarterial sympathectomy and bypass than in patients treated by periarterial sympathectomy alone. Although there were more digital amputations in patients treated by periarterial sympathectomy alone, the difference was not statistically significant. Vascular bypass in conjunction with sympathectomy may be better than sympathectomy alone in patients with digital ischaemia related to connective tissue disorders. IV.

Personal Authentication Analysis Using Finger-Vein Patterns in Patients with Connective Tissue Diseases—Possible Association with Vascular Disease and Seasonal Change -

PubMed Central

Kono, Miyuki; Miura, Naoto; Fujii, Takao; Ohmura, Koichiro; Yoshifuji, Hajime; Yukawa, Naoichiro; Imura, Yoshitaka; Nakashima, Ran; Ikeda, Takaharu; Umemura, Shin-ichiro; Miyatake, Takafumi; Mimori, Tsuneyo

2015-01-01

Objective To examine how connective tissue diseases affect finger-vein pattern authentication. Methods The finger-vein patterns of 68 patients with connective tissue diseases and 24 healthy volunteers were acquired. Captured as CCD (charge-coupled device) images by transmitting near-infrared light through fingers, they were followed up in once in each season for one year. The similarity of the follow-up patterns and the initial one was evaluated in terms of their normalized cross-correlation C. Results The mean C values calculated for patients tended to be lower than those calculated for healthy volunteers. In midwinter (February in Japan) they showed statistically significant reduction both as compared with patients in other seasons and as compared with season-matched healthy controls, whereas the values calculated for healthy controls showed no significant seasonal changes. Values calculated for patients with systemic sclerosis (SSc) or mixed connective tissue disease (MCTD) showed major reductions in November and, especially, February. Patients with rheumatoid arthritis (RA) and patients with dermatomyositis or polymyositis (DM/PM) did not show statistically significant seasonal changes in C values. Conclusions Finger-vein patterns can be used throughout the year to identify patients with connective tissue diseases, but some attention is needed for patients with advanced disease such as SSc. PMID:26701644

Recessive and dominant mutations in COL12A1 cause a novel EDS/myopathy overlap syndrome in humans and mice

PubMed Central

Zou, Yaqun; Zwolanek, Daniela; Izu, Yayoi; Gandhy, Shreya; Schreiber, Gudrun; Brockmann, Knut; Devoto, Marcella; Tian, Zuozhen; Hu, Ying; Veit, Guido; Meier, Markus; Stetefeld, Jörg; Hicks, Debbie; Straub, Volker; Voermans, Nicol C.; Birk, David E.; Barton, Elisabeth R.; Koch, Manuel; Bönnemann, Carsten G.

2014-01-01

Collagen VI-related myopathies are disorders of connective tissue presenting with an overlap phenotype combining clinical involvement from the muscle and from the connective tissue. Not all patients displaying related overlap phenotypes between muscle and connective tissue have mutations in collagen VI. Here, we report a homozygous recessive loss of function mutation and a de novo dominant mutation in collagen XII (COL12A1) as underlying a novel overlap syndrome involving muscle and connective tissue. Two siblings homozygous for a loss of function mutation showed widespread joint hyperlaxity combined with weakness precluding independent ambulation, while the patient with the de novo missense mutation was more mildly affected, showing improvement including the acquisition of walking. A mouse model with inactivation of the Col12a1 gene showed decreased grip strength, a delay in fiber-type transition and a deficiency in passive force generation while the muscle seems more resistant to eccentric contraction induced force drop, indicating a role for a matrix-based passive force-transducing elastic element in the generation of the weakness. This new muscle connective tissue overlap syndrome expands on the emerging importance of the muscle extracellular matrix in the pathogenesis of muscle disease. PMID:24334604

Esophageal involvement and interstitial lung disease in mixed connective tissue disease.

PubMed

Fagundes, M N; Caleiro, M T C; Navarro-Rodriguez, T; Baldi, B G; Kavakama, J; Salge, J M; Kairalla, R; Carvalho, C R R

2009-06-01

Mixed connective tissue disease is a systemic inflammatory disorder that results in both pulmonary and esophageal manifestations. We sought to evaluate the relationship between esophageal dysfunction and interstitial lung disease in patients with mixed connective tissue disease. We correlated the pulmonary function data and the high-resolution computed tomography findings of interstitial lung disease with the results of esophageal evaluation in manometry, 24-hour intraesophageal pH measurements, and the presence of esophageal dilatation on computed tomography scan. Fifty consecutive patients with mixed connective tissue disease, according to Kasukawa's classification criteria, were included in this prospective study. High-resolution computed tomography parenchymal abnormalities were present in 39 of 50 patients. Esophageal dilatation, gastroesophageal reflux, and esophageal motor impairment were also very prevalent (28 of 50, 18 of 36, and 30 of 36, respectively). The presence of interstitial lung disease on computed tomography was significantly higher among patients with esophageal dilatation (92% vs. 45%; p<0.01) and among patients with severe motor dysfunction (90% vs. 35%; p<0.001). Although we were not able to prove a causal relationship between esophageal and pulmonary involvement, our series revealed a strong association between esophageal motor dysfunction and interstitial lung disease in patients with mixed connective tissue disease.

PDGFRα plays a crucial role in connective tissue remodeling.

PubMed

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

2015-12-07

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

PDGFRα plays a crucial role in connective tissue remodeling

PubMed Central

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

2015-01-01

Platelet derived growth factor (PDGF) plays a pivotal role in the remodeling of connective tissues. Emerging data indicate the distinctive role of PDGF receptor-α (PDGFRα) in this process. In the present study, the Pdgfra gene was systemically inactivated in adult mouse (α-KO mouse), and the role of PDGFRα was examined in the subcutaneously implanted sponge matrices. PDGFRα expressed in the fibroblasts of Pdgfra-preserving control mice (Flox mice), was significantly reduced in the sponges in α-KO mice. Neovascularized areas were largely suppressed in the α-KO mice than in the Flox mice, whereas the other parameters related to the blood vessels and endothelial cells were similar. The deposition of collagen and fibronectin and the expression of collagen 1a1 and 3a1 genes were significantly reduced in α-KO mice. There was a significantly decrease in the number and dividing fibroblasts in the α-KO mice, and those of macrophages were similar between the two genotypes. Hepatocyte growth factor (Hgf) gene expression was suppressed in Pdgfra-inactivated fibroblasts and connective tissue. The findings implicate the role of PDGFRα-dependent ECM and HGF production in fibroblasts that promotes the remodeling of connective tissue and suggest that PDGFRα may be a relevant target to regulate connective tissue remodeling. PMID:26639755

Severe periodontitis in Marfan's syndrome: a case report.

PubMed

Straub, Antje M; Grahame, Rodney; Scully, Crispian; Tonetti, Maurizio S

2002-07-01

Connective tissue disorders, such as some forms of Ehlers-Danlos syndrome, have been associated with severe periodontitis. This report describes a case of Marfan's syndrome, an inherited disorder of connective tissue caused by mutations in the fibrillin-1 gene, in which the patient presented with severe periodontitis. At examination, an average full-mouth clinical attachment level loss of 5.6+/-2.1 mm, furcation involvement, and severe alveolar bone loss were observed in a 41-year-old Caucasian male. Tooth hypermobility was also present. This case appears to be the first documentation of severe periodontitis in a patient with Marfan's syndrome. It supports the hypothesis that a variety of connective tissue disorders may confer increased susceptibility to periodontal tissue breakdown.

Comparative clinical study of a subepithelial connective tissue graft and acellular dermal matrix graft for the treatment of gingival recessions: six- to 12-month changes.

PubMed

de Souza, Sérgio Luís Scombatti; Novaes, Arthur Belém; Grisi, Daniela Corrêa; Taba, Mário; Grisi, Márcio Fernando de Moraes; de Andrade, Patrícia Freitas

2008-07-01

Different techniques have been proposed for the treatment of gingival recession. This study compared the clinical results of gingival recession treatment using a subepithelial connective tissue graft and an acellular dermal matrix allograft. Seven patients with bilateral Miller class I or II gingival recession were selected. Twenty-six recessions were treated and randomly assigned to the test group. In each case the contralateral recession was assigned to the control group. In the control group, a connective tissue graft in combination with a coronally positioned flap was used; in the test group, an acellular dermal matrix allograft was used as a substitute for palatal donor tissue. Probing depth, clinical attachment level, gingival recession, and width of keratinized tissue were measured two weeks prior to surgery and at six and 12 months post-surgery. There were no statistically significant differences between the groups in terms of recession reduction, clinical attachment gain, probing pocket depth, and increase in the width of the keratinized tissue after six or 12 months. There was no statistically significant increase in the width of keratinized tissue between six and 12 months for either group. Within the limitations of this study, it can be suggested that the acellular dermal matrix allograft may be a substitute for palatal donor tissue in root coverage procedures and that the time required for additional gain in the amount of keratinized tissue may be greater for the acellular dermal matrix than for the connective tissue procedures.

Viscoelastic Properties of Human Tracheal Tissues.

PubMed

Safshekan, Farzaneh; Tafazzoli-Shadpour, Mohammad; Abdouss, Majid; Shadmehr, Mohammad B

2017-01-01

The physiological performance of trachea is highly dependent on its mechanical behavior, and therefore, the mechanical properties of its components. Mechanical characterization of trachea is key to succeed in new treatments such as tissue engineering, which requires the utilization of scaffolds which are mechanically compatible with the native human trachea. In this study, after isolating human trachea samples from brain-dead cases and proper storage, we assessed the viscoelastic properties of tracheal cartilage, smooth muscle, and connective tissue based on stress relaxation tests (at 5% and 10% strains for cartilage and 20%, 30%, and 40% for smooth muscle and connective tissue). After investigation of viscoelastic linearity, constitutive models including Prony series for linear viscoelasticity and quasi-linear viscoelastic, modified superposition, and Schapery models for nonlinear viscoelasticity were fitted to the experimental data to find the best model for each tissue. We also investigated the effect of age on the viscoelastic behavior of tracheal tissues. Based on the results, all three tissues exhibited a (nonsignificant) decrease in relaxation rate with increasing the strain, indicating viscoelastic nonlinearity which was most evident for cartilage and with the least effect for connective tissue. The three-term Prony model was selected for describing the linear viscoelasticity. Among different models, the modified superposition model was best able to capture the relaxation behavior of the three tracheal components. We observed a general (but not significant) stiffening of tracheal cartilage and connective tissue with aging. No change in the stress relaxation percentage with aging was observed. The results of this study may be useful in the design and fabrication of tracheal tissue engineering scaffolds.

Microfocused ultrasound for skin tightening.

PubMed

MacGregor, Jennifer L; Tanzi, Elizabeth L

2013-03-01

The demand for noninvasive skin tightening procedures is increasing as patients seek safe and effective alternatives to aesthetic surgical procedures of the face, neck, and body. Over the past decade, radiofrequency and infrared laser devices have been popularized owing to their ability to deliver controlled heat to the dermis, stimulate neocollagenesis, and effect modest tissue tightening with minimal recovery. However, these less invasive approaches are historically associated with inferior efficacy so that surgery still remains the treatment of choice to address moderate to severe tissue laxity. Microfocused ultrasound was recently introduced as a novel energy modality for transcutaneous heat delivery that reaches the deeper subdermal connective tissue in tightly focused zones at consistent programmed depths. The goal is to produce a deeper wound healing response at multiple levels with robust collagen remodeling and a more durable clinical response. The Ulthera device (Ulthera, Inc, Meza, AZ), with refined microfocused ultrasound technology, has been adapted specifically for skin tightening and lifting with little recovery or risk of complications since its introduction in 2009. As clinical parameters are studied and optimized, enhanced efficacy and consistency of clinical improvement is expected.

The clinical and pathological characteristics of nephropathies in connective tissue diseases in the Japan Renal Biopsy Registry (J-RBR).

PubMed

Ichikawa, Kazunobu; Konta, Tsuneo; Sato, Hiroshi; Ueda, Yoshihiko; Yokoyama, Hitoshi

2017-12-01

In connective tissue diseases, a wide variety of glomerular, tubulointerstitial, and vascular lesions of the kidney are observed. Nonetheless, recent information is limited regarding renal lesions in connective tissue diseases, except in systemic lupus erythematosus (SLE). In this study, we used a nationwide database of biopsy-confirmed renal diseases in Japan (J-RBR) (UMIN000000618). In total, 20,523 registered patients underwent biopsy between 2007 and 2013; from 110 patients with connective tissue diseases except SLE, we extracted data regarding the clinico-pathological characteristics of the renal biopsy. Our analysis included patients with rheumatoid arthritis (RA) (n = 52), Sjögren's syndrome (SjS) (n = 35), scleroderma (n = 10), mixed connective tissue disease (MCTD; n = 5), anti-phospholipid syndrome (APS; n = 3), polymyositis/dermatomyositis (PM/DM; n = 1), Behçet's disease (n = 1) and others (n = 3). The clinico-pathological features differed greatly depending on the underlying disease. The major clinical diagnosis was nephrotic syndrome in RA; chronic nephritic syndrome with mild proteinuria and reduced renal function in SjS; rapidly progressive nephritic syndrome in scleroderma. The major pathological diagnosis was membranous nephropathy (MN) and amyloidosis in RA; tubulointerstitial nephritis in SjS; proliferative obliterative vasculopathy in scleroderma; MN in MCTD. In RA, most patients with nephrosis were treated using bucillamine, and showed membranous nephropathy. Using the J-RBR database, our study revealed that biopsy-confirmed cases of connective tissue diseases such as RA, SjS, scleroderma, and MCTD show various clinical and pathological characteristics, depending on the underlying diseases and the medication used.

An extended OpenSim knee model for analysis of strains of connective tissues.

PubMed

Marieswaran, M; Sikidar, Arnab; Goel, Anu; Joshi, Deepak; Kalyanasundaram, Dinesh

2018-04-17

OpenSim musculoskeletal models provide an accurate simulation environment that eases limitations of in vivo and in vitro studies. In this work, a biomechanical knee model was formulated with femoral articular cartilages and menisci along with 25 connective tissue bundles representing ligaments and capsules. The strain patterns of the connective tissues in the presence of femoral articular cartilage and menisci in the OpenSim knee model was probed in a first of its kind study. The effect of knee flexion (0°-120°), knee rotation (- 40° to 30°) and knee adduction (- 15° to 15°) on the anterior cruciate, posterior cruciate, medial collateral, lateral collateral ligaments and other connective tissues were studied by passive simulation. Further, a new parameter for assessment of strain namely, the differential inter-bundle strain of the connective tissues were analyzed to provide new insights for injury kinematics. ACL, PCL, LCL and PL was observed to follow a parabolic strain pattern during flexion while MCL represented linear strain patterns. All connective tissues showed non-symmetric parabolic strain variation during rotation. During adduction, the strain variation was linear for the knee bundles except for FL, PFL and TL. Strains higher than 0.1 were observed in most of the bundles during lateral rotation followed by abduction, medial rotation and adduction. In the case of flexion, highest strains were observed in aACL and aPCL. A combination of strains at a flexion of 0° with medial rotation of 30° or a flexion of 80° with rotation of 30° are evaluated as rupture-prone kinematics.

Selective reactivation of human herpesvirus 6 in patients with autoimmune connective tissue diseases.

PubMed

Broccolo, Francesco; Drago, Francesco; Cassina, Giulia; Fava, Andrea; Fusetti, Lisa; Matteoli, Barbara; Ceccherini-Nelli, Luca; Sabbadini, Maria Grazia; Lusso, Paolo; Parodi, Aurora; Malnati, Mauro S

2013-11-01

Viral infections have been associated with autoimmune connective tissue diseases. To evaluate whether active infection by Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus (HHV)-6, -7, -8, as well as parvovirus B19 (B19V) occur in patients with autoimmune connective tissue diseases, viral DNA loads were assessed in paired samples of serum and peripheral blood mononuclear cells (PBMCs) of 115 patients affected by different disorders, including systemic sclerosis, systemic, and discoid lupus erythematosus, rheumatoid arthritis, and dermatomyositis. Two additional groups, patients affected by inflammatory diseases (n=51) and healthy subjects (n=58) were studied as controls. The titers of anti-HHV-6 and anti-EBV antibodies were also evaluated. Cell-free HHV-6 serum viremia was detected in a significantly higher proportion of connective tissue diseases patients compared to controls (P<0.0002); a significant association between HHV-6 reactivation and the active disease state was found only for lupus erythematosus (P=0.021). By contrast, the rate of cell-free EBV viremia was similar in patients and controls groups. Cell-free CMV, HHV-8, and B19V viremia was not detected in any subject. Anti-HHV-6 and anti-EBV early antigen IgG titers were both significantly higher in autoimmune diseases patients as compared to healthy controls, although they were not associated with the presence of viremia. EBV, HHV-6, -7 prevalence and viral load in PBMCs of patients with connective tissue diseases and controls were similar. These data suggest that HHV-6 may act as a pathogenic factor predisposing patients to the development of autoimmune connective tissue diseases or, conversely, that these disorders may predispose patients to HHV-6 reactivation. © 2013 Wiley Periodicals, Inc.

Evaluation of human recession defects treated with coronally advanced flaps and either purified recombinant human platelet-derived growth factor-BB with beta tricalcium phosphate or connective tissue: a histologic and microcomputed tomographic examination.

PubMed

McGuire, Michael K; Scheyer, Todd; Nevins, Myron; Schupbach, Peter

2009-02-01

The current study examined the histologic and microcomputed tomographic (micro CT) outcomes of the treatment of gingival recession defects with either a subepithelial connective tissue graft (CTG) or 0.3 mg/mL recombinant human platelet-derived growth factor (rhPDGF-BB) on a beta tricalcium phosphate (beta-TCP) matrix. Gingival recession defects were surgically created in six premolar teeth with no more than 3 mm of keratinized marginal tissue, an osseous crest 2 to 3 mm apical to the newly created gingival margin, and recession depth of at least 3 mm. The defects were left untouched for 2 months; then, four defects were grafted with rhPDGF-BB + beta-TCP + a wound healing dressing, and two defects received CTGs. A coronally advanced flap covered each grafted site. Nine months later, sections were obtained for examination. All four sites treated with rhPDGF-BB + beta-TCP showed connective tissue fibers (Sharpey fibers) perpendicularly inserting into newly formed cementum and alveolar bone. In the two sites treated with CTGs, a long junctional epithelium was seen coronal to the osseous crest and connective tissue fibers ran parallel to the adjacent root surfaces, with no evidence of insertion into cementum or bone. There was no evidence of regeneration of cementum, inserting connective tissue fibers, or supporting alveolar bone. Regeneration of the periodontium in gingival recession defects is possible through growth factor-mediated therapy.

Mechanical model for a collagen fibril pair in extracellular matrix.

PubMed

Chan, Yue; Cox, Grant M; Haverkamp, Richard G; Hill, James M

2009-04-01

In this paper, we model the mechanics of a collagen pair in the connective tissue extracellular matrix that exists in abundance throughout animals, including the human body. This connective tissue comprises repeated units of two main structures, namely collagens as well as axial, parallel and regular anionic glycosaminoglycan between collagens. The collagen fibril can be modeled by Hooke's law whereas anionic glycosaminoglycan behaves more like a rubber-band rod and as such can be better modeled by the worm-like chain model. While both computer simulations and continuum mechanics models have been investigated for the behavior of this connective tissue typically, authors either assume a simple form of the molecular potential energy or entirely ignore the microscopic structure of the connective tissue. Here, we apply basic physical methodologies and simple applied mathematical modeling techniques to describe the collagen pair quantitatively. We found that the growth of fibrils was intimately related to the maximum length of the anionic glycosaminoglycan and the relative displacement of two adjacent fibrils, which in return was closely related to the effectiveness of anionic glycosaminoglycan in transmitting forces between fibrils. These reveal the importance of the anionic glycosaminoglycan in maintaining the structural shape of the connective tissue extracellular matrix and eventually the shape modulus of human tissues. We also found that some macroscopic properties, like the maximum molecular energy and the breaking fraction of the collagen, were also related to the microscopic characteristics of the anionic glycosaminoglycan.

Oral telangiectatic granuloma with an intrabony defect.

PubMed

Rathore, Akanksha; Jadhav, Tanya; Kulloli, Anita; Singh, Archana

2015-01-01

Oral telangiectatic granuloma is a benign hyperplastic lesion occurring in response to trauma or chronic irritation in the oral cavity. The characteristic histological appearance comprises of typical granulation tissue with a proliferation of small thin-walled blood vessels in the loose connective tissue. We describe a case of a 36-year-old female who had a swelling in the left maxillary region which was associated with the intrabony defect. An internal bevel gingivectomy was performed, and the histopathological report was suggestive of telangiectatic granuloma. The intrabony defect was managed with the placement of platelet rich fibrin plug in the defect. A follow-up at 6 months showed no recurrence and no loss in the width of keratinized tissue. The aim of this case is to highlight the rare association of intrabony defect with telangiectatic granuloma and the need for histopathological diagnosis in such lesions.

Two-photon excitation based photochemistry and neural imaging

NASA Astrophysics Data System (ADS)

Hatch, Kevin Andrew

Two-photon microscopy is a fluorescence imaging technique which provides distinct advantages in three-dimensional cellular and molecular imaging. The benefits of this technology may extend beyond imaging capabilities through exploitation of the quantum processes responsible for fluorescent events. This study utilized a two-photon microscope to investigate a synthetic photoreactive collagen peptidomimetic, which may serve as a potential material for tissue engineering using the techniques of two-photon photolysis and two-photon polymerization. The combination of these techniques could potentially be used to produce a scaffold for the vascularization of engineered three-dimensional tissues in vitro to address the current limitations of tissue engineering. Additionally, two-photon microscopy was used to observe the effects of the application of the neurotransmitter dopamine to the mushroom body neural structures of Drosophila melanogaster to investigate dopamine's connection to cognitive degeneration.

Interdisciplinary approach to enhance the esthetics of maxillary anterior region using soft- and hard-tissue ridge augmentation in conjunction with a fixed partial prosthesis.

PubMed

Khetarpal, Shaleen; Chouksey, Ajay; Bele, Anand; Vishnoi, Rahul

2018-01-01

Favorable esthetics is one of the most important treatment outcomes in dentistry, and to achieve this, interdisciplinary approaches are often required. Ridge deficiencies can be corrected for both, soft- and hard-tissue discrepancies. To overcome such defects, not only a variety of prosthetic options are at our disposal but also several periodontal plastic surgical techniques are available as well. Various techniques have been described and revised, over the year to correct ridge defects. For enhancing soft-tissue contours in the anterior region, the subepithelial connective tissue graft is the treatment of choice. A combination of alloplastic bone graft in adjunct to connective tissue graft optimizes ridge augmentation and minimizes defects. The present case report describes the use of vascular interpositional connective tissue graft in combination with alloplastic bone graft for correction of Seibert's Class III ridge deficiency followed by a fixed partial prosthesis to achieve a better esthetic outcome.

Interdisciplinary approach to enhance the esthetics of maxillary anterior region using soft- and hard-tissue ridge augmentation in conjunction with a fixed partial prosthesis

PubMed Central

Khetarpal, Shaleen; Chouksey, Ajay; Bele, Anand; Vishnoi, Rahul

2018-01-01

Favorable esthetics is one of the most important treatment outcomes in dentistry, and to achieve this, interdisciplinary approaches are often required. Ridge deficiencies can be corrected for both, soft- and hard-tissue discrepancies. To overcome such defects, not only a variety of prosthetic options are at our disposal but also several periodontal plastic surgical techniques are available as well. Various techniques have been described and revised, over the year to correct ridge defects. For enhancing soft-tissue contours in the anterior region, the subepithelial connective tissue graft is the treatment of choice. A combination of alloplastic bone graft in adjunct to connective tissue graft optimizes ridge augmentation and minimizes defects. The present case report describes the use of vascular interpositional connective tissue graft in combination with alloplastic bone graft for correction of Seibert's Class III ridge deficiency followed by a fixed partial prosthesis to achieve a better esthetic outcome. PMID:29568176

Soft Tissue Closure of Grafted Extraction Sockets in the Anterior Maxilla: A Modified Palatal Pedicle Connective Tissue Flap Technique.

PubMed

El Chaar, Edgard; Oshman, Sarah; Cicero, Giuseppe; Castano, Alejandro; Dinoi, Cinzia; Soltani, Leila; Lee, Yoonjung Nicole

Localized ridge resorption, the consequence of socket collapse, following tooth extraction in the anterior maxilla can adversely affect esthetics, function, and future implant placement. Immediate grafting of extraction sockets may help preserve natural ridge contours, but a lack of available soft tissue can compromise the final esthetic outcome. The presented modified rotated palatal pedicle connective tissue flap is a useful technique for simultaneous soft tissue coverage and augmentation of grafted sockets to improve esthetic outcome. This article delineates its advantages through the presentation of a four-case series using this new technique.

[Technical peculiarities of the argon-plasma welding of gastrointestinal walls wounds in experimental environment].

PubMed

Terekhov, G V; Furmanov, Iu A; Gvozdetskiĭ, V S; Savitskaia, I M

2008-06-01

A new method of the live biological tissues connection, using thermal energy of a high-temperature argon plasma, constituting perspective trend of application of a new nonsuture methods of the tissues connection, original for the world practice, was elaborated in the Department of Experimental Surgery together with the Institute of welding named after Academician E. O. Paton NAS of Ukraine. The argon-plasma welding application secure safe adhesion of the connecting surfaces formation due to the protein complexes temperature denaturation occurrence. The absence of foreign bodies in the connection zone as well as the presence of the plasma flow bacterocidal properties secure, while application of this new method, a significant lowering of a bacterial soiling of the formatted anastomoses, not interfering with the tissue natural regeneration process course.

The Possible Potential Therapeutic Targets for Drug Induced Gingival Overgrowth

PubMed Central

Alitheen, Noorjahan Banu

2013-01-01

Gingival overgrowth is a side effect of certain medications. The most fibrotic drug-induced lesions develop in response to therapy with phenytoin, the least fibrotic lesions are caused by cyclosporin A, and the intermediate fibrosis occurs in nifedipine-induced gingival overgrowth. Fibrosis is one of the largest groups of diseases for which there is no therapy but is believed to occur because of a persistent tissue repair program. During connective tissue repair, activated gingival fibroblasts synthesize and remodel newly created extracellular matrix. Proteins such as transforming growth factor (TGF), endothelin-1 (ET-1), angiotensin II (Ang II), connective tissue growth factor (CCN2/CTGF), insulin-like growth factor (IGF), and platelet-derived growth factor (PDGF) appear to act in a network that contributes to the development of gingival fibrosis. Since inflammation is the prerequisite for gingival overgrowth, mast cells and its protease enzymes also play a vital role in the pathogenesis of gingival fibrosis. Drugs targeting these proteins are currently under consideration as antifibrotic treatments. This review summarizes recent observations concerning the contribution of TGF-β, CTGF, IGF, PDGF, ET-1, Ang II, and mast cell chymase and tryptase enzymes to fibroblast activation in gingival fibrosis and the potential utility of agents blocking these proteins in affecting the outcome of drug-induced gingival overgrowth. PMID:23690667

TRIENNIAL LACTATION SYMPOSIUM/BOLFA: Plasticity of mammary development in the prepubertal bovine mammary gland.

PubMed

Akers, R M

2017-12-01

Although peripubertal mammary development represents only a small fraction of the total mass of mammary parenchyma present in the udder at the end of gestation and into lactation, there is increasing evidence that the tissue foundations created in early life can affect future mammary development and function. Studies on expression of estrogen and progesterone receptors seem to confirm the relevance of these steroids in prepubertal mammary development, but connections with other growth factors, hormones, and local tissue factors remain elusive. Enhanced preweaning feeding in the bovine appears to enhance the capacity of mammary tissue to response to mammogenic stimulation. This suggests the possibility that improved early nutrition might allow for creation of stem or progenitor cell populations to better support the massive ductal growth and lobulo-alveolar development during gestation. Increasing evidence that immune cells are involved in mammary development suggests there are unexpected and poorly understood connections between the immune system and mammary development. This is nearly unexplored in ruminants. Development of new tools to identify, isolate, and characterize cell populations within the developing bovine mammary gland offer the possibility of identifying and perhaps altering populations of mammary stem cells or selected progenitor cells to modulate mammary development and, possibly, mammary function.

FOXO1 expression in keratinocytes promotes connective tissue healing

PubMed Central

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

2017-01-01

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

Animal models for periodontal regeneration and peri-implant responses.

PubMed

Kantarci, Alpdogan; Hasturk, Hatice; Van Dyke, Thomas E

2015-06-01

Translation of experimental data to the clinical setting requires the safety and efficacy of such data to be confirmed in animal systems before application in humans. In dental research, the animal species used is dependent largely on the research question or on the disease model. Periodontal disease and, by analogy, peri-implant disease, are complex infections that result in a tissue-degrading inflammatory response. It is impossible to explore the complex pathogenesis of periodontitis or peri-implantitis using only reductionist in-vitro methods. Both the disease process and healing of the periodontal and peri-implant tissues can be studied in animals. Regeneration (after periodontal surgery), in response to various biologic materials with potential for tissue engineering, is a continuous process involving various types of tissue, including epithelia, connective tissues and alveolar bone. The same principles apply to peri-implant healing. Given the complexity of the biology, animal models are necessary and serve as the standard for successful translation of regenerative materials and dental implants to the clinical setting. Smaller species of animal are more convenient for disease-associated research, whereas larger animals are more appropriate for studies that target tissue healing as the anatomy of larger animals more closely resembles human dento-alveolar architecture. This review focuses on the animal models available for the study of regeneration in periodontal research and implantology; the advantages and disadvantages of each animal model; the interpretation of data acquired; and future perspectives of animal research, with a discussion of possible nonanimal alternatives. Power calculations in such studies are crucial in order to use a sample size that is large enough to generate statistically useful data, whilst, at the same time, small enough to prevent the unnecessary use of animals. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Genipin crosslinker releasing sutures for improving the mechanical/repair strength of damaged connective tissue.

PubMed

Sundararaj, Sharath; Slusarewicz, Paul; Brown, Matt; Hedman, Thomas

2017-11-01

The most common mode of surgical repair of ruptured tendons and ligaments involves the use of sutures for reattachment. However, there is a high incidence of rerupture and repair failure due to pulling out of the suture material from the damaged connective tissue. The main goal of this research was to achieve a localized delivery of crosslinking agent genipin (GP) from rapid-release biodegradable coatings on sutures, for strengthening the repair of ruptured connective tissue. Our hypothesis is that GP released from the suture coating will lead to exogenous crosslinking of native connective tissue resulting in beneficial effects on clinically relevant mechanical parameters such as tear resistance, tissue strength, and energy required to rupture the tissue (toughness). Sutures were successfully coated with a biodegradable polymer layer loaded with the crosslinking agent genipin, without compromising the mechanical properties of the suture. The rapid-release of genipin was achieved under both in vitro and ex vivo conditions. Exogenous crosslinking using these genipin releasing sutures was demonstrated using equine tendons. The tendons treated with genipin releasing sutures showed significant improvement in failure load, energy required for pull-out failure, and stiffness. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2199-2205, 2017. © 2016 Wiley Periodicals, Inc.

Microscopic and ultrastructural evidences in human skin following calcium hydroxylapatite filler treatment.

PubMed

Zerbinati, Nicola; D'Este, Edoardo; Parodi, Pier Camillo; Calligaro, Alberto

2017-07-01

This study uses light and electron microscopes to gain a better knowledge of the interactions of calcium hydroxylapatite filler with the connective tissue of the skin and the modifications of the human deep dermis, after 2 months of treatment. Some morphological evidences of this observational study of filler treated tissue support-specific mechanism involved in the structural modifications of both filler microspherules and cells of the connective tissue. They demonstrate the absence of any immunological reaction and show that the used filler is modified very slowly over time by the action of cells of the connective tissue closely related to the filler without any activity of phagocytosis. Furthermore, associated with the modifications of the filler, evidences of stimulatory effects on dermal fibroblasts are reported.

[Imaging of alloplastic ligament implant. An in vivo and in vitro study exemplified by Kevlar].

PubMed

Wening, J V; Katzer, A; Nicolas, V; Hahn, M; Jungbluth, K H; Kratzer A [corrected to Katzer, A

1994-04-01

Neither native X-ray nor CT or NMR allow to evaluate intraarticular implantation results of Kevlar -49 directly. In animal trials, the course of an artificial ligament may only be presumed from connective tissue ingrowth. Although soft tissue structure appears much better in NMR than in CT, direct proof of ligament continuity is still impossible. As soon as the connective tissue becomes continuous, it appears clearly and allows indirect evaluation of the prosthesis, as integrity can be judged by its shape like in natural cruciate ligament. Anatomic preparations show that connective tissue fills up the small space between the two cords of a Kevlar -49 two bundle prosthesis eight weeks after implantation, so that imaging systems show only one intraarticular bundle.

WE-DE-202-02: Are Track Structure Simulations Truly Needed for Radiobiology at the Cellular and Tissue Levels?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stewart, R.

Radiation therapy for the treatment of cancer has been established as a highly precise and effective way to eradicate a localized region of diseased tissue. To achieve further significant gains in the therapeutic ratio, we need to move towards biologically optimized treatment planning. To achieve this goal, we need to understand how the radiation-type dependent patterns of induced energy depositions within the cell (physics) connect via molecular, cellular and tissue reactions to treatment outcome such as tumor control and undesirable effects on normal tissue. Several computational biology approaches have been developed connecting physics to biology. Monte Carlo simulations are themore » most accurate method to calculate physical dose distributions at the nanometer scale, however simulations at the DNA scale are slow and repair processes are generally not simulated. Alternative models that rely on the random formation of individual DNA lesions within one or two turns of the DNA have been shown to reproduce the clusters of DNA lesions, including single strand breaks (SSBs), double strand breaks (DSBs) without the need for detailed track structure simulations. Efficient computational simulations of initial DNA damage induction facilitate computational modeling of DNA repair and other molecular and cellular processes. Mechanistic, multiscale models provide a useful conceptual framework to test biological hypotheses and help connect fundamental information about track structure and dosimetry at the sub-cellular level to dose-response effects on larger scales. In this symposium we will learn about the current state of the art of computational approaches estimating radiation damage at the cellular and sub-cellular scale. How can understanding the physics interactions at the DNA level be used to predict biological outcome? We will discuss if and how such calculations are relevant to advance our understanding of radiation damage and its repair, or, if the underlying biological processes are too complex for a mechanistic approach. Can computer simulations be used to guide future biological research? We will debate the feasibility of explaining biology from a physicists’ perspective. Learning Objectives: Understand the potential applications and limitations of computational methods for dose-response modeling at the molecular, cellular and tissue levels Learn about mechanism of action underlying the induction, repair and biological processing of damage to DNA and other constituents Understand how effects and processes at one biological scale impact on biological processes and outcomes on other scales J. Schuemann, NCI/NIH grantsS. McMahon, Funding: European Commission FP7 (grant EC FP7 MC-IOF-623630)« less

Histopathology of lung disease in the connective tissue diseases.

PubMed

Vivero, Marina; Padera, Robert F

2015-05-01

The pathologic correlates of interstitial lung disease (ILD) secondary to connective tissue disease (CTD) comprise a diverse group of histologic patterns. Lung biopsies in patients with CTD-associated ILD tend to demonstrate simultaneous involvement of multiple anatomic compartments of the lung. Certain histologic patterns tend to predominate in each defined CTD, and it is possible in many cases to confirm connective tissue-associated lung disease and guide patient management using surgical lung biopsy. This article will cover the pulmonary pathologies seen in rheumatoid arthritis, systemic sclerosis, myositis, systemic lupus erythematosus, Sjögren syndrome, and mixed CTD. Copyright © 2015 Elsevier Inc. All rights reserved.

Exploring the potential of polyurethane-based soft foam as cell-free scaffold for soft tissue regeneration.

PubMed

Gerges, Irini; Tamplenizza, Margherita; Martello, Federico; Recordati, Camilla; Martelli, Cristina; Ottobrini, Luisa; Tamplenizza, Mariacaterina; Guelcher, Scott A; Tocchio, Alessandro; Lenardi, Cristina

2018-06-01

Reconstructive treatment after trauma and tumor resection would greatly benefit from an effective soft tissue regeneration. The use of cell-free scaffolds for adipose tissue regeneration in vivo is emerging as an attractive alternative to tissue-engineered constructs, since this approach avoids complications due to cell manipulation and lack of synchronous vascularization. In this study, we developed a biodegradable polyurethane-based scaffold for soft tissue regeneration, characterized by an exceptional combination between softness and resilience. Exploring the potential as a cell-free scaffold required profound understanding of the impact of its intrinsic physico-chemical properties on the biological performance in vivo. We investigated the effect of the scaffold's hydrophilic character, degradation kinetics, and internal morphology on (i) the local inflammatory response and activation of MGCs (foreign body response); (ii) its ability to promote rapid vascularisation, cell infiltration and migration through the scaffold over time; and (iii) the grade of maturation of the newly formed tissue into vascularized soft tissue in a murine model. The study revealed that soft tissue regeneration in vivo proceeded by gradual infiltration of undifferentiated mesenchymal cells though the periphery toward the center of the scaffold, where the rapid formation of a functional and well-formed vascular network supported cell viability overtime. Exploring the potential of polyurethane-based soft foam as cell-free scaffold for soft tissue regeneration. In this work, we address the unmet need for synthetic functional soft tissue substitutes that provide adequate biological and mechanical support to soft tissue. We developed a series of flexible cross-linked polyurethane copolymer scaffolds with remarkable fatigue-resistance and tunable physico-chemical properties for soft tissue regeneration in vivo. Accordingly, we could extend the potential of this class of biomaterials, which was so far confined for bone and osteochondral tissue regeneration, to other types of connective tissue. Copyright © 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Muscular force transmission: a unified, dual or multiple system? A review and some explorative experimental results.

