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.

[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.

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.

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

The dynamics of spiral tip adjacent to inhomogeneity in cardiac tissue

NASA Astrophysics Data System (ADS)

Zhang, Juan; Tang, Jun; Ma, Jun; Luo, Jin Ming; Yang, Xian Qing

2018-02-01

Rotating spiral waves in cardiac tissue are implicated in life threatening cardiac arrhythmias. Experimental and theoretical evidences suggest the inhomogeneities in cardiac tissue play a significant role in the dynamics of spiral waves. Based on a modified 2D cardiac tissue model, the interaction of inhomogeneity on the nearby rigidly rotating spiral wave is numerically studied. The adjacent area of the inhomogeneity is divided to two areas, when the initial rotating center of the spiral tip is located in the two areas, the spiral tip will be attracted and anchor on the inhomogeneity finally, or be repulsed away. The width of the area is significantly dependent on the intensity and size of the inhomogeneity. Our numerical study sheds some light on the mechanism of the interaction of inhomogeneity on the spiral wave in cardiac tissue.

Sucrose-Metabolizing Enzymes in Transport Tissues and Adjacent Sink Structures in Developing Citrus Fruit 1

PubMed Central

Lowell, Cadance A.; Tomlinson, Patricia T.; Koch, Karen E.

1989-01-01

Juice tissues of citrus lack phloem; therefore, photosynthates enroute to juice sacs exit the vascular system on the surface of each segment. Areas of extensive phloem unloading and transport (vascular bundles + segment epidermis) can thus be separated from those of assimilate storage (juice sacs) and adjacent tissues where both processes occur (peel). Sugar composition, dry weight accumulation, and activities of four sucrose-metabolizing enzymes (soluble and cell-wall-bound acid invertase, alkaline invertase, sucrose synthase, and sucrose phosphate synthase) were measured in these transport and sink tissues of grapefruit (Citrus paradisi Macf.) to determine more clearly whether a given enzyme appeared to be more directly associated with assimilate transport versus deposition or utilization. Results were compared at three developmental stages. Activity of sucrose (per gram fresh weight and per milligram protein) extracted from zones of extensive phloem unloading and transport was significantly greater than from adjacent sink tissues during the stages (II and III) when juice sacs grow most rapidly. In stage II fruit, activity of sucrose synthase also significantly surpassed that of all other sucrose-metabolizing enzymes in extracts from the transport tissues (vascular bundles + segment epidermis). In contrast, sucrose phosphate synthase and alkaline invertase at this stage of growth were the most active enzymes from adjacent, rapidly growing, phloem-free sink tissues (juice sacs). Activity of these two enzymes in extracts from juice sacs was significantly greater than that form the transport tissues (vascular bundles + segment epidermis). Soluble acid invertase was the most active enzyme in extracts from all tissues of very young fruit (stage I), including nonvascular regions, but nearly disappeared prior to the onset of juice sac sugar accumulation. The physiological function of high sucrose synthase activity in the transport tissues during rapid sucrose import

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

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.

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

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

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 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

Distinctive Glycerophospholipid Profiles of Human Seminoma and Adjacent Normal Tissues by Desorption Electrospray Ionization Imaging Mass Spectrometry

NASA Astrophysics Data System (ADS)

Masterson, Timothy A.; Dill, Allison L.; Eberlin, Livia S.; Mattarozzi, Monica; Cheng, Liang; Beck, Stephen D. W.; Bianchi, Federica; Cooks, R. Graham

2011-08-01

Desorption electrospray ionization mass spectrometry (DESI-MS) has been successfully used to discriminate between normal and cancerous human tissue from different anatomical sites. On the basis of this, DESI-MS imaging was used to characterize human seminoma and adjacent normal tissue. Seminoma and adjacent normal paired human tissue sections (40 tissues) from 15 patients undergoing radical orchiectomy were flash frozen in liquid nitrogen and sectioned to 15 μm thickness and thaw mounted to glass slides. The entire sample was two-dimensionally analyzed by the charged solvent spray to form a molecular image of the biological tissue. DESI-MS images were compared with formalin-fixed, hematoxylin and eosin (H&E) stained slides of the same material. Increased signal intensity was detected for two seminolipids [seminolipid (16:0/16:0) and seminolipid (30:0)] in the normal tubule testis tissue; these compounds were undetectable in seminoma tissue, as well as from the surrounding fat, muscle, and blood vessels. A glycerophosphoinositol [PI(18:0/20:4)] was also found at increased intensity in the normal testes tubule tissue when compared with seminoma tissue. Ascorbic acid (i.e., vitamin C) was found at increased amounts in seminoma tissue when compared with normal tissue. DESI-MS analysis was successfully used to visualize the location of several types of molecules across human seminoma and normal tissues. Discrimination between seminoma and adjacent normal testes tubules was achieved on the basis of the spatial distributions and varying intensities of particular lipid species as well as ascorbic acid. The increased presence of ascorbic acid within seminoma compared with normal seminiferous tubules was previously unknown.

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

PubMed Central

Yoo, Lawrence; Gupta, Vijay; Lee, Choongyeop; Kavehpore, Pirouz

2012-01-01

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

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

PubMed

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

2011-12-01

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

Fibroblastic connective tissue nevus.

PubMed

Velez, Moises J; Billings, Steven D; Weaver, Joshua A

2016-01-01

Fibroblastic connective tissue nevus (FCTN) is a newly recognized, benign cutaneous mesenchymal lesion of fibroblasts/myofibroblastic lineage, which expands the classification of connective tissue nevi. We present three cases of FCTN and discuss significant clinical, morphologic and immunophenotypic overlap with dermatomyofibroma. Our cases were from young women, aged 32, 24 and 10, and presented as 1.2 and 1 cm nodules on the posterior neck and right upper flank, respectively while presenting as a linear plaque of the right posterior thigh in the latter case. The lesions showed a poorly circumscribed proliferation of hypercellular spindle cells arranged in short to longer intersecting fascicles entrapping adnexal structures. Superficial adipose tissue was also entrapped in one case. The spindle cells had fibroblastic features with pale eosinophilic cytoplasmic extensions and inconspicuous nucleoli. The spindle cells were positive for CD34 in two cases. One case was negative for CD34, smooth muscle actin (SMA), desmin and S100. The overall features were consistent with a diagnosis of FCTN. In two cases, we further elucidated the fibroblastic differentiation of the spindle cells in FCTN with electron microscopy, which has not been previously described. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

[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

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.

Tookad-mediated photodynamic effects on the prostate and its adjacent tissues: in vivo study in canine models

NASA Astrophysics Data System (ADS)

Huang, Zheng; Chen, Qun; Luck, David; Beckers, Jill; Blanc, Dominique; Hetzel, Fred W.

2005-04-01

Photodynamic therapy (PDT) mediated with a vascular acting photosensitizer Tookad (pd-bacteriopheophorbide), was investigated as an alternative treatment modality for prostate cancer. Tookad photodynamic effects on the prostate and its adjacent tissues were evaluated in canine models. Interstitial prostate PDT was performed by irradiating individual lobes with a diode laser (763 nm) and 1-cm cylindrical diffuser fibers at various light doses to activate the IV administered photosensitizer Tookad (1 - 2 mg/kg). The sensitivity of the adjacent tissues to Tookad-PDT was determined by superficially irradiating the surfaces of the bladder, colon, abdominal muscle and pelvic plexus with a microlens fiber at various drug/light doses. PDT effect on the prostatic urethra was evaluated by transurethral irradiation. The prostate and adjacent tissues were harvested one-week after the treatment and subjected to histopathologic examination. At one-week post interstitial prostate PDT, the animals recovered well with little or no urethral complications. PDT induced prostate lesions were characterized by marked hemorrhagic necrosis. The bladder, colon, abdominal muscle and pelvic plexus, appeared to also be sensitive to Tookad-PDT at light dose levels greater than 40 Jcm2. Urethral mucosa appeared less sensitive to Tookad-PDT. In conclusion, Tookad-mediated PDT demonstrates very strong vascular effects and can provide an effective alternative for the treatment of localized prostate cancer. Protection of the adjacent tissues should be taken into consideration in the total prostate ablation process due to their sensitivity to the Tookad-mediated PDT.

[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.

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.

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- ...

Screening of the residual normal ovarian tissue adjacent to orthotopic epithelial ovarian carcinomas in nude mice.