PubMed

Huijing, P

1999-10-01

Structures contributing to force transmission in muscle are reviewed combining some historical and relatively recently published experimental data. Also, effects of aponeurotomy and tenotomy are reviewed shortly as well as some new experimental results regarding these interventions that reinforce the concept of myofascial force transmission. The review is also illustrated by some new images of single muscle fibres from Xenopus Laevis indicative of such transmission and some data about locations of insertion of human gluteus maximus muscle. From this review and the new material, emerges a line of thought indicating that mechanical connections between muscle fibres and intramuscular connective tissue play an important role in force transmission. New experimental observations are presented for non-spanning muscle (i.c., rat biceps femoris muscle), regarding the great variety of types of intramuscular connections that exist i n addition to myo-tendinous junctions at the perimuscular ends of muscle fibres. Such connections are classified as (1) tapered end connections, (2) Myo-myonal junctions, (3) myo-epimysial junctions and (3) Myo-endomysial junctions. This line of thought is followed up by consideration of a possible role of connections of intra- and extramuscular connective tissue in force transmission out of the muscle. Experimental results of an explorative nature, regarding the interactions of extensor digitorum longus (EDL), tibialis anterior (TA) and hallucis longus (HAL) muscles within a relatively intact dorsal flexor compartment of the rat hind leg, indicate that: (1) length force properties of EDL are influenced by TA activity in a length dependent fashion. Depending on TA length, force exerted by EDL, kept at constant origin insertion distance, is variable and the effect is influenced by EDL length itself as well; (2) Force is transmitted from muscle to extramuscular connective tissue and vice versa. As a consequence force exerted at proximal and distal tendons of a muscle are not always equal. The difference being transmitted by extramuscular connective tissue and may appear at the tendons of other muscles or may be transmitted via connective tissue directly to bone. It is concluded that the system of force transmission from skeletal muscle should be considered as a multiple system.

Connective tissue grafts for thickening peri-implant tissues at implant placement. One-year results from an explanatory split-mouth randomised controlled clinical trial.

PubMed

Wiesner, Günter; Esposito, Marco; Worthington, Helen; Schlee, Markus

2010-01-01

Nothing to declare. To evaluate whether connective tissue grafts performed at implant placement could be effective in augmenting peri-implant soft tissues. Ten partially edentulous patients requiring at least one single implant in the premolar or molar areas of both sides of the mandible were randomised to have one side augmented at implant placement with a connective soft tissue graft harvested from the palate or no augmentation. After 3 months of submerged healing, abutments were placed and within 1 month definitive crowns were permanently cemented. Outcome measures were implant success, any complications, peri-implant marginal bone level changes, patient satisfaction and preference, thickness of the soft tissues and aesthetics (pink aesthetic score) evaluated by an independent and blinded assessor 1 year after loading. One year after loading, no patients dropped out, no implants failed and no complications occurred. Both groups lost statistically significant amounts of peri-implant bone 1 year after loading (0.8 mm in the grafted group and 0.6 mm in the non-grafted group), but there was no statistically significant difference between groups. Soft tissues at augmented sites were 1.3 mm thicker (P < 0.001) and had a significantly better pink aesthetic score (P < 0.001). Patients were highly satisfied (no statistically significant differences between treatments) though they preferred the aesthetics of the augmented sites (P = 0.031). However, five patients would not undergo the grafting procedure again and two were uncertain. Connective tissue grafts are effective in increasing soft tissue thickness, thus improving aesthetics. Longer follow-ups are needed to evaluate the stability of peri-implant tissues over time.

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

USDA-ARS?s Scientific Manuscript database

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

Biophysics of cancer progression and high-throughput mechanical characterization of biomaterials

NASA Astrophysics Data System (ADS)

Osborne, Lukas Dylan

Cancer metastasis involves a series of events known as the metastatic cascade. In this complex progression, cancer cells detach from the primary tumor, invade the surrounding stromal space, transmigrate the vascular system, and establish secondary tumors at distal sites. Specific mechanical phenotypes are likely adopted to enable cells to successfully navigate the mechanical environments encountered during metastasis. To examine the role of cell mechanics in cancer progression, I employed force-consistent biophysical and biochemical assays to characterize the mechanistic links between stiffness, stiffness response and cell invasion during the epithelial to mesenchymal transition (EMT). EMT is an essential physiological process, whose abnormal reactivation has been implicated in the detachment of cancer cells from epithelial tissue and their subsequent invasion into stromal tissue. I demonstrate that epithelial-state cells respond to force by evoking a stiffening response, and that after EMT, mesenchymal-state cells have reduced stiffness but also lose the ability to increase their stiffness in response to force. Using loss and gain of function studies, two proteins are established as functional connections between attenuated stiffness and stiffness response and the increased invasion capacity acquired after EMT. To enable larger scale assays to more fully explore the connection between biomechanics and cancer, I discuss the development of an automated array high throughput (AHT) microscope. The AHT system is shown to implement passive microbead rheology to accurately characterize the mechanical properties of biomaterials. Compared to manually performed mechanical characterizations, the AHT system executes experiments in two orders of magnitude less time. Finally, I use the AHT microscope to study the effect of gain of function oncogenic molecules on cell stiffness. I find evidence that our assay can identify alterations in cell stiffness due to constitutive activation of cancer pathways.

Dense Breasts

MedlinePlus

... fatty tissue. On a mammogram, fatty tissue appears dark (radio-lucent) and the glandular and connective tissues ... white on mammography) and non-dense fatty tissue (dark on mammography) using a visual scale and assign ...

Optical Histology: High-Resolution Visualization of Tissue Microvasculature

NASA Astrophysics Data System (ADS)

Moy, Austin Jing-Ming

Mammalian tissue requires the delivery of nutrients, growth factors, and the exchange of oxygen and carbon dioxide gases to maintain normal function. These elements are delivered by the blood, which travels through the connected network of blood vessels, known as the vascular system. The vascular system consists of large feeder blood vessels (arteries and veins) that are connected to the small blood vessels (arterioles and venules), which in turn are connected to the capillaries that are directly connected to the tissue and facilitate gas exchange and nutrient delivery. These small blood vessels and capillaries make up an intricate but organized network of blood vessels that exist in all mammalian tissues known as the microvasculature and are very important in maintaining the health and proper function of mammalian tissue. Due to the importance of the microvasculature in tissue survival, disruption of the microvasculature typically leads to tissue dysfunction and tissue death. The most prevalent method to study the microvasculature is visualization. Immunohistochemistry (IHC) is the gold-standard method to visualize tissue microvasculature. IHC is very well-suited for highly detailed interrogation of the tissue microvasculature at the cellular level but is unwieldy and impractical for wide-field visualization of the tissue microvasculature. The objective my dissertation research was to develop a method to enable wide-field visualization of the microvasculature, while still retaining the high-resolution afforded by optical microscopy. My efforts led to the development of a technique dubbed "optical histology" that combines chemical and optical methods to enable high-resolution visualization of the microvasculature. The development of the technique first involved preliminary studies to quantify optical property changes in optically cleared tissues, followed by development and demonstration of the methodology. Using optical histology, I successfully obtained high resolution, depth sectioned images of the microvasculature in mouse brain and the coronary microvasculature in mouse heart. Future directions of optical histology include the potential to facilitate visualization of the entire microvascular structure of an organ as well as visualization of other tissue molecular markers of interest.

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

PubMed

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

2015-11-01

The axial connective tissue system is a fiber continuum of the lung that maintains alveolar surface area during changes in lung volume. Although the molecular anatomy of the axial system remains undefined, the fiber continuum of the lung is central to contemporary models of lung micromechanics and alveolar regeneration. To provide a detailed molecular structure of the axial connective tissue system, we examined the extracellular matrix of murine lungs. The lungs were decellularized using a 24 hr detergent treatment protocol. Systematic evaluation of the decellularized lungs demonstrated no residual cellular debris; morphometry demonstrated a mean 39 ± 7% reduction in lung dimensions. Scanning electron microscopy (SEM) demonstrated an intact structural hierarchy within the decellularized lung. Light, fluorescence, and SEM of precision-cut lung slices demonstrated that alveolar duct structure was defined by a cable line element encased in basement membrane. The cable line element arose in the distal airways, passed through septal tips and inserted into neighboring blood vessels and visceral pleura. The ropelike appearance, collagenase resistance and anti-elastin immunostaining indicated that the cable was an elastin macromolecule. Our results indicate that the helical line element of the axial connective tissue system is composed of an elastin cable that not only defines the structure of the alveolar duct, but also integrates the axial connective tissue system into visceral pleura and peripheral blood vessels. © 2015 Wiley Periodicals, Inc.

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

NASA Technical Reports Server (NTRS)

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

1994-01-01

Myofiber injury-repair was studied in the rat gastrocnemius following a crush injury to the lower leg prior to flight in order to understand if the regenerative responses of muscles are altered by the lack of gravitational forces during Cosmos 2044 flight. After 14 days of flight, the gastrocnemius muscle was removed from the 5 injured flight rodents and various Earth-based treatment groups for comparison. The Earth-based animals consisted of three groups of five rats with injured muscles from a simulated, tail-suspended, and vivarium as well as an uninjured basal group. The gastrocnemius muscle from each was evaluated by histochemical and immunohistochemical techniques to document myofiber, vascular, and connective tissue alterations following injury. In general the repair process was somewhat similar in all injured muscle samples with regard to extracellular matrix organization and myofiber regeneration. Small and large myofibers were present with a newly organized extracellular matrix indicative of myogenesis and muscle regeneration. In the tail-suspended animals, a more complete repair was observed with no enlarged area of non-muscle cells or matrix material visible. In contrast, the muscle samples from the flight animals were less well differentiated with more macrophages and blood vessels in the repair region but small myofibers and proteoglycans, nevertheless, were in their usual configuration. Thus, myofiber repair did vary in muscles from the different groups, but for the most part, resulted in functional muscle tissue.

[Evaluation of Cepan Cream after 15 years of treatment of burn scars].

PubMed

Stozkowska, Wiesława

2002-01-01

Cepan Cream is used for the topical treatment of scars and keloids resulting from burns, post-operative scars, and contractures. Cepan Cream makes scars more elastic, softer and paler. Plant extracts, heparin and allantoin in Cepan act on the biochemical processes in the developing connective tissue, preventing the formation of hyperplastic scars. These active ingredients enhance swelling, softening and loosening of connective tissue. It exerts softening and smoothing action on indurated and hyperplastic scar tissue, improving collagen structure. It promotes tissue regeneration and reduces exuberant granulation. Cepan is well tolerated.

The effects of different lying positions on interface pressure, skin temperature, and tissue blood flow in nursing home residents.

PubMed

Källman, Ulrika; Engström, Maria; Bergstrand, Sara; Ek, Anna-Christina; Fredrikson, Mats; Lindberg, Lars-Göran; Lindgren, Margareta

2015-03-01

Although repositioning is considered an important intervention to prevent pressure ulcers, tissue response during loading in different lying positions has not been adequately explored. To compare the effects of different lying positions on interface pressure, skin temperature, and tissue blood flow in nursing home residents. From May 2011 to August 2012, interface pressure, skin temperature, and blood flow at three tissue depths were measured for 1 hr over the sacrum in 30° supine tilt and 0° supine positions and over the trochanter major in 30° lateral and 90° lateral positions in 25 residents aged 65 years or older. Measurement of interface pressure was accomplished using a pneumatic pressure transmitter connected to a digital manometer, skin temperature using a temperature sensor, and blood flow using photoplethysmography and laser Doppler flowmetry. Interface pressure was significantly higher in the 0° supine and 90° lateral positions than in 30° supine tilt and 30° lateral positions. The mean skin temperature increased from baseline in all positions. Blood flow was significantly higher in the 30° supine tilt position compared to the other positions. A hyperemic response in the post pressure period was seen at almost all tissue depths and positions. The 30° supine tilt position generated less interface pressure and allowed greater tissue perfusion, suggesting that this position is the most beneficial. © The Author(s) 2014.

Ultrastructural analysis of metal particles released from stainless steel and titanium miniplate components in an animal model.

PubMed

Matthew, I R; Frame, J W

1998-01-01

Low-vacuum scanning electron microscopy (Ivac SEM) was used to characterize the appearance of metal particles released from stressed and unstressed Champy miniplates placed in dogs and to study the relationship of the debris to the surrounding tissues. Under general endotracheal anesthesia, two Champy miniplates (titanium or stainless steel) were placed on the frontal bone in an animal model. One miniplate was bent to fit the curvature of the frontal bone (unstressed) and another miniplate of the same material was bent in a curve until the midpoint was raised 3 mm above the ends. The latter miniplate adapted to the skull curvature under tension during screw insertion (stressed). The miniplates and surrounding tissues were retrieved after intervals of 4, 12, and 24 weeks. Decalcified sections were prepared and examined by light microscopy and Ivac SEM. Under Ivac SEM examination, the titanium particles had a smooth, polygonal outline. Stainless steel particles were typically spherical, with numerous small projections on the surface. Most particles were 1 to 10 microns in diameter. The tissue response to the particles was variable; some particles were covered by fibrous connective tissue or enclosed by bone, and others were intracellular. The metal particles released from stressed or unstressed Champy miniplates were similar, and this was related to their source of origin and duration within the tissues. The tissue response to the particles appeared to depend on their location.

Fibrous tissues growth and remodeling: Evolutionary micro-mechanical theory

NASA Astrophysics Data System (ADS)

Lanir, Yoram

2017-10-01

Living fibrous tissues are composite materials having the unique ability to adapt their size, shape, structure and mechanical properties in response to external loading. This adaptation, termed growth and remodeling (G&R), occurs throughout life and is achieved via cell-induced turnover of tissue constituents where some are degraded and new ones are produced. Realistic mathematical modeling of G&R provides insight into the basic processes, allows for hypotheses testing, and constitutes an essential tool for establishing clinical thresholds of pathological remodeling and for the production of tissue substitutes aimed to achieve target structure and properties. In this study, a general 3D micro-mechanical multi-scale theory of G&R in fibrous tissue was developed which connects between the evolution of the tissue structure and properties, and the underlying mechano-biological turnover events of its constituents. This structural approach circumvents a fundamental obstacle in modeling growth mechanics since the growth motion is not bijective. The model was realized for a flat tissue under two biaxial external loadings using data-based parameter values. The predictions show close similarity to characteristics of remodeled adult tissue including its structure, anisotropic and non-linear mechanical properties, and the onset of in situ pre-strain and pre-stress. The results suggest that these important features of living fibrous tissues evolve as they grow.

Clinical Evaluation of Papilla Reconstruction Using Subepithelial Connective Tissue Graft

PubMed Central

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

2014-01-01

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

A novel TaqI polymorphism in the coding region of the ovine TNXB gene in the MHC class III region: morphostructural and physiological influences.

PubMed

Ajayi, Oyeyemi O; Adefenwa, Mufliat A; Agaviezor, Brilliant O; Ikeobi, Christian O N; Wheto, Matthew; Okpeku, Moses; Amusan, Samuel A; Yakubu, Abdulmojeed; De Donato, Marcos; Peters, Sunday O; Imumorin, Ikhide G

2014-02-01

The tenascin-XB (TNXB) gene has antiadhesive effects, functions in matrix maturation in connective tissues, and localizes to the major histocompatibility complex class III region. We hypothesized that it may influence adaptive physiological response through an effect on blood vessel function. We identified a novel g.1324 A→G polymorphism at a TaqI recognition site in a 454 bp fragment of ovine TNXB and genotyped it in 150 Nigerian sheep using PCR-RFLP. The missense mutation changes glutamic acid (GAA) to glycine (GGA). Among SNP genotypes, significant differences (P < 0.05) were observed in body weight and fore cannon bone length. Interaction effects of breed, SNP genotype, and geographic location had a significant effect (P < 0.05) on chest girth. The SNP genotype was significantly (P < 0.05) associated with physiological traits of pulse rate and skin temperature. The observed effect of this novel polymorphism may be mediated through its role in connective tissue biology, requiring further association and functional studies.

Composition, Architecture, and Functional Implications of the Connective Tissue Network of the Extraocular Muscles

PubMed Central

McLoon, Linda K.; Vicente, André; Fitzpatrick, Krysta R.; Lindström, Mona

2018-01-01

Purpose We examined the pattern and extent of connective tissue distribution in the extraocular muscles (EOMs) and determined the ability of the interconnected connective tissues to disseminate force laterally. Methods Human EOMs were examined for collagens I, III, IV, and VI; fibronectin; laminin; and elastin using immunohistochemistry. Connective tissue distribution was examined with scanning electron microscopy. Rabbit EOMs were examined for levels of force transmission longitudinally and transversely using in vitro force assessment. Results Collagens I, III, and VI localized to the endomysium, perimysium, and epimysium. Collagen IV, fibronectin, and laminin localized to the basal lamina surrounding all myofibers. All collagens localized similarly in the orbital and global layers throughout the muscle length. Elastin had the most irregular pattern and ran longitudinally and circumferentially throughout the length of all EOMs. Scanning electron microscopy showed these elements to be extensively interconnected, from endomysium through the perimysium to the epimysium surrounding the whole muscle. In vitro physiology demonstrated force generation in the lateral dimension, presumably through myofascial transmission, which was always proportional to the force generated in the longitudinally oriented muscles. Conclusions A striking connective tissue matrix interconnects all the myofibers and extends, via perimysial connections, to the epimysium. These interconnections are significant and allow measurable force transmission laterally as well as longitudinally, suggesting that they may contribute to the nonlinear force summation seen in motor unit recording studies. This provides strong evidence that separate compartmental movements are unlikely as no region is independent of the rest of the muscle. PMID:29346490

Mesenchymal stem cells in tumor development

PubMed Central

Cuiffo, Benjamin G.; Karnoub, Antoine E.

2012-01-01

Mesenchymal stem cells (MSCs) are multipotent progenitor cells that participate in the structural and functional maintenance of connective tissues under normal homeostasis. They also act as trophic mediators during tissue repair, generating bioactive molecules that help in tissue regeneration following injury. MSCs serve comparable roles in cases of malignancy and are becoming increasingly appreciated as critical components of the tumor microenvironment. MSCs home to developing tumors with great affinity, where they exacerbate cancer cell proliferation, motility, invasion and metastasis, foster angiogenesis, promote tumor desmoplasia and suppress anti-tumor immune responses. These multifaceted roles emerge as a product of reciprocal interactions occurring between MSCs and cancer cells and serve to alter the tumor milieu, setting into motion a dynamic co-evolution of both tumor and stromal tissues that favors tumor progression. Here, we summarize our current knowledge about the involvement of MSCs in cancer pathogenesis and review accumulating evidence that have placed them at the center of the pro-malignant tumor stroma. PMID:22863739

A spectroscopic approach toward depression diagnosis: local metabolism meets functional connectivity.

PubMed

Demenescu, Liliana Ramona; Colic, Lejla; Li, Meng; Safron, Adam; Biswal, B; Metzger, Coraline Danielle; Li, Shijia; Walter, Martin

2017-03-01

Abnormal anterior insula (AI) response and functional connectivity (FC) is associated with depression. In addition to clinical features, such as severity, AI FC and its metabolism further predicted therapeutic response. Abnormal FC between anterior cingulate and AI covaried with reduced glutamate level within cingulate cortex. Recently, deficient glial glutamate conversion was found in AI in major depression disorder (MDD). We therefore postulate a local glutamatergic mechanism in insula cortex of depressive patients, which is correlated with symptoms severity and itself influences AI's network connectivity in MDD. Twenty-five MDD patients and 25 healthy controls (HC) matched on age and sex underwent resting state functional magnetic resonance imaging and magnetic resonance spectroscopy scans. To determine the role of local glutamate-glutamine complex (Glx) ratio on whole brain AI FC, we conducted regression analysis with Glx relative to creatine (Cr) ratio as factor of interest and age, sex, and voxel tissue composition as nuisance factors. We found that in MDD, but not in HC, AI Glx/Cr ratio correlated positively with AI FC to right supramarginal gyrus and negatively with AI FC toward left occipital cortex (p < 0.05 family wise error). AI Glx/Cr level was negatively correlated with HAMD score (p < 0.05) in MDD patients. We showed that the local AI ratio of glutamatergic-creatine metabolism is an underlying candidate subserving functional network disintegration of insula toward low level and supramodal integration areas, in MDD. While causality cannot directly be inferred from such correlation, our finding helps to define a multilevel network of response-predicting regions based on local metabolism and connectivity strength.

Tumor-induced osteomalacia with elevated fibroblast growth factor 23: a case of phosphaturic mesenchymal tumor mixed with connective tissue variants and review of the literature.

PubMed

Hu, Fang-Ke; Yuan, Fang; Jiang, Cheng-Ying; Lv, Da-Wei; Mao, Bei-Bei; Zhang, Qiang; Yuan, Zeng-Qiang; Wang, Yan

2011-11-01

Tumor-induced osteomalacia (TIO), or oncogenic osteomalacia (OOM), is a rare acquired paraneoplastic disease characterized by renal phosphate wasting and hypophosphatemia. Recent evidence shows that tumor-overexpressed fibroblast growth factor 23 (FGF23) is responsible for the hypophosphatemia and osteomalacia. The tumors associated with TIO are usually phosphaturic mesenchymal tumor mixed connective tissue variants (PMTMCT). Surgical removal of the responsible tumors is clinically essential for the treatment of TIO. However, identifying the responsible tumors is often difficult. Here, we report a case of a TIO patient with elevated serum FGF23 levels suffering from bone pain and hypophosphatemia for more than three years. A tumor was finally located in first metacarpal bone by octreotide scintigraphy and she was cured by surgery. After complete excision of the tumor, serum FGF23 levels rapidly decreased, dropping to 54.7% of the preoperative level one hour after surgery and eventually to a little below normal. The patient's serum phosphate level rapidly improved and returned to normal level in four days. Accordingly, her clinical symptoms were greatly improved within one month after surgery. There was no sign of tumor recurrence during an 18-month period of follow-up. According to pathology, the tumor was originally diagnosed as "lomangioma" based upon a biopsy sample, "proliferative giant cell tumor of tendon sheath" based upon sections of tumor, and finally diagnosed as PMTMCT by consultation one year after surgery. In conclusion, although an extremely rare disease, clinicians and pathologists should be aware of the existence of TIO and PMTMCT, respectively.

Spatial regulation of controlled bioactive factor delivery for bone tissue engineering

PubMed Central

Samorezov, Julia E.; Alsberg, Eben

2015-01-01

Limitations of current treatment options for critical size bone defects create a significant clinical need for tissue engineered bone strategies. This review describes how control over the spatiotemporal delivery of growth factors, nucleic acids, and drugs and small molecules may aid in recapitulating signals present in bone development and healing, regenerating interfaces of bone with other connective tissues, and enhancing vascularization of tissue engineered bone. State-of-the-art technologies used to create spatially controlled patterns of bioactive factors on the surfaces of materials, to build up 3D materials with patterns of signal presentation within their bulk, and to pattern bioactive factor delivery after scaffold fabrication are presented, highlighting their applications in bone tissue engineering. As these techniques improve in areas such as spatial resolution and speed of patterning, they will continue to grow in value as model systems for understanding cell responses to spatially regulated bioactive factor signal presentation in vitro, and as strategies to investigate the capacity of the defined spatial arrangement of these signals to drive bone regeneration in vivo. PMID:25445719

Clinical and biometrical evaluation of socket preservation using demineralized freeze-dried bone allograft with and without the palatal connective tissue as a biologic membrane.

PubMed

Moghaddas, Hamid; Amjadi, Mohammad Reza; Naghsh, Narges

2012-11-01

Alveolar ridge preservation following tooth extraction has the ability to maintain the ridge dimensions and allow the implant placement in an ideal position fulfilling both functional and aesthetic results. The aim of this study was to evaluate the efficacy of the palatal connective tissue as a biological membrane for socket preservation with demineralized freeze-dried bone allograft (DFDBA). Twelve extraction sites were treated with DFDBA with (case group) and without (control group) using autogenous palatal connective tissue membrane before placement of implants. Alveolar width and height, amount of keratinized tissue, and gingival level were measured at pre-determined points using a surgical stent at two times, the time of socket preservation surgery. In both groups a decrease in all socket dimensions was found. The average decrease in socket width, height, keratinized tissue, and gingival level in case group was 1.16, 0.72, 3.58, and 1.27 mm, and in control group was 2.08, 0.86, 4.52, and 1.58 mm respectively. Statistical analysis showed that decrease in socket width (P = 0.012), keratinized tissue (P ≤ 0.001), and gingival level (P = 0.031) in case group was significantly lower than that of the control group. Results showed no meaningful difference in socket height changes when compared with case and control groups (P = 0.148). Under the limits of this study, connective tissue membrane could preserve socket width, amount of keratinized tissue, and the gingival level more effectively than DFDBA alone.

A Digital Staining Algorithm for Optical Coherence Tomography Images of the Optic Nerve Head

PubMed Central

Mari, Jean-Martial; Aung, Tin; Cheng, Ching-Yu; Strouthidis, Nicholas G.; Girard, Michaël J. A.

2017-01-01

Purpose To digitally stain spectral-domain optical coherence tomography (OCT) images of the optic nerve head (ONH), and highlight either connective or neural tissues. Methods OCT volumes of the ONH were acquired from one eye of 10 healthy subjects. We processed all volumes with adaptive compensation to remove shadows and enhance deep tissue visibility. For each ONH, we identified the four most dissimilar pixel-intensity histograms, each of which was assumed to represent a tissue group. These four histograms formed a vector basis on which we ‘projected' each OCT volume in order to generate four digitally stained volumes P1 to P4. Digital staining was also verified using a digital phantom, and compared with k-means clustering for three and four clusters. Results Digital staining was able to isolate three regions of interest from the proposed phantom. For the ONH, the digitally stained images P1 highlighted mostly connective tissues, as demonstrated through an excellent contrast increase across the anterior lamina cribrosa boundary (3.6 ± 0.6 times). P2 highlighted the nerve fiber layer and the prelamina, P3 the remaining layers of the retina, and P4 the image background. Further, digital staining was able to separate ONH tissue layers that were not well separated by k-means clustering. Conclusion We have described an algorithm that can digitally stain connective and neural tissues in OCT images of the ONH. Translational Relevance Because connective and neural tissues are considerably altered in glaucoma, digital staining of the ONH tissues may be of interest in the clinical management of this pathology. PMID:28174676

Does rat granulation tissue maturation involve gap junction communications?

PubMed

Au, Katherine; Ehrlich, H Paul

2007-07-01

Wound healing, a coordinated process, proceeds by sequential changes in cell differentiation and terminates with the deposition of a new connective tissue matrix, a scar. Initially, there is the migratory fibroblast, followed by the proliferative fibroblast, then the synthetic fibroblast, which transforms into the myofibroblast, and finally the apoptotic fibroblast. Gap junction intercellular communications are proposed to coordinate the stringent control of fibroblast phenotypic changes. Does added oleamide, a natural fatty acid that blocks gap junction intercellular communications, alter the phenotypic progression of wound fibroblasts? Pairs of polyvinyl alcohol sponges attached to Alzet pumps, which constantly pumped either oleamide or vehicle solvent, were implanted subcutaneously into three rats. On day 8, implants were harvested and evaluated histologically and biochemically. The capsule of oleamide-treated sponge contained closely packed fibroblasts with little connective tissue between them. The birefringence intensity of that connective tissue was reduced, indicating a reduced density of collagen fiber bundles. Myofibroblasts, identified immunohistologically by alpha-smooth muscle actin-stained stress fibers, were reduced in oleamide-treated implants. Western blot analysis showing less alpha-smooth muscle actin confirmed the reduced density of myofibroblasts. It appears that oleamide retards the progression of wound repair, where less connective tissue is deposited, the collagen is less organized, and the appearance of myofibroblasts is impaired. These findings support the hypothesis that gap junction intercellular communications between wound fibroblasts in granulation tissue play a role in the progression of repair and the maturation of granulation tissue into scar.

Zebrafish collagen XII is present in embryonic connective tissue sheaths (fascia) and basement membranes.

PubMed

Bader, Hannah L; Keene, Douglas R; Charvet, Benjamin; Veit, Guido; Driever, Wolfgang; Koch, Manuel; Ruggiero, Florence

2009-01-01

Connective tissues ensure the cohesion of the tissues of the body, but also form specialized structures such as tendon and bone. Collagen XII may enhance the stability of connective tissues by bridging collagen fibrils, but its function is still unclear. Here, we used the zebrafish model to visualize its expression pattern in the whole organism. The zebrafish col12a1 gene is homologous to the small isoform of the tetrapod col12a1 gene. In agreement with the biochemical data reported for the small isoform, the zebrafish collagen XII alpha1 chain was characterized as a collagenase sensitive band migrating at approximately 200 kDa. Using newly generated polyclonal antibodies and anti-sense probes, we performed a comprehensive analysis of its expression in developing zebrafish. Collagen XII exhibited a much broader expression pattern than previously thought: it was ubiquitously expressed in the connective tissue sheaths (fascia) that encase the tissues and organs of the body. For example, it was found in sclera, meninges, epimysia and horizontal and vertical myosepta. Collagen XII was also detected in head mesenchyme, pharyngeal arches and within the spinal cord, where it was first expressed within and then at the lateral borders of the floor plate and at the dorsal midline. Furthermore, double immunofluorescence staining with laminin and immunogold electron microscopy revealed that collagen XII is associated with basement membranes. These data suggest that collagen XII is implicated in tissue cohesion by stabilizing fascia and by linking fascia to basement membranes.

Homeostatic and pathogenic extramedullary hematopoiesis

PubMed Central

Kim, Chang H

2010-01-01

Extramedullary hematopoiesis (EH) is defined as hematopoiesis occurring in organs outside of the bone marrow; it occurs in diverse conditions, including fetal development, normal immune responses, and pathological circumstances. During fetal development, before formation of mature marrow, EH occurs in the yolk sac, fetal liver, and spleen. EH also occurs during active immune responses to pathogens. Most frequently, this response occurs in the spleen and liver for the production of antigen-presenting cells and phagocytes. EH also occurs when the marrow becomes inhabitable for stem and progenitor cells in certain pathological conditions, including myelofibrosis, where marrow cells are replaced with collagenous connective tissue fibers. Thus, EH occurs either actively or passively in response to diverse changes in the hematopoietic environment. This article reviews the key features and regulators of the major types of EH. PMID:22282679

Functional Morphology of the Arm Spine Joint and Adjacent Structures of the Brittlestar Ophiocomina nigra (Echinodermata: Ophiuroidea)

PubMed Central

Wilkie, Iain C.

2016-01-01

The skeletal morphology of the arm spine joint of the brittlestar Ophiocomina nigra was examined by scanning electron microscopy and the associated epidermis, connective tissue structures, juxtaligamental system and muscle by optical and transmission electron microscopy. The behaviour of spines in living animals was observed and two experiments were conducted to establish if the spine ligament is mutable collagenous tissue: these determined (1) if animals could detach spines to which plastic tags had been attached and (2) if the extension under constant load of isolated joint preparations was affected by high potassium stimulation. The articulation normally operates as a flexible joint in which the articular surfaces are separated by compliant connective tissue. The articular surfaces comprise a reniform apposition and peg-in-socket mechanical stop, and function primarily to stabilise spines in the erect position. Erect spines can be completely immobilised, which depends on the ligament having mutable tensile properties, as was inferred from the ability of animals to detach tagged spines and the responsiveness of isolated joint preparations to high potassium. The epidermis surrounding the joint has circumferential constrictions that facilitate compression folding and unfolding when the spine is inclined. The interarticular connective tissue is an acellular meshwork of collagen fibril bundles and may serve to reduce frictional forces between the articular surfaces. The ligament consists of parallel bundles of collagen fibrils and 7–14 nm microfibrils. Its passive elastic recoil contributes to the re-erection of inclined spines. The ligament is permeated by cell processes containing large dense-core vesicles, which belong to two types of juxtaligamental cells, one of which is probably peptidergic. The spine muscle consists of obliquely striated myocytes that are linked to the skeleton by extensions of their basement membranes. Muscle contraction may serve mainly to complete the process of spine erection by ensuring close contact between the articular surfaces. PMID:27974856

Xenogeneic Collagen Matrix Versus Connective Tissue Graft: Case Series of Various Gingival Recession Treatments.

PubMed

Chevalier, Grégoire; Cherkaoui, Selma; Kruk, Hanna; Bensaïd, Xavier; Danan, Marc

A xenogeneic collagen matrix recently has been suggested as an alternative to connective tissue graft for the treatment of gingival recession. The matrix avoids the second surgical site, and as a consequence could decrease surgical morbidity. This new matrix was used in various clinical situations and compared to connective tissue graft (CTG) in a split-mouth design case series. A total of 17 recessions were treated with a coronally advanced flap, 9 with CTG, and 8 with the matrix. Mean recession reduction was 2.00 mm with the CTG and 2.00 mm with the matrix. No significant statistical differences between the techniques were observed in this case report.

Xenogeneic Collagen Matrix Versus Connective Tissue Graft: Case Series of Various Gingival Recession Treatments.

PubMed

Chevalier, Grégoire; Cherkaoui, Selma; Kruk, Hanna; Bensaïd, Xavier; Danan, Marc

2016-08-24

A xenogeneic collagen matrix recently has been suggested as an alternative to connective tissue graft for the treatment of gingival recession. The matrix avoids the second surgical site, and as a consequence could decrease surgical morbidity. This new matrix was used in various clinical situations and compared to connective tissue graft (CTG) in a split-mouth design case series. A total of 17 recessions were treated with a coronally advanced flap, 9 with CTG, and 8 with the matrix. Mean recession reduction was 2.00 mm with the CTG and 2.00 mm with the matrix. No significant statistical differences between the techniques were observed in this case report.

Systemic sclerosis-scleroderma.

PubMed

Haustein, U-F

2002-06-01

Systemic sclerosis is a clinically heterogeneous, systemic disorder which affects the connective tissue of the skin, internal organs and the walls of blood vessels. It is characterized by alterations of the microvasculature, disturbances of the immune system and by massive deposition of collagen and other matrix substances in the connective tissue. This review discusses epidemiology and survival, clinical features including subsets and internal organ involvement, pathophysiology and genetics, microvasculature, immunobiology, fibroblasts and connective tissue metabolism and environmental factors. Early diagnosis and individually tailored therapy help to manage this disorder, which is treatable, but not curable. Therapy involves immunomodulation as well as the targeting of blood vessel mechanics and fibrosis. Physical therapy and psychotherapy are also important adjunctive therapies in this multifactorial disease.

Porphyromonas gingivalis: An Overview of Periodontopathic Pathogen below the Gum Line

PubMed Central

How, Kah Yan; Song, Keang Peng; Chan, Kok Gan

2016-01-01

Periodontal disease represents a group of oral inflammatory infections initiated by oral pathogens which exist as a complex biofilms on the tooth surface and cause destruction to tooth supporting tissues. The severity of this disease ranges from mild and reversible inflammation of the gingiva (gingivitis) to chronic destruction of connective tissues, the formation of periodontal pocket and ultimately result in loss of teeth. While human subgingival plaque harbors more than 500 bacterial species, considerable research has shown that Porphyromonas gingivalis, a Gram-negative anaerobic bacterium, is the major etiologic agent which contributes to chronic periodontitis. This black-pigmented bacterium produces a myriad of virulence factors that cause destruction to periodontal tissues either directly or indirectly by modulating the host inflammatory response. Here, this review provides an overview of P. gingivalis and how its virulence factors contribute to the pathogenesis with other microbiome consortium in oral cavity. PMID:26903954

CHANGES IN LUNG PARENCHYMA WITH PREOPERATIVE Co$sup 60$-IRRADIATION OF BRONCHIAL CARCINOMA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Widow, W.

1959-01-01

Histologic studies were made of resected lung tissue of 24 patients subjected to radiotherapy. Radiation pneumonitis with incipient fibrosis was observed in 14 cases. In only five of these cases could the histologic findings be confirmed radiologically. The histologic changes included swelling of alveolar septa, interstitial edema, increase of connective tissue components, giant cell formation, exfoliation of alveolar cells, intra-alveolar edema, depositio of cellular debris in small bronchi with apparent injury to the ciliated epithelial and mucous cells, and swelling of the peribronchial and perivascular tissue and pleura. Only a sparse inflammatory cell infiltrate was noted. These responses could notmore » be closely correlated with the radiation dose. The radiation reaction was most marked in the vicinity of old tuberculous lesions. No permanent impairment of pulmonary function would be expected from the observed histologic changes. (H.H.D.)« less

An Analysis of Pathological Activities of CCN Proteins in Joint Disorders: Mechanical Stretch-Mediated CCN2 Expression in Cultured Meniscus Cells.

PubMed

Furumatsu, Takayuki; Ozaki, Toshifumi

2017-01-01

The multifunctional growth factor CYR61/CTGF/NOV (CCN) 2, also known as connective tissue growth factor, regulates cellular proliferation, differentiation, and tissue regeneration. Recent literatures have described important roles of CCN2 in the meniscus metabolism. However, the mechanical stress-mediated transcriptional regulation of CCN2 in the meniscus remains unclear. The meniscus is a fibrocartilaginous tissue that controls complex biomechanics of the knee joint. Therefore, the injured unstable meniscus has a poor healing potential especially in the avascular inner region. In addition, dysfunction of the meniscus correlates with the progression of degenerative knee joint disorders and joint space narrowing. Here, we describe an experimental approach that investigates the distinct cellular behavior of inner and outer meniscus cells in response to mechanical stretch. Our experimental model can analyze the relationships between stretch-induced CCN2 expression and its functional role in the meniscus homeostasis.

Electromechanical integration of cardiomyocytes derived from human embryonic stem cells.

PubMed

Kehat, Izhak; Khimovich, Leonid; Caspi, Oren; Gepstein, Amira; Shofti, Rona; Arbel, Gil; Huber, Irit; Satin, Jonathan; Itskovitz-Eldor, Joseph; Gepstein, Lior

2004-10-01

Cell therapy is emerging as a promising strategy for myocardial repair. This approach is hampered, however, by the lack of sources for human cardiac tissue and by the absence of direct evidence for functional integration of donor cells into host tissues. Here we investigate whether cells derived from human embryonic stem (hES) cells can restore myocardial electromechanical properties. Cardiomyocyte cell grafts were generated from hES cells in vitro using the embryoid body differentiating system. This tissue formed structural and electromechanical connections with cultured rat cardiomyocytes. In vivo integration was shown in a large-animal model of slow heart rate. The transplanted hES cell-derived cardiomyocytes paced the hearts of swine with complete atrioventricular block, as assessed by detailed three-dimensional electrophysiological mapping and histopathological examination. These results demonstrate the potential of hES-cell cardiomyocytes to act as a rate-responsive biological pacemaker and for future myocardial regeneration strategies.

Oral telangiectatic granuloma with an intrabony defect

PubMed Central

Rathore, Akanksha; Jadhav, Tanya; Kulloli, Anita; Singh, Archana

2015-01-01

Oral telangiectatic granuloma is a benign hyperplastic lesion occurring in response to trauma or chronic irritation in the oral cavity. The characteristic histological appearance comprises of typical granulation tissue with a proliferation of small thin-walled blood vessels in the loose connective tissue. We describe a case of a 36-year-old female who had a swelling in the left maxillary region which was associated with the intrabony defect. An internal bevel gingivectomy was performed, and the histopathological report was suggestive of telangiectatic granuloma. The intrabony defect was managed with the placement of platelet rich fibrin plug in the defect. A follow-up at 6 months showed no recurrence and no loss in the width of keratinized tissue. The aim of this case is to highlight the rare association of intrabony defect with telangiectatic granuloma and the need for histopathological diagnosis in such lesions. PMID:26941527

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

PubMed Central

Li, Qiaoli; Uitto, Jouni

2014-01-01

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

In vitro fabrication of functional three-dimensional tissues with perfusable blood vessels

PubMed Central

Sekine, Hidekazu; Shimizu, Tatsuya; Sakaguchi, Katsuhisa; Dobashi, Izumi; Wada, Masanori; Yamato, Masayuki; Kobayashi, Eiji; Umezu, Mitsuo; Okano, Teruo

2013-01-01

In vitro fabrication of functional vascularized three-dimensional tissues has been a long-standing objective in the field of tissue engineering. Here we report a technique to engineer cardiac tissues with perfusable blood vessels in vitro. Using resected tissue with a connectable artery and vein as a vascular bed, we overlay triple-layer cardiac cell sheets produced from coculture with endothelial cells, and support the tissue construct with media perfused in a bioreactor. We show that endothelial cells connect to capillaries in the vascular bed and form tubular lumens, creating in vitro perfusable blood vessels in the cardiac cell sheets. Thicker engineered tissues can be produced in vitro by overlaying additional triple-layer cell sheets. The vascularized cardiac tissues beat and can be transplanted with blood vessel anastomoses. This technique may create new opportunities for in vitro tissue engineering and has potential therapeutic applications. PMID:23360990

The role of Toll-like receptor 2 and 4 in gingival tissues of chronic periodontitis subjects with type 2 diabetes.

PubMed

Promsudthi, A; Poomsawat, S; Limsricharoen, W

2014-06-01

Diabetes is one important risk factor of chronic periodontitis. However, the roles of toll-like receptor (TLR) 2 and TLR4, which are implicated in the inflammatory process in both chronic periodontitis and diabetes, have not been studied. This study aimed to determine whether TLR2 and TLR4 might be involved in the relationship between chronic periodontitis and diabetes by examining TLR2 and TLR4 expression in gingival tissues from subjects with chronic periodontitis without diabetes (CP) and with diabetes (CP+DM) and from periodontally healthy subjects without diabetes (PH) and with diabetes (PH+DM). Gingival tissues were collected from 23 CP subjects, 21 CP+DM subjects, 22 PH subjects and 20 PH+DM subjects. The expression of TLR2 and TLR4 in gingival tissues was determined using an immunohistochemical method. In gingival epithelium, staining patterns and intensity levels of TLR2 and TLR4 expression were studied. In connective tissues, the percentages of TLR2- and TLR4-positive cells were calculated. The intensity levels and the percentages of positive cells were statistically analyzed. Chronic periodontitis or diabetes showed no significant effect on TLR2 expression in the oral epithelium. However, diabetes increased the expression of TLR2 in sulcular epithelium and changed the pattern of TLR2 expression in gingival epithelium. Chronic periodontitis decreased the expression of TLR4 in gingival epithelium. In connective tissue under sulcular epithelium, CP+DM subjects showed statistically significant higher percentages of TLR2- and TLR4-positive cells compared with PH and PH+DM subjects. Our results suggest that hyperglycemia and chronic periodontitis had effects on TLR2 and TLR4 expression in gingival tissue. The differences in TLR2 and TLR4 expression could contribute to a greater inflammatory response, leading to periodontal disease initiation and progression. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Histologic analysis of the acellular dermal matrix graft incorporation process: a pilot study in dogs.

PubMed

Luczyszyn, Sonia M; Grisi, Márcio F M; Novaes, Arthur B; Palioto, Daniela B; Souza, Sérgio L S; Taba, Mario

2007-08-01

Clinical results with acellular dermal matrix graft (ADMG) in periodontal surgeries suggest that the material is incorporated by the host tissues. However, histologic studies of the ADMG incorporation process are limited. The objective of this study was to evaluate the incorporation of ADMG into gingival tissues in a dog model. Gingival recession-type defects were created at the canines of six dogs. After 6 weeks, periodontal surgeries to repair the defects were performed using ADMG. Two animals each were sacrificed after 4, 8, and 12 weeks. At 4 weeks, thick collagen fibers from the ADMG were clearly seen in the connective tissue, and some blood vessels were penetrating into the ADMG. At 8 weeks, blood vessel penetration was enhanced, and collagen fiber bundles from the ADMG were seen sending branches into the connective tissue in all directions. After 12 weeks, the ADMG and the connective tissue seemed to be well integrated into a single highly vascularized structure, indicating almost complete incorporation of the ADMG.

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

PubMed

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

2016-11-21

Connective tissues-skeleton, dermis, pericytes, fascia-are a key cell source for regenerating the patterned skeleton during axolotl appendage regeneration. This complexity has made it difficult to identify the cells that regenerate skeletal tissue. Inability to identify these cells has impeded a mechanistic understanding of blastema formation. By tracing cells during digit tip regeneration using brainbow transgenic axolotls, we show that cells from each connective tissue compartment have distinct spatial and temporal profiles of proliferation, migration, and differentiation. Chondrocytes proliferate but do not migrate into the regenerate. In contrast, pericytes proliferate, then migrate into the blastema and give rise solely to pericytes. Periskeletal cells and fibroblasts contribute the bulk of digit blastema cells and acquire diverse fates according to successive waves of migration that choreograph their proximal-distal and tissue contributions. We further show that platelet-derived growth factor signaling is a potent inducer of fibroblast migration, which is required to form the blastema. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Visualisation of Collagen in fixed skeletal muscle tissue using fluorescently tagged Collagen binding protein CNA35.

PubMed

Mohammadkhah, Melika; Simms, Ciaran K; Murphy, Paula

2017-02-01

Detection and visualisation of Collagen structure are important to understand the relationship between mechanical behaviour and microstructure in skeletal muscle since Collagen is the main structural protein in animal connective tissues, and is primarily responsible for their passive load-bearing properties. In the current study, the direct detection and visualization of Collagen using fluorescently tagged CNA35 binding protein (fused to EGFP or tdTomato) is reported for the first time on fixed skeletal muscle tissue. This Technical Note also establishes a working protocol by examining tissue preparation, dilution factor, exposure time etc. for sensitivity and specificity. Penetration of the binding protein into intact mature skeletal muscle was found to be very limited, but detection works well on tissue sections with higher sensitivity on wax embedded sections compared to frozen sections. CNA35 fused to tdTomato has a higher sensitivity than CNA35 fused to EGFP but both show specific detection. Best results were obtained with 15μm wax embedded sections, with blocking of non-specific binding in 1% BSA and antigen retrieval in Sodium Citrate. There was a play-off between dilution of the binding protein and time of incubation but both CNA35-tdTomato and CNA35-EGFP worked well with approximately 100μg/ml of purified protein with overnight incubation, while CNA35-tdTomato could be utilized at 5 fold less concentration. This approach can be applied to study the relationship between skeletal muscle micro-structure and to observe mechanical response to applied deformation. It can be used more broadly to detect Collagen in a variety of fixed tissues, useful for structure-functions studies, constitutive modelling, tissue engineering and assessment of muscle tissue pathologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Recombinant Amelogenin Protein Induces Apical Closure and Pulp Regeneration in Open-apex, Non-vital Permanent Canine Teeth

PubMed Central

Mounir, Maha M.F.; Matar, Moustafa A.; Lei, Yaping; Snead, Malcolm L.

2015-01-01

Introduction Recombinant DNA produced amelogenin protein was compared to calcium hydroxide in a study of immature apex closure conducted in 24 young mongrel dogs. Methods Root canals of maxillary and mandibular right premolars (n = 240) were instrumented and left open for 14 days. Canals were cleansed, irrigated and split equally for treatment with recombinant mouse amelogenin (n = 120) or calcium hydroxide (n = 120). Results After 1, 3, and 6 months, the animals were sacrificed and the treated teeth recovered for histological assessment and immunodetection of protein markers associated with odontogenic cells. After 1 month, amelogenin-treated canals revealed calcified tissue formed at the apical foramen and a pulp chamber containing soft connective tissue and hard tissue; amelogenin-treated canals assessed after 3 and 6 month intervals further included apical tissue functionally attached to bone by a periodontal ligament. In contrast, calcified apical tissue was poorly formed in the calcium hydroxide group and soft connective tissue within the pulp chamber was not observed. Conclusions The findings from this experimental strategy suggest recombinant amelogenin protein can signal cells to enhance apex formation in non-vital immature teeth and promote soft connective tissue regeneration. PMID:26709200

Pulmonary hypertension in rheumatic diseases: epidemiology and pathogenesis.

PubMed

Shahane, Anupama

2013-07-01

The focus of this review is to increase awareness of pulmonary arterial hypertension (PAH) in patients with rheumatic diseases. Epidemiology and pathogenesis of PAH in rheumatic diseases is reviewed, with recommendations for early screening and diagnosis and suggestion of possible role of immunosuppressive therapy in treatment for PAH in rheumatic diseases. A MEDLINE search for articles published between January 1970 and June 2012 was conducted using the following keywords: pulmonary hypertension, scleroderma, systemic sclerosis, pulmonary arterial hypertension, connective tissues disease, systemic lupus erythematosus, mixed connective tissue disease, rheumatoid arthritis, Sjogren's syndrome, vasculitis, sarcoidosis, inflammatory myopathies, dermatomyositis, ankylosing spondylitis, spondyloarthropathies, diagnosis and treatment. Pathogenesis and disease burden of PAH in rheumatic diseases was highlighted, with emphasis on early consideration and workup of PAH. Screening recommendations and treatment were touched upon. PAH is most commonly seen in systemic sclerosis and may be seen in isolation or in association with interstitial lung disease. Several pathophysiologic processes have been identified including an obliterative vasculopathy, veno-occlusive disease, formation of microthrombi and pulmonary fibrosis. PAH in systemic lupus erythematosus is associated with higher prevalence of antiphospholipid and anticardiolipin antibodies and the presence of Raynaud's phenomenon. Endothelial proliferation with vascular remodeling, abnormal coagulation with thrombus formation and immune-mediated vasculopathy are the postulated mechanisms. Improvement with immunosuppressive medications has been reported. Pulmonary fibrosis, extrinsic compression of pulmonary arteries and granulomatous vasculitis have been reported in patients with sarcoidosis. Intimal and medial hyperplasia with luminal narrowing has been observed in Sjogren's syndrome, mixed connective tissue disease and inflammatory myopathies. Pulmonary arterial hypertension (PAH) associated with rheumatic diseases carries a particularly grim prognosis with faster progression of disease and poor response to therapy. Though largely associated with systemic sclerosis, it is being increasingly recognized in other rheumatic diseases. An underlying inflammatory component may explain the poor response to therapy in patients with rheumatic diseases and is a rationale for consideration of immunosuppressive therapy in conjunction with vasodilator therapy in treatment for PAH. Further studies identifying pathogenetic pathways and possible targets of therapy, especially the role of immunomodulatory medications, are warranted.

Mandibular phosphaturic mesenchymal tumor-mixed connective tissue variant in a young girl.

PubMed

Luo, Lisa; Low, Nelson; Vandervord, John

2013-11-01

Phosphaturic mesenchymal tumor-mixed connective tissue variant (PMTMCT) is an extremely rare tumor associated with tumor-induced osteomalacia. The majority occur in middle age and arise from the extremities. This report describes a young girl with PMTMCT arising in the mandible and with no evidence of paraneoplastic syndrome.

Phototropism: translating light into directional growth.

PubMed

Hohm, Tim; Preuten, Tobias; Fankhauser, Christian

2013-01-01

Phototropism allows plants to align their photosynthetic tissues with incoming light. The direction of incident light is sensed by the phototropin family of blue light photoreceptors (phot1 and phot2 in Arabidopsis), which are light-activated protein kinases. The kinase activity of phototropins and phosphorylation of residues in the activation loop of their kinase domains are essential for the phototropic response. These initial steps trigger the formation of the auxin gradient across the hypocotyl that leads to asymmetric growth. The molecular events between photoreceptor activation and the growth response are only starting to be elucidated. In this review, we discuss the major steps leading from light perception to directional growth concentrating on Arabidopsis. In addition, we highlight links that connect these different steps enabling the phototropic response.

Development of spermatic granuloma in albino rats following administration of water extract of Heliotropium bacciferum Forssk

PubMed Central

Alanazi, Khalid; Alahmadi, Bassam A.; Alhimaidi, Ahmed; Abou-Tarboush, Faisal M.; Farah, Mohammad Abul; Mahmoud, Ahmed; Alfaifi, Mohamed

2015-01-01

A spermatic granuloma is a chronic inflammatory reaction produced in response to extravasated sperm within the intertubular connective tissue. The present study investigates the possible toxic effects of water extract of Heliotropium bacciferum on the reproductive system of male albino rats and the associated potential for the development of spermatic granulomas. H. bacciferum is a herbal plant used in traditional medicine and reported to have cytotoxic effects due to pyrrolizidine alkaloids. Histological examinations revealed no changes in the tissues of the testes, although, some changes were detected in the cauda epididymis, the most important of which was the development of small lesions of spermatic granulomas. Clear gaps were observed between the epithelial linings of the epididymal tubules. PMID:26858543

Development of spermatic granuloma in albino rats following administration of water extract of Heliotropium bacciferum Forssk.

PubMed

Alanazi, Khalid; Alahmadi, Bassam A; Alhimaidi, Ahmed; Abou-Tarboush, Faisal M; Farah, Mohammad Abul; Mahmoud, Ahmed; Alfaifi, Mohamed

2016-01-01

A spermatic granuloma is a chronic inflammatory reaction produced in response to extravasated sperm within the intertubular connective tissue. The present study investigates the possible toxic effects of water extract of Heliotropium bacciferum on the reproductive system of male albino rats and the associated potential for the development of spermatic granulomas. H. bacciferum is a herbal plant used in traditional medicine and reported to have cytotoxic effects due to pyrrolizidine alkaloids. Histological examinations revealed no changes in the tissues of the testes, although, some changes were detected in the cauda epididymis, the most important of which was the development of small lesions of spermatic granulomas. Clear gaps were observed between the epithelial linings of the epididymal tubules.

Broadband diffuse optical characterization of elastin for biomedical applications.

PubMed

Konugolu Venkata Sekar, Sanathana; Beh, Joo Sin; Farina, Andrea; Dalla Mora, Alberto; Pifferi, Antonio; Taroni, Paola

2017-10-01

Elastin is a key structural protein of dynamic connective tissues widely found in the extracellular matrix of skin, arteries, lungs and ligaments. It is responsible for a range of diseases related to aging of biological tissues. The optical characterization of elastin can open new opportunities for its investigation in biomedical studies. In this work, we present the absorption spectra of elastin using a broadband (550-1350nm) diffuse optical spectrometer. Distortions caused by fluorescence and finite bandwidth of the laser source on estimated absorption were effectively accounted for in measurements and data analysis and compensated. A comprehensive summary and comparison between collagen and elastin is presented, highlighting distinct features for its accurate quantification in biological applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Editorial. Oral submucous fibrosis: revised hypotheses as to its cause.

PubMed

Rajendran, R; Sukumaran, Anil

2013-09-01

Oral submucous fbrosis (OSF), being a prototype of pathological fbrosis, remains enigmatic as regards its causation. The connective tissue production is permanent and there is no reversal of the condition even after cessation of the habit of areca-nut usage; prime suspect in its causation.(1) The bulk of the connective tissue consists of type-1 collagen(2) and its formation does not appears to be caused by excessive proliferation of fbroblasts.(3) The effect of areca nut extract on in vitro fbroblasts varies on a concentration gradient, predominantly suppressing rather than stimulating the growth of the cells.(4) Based on morphological characteristics, the fbroblast population in the diseased mucosa has been classifed in to types F1, F2 and F3 with F3 cells producing signifcantly more collagen than the other two cell types. It was concluded that a change of fbroblast population has occurred in OSF and that this relative increase of F3 cells in humans, could be committed to the production of large quantities of collagen formation in OSF. It has been proposed that fbroblasts are functionally heterogeneous, the composition of any given normal or diseased connective tissue being a consequence in part of its particular mixture of fbroblast subtypes and density. Subtype deletion or amplifcation can result from selective cytotoxic or mitogenic responses induced by the binding environmental ligands.(5) Against this backdrop, we propose few de-novo attributes, hitherto unreported, and seem to be of relevance in the pathogenesis of OSF; namely the role of autophagy in basic cellular homeostatic process, important to cell fate decisions under conditions of stress and also ECM producing cells (fbroblasts, myofbroblasts and smooth muscle cells) derived from epithelial and endothelial cells through process termed epithelial and endothelial-mesenchymal transition.

Biomaterial-Mediated Delivery of Degradative Enzymes to Improve Meniscus Integration and Repair

PubMed Central

Qu, Feini; Lin, Jung-Ming G.; Esterhai, John L.; Fisher, Matthew B.; Mauck, Robert L.

2013-01-01

Endogenous repair of fibrous connective tissues is limited, and there exist few successful strategies to improve healing after injury. As such, new methods that advance repair by promoting cell growth, extracellular matrix (ECM) production, and tissue integration would represent a marked clinical advance. Using the meniscus as a test platform, we sought to develop an enzyme-releasing scaffold that enhances integrative repair. We hypothesized that the high ECM density and low cellularity present physical and biologic barriers to endogenous healing, and that localized collagenase treatment might expedite cell migration to the wound edge and tissue remodeling. To test this hypothesis, we fabricated a delivery system in which collagenase was stored inside electrospun poly(ethylene oxide) (PEO) nanofibers and released upon hydration. In vitro results showed that partial digestion of the wound interface improved repair by creating a microenvironment that facilitated cell migration, proliferation, and matrix deposition. Specifically, treatment with high-dose collagenase led to a 2-fold increase in cell density at the wound margin and a 2-fold increase in integrative tissue compared to untreated controls at 4 weeks (p≤0.05). Furthermore, when composite scaffolds containing both collagenase-releasing and structural fiber fractions were placed inside meniscal tears in vitro, enzyme release acted locally and resulted in a positive cellular response similar to that of global treatment with aqueous collagenase. This innovative approach of targeted enzyme delivery may aid the many patients that exhibit meniscal tears by promoting integration of the defect, thereby circumventing the pathologic consequences of partial meniscus removal, and may find widespread application in the treatment of injuries to a variety of dense connective tissues. PMID:23376132

Effects of protein-coated nanofibers on conformation of gingival fibroblast spheroids: potential utility for connective tissue regeneration.

PubMed

Kaufman, Gili; Whitescarver, Ryan A; Nunes, Laiz; Palmer, Xavier-Lewis; Skrtic, Drago; Tutak, Wojtek

2018-01-24

Deep wounds in the gingiva caused by trauma or surgery require a rapid and robust healing of connective tissues. We propose utilizing gas-brushed nanofibers coated with collagen and fibrin for that purpose. Our hypotheses are that protein-coated nanofibers will: (i) attract and mobilize cells in various spatial orientations, and (ii) regulate the expression levels of specific extracellular matrix (ECM)-associated proteins, determining the initial conformational nature of dense and soft connective tissues. Gingival fibroblast monolayers and 3D spheroids were cultured on ECM substrate and covered with gas-blown poly-(DL-lactide-co-glycolide) (PLGA) nanofibers (uncoated/coated with collagen and fibrin). Cell attraction and rearrangement was followed by F-actin staining and confocal microscopy. Thicknesses of the cell layers, developed within the nanofibers, were quantified by ImageJ software. The expression of collagen1α1 chain (Col1α1), fibronectin, and metalloproteinase 2 (MMP2) encoding genes was determined by quantitative reverse transcription analysis. Collagen- and fibrin- coated nanofibers induced cell migration toward fibers and supported cellular growth within the scaffolds. Both proteins affected the spatial rearrangement of fibroblasts by favoring packed cell clusters or intermittent cell spreading. These cell arrangements resembled the structural characteristic of dense and soft connective tissues, respectively. Within three days of incubation, fibroblast spheroids interacted with the fibers, and grew robustly by increasing their thickness compared to monolayers. While the ECM key components, such as fibronectin and MMP2 encoding genes, were expressed in both protein groups, Col1α1 was predominantly expressed in bundled fibroblasts grown on collagen fibers. This enhanced expression of collagen1 is typical for dense connective tissue. Based on results of this study, our gas-blown, collagen- and fibrin-coated PLGA nanofibers are viable candidates for engineering soft and dense connective tissues with the required structural characteristics and functions needed for wound healing applications. Rapid regeneration of these layers should enhance healing of open wounds in a harsh oral environment.

Systemic connective tissue features in women with fibromuscular dysplasia.

PubMed

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

2015-10-01

Fibromuscular dysplasia (FMD) is a non-atherosclerotic disease associated with hypertension, headache, dissection, stroke, and aneurysm. The etiology is unknown but hypothesized to involve genetic and environmental components. Previous studies suggest a possible overlap of FMD with other connective tissue diseases that present with dissections and aneurysms. The aim of this study was to investigate the prevalence of connective tissue physical features in FMD. A total of 142 FMD patients were consecutively enrolled at a single referral center (97.9% female, 92.1% of whom had multifocal FMD). Data are reported for 139 female patients. Moderately severe myopia (29.1%), high palate (33.1%), dental crowding (29.7%), and early-onset arthritis (15.6%) were prevalent features. Classic connective features such as hypertelorism, cleft palate, and hypermobility were uncommon. The frequency of systemic connective tissue features was compared between FMD patients with a high vascular risk profile (having had ⩾1 dissection and/or ⩾2 aneurysms) and those with a standard vascular risk profile. A history of spontaneous pneumothorax (5.9% high risk vs 0% standard risk) and atrophic scarring (17.6% high risk vs 6.8% standard risk) were significantly more prevalent in the high risk group, p<0.05. High palate was observed in 43.1% of the high risk group versus 27.3% in the standard risk group, p=0.055. In conclusion, in a cohort of women with FMD, there was a prevalence of moderately severe myopia, high palate, dental crowding, and early-onset osteoarthritis. However, a characteristic phenotype was not discovered. Several connective tissue features such as high palate and pneumothorax were more prominent among FMD patients with a high vascular risk profile. © The Author(s) 2015.

Systemic Connective Tissue Features in Women with Fibromuscular Dysplasia

PubMed Central

O’Connor, Sarah; Kim, Esther S. H.; Brinza, Ellen; Moran, Rocio; Fendrikova-Mahlay, Natalia; Wolski, Kathy; Gornik, Heather L.

2016-01-01

Background Fibromuscular Dysplasia (FMD) is an non-atherosclerotic disease associated with hypertension, headache, dissection, stroke, and aneurysm. The etiology is unknown but hypothesized to involve genetic and environmental components. Previous studies suggest a possible overlap of FMD with other connective tissue diseases that present with dissections and aneurysms. The aim of this study was to investigate the prevalence of connective tissue physical features in FMD. Methods and Results 142 FMD patients were consecutively enrolled at a single referral center (97.9% female, 92.3% had multifocal FMD). Data are reported for 139 female patients. Moderately severe myopia (29.1%), high palate (33.1%), dental crowding (29.7%), and early onset arthritis (15.6%) were prevalent features. Classic connective features such as hypertelorism, cleft palate, and hypermobility were uncommon. Frequency of systemic connective tissue features was compared between FMD patients with a high vascular risk profile (having had ≥1 dissection and/or ≥2 aneurysms) and those with a standard vascular risk profile. History of spontaneous pneumothorax (5.9% high risk vs. 0% standard risk) and atrophic scarring (17.3% high risk vs. 6.8% standard risk) were significantly more prevalent in the high risk group, p<0.05. High palate was observed in 43.1% of the high risk group vs. 27.3% in the standard risk group, p=0.055. Conclusions In a cohort of women with FMD, there was a prevalence of moderately severe myopia, high palate, dental crowding, and early onset osteoarthritis. However, a characteristic phenotype was not discovered. Several connective tissue features such as high palate and pneumothorax were more prominent among FMD patients with a high vascular risk profile. PMID:26156071

Acellular dermal matrix in soft tissue reconstruction prior to bone grafting. A case report.

PubMed

Ruiz-Magaz, Vanessa; Hernández-Alfaro, Federico; Díaz-Carandell, Artur; Biosca-Gómez-de-Tejada, María-José

2010-01-01

When hard tissue augmentation is scheduled as a part of an oral rehabilitation, prior to the treatment, it is important to assess if the quality of the underlying gingiva at the recipient site can support the bone grafting procedure. The most frequent complication during autologous onlay grafts are wound dehiscences in the recipient site, so the integrity of soft tissues is a basic aspect of successful reconstructive and plastic surgical procedure. Connective tissue grafts can improve the quality and quantity of soft tissue in oral sites where a hard tissue reconstruction is going to take place. However, particularly when large grafts are harvested, the autogenous donor site can present significant postoperative morbidity, such as necrosis of the palate fibromucosa and bone exposition, pain and bleeding. Another important limitation with the use of autogenous grafts is the limited supply of donor connective tissue. If a large site needs to be grafted, more than one surgical procedure may be required. An Acellular Dermal Matrix (ADM) graft has become increasingly popular as a substitute for donor connective tissue, eliminating the disadvantages described for the autogenous donor graft. The amount of tissue harvested is unlimited, so it gives an option for treating patients that have inadequate harvestable tissue or that present a large defect to be treated. The outcome of using ADM as a matrix for soft tissue reconstruction 12 weeks before bone grafting can reduce the risk of exposure and failure of the bone graft.

Humanized Androgen Receptor Mice: A Genetic Model for Differential Response to Prostate Cancer Therapy

DTIC Science & Technology

2012-07-01

prostate lobes were dissected free of fat and connective tissue and weighed separately. 2.3. Hormone assays All assays were performed in a single batch...Ferrell, R.E., Roth, S.M., 2005. Androgen receptor CAG repeat polymorphism is associated with fat -free mass in men. J. Appl. Physiol. 98, 132–137. Wu, C.T...S., Kennemer, M.I., Mohan, S., Nazarenko, I., Watanabe, C., Sparks, A.B., Shames , D.S., Gentleman, R., de Sauvage, F.J., Stern, H., Pandita, A

Investigation of Hematologic and Pathologic Response to Decompression.

DTIC Science & Technology

1978-05-10

in tadpole and very young kangaroos . Am. J. Physiol. 120:59—74 , 1937. 12. D’ C’~~~’ B.G. and Swanson , H. Bubble free decompression of blood samples...1955. 24. Takeda , Y. Studies of the metabol i~~ 5 and distribution of fibrino— gen in healthy men with autologous I-labe led fibrinogen. J. Clin...this connective tissue protein. However , the metabolism of bone collagen is affected by hormonal control (l0; 3l) and vitamin influences (3 ;ll). It

THE COMPARATIVE RESISTANCE OF BACTERIA AND HUMAN TISSUE CELLS TO CERTAIN COMMON ANTISEPTICS

PubMed Central

Lambert, Robert A.

1916-01-01

The comparative resistance of bacteria and human tissue cells to antiseptics and other chemicals may be easily tested by tissue cultures under conditions which approximate those found in the living body. A comparative study shows that while human cells (connective tissue and wandering cells) are highly resistant to many antiseptics, they are in general more easily killed than bacteria (Staphylococcus aureus). Of the antiseptics tested, which include mercuric chloride, iodine, potassium mercuric iodide, phenol, tricresol, hydrogen peroxide, hypochlorites (Dakin's solution), argyrol, and alcohol, the one which approaches most closely the ideal disinfectant is iodine, which kills bacteria in strengths that do not seriously injure connective tissue cells or wandering cells. PMID:19868066

Glycosaminoglycans and fibrillar collagen in Priapulida: a histo- and cytochemical study.

PubMed

Welsch, U; Erlinger, R; Storch, V

1992-12-01

The distribution of glycosaminoglycans and fibrillar collagen was studied in various tissues of priapulids, which represent an ancient group of marine metazoa. Sulphated glycosaminoglycans, as demonstrated at the electron microscopical level by Cupromeronic blue, were predominantly found in the cuticle, in basement membranes and also in the narrow connective tissue space below epidermis and anterior intestine. On the basis of their morphology the Cupromeronic blue precipitates could be divided into several groups. Fibrillar collagen occurred in the connective tissue under the epidermis and the epithelium of the anterior intestine. The spatial interrelationship between fibrillar collagen and glycosaminoglycans lacked with some exceptions, the high regularity found in connective tissues of other invertebrates and of vertebrates. This might be related to the special skeletal system of priapulids, consisting mainly of a strong extracellular cuticle and the turgor of the fluid-filled body cavity. In such a system the usual supportive structures seem to be of less functional significance.

How Muscle Structure and Composition Influence Meat and Flesh Quality

PubMed Central

Listrat, Anne; Lebret, Bénédicte; Louveau, Isabelle; Astruc, Thierry; Bonnet, Muriel; Lefaucheur, Louis; Picard, Brigitte; Bugeon, Jérôme

2016-01-01

Skeletal muscle consists of several tissues, such as muscle fibers and connective and adipose tissues. This review aims to describe the features of these various muscle components and their relationships with the technological, nutritional, and sensory properties of meat/flesh from different livestock and fish species. Thus, the contractile and metabolic types, size and number of muscle fibers, the content, composition and distribution of the connective tissue, and the content and lipid composition of intramuscular fat play a role in the determination of meat/flesh appearance, color, tenderness, juiciness, flavor, and technological value. Interestingly, the biochemical and structural characteristics of muscle fibers, intramuscular connective tissue, and intramuscular fat appear to play independent role, which suggests that the properties of these various muscle components can be independently modulated by genetics or environmental factors to achieve production efficiency and improve meat/flesh quality. PMID:27022618

The morphological difference between glaucoma and other optic neuropathies

PubMed Central

Burgoyne, Claude

2016-01-01

The clinical phenomenon of cupping has two principal pathophysiologic components in all optic neuropathies: prelaminar thinning and laminar deformation. We define prelaminar thinning to be the portion of cup enlargement that results from thinning of the prelaminar tissues due to physical compression and/or loss of Retinal Ganglion Cell axons. We define laminar deformation or laminar cupping to be the portion of cup enlargement that results from permanent, intraocular pressure-(IOP) induced deformation of the lamina cribrosa and peripapillary scleral connective tissues following damage and/or remodeling. We propose that the defining phenomenon of glaucomatous cupping is deformation and/or remodeling of the neural and connective tissues of the optic nerve head (ONH), which is governed by the distribution of IOP-related connective tissue stress and strain, regardless of the mechanism of insult or the level of IOP at which that deformation and/or remodeling occurs. Said in another way, “glaucomatous cupping” is the term clinicians use to describe the clinical appearance and behavior the ONH assumes as its neural and connective tissues deform, remodel or mechanically fail: 1) in a pattern and 2) by the several pathophysiologic processes governed by IOP-related connective tissue stress and strain. ONH Biomechanics explains why a given optic nerve head will demonstrate a certain form of “cupping” and at what level of IOP that might happen. Animal models are allowing us to tease apart the important components of cupping in IOP-related and non-IOP-related forms of optic neuropathy. A paradigm change in spectral domain optical coherence tomography ONH, retinal nerve fiber layer and Macular imaging should improve our ability to phenotype all forms of damage to the visual system including glaucoma. PMID:26274837

Nanomechanical signatures of oral submucous fibrosis in sub-epithelial connective tissue.

PubMed

Anura, Anji; Das, Debanjan; Pal, Mousumi; Paul, Ranjan Rashmi; Das, Soumen; Chatterjee, Jyotirmoy

2017-01-01

Oral sub-mucous fibrosis (OSF), a potentially malignant disorder, exhibits extensive remodeling of extra-cellular matrix in the form of sub-epithelial fibrosis which is a possible sequel of assaults from different oral habit related irritants. It has been assumed that micro/nanobio-mechanical imbalance experienced in the oral mucosa due to fibrosis may be deterministic for malignant potential (7-13%) of this pathosis. Present study explores changes in mechanobiological attributes of sub-epithelial connective tissue of OSF and the normal counterpart. The atomic force microscopy was employed to investigate tissue topography at micro/nano levels. It documented the presence of closely packed parallel arrangement of dense collagen fibers with wide variation in bandwidth and loss of D-space in OSF as compared to normal. The AFM based indentation revealed that sub-epithelium of OSF tissue has lost its flexibility with increased Young's modulus, stiffness, adhesiveness and reduced deformation of the juxta-epithealial connective tissue towards the deeper layer. These significant variations in nano-mechanical properties of the connective tissue indicated plausible impacts on patho-physiological microenvironment. Excessive deposition of collagen I and diminished expression of collagen III, fibronectin along with presence of α-SMA positive myofibroblast in OSF depicted its pathological basis and indicated the influence of altered ECM on this pathosis. The mechanobiological changes in OSF were corroborative with change in collagen composition recorded through immunohistochemistry and RT-PCR. The revelation of comparative nanomechanical profiles of normal oral mucosa and OSF in the backdrop of their structural and cardinal molecular attributes thus became pivotal for developing holistic pathobiological insight about possible connects for malignant transformation of this pre-cancer. Copyright © 2016 Elsevier Ltd. All rights reserved.