PubMed

Zhu, G H; Wang, S T; Yao, M Z; Cai, J H; Chen, C Y; Yang, Z X; Hong, L; Yang, S Y

2014-04-16

The objective of this study was to explore the feasibility and methods of screening the residual normal ovarian tissue adjacent to orthotopic ovarian carcinomas in nude mice. Human epithelial ovarian cancer cells (OVCAR3) were subcutaneously implanted for a tumor source and ovarian orthotopic transplantation. The cancer tissue, proximal paraneoplastic tissue, middle paraneoplastic tissue, remote paraneoplastic tissue, and normal ovarian tissue were removed. CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was detected by reverse transcription polymerase chain reaction. We obtained 35 paraneoplastic residual ovarian tissues with normal biopsies from 40 cases of an orthotopic epithelial ovarian carcinoma model (87.5%). CK-7, CA125, p53, survivin, MMP-2, and TIMP-2 expression was lower in proximal paraneoplastic tissue than in cancer tissue (P < 0.05) and higher than in middle and remote paraneoplastic tissue (P < 0.01). There was no statistically significant difference between the expression of these genes in middle and proximal paraneoplastic tissue as well as among residual normal ovarian tissues with different severity (P > 0.05). In ovarian tissues of 20 normal nude mice, the expression of CK- 7, CA125, p53, survivin, MMP-2, and TIMP-2 was negative. Overall, the expression levels of CK-7, CA125, p53, survivin, MMP-2, TIMP-2, and other molecular markers showed a decreasing trend in the non-cancer tissue direction. The expression levels can be used as standards to screen residual normal ovarian tissue. We can obtain relatively safe normal ovarian tissues adjacent to epithelial ovarian cancer.

Adipose-Derived Stromal Vascular Fraction Differentially Expands Breast Progenitors in Tissue Adjacent to Tumors Compared to Healthy Breast Tissue

PubMed Central

Chatterjee, Sumanta; Laliberte, Mike; Blelloch, Sarah; Ratanshi, Imran; Safneck, Janice; Buchel, Ed

2015-01-01

Background: Autologous fat grafts supplemented with adipose-derived stromal vascular fraction are used in reconstructive and cosmetic breast procedures. Stromal vascular fraction contains adipose-derived stem cells that are thought to encourage wound healing, tissue regeneration, and graft retention. Although use of stromal vascular fraction has provided exciting perspectives for aesthetic procedures, no studies have yet been conducted to determine whether its cells contribute to breast tissue regeneration. The authors examined the effect of these cells on the expansion of human breast epithelial progenitors. Methods: From patients undergoing reconstructive breast surgery following mastectomies, abdominal fat, matching tissue adjacent to breast tumors, and the contralateral non–tumor-containing breast tissue were obtained. Ex vivo co-cultures using breast epithelial cells and the stromal vascular fraction cells were used to study the expansion potential of breast progenitors. Breast reduction samples were collected as a source of healthy breast cells. Results: The authors observed that progenitors present in healthy breast tissue or contralateral non–tumor-containing breast tissue showed significant and robust expansion in the presence of stromal vascular fraction (5.2- and 4.8-fold, respectively). Whereas the healthy progenitors expanded up to 3-fold without the stromal vascular fraction cells, the expansion of tissue adjacent to breast tumor progenitors required the presence of stromal vascular fraction cells, leading to a 7-fold expansion, which was significantly higher than the expansion of healthy progenitors with stromal vascular fraction. Conclusions: The use of stromal vascular fraction might be more beneficial to reconstructive operations following mastectomies compared with cosmetic corrections of the healthy breast. Future studies are required to examine the potential risk factors associated with its use. CLINICAL QUESTION/LEVEL OF EVIDENCE

Connective tissue growth factor is activated by gastrin and involved in gastrin-induced migration and invasion.

PubMed

Bhandari, Sabin; Bakke, Ingunn; Kumar, J; Beisvag, Vidar; Sandvik, Arne K; Thommesen, Liv; Varro, Andrea; Nørsett, Kristin G

2016-06-17

Connective tissue growth factor (CTGF) has been reported in gastric adenocarcinoma and in carcinoid tumors. The aim of this study was to explore a possible link between CTGF and gastrin in gastric epithelial cells and to study the role of CTGF in gastrin induced migration and invasion of AGS-GR cells. The effects of gastrin were studied using RT-qPCR, Western blot and assays for migration and invasion. We report an association between serum gastrin concentrations and CTGF abundancy in the gastric corpus mucosa of hypergastrinemic subjects and mice. We found a higher expression of CTGF in gastric mucosa tissue adjacent to tumor compared to normal control tissue. We showed that gastrin induced expression of CTGF in gastric epithelial AGS-GR cells via MEK, PKC and PKB/AKT pathways. CTGF inhibited gastrin induced migration and invasion of AGS-GR cells. We conclude that CTGF expression is stimulated by gastrin and involved in remodeling of the gastric epithelium. Copyright © 2016 Elsevier Inc. All rights reserved.

Expression of cyclooxygenase-1 and cyclooxygenase-2, syndecan-1 and connective tissue growth factor in benign and malignant breast tissue from premenopausal women.

PubMed

Fahlén, M; Zhang, H; Löfgren, L; Masironi, B; von Schoultz, E; von Schoultz, B; Sahlin, L

2017-05-01

Stromal factors have been identified as important for tumorigenesis and metastases of breast cancer. From 49 premenopausal women, samples were collected from benign or malignant tumors and the seemingly normal tissue adjacent to the tumor. The factors studied, with real-time polymerase chain reaction (PCR) and immunohistochemistry, were cyclooxygenase-1 and cyclooxygenase-2 (COX-1 and COX-2), syndecan-1 (S-1) and connective tissue growth factor (CTGF). COX-1 and S-1 mRNA levels were higher in the malignant tumors than in normal and benign tissues. The COX-2 mRNA level was lower in the malignant tumor than in the normal tissue, while CTGF mRNA did not differ between the groups. COX-1 immunostaining was higher in stroma from malignant tumors than in benign tissues, whereas COX-2 immunostaining was higher in the malignant tissue. Glandular S-1 immunostaining was lower in malignant tumors compared to benign and normal tissues, and the opposite was found in stroma. Conclusively, mRNA levels of COX-1 and COX-2 were oppositely regulated, with COX-1 being increased in the malignant tumor while COX-2 was decreased. S-1 protein localization switched from glandular to stromal cells in malignant tissues. Thus, these markers are, in premenopausal women, localized and regulated differently in normal/benign breast tissue as compared to the malignant tumor.

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

[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.

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

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

Quantitative Evaluation of Heavy Metals and Trace Elements in the Urinary Bladder: Comparison Between Cancerous, Adjacent Non-cancerous and Normal Cadaveric Tissue.

PubMed

Abdel-Gawad, Mahmoud; Elsobky, Emad; Shalaby, Mahmoud M; Abd-Elhameed, Mohamed; Abdel-Rahim, Mona; Ali-El-Dein, Bedeir

2016-12-01

The role of heavy metals and trace elements (HMTE) in the development of some cancers has been previously reported. Bladder carcinoma is a frequent malignancy of the urinary tract. The most common risk factors for bladder cancer are exposure to industrial carcinogens, cigarette smoking, gender, and possibly diet. The aim of this study was to evaluate HTME concentrations in the cancerous and adjacent non-cancerous tissues and compare them with those of normal cadaveric bladder. This prospective study included 102 paired samples of full-thickness cancer and adjacent non-cancerous bladder tissues of radical cystectomy (RC) specimens that were histologically proven as invasive bladder cancer (MIBC). We used 17 matched controls of non-malignant bladder tissue samples from cadavers. All samples were processed and evaluated for the concentration of 22 HMTE by using Inductively Coupled Plasma Optical Emission Spectrometry (ICP-OES). Outcome analysis was made by the Mann-Whitney U, chi-square, Kruskal-Wallis, and Wilcoxon signed ranks tests. When compared with cadaveric control or cancerous, the adjacent non-cancerous tissue had higher levels of six elements (arsenic, lead, selenium, strontium, zinc, and aluminum), and when compared with the control alone, it had a higher concentration of calcium, cadmium, chromium, potassium, magnesium, and nickel. The cancerous tissue had a higher concentration of cadmium, lead, chromium, calcium, potassium, phosphorous, magnesium, nickel, selenium, strontium, and zinc than cadaveric control. Boron level was higher in cadaveric control than cancerous and adjacent non-cancerous tissue. Cadmium level was higher in cancerous tissue with node-positive than node-negative cases. The high concentrations of cadmium, lead, chromium, nickel, and zinc, in the cancerous together with arsenic in the adjacent non-cancerous tissues of RC specimens suggest a pathogenic role of these elements in BC. However, further work-up is needed to support this

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.

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.

Development of improved connection details for adjacent prestressed member bridges.

DOT National Transportation Integrated Search

2017-06-01

Adjacent prestressed member girder bridges are economical systems for short spans and generally come in two types: adjacent box beam bridges and adjacent voided slab bridges. Each type provides the advantages of having low clearances because of their...

Comparison of telomere length and insulin-like growth factor-binding protein 7 promoter methylation between breast cancer tissues and adjacent normal tissues in Turkish women.