Cell-based and biomaterial approaches to connective tissue repair

NASA Astrophysics Data System (ADS)

Stalling, Simone Suzette

Connective tissue injuries of skin, tendon and ligament, heal by a reparative process in adults, filling the wound site with fibrotic, disorganized scar tissue that poorly reflects normal tissue architecture or function. Conversely, fetal skin and tendon have been shown to heal scarlessly. Complete regeneration is not intrinsically ubiquitous to all fetal tissues; fetal diaphragmatic and gastrointestinal injuries form scars. In vivo studies suggest that the presence of fetal fibroblasts is essential for scarless healing. In the orthopaedic setting, adult anterior cruciate ligament (ACL) heals poorly; however, little is known about the regenerative capacity of fetal ACL or fetal ACL fibroblasts. We characterized in vitro wound healing properties of fetal and adult ACL fibroblasts demonstrating that fetal ACL fibroblasts migrate faster and elaborate greater quantities of type I collagen, suggesting the healing potential of the fetal ACL may not be intrinsically poor. Similar to fetal ACL fibroblasts, fetal dermal fibroblasts also exhibit robust cellular properties. We investigated the age-dependent effects of dermal fibroblasts on tendon-to-bone healing in rat supraspinatus tendon injuries, a reparative injury model. We hypothesized delivery of fetal dermal fibroblasts would increase tissue organization and mechanical properties in comparison to adult dermal fibroblasts. However, at 1 and 8 weeks, the presence of dermal fibroblasts, either adult or fetal, had no significant effect on tissue histology or mechanical properties. There was a decreasing trend in cross-sectional area of repaired tendons treated with fetal dermal fibroblasts in comparison to adult, but this finding was not significant in comparison to controls. Finally, we synthesized a novel polysaccharide, methacrylated methylcellulose (MA-MC), and fabricated hydrogels using a well-established photopolymerization technique. We characterized the physical and mechanical properties of MA-MC hydrogels in 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.

Comparison of Demineralized Dentin and Demineralized Freeze Dried Bone as Carriers for Enamel Matrix Proteins in a Rat Critical Size Defect

DTIC Science & Technology

2005-05-01

matrix derivative or connective tissue . Part 1: comparison of clinical parameters. J Periodontol 2003;74:1110-1125. Minabe M.: A critical review of the... connective tissue , both bone and PDL can serve as sources of progenitor cells for regeneration. Surgical techniques started to evolve with the knowledge...regeneration was Prichard in 1977. This technique involved removal of overlying gingival tissue leaving interdental bone denuded (Prichard 1977). In 1983

Transcriptional Activation by NFκB Increases Perlecan/HSPG2 Expression in the Desmoplastic Prostate Tumor Microenvironment

PubMed Central

Warren, Curtis R.; Grindel, Brian J.; Francis, Lewis; Carson, Daniel D.; Farach-Carson, Mary C.

2014-01-01

Perlecan/HSPG2, a heparan sulfate proteoglycan typically found at tissue borders including those separating epithelia and connective tissue, increases near sites of invasion of primary prostatic tumors as previously shown for other proteins involved in desmoplastic tissue reaction. Studies of prostate cancer cells and stromal cells from both prostate and bone, the major site for prostate cancer metastasis, showed that cancer cells and a subset of stromal cells increased production of perlecan in response to cytokines present in the tumor microenvironment. In silico analysis of the HSPG2 promoter revealed two conserved NFκB binding sites, in addition to the previously reported SMAD3 binding sites. By systematically transfecting cells with a variety of reporter constructs including sequences up to 2.6 kb from the start site of transcription, we identified an active cis element in the distal region of the HSPG2 promoter, and showed that it functions in regulating transcription of HSPG2. Treatment with TNF-α and/or TGFβ1 identified TNF-α as a major cytokine regulator of perlecan production. TNF-α treatment also triggered p65 nuclear translocation and binding to the HSPG2 regulatory region in stromal cells and cancer cells. In addition to stromal induction of perlecan production in the prostate, we identified a matrix-secreting bone marrow stromal cell type that may represent the source for increases in perlecan in the metastatic bone marrow environment. These studies implicate perlecan in cytokine-mediated, innate tissue responses to cancer cell invasion, a process we suggest reflects a modified wound healing tissue response co-opted by prostate cancer cells. PMID:24700612

Immunohistochemical Analysis of the Role Connective Tissue Growth Factor in Drug-induced Gingival Overgrowth in Response to Phenytoin, Cyclosporine, and Nifedipine

PubMed Central

Anand, A. J.; Gopalakrishnan, Sivaram; Karthikeyan, R.; Mishra, Debasish; Mohapatra, Shreeyam

2018-01-01

Objective: To evaluate for the presence of connective tissue growth factor (CTGF) in drug (phenytoin, cyclosporine, and nifedipine)-induced gingival overgrowth (DIGO) and to compare it with healthy controls in the absence of overgrowth. Materials and Methods: Thirty-five patients were chosen for the study and segregated into study (25) and control groups (10). The study group consisted of phenytoin-induced (10), cyclosporine-induced (10), and nifedipine-induced (5) gingival overgrowth. After completing necessary medical evaluations, biopsy was done. The tissue samples were fixed in 10% formalin and then immunohistochemically evaluated for the presence of CTGF. The statistical analysis of the values was done using statistical package SPSS PC+ (Statistical Package for the Social Sciences, version 4.01). Results: The outcome of immunohistochemistry shows that DIGO samples express more CTGF than control group and phenytoin expresses more CTGF followed by nifedipine and cyclosporine. Conclusion: The study shows that there is an increase in the levels of CTGF in patients with DIGO in comparison to the control group without any gingival overgrowth. In the study, we compared the levels of CTGF in DIGO induced by three most commonly used drugs phenytoin, cyclosporine, and nifedipine. By comparing the levels of CTGF, we find that cyclosporine induces the production of least amount of CTGF. Therefore, it might be a more viable drug choice with reduced side effects. PMID:29629324

Epilobium angustifolium extract demonstrates multiple effects on dermal fibroblasts in vitro and skin photo-protection in vivo.

PubMed

Ruszová, Ema; Cheel, José; Pávek, Stanislav; Moravcová, Martina; Hermannová, Martina; Matějková, Ilona; Spilková, Jiřina; Velebný, Vladimír; Kubala, Lukáš

2013-09-01

Stress-induced fibroblast senescence is thought to contribute to skin aging. Ultraviolet light (UV) radiation is the most potent environmental risk factor in these processes. An Epilobium angustifolium (EA) extract was evaluated for its capacity to reverse the senescent response of normal human dermal fibroblasts (NHDF) in vitro and to exhibit skin photo-protection in vivo. The HPLC-UV-MS analysis of the EA preparation identified three major polyphenol groups: tannins (oenothein B), phenolic acids (gallic and chlorogenic acids) and flavonoids. EA extract increased the cell viability of senescent NHDF induced by serum deprivation. It diminished connective tissue growth factor and fibronectin gene expressions in senescent NHDF. Down-regulation of the UV-induced release of both matrix metalloproteinase-1 and -3 and the tissue inhibitor of matrix metalloproteinases-1 and -2, and also down-regulation of the gene expression of hyaluronidase 2 were observed in repeatedly UV-irradiated NHDF after EA extract treatment. Interestingly, EA extract diminished the down-regulation of sirtuin 1 dampened by UV-irradiation. The application of EA extract using a sub-irritating dose protected skin against UV-induced erythema formation in vivo. In summary, EA extract diminished stress-induced effects on NHDF, particularly on connective tissue growth factor, fibronectin and matrix metalloproteinases. These results collectively suggest that EA extract may possess anti-aging properties and that the EA polyphenols might account for these benefits.

Alterations of Dermal Connective Tissue Collagen in Diabetes: Molecular Basis of Aged-Appearing Skin

PubMed Central

Argyropoulos, Angela J.; Robichaud, Patrick; Balimunkwe, Rebecca Mutesi; Fisher, Gary J.; Hammerberg, Craig; Yan, Yan

2016-01-01

Alterations of the collagen, the major structural protein in skin, contribute significantly to human skin connective tissue aging. As aged-appearing skin is more common in diabetes, here we investigated the molecular basis of aged-appearing skin in diabetes. Among all known human matrix metalloproteinases (MMPs), diabetic skin shows elevated levels of MMP-1 and MMP-2. Laser capture microdissection (LCM) coupled real-time PCR indicated that elevated MMPs in diabetic skin were primarily expressed in the dermis. Furthermore, diabetic skin shows increased lysyl oxidase (LOX) expression and higher cross-linked collagens. Atomic force microscopy (AFM) further indicated that collagen fibrils were fragmented/disorganized, and key mechanical properties of traction force and tensile strength were increased in diabetic skin, compared to intact/well-organized collagen fibrils in non-diabetic skin. In in vitro tissue culture system, multiple MMPs including MMP-1 and MM-2 were induced by high glucose (25 mM) exposure to isolated primary human skin dermal fibroblasts, the major cells responsible for collagen homeostasis in skin. The elevation of MMPs and LOX over the years is thought to result in the accumulation of fragmented and cross-linked collagen, and thus impairs dermal collagen structural integrity and mechanical properties in diabetes. Our data partially explain why old-looking skin is more common in diabetic patients. PMID:27104752

Relative Composition of Fibrous Connective and Fatty/Glandular Tissue in Connective Tissue Grafts Depends on the Harvesting Technique but not the Donor Site of the Hard Palate.

PubMed

Bertl, Kristina; Pifl, Markus; Hirtler, Lena; Rendl, Barbara; Nürnberger, Sylvia; Stavropoulos, Andreas; Ulm, Christian

2015-12-01

Whether the composition of palatal connective tissue grafts (CTGs) varies depending on donor site or harvesting technique in terms of relative amounts of fibrous connective tissue (CT) and fatty/glandular tissue (FGT) is currently unknown and is histologically assessed in the present study. In 10 fresh human cadavers, tissue samples were harvested in the anterior and posterior palate and in areas close to (marginal) and distant from (apical) the mucosal margin. Mucosal thickness, lamina propria thickness (defined as the extent of subepithelial portion of the biopsy containing ≤25% or ≤50% FGT), and proportions of CT and FGT were semi-automatically estimated for the entire mucosa and for CTGs virtually harvested by split-flap (SF) preparation minimum 1 mm deep or after deepithelialization (DE). Palatal mucosal thickness, ranging from 2.35 to 6.89 mm, and histologic composition showed high interindividual variability. Lamina propria thickness (P >0.21) and proportions of CT (P = 0.48) and FGT (P = 0.15) did not differ significantly among the donor sites (anterior, posterior, marginal, apical). However, thicker palatal tissue was associated with higher FGT content (P <0.01) and thinner lamina propria (P ≤0.03). Independent of the donor site, DE-harvested CTG contained a significantly higher proportion of CT and a lower proportion of FGT than an SF-harvested CTG (P <0.04). Despite high interindividual variability in terms of relative tissue composition in the hard palate, DE-harvested CTG contains much larger amounts of CT and much lower amounts of FGT than SF-harvested CTG, irrespective of the harvesting site.

Pregnancy and autoimmune connective tissue diseases

PubMed Central

Marder, Wendy; Littlejohn, Emily A

2016-01-01

The autoimmune connective tissue diseases predominantly affect women and often occur during the reproductive years. Thus, specialized issues in pregnancy planning and management are commonly encountered in this patient population. This chapter provides a current overview of pregnancy as a risk factor for onset of autoimmune disease, considerations related to the course of pregnancy in several autoimmune connective tissue diseases, and disease management and medication issues before and during pregnancy and the postpartum period. A major theme that has emerged across these inflammatory diseases is that active maternal disease during pregnancy is associated with adverse pregnancy outcomes, and that maternal and fetal health can be optimized when conception is planned during times of inactive disease and through maintaining treatment regimens compatible with pregnancy. PMID:27421217

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

PubMed

Vij, Mukul; Agrawal, Vinita; Jain, Manoj

2014-07-01

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

Pathway Model of the Kinetics of the TGFbeta Antagonist Smad7 and Cross-Talk with the ATM and WNT Pathways

NASA Technical Reports Server (NTRS)

Carra, Claudio; Wang, Minli; Huff, Janice L.; Hada, Megumi; ONeill, Peter; Cucinotta, Francis A.

2010-01-01

Signal transduction controls cellular and tissue responses to radiation. Transforming growth factor beta (TGFbeta) is an important regulator of cell growth and differentiation and tissue homeostasis, and is often dis-regulated in tumor formation. Mathematical models of signal transduction pathways can be used to elucidate how signal transduction varies with radiation quality, and dose and dose-rate. Furthermore, modeling of tissue specific responses can be considered through mechanistic based modeling. We developed a mathematical model of the negative feedback regulation by Smad7 in TGFbeta-Smad signaling and are exploring possible connections to the WNT/beta -catenin, and ATM/ATF2 signaling pathways. A pathway model of TGFbeta-Smad signaling that includes Smad7 kinetics based on data in the scientific literature is described. Kinetic terms included are TGFbeta/Smad transcriptional regulation of Smad7 through the Smad3-Smad4 complex, Smad7-Smurf1 translocation from nucleus to cytoplasm, and Smad7 negative feedback regulation of the TGFO receptor through direct binding to the TGFO receptor complex. The negative feedback controls operating in this pathway suggests non-linear responses in signal transduction, which are described mathematically. We then explored possibilities for cross-talk mediated by Smad7 between DNA damage responses mediated by ATM, and with the WNT pathway and consider the design of experiments to test model driven hypothesis. Numerical comparisons of the mathematical model to experiments and representative predictions are described.

Preliminary embryological study of the radiological concept of retroperitoneal interfascial planes: what are the interfascial planes?

PubMed

Ishikawa, Kazuo; Nakao, Shota; Murakami, Gen; Rodríguez-Vázquez, Jose Francisco; Matsuoka, Tetsuya; Nakamuro, Makoto; Shimazu, Takeshi

2014-12-01

Recently, the radiological concept of retroperitoneal interfascial planes has been widely accepted to explain the extension of retroperitoneal pathologies. This study aimed to explore embryologically based corroborative evidence, which remains to be elucidated, for this concept. Using serial or semi-serial transverse sections from 29 human fetuses at the 5th-25th week of fetal age, we microscopically observed the development of the retroperitoneal fasciae and other structures in the retroperitoneal connective tissue. A hypothesis for the formation of the interfascial planes was generated from the developmental study and analysis of retroperitoneal fasciae in computed tomography images from 224 patients. Whereas the loose connective tissue was uniformly distributed in the retroperitoneum by the 9th week, the primitive renal and transversalis fasciae appeared at the 10th-12th week, as previous research has noted. By the 23rd week, the renal fascia, transversalis fascia, and primitive adipose tissue of the flank pad emerged. In addition, the primitive lateroconal fascia, which runs parallel to and close to the posterior renal fascia, emerged between the renal fascia and the adipose tissue of the flank pad. Conversely, pre-existing loose connective tissue was sandwiched between the opposing fasciae and was compressed and narrowed by the developing organs and fatty tissues. Through this developmental study, we provided the hypothesis that the compressed loose connective tissue and both opposed fasciae compose the interfascial planes. Analysis of the thickened retroperitoneal fasciae in computed tomography images supported this hypothesis. Further developmental or histological studies are required to verify our hypothesis.

Defining the hierarchical organisation of collagen VI microfibrils at nanometre to micrometre length scales.

PubMed

Godwin, Alan R F; Starborg, Tobias; Sherratt, Michael J; Roseman, Alan M; Baldock, Clair

2017-04-01

Extracellular matrix microfibrils are critical components of connective tissues with a wide range of mechanical and cellular signalling functions. Collagen VI is a heteromeric network-forming collagen which is expressed in tissues such as skin, lung, blood vessels and articular cartilage where it anchors cells into the matrix allowing for transduction of biochemical and mechanical signals. It is not understood how collagen VI is arranged into microfibrils or how these microfibrils are arranged into tissues. Therefore we have characterised the hierarchical organisation of collagen VI across multiple length scales. The frozen hydrated nanostructure of purified collagen VI microfibrils was reconstructed using cryo-TEM. The bead region has a compact hollow head and flexible tail regions linked by the collagenous interbead region. Serial block face SEM imaging coupled with electron tomography of the pericellular matrix (PCM) of murine articular cartilage revealed that the PCM has a meshwork-like organisation formed from globular densities ∼30nm in diameter. These approaches can characterise structures spanning nanometer to millimeter length scales to define the nanostructure of individual collagen VI microfibrils and the micro-structural organisation of these fibrils within tissues to help in the future design of better mimetics for tissue engineering. Cartilage is a connective tissue rich in extracellular matrix molecules and is tough and compressive to cushion the bones of joints. However, in adults cartilage is poorly repaired after injury and so this is an important target for tissue engineering. Many connective tissues contain collagen VI, which forms microfibrils and networks but we understand very little about these assemblies or the tissue structures they form. Therefore, we have use complementary imaging techniques to image collagen VI microfibrils from the nano-scale to the micro-scale in order to understand the structure and the assemblies it forms. These findings will help to inform the future design of scaffolds to mimic connective tissues in regenerative medicine applications. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Dynamic Hydrostatic Pressure Promotes Differentiation of Human Dental Pulp Stem Cells

PubMed Central

Yu, V; Damek-Poprawa, M.; Nicoll, S. B.; Akintoye, S.O.

2009-01-01

The masticatory apparatus absorbs high occlusal forces, but uncontrolled parafunctional or orthodontic forces damage periodontal ligament (PDL), cause pulpal calcification, pulp necrosis and tooth loss. Morphology and functional differentiation of connective tissue cells can be controlled by mechanical stimuli but effects of uncontrolled forces on intra-pulpal homeostasis and ability of dental pulp stem cells (DPSCs) to withstand direct external forces are unclear. Using dynamic hydrostatic pressure (HSP), we tested the hypothesis that direct HSP disrupts DPSC survival and odontogenic differentiation. DPSCs from four teenage patients were subjected to HSP followed by assessment of cell adhesion, survival and recovery capacity based on odontogenic differentiation, mineralization and responsiveness to bone morphogenetic protein-2 (BMP-2). HSP down-regulated DPSC adhesion and survival but promoted differentiation by increasing mineralization, in vivo hard tissue regeneration and BMP-2 responsiveness despite reduced cell numbers. HSP-treated DPSCs displayed enhanced odontogenic differentiation, an indication of favorable recovery from HSP-induced cellular stress. PMID:19555657

Immunosuppressive therapy in polymyositis

PubMed Central

Currie, S.; Walton, J. N.

1971-01-01

Immunosuppressive drugs were given to seven patients with polymyositis. The in-vitro activity of peripheral blood lymphocytes had previously been studied in five of these patients with findings suggestive of disturbed immunological processes. Some improvement occurred in five cases, but only in two was the improvement marked and sustained. In this small series of cases, the response to treatment was best in a patient with polymyositis who showed no evidence of involvement of tissues or organs other than muscle and in a second case with subacute polymyositis occurring in association with an unidentified connective tissue disorder. The response was less satisfactory in two patients with dermatomyositis, in two with polymyositis associated with systemic sclerosis, and in one in whom the muscle disorder complicated rheumatoid arthritis. At present such treatment is usually given only in cases which are resistant to, or intolerant of, steroids. The relative values of steroid and immunosuppressive therapy are discussed; a combination of the two in moderate doses may eventually prove to be the best initial treatment for the disorder. PMID:5096559

Stimulation artifact correction method for estimation of early cortico-cortical evoked potentials.

PubMed

Trebaul, Lena; Rudrauf, David; Job, Anne-Sophie; Mălîia, Mihai Dragos; Popa, Irina; Barborica, Andrei; Minotti, Lorella; Mîndruţă, Ioana; Kahane, Philippe; David, Olivier

2016-05-01

Effective connectivity can be explored using direct electrical stimulations in patients suffering from drug-resistant focal epilepsies and investigated with intracranial electrodes. Responses to brief electrical pulses mimic the physiological propagation of signals and manifest as cortico-cortical evoked potentials (CCEP). The first CCEP component is believed to reflect direct connectivity with the stimulated region but the stimulation artifact, a sharp deflection occurring during a few milliseconds, frequently contaminates it. In order to recover the characteristics of early CCEP responses, we developed an artifact correction method based on electrical modeling of the electrode-tissue interface. The biophysically motivated artifact templates are then regressed out of the recorded data as in any classical template-matching removal artifact methods. Our approach is able to make the distinction between the physiological responses time-locked to the stimulation pulses and the non-physiological component. We tested the correction on simulated CCEP data in order to quantify its efficiency for different stimulation and recording parameters. We demonstrated the efficiency of the new correction method on simulations of single trial recordings for early responses contaminated with the stimulation artifact. The results highlight the importance of sampling frequency for an accurate analysis of CCEP. We then applied the approach to experimental data. The model-based template removal was compared to a correction based on the subtraction of the averaged artifact. This new correction method of stimulation artifact will enable investigators to better analyze early CCEP components and infer direct effective connectivity in future CCEP studies. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Phagocytic response of astrocytes to damaged neighboring cells

PubMed Central

Cruz, Gladys Mae S.; Ro, Clarissa C.; Moncada, Emmanuel G.; Khatibzadeh, Nima; Flanagan, Lisa A.; Berns, Michael W.

2018-01-01

This study aims to understand the phagocytic response of astrocytes to the injury of neurons or other astrocytes at the single cell level. Laser nanosurgery was used to damage individual cells in both primary mouse cortical astrocytes and an established astrocyte cell line. In both cases, the release of material/substances from laser-irradiated astrocytes or neurons induced a phagocytic response in near-by astrocytes. Propidium iodide stained DNA originating from irradiated cells was visible in vesicles of neighboring cells, confirming phagocytosis of material from damaged cortical cells. In the presence of an intracellular pH indicator dye, newly formed vesicles correspond to acidic pH fluorescence, thus suggesting lysosome bound degradation of cellular debris. Cells with shared membrane connections prior to laser damage had a significantly higher frequency of induced phagocytosis compared to isolated cells with no shared membrane. The increase in phagocytic response of cells with a shared membrane occurred regardless of the extent of shared membrane (a thin filopodial connection vs. a cell cluster with significant shared membrane). In addition to the presence (or lack) of a membrane connection, variation in phagocytic ability was also observed with differences in injury location within the cell and distance separating isolated astrocytes. These results demonstrate the ability of an astrocyte to respond to the damage of a single cell, be it another astrocyte, or a neuron. This single-cell level of analysis results in a better understanding of the role of astrocytes to maintain homeostasis in the CNS, particularly in the sensing and removal of debris in damaged or pathologic nervous tissue. PMID:29708987

Dielectric properties of biological tissues in which cells are connected by communicating junctions

NASA Astrophysics Data System (ADS)

Asami, Koji

2007-06-01

The frequency dependence of the complex permittivity of biological tissues has been simulated using a simple model that is a cubic array of spherical cells in a parallel plate capacitor. The cells are connected by two types of communicating junctions: one is a membrane-lined channel for plasmodesmata in plant tissues, and the other is a conducting patch of adjoining plasma membranes for gap junctions in animal tissues. Both junctions provided similar effects on the dielectric properties of the tissue model. The model without junction showed a dielectric relaxation (called β-dispersion) that was expected from an interfacial polarization theory for a concentrated suspension of spherical cells. The dielectric relaxation was the same as that of the model in which neighbouring cells were connected by junctions perpendicular to the applied electric field. When neighbouring cells were connected by junctions parallel to the applied electric field or in all directions, a dielectric relaxation appeared at a lower frequency side in addition to the β-dispersion, corresponding to the so called α-dispersion. When junctions were randomly introduced at varied probabilities Pj, the low-frequency (LF) relaxation curve became broader, especially at Pj of 0.2-0.5, and its intensity was proportional to Pj up to 0.7. The intensity and the characteristic frequency of the LF relaxation both decreased with decreasing junction conductance. The simulations indicate that communicating junctions are important for understanding the LF dielectric relaxation in tissues.

Connective tissue growth factor immunohistochemical expression is associated with gallbladder cancer progression.

PubMed

Garcia, Patricia; Leal, Pamela; Alvarez, Hector; Brebi, Priscilla; Ili, Carmen; Tapia, Oscar; Roa, Juan C

2013-02-01

Gallbladder cancer (GBC) is an aggressive neoplasia associated with late diagnosis, unsatisfactory treatment, and poor prognosis. Molecular mechanisms involved in GBC pathogenesis remain poorly understood. Connective tissue growth factor (CTGF) is thought to play a role in the pathologic processes and is overexpressed in several human cancers, including GBC. No information is available about CTGF expression in early stages of gallbladder carcinogenesis. Objective.- To evaluate the expression level of CTGF in benign and malignant lesions of gallbladder and its correlation with clinicopathologic features and GBC prognosis. Connective tissue growth factor protein was examined by immunohistochemistry on tissue microarrays containing tissue samples of chronic cholecystitis (n = 51), dysplasia (n = 15), and GBC (n = 169). The samples were scored according to intensity of staining as low/absent and high CTGF expressers. Statistical analysis was performed using the χ(2) test or Fisher exact probability test with a significance level of P < .05. Survival analysis was assessed by the Kaplan-Meier method and the log-rank test. Connective tissue growth factor expression showed a progressive increase from chronic cholecystitis to dysplasia and then to early and advanced carcinoma. Immunohistochemical expression (score ≥2) was significantly higher in advanced tumors, in comparison with chronic cholecystitis (P < .001) and dysplasia (P = .03). High levels of CTGF expression correlated with better survival (P = .04). Our results suggest a role for CTGF in GBC progression and a positive association with better prognosis. In addition, they underscore the importance of considering the involvement of inflammation on GBC development.

Modulation of inflammation and disease tolerance by DNA damage response pathways.

PubMed

Neves-Costa, Ana; Moita, Luis F

2017-03-01

The accurate replication and repair of DNA is central to organismal survival. This process is challenged by the many factors that can change genetic information such as replication errors and direct damage to the DNA molecule by chemical and physical agents. DNA damage can also result from microorganism invasion as an integral step of their life cycle or as collateral damage from host defense mechanisms against pathogens. Here we review the complex crosstalk of DNA damage response and immune response pathways that might be evolutionarily connected and argue that DNA damage response pathways can be explored therapeutically to induce disease tolerance through the activation of tissue damage control processes. Such approach may constitute the missing pillar in the treatment of critical illnesses caused by multiple organ failure, such as sepsis and septic shock. © 2016 Federation of European Biochemical Societies.

Recombinant Amelogenin Protein Induces Apical Closure and Pulp Regeneration in Open-apex, Nonvital Permanent Canine Teeth.

PubMed

Mounir, Maha M F; Matar, Moustafa A; Lei, Yaping; Snead, Malcolm L

2016-03-01

Recombinant DNA-produced amelogenin protein was compared with calcium hydroxide in a study of immature apex closure conducted in 24 young mongrel dogs. Root canals of maxillary and mandibular right premolars (n = 240) were instrumented and left open for 14 days. Canals were cleansed, irrigated, and split equally for treatment with recombinant mouse amelogenin (n = 120) or calcium hydroxide (n = 120). After 1, 3, and 6 months, the animals were sacrificed and the treated teeth recovered for histologic assessment and immunodetection of protein markers associated with odontogenic cells. After 1 month, amelogenin-treated canals revealed calcified tissue formed at the apical foramen and a pulp chamber containing soft connective tissue and hard tissue; amelogenin-treated canals assessed after 3- and 6-month intervals further included apical tissue functionally attached to bone by a periodontal ligament. In contrast, calcified apical tissue was poorly formed in the calcium hydroxide group, and soft connective tissue within the pulp chamber was not observed. The findings from this experimental strategy suggest recombinant amelogenin protein can signal cells to enhance apex formation in nonvital immature teeth and promote soft connective tissue regeneration. Copyright © 2016 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Morphological Evaluation of Soft Tissue Augmentation Using Porous Poly-DL-Lactic Acid With Straight Holes.

PubMed

Ken, Yukawa; Noriko, Tachikawa; Furuichi, Akiko; Shohei, Kasugai

2016-12-01

This study investigated the biological reaction to porous poly-DL-lactic acid (PDLLA) scaffolds with holes for soft tissue augmentation. The control group was porous PDLLA with a diameter of 5.0 mm and a height of 2.0 mm. For the 2 test groups, 7 holes were drilled from the upper to the lower base of the scaffolds; the holes had diameters of 0.5 and 1.0 mm. A scaffold was placed in the periosteum of the cranium. The height and molecular weight (Mw) of the scaffolds were measured at 4 and 8 weeks. Hematoxylin and eosin staining was used to measure the connective tissue and blood vessel areas. All groups had similar scaffold heights, but the Mw decreased significantly over time. There were significant differences in the connective tissue and blood vessel areas among the control, 0.5-mm, and 1.0-mm groups at the same time point. The soft tissue was increased by drilling holes in the scaffolds. Porous poly-DL-lactic acid (PDLLA) contributed favorable prognosis for soft tissue. A wider hole was associated with increased connective tissue and blood vessel areas. The scaffold height and Mw were not impacted by size of the holes.

Treatment of chronic desquamative gingivitis using tissue-engineered human cultured gingival epithelial sheets: a case report.

PubMed

Okuda, Kazuhiro; Momose, Manabu; Murata, Masashi; Saito, Yoshinori; lnoie, Masukazu; Shinohara, Chikara; Wolff, Larry F; Yoshie, Hiromasa

2004-04-01

Human cultured gingival epithelial sheets were used as an autologous grafting material for regenerating gingival tissue in the maxillary left and mandibular right quadrants of a patient with chronic desquamative gingivitis. Six months post-surgery in both treated areas, there were gains in keratinized gingiva and no signs of gingival inflammation compared to presurgery. In the maxillary left quadrant, preoperative histopathologic findings revealed the epithelium was separated from the connective tissue and inflammatory cells were extensive. After grafting with the gingival epithelial sheets, inflammatory cells were decreased and separation between epithelium and connective tissue was not observed. The human cultured gingival epithelial sheets fabricated using tissue engineering technology showed significant promise for gingival augmentation in periodontal therapy.

Morphogenetic events in the perinodal connective tissue in a metastatic cancer model.

PubMed

Conti, G; Minicozzi, A; Merigo, F; Marzola, P; Osculati, F; Cordiano, C; Sbarbati, A

2013-02-01

The modifications of connective tissue surrounding metastatic lymph nodes in a murine model of rectal cancer are described. Athymic nude mice (n=36) were inoculated with 10×10(5) ht-29 cancer cells into the submucosal layer of the rectum. Control mice (n=5) were treated with a sterile buffer. Tumor and the involved lymph nodes were visualized in vivo by magnetic resonance imaging at 1 to 4 weeks after cell injection. After the sacrifice, the excised samples were processed for histology. After one week from cell injection all treated animals developed rectal cancer. Since the first week, neoplastic cells were visible in the nodes. In the surrounding connective tissue, the diameter of the adipocytes was reduced and a mesenchymal-like pattern with stellate cells embedded in an oedematous environment was visible. Since the second week, in the perinodal connective an enlargement of the stroma was present. The tissue was organized in cords and areas with extracellular accumulation of lipids were found. At the fourth week, we observed an enlargement of multilocular areas and lobules of elongated elements almost devoid of lipid droplets. In control animals, in absence of neoplastic masses, pelvic nodes were surrounded by a typical connective tissue characterized by unilocular adipocytes with groups of multilocular adipocytes. We have developed a model of rectal cancer with nodal metastases. Using this model, the work demonstrates that around secondary lesions, the morphogenetic events follow a standard evolution characterized by an early phase with lipolysis and mesenchymalization and later phases with a brown-like phenotype acquisition. Copyright © 2012. Published by Elsevier SAS.

Differential diagnosis and diagnostic flow chart of joint hypermobility syndrome/ehlers-danlos syndrome hypermobility type compared to other heritable connective tissue disorders.

PubMed

Colombi, Marina; Dordoni, Chiara; Chiarelli, Nicola; Ritelli, Marco

2015-03-01

Joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT) is an evolving and protean disorder mostly recognized by generalized joint hypermobility and without a defined molecular basis. JHS/EDS-HT also presents with other connective tissue features affecting a variety of structures and organs, such as skin, eye, bone, and internal organs. However, most of these signs are present in variable combinations and severity in many other heritable connective tissue disorders. Accordingly, JHS/EDS-HT is an "exclusion" diagnosis which needs the absence of any consistent feature indicative of other partially overlapping connective tissue disorders. While both Villefranche and Brighton criteria include such an exclusion as a mandatory item, a systematic approach for reaching a stringent clinical diagnosis of JHS/EDS-HT is still lacking. The absence of a consensus on the diagnostic approach to JHS/EDS-HT concerning its clinical boundaries with similar conditions contribute to limit our actual understanding of the pathologic and molecular bases of this disorder. In this review, we revise the differential diagnosis of JHS/EDS-HT with those heritable connective tissue disorders which show a significant overlap with the former and mostly include EDS classic, vascular and kyphoscoliotic types, osteogenesis imperfecta, Marfan syndrome, Loeys-Dietz syndrome, arterial tortuosity syndrome, and lateral meningocele syndrome. A diagnostic flow chart is also offered with the attempt to support the less experienced clinician in stringently recognizing JHS/EDS-HT and stimulate the debate in the scientific community for both management and research purposes. © 2015 Wiley Periodicals, Inc.

Early postnatal feed restriction reduces liver connective tissue levels and affects H3K9 acetylation state of regulated genes associated with protein metabolism in low birth weight pigs.

PubMed

Nebendahl, Constance; Görs, Solvig; Albrecht, Elke; Krüger, Ricarda; Martens, Karen; Giller, Katrin; Hammon, Harald M; Rimbach, Gerald; Metges, Cornelia C

2016-03-01

Intrauterine growth retardation is associated with metabolic consequences in adulthood. Since our previous data indicate birth weight-dependent effects of feed restriction (R) on protein degradation processes in the liver, it should be investigated whether effects on connective tissue turnover are obvious and could be explained by global changes of histone H3K9me3 and H3K9ac states in regulated genes. For this purpose, female littermate pigs with low (U) or normal (N) birth weight were subjected to 3-week R (60% of ad libitum fed controls) with subsequent refeeding (REF) for further 5 weeks. The 3-week R-period induced a significant reduction of connective tissue area by 43% in the liver of U animals at 98 d of age, which was not found in age-matched N animals. Of note, after REF at 131 d of age, in previously feed-restricted U animals (UR), the percentage of mean connective tissue was only 53% of ad libitum fed controls (UK), indicating a persistent effect. In U animals, R induced H3K9 acetylation of regulated genes (e.g. XBP1, ERLEC1, GALNT2, PTRH2), which were inter alia associated with protein metabolism. In contrast, REF was mostly accompanied by deacetylation in U and N animals. Thus, our epigenetic data may give a first explanation for the observed birth weight-dependent differences in this connective tissue phenotype. Copyright © 2015 Elsevier Inc. All rights reserved.

Long palatal connective tissue rolled pedicle graft with demineralized freeze-dried bone allograft plus platelet-rich fibrin combination: A novel technique for ridge augmentation - Three case reports

PubMed Central

Reddy, Pathakota Krishnajaneya; Bolla, Vijayalakshmi; Koppolu, Pradeep; Srujan, Peruka

2015-01-01

Replacement of missing maxillary anterior tooth with localized residual alveolar ridge defect is challenging, considering the high esthetic demand. Various soft and hard tissue procedures were proposed to correct alveolar ridge deformities. Novel techniques have evolved in treating these ridge defects to improve function and esthetics. In the present case reports, a novel technique using long palatal connective tissue rolled pedicle graft with demineralized freeze-dried bone allografts (DFDBAs) plus Platelet-rich fibrin (PRF) combination was proposed to correct the Class III localized anterior maxillary anterior alveolar ridge defect. The present technique resulted in predictable ridge augmentation, which can be attributed to the soft and hard tissue augmentation with a connective tissue pedicle and DFDBA plus PRF combination. This technique suggests a variation in roll technique with DFDBA plus PRF and appears to promise in gaining predictable volume in the residual ridge defect and can be considered for the treatment of moderate to severe maxillary anterior ridge defects. PMID:26015679

Heterogeneous structure and surface tension effects on mechanical response in pulmonary acinus: A finite element analysis.

PubMed

Koshiyama, Kenichiro; Nishimoto, Keisuke; Ii, Satoshi; Sera, Toshihiro; Wada, Shigeo

2018-01-20

The pulmonary acinus is a dead-end microstructure that consists of ducts and alveoli. High-resolution micro-CT imaging has recently provided detailed anatomical information of a complete in vivo acinus, but relating its mechanical response with its detailed acinar structure remains challenging. This study aimed to investigate the mechanical response of acinar tissue in a whole acinus for static inflation using computational approaches. We performed finite element analysis of a whole acinus for static inflation. The acinar structure model was generated based on micro-CT images of an intact acinus. A continuum mechanics model of the lung parenchyma was used for acinar tissue material model, and surface tension effects were explicitly included. An anisotropic mechanical field analysis based on a stretch tensor was combined with a curvature-based local structure analysis. The airspace of the acinus exhibited nonspherical deformation as a result of the anisotropic deformation of acinar tissue. A strain hotspot occurred at the ridge-shaped region caused by a rod-like deformation of acinar tissue on the ridge. The local structure becomes bowl-shaped for inflation and, without surface tension effects, the surface of the bowl-shaped region primarily experiences isotropic deformation. Surface tension effects suppressed the increase in airspace volume and inner surface area, while facilitating anisotropic deformation on the alveolar surface. In the lungs, the heterogeneous acinar structure and surface tension induce anisotropic deformation at the acinar and alveolar scales. Further research is needed on structural variation of acini, inter-acini connectivity, or dynamic behavior to understand multiscale lung mechanics. Copyright © 2018 Elsevier Ltd. All rights reserved.

Immunohistochemical distribution of chromogranin A in medicolegal autopsy materials.