PubMed

Kaya, Zehra; Akkiprik, Mustafa; Karabulut, Sevgi; Peker, Irem; Gullu Amuran, Gokce; Ozmen, Tolga; Gulluoglu, Bahadır M; Kaya, Handan; Ozer, Ayse

2017-09-01

Both insulin-like growth factor-binding protein 7 (IGFBP7) and telomere length (TL) are associated with proliferation and senescence of human breast cancer. This study assessed the clinical significance of both TL and IGFBP7 methylation status in breast cancer tissues compared with adjacent normal tissues. We also investigated whether IGFBP7 methylation status could be affecting TL. Telomere length was measured by quantitative PCR to compare tumors with their adjacent normal tissues. The IGFBP7 promoter methylation status was evaluated by methylation-specific PCR and its expression levels were determined by western blotting. Telomeres were shorter in tumor tissues compared to controls (P<.0001). The mean TL was higher in breast cancer with invasive ductal carcinoma (IDC; n=72; P=.014) compared with other histological type (n=29), and TL in IDC with HER2 negative (n=53; P=.017) was higher than TL in IDC with HER2 positive (n=19). However, telomeres were shortened in advanced stages and growing tumors. IGFBP7 methylation was observed in 90% of tumor tissues and 59% of controls (P=.0002). Its frequency was significantly higher in IDC compared with invasive mixed carcinoma (IMC; P=.002) and it was not correlated either with protein expression or the other clinicopathological parameters. These results suggest that IGFBP7 promoter methylation and shorter TL in tumor compared with adjacent tissues may be predictive biomarkers for breast cancer. Telomere maintenance may be indicative of IDC and IDC with HER2 (-) of breast cancer. Further studies with larger number of cases are necessary to verify this association. © 2016 Wiley Periodicals, Inc.

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

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).

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.

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.

Designing the stem cell microenvironment for guided connective tissue regeneration.

PubMed

Bogdanowicz, Danielle R; Lu, Helen H

2017-12-01

Adult mesenchymal stem cells (MSCs) are an attractive cell source for regenerative medicine because of their ability to self-renew and their capacity for multilineage differentiation and tissue regeneration. For connective tissues, such as ligaments or tendons, MSCs are vital to the modulation of the inflammatory response following acute injury while also interacting with resident fibroblasts to promote cell proliferation and matrix synthesis. To date, MSC injection for connective tissue repair has yielded mixed results in vivo, likely due to a lack of appropriate environmental cues to effectively control MSC response and promote tissue healing instead of scar formation. In healthy tissues, stem cells reside within a complex microenvironment comprising cellular, structural, and signaling cues that collectively maintain stemness and modulate tissue homeostasis. Changes to the microenvironment following injury regulate stem cell differentiation, trophic signaling, and tissue healing. Here, we focus on models of the stem cell microenvironment that are used to elucidate the mechanisms of stem cell regulation and inspire functional approaches to tissue regeneration. Recent studies in this frontier area are highlighted, focusing on how microenvironmental cues modulate MSC response following connective tissue injury and, more importantly, how this unique cell environment can be programmed for stem cell-guided tissue regeneration. © 2017 New York Academy of Sciences.

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

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.

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

NASA Astrophysics Data System (ADS)

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

2005-04-01

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

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.

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.

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.

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.

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

Smooth Muscle-Mediated Connective Tissue Remodeling in Pulmonary Hypertension

NASA Astrophysics Data System (ADS)

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

1987-07-01

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

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.

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.

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

Visual Receptive Field Heterogeneity and Functional Connectivity of Adjacent Neurons in Primate Frontoparietal Association Cortices.

PubMed

Viswanathan, Pooja; Nieder, Andreas

2017-09-13

The basic organization principles of the primary visual cortex (V1) are commonly assumed to also hold in the association cortex such that neurons within a cortical column share functional connectivity patterns and represent the same region of the visual field. We mapped the visual receptive fields (RFs) of neurons recorded at the same electrode in the ventral intraparietal area (VIP) and the lateral prefrontal cortex (PFC) of rhesus monkeys. We report that the spatial characteristics of visual RFs between adjacent neurons differed considerably, with increasing heterogeneity from VIP to PFC. In addition to RF incongruences, we found differential functional connectivity between putative inhibitory interneurons and pyramidal cells in PFC and VIP. These findings suggest that local RF topography vanishes with hierarchical distance from visual cortical input and argue for increasingly modified functional microcircuits in noncanonical association cortices that contrast V1. SIGNIFICANCE STATEMENT Our visual field is thought to be represented faithfully by the early visual brain areas; all the information from a certain region of the visual field is conveyed to neurons situated close together within a functionally defined cortical column. We examined this principle in the association areas, PFC, and ventral intraparietal area of rhesus monkeys and found that adjacent neurons represent markedly different areas of the visual field. This is the first demonstration of such noncanonical organization of these brain areas. Copyright © 2017 the authors 0270-6474/17/378919-10$15.00/0.

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.

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.

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.

Coordinated tissue-specific regulation of adjacent alternative 3′ splice sites in C. elegans

PubMed Central

Ragle, James Matthew; Katzman, Sol; Akers, Taylor F.; Barberan-Soler, Sergio; Zahler, Alan M.

2015-01-01

Adjacent alternative 3′ splice sites, those separated by ≤18 nucleotides, provide a unique problem in the study of alternative splicing regulation; there is overlap of the cis-elements that define the adjacent sites. Identification of the intron's 3′ end depends upon sequence elements that define the branchpoint, polypyrimidine tract, and terminal AG dinucleotide. Starting with RNA-seq data from germline-enriched and somatic cell-enriched Caenorhabditis elegans samples, we identify hundreds of introns with adjacent alternative 3′ splice sites. We identify 203 events that undergo tissue-specific alternative splicing. For these, the regulation is monodirectional, with somatic cells preferring to splice at the distal 3′ splice site (furthest from the 5′ end of the intron) and germline cells showing a distinct shift toward usage of the adjacent proximal 3′ splice site (closer to the 5′ end of the intron). Splicing patterns in somatic cells follow C. elegans consensus rules of 3′ splice site definition; a short stretch of pyrimidines preceding an AG dinucleotide. Splicing in germline cells occurs at proximal 3′ splice sites that lack a preceding polypyrimidine tract, and in three instances the germline-specific site lacks the AG dinucleotide. We provide evidence that use of germline-specific proximal 3′ splice sites is conserved across Caenorhabditis species. We propose that there are differences between germline and somatic cells in the way that the basal splicing machinery functions to determine the intron terminus. PMID:25922281

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.

[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.

[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.

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.

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.

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

PubMed Central

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

2012-01-01

In areolar “loose” connective tissue, fibroblasts remodel their cytoskeleton within minutes in response to static stretch resulting in increased cell body cross-sectional area that relaxes the tissue to a lower state of resting tension. It remains unknown whether the loosely arranged collagen matrix, characteristic of areolar connective tissue, is required for this cytoskeletal response to occur. The purpose of this study was to evaluate cytoskeletal remodeling of fibroblasts in and dissociated from areolar and dense connective tissue in response to 2 hours of static stretch in both native tissue and collagen gels of varying crosslinking. Rheometric testing indicated that the areolar connective tissue had a lower dynamic modulus and was more viscous than the dense connective tissue. In response to stretch, cells within the more compliant areolar connective tissue adopted a large “sheet-like” morphology that was in contrast to the smaller dendritic morphology in the dense connective tissue. By adjusting the in vitro collagen crosslinking, and the resulting dynamic modulus, it was demonstrated that cells dissociated from dense connective tissue are capable of responding when seeded into a compliant matrix, while cells dissociated from areolar connective tissue can lose their ability to respond when their matrix becomes stiffer. This set of experiments indicated stretch-induced fibroblast expansion was dependent on the distinct matrix material properties of areolar connective tissues as opposed to the cells’ tissue of origin. These results also suggest that disease and pathological processes with increased crosslinks, such as diabetes and fibrosis, could impair fibroblast responsiveness in connective tissues. PMID:22552950

Connective tissue regeneration in skeletal muscle after eccentric contraction-induced injury.

PubMed

Mackey, Abigail L; Kjaer, Michael

2017-03-01

Human skeletal muscle has the potential to regenerate completely after injury induced under controlled experimental conditions. The events inside the myofibers as they undergo necrosis, followed closely by satellite cell-mediated myogenesis, have been mapped in detail. Much less is known about the adaptation throughout this process of both the connective tissue structures surrounding the myofibers and the fibroblasts, the cells responsible for synthesizing this connective tissue. However, the few studies investigating muscle connective tissue remodeling demonstrate a strong response that appears to be sustained for a long time after the major myofiber responses have subsided. While the use of electrical stimulation to induce eccentric contractions vs. voluntary eccentric contractions appears to lead to a greater extent of myofiber necrosis and regenerative response, this difference is not apparent when the muscle connective tissue responses are compared, although further work is required to confirm this. Pharmacological agents (growth hormone and angiotensin II type I receptor blockers) are considered in the context of accelerating the muscle connective tissue adaptation to loading. Cautioning against this, however, is the association between muscle matrix protein remodeling and protection against reinjury, which suggests that a (so far undefined) period of vulnerability to reinjury may exist during the remodeling phases. The role of individual muscle matrix components and their spatial interaction during adaptation to eccentric contractions is an unexplored field in human skeletal muscle and may provide insight into the optimal timing of rest vs. return to activity after muscle injury. Copyright © 2017 the American Physiological Society.

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

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.

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.

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

PubMed

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

2014-07-01

We propose the progressive mechanical expansion of cell-derived tissue analogues as a novel, growth-based approach to in vitro tissue engineering. The prevailing approach to producing tissue in vitro is to culture cells in an exogenous "scaffold" that provides a basic structure and mechanical support. This necessarily pre-defines the final size of the implantable material, and specific signals must be provided to stimulate appropriate cell growth, differentiation and matrix formation. In contrast, surgical skin expansion, driven by increments of stretch, produces increasing quantities of tissue without trauma or inflammation. This suggests that connective tissue cells have the innate ability to produce growth in response to elevated tension. We posit that this capacity is maintained in vitro, and that order-of-magnitude growth may be similarly attained in self-assembling cultures of cells and their own extracellular matrix. The hypothesis that growth of connective tissue analogues can be induced by mechanical expansion in vitro may be divided into three components: (1) tension stimulates cell proliferation and extracellular matrix synthesis; (2) the corresponding volume increase will relax the tension imparted by a fixed displacement; (3) the repeated application of static stretch will produce sustained growth and a tissue structure adapted to the tensile loading. Connective tissues exist in a state of residual tension, which is actively maintained by resident cells such as fibroblasts. Studies in vitro and in vivo have demonstrated that cellular survival, reproduction, and matrix synthesis and degradation are regulated by the mechanical environment. Order-of-magnitude increases in both bone and skin volume have been achieved clinically through staged expansion protocols, demonstrating that tension-driven growth can be sustained over prolonged periods. Furthermore, cell-derived tissue analogues have demonstrated mechanically advantageous structural adaptation in

Compensatory immigration depends on adjacent population size and habitat quality but not on landscape connectivity.

PubMed

Turgeon, Katrine; Kramer, Donald L

2012-11-01

1. Populations experiencing localized mortality can recover in the short term by net movement of individuals from adjacent areas, a process called compensatory immigration or spillover. Little is known about the factors influencing the magnitude of compensatory immigration or its impact on source populations. Such information is important for understanding metapopulation dynamics, the use of protected areas for conservation, management of exploited populations and pest control. 2. Using two small, territorial damselfish species (Stegastes diencaeus and S. adustus) in their naturally fragmented habitat, we quantified compensatory immigration in response to localized mortality, assessed its impact on adjacent source populations and examined the importance of potential immigrants, habitat quality and landscape connectivity as limiting factors. On seven experimental sites, we repeatedly removed 15% of the initial population size until none remained and immigration ceased. 3. Immigrants replaced 16-72% of original residents in S. diencaeus and 0-69% in S. adustus. The proportion of the source population that immigrated into depleted areas varied from 9% to 61% in S. diencaeus and from 3% to 21% in S. adustus. In S. diencaeus, compensatory immigration was strongly affected by habitat quality, to a lesser extent by the abundance of potential immigrants and not by landscape connectivity. In S. adustus, immigration was strongly affected by the density of potential migrants and not by habitat quality and landscape connectivity. On two control sites, immigration in the absence of creation of vacancies was extremely rare. 4. Immigration occurred in response to localized mortality and was therefore compensatory. It was highly variable, sometimes producing substantial impacts on both depleted and source populations. The magnitude of compensatory immigration was influenced primarily by the availability of immigrants and by the potential improvement in territory quality that they

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

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.

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.

PIXE analysis of elements in gastric cancer and adjacent mucosa

NASA Astrophysics Data System (ADS)

Liu, Qixin; Zhong, Ming; Zhang, Xiaofeng; Yan, Lingnuo; Xu, Yongling; Ye, Simao

1990-04-01

The elemental regional distributions in 20 resected human stomach tissues were obtained using PIXE analysis. The samples were pathologically divided into four types: normal, adjacent mucosa A, adjacent mucosa B and cancer. The targets for PIXE analysis were prepared by wet digestion with a pressure bomb system. P, K, Fe, Cu, Zn and Se were measured and statistically analysed. We found significantly higher concentrations of P, K, Cu, Zn and a higher ratio of Cu compared to Zn in cancer tissue as compared with normal tissue, but statistically no significant difference between adjacent mucosa and cancer tissue was found.

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.

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

A Method for Using Adjacency Matrices to Analyze the Connections Students Make within and between Concepts: The Case of Linear Algebra

ERIC Educational Resources Information Center

Selinski, Natalie E.; Rasmussen, Chris; Wawro, Megan; Zandieh, Michelle

2014-01-01

The central goals of most introductory linear algebra courses are to develop students' proficiency with matrix techniques, to promote their understanding of key concepts, and to increase their ability to make connections between concepts. In this article, we present an innovative method using adjacency matrices to analyze students' interpretation…

The regulatory role of SLP-2 and mechanism on CCBE1 gene expression in rectal carcinoma and adjacent lymphatic tube tissues.

PubMed

Guo, R-L; Wang, X-R; Wang, Q-G; Li, Z; Lu, X; Miao, R-Z; Chang, H

2018-01-01

  The incidence of rectal carcinoma (RC) has been increasing recently, and becomes the second most common digestive tumors besides gastric cancer, with a rise in the incidence of RC in younger populations. The early diagnosis and treatment are thus critical for the improvement of survival rate and life quality of patients. Stomatin-like protein 2 (SLP-2) is a type of membrane factor, which is generally found highly expressed in various tumors. Collagen and calcium-binding EGF domain (CCBE1) belongs to lymphatic tube genesis factor. The regulatory role of SLP-2 gene on CCBE1 expression in RC tumor and adjacent lymphatic tube tissues, however, has not been studied. 52 RC patients were recruited, and tumor and adjacent lymphatic tube tissues were collected. Real-time PCR, western blotting and immunohistochemistry (IHC) staining were used to analyze SLP-2 and CCBE1 expressions. Human lymphatic endothelial cells (LECs) were cultured in vitro and were assigned to control, scramble, and SLP-2 siRNA group. MTT assay was used to detect cell proliferation, while caspase 3 activity was detected. SLP-2 and CCBE1 levels were significantly elevated in tumor lymphatic tissues, compared to that in adjacent tissues. Statistically positive correlation between SLP-1 and CCBE2 was found (p<0.05). The downregulation of SLP-2 by siRNA inhibited cell proliferation, elevated caspase3 activity, and decreased CCBE1 expression (p<0.05 compared to control group). SLP-2 is up-regulated in RC lymphatic tissues, and is positively correlated with the level of CCBE1, which provides the academic the basis for the development of medicine targeting SLP-2 in the anti-rectal carcinoma therapy.

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.

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.

Signaling pathways effecting crosstalk between cartilage and adjacent tissues: Seminars in cell and developmental biology: The biology and pathology of cartilage.

PubMed

Maes, Christa

2017-02-01

Endochondral ossification, the mechanism responsible for the development of the long bones, is dependent on an extremely stringent coordination between the processes of chondrocyte maturation in the growth plate, vascular expansion in the surrounding tissues, and osteoblast differentiation and osteogenesis in the perichondrium and the developing bone center. The synchronization of these processes occurring in adjacent tissues is regulated through vigorous crosstalk between chondrocytes, endothelial cells and osteoblast lineage cells. Our knowledge about the molecular constituents of these bidirectional communications is undoubtedly incomplete, but certainly some signaling pathways effective in cartilage have been recognized to play key roles in steering vascularization and osteogenesis in the perichondrial tissues. These include hypoxia-driven signaling pathways, governed by the hypoxia-inducible factors (HIFs) and vascular endothelial growth factor (VEGF), which are absolutely essential for the survival and functioning of chondrocytes in the avascular growth plate, at least in part by regulating the oxygenation of developing cartilage through the stimulation of angiogenesis in the surrounding tissues. A second coordinating signal emanating from cartilage and regulating developmental processes in the adjacent perichondrium is Indian Hedgehog (IHH). IHH, produced by pre-hypertrophic and early hypertrophic chondrocytes in the growth plate, induces the differentiation of adjacent perichondrial progenitor cells into osteoblasts, thereby harmonizing the site and time of bone formation with the developmental progression of chondrogenesis. Both signaling pathways represent vital mediators of the tightly organized conversion of avascular cartilage into vascularized and mineralized bone during endochondral ossification. Copyright © 2016. Published by Elsevier Ltd.

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.

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.

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.

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

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.

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/

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

Effects of large pressure amplitude low frequency noise in the parotid gland perivasculo-ductal connective tissue.