PubMed

Yoshida, Chiemi; Ishikawa, Takaki; Michiue, Tomomi; Zhao, Dong; Komatsu, Ayumi; Quan, Li; Maeda, Hitoshi

2009-04-01

Chromogranin A (CgA) was recently reported as a marker of various stress responses. The aim of this study was to investigate the immunohistochemical distribution of CgA in human tissues in medicolegal autopsy cases as a basis for postmortem investigation of stress responses. The autopsy cases (n=30, within 48 h postmortem) comprised cases of mechanical asphyxia (n=15: strangulation, n=8; hanging, n=7) and acute myocardial infarction/ischemia (AMI, n=15). Routinely formalin-fixed paraffin-embedded tissue sections, including those of the hypothalamus, pituitary gland, cardiac muscle, lungs, liver, kidneys, spleen, skeletal muscle, skin, thyroid gland, submandibular gland, pancreas, and adrenal gland, were stained with polyclonal anti-human CgA antibodies and CgA positivity was quantitatively examined. Localization of CgA immunopositivity was clearly demonstrated in specific cell components in all tissue sections. CgA was mainly observed in the anterior lobe of the pituitary, adrenal medulla, neurons and some gliocytes in the hypothalamus, submandibular gland, follicular epithelial cells and connective tissue in the thyroid gland and pancreatic islet cells. CgA immunopositivity showed no significant difference between mechanical asphyxia and AMI cases. Positivity was slightly higher in adenohypophysis, adrenal medullar, and pancreatic islet cells (approximately 50-80%) than in the thyroid and submandibular glands (approximately 30-60%); however, a large case difference was observed in hypothalamic CgA immunopositivity (0-100%). These findings suggest that hypothalamic CgA immunopositivity can be used as a marker for investigating individual differences in stress responses during the death process. Further investigation of other causes of death is needed.

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

PubMed Central

Ram, Saravanan; Sedghizadeh, Parish P.

2013-01-01

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

Foreign body in the oral cavity mimicking a benign connective tissue tumor.

PubMed

Puliyel, Divya; Balouch, Amir; Ram, Saravanan; Sedghizadeh, Parish P

2013-01-01

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

Conformal, wearable, thin microwave antenna for sub-skin and skin surface monitoring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Converse, Mark C.; Chang, John T.; Duoss, Eric B.

A wearable antenna is operably positioned on a wearer's skin and is operably connected the wearer's tissue. A first antenna matched to the wearer's tissue is operably positioned on the wearer's skin. A second antenna matched to the air is operably positioned on the wearer's skin. Transmission lines connect the first antenna and the second antenna.

The role of focal adhesion kinase in the regulation of cellular mechanical properties

NASA Astrophysics Data System (ADS)

Mierke, Claudia Tanja

2013-12-01

The regulation of mechanical properties is necessary for cell invasion into connective tissue or intra- and extravasation through the endothelium of blood or lymph vessels. Cell invasion is important for the regulation of many healthy processes such as immune response reactions and wound healing. In addition, cell invasion plays a role in disease-related processes such as tumor metastasis and autoimmune responses. Until now the role of focal adhesion kinase (FAK) in regulating mechanical properties of cells and its impact on cell invasion efficiency is still not well known. Thus, this review focuses on mechanical properties regulated by FAK in comparison to the mechano-regulating protein vinculin. Moreover, it points out the connection between cancer cell invasion and metastasis and FAK by showing that FAK regulates cellular mechanical properties required for cellular motility. Furthermore, it sheds light on the indirect interaction of FAK with vinculin by binding to paxillin, which then impairs the binding of paxillin to vinculin. In addition, this review emphasizes whether FAK fulfills regulatory functions similar to vinculin. In particular, it discusses the differences and the similarities between FAK and vinculin in regulating the biomechanical properties of cells. Finally, this paper highlights that both focal adhesion proteins, vinculin and FAK, synergize their functions to regulate the mechanical properties of cells such as stiffness and contractile forces. Subsequently, these mechanical properties determine cellular invasiveness into tissues and provide a source sink for future drug developments to inhibit excessive cell invasion and hence, metastases formation.

Fetal programming of fat and collagen in porcine skeletal muscles

PubMed Central

Karunaratne, JF; Ashton, CJ; Stickland, NC

2005-01-01

Connective tissue plays a key role in the scaffolding and development of skeletal muscle. Pilot studies carried out in our laboratory have shown that the smallest porcine littermate has a higher content of connective tissue within skeletal muscle compared with its largest littermate. The present study investigated the prenatal development of intralitter variation in terms of collagen content within connective tissue and intramuscular fat of the M. semitendinosus. Twenty-three pairs of porcine fetuses from a Large White–Landrace origin were used aged from 36 to 86 days of gestation. The largest and smallest littermates were chosen by weight and the M. semitendinosus was removed from each. Complete transverse muscle sections were stained with Oil Red O (detection of lipids) and immunocytochemistry was performed using an antibody to collagen I. Slides were analysed and paired t-Tests revealed the smallest littermate contained a significantly higher proportion of fat deposits and collagen I content compared with the largest littermate. Recent postnatal studies showing elevated levels of intramuscular lipids and low scores for meat tenderness in the smallest littermate corroborate our investigations. It can be concluded that the differences seen in connective tissue elements have a fetal origin that may continue postnatally. PMID:16367803

A cytogenetic analysis of 2 cases of phosphaturic mesenchymal tumor of mixed connective tissue type.

PubMed

Graham, Rondell P; Hodge, Jennelle C; Folpe, Andrew L; Oliveira, Andre M; Meyer, Kevin J; Jenkins, Robert B; Sim, Franklin H; Sukov, William R

2012-08-01

Phosphaturic mesenchymal tumor of mixed connective tissue type is a rare, histologically distinctive mesenchymal neoplasm associated with tumor-induced osteomalacia resulting from production of the phosphaturic hormone fibroblast growth factor 23. Because of its rarity, specific genetic alterations that contribute to the pathogenesis of these tumors have yet to be elucidated. Herein, we report the abnormal karyotypes from 2 cases of confirmed phosphaturic mesenchymal tumor of mixed connective tissue type. G-banded analysis demonstrated the first tumor to have a karyotype of 46,Y,t(X;3;14)(q13;p25;q21)[15]/46XY[5], and the second tumor to have a karyotype of 46, XY,add(2)(q31),add(4)(q31.1)[2]/92,slx2[3]/46,sl,der(2)t(2;4)(q14.2;p14),der(4)t(2;4)(q14.2;p14),add(4)(q31.1)[10]/46,sdl,add(13)(q34)[4]/92,sdl2x2[1]. These represent what is, to our knowledge, the first examples of abnormal karyotypes obtained from phosphaturic mesenchymal tumor of mixed connective tissue type. Copyright © 2012 Elsevier Inc. All rights reserved.

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

PubMed Central

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

2004-01-01

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

Pathological changes in the subsynovial connective tissue increase with self-reported carpal tunnel syndrome symptoms.

PubMed

Tat, Jimmy; Wilson, Katherine E; Keir, Peter J

2015-05-01

Fibrosis and thickening of the subysnovial connective tissue are the most common pathological findings in carpal tunnel syndrome. The relationship between subsynovial connective tissue characteristics and self-reported carpal tunnel syndrome symptoms was assessed. Symptoms were characterized using the Boston Carpal Tunnel Questionnaire and Katz hand diagram in twenty-two participants (11 with symptoms, 11 with no symptoms). Using ultrasound, the thickness of the subsynovial connective tissue was measured using a thickness ratio (subsynovial thickness/tendon thickness) and gliding function was assessed using a shear strain index ((Displacement(tendon)-Displacement(subsynovial))/Displacement(tendon)x 100). For gliding function, participants performed 10 repeated flexion-extension cycles of the middle finger at a rate of one cycle per second. Participants with symptoms had a 38.5% greater thickness ratio and 39.2% greater shear strain index compared to participants without symptoms (p<0.05). Ultrasound detected differences the SSCT in symptomatic group that was characterized by low self-reported symptom severity scores. This study found ultrasound useful for measuring structural and functional changes in the SSCT that could provide insight in the early pathophysiology associated with carpal tunnel syndrome symptoms. Copyright © 2015 Elsevier Ltd. All rights reserved.

Differential immunoglobulin class-mediated responses to components of the U1 small nuclear ribonucleoprotein particle in systemic lupus erythematosus and mixed connective tissue disease.

PubMed

Mesa, A; Somarelli, J A; Wu, W; Martinez, L; Blom, M B; Greidinger, E L; Herrera, R J

2013-11-01

The objective of this paper is to determine whether patients with systemic lupus erythematosus (SLE) and mixed connective tissue disease (MCTD) possess differential IgM- and IgG-specific reactivity against peptides from the U1 small nuclear ribonucleoprotein particle (U1 snRNP). The IgM- and IgG-mediated responses against 15 peptides from subunits of the U1 snRNP were assessed by indirect enzyme linked immunosorbent assays (ELISAs) in sera from patients with SLE and MCTD and healthy individuals (n = 81, 41, and 31, respectively). Additionally, 42 laboratory tests and 40 clinical symptoms were evaluated to uncover potential differences. Binomial logistic regression analyses (BLR) were performed to construct models to support the independent nature of SLE and MCTD. Receiver operating characteristic (ROC) curves corroborated the classification power of the models. We analyzed IgM and IgG anti-U1 snRNP titers to classify SLE and MCTD patients. IgG anti-U1 snRNP reactivity segregates SLE and MCTD from nondisease controls with an accuracy of 94.1% while IgM-specific anti-U1 snRNP responses distinguish SLE from MCTD patients with an accuracy of 71.3%. Comparison of the IgG and IgM anti-U1 snRNP approach with clinical tests used for diagnosing SLE and MCTD revealed that our method is the best classification tool of those analyzed (p ≤ 0.0001). Our IgM anti-U1 snRNP system along with lab tests and symptoms provide additional molecular and clinical evidence to support the hypothesis that SLE and MCTD may be distinct syndromes.

Mechanisms of bradykinin-induced expression of connective tissue growth factor and nephrin in podocytes

PubMed Central

Msallem, J. Abou; Chalhoub, H.; Al-Hariri, M.; Saad, L.; Jaffa, M. A.; Ziyadeh, F. N.

2015-01-01

Diabetic nephropathy (DN) is the main cause of morbidity and mortality in diabetes and is characterized by mesangial matrix deposition and podocytopathy, including podocyte loss. The risk factors and mechanisms involved in the pathogenesis of DN are still not completely defined. In the present study, we aimed to understand the cellular mechanisms through which activation of B2 kinin receptors contribute to the initiation and progression of DN. Stimulation of cultured rat podocytes with bradykinin (BK) resulted in a significant increase in ROS generation, and this was associated with a significant increase in NADPH oxidase (NOX)1 and NOX4 protein and mRNA levels. BK stimulation also resulted in a signicant increase in the phosphorylation of ERK1/2 and Akt, and this effect was inhibited in the presence of NOX1 and Nox4 small interfering (si)RNA. Furthermore, podocytes stimulated with BK resulted in a significant increase in protein and mRNA levels of connective tissue growth factor (CTGF) and, at the same time, a significant decrease in protein and mRNA levels of nephrin. siRNA targeted against NOX1 and NOX4 significantly inhibited the BK-induced increase in CTGF. Nephrin expression was increased in response to BK in the presence of NOX1 and NOX4 siRNA, thus implicating a role for NOXs in modulating the BK response in podocytes. Moreover, nephrin expression in response to BK was also significantly increased in the presence of siRNA targeted against CTGF. These findings provide novel aspects of BK signal transduction pathways in pathogenesis of DN and identify novel targets for interventional strategies. PMID:26447218

Fascia: A missing link in our understanding of the pathology of fibromyalgia.

PubMed

Liptan, Ginevra L

2010-01-01

Significant evidence exists for central sensitization in fibromyalgia, however the cause of this process in fibromyalgia-and how it relates to other known abnormalities in fibromyalgia-remains unclear. Central sensitization occurs when persistent nociceptive input leads to increased excitability in the dorsal horn neurons of the spinal cord. In this hyperexcited state, spinal cord neurons produce an enhanced responsiveness to noxious stimulation, and even to formerly innocuous stimulation. No definite evidence of muscle pathology in fibromyalgia has been found. However, there is some evidence for dysfunction of the intramuscular connective tissue, or fascia, in fibromyalgia. This paper proposes that inflammation of the fascia is the source of peripheral nociceptive input that leads to central sensitization in fibromyalgia. The fascial dysfunction is proposed to be due to inadequate growth hormone production and HPA axis dysfunction in fibromyalgia. Fascia is richly innervated, and the major cell of the fascia, the fibroblast, has been shown to secrete pro-inflammatory cytokines, particularly IL-6, in response to strain. Recent biopsy studies using immuno-histochemical staining techniques have found increased levels of collagen and inflammatory mediators in the connective tissue surrounding the muscle cells in fibromyalgia patients. The inflammation of the fascia is similar to that described in conditions such as plantar fasciitis and lateral epicondylitis, and may be better described as a dysfunctional healing response. This may explain why NSAIDs and oral steroids have not been found effective in fibromyalgia. Inflammation and dysfunction of the fascia may lead to central sensitization in fibromyalgia. If this hypothesis is confirmed, it could significantly expand treatment options to include manual therapies directed at the fascia such as Rolfing and myofascial release, and direct further research on the peripheral pathology in fibromyalgia to the fascia.

Tumor-induced osteomalacia with elevated fibroblast growth factor 23: a case of phosphaturic mesenchymal tumor mixed with connective tissue variants and review of the literature

PubMed Central

Hu, Fang-Ke; Yuan, Fang; Jiang, Cheng-Ying; Lv, Da-Wei; Mao, Bei-Bei; Zhang, Qiang; Yuan, Zeng-Qiang; Wang, Yan

2011-01-01

Tumor-induced osteomalacia (TIO), or oncogenic osteomalacia (OOM), is a rare acquired Paraneoplastic disease characterized by renal phosphate wasting and hypophosphatemia. Recent evidence shows that tumor-overexpressed fibroblast growth factor 23 (FGF23) is responsible for the hypophosphatemia and osteomalacia. The tumors associated with TIO are usually phosphaturic mesenchymal tumor mixed connective tissue variants (PMTMCT). Surgical removal of the responsible tumors is clinically essential for the treatment of TIO. However, identifying the responsible tumors is often difficult. Here, we report a case of a TIO patient with elevated serum FGF23 levels suffering from bone pain and hypophosphatemia for more than three years. A tumor was finally located in first metacarpal bone by octreotide scintigraphy and she was cured by surgery. After complete excision of the tumor, serum FGF23 levels rapidly decreased, dropping to 54.7% of the preoperative level one hour after surgery and eventually to a little below normal. The patient's serum phosphate level rapidly improved and returned to normal level in four days. Accordingly, her clinical symptoms were greatly improved within one month after surgery. There was no sign of tumor recurrence during an 18-month period of follow-up. According to pathology, the tumor was originally diagnosed as “glomangioma” based upon a biopsy sample, “proliferative giant cell tumor of tendon sheath” based upon sections of tumor, and finally diagnosed as PMTMCT by consultation one year after surgery. In conclusion, although an extremely rare disease, clinicians and pathologists should be aware of the existence of TIO and PMTMCT, respectively. PMID:22035861

Multifidus Muscle Changes After Back Injury Are Characterized by Structural Remodeling of Muscle, Adipose and Connective Tissue, but Not Muscle Atrophy: Molecular and Morphological Evidence.

PubMed

Hodges, Paul W; James, Gregory; Blomster, Linda; Hall, Leanne; Schmid, Annina; Shu, Cindy; Little, Chris; Melrose, James

2015-07-15

Longitudinal case-controlled animal study. To investigate putative cellular mechanisms to explain structural changes in muscle and adipose and connective tissues of the back muscles after intervertebral disc (IVD) injury. Structural back muscle changes are ubiquitous with back pain/injury and considered relevant for outcome, but their exact nature, time course, and cellular mechanisms remain elusive. We used an animal model that produces phenotypic back muscle changes after IVD injury to study these issues at the cellular/molecular level. Multifidus muscle was harvested from both sides of the spine at L1-L2 and L3-L4 IVDs in 27 castrated male sheep at 3 (n = 10) or 6 (n = 17) months after a surgical anterolateral IVD injury at both levels. Ten control sheep underwent no surgery (3 mo, n = 4; 6 mo, n = 6). Tissue was harvested at L4 for histological analysis of cross-sectional area of muscle and adipose and connective tissue (whole muscle), plus immunohistochemistry to identify proportion and cross-sectional area of individual muscle fiber types in the deepest fascicle. Quantitative polymerase chain reaction measured gene expression of typical cytokines/signaling molecules at L2. Contrary to predictions, there was no multifidus muscle atrophy (whole muscle or individual fiber). There was increased adipose and connective tissue (fibrotic proliferation) cross-sectional area and slow-to-fast muscle fiber transition at 6 but not 3 months. Within the multifidus muscle, increases in the expression of several cytokines (tumor necrosis factor α and interleukin-1β) and molecules that signal trophic/atrophic processes for the 3 tissue types (e.g., growth factor pathway [IGF-1, PI3k, Akt1, mTOR], potent tissue modifiers [calcineurin, PCG-1α, and myostatin]) were present. This study provides cellular evidence that refutes the presence of multifidus muscle atrophy accompanying IVD degeneration at this intermediate time point. Instead, adipose/connective tissue increased in parallel with the expression of the genes that provide putative mechanisms for multifidus structural remodeling. This provides novel targets for pharmacological and physical interventions. N/A.

Tracing the evolutionary origin of vertebrate skeletal tissues: insights from cephalochordate amphioxus.

PubMed

Yong, Luok Wen; Yu, Jr-Kai

2016-08-01

Vertebrate mineralized skeletal tissues are widely considered as an evolutionary novelty. Despite the importance of these tissues to the adaptation and radiation of vertebrate animals, the evolutionary origin of vertebrate skeletal tissues remains largely unclear. Cephalochordates (Amphioxus) occupy a key phylogenetic position and can serve as a valuable model for studying the evolution of vertebrate skeletal tissues. Here we summarize recent advances in amphioxus developmental biology and comparative genomics that can help to elucidate the evolutionary origins of the vertebrate skeletal tissues and their underlying developmental gene regulatory networks (GRN). By making comparisons to the developmental studies in vertebrate models and recent discoveries in paleontology and genomics, it becomes evident that the collagen matrix-based connective tissues secreted by the somite-derived cells in amphioxus likely represent the rudimentary skeletal tissues in chordates. We propose that upon the foundation of this collagenous precursor, novel tissue mineralization genes that arose from gene duplications were incorporated into an ancestral mesodermal GRN that makes connective and supporting tissues, leading to the emergence of highly-mineralized skeletal tissues in early vertebrates. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

PubMed

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

2015-01-01

Localized changes in cutaneous elastic tissue often manifest with flesh-colored, hypopigmented, or yellow papules, plaques, and nodules. We present five children with clinically similar cobblestone plaques composed of multiple hypopigmented, nonfollicular, pinpoint papules located unilaterally over the upper chest. All lesions first appeared at birth or during early infancy. No associated extracutaneous abnormalities have been identified. Histopathology was remarkable for many, thick elastic fibers with elastorrhexis. We believe that these cases represent a distinct and unique variant of connective tissue nevi. © 2014 Wiley Periodicals, Inc.

Oncogenic osteomalacia associated with phosphaturic mesenchymal tumour, mixed connective tissue type of the knee.

PubMed

Szumera-Ciećkiewicz, Anna; Ptaszyński, Konrad; Pawełas, Andrzej; Rutkowski, Piotr

2009-01-01

One of the most unusual and uncommon types of osteomalacia is the oncogenic osteomalacia that is predominantly caused by a soft tissue or bone tumour, mostly by a phosphaturic mesenchymal tumour, mixed connective tissue type (PMTMCT). We report a case of a 27-year-old male presented with complaints of progressive and generalized muscle weakness, bone pains and multiple fractures. Intra-articular PMTMCT of the knee was diagnosed and surgically removed. We describe histopathological features of PMTMCT and review the most recent studies concerning this diagnostic problem.

Effects of long-duration bed rest on structural compartments of m. soleus in man

NASA Technical Reports Server (NTRS)

Belozerova, I.; Shenkman, B.; Mazin, M.; Leblanc, A.; LeBlanc, A. D. (Principal Investigator)

2001-01-01

Magnetic resonance imaging (MRI), histomorphometry and electron microscopy of muscle demonstrate that long-term exposure to actual or simulated weightlessness (including head down bed rest) leads to decreased volume of antigravity muscles in mammals. In muscles interbundle space is occupied by the connective tissue. Rat studies show that hindlimb unloading induces muscle fiber atrophy along with increase in muscle non-fiber connective tissue compartment. Beside that, usually 20% of the muscle fiber volume is comprised by non-contractile (non-myofibrillar) compartment. The aim of the present study was to compare changes in muscle volume, and in muscle fiber size with alterations in myofibrillar apparatus, and in connective tissue compartment in human m. soleus under conditions of 120 day long head down bed rest (HDBR).

Surgical anatomy of the retroperitoneal spaces--part I: embryogenesis and anatomy.

PubMed

Mirilas, Petros; Skandalakis, John E

2009-11-01

Embryologically, the retroperitoneal (extraperitoneal) connective tissue includes three strata, which respectively form the internal fascia lining of the body wall, the renal fascia, and the covering of the gastrointestinal viscera. All organs, vessels, and nerves, that lie on the posterior abdominal wall, along with their tissues and surrounding connective and fascial planes, are collectively referred to as the retroperitoneum. The retroperitoneal space is the area of the posterior abdominal wall that is located between the parietal peritoneum and the fascia. Within the greater retroperitoneal space, there are also several small spaces, or subcompartments. Loose connective tissue and fat surround the anatomic entities, and, to a variable degree, occupy the subcompartments. The multilaminar thoracolumbar (lumbodorsal) fascia begins at the occipital area and terminates at the sacrum.

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

PubMed

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

2010-10-01

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

New perspectives on rare connective tissue calcifying diseases.

PubMed

Rashdan, Nabil A; Rutsch, Frank; Kempf, Hervé; Váradi, András; Lefthériotis, Georges; MacRae, Vicky E

2016-06-01

Connective tissue calcifying diseases (CTCs) are characterized by abnormal calcium deposition in connective tissues. CTCs are caused by multiple factors including chronic diseases (Type II diabetes mellitus, chronic kidney disease), the use of pharmaceuticals (e.g. warfarin, glucocorticoids) and inherited rare genetic diseases such as pseudoxanthoma elasticum (PXE), generalized arterial calcification in infancy (GACI) and Keutel syndrome (KTLS). This review explores our current knowledge of these rare inherited CTCs, and highlights the most promising avenues for pharmaceutical intervention. Advancing our understanding of rare inherited forms of CTC is not only essential for the development of therapeutic strategies for patients suffering from these diseases, but also fundamental to delineating the mechanisms underpinning acquired chronic forms of CTC. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Patch esophagoplasty using an in-body-tissue-engineered collagenous connective tissue membrane.

PubMed

Okuyama, Hiroomi; Umeda, Satoshi; Takama, Yuichi; Terasawa, Takeshi; Nakayama, Yasuhide

2018-02-01

Although many approaches to esophageal replacement have been investigated, these efforts have thus far only met limited success. In-body-tissue-engineered connective tissue tubes have been reported to be effective as vascular replacement grafts. The aim of this study was to investigate the usefulness of an In-body-tissue-engineered collagenous connective tissue membrane, "Biosheet", as a novel esophageal scaffold in a beagle model. We prepared Biosheets by embedding specially designed molds into subcutaneous pouches in beagles. After 1-2months, the molds, which were filled with ingrown connective tissues, were harvested. Rectangular-shaped Biosheets (10×20mm) were then implanted to replace defects of the same size that had been created in the cervical esophagus of the beagle. An endoscopic evaluation was performed at 4 and 12weeks after implantation. The esophagus was harvested and subjected to a histological evaluation at 4 (n=2) and 12weeks (n=2) after implantation. The animal study protocols were approved by the National Cerebral and Cardiovascular Centre Research Institute Committee (No. 16048). The Biosheets showed sufficient strength and flexibility to replace the esophagus defect. All animals survived with full oral feeding during the study period. No anastomotic leakage was observed. An endoscopic study at 4 and 12weeks after implantation revealed that the anastomotic sites and the internal surface of the Biosheets were smooth, without stenosis. A histological analysis at 4weeks after implantation demonstrated that stratified squamous epithelium was regenerated on the internal surface of the Biosheets. A histological analysis at 12weeks after implantation showed the regeneration of muscle tissue in the implanted Biosheets. The long-term results of patch esophagoplasty using Biosheets showed regeneration of stratified squamous epithelium and muscular tissues in the implanted sheets. These results suggest that Biosheets may be useful as a novel esophageal scaffold. Copyright © 2017 Elsevier Inc. All rights reserved.

Immunohistochemical expression of matrix metalloproteinase 13 in chronic periodontitis.

PubMed

Nagasupriya, Alapati; Rao, Donimukkala Bheemalingeswara; Ravikanth, Manyam; Kumar, Nalabolu Govind; Ramachandran, Cinnamanoor Rajmani; Saraswathi, Thillai Rajashekaran

2014-01-01

The extracellular matrix is a complex integrated system responsible for the physiologic properties of connective tissue. Collagen is the major extracellular component that is altered in pathologic conditions, mainly periodontitis. The destruction involves proteolytic enzymes, primarily matrix metalloproteinases (MMPs), which play a key role in mediating and regulating the connective tissue destruction in periodontitis. The study group included 40 patients with clinically diagnosed chronic periodontitis. The control group included 20 patients with clinically normal gingiva covering impacted third molars undergoing extraction or in areas where crown-lengthening procedures were performed. MMP-13 expression was demonstrated using immunohistochemistry in all the gingival biopsies, and the data were analyzed statistically. MMP-13 expression was observed more in chronic periodontitis when compared with normal gingiva. MMP-13 expression was expressed by fibroblasts, lymphocytes, macrophages, plasma cells, and basal cells of the sulcular epithelium. Comparative evaluation of all the clinical and histologic parameters with MMP-13 expression showed high statistical significance with Spearman correlation coefficient. Elevated levels of MMP-13 may play a role in the pathogenesis of chronic periodontitis. There is a direct correlation of increased expression of MMP-13 with various clinical and histologic parameters in disease severity.

Effects of repeated cycles of starvation and refeeding on lungs of growing rats.

PubMed

Sahebjami, H; Domino, M

1992-12-01

Adult male rats were subjected to four cycles of mild starvation (2 wk) and refeeding (1 wk) and were compared with a fed group. Starvation was induced by giving rats one-third of their measured daily food consumption. During each starvation cycle, rats lost approximately 20% of their body weight. Despite catch-up growth and overall weight gain, starved rats had lower final body weight than fed rats. Lung dry weight and lung volumes were also reduced in the starved group. The mechanical properties of air- and saline-filled lungs did not change significantly with repeated cycles of starvation. Mean linear intercept was similar in the two groups, but alveolar surface area was reduced in the starved rats. Total content of crude connective tissue and concentration per lung dry weight of hydroxyproline and crude connective tissue were reduced in starved rats. We conclude that lung growth is retarded in growing rats subjected to repeated cycles of mild starvation and refeeding, as manifested by smaller lung volume and reduced alveolar surface area. Because alveolar size is unchanged, a reduced number of alveoli is most likely responsible for decreased lung volumes.

[REACTIVE CHANGES IN SPINAL CORD MOTONEURONS AFTER SCIATIC NERVE INJURY AFTER HIGH-FREQUENCY ELECTROSURGICAL INSTRUMENT APPLICATION].

PubMed

Korsak, A; Chaikovsky, Yu; Sokurenko, L; Likhodiievskyi, V; Neverovskyi, A

2016-02-01

A new experimental model for tissues connection at peripheral nerve injury site in form of tissues welding was designed. In current study we investigated motoneuron state 1, 3, 6 and 12 weeks after peripheral nerve injury and surgical repair with high-frequency electrosurgical technology. Spinal cord sections was stained by Nissl method and observed with light microscopy. We found that postoperative period in animals from experimental groups characterized by qualitative changes in neurons from spinal motor centers that can be interpreted as compensatory processes as response to alteration. In animals from group with high-frequency electrosurgical technology usage stabilization processes passes more quickly comparatively to animals with epineural sutures. High-frequency electrosurgical technology usage provides less harmful effects on motoneurons than epineural suturing.

DOE Office of Scientific and Technical Information (OSTI.GOV)

McMahon, S.

Radiation therapy for the treatment of cancer has been established as a highly precise and effective way to eradicate a localized region of diseased tissue. To achieve further significant gains in the therapeutic ratio, we need to move towards biologically optimized treatment planning. To achieve this goal, we need to understand how the radiation-type dependent patterns of induced energy depositions within the cell (physics) connect via molecular, cellular and tissue reactions to treatment outcome such as tumor control and undesirable effects on normal tissue. Several computational biology approaches have been developed connecting physics to biology. Monte Carlo simulations are themore » most accurate method to calculate physical dose distributions at the nanometer scale, however simulations at the DNA scale are slow and repair processes are generally not simulated. Alternative models that rely on the random formation of individual DNA lesions within one or two turns of the DNA have been shown to reproduce the clusters of DNA lesions, including single strand breaks (SSBs), double strand breaks (DSBs) without the need for detailed track structure simulations. Efficient computational simulations of initial DNA damage induction facilitate computational modeling of DNA repair and other molecular and cellular processes. Mechanistic, multiscale models provide a useful conceptual framework to test biological hypotheses and help connect fundamental information about track structure and dosimetry at the sub-cellular level to dose-response effects on larger scales. In this symposium we will learn about the current state of the art of computational approaches estimating radiation damage at the cellular and sub-cellular scale. How can understanding the physics interactions at the DNA level be used to predict biological outcome? We will discuss if and how such calculations are relevant to advance our understanding of radiation damage and its repair, or, if the underlying biological processes are too complex for a mechanistic approach. Can computer simulations be used to guide future biological research? We will debate the feasibility of explaining biology from a physicists’ perspective. Learning Objectives: Understand the potential applications and limitations of computational methods for dose-response modeling at the molecular, cellular and tissue levels Learn about mechanism of action underlying the induction, repair and biological processing of damage to DNA and other constituents Understand how effects and processes at one biological scale impact on biological processes and outcomes on other scales J. Schuemann, NCI/NIH grantsS. McMahon, Funding: European Commission FP7 (grant EC FP7 MC-IOF-623630)« less

Automatic recognition of fundamental tissues on histology images of the human cardiovascular system.

PubMed

Mazo, Claudia; Trujillo, Maria; Alegre, Enrique; Salazar, Liliana

2016-10-01

Cardiovascular disease is the leading cause of death worldwide. Therefore, techniques for improving diagnosis and treatment in this field have become key areas for research. In particular, approaches for tissue image processing may support education system and medical practice. In this paper, an approach to automatic recognition and classification of fundamental tissues, using morphological information is presented. Taking a 40× or 10× histological image as input, three clusters are created with the k-means algorithm using a structural tensor and the red and the green channels. Loose connective tissue, light regions and cell nuclei are recognised on 40× images. Then, the cell nuclei's features - shape and spatial projection - and light regions are used to recognise and classify epithelial cells and tissue into flat, cubic and cylindrical. In a similar way, light regions, loose connective and muscle tissues are recognised on 10× images. Finally, the tissue's function and composition are used to refine muscle tissue recognition. Experimental validation is then carried out by histologist following expert criteria, along with manually annotated images that are used as a ground-truth. The results revealed that the proposed approach classified the fundamental tissues in a similar way to the conventional method employed by histologists. The proposed automatic recognition approach provides for epithelial tissues a sensitivity of 0.79 for cubic, 0.85 for cylindrical and 0.91 for flat. Furthermore, the experts gave our method an average score of 4.85 out of 5 in the recognition of loose connective tissue and 4.82 out of 5 for muscle tissue recognition. Copyright © 2016 Elsevier Ltd. All rights reserved.

The structure-mechanical relationship of palm vascular tissue.

PubMed

Wang, Ningling; Liu, Wangyu; Huang, Jiale; Ma, Ke

2014-08-01

The structure-mechanical relationship of palm sheath is studied with numerical and experimental methods. The cellular structure of the vascular tissue is rebuilt with an image-based reconstruction method and used to create finite element models. The validity of the models is firstly verified with the results from the tensile tests. Then, the cell walls inside each of the specific regions (fiber cap, vessel, xylem, etc.) are randomly removed to obtain virtually imperfect structures. By comparing the magnitudes of performance degradation in the different imperfect structures, the influences of each region on the overall mechanical performances of the vascular tissue are discussed. The longitudinal stiffness and yield strength are sensitive to the defects in the vessel regions. While in the transverse directions (including the radial and tangential directions), the parenchymatous tissue determines the mechanical properties of the vascular tissue. Moreover, the hydraulic, dynamic response and energy absorption behavior of the vascular tissue are numerically explored. The flexibility of natural palm tissue enhances its impact resistance. Under the quasi-static compression, the cell walls connecting the fiber cap and the vessel dissipate more energy. The dominant role of the fiber cap in the plastic energy dissipation under high-speed impact is observed. And the radially-arranged fiber cap also allows the palm tissue to improve its tangential mechanical performances under hydraulic pressure. Copyright © 2014 Elsevier Ltd. All rights reserved.

Modeling of Tool-Tissue Interactions for Computer-Based Surgical Simulation: A Literature Review

PubMed Central

Misra, Sarthak; Ramesh, K. T.; Okamura, Allison M.

2009-01-01

Surgical simulators present a safe and potentially effective method for surgical training, and can also be used in robot-assisted surgery for pre- and intra-operative planning. Accurate modeling of the interaction between surgical instruments and organs has been recognized as a key requirement in the development of high-fidelity surgical simulators. Researchers have attempted to model tool-tissue interactions in a wide variety of ways, which can be broadly classified as (1) linear elasticity-based, (2) nonlinear (hyperelastic) elasticity-based finite element (FE) methods, and (3) other techniques that not based on FE methods or continuum mechanics. Realistic modeling of organ deformation requires populating the model with real tissue data (which are difficult to acquire in vivo) and simulating organ response in real time (which is computationally expensive). Further, it is challenging to account for connective tissue supporting the organ, friction, and topological changes resulting from tool-tissue interactions during invasive surgical procedures. Overcoming such obstacles will not only help us to model tool-tissue interactions in real time, but also enable realistic force feedback to the user during surgical simulation. This review paper classifies the existing research on tool-tissue interactions for surgical simulators specifically based on the modeling techniques employed and the kind of surgical operation being simulated, in order to inform and motivate future research on improved tool-tissue interaction models. PMID:20119508

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

PubMed Central

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

2017-01-01

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

Clinical Characteristics of Connective Tissue Nevi in Tuberous Sclerosis Complex With Special Emphasis on Shagreen Patches.

PubMed

Bongiorno, Michelle A; Nathan, Neera; Oyerinde, Oyetewa; Wang, Ji-An; Lee, Chyi-Chia Richard; Brown, G Thomas; Moss, Joel; Darling, Thomas N

2017-07-01

Patients with tuberous sclerosis complex (TSC) frequently develop collagenous connective tissue nevi. The prototypical lesion is a large shagreen patch located on the lower back, but some patients only manifest small collagenomas or have lesions elsewhere on the body. The ability to recognize these variable presentations can be important for the diagnosis of TSC. To describe the clinical characteristics of connective tissue nevi on the trunk and extremities of patients with tuberous sclerosis complex. A retrospective analysis of patient medical records and skin photography was performed; 104 adult patients with TSC were enrolled in an observational cohort study that was enriched for those with pulmonary lymphangioleiomyomatosis, and was therefore composed mostly of women (99 women, 5 men). All patients included were examined at the National Institutes of Health (NIH) in Bethesda, Maryland, from 1998 to 2013. Connective tissue nevi were categorized per anatomic location and size. Lesions less than 1 cm in diameter were termed collagenomas. Shagreen patches were characterized as small (1 to <4 cm), medium (4 to <8 cm), and large (≥8 cm). Frequency, anatomic location, size, and histological appearance of connective tissue nevi in patients with TSC. Overall, 58 of 104 patients (median [range] age, 42 [19-70] years) with TSC (56%) had at least 1 connective tissue nevus on the trunk or thighs; of these, 28 of 58 patients (48%) had a solitary lesion, and 30 of 58 patients (52%) had 2 or more lesions. Overall, 120 lesions from 55 patients were classified by size; 46 lesions (38%) were collagenomas; 39 lesions (32%) were small shagreen patches; 21 lesions (18%), medium shagreen patches; and 14 lesions (12%), large shagreen patches. The distribution of lesions was 9% (n = 11), upper back; 29% (n = 35), middle back; 51% (n = 61), lower back; and 11% (n = 13), other locations. All 26 shagreen patches that were analyzed histopathologically had coarse collagen fibers and 24 of 26 stained with Miller elastic stain had decreased elastic fibers. On immunoblot analysis, fibroblasts grown from shagreen patches expressed higher levels of phosphorylated ribosomal protein S6 than paired fibroblasts from normal-appearing skin. Tuberous sclerosis complex-related connective tissue nevi are not limited to the lower back, and occasionally present on the central or upper back, buttocks, or thighs. Elastic fibers are typically decreased. Recognition of these variable presentations can be important for TSC diagnosis.