PubMed

Oliveira, Pedro; Brito, José; Mendes, João; da Fonseca, Jorge; Águas, Artur; Martins dos Santos, José

2013-01-01

In tissues and organs exposed to large pressure amplitude low frequency noise fibrosis occurs in the absence of inflammatory signs, which is thought to be a protective response. In the parotid gland the perivasculo-ductal connective tissue surrounds arteries, veins and the ductal tree. Perivasculo-ductal connective tissue is believed to function as a mechanical stabilizer of the glandular tissue. In order to quantify the proliferation of perivasculo-ductal connective tissue in large pressure amplitude low frequency noise-exposed rats we used sixty Wistar rats which were equally divided into 6 groups. One group kept in silence, and the remaining five exposed to continuous large pressure amplitude low frequency noise: g1-168h (1 week); g2-504h (3 weeks); g3-840h (5 weeks); g4-1512h (9 weeks); and g5-2184h (13 weeks). After exposure, parotid glands were removed and the perivasculo-ductal connective tissue area was measured in all groups. We applied ANOVA statistical analysis, using SPSS 13.0. The global trend is an increase in the average perivasculo-ductal connective tissue areas, that develops linearly and significantly with large pressure amplitude low frequency noise exposure time (p < 0.001). It has been suggested that the biological response to large pressure amplitude low frequency noise exposure is associated with the need to maintain structural integrity. The structural reinforcement would be achieved by increased perivasculo-ductal connective tissue. Hence, these results show that in response to large pressure amplitude low frequency noise exposure, rat parotid glands increase their perivasculo-ductal 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

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.

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

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

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

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.

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.

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.

Cell migration through connective tissue in 3-D

NASA Astrophysics Data System (ADS)

Fabry, Ben

2008-03-01

A prerequisite for metastasis formation is the ability of tumor cells to invade and migrate through connective tissue. Four key components endow tumor cells with this ability: secretion of matrix-degrading enzymes, firm but temporary adhesion onto connective tissue fibers, contractile force generation, and rapid remodeling of cytoskeletal structures. Cell adhesion, contraction, and cytoskeletal remodeling are biomechanical parameter that can be measured on single cells using a panel of biophysical methods. We use 2-D and 3-D traction microscopy to measure contractile forces; magnetic tweezer microrheology to estimate adhesion strengths, cytoskeletal stiffness and molecular turn-over rates; and nanoscale particle tracking to measure cytoskeletal remodeling. On a wide range of tumor cell lines we could show that cell invasiveness correlates with increased expression of integrin adhesion receptors, increased contractile force generation, and increased speed of cytoskeletal reorganization. Each of those biomechanical parameters, however, varied considerably between cell lines of similar invasivity, suggesting that tumor cells employ multiple invasion strategies that cannot be unambiguously characterized using a single assay.

Treatment of multiple adjacent Miller Class I and II gingival recessions with collagen matrix and the modified coronally advanced tunnel technique.

PubMed

Molnár, Bálint; Aroca, Sofia; Keglevich, Tibor; Gera, István; Windisch, Péter; Stavropoulos, Andreas; Sculean, Anton

2013-01-01

To clinically evaluate the treatment of Miller Class I and II multiple adjacent gingival recessions using the modified coronally advanced tunnel technique combined with a newly developed bioresorbable collagen matrix of porcine origin. Eight healthy patients exhibiting at least three multiple Miller Class I and II multiple adjacent gingival recessions (a total of 42 recessions) were consecutively treated by means of the modified coronally advanced tunnel technique and collagen matrix. The following clinical parameters were assessed at baseline and 12 months postoperatively: full mouth plaque score (FMPS), full mouth bleeding score (FMBS), probing depth (PD), recession depth (RD), recession width (RW), keratinized tissue thickness (KTT), and keratinized tissue width (KTW). The primary outcome variable was complete root coverage. Neither allergic reactions nor soft tissue irritations or matrix exfoliations occurred. Postoperative pain and discomfort were reported to be low, and patient acceptance was generally high. At 12 months, complete root coverage was obtained in 2 out of the 8 patients and 30 of the 42 recessions (71%). Within their limits, the present results indicate that treatment of Miller Class I and II multiple adjacent gingival recessions by means of the modified coronally advanced tunnel technique and collagen matrix may result in statistically and clinically significant complete root coverage. Further studies are warranted to evaluate the performance of collagen matrix compared with connective tissue grafts and other soft tissue grafts.

Sustained deep-tissue pain alters functional brain connectivity.

PubMed

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

2013-08-01

Recent functional brain connectivity studies have contributed to our understanding of the neurocircuitry supporting pain perception. However, evoked-pain connectivity studies have employed cutaneous and/or brief stimuli, which induce sensations that differ appreciably from the clinical pain experience. Sustained myofascial pain evoked by pressure cuff affords an excellent opportunity to evaluate functional connectivity change to more clinically relevant sustained deep-tissue pain. Connectivity in specific networks known to be modulated by evoked pain (sensorimotor, salience, dorsal attention, frontoparietal control, and default mode networks: SMN, SLN, DAN, FCN, and DMN) was evaluated with functional-connectivity magnetic resonance imaging, both at rest and during a sustained (6-minute) pain state in healthy adults. We found that pain was stable, with no significant changes of subjects' pain ratings over the stimulation period. Sustained pain reduced connectivity between the SMN and the contralateral leg primary sensorimotor (S1/M1) representation. Such SMN-S1/M1 connectivity decreases were also accompanied by and correlated with increased SLN-S1/M1 connectivity, suggesting recruitment of activated S1/M1 from SMN to SLN. Sustained pain also increased DAN connectivity to pain processing regions such as mid-cingulate cortex, posterior insula, and putamen. Moreover, greater connectivity during pain between contralateral S1/M1 and posterior insula, thalamus, putamen, and amygdala was associated with lower cuff pressures needed to reach the targeted pain sensation. These results demonstrate that sustained pain disrupts resting S1/M1 connectivity by shifting it to a network known to process stimulus salience. Furthermore, increased connectivity between S1/M1 and both sensory and affective processing areas may be an important contribution to interindividual differences in pain sensitivity. Copyright © 2013 International Association for the Study of Pain. Published by

Sustained deep-tissue pain alters functional brain connectivity

PubMed Central

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

2013-01-01

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

MicroRNA-145 Inhibits Cell Migration and Invasion and Regulates Epithelial-Mesenchymal Transition (EMT) by Targeting Connective Tissue Growth Factor (CTGF) in Esophageal Squamous Cell Carcinoma.

PubMed

Han, Qiang; Zhang, Hua-Yong; Zhong, Bei-Long; Wang, Xiao-Jing; Zhang, Bing; Chen, Hua

2016-10-23

BACKGROUND This study investigated the mechanism of miR-145 in targeting connective tissue growth factor (CTGF), which affects the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of ESCC cells. MATERIAL AND METHODS A total of 50 ESCC tissues and their corresponding normal adjacent esophageal tissue samples were collected. Then, miR-145 expression in both ESCC clinical specimens and cell lines was detected using quantitative real-time PCR. CTGF protein was detected using immunohistochemistry. Dual luciferase reporter gene assay was employed to assess the effect of miR-145 on the 3'UTR luciferase activity of CTGF. Eca109 cells were transfected with miR-145 mimics and CTGF siRNA, respectively, and changes in cellular proliferation, migration, and invasion were detected via MTT assay, wound-healing assay, and Transwell assay, respectively. Western blotting assay was used to detect the expression of marker genes related to EMT. RESULTS MiR-145 was significantly down-regulated in ESCC tissues and cell lines compared with normal tissues and cell lines (P<0.05). We found significantly more positively expressed CTGF protein in ESCC tissues was than in normal adjacent esophageal tissues (P<0.01). Dual luciferase reporter gene assay showed that miR-145 can specifically bind with the 3'UTR of CTGF and significantly inhibit the luciferase activity by 55% (P<0.01). Up-regulation of miR-145 or down-regulation of CTGF can suppress the proliferation, migration, invasion, and EMT process of ESCC cells. CONCLUSIONS MiR-145 was significantly down-regulated in ESCC tissues and cell lines, while the protein expression of CTGF exhibited the opposite trend. MiR-145 inhibited the proliferation, migration, invasiveness, and the EMT process of ESCC cells through targeted regulation of CTGF expression.

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.

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.

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

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

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.

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.

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

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

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.

Facts and controversies in mixed connective tissue disease.

PubMed

Martínez-Barrio, Julia; Valor, Lara; López-Longo, F Javier

2018-01-12

Mixed connective tissue disease (MCTD) is a systemic autoimmune rheumatic disease (SARD) characterised by the combination of clinical manifestations of systemic lupus erythematosus (SLE), cutaneous systemic sclerosis (SSc) and polymyositis-dermatomyositis, in the presence of elevated titers of anti-U1-RNP antibodies. Main symptoms of the disease are polyarthritis, hand oedema, Raynaud's phenomenon, sclerodactyly, myositis and oesophageal hypomobility. Although widely discussed, most authors today accept MCTD as an independent entity. Others, however, suggest that these patients may belong to subgroups or early stages of certain definite connective diseases, such as SLE or SSc, or are, in fact, SARD overlap syndromes. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

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.

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.

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.

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.

Connective tissue activation. XXXII. Structural and biologic characteristics of mesenchymal cell-derived connective tissue activating peptide-V.

PubMed

Cabral, A R; Cole, L A; Walz, D A; Castor, C W

1987-12-01

Connective tissue activating peptide-V (CTAP-V) is a single-chain, mesenchymal cell-derived anionic protein with large and small molecular forms (Mr of 28,000 and 16,000, respectively), as defined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The proteins have similar specific activities with respect to stimulation of hyaluronic acid and DNA formation in human synovial fibroblast cultures. S-carboxymethylation or removal of sialic acid residues did not modify CTAP-V biologic activity. Rabbit antibodies raised separately against each of the purified CTAP-V proteins reacted, on immunodiffusion and on Western blot, with each antigen and neutralized mitogenic activity. The amino-terminal amino acid sequence of the CTAP-V proteins, determined by 2 laboratories, confirmed their structural similarities. The amino-terminal sequence through 37 residues was demonstrated for the smaller protein. The first 10 residues of CTAP-V (28 kd) were identical to the N-terminal decapeptide of CTAP-V (16 kd). The C-terminal sequence, determined by carboxypeptidase Y digestion, was the same for both CTAP-V molecular species. The 2 CTAP-V peptides had similar amino acid compositions, whether residues were expressed as a percent of the total or were normalized to mannose. Reduction of native CTAP-V protein released sulfhydryl groups in a protein:disulfide ratio of 1:2; this suggests that CTAP-V contains 2 intramolecular disulfide bonds. Clearly, CTAP-V is a glycoprotein. The carbohydrate content of CTAP-V (16 kd) and CTAP-V (28 kd) is 27% and 25%, respectively. CTAP-V may have significance in relation to autocrine mechanisms for growth regulation of connective tissue cells and other cell types.

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

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

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.

RASSF1A promoter methylation in high-grade serous ovarian cancer: A direct comparison study in primary tumors, adjacent morphologically tumor cell-free tissues and paired circulating tumor DNA.

PubMed

Giannopoulou, Lydia; Chebouti, Issam; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S

2017-03-28

The RASSF1A promoter is frequently methylated in high-grade serous ovarian cancer (HGSC). We examined RASSF1A promoter methylation in primary tumors, adjacent morphologically tumor cell-free tissues and corresponding circulating tumor DNA (ctDNA) samples of patients with HGSC, using a real-time methylation specific PCR (real-time MSP) and a methylation-sensitive high-resolution melting analysis (MS-HRMA) assay for the detection and semi-quantitative estimation of methylation, respectively. Two groups of primary HGSC tumor FFPE samples were recruited (Group A n=67 and Group B n=61), along with matched adjacent morphologically tumor cell-free tissues (n=58) and corresponding plasma samples (n=59) for group B. Using both assays, RASSF1A promoter was found highly methylated in primary tumors of both groups, and at lower percentages in the adjacent morphologically tumor cell-free tissues. Interestingly, RASSF1A promoter methylation was also observed in ctDNA by real-time MSP. Overall survival (OS) was significantly associated with RASSF1A promoter methylation in primary tumor samples using MS-HRMA (P=0.023). Our results clearly indicate that RASSF1A promoter is methylated in adjacent tissue surrounding the tumor in HGSC patients. We report for the first time that RASSF1A promoter methylation provides significant prognostic information in HGSC patients.

RASSF1A promoter methylation in high-grade serous ovarian cancer: A direct comparison study in primary tumors, adjacent morphologically tumor cell-free tissues and paired circulating tumor DNA

PubMed Central

Giannopoulou, Lydia; Chebouti, Issam; Pavlakis, Kitty; Kasimir-Bauer, Sabine; Lianidou, Evi S.

2017-01-01

The RASSF1A promoter is frequently methylated in high-grade serous ovarian cancer (HGSC). We examined RASSF1A promoter methylation in primary tumors, adjacent morphologically tumor cell-free tissues and corresponding circulating tumor DNA (ctDNA) samples of patients with HGSC, using a real-time methylation specific PCR (real-time MSP) and a methylation-sensitive high-resolution melting analysis (MS-HRMA) assay for the detection and semi-quantitative estimation of methylation, respectively. Two groups of primary HGSC tumor FFPE samples were recruited (Group A n=67 and Group B n=61), along with matched adjacent morphologically tumor cell-free tissues (n=58) and corresponding plasma samples (n=59) for group B. Using both assays, RASSF1A promoter was found highly methylated in primary tumors of both groups, and at lower percentages in the adjacent morphologically tumor cell-free tissues. Interestingly, RASSF1A promoter methylation was also observed in ctDNA by real-time MSP. Overall survival (OS) was significantly associated with RASSF1A promoter methylation in primary tumor samples using MS-HRMA (P=0.023). Our results clearly indicate that RASSF1A promoter is methylated in adjacent tissue surrounding the tumor in HGSC patients. We report for the first time that RASSF1A promoter methylation provides significant prognostic information in HGSC patients. PMID:28206954

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

PubMed

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

2012-03-01

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

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.

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

PubMed Central

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

2015-01-01

Context: Nowadays esthetics plays an important role in dentistry along with function of the prosthesis. Various soft tissue augmentation procedures are available to correct the ridge defects in the anterior region. The newer technique, vascularized interpositional periosteal connective tissue (VIP-CT) flap has been introduced, which has the potential to augment predictable amount of tissue and has many benefits when compared to other techniques. Aim: The study was designed to determine the efficacy of the VIP-CT flap in augmenting the ridge defect. Materials and Methods: Ten patients with Class III (Seibert's) ridge defects were treated with VIP-CT flap technique before fabricating fixed partial denture. Height and width of the ridge defects were measured before and after the procedure. Subsequent follow-up was done every 3 months for 1-year. Statistical Analysis Used: Paired t-test was performed to detect the significance of the procedure. Results: The surgical site healed uneventfully. The predictable amount of soft tissue augmentation had been achieved with the procedure. The increase in height and width of the ridge was statistically highly significant. Conclusion: The VIP-CT flap technique was effective in augmenting the soft tissue in esthetic area that remained stable over a long period. PMID:25810597

[Feasibility of using connective tissue prosthesis for autoplastic repair of urinary bladder wall defects (an experimental study)].

PubMed

Tyumentseva, N V; Yushkov, B G; Medvedeva, S Y; Kovalenko, R Y; Uzbekov, O K; Zhuravlev, V N

2016-12-01

Experiments on laboratory rats have shown the feasibility of autoplastic repair of urinary bladder wall defects using a connective-tissue capsule formed as the result of an inflammatory response to the presence of a foreign body. The formation of connective tissue prosthesis is characterized by developing fibrous connective tissue, ordering of collagen fibers, reducing the number of cells per unit area with a predominance of more mature cells - fibroblasts. With increasing time of observation, connective tissue prostheses were found to acquire a morphological structure similar to that of the urinary bladder wall. By month 12, the mucosa, the longitudinal and circular muscle layers were formed. The proposed method of partial autoplastic repair of urinary bladder wall is promising, has good long-term results, but requires further experimental studies.

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

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.

Lipid Profiles of Canine Invasive Transitional Cell Carcinoma of the Urinary Bladder and Adjacent Normal Tissue by Desorption Electrospray Ionization Imaging Mass Spectrometry

PubMed Central

Dill, Allison L.; Ifa, Demian R.; Manicke, Nicholas E.; Costa, Anthony B.; Ramos-Vara, José A.; Knapp, Deborah W.; Cooks, R. Graham

2009-01-01

Desorption electrospray ionization (DESI) mass spectrometry (MS) was used in an imaging mode to interrogate the lipid profiles of thin tissue sections of canine spontaneous invasive transitional cell carcinoma (TCC) of the urinary bladder (a model of human invasive bladder cancer) as well as adjacent normal tissue from four different dogs. The glycerophospholipids and sphingolipids that appear as intense signals in both the negative ion and positive ion modes were identified by tandem mass spectrometry (MS/MS) product ion scans using collision-induced dissociation. Differences in the relative distributions of the lipid species were present between the tumor and adjacent normal tissue in both the negative and positive ion modes. DESI-MS images showing the spatial distributions of particular glycerophospholipids, sphinoglipids and free fatty acids in both the negative and positive ion modes were compared to serial tissue sections that were stained with hematoxylin and eosin (H&E). Increased absolute and relative intensities for at least five different glycerophospholipids and three free fatty acids in the negative ion mode and at least four different lipid species in the positive ion mode were seen in the tumor region of the samples in all four dogs. In addition, one sphingolipid species exhibited increased signal intensity in the positive ion mode in normal tissue relative to the diseased tissue. Principal component analysis (PCA) was also used to generate unsupervised statistical images from the negative ion mode data and these images are in excellent agreement with the DESI images obtained from the selected ions and also the H&E stained tissue PMID:19810710

[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.

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

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.