Differentiated embryonic chondrocytes 1 expression of periodontal ligament tissue and gingival tissue in the patients with chronic periodontitis.

PubMed

Hu, Shenlin; Shang, Wei; Yue, Haitao; Chen, Ruini; Dong, Zheng; Hu, Jinhua; Mao, Zhao; Yang, Jian

2015-04-01

To evaluate the DEC1 expression of periodontal ligament tissue and gingival tissue in the patients with chronic periodontitis. 20 non-smoking patients with chronic periodontitis and 20 healthy individuals were enrolled. Periodontal ligament tissue and gingival tissue samples from healthy subjects were collected during teeth extraction for orthodontic reason or the third molar extraction. The parallel samples from patients with chronic periodontitis were obtained during periodontal flap operations or teeth extraction as part of periodontal treatment. The DEC1 expression and the alkaline phosphatase (ALP) activity of both the periodontal ligament tissue and gingival tissue were determined by Western blot, Immunohistochemistry and ALP Detection Kit. The DEC1 expression of periodontal ligament tissue in the patients with chronic periodontitis decreased significantly along with the decreased ALP activity. On the contrary, the DEC1 expression of gingival tissue in the patients with chronic periodontitis increased significantly. Further study found that the DEC1 expression of gingival tissue increased mainly in the suprabasal layer of gingival epithelial cells but decreased in the gingival connective tissue of the patients with chronic periodontitis. The DEC1 expression decreases in the periodontal ligament tissue which is related to the osteogenic capacity, whereas the DEC1 expression increases in the suprabasal layer of gingival epithelial cells which are involved in immune inflammatory response in the patients with chronic periodontitis. The findings provide a new target to explore the pathology and the therapy of periodontitis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of protein-coated nanofibers on conformation of gingival fibroblast spheroids: potential utility for connective tissues regeneration.

PubMed

Kaufman, Gili; Whitescarver, Ryan; Nunes, Laiz; Palmer, Xavier-Lewis; Skrtic, Drago; Tutak, Wojtek

2017-10-09

Deep wounds in the gingiva caused by trauma or surgery require a rapid and robust healing of connective tissues. We propose utilizing gas-brushed nanofibers coated with collagen and fibrin for that purpose. Our hypotheses are that protein-coated nanofibers will: (i) attract and mobilize cells in various spatial orientations, and (ii) regulate the expression levels of specific extracellular matrix (ECM)-associated proteins, determining the initial conformational nature of dense and soft connective tissues. Gingival fibroblast monolayers and 3D spheroids were cultured on ECM substrate and covered with gas-blown poly-(DL-lactide-co-glycolide) (PLGA) nanofibers (uncoated/coated with collagen and fibrin). Cell attraction and rearrangement was followed by F-actin staining and confocal microscopy. Thicknesses of the cell layers, developed within the nanofibers, were quantified by imageJ software. The expression of collagen1α1 chain (Col1α1), fibronectin, and metalloproteinase 2 (MMP2) encoding genes was determined by quantitative reverse transcription analysis. Collagen- and fibrin- coated nanofibers induced cell migration toward fibers and supported cellular growth within the scaffolds. Both proteins affected the spatial rearrangement of fibroblasts by favoring packed cell clusters or intermittent cell spreading. These cell arrangements resembled the structural characteristic of dense and soft connective tissues, respectively. Within 3 days of incubation, fibroblast spheroids interacted with the fibers and grew robustly by increasing their thickness compared to monolayers. While the ECM key components, such as fibronectin and MMP2 encoding genes, were expressed in both protein groups, Col1α1 was predominantly expressed in bundled fibroblasts grown on collagen fibers. This enhanced expression of collagen1 is typical for dense connective tissue. Based on results of this study, our gas-blown, collagen- and fibrin-coated PLGA nanofibers are viable candidates for engineering soft and dense connective tissues with the required structural characteristics and functions needed for wound healing applications. Rapid regeneration of these layers should enhance healing of open wounds in a harsh oral environment. © 2017 IOP Publishing Ltd.

Genetic parameters for sensory traits in longissimus muscle and their associations with tenderness, marbling score, and intramuscular fat in Angus cattle.

PubMed

Mateescu, R G; Garrick, D J; Garmyn, A J; VanOverbeke, D L; Mafi, G G; Reecy, J M

2015-01-01

The objective of this study was to estimate heritabilities for sensory traits and genetic correlations among sensory traits and with marbling score (MS), Warner-Bratzler shear force (WBSF), and intramuscular fat content (IMFC). Samples of LM from 2,285 Angus cattle were obtained and fabricated into steaks for laboratory analysis and 1,720 steaks were analyzed by a trained sensory panel. Restricted maximum likelihood procedures were used to obtain estimates of variance and covariance components under a multitrait animal model. Estimates of heritability for MS, IMFC, WBSF, tenderness, juiciness, and connective tissue traits were 0.67, 0.38, 0.19, 0.18, 0.06, and 0.25, respectively. The genetic correlations of MS with tenderness, juiciness, and connective tissue were estimated to be 0.57 ± 0.14, 1.00 ± 0.17, and 0.49 ± 0.13, all positive and strong. Estimated genetic correlations of IMFC with tenderness, juiciness, and connective tissue were 0.56 ± 0.16, 1.00 ± 0.21, and 0.50 ± 0.15, respectively. The genetic correlations of WBSF with tenderness, juiciness, and connective tissue were all favorable and estimated to be -0.99 ± 0.08, -0.33 ± 0.30 and -0.99 ± 0.07, respectively. Strong and positive genetic correlations were estimated between tenderness and juiciness (0.54 ± 0.28) and between connective tissue and juiciness (0.58 ± 0.26). In general, genetic correlations were large and favorable, which indicated that strong relationships exist and similar gene and gene networks may control MS, IMFC, and juiciness or WBSF, panel tenderness, and connective tissue. The results from this study confirm that MS currently used in selection breeding programs has positive genetic correlations with tenderness and juiciness and, therefore, is an effective indicator trait for the improvement of tenderness and juiciness in beef. This study also indicated that a more objective measure, particularly WBSF, a trait not easy to improve through phenotypic selection, is an excellent candidate trait for genomic selection aimed at improving eating satisfaction.

Celebration of the 50th anniversary of the foundation of the French society for connective tissue research. Its short history in the frame of the origin and development of this discipline.

PubMed

Borel, J P; Maquart, F X; Robert, A M; Labat-Robert, J; Robert, L

2012-02-01

The science of connective tissues has (at least) a double origin. Collagen, their major constituent was first studied in conjunction with the leather industry. Acid mucopolysaccharides (now glycosaminoglycans) were characterised by (bio)-chemists interested in glycoconjugates. They joined mainly hospital-based rheumatology departments. Later started the study of elastin with the discovery of elastases and of connective tissue-born (structural) glycoproteins. Besides rhumatologists and leather-chemists mainly pathologists became involved in this type of research, followed closely by ophthalmology research. The first important meetings of these diverse specialists were organised under the auspices of NATO, first in Saint-Andrew's in GB in 1964 and a few years later (1969) in Santa Margareta, Italy. With the discovery of fibronectin, a "structural glycoprotein", started the study of cell-matrix interactions, reinforced by the identification of cell-receptors mediating them and the "cross-talk" between cells and matrix constituents. The first initiative to organise societies for this rapidly growing discipline was that of Ward Pigman in New York in 1961, restricted however to glycol-conjugates. Next year, in 1962 was founded the first European Connective Tissue Society in Paris: the "Club français du tissu conjonctif", which played a crucial role in the establishment of schools, laboratories, national and international meetings in the major cities of France: Paris, Lyon, Reims, Caen,Toulouse. A second European society was born in Great Britain, and at a joint meeting with the French society at the Paris Pasteur Institute, was founded in 1967 by these societies the Federation of European Connective Tissue Societies (FECTS). Their meetings, organised every second year, drained a wide attendance from all over the world. An increasing number of young scientists joined since then this branch of biomedical discipline with several international journals devoted to connective tissue research, to matrix biology. The increasing number and quality of the young generation of scientists engaged in research related to the extracellular matrix or better Biomatrix and cell-matrix interactions is a further guarantee for the continued interest in this crucial field of science at the interface of basic and medically oriented research. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

Unique transcriptomic signature of omental adipose tissue in Ossabaw swine: a model of childhood obesity.

PubMed

Toedebusch, Ryan G; Roberts, Michael D; Wells, Kevin D; Company, Joseph M; Kanosky, Kayla M; Padilla, Jaume; Jenkins, Nathan T; Perfield, James W; Ibdah, Jamal A; Booth, Frank W; Rector, R Scott

2014-05-15

To better understand the impact of childhood obesity on intra-abdominal adipose tissue phenotype, a complete transcriptomic analysis using deep RNA-sequencing (RNA-seq) was performed on omental adipose tissue (OMAT) obtained from lean and Western diet-induced obese juvenile Ossabaw swine. Obese animals had 88% greater body mass, 49% greater body fat content, and a 60% increase in OMAT adipocyte area (all P < 0.05) compared with lean pigs. RNA-seq revealed a 37% increase in the total transcript number in the OMAT of obese pigs. Ingenuity Pathway Analysis showed transcripts in obese OMAT were primarily enriched in the following categories: 1) development, 2) cellular function and maintenance, and 3) connective tissue development and function, while transcripts associated with RNA posttranslational modification, lipid metabolism, and small molecule biochemistry were reduced. DAVID and Gene Ontology analyses showed that many of the classically recognized gene pathways associated with adipose tissue dysfunction in obese adults including hypoxia, inflammation, angiogenesis were not altered in OMAT in our model. The current study indicates that obesity in juvenile Ossabaw swine is characterized by increases in overall OMAT transcript number and provides novel data describing early transcriptomic alterations that occur in response to excess caloric intake in visceral adipose tissue in a pig model of childhood obesity.

Unique transcriptomic signature of omental adipose tissue in Ossabaw swine: a model of childhood obesity

PubMed Central

Toedebusch, Ryan G.; Roberts, Michael D.; Wells, Kevin D.; Company, Joseph M.; Kanosky, Kayla M.; Padilla, Jaume; Jenkins, Nathan T.; Perfield, James W.; Ibdah, Jamal A.; Booth, Frank W.

2014-01-01

To better understand the impact of childhood obesity on intra-abdominal adipose tissue phenotype, a complete transcriptomic analysis using deep RNA-sequencing (RNA-seq) was performed on omental adipose tissue (OMAT) obtained from lean and Western diet-induced obese juvenile Ossabaw swine. Obese animals had 88% greater body mass, 49% greater body fat content, and a 60% increase in OMAT adipocyte area (all P < 0.05) compared with lean pigs. RNA-seq revealed a 37% increase in the total transcript number in the OMAT of obese pigs. Ingenuity Pathway Analysis showed transcripts in obese OMAT were primarily enriched in the following categories: 1) development, 2) cellular function and maintenance, and 3) connective tissue development and function, while transcripts associated with RNA posttranslational modification, lipid metabolism, and small molecule biochemistry were reduced. DAVID and Gene Ontology analyses showed that many of the classically recognized gene pathways associated with adipose tissue dysfunction in obese adults including hypoxia, inflammation, angiogenesis were not altered in OMAT in our model. The current study indicates that obesity in juvenile Ossabaw swine is characterized by increases in overall OMAT transcript number and provides novel data describing early transcriptomic alterations that occur in response to excess caloric intake in visceral adipose tissue in a pig model of childhood obesity. PMID:24642759

Foreign Body Giant Cell-Related Encapsulation of a Synthetic Material Three Years After Augmentation.

PubMed

Lorenz, Jonas; Barbeck, Mike; Sader, Robert A; Kirkpatrick, Charles J; Russe, Philippe; Choukroun, Joseph; Ghanaati, Shahram

2016-06-01

Bone substitute materials of different origin and chemical compositions are frequently used in augmentation procedures to enlarge the local bone amount. However, relatively little data exist on the long-term tissue reactions. The presented case reports for the first time histological and histomorphometrical analyses of a nanocrystaline hydroxyapatite-based bone substitute material implanted in the human sinus cavity after an integration period of 3 years. The extracted biopsy was analyzed histologically and histomorphometrically with focus on the tissue reactions, vascularization, new bone formation, and the induction of a foreign body reaction. A comparably high rate of connective tissue (48.25%) surrounding the remaining bone substitute granules (42.13%) was observed. Accordingly, the amount of bone tissue (9.62%) built the smallest fraction within the biopsy. Further, tartrate-resistant acid phosphatase-positive and -negative multinucleated giant cells (4.35 and 3.93 cells/mm(2), respectively) were detected on the material-tissue interfaces. The implantation bed showed a mild vascularization of 10.03 vessels/mm(2) and 0.78%. The present case report shows that after 3 years, a comparable small amount of bone tissue was observable. Thus, the foreign body response to the bone substitute seems to be folded without further degradation or regeneration.

[Silicone in autoimmune diseases and cancer].

PubMed

Elejabeitia, J

1999-01-01

In 1992 the Food and Drug Administration (FDA) announced the restriction of silicone gel-filled breast implants until research protocol studies evaluate the relationship of silicone to connective tissue diseases, and the association of the silicone implants with breast carcinoma. Since them comprehensive epidemiologic studies have concluded that there is no connection between breast implants and the known connective tissue diseases or between the implants and breast carcinoma. During the same year, The American College of Rheumatology said that it have not been demonstrated the relationship between silicone gel breast implants and any systemic disease. Although this, the FDA restriction continues.

Subperiosteal and intraosseous connective tissue grafts for pocket reduction: a 9- to 13-year retrospective case series report.

PubMed

Nelson, S W

2001-10-01

Recent histological evidence has documented that grafted palatal connective tissue is capable of forming a new attachment to previously exposed roots in the treatment of gingival recession. No clinical studies have tested the ability of connective tissue that has been implanted beneath the periosteum into periodontal osseous defects to reduce probing depth and increase clinical attachment levels. This study reports the long-term clinical effect of subperiosteal and intraosseous connective tissue grafts on deep periodontal pockets. Connective tissue (CT) grafts were placed in 32 periodontal pockets on 27 patients. Grafts were classified into 3 groups. Type I grafts had 50% or more vascular surface contact and were < or = 2.5 mm thick. Type II grafts had 50% or more contact but were > 2.5 mm thick, and Type III grafts had less than 50% vascular contact regardless of thickness. Twelve of 14 Type I sites, 9 of 15 Type II sites, and 3 of 3 Type III sites were analyzed 9 to 13 years following treatment. Clinical attachment level change differed significantly between the graft types on survivor teeth (P < 0.05): Type III had 2 mm loss (95% confidence interval [CI]: 0.4 to 3.6), while Type II and Type I grafts had a 2.7 mm gain (95% CI: 2.0 to 3.4) and 4.3 mm gain (95% CI: 3.3 to 5.2), respectively. Similar substantial differences were presented for changes in probing depth and recession. This long-term (9 to 13 years) retrospective case-series analysis suggests substantial improvements in periodontal clinical measures for Type I CT grafts in deep periodontal pockets. Randomized trials are required to evaluate this promising procedure.

Deformation of the Early Glaucomatous Monkey Optic Nerve Head Connective Tissue after Acute IOP Elevation in 3-D Histomorphometric Reconstructions

PubMed Central

Yang, Hongli; Thompson, Hilary; Roberts, Michael D.; Sigal, Ian A.; Downs, J. Crawford

2011-01-01

Purpose. To retest the hypothesis that monkey ONH connective tissues become hypercompliant in early experimental glaucoma (EEG), by using 3-D histomorphometric reconstructions, and to expand the characterization of EEG connective tissue deformation to nine EEG eyes. Methods. Trephinated ONH and peripapillary sclera from both eyes of nine monkeys that were perfusion fixed, with one normal eye at IOP 10 mm Hg and the other EEG eye at 10 (n = 3), 30 (n = 3), or 45 (n = 3) mm Hg were serial sectioned, 3-D reconstructed, 3-D delineated, and quantified with 3-D reconstruction techniques developed in prior studies by the authors. Overall, and for each monkey, intereye differences (EEG eye minus normal eye) for each parameter were calculated and compared by ANOVA. Hypercompliance in the EEG 30 and 45 eyes was assessed by ANOVA, and deformations in all nine EEG eyes were separately compared by region without regard for fixation IOP. Results. Hypercompliant deformation was not significant in the overall ANOVA, but was suggested in a subset of EEG 30/45 eyes. EEG eye deformations included posterior laminar deformation, neural canal expansion, lamina cribrosa thickening, and posterior (outward) bowing of the peripapillary sclera. Maximum posterior laminar deformation and scleral canal expansion co-localized to either the inferior nasal or superior temporal quadrants in the eyes with the least deformation and involved both quadrants in the eyes achieving the greatest deformation. Conclusions. The data suggest that, in monkey EEG, ONH connective tissue hypercompliance may occur only in a subset of eyes and that early ONH connective tissue deformation is maximized in the superior temporal and/or inferior nasal quadrants. PMID:20702834

Elastic model for crimped collagen fibrils

NASA Technical Reports Server (NTRS)

Freed, Alan D.; Doehring, Todd C.

2005-01-01

A physiologic constitutive expression is presented in algorithmic format for the nonlinear elastic response of wavy collagen fibrils found in soft connective tissues. The model is based on the observation that crimped fibrils in a fascicle have a three-dimensional structure at the micron scale that we approximate as a helical spring. The symmetry of this wave form allows the force/displacement relationship derived from Castigliano's theorem to be solved in closed form: all integrals become analytic. Model predictions are in good agreement with experimental observations for mitral-valve chordae tendinece.

Lasers in Apicoectomy: A Brief Review.

PubMed

Mohammadi, Zahed; Jafarzadeh, Hamid; Shalavi, Sousan; Kinoshita, Jun-Ichiro; Giardino, Luciano

2017-02-01

Since the invention of laser, various applications for lasers in endodontics have been proposed, such as disinfection of the root canal system, canal shaping, pulp diagnosis, and apico-ectomy. One of the major applications of laser in endodontics is apicoectomy. The aim of this article is to review the benefits and drawbacks of laser applications in apicoectomy, including effect on apical seal, effect on dentin permeability, effect on postsurgery pain, effect on crack formation, effect on root-end morphology, effect on treatment outcome, and connective tissue response to laser-treated dentin.

Upregulation of angiogenesis in oral lichen planus.

PubMed

Al-Hassiny, A; Friedlander, L T; Parachuru, V P B; Seo, B; Hussaini, H M; Rich, A M

2018-02-01

As angiogenesis is fundamental to the pathogenesis of many chronic inflammatory disorders, this study investigated the expression of various vascular markers in oral lichen planus and non-specific oral mucosal inflammatory tissues. Archival specimens of oral lichen planus (n = 15) and inflamed tissues (n = 13) were stained using immunohistochemistry with antibodies to CD34, vascular endothelial growth factor, vascular endothelial growth factor receptor and vasohibin. Nine representative sites at the epithelial-connective tissue junction and through the fibrous connective tissue were selected, and automated analysis techniques were used to determine the extent of positivity expressed as the percentage of positive cells. Significance was denoted when P < .05. The expression of pro-angiogenic factors was higher in lichen planus samples compared with inflamed controls. A higher level of CD34 was observed in the deeper parts of the connective tissue of Oral lichen planus (OLP) (P = .04), whereas VEGF and VEGFR2 expressions were higher all through the tissues (respectively, P < .02 and P < .01). The expression of the anti-angiogenic VASH1 was higher in inflamed tissue compared with lichen planus in all sites evaluated (P < .01). The findings indicate that angiogenic factors are differentially expressed in oral lichen planus compared with inflamed controls, with increased expression of pro-angiogenic factors and decreased anti-angiogenic expression. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Role of PTPα in the Destruction of Periodontal Connective Tissues

PubMed Central

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

2013-01-01

IL-1β contributes to connective tissue destruction in part by up-regulating stromelysin-1 (MMP-3), which in fibroblasts is a focal adhesion-dependent process. Protein tyrosine phosphatase-α (PTPα) is enriched in and regulates the formation of focal adhesions, but the role of PTPα in connective tissue destruction is not defined. We first examined destruction of periodontal connective tissues in adult PTPα+/+ and PTPα−/− mice subjected to ligature-induced periodontitis, which increases the levels of multiple cytokines, including IL-1β. Three weeks after ligation, maxillae were processed for morphometry, micro-computed tomography and histomorphometry. Compared with unligated controls, there was ∼1.5–3 times greater bone loss as well as 3-fold reduction of the thickness of the gingival lamina propria and 20-fold reduction of the amount of collagen fibers in WT than PTPα−/− mice. Immunohistochemical staining of periodontal tissue showed elevated expression of MMP-3 at ligated sites. Second, to examine mechanisms by which PTPα may regulate matrix degradation, human MMP arrays were used to screen conditioned media from human gingival fibroblasts treated with vehicle, IL-1β or TNFα. Although MMP-3 was upregulated by both cytokines, only IL-1β stimulated ERK activation in human gingival fibroblasts plated on fibronectin. TIRF microscopy and immunoblotting analyses of cells depleted of PTPα activity with the use of various mutated constructs or with siRNA or PTPαKO and matched wild type fibroblasts were plated on fibronectin to enable focal adhesion formation and stimulated with IL-1β. These data showed that the catalytic and adaptor functions of PTPα were required for IL-1β-induced focal adhesion formation, ERK activation and MMP-3 release. We conclude that inflammation-induced connective tissue degradation involving fibroblasts requires functionally active PTPα and in part is mediated by IL-1β signaling through focal adhesions. PMID:23940616

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mori, Yasuji; Hinchcliff, Monique; Wu, Minghua

2008-03-10

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Harper, J.; Amiel, D.; Harper, E.

The authors examined the patellar tendon (PT), anterior cruciate ligament (ACL) and medial collateral ligament (MCL) from normal rabbits for collagenase activity. All three connective tissues contain large amounts of collagen and the catabolism of this structural protein is important to their integrity. The authors cultured each tissue in serum free medium for 14 days. Collagenase was produced by all three connective tissues after a lag period of up to 7 days, as detected by the /sup 14/C-glycine peptide-release assay. Culture media that did not express enzyme the authors found to contain inhibitory activity. The collagenases and inhibitors from eachmore » tissue have been quantitated and characterized. After 9 days the collagenase activity for the rabbit periarticular tissues was 6.1 (PT), 4.4 (MCL) and 8.6 (ACL) units per milligram of secreted protein. The cleavage site of all three collagenases was found to be similar to that observed for rabbit skin collagenase, and generation of reaction products TC/sup A/ and TC/sup B/ was demonstrated by collagenases from PT, MCL and ACL. These results suggest that the metabolism of ligaments and tendon is regulated by the production of zymogen, active collagenase and inhibitor, similar to other connective tissues. The role of these components in joint injury and joint diseases is currently being investigated.« less

Flagellin peptide flg22 gains access to long-distance trafficking in Arabidopsis via its receptor, FLS2

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jelenska, Joanna; Davern, Sandra M.; Standaert, Robert F.

Diverse pathogen-derived molecules, such as bacterial flagellin and its conserved peptide flg22, are recognized in plants via plasma membrane receptors and induce both local and systemic immune responses. The fate of such ligands was unknown: whether and by what mechanism(s) they enter plant cells and whether they are transported to distal tissues. We used biologically active fluorophore and radiolabeled peptides to establish that flg22 moves to distal organs with the closest vascular connections. Remarkably, entry into the plant cell via endocytosis together with the FLS2 receptor is needed for delivery to vascular tissue and long-distance transport of flg22. This contrastsmore » with known routes of long distance transport of other non-cell-permeant molecules in plants, which require membrane-localized transporters for entry to vascular tissue. Thus, a plasma membrane receptor acts as a transporter to enable access of its ligand to distal trafficking routes.« less

Flagellin peptide flg22 gains access to long-distance trafficking in Arabidopsis via its receptor, FLS2

DOE PAGES

Jelenska, Joanna; Davern, Sandra M.; Standaert, Robert F.; ...

2017-03-01

Diverse pathogen-derived molecules, such as bacterial flagellin and its conserved peptide flg22, are recognized in plants via plasma membrane receptors and induce both local and systemic immune responses. The fate of such ligands was unknown: whether and by what mechanism(s) they enter plant cells and whether they are transported to distal tissues. We used biologically active fluorophore and radiolabeled peptides to establish that flg22 moves to distal organs with the closest vascular connections. Remarkably, entry into the plant cell via endocytosis together with the FLS2 receptor is needed for delivery to vascular tissue and long-distance transport of flg22. This contrastsmore » with known routes of long distance transport of other non-cell-permeant molecules in plants, which require membrane-localized transporters for entry to vascular tissue. Thus, a plasma membrane receptor acts as a transporter to enable access of its ligand to distal trafficking routes.« less

Pain and flare-up after endodontic treatment procedures.

PubMed

Sipavičiūtė, Eglė; Manelienė, Rasmutė

2014-01-01

Flare-ups can occur after root canal treatment and consist of acute exacerbations of an asymptomatic pulpal and/or periradicular pathologic condition. The causative factors of interappointment pain encompass mechanical, chemical, and/or microbial injury to the pulp or periradicular tissues. Microorganisms can participate in causation of interappointment pain in the following situations: apical extrusion of debris; incomplete instrumentation leading to changes in the endodontic microbiota or in environmental conditions; and secondary intraradicular infections. Interappointment pain is almost exclusively due to the development of acute inflammation at the periradicular tissues in response to an increase in the intensity of injury coming from the root canal system. The mechanical irritation of apical periodontal tissue is caused by overinstrumentation of the root canal and filling material extrusion through the apical foramen. Incorrectly measured working length of the root canal has inherent connection with these causative factors of endodontic flare - up. This review article discusses these many facets of the flare-up: definition, incidence causes and predisposing factors.

Effects of microgravity on rat bone, cartlage and connective tissues

NASA Technical Reports Server (NTRS)

Doty, S.

1990-01-01

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

Rheological characterization of human fibrin and fibrin-agarose oral mucosa substitutes generated by tissue engineering.

PubMed

Rodríguez, I A; López-López, M T; Oliveira, A C X; Sánchez-Quevedo, M C; Campos, A; Alaminos, M; Durán, J D G

2012-08-01

In regenerative medicine, the generation of biocompatible substitutes of tissues by in vitro tissue engineering must fulfil certain requirements. In the case of human oral mucosa, the rheological properties of tissues deserve special attention because of their influence in the acoustics and biomechanics of voice production. This work is devoted to the rheological characterization of substitutes of the connective tissue of the human oral mucosa. Two substitutes, composed of fibrin and fibrin-agarose, were prepared in cell culture for periods in the range 1-21 days. The time evolution of the rheological properties of both substitutes was studied by two different experimental procedures: steady-state and oscillatory measurements. The former allows the plastic behaviour of the substitutes to be characterized by estimating their yield stress; the latter is employed to quantify their viscoelastic responses by obtaining the elastic (G') and viscous (G'') moduli. The results demonstrate that both substitutes are characterized by a predominant elastic response, in which G' (order 100 Pa) is roughly one order of magnitude larger than G'' (order 10 Pa). But the most relevant insight is the stability, throughout the 21 days of culture time, of the rheological quantities in the case of fibrin-agarose, whereas the fibrin substitute shows a significant hardening. This result provides evidence that the addition to fibrin of a small amount of agarose allows the rheological stability of the oral mucosa substitute to be maintained. This feature, together with its viscoelastic similitude with native tissues, makes this biomaterial appropriate for potential use as a scaffold in regenerative therapies of human oral mucosa. Copyright © 2011 John Wiley & Sons, Ltd.

The component leaching from decellularized pericardial bioscaffolds and its implication in the macrophage response.

PubMed

Mendoza-Novelo, Birzabith; Castellano, Laura E; Padilla-Miranda, Ruth G; Lona-Ramos, María C; Cuéllar-Mata, Patricia; Vega-González, Arturo; Murguía-Pérez, Mario; Mata-Mata, José L; Ávila, Eva E

2016-11-01

The extracellular matrix molecules remaining in bioscaffolds derived from decellularized xenogeneic tissues appear to be important for inducing cell functions conducting tissue regeneration. Here, we studied whether decellularization methods, that is, detergent Triton X-100 (TX) alone and TX combined with reversible alkaline swelling (STX), applied to bovine pericardial tissue, could affect the bioscaffold components. The in vitro macrophage response, subdermal biodegradation, and cell infiltration were also studied. The results indicate a lower leaching of fibronectin, but a higher leaching of laminin and sulfated glycosaminoglycans from tissues decellularized with STX and TX, respectively. The in vitro secretion of interleukin-6 and monocyte chemoattractant protein by RAW264.7 macrophages is promoted by decellularized bioscaffold leachates. A lower polymorphonuclear cell density is observed around decellularized bioscaffolds at 1-day implantation; concurrently showing a higher cell infiltration in STX- than in TX-implant. Cells infiltrated into TX-implant show a fibroblastic morphology at 7-day implantation, concurrently the capillary formation is observed at 14-day. Pericardial bioscaffolds suffer biodegradation more pronounced in STX- than in TX-implant. Both TX and STX decellularization methods favor a high leaching of basal lamina components, which presumably promotes a faster macrophage stimulation compared to nondecellularized tissue, and appear to be associated with an increased host cell infiltration in a rat subdermal implantation. Meanwhile, the connective tissue components leaching from TX decellularized bioscaffolds, unlike the STX ones, appear to be associated with an enhanced angiogenesis accompanied by an early-promoted fibroblastic cell transition. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2810-2822, 2016. © 2016 Wiley Periodicals, Inc.

Approaches to Study Light Effects on Brassinosteroid Sensitivity.

PubMed

Paulišić, Sandi; Molina-Contreras, Maria José; Roig-Villanova, Irma; Martínez-García, Jaime F

2017-01-01

Light perception and hormone signaling in plants are likely connected at multiple points. Light conditions, perceived by photoreceptors, control plant responses by altering hormone concentration, tissue sensitivity, or a combination of both. Whereas it is relatively straightforward to assess the light effects on hormone levels, hormone sensitivity is subjected to interpretation. In Arabidopsis thaliana seedlings, hypocotyl length is strongly affected by light conditions. As hypocotyl elongation also depends on brassinosteroids (BRs), assaying this response provides a valuable and easy way to measure the responsiveness of seedlings to BRs and the impact of light. We describe a simple protocol to evaluate the responsiveness of hypocotyls to commercial BRs and/or BR inhibitors under a range of light conditions. These assays can be used to establish whether light affects BR sensitivity or whether BRs affect light sensitivity. Overall, our protocol can be easily applied for deetiolation (under polychromatic or monochromatic light) and simulated shade treatments combined with BR treatments.

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

PubMed

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

2014-03-01

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

Overexpressed connective tissue growth factor in cardiomyocytes attenuates left ventricular remodeling induced by angiotensin II perfusion.

PubMed

Zhang, Ying; Yan, Hua; Guang, Gong-Chang; Deng, Zheng-Rong

2017-01-01

To evaluate the improving effects of specifically overexpressed connective tissue growth factor (CTGF) in cardiomyocytes on mice with hypertension induced by angiotensin II (AngII) perfusion, 24 transgenic mice with cardiac-restricted overexpression of CTGF (Tg-CTGF) were divided into two equal groups that were perfused with acetic acid and AngII, respectively, for 7 days. Another 24 cage-control wild-type C57BL/6 mice (NLC) were divided and treated identically. Blood pressure was detected by caudal artery cannulation. Cardiac structural and functional changes were observed by echocardiography. Cardiac fibrosis was detected by Masson staining. After AngII perfusion, blood pressures of NLC and Tg-CTGF mice, especially those of the formers, significantly increased. Compared with NLC + AngII group, Tg-CTGF + AngII group had significantly lower left ventricular posterior wall thickness at end-diastole and left ventricular posterior wall thickness at end-systole as well as significantly higher left ventricular end-systolic diameter and left ventricular end-diastolic diameter (P < 0.05). Reverse transcription-polymerase chain reaction (RT-PCR) showed that Tg-CTGF + AngII group had significantly lower collagen I, α-SMA, and TGF-β mRNA expressions in cardiac tissues (P < 0.05). Tg-CTGF can protect AngII-induced cardiac remodeling of mice with hypertension by mitigating inflammatory response. CTGF may be a therapy target for hypertension-induced myocardial fibrosis, but the detailed mechanism still needs in-depth studies.

Matrix stiffness-modulated proliferation and secretory function of the airway smooth muscle cells.

PubMed

Shkumatov, Artem; Thompson, Michael; Choi, Kyoung M; Sicard, Delphine; Baek, Kwanghyun; Kim, Dong Hyun; Tschumperlin, Daniel J; Prakash, Y S; Kong, Hyunjoon

2015-06-01

Multiple pulmonary conditions are characterized by an abnormal misbalance between various tissue components, for example, an increase in the fibrous connective tissue and loss/increase in extracellular matrix proteins (ECM). Such tissue remodeling may adversely impact physiological function of airway smooth muscle cells (ASMCs) responsible for contraction of airways and release of a variety of bioactive molecules. However, few efforts have been made to understand the potentially significant impact of tissue remodeling on ASMCs. Therefore, this study reports how ASMCs respond to a change in mechanical stiffness of a matrix, to which ASMCs adhere because mechanical stiffness of the remodeled airways is often different from the physiological stiffness. Accordingly, using atomic force microscopy (AFM) measurements, we found that the elastic modulus of the mouse bronchus has an arithmetic mean of 23.1 ± 14 kPa (SD) (median 18.6 kPa). By culturing ASMCs on collagen-conjugated polyacrylamide hydrogels with controlled elastic moduli, we found that gels designed to be softer than average airway tissue significantly increased cellular secretion of vascular endothelial growth factor (VEGF). Conversely, gels stiffer than average airways stimulated cell proliferation, while reducing VEGF secretion and agonist-induced calcium responses of ASMCs. These dependencies of cellular activities on elastic modulus of the gel were correlated with changes in the expression of integrin-β1 and integrin-linked kinase (ILK). Overall, the results of this study demonstrate that changes in matrix mechanics alter cell proliferation, calcium signaling, and proangiogenic functions in ASMCs. Copyright © 2015 the American Physiological Society.

Pruritus in Autoimmune Connective Tissue Diseases.

PubMed

Smith, Gideon P; Argobi, Yahya

2018-07-01

Pruritus in autoimmune connective tissue diseases is a common symptom that can be severe and affect the quality of life of patients. It can be related to disease activity and severity or occur independent of the disease. Appropriate therapy to control the itch depends on the etiology, and it is therefore essential to first work-up these patients for the underlying trigger. Copyright © 2018 Elsevier Inc. All rights reserved.

Lipoic acid prevents suppression of connective tissue proliferation in the rat liver induced by n-3 PUFAs. A pilot study.

PubMed

Arend, A; Zilmer, M; Vihalemm, T; Selstam, G; Sepp, E

2000-01-01

As previously shown, dietary n-3 polyunsaturated fatty acids (n-3 PUFAs) suppress connective tissue proliferation in the rat liver wound concurrent with an elevated level of lipid peroxidation. The present study was undertaken to investigate the influence of alpha-lipoic acid (LA), a natural anti-oxidant, on these effects of n-3 PUFAs. Rats were fed with a commercial pellet diet (control group) or with diets enriched with 10% of sunflower oil (n-6 group) or 10% of fish oil (n-3 group) for 8 weeks followed by addition of LA to the same diets for 10 days. Then a liver thermic wound was induced and the administration of LA was continued for 6 days. The proliferation of the connective tissue, the level of lipid peroxidation and their peroxidizability and the content of prostaglandins E2 and F2alpha were measured in the liver wounds. LA prevented the suppression of connective tissue proliferation in the healing wound induced by n-3 PUFAs, avoided the increase in peroxidation of lipids, reduced peroxidizability of lipids and modulated the decrease in PGE2 and PGF2alpha. The results indicate that dietary LA may prevent the suppression of liver wound healing induced by n-3 PUFAs.

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

PubMed Central

LaRusso, Jennifer; Li, Qiaoli; Jiang, Qiujie; Uitto, Jouni

2010-01-01

Pseudoxanthoma elasticum (PXE) is an autosomal recessive multi-system disorder characterized by ectopic connective tissue mineralization, with clinical manifestations primarily in the skin, eyes and the cardiovascular system. There is considerable, both intra-and inter-familial 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. In this study, we utilized a targeted mutant mouse (Abcc6−/−) as a model system for PXE. We examined the effects of changes in dietary phosphate and magnesium on the mineralization process using calcification of the connective tissue capsule surrounding the vibrissae as an early phenotypic biomarker. Mice placed on custom-designed diets either high or low in phosphate did not show changes in mineralization, which was similar to that noted in Abcc6−/− mice on control diet. However, mice placed on diet enriched in magnesium (5-fold) showed no evidence of connective tissue mineralization in this mouse model of PXE. The inhibitory capacity of magnesium was confirmed in a cell-based mineralization assay system in vitro. Collectively, our observations suggest that assessment of dietary magnesium in patients with PXE may be warranted. PMID:19122649

Chloroquine cardiotoxicity mimicking connective tissue disease heart involvement.