Generalized Connective Tissue Disease in Crtap-/- Mouse

PubMed Central

Baldridge, Dustin; Lennington, Jennifer; Weis, MaryAnn; Homan, Erica P.; Jiang, Ming-Ming; Munivez, Elda; Keene, Douglas R.; Hogue, William R.; Pyott, Shawna; Byers, Peter H.; Krakow, Deborah; Cohn, Daniel H.; Eyre, David R.; Lee, Brendan; Morello, Roy

2010-01-01

Mutations in CRTAP (coding for cartilage-associated protein), LEPRE1 (coding for prolyl 3-hydroxylase 1 [P3H1]) or PPIB (coding for Cyclophilin B [CYPB]) cause recessive forms of osteogenesis imperfecta and loss or decrease of type I collagen prolyl 3-hydroxylation. A comprehensive analysis of the phenotype of the Crtap-/- mice revealed multiple abnormalities of connective tissue, including in the lungs, kidneys, and skin, consistent with systemic dysregulation of collagen homeostasis within the extracellular matrix. Both Crtap-/- lung and kidney glomeruli showed increased cellular proliferation. Histologically, the lungs showed increased alveolar spacing, while the kidneys showed evidence of segmental glomerulosclerosis, with abnormal collagen deposition. The Crtap-/- skin had decreased mechanical integrity. In addition to the expected loss of proline 986 3-hydroxylation in α1(I) and α1(II) chains, there was also loss of 3Hyp at proline 986 in α2(V) chains. In contrast, at two of the known 3Hyp sites in α1(IV) chains from Crtap-/- kidneys there were normal levels of 3-hydroxylation. On a cellular level, loss of CRTAP in human OI fibroblasts led to a secondary loss of P3H1, and vice versa. These data suggest that both CRTAP and P3H1 are required to maintain a stable complex that 3-hydroxylates canonical proline sites within clade A (types I, II, and V) collagen chains. Loss of this activity leads to a multi-systemic connective tissue disease that affects bone, cartilage, lung, kidney, and skin. PMID:20485499

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

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.

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.

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.

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�

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

PubMed

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

2010-11-02

Tumor-induced or oncogenic osteomalacia is a rare paraneoplastic syndrome characterized by overproduction of fibroblast growth factor-23 as a phosphaturic agent and renal phosphate wasting. A range of predominantly mesenchymal neoplasms have been associated with tumor-induced osteomalacia and classified as phosphaturic mesenchymal tumor mixed connective tissues. However, phosphaturic mesenchymal tumor mixed connective tissues could be nonphosphaturic in the first stage of the disease, either because the tumors are resected early in the clinical course or because the patient's osteomalacia was attributed to another cause. This article presents a case of a 42-year-old woman with a 2-year history of low back and right leg pain. Laboratory examinations including serum and urine calcium and phosphorous were within normal values. Imaging of the lumbar spine and pelvis showed an osteolytic lesion occupying the right sacral wing. Histology was unclear. Reverse-transcription polymerase chain reaction analysis for fibroblast growth factor-23 was positive and confirmed the diagnosis of phosphaturic mesenchymal tumor mixed connective tissues. Preoperative selective arterial embolization and complete intralesional excision, bone grafting, and instrumented fusion from L4 to L5 to the iliac wings bilaterally was performed. Postoperative recovery was uneventful. Neurological deficits were not observed. A lumbopelvic corset was applied for 3 months. At 12 months, the patient was asymptomatic. Serum and urine values of calcium and phosphorous were normal throughout the follow-up evaluation. Copyright 2010, SLACK Incorporated.

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.

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

NASA Astrophysics Data System (ADS)

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

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

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.

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

Mechanisms of lamellar collagen formation in connective tissues.

PubMed

Ghazanfari, Samaneh; Khademhosseini, Ali; Smit, Theodoor H

2016-08-01

The objective of tissue engineering is to regenerate functional tissues. Engineering functional tissues requires an understanding of the mechanisms that guide the formation and evolution of structure in the extracellular matrix (ECM). In particular, the three-dimensional (3D) collagen fiber arrangement is important as it is the key structural determinant that provides mechanical integrity and biological function. In this review, we survey the current knowledge on collagen organization mechanisms that can be applied to create well-structured functional lamellar tissues and in particular intervertebral disc and cornea. Thus far, the mechanisms behind the formation of cross-aligned collagen fibers in the lamellar structures is not fully understood. We start with cell-induced collagen alignment and strain-stabilization behavior mechanisms which can explain a single anisotropically aligned collagen fiber layer. These mechanisms may explain why there is anisotropy in a single layer in the first place. However, they cannot explain why a consecutive collagen layer is laid down with an alternating alignment. Therefore, we explored another mechanism, called liquid crystal phasing. While dense concentrations of collagen show such behavior, there is little evidence that the conditions for liquid crystal phasing are actually met in vivo. Instead, lysyl aldehyde-derived collagen cross-links have been found essential for correct lamellar matrix deposition. Furthermore, we suggest that supra-cellular (tissue-level) shear stress may be instrumental in the alignment of collagen fibers. Understanding the potential mechanisms behind the lamellar collagen structure in connective tissues will lead to further improvement of the regeneration strategies of functional complex lamellar tissues. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

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.

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

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

Immunohistochemical quantification of the cobalamin transport protein, cell surface receptor and Ki-67 in naturally occurring canine and feline malignant tumors and in adjacent normal tissues

PubMed Central

Sysel, Annette M.; Valli, Victor E.; Bauer, Joseph A.

2015-01-01

Cancer cells have an obligate need for cobalamin (vitamin B12) to enable DNA synthesis necessary for cellular replication. This study quantified the immunohistochemical expression of the cobalamin transport protein (transcobalamin II; TCII), cell surface receptor (transcobalamin II-R; TCII-R) and proliferation protein (Ki-67) in naturally occurring canine and feline malignant tumors, and compared these results to expression in corresponding adjacent normal tissues. All malignant tumor tissues stained positively for TCII, TCII-R and Ki-67 proteins; expression varied both within and between tumor types. Expression of TCII, TCII-R and Ki-67 was significantly higher in malignant tumor tissues than in corresponding adjacent normal tissues in both species. There was a strong correlation between TCII and TCII-R expression, and a modest correlation between TCII-R and Ki-67 expression in both species; a modest association between TCII and Ki-67 expression was present in canine tissues only. These results demonstrate a quantifiable, synchronous up-regulation of TCII and TCII-R expression by proliferating canine and feline malignant tumors. The potential to utilize these proteins as biomarkers to identify neoplastic tissues, streamline therapeutic options, evaluate response to anti-tumor therapy and monitor for recurrent disease has important implications in the advancement of cancer management for both human and companion animal patients. PMID:25633912

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.

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

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.

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.

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

Fibrosing connective tissue disorders of the skin: molecular similarities and distinctions.

PubMed

Canady, Johanna; Karrer, Sigrid; Fleck, Martin; Bosserhoff, Anja K

2013-06-01

A variety of fibrosing connective tissue disorders of the skin have been described. They all share a characteristic activation of fibroblasts resulting in excessive production and deposition of extracellular matrix whereas their etiologies, incidence rates and clinical appearances differ dramatically in part. As effective treatment options are still not on hand, the understanding of cutaneous fibrogenesis needs to be improved. This review focuses on the molecular differences and similarities of the major fibrosing skin disorders namely systemic sclerosis, localized scleroderma, keloid and hypertrophic scars, Eosinophilic fasciitis, Lichen sclerosus and graft-versus-host-disease. Abnormalities in ECM turnover and the impact of matrix-metalloproteases were closely examined. It could be concluded, that besides increased collagen synthesis, modified ECM degradation is an as important factor in cutaneous fibrogenesis. The influence of immune components such as HLA haplotypes and the production of auto-antibodies is crucial for some of the diseases, but not decisive for skin fibrosis in general. A great number of cytokines was reported to be differentially regulated in the respective disorders among whom the components of the gp130/STAT3 signaling pathway seem to be of pivotal importance. Furthermore, the role of miRNAs in the pathogenesis of fibrosing connective tissue diseases of the skin was analyzed according to the current state of knowledge. In summary, this review gives an explicit overview of the various molecular mechanisms leading to fibrosis in the skin and the underlying connective tissue and reveals the most promising targets for future therapeutic approaches. Copyright © 2013 Japanese Society for Investigative Dermatology. Published by Elsevier Ireland Ltd. All rights reserved.

Connective tissue graft vs. emdogain: A new approach to compare the outcomes.

PubMed

Sayar, Ferena; Akhundi, Nasrin; Gholami, Sanaz

2013-01-01

The aim of this clinical trial study was to clinically evaluate the use of enamel matrix protein derivative combined with the coronally positioned flap to treat gingival recession compared to the subepithelial connective tissue graft by a new method to obtain denuded root surface area. Thirteen patients, each with two or more similar bilateral Miller class I or II gingival recession (40 recessions) were randomly assigned to the test (enamel matrix protein derivative + coronally positioned flap) or control group (subepithelial connective tissue graft). Recession depth, width, probing depth, keratinized gingival, and plaque index were recorded at baseline and at one, three, and six months after treatment. A stent was used to measure the denuded root surface area at each examination session. Results were analyzed using Kolmogorov-Smirnov, Wilcoxon, Friedman, paired-sample t test. The average percentages of root coverage for control and test groups were 63.3% and 55%, respectively. Both groups showed significant keratinized gingival increase (P < 0.05). Recession depth decreased significantly in both groups. Root surface area was improved significantly from baseline with no significant difference between the two study groups (P > 0.05). The results of Friedman test were significant for clinical indices (P < 0.05), except for probing depth in control group (P = 0.166). Enamel matrix protein derivative showed the same results as subepithelial connective tissue graft with relatively easy procedure to perform and low patient morbidity.