PubMed

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

2013-04-01

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

Dynamic Vibration Cooperates with Connective Tissue Growth Factor to Modulate Stem Cell Behaviors

PubMed Central

Tong, Zhixiang; Zerdoum, Aidan B.; Duncan, Randall L.

2014-01-01

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(ɛ-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 naïve 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

Comparison of NMDA and AMPA Channel Expression and Function between Embryonic and Adult Neurons Utilizing Microelectrode Array Systems.

PubMed

Edwards, Darin; Sommerhage, Frank; Berry, Bonnie; Nummer, Hanna; Raquet, Martina; Clymer, Brad; Stancescu, Maria; Hickman, James J

2017-12-11

Microelectrode arrays (MEAs) are innovative tools used to perform electrophysiological experiments for the study of electrical activity and connectivity in populations of neurons from dissociated cultures. Reliance upon neurons derived from embryonic tissue is a common limitation of neuronal/MEA hybrid systems and perhaps of neuroscience research in general, and the use of adult neurons could model fully functional in vivo parameters more closely. Spontaneous network activity was concurrently recorded from both embryonic and adult rat neurons cultured on MEAs for up to 10 weeks in vitro to characterize the synaptic connections between cell types. The cultures were exposed to synaptic transmission antagonists against NMDA and AMPA channels, which revealed significantly different receptor profiles of adult and embryonic networks in vitro. In addition, both embryonic and adult neurons were evaluated for NMDA and AMPA channel subunit expression over five weeks in vitro. The results established that neurons derived from embryonic tissue did not express mature synaptic channels for several weeks in vitro under defined conditions. Consequently, the embryonic response to synaptic antagonists was significantly different than that of neurons derived from adult tissue sources. These results are especially significant because most studies reported with embryonic hippocampal neurons do not begin at two to four weeks in culture. In addition, the utilization of MEAs in lieu of patch-clamp electrophysiology avoided a large-scale, labor-intensive study. These results establish the utility of this unique hybrid system derived from adult hippocampal tissue in combination with MEAs and offer a more appropriate representation of in vivo function for drug discovery. It has application for neuronal development and regeneration as well as for investigations into neurodegenerative disease, traumatic brain injury, and stroke.

Pattern Genes Suggest Functional Connectivity of Organs

NASA Astrophysics Data System (ADS)

Qin, Yangmei; Pan, Jianbo; Cai, Meichun; Yao, Lixia; Ji, Zhiliang

2016-05-01

Human organ, as the basic structural and functional unit in human body, is made of a large community of different cell types that organically bound together. Each organ usually exerts highly specified physiological function; while several related organs work smartly together to perform complicated body functions. In this study, we present a computational effort to understand the roles of genes in building functional connection between organs. More specifically, we mined multiple transcriptome datasets sampled from 36 human organs and tissues, and quantitatively identified 3,149 genes whose expressions showed consensus modularly patterns: specific to one organ/tissue, selectively expressed in several functionally related tissues and ubiquitously expressed. These pattern genes imply intrinsic connections between organs. According to the expression abundance of the 766 selective genes, we consistently cluster the 36 human organs/tissues into seven functional groups: adipose & gland, brain, muscle, immune, metabolism, mucoid and nerve conduction. The organs and tissues in each group either work together to form organ systems or coordinate to perform particular body functions. The particular roles of specific genes and selective genes suggest that they could not only be used to mechanistically explore organ functions, but also be designed for selective biomarkers and therapeutic targets.

Advances in biomimetic regeneration of elastic matrix structures

PubMed Central

Sivaraman, Balakrishnan; Bashur, Chris A.

2012-01-01

Elastin is a vital component of the extracellular matrix, providing soft connective tissues with the property of elastic recoil following deformation and regulating the cellular response via biomechanical transduction to maintain tissue homeostasis. The limited ability of most adult cells to synthesize elastin precursors and assemble them into mature crosslinked structures has hindered the development of functional tissue-engineered constructs that exhibit the structure and biomechanics of normal native elastic tissues in the body. In diseased tissues, the chronic overexpression of proteolytic enzymes can cause significant matrix degradation, to further limit the accumulation and quality (e.g., fiber formation) of newly deposited elastic matrix. This review provides an overview of the role and importance of elastin and elastic matrix in soft tissues, the challenges to elastic matrix generation in vitro and to regenerative elastic matrix repair in vivo, current biomolecular strategies to enhance elastin deposition and matrix assembly, and the need to concurrently inhibit proteolytic matrix disruption for improving the quantity and quality of elastogenesis. The review further presents biomaterial-based options using scaffolds and nanocarriers for spatio-temporal control over the presentation and release of these biomolecules, to enable biomimetic assembly of clinically relevant native elastic matrix-like superstructures. Finally, this review provides an overview of recent advances and prospects for the application of these strategies to regenerating tissue-type specific elastic matrix structures and superstructures. PMID:23355960

[Histomorphometric evaluation of ridge preservation after molar tooth extraction].

PubMed

Zhan, Y L; Hu, W J; Xu, T; Zhen, M; Lu, R F

2017-02-18

To evaluate bone formation in human extraction sockets with absorbed surrounding walls augmented with Bio-Oss and Bio-Gide after a 6-month healing period by histologic and histomorphometric analyses. Six fresh molar tooth extraction sockets in 6 patients who required periodontally compromised moral tooth extraction were included in this study. The six fresh extraction sockets were grafted with Bio-Oss particle covered with Bio-Gide. The 2.8 mm×6.0 mm cylindric bone specimens were taken from the graft sites with aid of stent 6 months after the surgery. Histologic and histomorphometric analyses were performed. The histological results showed Bio-Oss particles were easily distinguished from the newly formed bone, small amounts of new bone were formed among the Bio-Oss particles, large amounts of connective tissue were found. Intimate contact between the newly formed bone and the small part of Bio-Oss particles was present. All the biopsy cylinders measurement demonstrated a high inter-individual variability in the percentage of the bone, connective tissues and Bio-Oss particles. The new bone occupied 11.54% (0-28.40%) of the total area; the connective tissues were 53.42% (34.08%-74.59%) and the Bio-Oss particles were 35.04% (13.92%-50.87%). The percentage of the particles, which were in contact with bone tissues, amounted to 20.13% (0-48.50%). Sites grafted with Bio-Oss particles covered with Bio-Gide were comprised of connective tissues and small amounts of newly formed bone surrounding the graft particles.

Surgical anatomy of the posterior liver surface: the retrohepatic lamina as the basis for mobilisation of the right liver.

PubMed

Macchi, Veronica; Porzionato, Andrea; Bardini, Romeo; Picardi, Edgardo Enrico Edoardo; De Caro, Raffaele

2013-10-01

During right hepatectomies, dissection of the bare area is performed to obtain mobilisation of the liver. Fifty computed tomography scans of the upper abdomen of patients were examined. Specimens of supramesocolic compartment were sampled from 10 un-embalmed cadavers. Macrosections were cut for histotopographic study. In four cadavers, in situ dissection of the posterior liver surface was performed. The hepatophrenic tissue showed a stratigraphic organisation resulting from the juxtaposition of thin layer of dense connective tissue corresponding to the inferior diaphragmatic fascia (mean thickness is 30 ± 4 μm); variable amount of fibroadipose tissue corresponding to retroperitoneal fibroadipose tissue (mean thickness is 34 ± 8 μm); two connective layers with nets of flat cells forming a fusion fascia, the retrohepatic lamina (mean thickness 24 ± 6 μm); and layer of connective tissue corresponding to the hepatic capsule. The juxta-caval portion of the retrohepatic lamina, connecting the right and left sides of the caval groove, forms the inferior vena cava ligament. During dissection, fluid injection developed a preferential plane between the two layers of the retrohepatic lamina, close to the hepatic surface, and no major or minor vessels were ever found along this plane. During right hepatectomy, to reduce the risk of dissemination of tumour cells, the dissection plane should be performed between the two layers of the retrohepatic lamina.

Non-interventional 1-year follow-up study of peri-implant soft tissues following previous soft tissue augmentation and crown insertion in single-tooth gaps.

PubMed

Huber, Samuel; Zeltner, Marco; Hämmerle, Christoph H F; Jung, Ronald E; Thoma, Daniel S

2018-04-01

To assess peri-implant soft tissue dimensions at implant sites, previously augmented with a collagen matrix (VCMX) or an autogenous subepithelial connective tissue graft (SCTG), between crown insertion and 1 year. Twenty patients with single-tooth implants received soft tissue augmentation prior to abutment connection randomly using VCMX or SCTG. Following abutment connection 3 months later, final reconstructions were fabricated and inserted (baseline). Patients were recalled at 6 months (6M) and at 1 year (FU-1). Measurements included clinical data, soft tissue thickness, volumetric outcomes and patient-reported outcome measures (PROMs). The buccal soft tissue thickness showed a median decrease of -0.5 mm (-1.0;0.3) (VCMX) and 0.0 mm (-0.5;1.0) (SCTG) (p = .243) up to FU-1. The soft tissue volume demonstrated a median decrease between BL and FU-1 of -0.1 mm (-0.2;0.0) (p = .301) for VCMX and a significant decrease of -0.2 mm (-0.4; -0.1) (p = .002) for SCTG, respectively. Intergroup comparisons did not reveal any significant differences between the groups for peri-implant soft tissue dimensions and changes up to FU-1 (p > .05). PROMs did not show any significant changes over time nor differences between the groups. Between crown insertion and 1 year, the buccal peri-implant soft tissue dimensions remained stable without relevant differences between sites that had previously been grafted with VCMX or SCTG. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Soft tissue volume alterations after connective tissue grafting at teeth: the subepithelial autologous connective tissue graft versus a porcine collagen matrix - a pre-clinical volumetric analysis.

PubMed

Schmitt, Christian M; Matta, Ragai E; Moest, Tobias; Humann, Julia; Gammel, Lisa; Neukam, Friedrich W; Schlegel, Karl A

2016-07-01

This study evaluates a porcine collagen matrix (CM) for soft tissue thickening in comparison to the subepithelial connective tissue graft (SCTG). In eight beagle dogs, soft tissue thickening was performed at the buccal aspects of the upper canines (SCTG and CM). Impressions were taken before augmentation (i1), after surgery (i2), after one (i3), three (i4) and ten month (i5). Casts were optically scanned with a 3D scanner and each augmented region (unit of analysis) evaluated (primary outcome variable: volume increase in mm(3) ; secondary outcome variables: volume increase in percent, mean and maximum thickness increases in mm). 3D tissue measurements after surgery revealed a significant higher volume increase in the CM (86.37 mm(3)  ± 35.16 mm(3) ) than in the SCTG group (47.65 mm(3)  ± 17.90 mm(3) ). After 10 months, volume increase was non-significant between groups (SCTG:11.36 mm(3)  ± 9.26 mm(3) ; CM: 8.67 mm(3)  ± 13.67 mm(3) ). Maximum soft tissue thickness increase (i1-i5) was 0.66 mm ± 0.29 mm (SCTG) and 0.79 mm ± 0.37 mm (CM) with no significant difference. Ten months after soft tissue thickening, the CM is statistically non-inferior to the SCTG in terms of soft tissue volume and thickness increase. Further 3D studies are needed to confirm the data. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Advanced glycation end-products: Mechanics of aged collagen from molecule to tissue.

PubMed

Gautieri, Alfonso; Passini, Fabian S; Silván, Unai; Guizar-Sicairos, Manuel; Carimati, Giulia; Volpi, Piero; Moretti, Matteo; Schoenhuber, Herbert; Redaelli, Alberto; Berli, Martin; Snedeker, Jess G

2017-05-01

Concurrent with a progressive loss of regenerative capacity, connective tissue aging is characterized by a progressive accumulation of Advanced Glycation End-products (AGEs). Besides being part of the typical aging process, type II diabetics are particularly affected by AGE accumulation due to abnormally high levels of systemic glucose that increases the glycation rate of long-lived proteins such as collagen. Although AGEs are associated with a wide range of clinical disorders, the mechanisms by which AGEs contribute to connective tissue disease in aging and diabetes are still poorly understood. The present study harnesses advanced multiscale imaging techniques to characterize a widely employed in vitro model of ribose induced collagen aging and further benchmarks these data against experiments on native human tissues from donors of different age. These efforts yield unprecedented insight into the mechanical changes in collagen tissues across hierarchical scales from molecular, to fiber, to tissue-levels. We observed a linear increase in molecular spacing (from 1.45nm to 1.5nm) and a decrease in the D-period length (from 67.5nm to 67.1nm) in aged tissues, both using the ribose model of in vitro glycation and in native human probes. Multiscale mechanical analysis of in vitro glycated tendons strongly suggests that AGEs reduce tissue viscoelasticity by severely limiting fiber-fiber and fibril-fibril sliding. This study lays an important foundation for interpreting the functional and biological effects of AGEs in collagen connective tissues, by exploiting experimental models of AGEs crosslinking and benchmarking them for the first time against endogenous AGEs in native tissue. Copyright © 2016 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Possibility of Aggravation of Tissue Sclerosis after Injection of Multipotent Mesenchymal Stromal Cells Near the Forming Cicatrix in the Experiment.

PubMed

Maiborodin, I V; Morozov, V V; Anikeev, A A; Figurenko, N F; Maslov, R V; Matveeva, V A; Chastikina, G A; Maiborodina, V I

2017-08-01

The peculiarities of tissue sclerosis after injection of autologous bone marrow multipotent mesenchymal stromal cells transfected with GFP gene and stained with Vybrant CM-Dil cell membrane dye were studied by light microscopy with luminescence. The surgical intervention consisting in ligation of the great vein was followed by tissue sclerotic transformation caused by direct damage and chronic inflammation caused by the presence of slowly resorbed ligature. Injection of stromal cells after this intervention led to formation of more extensive scar. This can attest to the possibility of stromal cells differentiation into connective tissue cells, fibroblasts, and stimulation of proliferation and collagen synthesis by host fibroblasts. A decrease in the volume of dense fibrous connective tissue due to scar reorganization at latter terms cannot not excluded.

Use of the tunnel technique and an acellular dermal matrix in the treatment of multiple adjacent teeth with gingival recession in the esthetic zone.

PubMed

Mahn, Douglas H

2010-12-01

The proper management of gingival recession is critical to the establishment of a natural-appearing soft tissue architecture. Subepithelial connective tissue grafts have been considered the "gold standard" but are limited by the availability of palatal donor tissue. Tunnel techniques have improved the esthetic results of connective tissue grafting. Acellular dermal matrices have been successful in the treatment of gingival recession and are not limited by the palatal anatomy. The aim of this report is to describe the application of the tunnel technique, with use of an acellular dermal matrix, in the correction of gingival recession affecting multiple adjacent teeth in the esthetic zone.

The role of microRNAs in the pathogenesis of MMPi-induced skin fibrodysplasia

PubMed Central

2013-01-01

Background Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes involved in extracellular matrix (ECM) homeostasis. MMPs have been an attractive pharmacological target for a number of indications. However, development has been hampered by the propensity of compounds targeting these enzymes to cause connective-tissue pathologies. The broad-spectrum MMP-inhibitor (MMPi) AZM551248 has been shown to induce such effects in the dog. Histopathological changes were consistent with fibrodysplasia (FD), characterised by fibroblast proliferation and the deposition of collagen in the subcutaneous tissues. We conducted a time-course study administering 20mg/kg/day AZM551248 between 4 and 17 days. Cervical subcutaneous tissue and plasma were sampled during the time-course. miRNA expression profiles in subcutaneous skin specimens following the administration of AZM551248 were determined by high-throughput-sequencing. Results An increasing number of miRNAs were differentially expressed compared with vehicle treated control animals as the study progressed. Several of these were members of the miR-200 family and were significantly attenuated in response to MMPi. As the severity of FD increased at the later time-points, other miRNAs associated with TGFβ synthesis and regulation of the acute inflammatory response were modulated. Evidence indicative of epithelial to mesenchymal transition was present at all study time points. Receiver operator curve (ROC) analysis revealed that miR-21 expression in the cervical subcutaneous tissue was a sensitive and specific biomarker of FD incidence. Conclusions Our data reveal significant perturbations in canine skin miRNA expression in response to MMPi administration. Furthermore, we have identified dysregulated miRNAs that are associated with processes relevant to the key histopathological events of MMPi-induced FD. PMID:23688202

Improved selectivity from a wavelength addressable device for wireless stimulation of neural tissue

PubMed Central

Seymour, Elif Ç.; Freedman, David S.; Gökkavas, Mutlu; Özbay, Ekmel; Sahin, Mesut; Ünlü, M. Selim

2014-01-01

Electrical neural stimulation with micro electrodes is a promising technique for restoring lost functions in the central nervous system as a result of injury or disease. One of the problems related to current neural stimulators is the tissue response due to the connecting wires and the presence of a rigid electrode inside soft neural tissue. We have developed a novel, optically activated, microscale photovoltaic neurostimulator based on a custom layered compound semiconductor heterostructure that is both wireless and has a comparatively small volume (<0.01 mm3). Optical activation provides a wireless means of energy transfer to the neurostimulator, eliminating wires and the associated complications. This neurostimulator was shown to evoke action potentials and a functional motor response in the rat spinal cord. In this work, we extend our design to include wavelength selectivity and thus allowing independent activation of devices. As a proof of concept, we fabricated two different microscale devices with different spectral responsivities in the near-infrared region. We assessed the improved addressability of individual devices via wavelength selectivity as compared to spatial selectivity alone through on-bench optical measurements of the devices in combination with an in vivo light intensity profile in the rat cortex obtained in a previous study. We show that wavelength selectivity improves the individual addressability of the floating stimulators, thus increasing the number of devices that can be implanted in close proximity to each other. PMID:24600390

Arabidopsis TCH4, regulated by hormones and the environment, encodes a xyloglucan endotransglycosylase

NASA Technical Reports Server (NTRS)

Xu, W.; Purugganan, M. M.; Polisensky, D. H.; Antosiewicz, D. M.; Fry, S. C.; Braam, J.

1995-01-01

Adaptation of plants to environmental conditions requires that sensing of external stimuli be linked to mechanisms of morphogenesis. The Arabidopsis TCH (for touch) genes are rapidly upregulated in expression in response to environmental stimuli, but a connection between this molecular response and developmental alterations has not been established. We identified TCH4 as a xyloglucan endotransglycosylase by sequence similarity and enzyme activity. Xyloglucan endotransglycosylases most likely modify cell walls, a fundamental determinant of plant form. We determined that TCH4 expression is regulated by auxin and brassinosteroids, by environmental stimuli, and during development, by a 1-kb region. Expression was restricted to expanding tissues and organs that undergo cell wall modification. Regulation of genes encoding cell wall-modifying enzymes, such as TCH4, may underlie plant morphogenetic responses to the environment.

Topological and organizational properties of the products of house-keeping and tissue-specific genes in protein-protein interaction networks.

PubMed

Lin, Wen-Hsien; Liu, Wei-Chung; Hwang, Ming-Jing

2009-03-11

Human cells of various tissue types differ greatly in morphology despite having the same set of genetic information. Some genes are expressed in all cell types to perform house-keeping functions, while some are selectively expressed to perform tissue-specific functions. In this study, we wished to elucidate how proteins encoded by human house-keeping genes and tissue-specific genes are organized in human protein-protein interaction networks. We constructed protein-protein interaction networks for different tissue types using two gene expression datasets and one protein-protein interaction database. We then calculated three network indices of topological importance, the degree, closeness, and betweenness centralities, to measure the network position of proteins encoded by house-keeping and tissue-specific genes, and quantified their local connectivity structure. Compared to a random selection of proteins, house-keeping gene-encoded proteins tended to have a greater number of directly interacting neighbors and occupy network positions in several shortest paths of interaction between protein pairs, whereas tissue-specific gene-encoded proteins did not. In addition, house-keeping gene-encoded proteins tended to connect with other house-keeping gene-encoded proteins in all tissue types, whereas tissue-specific gene-encoded proteins also tended to connect with other tissue-specific gene-encoded proteins, but only in approximately half of the tissue types examined. Our analysis showed that house-keeping gene-encoded proteins tend to occupy important network positions, while those encoded by tissue-specific genes do not. The biological implications of our findings were discussed and we proposed a hypothesis regarding how cells organize their protein tools in protein-protein interaction networks. Our results led us to speculate that house-keeping gene-encoded proteins might form a core in human protein-protein interaction networks, while clusters of tissue-specific gene-encoded proteins are attached to the core at more peripheral positions of the networks.

Microscopic anatomy of the visceral fasciae.

PubMed

Stecco, Carla; Sfriso, Maria Martina; Porzionato, Andrea; Rambaldo, Anna; Albertin, Giovanna; Macchi, Veronica; De Caro, Raffaele

2017-07-01

The term 'visceral fascia' is a general term used to describe the fascia lying immediately beneath the mesothelium of the serosa, together with that immediately surrounding the viscera, but there are many types of visceral fasciae. The aim of this paper was to identify the features they have in common and their specialisations. The visceral fascia of the abdomen (corresponding to the connective tissue lying immediately beneath the mesothelium of the parietal peritoneum), thorax (corresponding to the connective tissue lying immediately beneath the mesothelium of the parietal pleura), lung (corresponding to the connective tissue under the mesothelium of the visceral pleura), liver (corresponding to the connective tissue under the mesothelium of the visceral peritoneum), kidney (corresponding to the Gerota fascia), the oesophagus (corresponding to its adventitia) and heart (corresponding to the fibrous layer of the pericardial sac) from eight fresh cadavers were sampled and analysed with histological and immunohistochemical stains to evaluate collagen and elastic components and innervation. Although the visceral fasciae make up a well-defined layer of connective tissue, the thickness, percentage of elastic fibres and innervation vary among the different viscera. In particular, the fascia of the lung has a mean thickness of 134 μm (± 21), that of heart 792 μm (± 132), oesophagus 105 μm (± 10), liver 131 μm (± 18), Gerota fascia 1009 μm (± 105) and the visceral fascia of the abdomen 987 μm (± 90). The greatest number of elastic fibres (9.79%) was found in the adventitia of the oesophagus. The connective layers lying immediately outside the mesothelium of the pleura and peritoneum also have many elastic fibres (4.98% and 4.52%, respectively), whereas the pericardium and Gerota fascia have few (0.27% and 1.38%). In the pleura, peritoneum and adventitia of the oesophagus, elastic fibres form a well-defined layer, corresponding to the elastic lamina, while in the other cases they are thinner and scattered in the connective tissue. Collagen fibres also show precise spatial organisation, being arranged in several layers. In each layer, all the fibrous bundles are parallel with each other, but change direction among layers. Loose connective tissue rich in elastic fibres is found between contiguous fibrous layers. Unmyelinated nerve fibres were found in all samples, but myelinated fibres were only found in some fasciae, such as those of the liver and heart, and the visceral fascia of the abdomen. According to these findings, we propose distinguishing the visceral fasciae into two large groups. The first group includes all the fasciae closely related to the individual organ and giving shape to it, supporting the parenchyma; these are thin, elastic and very well innervated. The second group comprises all the fibrous sheets forming the compartments for the organs and also connecting the internal organs to the musculoskeletal system. These fasciae are thick, less elastic and less innervated, but they contain larger and myelinated nerves. We propose to call the first type of fasciae 'investing fasciae', and the second type 'insertional fasciae'. © 2017 Anatomical Society.

Noncoding RNAs and chronic inflammation: Micro-managing the fire within.

PubMed

Alexander, Margaret; O'Connell, Ryan M

2015-09-01

Inflammatory responses are essential for the clearance of pathogens and the repair of injured tissues; however, if these responses are not properly controlled chronic inflammation can occur. Chronic inflammation is now recognized as a contributing factor to many age-associated diseases including metabolic disorders, arthritis, neurodegeneration, and cardiovascular disease. Due to the connection between chronic inflammation and these diseases, it is essential to understand underlying mechanisms behind this process. In this review, factors that contribute to chronic inflammation are discussed. Further, we emphasize the emerging roles of microRNAs (miRNAs) and other noncoding RNAs (ncRNA) in regulating chronic inflammatory states, making them important future diagnostic markers and therapeutic targets. © 2015 The Authors. BioEssays published by WILEY Periodicals, Inc.

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

PubMed Central

Ranjbari, Ardeshir; Gholami, Gholam Ali; Amid, Reza; Kadkhodazadeh, Mahdi; Youssefi, Navid; Mehdizadeh, Amir Reza; Aghaloo, Maryam

2016-01-01

Statement of the Problem Gingival recession has been considered as the most challenging issue in the field of periodontal plastic surgery. Purpose The purpose of this study was to evaluate the clinical efficacy of root coverage procedures by using partial thickness double pedicle graft and compare it with full thickness double pedicle graft. Materials and Method Eight patients, aged 15 to 58 years including 6 females and 2 males with 20 paired (mirror image) defects with class I and II gingival recession were randomly assigned into two groups. Clinical parameters such as recession depth, recession width, clinical attachment level, probing depth, and width of keratinized tissue were measured at the baseline and 6 months post-surgery. A mucosal double papillary flap was elevated and the respective root was thoroughly planed. The connective tissue graft was harvested from the palate, and then adapted over the root. The pedicle flap was secured over the connective tissue graft and sutured. The surgical technique was similar in the control group except for the prepared double pedicle graft which was full thickness. Results The mean root coverage was 88.14% (2.83 mm) in the test group and 85.7% (2.75 mm) in the control group. No statistical differences were found in the mean reduction of vertical recession, width of recession, or probing depth between the test and control groups. In both procedures, the width of keratinized tissue increased after three months and the difference between the two groups was not statistically significant in this respect. Conclusion Connective tissue with partial and full thickness double pedicle grafts can be successfully used for treatment of marginal gingival recession. PMID:27602394

Improvement in skin elasticity in the treatment of cellulite and connective tissue weakness by means of extracorporeal pulse activation therapy.

PubMed

Christ, Christophe; Brenke, Rainer; Sattler, Gerhard; Siems, Werner; Novak, Pavel; Daser, A

2008-01-01

Extracorporeal pulse activation therapy (EPAT), also called extracorporeal acoustic wave therapy, seeks to achieve effective and long-lasting improvement of age-related connective tissue weakness in the extremities, especially in the treatment of unsightly cosmetic skin defects referred to as cellulite. The objective of this study was to stimulate metabolic activity in subcutaneous fat tissue by means of EPAT in order evaluate its effectiveness in enhancing connective tissue firmness and improving skin texture and structure. Fifty-nine women with advanced cellulite were divided into 2 groups; one group of 15 patients received planar acoustic wave treatment for 6 therapy sessions within 3 weeks; a second group of 44 patients received 8 therapy sessions within 4 weeks. Changes in connective tissue were evaluated using the DermaScan C ultrasound system (Cortex Technology, Hadsund, Denmark). Skin elasticity measurements were performed using the DermaLab system (Cortex Technology). Photographs of treated areas were taken at each therapy session and at follow-up sessions. Skin elasticity values gradually improved over the course of EPAT therapy and revealed a 73% increase at the end of therapy. At 3- and 6-month follow-ups, skin elasticity had even improved by 95% and 105%, respectively. Side effects included minor pain for 3 patients during therapy and slight skin reddening. This study confirmed the effects of acoustic wave therapy on biologic tissue, including stimulation of microcirculation and improvement of cell permeability. Ultrasound evaluation demonstrated increased density and firmness in the network of collagen/elastic fibers in the dermis and subcutis. Treatment was most effective in older patients with a long history of cellulite.

Effect of defective collagen synthesis on epithelial implant interface: lathyritic model in dogs. An experimental preliminary study.

PubMed

Cengiz, Murat Inanç; Kirtiloğlu, Tuğrul; Acikgoz, Gökhan; Trisi, Paolo; Wang, Hom-Lay

2012-04-01

Peri-implant mucosa is composed of 2 compartments: a marginal junctional epithelium and a zone of connective tissue attachment. Both structures consist mainly of collagen. Lathyrism is characterized by defective collagen synthesis due to inhibition of lysyl oxidase, an enzyme that is essential for interfibrillar collagen cross-linking. The lathyritic agent beta-aminoproprionitrile (β-APN) is considered a suitable agent to disrupt the connective tissue metabolism. Therefore, the purpose of this study was to assess the effect of defective connective tissue metabolism on epithelial implant interface by using β-APN created chronic lathyrism in the canine model. Two 1-year-old male dogs were included in this study. A β-APN dosage of 5 mg/0.4 mL/volume 100 g/body weight was given to the test dog for 10 months, until lathyritic symptoms developed. After this, the mandibular premolar teeth (p2, p3, p4) of both dogs were atraumatically extracted, and the investigators waited 3 months before implants were placed. In the test dog, 3 implants were placed in the left mandible, and 2 implants were placed in the right mandible. In the control dog, 2 implants were placed in the left mandibular premolar site. The dogs were sacrificed 10 months after healing. Peri-implant tissues obtained from the dogs were examined histomorphologically and histopathologically. Bone to implant contact (BIC) values and bone volumes (BV) were lower in the lathyritic group compared to the control group; however, no statistical significance was found. Significant histologic and histomorphometric changes were observed in peri-implant bone, connective tissue, and peri-implant mucosal width between test and control implants. Defective collagen metabolism such as lathyrism may negatively influence the interface between implant and surrounding soft tissue attachment.

Advanced glycation products' levels and mechanical properties of vaginal tissue in pregnancy.

PubMed

Weli, Homayemem K; Akhtar, Riaz; Chang, Zhuo; Li, Wen-Wu; Cooper, Jason; Yang, Ying

2017-07-01

Non-enzymatic glycation is closely associated with altered mechanical properties of connective tissue. Pregnancy, marked with high levels of female hormones, confers unique alteration to the mechanical properties of pelvic connective tissues in order to meet their physiological demands. However, there are few studies on glycation content and its influence on the mechanical properties of pelvic connective tissues during pregnancy. We hypothesise that the glycation content in pelvic tissues will change with a corresponding alteration in their mechanical properties, and that these changes are influenced by hormone levels. This study aims to investigate the correlation of vaginal tissue glycation content and mechanical property changes during pregnancy in association with the expression of a key pregnancy hormone (oestrogen) receptor, and an antioxidant enzyme, glyoxalase I. A rat vaginal tissue model (tissues from non-pregnant and E15-E18 (last trimester) pregnant rats) was used in this study. Mechanical characteristics of vaginal tissues were analysed by a ball-indentation technique while modulus and morphology of the collagen fibrils within the tissues were measured with atomic force microscopy. A glycation marker, pentosidine, was quantified by a high performance liquid chromatography. The expression of oestrogen receptor and glyoxalase I in the tissue was qualified by immunochemical staining. The glycosaminoglycan (GAG) concentration difference in the tissues were quantified by a biochemical assay. Pregnant rat vaginal tissue was characterised by significantly lower amounts of pentosidine, higher oestrogen receptor and glyoxalase I expression with larger creep, lower elastic modulus, larger fibril diameter and higher GAG content than their non-pregnant counterpart. There was a negative correlation between pentosidine and vaginal tissue creep. There was a reduction in vaginal tissue pentosidine in pregnancy with an associated increase in oestrogen receptor and glyoxalase I immunoexpression. Reduced glycation was associated with increased creeping of vaginal tissue. Oestrogen may therefore play a role in the increase of the vaginal wall's capacity to stretch through glyoxalase I up-regulation and subsequent glycation reduction. The new insight of the correlation of women's oestrogen level, glycation reaction and pelvic tissue mechanical property from this study may enhance our understanding of some pelvic organ diseases. Copyright © 2017 Elsevier B.V. All rights reserved.

Intercellular communication via gap junctions affected by mechanical load in the bovine annulus fibrosus.

PubMed

Desrochers, Jane; Duncan, Neil A

2014-01-01

Cells in the intervertebral disc, as in other connective tissues including tendon, ligament and bone, form interconnected cellular networks that are linked via functional gap junctions. These cellular networks may be necessary to affect a coordinated response to mechanical and environmental stimuli. Using confocal microscopy with fluorescence recovery after photobleaching methods, we explored the in situ strain environment of the outer annulus of an intact bovine disc and the effect of high-level flexion on gap junction signalling. The in situ strain environment in the extracellular matrix of the outer annulus under high flexion load was observed to be non-uniform with the extensive cellular processes remaining crimped sometimes at flexion angles greater than 25°. A significant transient disruption of intercellular communication via functional gap junctions was measured after 10 and 20 min under high flexion load. This study illustrates that in healthy annulus fibrosus tissue, high mechanical loads can impede the functioning of the gap junctions. Future studies will explore more complex loading conditions to determine whether losses in intercellular communication can be permanent and whether gap junctions in aged and degenerated tissues become more susceptible to load. The current research suggests that cellular structures such as gap junctions and intercellular networks, as well as other cell-cell and cell-matrix interconnections, need to be considered in computational models in order to fully understand how macroscale mechanical signals are transmitted across scales to the microscale and ultimately into a cellular biosynthetic response in collagenous tissues.

[MCTD--mixed connective tissue disease].

PubMed

Haustein, Uwe-Frithjof

2005-02-01

Mixed connective tissue disease is a disease entity characterized by overlapping symptoms of lupus erythematosus (LE), systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM) and rheumatoid arthritis (RA). Diagnostic criteria include high titers of antibodies against U1RNP as well as the presence of at least 3 of 5 of the following clinical features: edema of hands, synovitis, myositis, Raynaud phenomenon and acroscierosis. In terms of the pathogenesis, genetic as well as infectious (viral) factors appear to play a role. The acceptance of MCTD as a distinct disease entity is controversial. Terms such as "undifferentiated connective tissue disease" or "overlapping syndromes" are not helpful. One-quarter of MCTD patients transform into LE, while one-third progress to SSc. Therapeutic recommendations are glucocorticoids in combination with immunosuppressive agents and endothelin receptor antagonists. Double blind studies are not available. The prognosis is relatively good. Causes of death include pulmonary hypertension, infections and both pulmonary and cardiac failure.

Reference spectra from squamous epithelium and connective tissue allow whole section proteomics analysis.

PubMed

Roesch-Ely, Mariana; Schnölzer, Martina; Nees, Matthias; Plinkert, Peter K; Bosch, Franz X

2010-01-01

We reasoned that micro-dissection of tumour cells for protein expression studies should be omitted since tumour-stroma interactions are an important part of the biology of solid tumours. To study such interactions in head and neck squamous cell carcinoma (HNSCC) development, we generated reference protein spectra for normal squamous epithelium and connective tissue by SELDI-TOF-MS. Calgranulins A and B, Annexin1 and Histone H4 were found to be strongly enriched in the epithelium. The alpha-defensins 1-3 and the haemoglobin subunits were identified in the connective tissue. Tumour-distant epithelia, representing early pre-malignant lesions, showed up-regulated expression of the stromal alpha-defensins, whereas the epithelial Annexin 1 was down-regulated. Thus, tumour microenvironment interactions occur very early in the carcinogenic process. These data demonstrate that omitting micro-dissection is actually beneficial for studying changes in protein expression during development and progression of solid tumours.

Marshall-Smith syndrome: natural history and evidence of an osteochondrodysplasia with connective tissue abnormalities.

PubMed

Adam, Margaret P; Hennekam, Raoul C M; Keppen, Laura Davis; Bull, Marilyn J; Clericuzio, Carol L; Burke, Leah W; Ormond, Kelly E; Hoyme, Eugene H

2005-08-30

The Marshall-Smith syndrome (MSS) is a distinct malformation syndrome characterized by accelerated skeletal maturation, relative failure to thrive, respiratory difficulties, mental retardation, and unusual facies, including prominent forehead, shallow orbits, blue sclerae, depressed nasal bridge, and micrognathia. At least 33 cases have been reported in the literature, mostly as single case reports or small series. The purpose of the present study is to report on the clinical findings and natural history of MSS in five children and to review the features of three others previously reported, with particular attention to the skeletal and connective tissue findings. Our study demonstrates an increased rate of nontraumatic fractures and other bony and connective tissue abnormalities that support the hypothesis that MSS should be considered an osteochondrodysplasia. In addition, long-term survival beyond infancy is possible if respiratory problems are expectantly and aggressively managed. (c) 2005 Wiley-Liss, Inc.

Degenerative alterations of the cementum-periodontal ligament complex and early tooth loss in a young patient with periodontal disease.

PubMed

Petruţiu, S A; Buiga, Petronela; Roman, Alexandra; Danciu, Theodora; Mihu, Carmen Mihaela; Mihu, D

2012-01-01

Premature exfoliation of primary or permanent teeth in children or adolescents is extremely rare and it can be a manifestation of an underlying systemic disease. This study aims to present the histological aspects associated with early tooth loss in a case of periodontal disease developed without local inflammation and with minimal periodontal pockets and attachment loss. The maxillary left second premolar was extracted together with a gingival collar attached to the root surface. The histological analysis recorded the resorption of the cementum in multiple areas of the entire root surface with the connective tissue of the desmodontium invading the lacunae defects. The connective tissue rich in cells occupied the periodontal ligamentar space and the resorptive areas. No inflammation was obvious in the periodontal ligament connective tissue. This report may warn clinicians about the possibility of the association of cemental abnormalities with early tooth loss.

[Systemic lupus erythematosus masking the acquired immunodeficiency syndrome. A report on four cases].

PubMed

Kotyla, Przemysław; Kucharz, Eugeniusz J

2012-01-01

Systemic lupus erythematosus (SLE) is a systemic inflammatory disease of connective tissue with an unknown etiology and a rich clinical picture with involvement of multiple organs. Given the rich symptomatology, application of the current classification criteria is associated with a significant risk of attributing symptoms of other pathologies to lupus and/or other connective tissue disease. Inherited and acquired immune deficiencies may sometimes demonstrate a lupus-like clinical symptomatology. In this work we reviewed 4 of cases referred to the Department of Internal Diseases and Rheumatology of the Silesian Medical University in Katowice with suspected or confirmed systemic lupus erythematosus. A positive anti-HIV antibody test led to the diagnosis of the acquired immunodeficiency syndrome (AIDS). Due to the close similarity of the clinical picture and the presence of antinuclear antibodies in both diseases, the authors postulate that the anti-HIV antibody test should be done routinely in patients with connective tissue diseases.

[Study of collagen and elastic fibers of connective tissue in patients with and without primary inguinal hernia].

PubMed

Bórquez, Pablo; Garrido, Luis; Manterola, Carlos; Peña, Patricio; Schlageter, Carol; Orellana, Juan José; Ulloa, Hugo; Peña, Juan Luis

2003-11-01

There are few studies looking for collagen matrix defects in patients with inguinal bernia. To study the skin connective tissue in patients with and without inguinal bernia. Skin from the surgical wound was obtained from 23 patients with and 23 patients without inguinal bernia. The samples were processed for conventional light microscopy. Collagen fibers were stained with Van Giesson and elastic fibers with Weigert stain. Patients without hernia had compact collagen tracts homogeneously distributed towards the deep dermis. In contrast, patients with hernia had zones in the dermis with thinner and disaggregated collagen tracts. Connective tissue had a lax aspect in these patients. Collagen fiber density was 52% lower in patients with hernia, compared to subjects without hernia. No differences in elastic fiber density or distribution was observed between groups. Patients with inguinal bernia have alterations in skin collagen fiber quality and density.

Effects of Skin Thickness on Cochlear Input Signal using Transcutaneous Bone Conduction Implants

PubMed Central

Mattingly, Jameson K.; Greene, Nathaniel T.; Jenkins, Herman A.; Tollin, Daniel J.; Easter, James R.; Cass, Stephen P.

2015-01-01

Hypothesis Intracochlear sound pressures (PIC) and velocity measurements of the stapes, round window, and promontory (VStap/RW/Prom) will show frequency dependent attenuation using magnet-based, transcutaneous bone-conduction implants (TCBCI) in comparison to direct-connect, skin-penetrating implants (DCBCI). Background TCBCIs have recently been introduced as alternatives to DCBCIs. Clinical studies have demonstrated elevated high-frequency thresholds for TCBCIs as compared to DCBCIs; however, little data exists examining the direct effect of skin thickness on the cochlear input signal using TCBCIs. Methods Using seven cadveric heads, PIC was measured in the scala vestibuli and tympani with fiber-optic pressure sensors concurrently with VStap/RW/Prom via laser Doppler vibrometry. Ipsilateral titanium implant fixtures were placed and connected to either a DCBCI or TCBCI. Soft tissue flaps with varying thicknesses (no flap, 3, 6, and 9 mm) were placed successively between the magnetic plate and sound processor magnet. A bone-conduction transducer coupled to custom software provided pure tone stimuli between 120 to 10240 Hz. Results Stimulation via the DCBCI produced the largest response magnitudes. The TCBCI showed similar PSV/ST and VStap/RW/Prom with no intervening flap, and a frequency-dependent, non-linear reduction of magnitude with increasing flap thickness. Phase shows a comparable dependence on transmission delay as the acoustic baseline, and the slope steepens at higher frequencies as flap thickness increases suggesting a longer group delay. Conclusions Proper soft tissue management is critical to optimize the cochlear input signal. The skin thickness related effects on cochlear response magnitudes should be taken into account when selecting patients for a TCBCI. PMID:26164446

Platelet-derived chemokines CXC chemokine ligand (CXCL)7, connective tissue-activating peptide III, and CXCL4 differentially affect and cross-regulate neutrophil adhesion and transendothelial migration.

PubMed

Schenk, Birgit I; Petersen, Frank; Flad, Hans-Dieter; Brandt, Ernst

2002-09-01

In this study, we have examined the major platelet-derived CXC chemokines connective tissue-activating peptide III (CTAP-III), its truncation product neutrophil-activating peptide 2 (CXC chemokine ligand 7 (CXCL7)), as well as the structurally related platelet factor 4 (CXCL4) for their impact on neutrophil adhesion to and transmigration through unstimulated vascular endothelium. Using monolayers of cultured HUVEC, we found all three chemokines to promote neutrophil adhesion, while only CXCL7 induced transmigration. Induction of cell adhesion following exposure to CTAP-III, a molecule to date described to lack neutrophil-stimulating capacity, depended on proteolytical conversion of the inactive chemokine into CXCL7 by neutrophils. This was evident from experiments in which inhibition of the CTAP-III-processing protease and simultaneous blockade of the CXCL7 high affinity receptor CXCR-2 led to complete abrogation of CTAP-III-mediated neutrophil adhesion. CXCL4 at substimulatory dosages modulated CTAP-III- as well as CXCL7-induced adhesion. Although cell adhesion following exposure to CTAP-III was drastically reduced, CXCL7-mediated adhesion underwent significant enhancement. Transendothelial migration of neutrophils in response to CXCL7 or IL-8 (CXCL8) was subject to modulation by CTAP-III, but not CXCL4, as seen by drastic desensitization of the migratory response of neutrophils pre-exposed to CTAP-III, which was paralleled by selective down-modulation of CXCR-2. Altogether our results demonstrate that there exist multiple interactions between platelet-derived chemokines in the regulation of neutrophil adhesion and transendothelial migration.

Tissue Engineering Strategies for the Tendon/ligament-to-bone insertion

PubMed Central

Smith, Lester; Xia, Younan; Galatz, Leesa M.; Genin, Guy M.; Thomopoulos, Stavros

2012-01-01

Injuries to connective tissues are painful and disabling and result in costly medical expenses. These injuries often require re-attachment of an unmineralized connective tissue to bone. The uninjured tendon/ligament-to-bone insertion (enthesis) is a functionally graded material that exhibits a gradual transition from soft tissue (i.e., tendon or ligament) to hard tissue (i.e., mineralized bone) through a fibrocartilaginous transition region. This transition is believed to facilitate force transmission between the two dissimilar tissues by ameliorating potentially damaging interfacial stress concentrations. The transition region is impaired or lost upon tendon/ligament injury and is not regenerated following surgical repair or natural healing, exposing the tissue to risk of re-injury. The need to regenerate a robust tendon-to-bone insertion has led a number of tissue engineering repair strategies. This review treats the tendon-to-bone insertion site as a tissue structure whose primary role is mechanical and discusses current and emerging strategies for engineering the tendon/ligament-to-bone insertion in this context. The focus lies on strategies for producing mechanical structures that can guide and subsequently sustain a graded tissue structure and the associated cell populations. PMID:22185608

Tissue-engineering strategies for the tendon/ligament-to-bone insertion.

PubMed

Smith, Lester; Xia, Younan; Galatz, Leesa M; Genin, Guy M; Thomopoulos, Stavros

2012-01-01

Injuries to connective tissues are painful and disabling and result in costly medical expenses. These injuries often require reattachment of an unmineralized connective tissue to bone. The uninjured tendon/ligament-to-bone insertion (enthesis) is a functionally graded material that exhibits a gradual transition from soft tissue (i.e., tendon or ligament) to hard tissue (i.e., mineralized bone) through a fibrocartilaginous transition region. This transition is believed to facilitate force transmission between the two dissimilar tissues by ameliorating potentially damaging interfacial stress concentrations. The transition region is impaired or lost upon tendon/ligament injury and is not regenerated following surgical repair or natural healing, exposing the tissue to risk of reinjury. The need to regenerate a robust tendon-to-bone insertion has led a number of tissue engineering repair strategies. This review treats the tendon-to-bone insertion site as a tissue structure whose primary role is mechanical and discusses current and emerging strategies for engineering the tendon/ligament-to-bone insertion in this context. The focus lies on strategies for producing mechanical structures that can guide and subsequently sustain a graded tissue structure and the associated cell populations.

Cell Migration

PubMed Central

Trepat, Xavier; Chen, Zaozao; Jacobson, Ken

2015-01-01

Cell migration is fundamental to establishing and maintaining the proper organization of multicellular organisms. Morphogenesis can be viewed as a consequence, in part, of cell locomotion, from large-scale migrations of epithelial sheets during gastrulation, to the movement of individual cells during development of the nervous system. In an adult organism, cell migration is essential for proper immune response, wound repair, and tissue homeostasis, while aberrant cell migration is found in various pathologies. Indeed, as our knowledge of migration increases, we can look forward to, for example, abating the spread of highly malignant cancer cells, retarding the invasion of white cells in the inflammatory process, or enhancing the healing of wounds. This article is organized in two main sections. The first section is devoted to the single-cell migrating in isolation such as occurs when leukocytes migrate during the immune response or when fibroblasts squeeze through connective tissue. The second section is devoted to cells collectively migrating as part of multicellular clusters or sheets. This second type of migration is prevalent in development, wound healing, and in some forms of cancer metastasis. PMID:23720251

[Treatment of postburn and postoperative cicatrices using karipaine cream preparations and karipaine ultra gel].

PubMed

Zhernov, O A; Osadcha, O I; Zhernov, A O; Nazarenko, V M; Staskevych, S V

2011-07-01

Peculiarities of the burn wound course and the cicatricial tissue formation are shown. Clinical efficacy of application of cream Karipaine and gel Karipaine Ultra was proved, witnessed by improvement of the cell to tissue interaction as well as the connective tissue metabolism and the cicatricial tissue reconstruction.

MicroRNA-143-3p inhibits hyperplastic scar formation by targeting connective tissue growth factor CTGF/CCN2 via the Akt/mTOR pathway.

PubMed

Mu, Shengzhi; Kang, Bei; Zeng, Weihui; Sun, Yaowen; Yang, Fan

2016-05-01

Post-traumatic hypertrophic scar (HS) is a fibrotic disease with excessive extracellular matrix (ECM) production, which is a response to tissue injury by fibroblasts. Although emerging evidence has indicated that miRNA contributes to hypertrophic scarring, the role of miRNA in HS formation remains unclear. In this study, we found that miR-143-3p was markedly downregulated in HS tissues and fibroblasts (HSFs) using qRT-PCR. The expression of connective tissue growth factor (CTGF/CCN2) was upregulated both in HS tissues and HSFs, which is proposed to play a key role in ECM deposition in HS. The protein expression of collagen I (Col I), collagen III (Col III), and α-smooth muscle actin (α-SMA) was obviously inhibited after treatment with miR-143-3p in HSFs. The CCK-8 assay showed that miR-143-3p transfection reduced the proliferation ability of HSFs, and flow cytometry showed that either early or late apoptosis of HSFs was upregulated by miR-143-3p. In addition, the activity of caspase 3 and caspase 9 was increased after miR-143-3p transfection. On the contrary, the miR-143-3p inhibitor was demonstrated to increase cell proliferation and inhibit apoptosis of HSFs. Moreover, miR-143-3p targeted the 3'-UTR of CTGF and caused a significant decrease of CTGF. Western blot demonstrated that Akt/mTOR phosphorylation and the expression of CTGF, Col I, Col III, and α-SMA were inhibited by miR-143-3p, but increased by CTGF overexpression. In conclusion, we found that miR-143-3p inhibits hypertrophic scarring by regulating the proliferation and apoptosis of human HSFs, inhibiting ECM production-associated protein expression by targeting CTGF, and restraining the Akt/mTOR pathway.

Changes of the peri-implant soft tissue thickness after grafting with a collagen matrix.

PubMed

Zafiropoulos, Gregory-George; Deli, Giorgio; Hoffmann, Oliver; John, Gordon

2016-01-01

The aim of this study was to determine the treatment outcome of the use of a porcine monolayer collagen matrix (mCM) to increase soft-tissue volume as a part of implant site development. Implants were placed in single sites in 27 patients. In the test group, mCM was used for soft-tissue augmentation. No graft was placed in the control group. Soft-tissue thickness (STTh) was measured at the time of surgery (T0) and 6 months postoperatively (T1) at two sites (STTh 1, 1 mm below the gingival margin; STTh 2, 3 mm below the mucogingival margin). Significant increases ( P < 0.001) in STTh (STTh 1 = 1.06 mm, 117%; STTh 2 = 0.89 mm, 81%) were observed in the test group. Biopsy results showed angiogenesis and mature connective tissue covered by keratinized epithelium. Within the limitations of this study, it could be concluded that mCM leads to a significant increase of peri-implant soft-tissue thickness, with good histological integration and replacement by soft tissue and may serve as an alternative to connective tissue grafting.

In vivo characterization of Hyalonect, a novel biodegradable surgical mesh.

PubMed

Rhodes, Nicholas P; Hunt, John A; Longinotti, Cristina; Pavesio, Alessandra

2011-06-01

Musculoskeletal reconstructive surgery often requires removal of significant quantities of bone tissue, such as the periosteum, causing critical problems following surgery like friction between different tissues and adhesion of soft tissues to the underlying bone. We studied the long-term host response and closure of large bone defects for periosteal reconstruction using Hyalonect, a novel membrane comprising knitted fibers of esterified hyaluronan, (HYAFF11). For biological characterization, 162 rats were used in a defect model in which a section of the dorsal muscular fascia was removed, and the membrane behavior observed over 540 d using conventional histology, with sham operated rats as controls. In addition, Hyalonect was used to cover defects made in the humeri of 7 dogs, filled with a variety of conventional bone filling compounds, and the regeneration process observed after 6 wks using histology. Low levels of inflammation were observed in the dorsal muscle fascia defect model, with cellular colonization of the mesh by 30 d, vascularization by 120 days, matrix fiber organization by 270 d, and the appearance of connective tissue identical to the surrounding tissue between 365 and 540 d, without the formation of fibrotic tissue. In addition, Hyalonect was shown to allow the regeneration of bone within the humeral defects whilst preventing fibrotic tissue in-growth, and allowing regeneration of tissue which, by 6 wk, had begun to resemble natural periosteal tissue. Hyalonect is suitable for improving the outcome of the final phases of orthopedic and trauma reconstructive surgical procedures, especially in the reconstruction of periosteal tissue. Copyright © 2011. Published by Elsevier Inc.

Embryonic exposure to an aqueous coal dust extract results in gene expression alterations associated with the development and function of connective tissue and the hematological system, immunological and inflammatory disease, and cancer in zebrafish.

PubMed

Caballero-Gallardo, Karina; Wirbisky-Hershberger, Sara E; Olivero-Verbel, Jesus; de la Rosa, Jesus; Freeman, Jennifer L

2018-03-01

Coal mining is one of the economic activities with the greatest impact on environmental quality. At all stages contaminants are released as particulates such as coal dust. The first aim of this study was to obtain an aqueous coal dust extract and characterize its composition in terms of trace elements by ICP-MS. In addition, the developmental toxicity of the aqueous coal extract was evaluated using zebrafish (Danio rerio) after exposure to different concentrations (0-1000 ppm; μg mL -1 ) to establish acute toxicity, morphology and transcriptome changes. Trace elements within the aqueous coal dust extract present at the highest concentrations (>10 ppb) included Sr, Zn, Ba, As, Cu and Se. In addition, Cd and Pb were found in lower concentrations. No significant difference in mortality was observed (p > 0.05), but a delay in hatching was found at 0.1 and 1000 ppm (p < 0.05). No significant differences in morphological characteristics were observed in any of the treatment groups (p > 0.05). Transcriptomic results of zebrafish larvae revealed alterations in 77, 61 and 1376 genes in the 1, 10, and 100 ppm groups, respectively. Gene ontology analysis identified gene alterations associated with the development and function of connective tissue and the hematological system, as well as pathways associated with apoptosis, the cell cycle, transcription, and oxidative stress including the MAPK signaling pathway. In addition, altered genes were associated with cancer; connective tissue, muscular, and skeletal disorders; and immunological and inflammatory diseases. Overall, this is the first study to characterize gene expression alterations in response to developmental exposure to aqueous coal dust residue from coal mining with transcriptome results signifying functions and systems to target in future studies.

[Arterial involvements in hereditary dysplasia of the connective tissue].

PubMed

Beylot, C; Doutre, M S; Beylot-Barry, M; Busquet, M

1994-03-01

Arterial involvement is an important feature of the diagnosis and, above all, prognosis of heritable disorders of connective tissue. In pseudoxanthoma elasticum, a progressive occlusive syndrome is associated with hemorrhage and especially with gastrointestinal bleeding. Aneurysms are uncommon. Hypertension occurs frequently. Cutaneous signs (yellowish pseudo xanthomatous papules of the large folds) the ocular changes (angioid streaks) and pathology showing numerous, thickened, fragmented, disorganized, calcified elastic fibers in the deep dermis and arterial walls, allow the diagnosis to be made. In the heterogeneous group of Ehlers-Danlos syndromes, type IV is characterized by sudden spontaneous rupture of the large arteries. Aneurysms and carotido-cavernous fistulae are rather frequent. Owing to friability of the arterial walls, arteriograms and other procedure requiring arterial puncture may prove hazardous and surgery difficult. Such patients have an acrogeric morphotype, and thin, fragile skin, but cutaneous hyperelasticity and joint hyperlaxity are usually minimal. Pathology evidences collagen hypoplasia in the skin and arterial walls. The severity of Marfan syndrome is due to aortic involvement. A fusiform aneurysm of the ascending aorta represents a vital risk of rupture. Aortic root dilatation is associated and responsible of severe aortic regurgitation. Aortic dissection is also a serious threat. Improved surgical techniques for repairing a dilated or dissected aortic root with simultaneous replacement of the aortic valve increases the life expectancy of such patients. Dolichomorphism is the characteristic skeletal abnormality, particularly with arachnodactyly and upward ectopia lentis, which is almost bilateral, is a very frequent feature of Marfan syndrome. The most typical histological finding is aortic cystic median necrosis. The basic defect in Marfan syndrome concerns the fibrillin, whose gene is located on chromosome 15. The three diseases detailed in this paper constitute the main areas of this subject, but arterial involvement may occur in other inheritable disorders of connective tissue (osteogenesis imperfecta, cutis laxa, Werner syndrome, Menkes syndrome, etc).

Soft tissue engineering with micronized-gingival connective tissues.

PubMed

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

2018-01-01

The free gingival graft (FGG) and connective tissue graft (CTG) are currently considered to be the gold standards for keratinized gingival tissue reconstruction and augmentation. However, these procedures have some disadvantages in harvesting large grafts, such as donor-site morbidity as well as insufficient gingival width and thickness at the recipient site post-treatment. To solve these problems, we focused on an alternative strategy using micronized tissue transplantation (micro-graft). In this study, we first investigated whether transplantation of micronized gingival connective tissues (MGCTs) promotes skin wound healing. MGCTs (≤100 µm) were obtained by mincing a small piece (8 mm 3 ) of porcine keratinized gingiva using the RIGENERA system. The MGCTs were then transplanted to a full skin defect (5 mm in diameter) on the dorsal surface of immunodeficient mice after seeding to an atelocollagen matrix. Transplantations of atelocollagen matrixes with and without micronized dermis were employed as experimental controls. The results indicated that MGCTs markedly promote the vascularization and epithelialization of the defect area 14 days after transplantation compared to the experimental controls. After 21 days, complete wound closure with low contraction was obtained only in the MGCT grafts. Tracking analysis of transplanted MGCTs revealed that some mesenchymal cells derived from MGCTs can survive during healing and may function to assist in wound healing. We propose here that micro-grafting with MGCTs represents an alternative strategy for keratinized tissue reconstruction that is characterized by low morbidity and ready availability. © 2017 Wiley Periodicals, Inc.

Morphology and ultrastructure of the esophagus during the ontogeny of the spider crab Maja brachydactyla (Decapoda, Brachyura, Majidae).

PubMed

Castejón, Diego; Rotllant, Guiomar; Ribes, Enric; Durfort, Mercè; Guerao, Guillermo

2018-06-01

The esophagus of the eucrustaceans is known as a short tube that connects the mouth with the stomach but has generally received little attention by the carcinologists, especially during the larval stages. By this reason, the present study is focused on the morphology and ultrastructure of the esophagus in the brachyuran Maja brachydactyla during the larval development and adult stage. The esophagus shows internally four longitudinal folds. The simple columnar epithelium is covered by a thick cuticle. The epithelial cells of the adults are intensively interdigitated and show abundant apical mitochondria and bundles of filamentous structures. The cuticle surface has microspines and mutually exclusive pores. Three muscle layers surrounded by the connective tissue are reported: circular muscles forming a broad continuous band, longitudinal muscle bundles adjacent to the circular muscles, and dilator muscles crossing the connective tissue vertically toward the epithelium. The connective tissue has rosette glands. The esophagus of the larvae have epithelial cells with big vesicles but poorly developed interdigitations and filamentous structures, the cuticle is formed by a procuticle without differentiated exocuticle and endocuticle, the connective layer is thin and the rosette glands are absent. The observed features can be explained by his role in the swallowing of the food. © 2018 Wiley Periodicals, Inc.

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

PubMed Central

Ettl, A; Priglinger, S; Kramer, J; Koornneef, L

1996-01-01

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 fascial expansion (TSFE) of the SRM and LPS. It mainly extends from the connective tissue of the trochlea to the fascia of the lacrimal gland. A detailed description of the relation between the LPS and its connective tissue is presented. Furthermore, the course of the LPS in the orbit is described. The study was conducted to provide a morphological basis for biomechanical and clinical considerations regarding ptosis surgery. METHODS: Postmortem dissections were performed in 16 orbits from eight cadavers. The microscopical anatomy was demonstrated in six formalin preserved orbits from six cadavers which had been sectioned in the frontal and sagittal plane and stained with haematoxylin and azophloxin. Surface coil magnetic resonance imaging in the sagittal and coronal plane was performed in five orbits from five normal volunteers using a T1 weighted spin echo sequence. RESULTS: The STL and the TSFE surround the LPS to form a fascial sleeve around the muscle which has attachments to the medial and lateral orbital wall. The TSFE, which is thicker than the STL, blends with Tenon's capsule. The STL and the fascial sheath of the LPS muscle are suspended from the orbital roof by a framework of radial connective tissue septa. MR images show that the TSFE is located between the anterior third of the superior rectus muscle and the segment of the LPS muscle where it changes its course from upwards to downwards. In this area, the LPS reaches its highest point in the orbit (culmination point). The culmination point is located a few millimetres posterior to the equator and superior to the globe. CONCLUSION: Whitnall's ligament can be considered to consist of two distinct parts--the TSFE inferior to the LPS and the STL superior to the LPS. Since the medial and lateral main attachments of Whitnall's ligament are situated inferior to the level of the culmination point of the LPS, the ligament itself is unlikely to suspend the levator muscle. However, a suspension of the LPS may be achieved by the radial connective tissue septa of the superior orbit. The TSFE in connection with the globe may have an additional supporting function. The elasticity of Whitnall's ligament and its connections with highly elastic structures including Tenon's capsule, may provide the morphological substrate for the previously proposed passive (that is, without orbicularis action) lowering of the lid during downward saccades. Images PMID:8949713

Thalamotemporal impairment in temporal lobe epilepsy: a combined MRI analysis of structure, integrity, and connectivity.

PubMed

Keller, Simon S; O'Muircheartaigh, Jonathan; Traynor, Catherine; Towgood, Karren; Barker, Gareth J; Richardson, Mark P

2014-02-01

Thalamic abnormality in temporal lobe epilepsy (TLE) is well known from imaging studies, but evidence is lacking regarding connectivity profiles of the thalamus and their involvement in the disease process. We used a novel multisequence magnetic resonance imaging (MRI) protocol to elucidate the relationship between mesial temporal and thalamic pathology in TLE. For 23 patients with TLE and 23 healthy controls, we performed T1 -weighted (for analysis of tissue structure), diffusion tensor imaging (tissue connectivity), and T1 and T2 relaxation (tissue integrity) MRI across the whole brain. We used connectivity-based segmentation to determine connectivity patterns of thalamus to ipsilateral cortical regions (occipital, parietal, prefrontal, postcentral, precentral, and temporal). We subsequently determined volumes, mean tractography streamlines, and mean T1 and T2 relaxometry values for each thalamic segment preferentially connecting to a given cortical region, and of the hippocampus and entorhinal cortex. As expected, patients had significant volume reduction and increased T2 relaxation time in ipsilateral hippocampus and entorhinal cortex. There was bilateral volume loss, mean streamline reduction, and T2 increase of the thalamic segment preferentially connected to temporal lobe, corresponding to anterior, dorsomedial, and pulvinar thalamic regions, with no evidence of significant change in any other thalamic segments. Left and right thalamotemporal segment volume and T2 were significantly correlated with volume and T2 of ipsilateral (epileptogenic), but not contralateral (nonepileptogenic), mesial temporal structures. These convergent and robust data indicate that thalamic abnormality in TLE is restricted to the area of the thalamus that is preferentially connected to the epileptogenic temporal lobe. The degree of thalamic pathology is related to the extent of mesial temporal lobe damage in TLE. © 2014 The Authors. Epilepsia published by Wiley Periodicals, Inc. on behalf of International League Against Epilepsy.

[The relationship between the sympathetic nerves and immunocytes in the spleen].

PubMed

Saito, H

1991-02-01

Ever since Galen, the ancient Greek physician, said "Melancholic women develop disease more than sanguine women," it has been said that the mental condition affects the physical condition. However, there is hardly any scientific verification. About half a century ago, Selye (1936) proposed a relationship between stress and immune function, and it is becoming increasingly clear that the nervous system and immune system interact with each other. Also researchers have strongly hoped to demonstrate the existence of specific pathways by which immunocytes can be directly regulated by the nervous elements instead of by the humoral influence of immunomodulators. In this study, the author showed by electron microscopic observation how the immunocytes in the guinea pig spleen are directly innervated. The sustentacular supporting element of the guinea pig spleen is the connective tissue system which includes the capsulo-trabecular, peri-vascular and reticular systems. The latter system is composed of the outer sheath of the reticular cell or its cellular processes which have abundant microfilaments and the inner minute connective tissue space in which lamina densa-like material, collagenous fibrils, elastic fibers and nervous elements are present. The sympathetic adrenergic nerves for the spleen enter the organ, and scatter around the arterial walls. All components of the connective tissue system are continuous with each other, and the nervous elements appearing in the reticular system are the elongated ones from other connective tissue systems, especially peri-vascular connective tissue. Thus, the adrenergic nerves are more abundant in the white pulp, into which the central artery penetrates, than in the red pulp which arterioles or capillaries pass through. The minute connective tissue space of the reticular system may be called the noradrenalin (NA) canal because catecholamine released from the naked adrenergic nerve terminals in this tissue diffuses and is stored in this enclosed space. The reticular system in the spleen divides the parenchyma into small non-endothelial vascular spaces owing to its meshwork, and free mobile immunocytes, such as T-cells, B-cells and macrophages, stagnate in these spaces. This stagnation of the mobile immunocytes and the presence of the adrenergic nerves in the NA canals provide the chance for the immunocytes and nerves to meet each other in the following fashion; the reticular cell sheaths show the exposed phenomena owing to the contraction of the microfilament-rich reticular cell processes, caused by noradrenalin in the NA canal, and the nervous elements in the NA canals can face the nonendothelial vascular spaces where mobile immunocytes pass freely.(ABSTRACT TRUNCATED AT 400 WORDS)

Use of a new collagen matrix (mucograft) for the treatment of multiple gingival recessions: case reports.

PubMed

Rotundo, Roberto; Pini-Prato, Giovanpaolo

2012-08-01

The aim of this case report study was to demonstrate the use of a new collagen matrix as an alternative to the connective tissue graft for the treatment of multiple gingival recessions. Three women showing 11 maxillary gingival recessions were treated by means of the envelope flap technique associated with a novel collagen matrix as a substitute for the connective tissue graft. At 1 year, complete root coverage was achieved in 9 treated sites, with a mean keratinized tissue width of 3.1 mm, complete resolution of dental hypersensitivity, and a high level of esthetic satisfaction.

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

PubMed Central

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

2011-01-01

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, while 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

The Reaction and Regeneration of Cementum in Various Pathological Conditions : (Section of Odontology).

PubMed

Stones, H H

1934-04-01

(1) The reaction of cementum and its adjoining tissues to induced pathological conditions associated with the gingival sulcus is described.(2) After subjecting the sulcus to interference, its histological appearance is compared with that of definite parodontal disease.(3) Various methods were adopted for these experiments, which were performed on monkeys.(4) Artificial pockets were produced by detaching the subgingival epithelium and underlying connective tissue from the cementum. (a) Cementum is easily removed accidentally, when scraping monkeys' teeth. (b) Reattachment of connective tissues to cementum is effected, but is usually incomplete. (c) Epithelium always firmly reunites with cementum. (d) The artificial sulcus which is usually deeper than normal does not show, microscopically, the same pathological changes as in parodontal disease.(5) In other experiments, in addition to deepening the sulcus, the cementum lining the pockets was also removed, leaving denuded dentine in contact with the connective tissue. A similar condition was achieved by another method in which a dental bur was inserted between two teeth below the gum margin. (a) The gingival epithelium is capable of forming a weak attachment to the dentine, though this does not usually occur. It always proliferates down and unites with the nearest layer of cementum. It seems to have a peculiar affinity for this tissue. (b) Underlying connective tissue does not usually unite with the dentine. When this happens it is effected by the regeneration of cementum, this new tissue being lined by new cementoblasts. (c) The width of the periodontal membrane, which was increased by the experiment, is reduced to a more normal level by deposition of new alveolar bone, and to a lesser extent by regeneration of cementum. (d) In this series of experiments the artificial pocket is permanent and somewhat resembles that of parodontal disease. This is probably due, not so much to the injury, but to its effects creating a space which forms an area of chronic stagnation.

The in vitro inflation response of mouse sclera.

PubMed

Myers, Kristin M; Cone, Frances E; Quigley, Harry A; Gelman, Scott; Pease, Mary E; Nguyen, Thao D

2010-12-01

The purpose of this research was to develop a reliable and repeatable inflation protocol to measure the scleral inflation response of mouse eyes to elevations in intraocular pressure (IOP), comparing the inflation response exhibited by the sclera of younger and older C57BL/6 mice. Whole, enucleated eyes from younger (2 month) and older (11 month) C57BL/6 mice were mounted by the cornea on a custom fixture and inflated according to a load-unload, ramp-hold pressurization regimen via a cannula connected to a saline-filled programmable syringe pump. First, the tissue was submitted to three load-unload cycles from 6 mmHg to 15 mmHg at a rate of 0.25 mmHg/s with ten minutes of recovery between cycles. Next the tissue was submitted to a series of ramp-hold tests to measure the creep behavior at different pressure levels. For each ramp-hold test, the tissue was loaded from 6 mmHg to the set pressure at a rate of 0.25 mmHg/s and held for 30 min, and then the specimens were unloaded to 6 mmHg for 10 min. This sequence was repeated for set pressures of: 10.5, 15, 22.5, 30, 37.5, and 45 mmHg. Scleral displacement was measured using digital image correlation (DIC), and fresh scleral thickness was measured optically for each specimen after testing. For comparison, scleral thickness was measured on untested fresh tissue and epoxy-fixed tissue from age-matched animals. Comparing the apex displacement of the different aged specimens, the sclera of older animals had a statistically significant stiffer response to pressurization than the sclera of younger animals. The stiffness of the pressure-displacement response of the apex measured in the small-strain (6-15 mmHg) and the large-strain (37.5-45 mmHg) regime, respectively, were 287 ± 100 mmHg/mm and 2381 ± 191 mmHg/mm for the older tissue and 193 ± 40 mmHg/mm and 1454 ± 93 mmHg/mm for the younger tissue (Student t-test, p<0.05). The scleral thickness varied regionally, being thickest in the peripapillary region and thinnest at the equator. Fresh scleral thickness did not differ significantly by age in this group of animals. This study presents a reliable inflation test protocol to measure the mechanical properties of mouse sclera. The inflation methodology was sensitive enough to measure scleral response to changes in IOP elevations between younger and older C57BL/6 mice. Further, the specimen-specific scleral displacement profile and thickness measurements will enable future development of specimen-specific finite element models to analyze the inflation data for material properties. Copyright © 2010 Elsevier Ltd. All rights reserved.

A review on animal models and treatments for the reconstruction of Achilles and flexor tendons.

PubMed

Bottagisio, Marta; Lovati, Arianna B

2017-03-01

Tendon is a connective tissue mainly composed of collagen fibers with peculiar mechanical properties essential to functional movements. The increasing incidence of tendon traumatic injuries and ruptures-associated or not with the loss of tissue-falls on the growing interest in the field of tissue engineering and regenerative medicine. The use of animal models is mandatory to deepen the knowledge of the tendon healing response to severe damages or acute transections. Thus, the selection of preclinical models is crucial to ensure a successful translation of effective and safe innovative treatments to the clinical practice. The current review is focused on animal models of tendon ruptures and lacerations or defective injuries with large tissue loss that require surgical approaches or grafting procedures. Data published between 2000 and 2016 were examined. The analyzed articles were compiled from Pub Med-NCBI using search terms, including animal model(s) AND tendon augmentation OR tendon substitute(s) OR tendon substitution OR tendon replacement OR tendon graft(s) OR tendon defect(s) OR tendon rupture(s). This article presents the existing preclinical models - considering their advantages and disadvantages-in which translational progresses have been made by using bioactive sutures or tissue engineering that combines biomaterials with cells and growth factors to efficiently treat transections or large defects of Achilles and flexor tendons.

Reconciling healthcare professional and patient perspectives in the development of disease activity and response criteria in connective tissue disease-related interstitial lung diseases.

PubMed

Saketkoo, Lesley Ann; Mittoo, Shikha; Frankel, Sid; LeSage, Daphne; Sarver, Catherine; Phillips, Kristine; Strand, Vibeke; Matteson, Eric L

2014-04-01

Interstitial lung diseases (ILD), including those related to connective tissue disease (CTD), and idiopathic pulmonary fibrosis (IPF) carry high morbidity and mortality. Great efforts are under way to develop and investigate meaningful treatments in the context of clinical trials. However, efforts have been challenged by a lack of validated outcome measures and by inconsistent use of measures in clinical trials. Lack of consensus has fragmented effective use of strategies in CTD-ILD and IPF, with a history of resultant difficulties in obtaining agency approval of treatment interventions. Until recently, the patient perspective to determine domains and outcome measures in CTD-ILD and IPF had never been applied. Efforts described here demonstrate unequivocally the value and influence of patient involvement on core set development. Regarding CTD-ILD, this is the first OMERACT working group to directly address a manifestation/comorbidity of a rheumatic disease (ILD) as well as a disease not considered rheumatic (IPF). The OMERACT 11 proceedings of the CTD-ILD Working Group describe the forward and lateral process to include both the medical and patient perspectives in the urgently needed identification of a core set of preliminary domains and outcome measures in CTD-ILD and IPF.

Giant elephantiasis neuromatosa in the setting of neurofibromatosis type 1: A case report

PubMed Central

PONTI, GIOVANNI; PELLACANI, GIOVANNI; MARTORANA, DAVIDE; MANDEL, VICTOR DESMOND; LOSCHI, PIETRO; POLLIO, ANNAMARIA; PECCHI, ANNARITA; DEALIS, CRISTINA; SEIDENARI, STEFANIA; TOMASI, ALDO

2016-01-01

Elephantiasis neuromatosa (EN) can arise from a plexiform neurofibroma of the superficial and deep nerves developing from a hyperproliferation of the perineural connective tissue infiltrating adjacent fat and muscles. To date, the clinical association between EN and neurofibromatosis type 1 (NF1) has been poorly defined, particularly with regard to the role of lymphatic alterations and the consequent lymphedema. The present study reports the clinical and biomolecular features of EN in a NF1 patient with the clear clinical diagnostic criteria of multiple cafè-au-lait macules, neurofibromas, EN, a positive family history and a novel NF1 germline c.1541_1542del mutation. Lymphoscintigraphy (LS) highlighted marked dermal backflow in the affected limb, hypertrophy of the ipsilateral inguinal and external iliac lymph nodes, and a bilateral lower limb lymph flow delay. These data support the hypothesis that an extensive hyperproliferative process involving perineural connective, limb soft tissues, bones and the lymphatic system can be responsible for EN in NF1 patients, on the basis of adipocyte metaplasia triggered by lymphostasis and lymphedema, and bone overgrowth and gigantism caused by chronic hyperemia. LS and magnetic resonance imaging can be efficacious tools in the diagnosis and clinical characterization of the early onset of the disease. PMID:27284375