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.

Connective tissue growth factor (CTGF) from basics to clinics.

PubMed

Ramazani, Yasaman; Knops, Noël; Elmonem, Mohamed A; Nguyen, Tri Q; Arcolino, Fanny Oliveira; van den Heuvel, Lambert; Levtchenko, Elena; Kuypers, Dirk; Goldschmeding, Roel

2018-03-21

Connective tissue growth factor, also known as CCN2, is a cysteine-rich matricellular protein involved in the control of biological processes, such as cell proliferation, differentiation, adhesion and angiogenesis, as well as multiple pathologies, such as tumor development and tissue fibrosis. Here, we describe the molecular and biological characteristics of CTGF, its regulation and various functions in the spectrum of development and regeneration to fibrosis. We further outline the preclinical and clinical studies concerning compounds targeting CTGF in various pathologies with the focus on heart, lung, liver, kidney and solid organ transplantation. Finally, we address the advances and pitfalls of translational fibrosis research and provide suggestions to move towards a better management of fibrosis. Copyright © 2017 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

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.

[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.

Developmental tumors and adjacent cortical dysplasia: single or dual pathology?

PubMed

Palmini, André; Paglioli, Eliseu; Silva, Vinicius Duval

2013-12-01

Developmental tumors often lead to refractory partial seizures and constitute a well-defined, surgically remediable epilepsy syndrome. Dysplastic features are often associated with these tumors, and their significance carries both practical and conceptual relevance. If associated focal cortical dysplasia (FCD) relates to the extent of the epileptogenic tissue, then presurgical evaluation and surgical strategies should target both the tumor and the surrounding dyslaminated cortex. Furthermore, the association has been included in the recently revised classification of FCD and the epileptogenicity of this associated dysplastic tissue is crucial to validate such revision. In addition to the possibility of representing dual pathology, the association of developmental tumors and adjacent dysplasia may instead represent a single developmental lesion with distinct parts distributed along a histopathologic continuum. Moreover, the possibility that this adjacent dyslamination is of minor epileptogenic relevance should also be entertained. Surgical data show that complete resection of the solid tumors and immediately adjacent tissue harboring satellites may disrupt epileptogenic networks and lead to high rates of seizure freedom, challenging the epileptogenic relevance of more extensive adjacent dyslaminated cortex. Whether the latter is a primary or secondary abnormality and whether dyslaminated cortex in the context of a second lesion may produce seizures after complete resection of the main lesion is still to be proven. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Myoarchitecture and connective tissue in hearts with tricuspid atresia

PubMed Central

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

1999-01-01

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

 Keywords: tricuspid atresia; congenital heart defects; connective tissue; fibrosis PMID:9922357

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

NASA Technical Reports Server (NTRS)

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

1990-01-01

Findings on the connective tissue response to short-term space flight (12 days) are discussed. Specifically, data regarding the biochemical, biomechanical and morphological characteristics of selected connective tissues (humerus, vertebral body, tendon and skeletal muscle) of growing rats is given. Results are given concerning the humerus cortical bone, the vertebral bone, nutritional effects on bone biomechanical properties, and soft tense fiber connective tissue response.

[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.

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.

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...

Evaluation of thyroid tissue by Raman spectroscopy

NASA Astrophysics Data System (ADS)

Teixeira, C. S. B.; Bitar, R. A.; Santos, A. B. O.; Kulcsar, M. A. V.; Friguglietti, C. U. M.; Martinho, H. S.; da Costa, R. B.; Martin, A. A.

2010-02-01

Thyroid gland is a small gland in the neck consisting of two lobes connected by an isthmus. Thyroid's main function is to produce the hormones thyroxine (T4), triiodothyronine (T3) and calcitonin. Thyroid disorders can disturb the production of these hormones, which will affect numerous processes within the body such as: regulating metabolism and increasing utilization of cholesterol, fats, proteins, and carbohydrates. The gland itself can also be injured; for example, neoplasias, which have been considered the most important, causing damage of to the gland and are difficult to diagnose. There are several types of thyroid cancer: Papillary, Follicular, Medullary, and Anaplastic. The occurrence rate, in general is between 4 and 7%; which is on the increase (30%), probably due to new technology that is able to find small thyroid cancers that may not have been found previously. The most common method used for thyroid diagnoses are: anamnesis, ultrasonography, and laboratory exams (Fine Needle Aspiration Biopsy- FNAB). However, the sensitivity of those test are rather poor, with a high rate of false-negative results, therefore there is an urgent need to develop new diagnostic techniques. Raman spectroscopy has been presented as a valuable tool for cancer diagnosis in many different tissues. In this work, 27 fragments of the thyroid were collected from 18 patients, comprising the following histologic groups: goitre adjacent tissue, goitre nodular tissue, follicular adenoma, follicular carcinoma, and papillary carcinoma. Spectral collection was done with a commercial FTRaman Spectrometer (Bruker RFS100/S) using a 1064 nm laser excitation and Ge detector. Principal Component Analysis, Cluster Analysis, and Linear Discriminant Analysis with cross-validation were applied as spectral classification algorithm. Comparing the goitre adjacent tissue with the goitre nodular region, an index of 58.3% of correct classification was obtained. Between goitre (nodular region and

Mixed Connective Tissue Disease and Papillary Thyroid Cancer: A Case Report.

PubMed

Thongpooswan, Supat; Tushabe, Rachel; Song, Jeffrey; Kim, Paul; Abrudescu, Adriana

2015-08-06

Mixed connective tissue disease (MCTD) is a connective tissue disorder characterized by high titers of distinct antibodies: U1 ribonucleoprotein with clinical features seen in systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), dermatomyositis (DM), polymyositis, and scleroderma. The association of SLE and DM with various cancers of the thyroid has been reported in the literature. However, there have been no reports associating MCTD with thyroid cancer. We present a 58-year-old woman diagnosed with MCTD with co-morbid interstitial lung disease that has remained stable for 10 years, who developed papillary thyroid carcinoma (PTC) 10 years after initial diagnosis. We theorize that: 1) MCTD may have been a primary diagnosis complicated by PTC, or 2) MCTD may have been an initial presentation of paraneoplastic syndrome of silent PTC, because her symptoms of MCTD significantly improved after total thyroidectomy. To the best of our knowledge, this is the first case report to associate MCTD with PTC. It highlights the importance of maintaining a high index of suspicion for thyroid malignancy in MCTD patients.

Soft tissue grafting to improve implant esthetics

PubMed Central

Kassab, Moawia M

2010-01-01

Dental implants are becoming the treatment of choice to replace missing teeth, especially if the adjacent teeth are free of restorations. When minimal bone width is present, implant placement becomes a challenge and often resulting in recession and dehiscence around the implant that leads to subsequent gingival recession. To correct such defect, the author turned to soft tissue autografting and allografting to correct a buccal dehiscence around tooth #24 after a malpositioned implant placed by a different surgeon. A 25-year-old woman presented with the chief complaint of gingival recession and exposure of implant threads around tooth #24. The patient received three soft tissue grafting procedures to augment the gingival tissue. The first surgery included a connective tissue graft to increase the width of the keratinized gingival tissue. The second surgery included the use of autografting (connective tissue graft) to coronally position the soft tissue and achieve implant coverage. The third and final surgery included the use of allografting material Alloderm to increase and mask the implant from showing through the gingiva. Healing period was uneventful for the patient. After three surgical procedures, it appears that soft tissue grafting has increased the width and height of the gingiva surrounding the implant. The accomplished thickness of gingival tissue appeared to mask the showing of implant threads through the gingival tissue and allowed for achieving the desired esthetic that the patient desired. The aim of the study is to present a clinical case with soft tissue grafting procedures. PMID:23662087

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.

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.

5. VIEW OF CENTER PIER AND ADJACENT STRUCTURE, SHOWING PIER ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

5. VIEW OF CENTER PIER AND ADJACENT STRUCTURE, SHOWING PIER STONE MASONRY AND LOWER PIN CONNECTIONS, LOOKING SOUTH - Emlenton Bridge, Spanning Allegheny River, Travel Route 38 (Legislative Route 75), Emlenton, Venango County, PA

Optimizing Soft Tissue Management and Spacer Design in Segmental Bone Defects

DTIC Science & Technology

2014-10-01

the time of the “Pre-Procedure”. Autogenous Cancellous Bone Graft (ACBG harvested from the sternum at the time of the treatment surgery is used as...will receive more specialized training and orientation to microCT analysis, both on a theoretical and practical level. He will work with raw CT...adjacent to the PMMA) composed of mononuclear cells and exhibited extensive, diffuse fibrous connective tissue.  Performed histology on goat autogenous

Food Impaction and Periodontal/Peri-Implant Tissue Conditions in Relation to the Embrasure Dimensions Between Implant-Supported Fixed Dental Prostheses and Adjacent Teeth: A Cross-Sectional Study.

PubMed

Jeong, Jin-Seok; Chang, Moontaek

2015-12-01

Food impaction and periodontal/peri-implant tissue conditions were evaluated in relation to the embrasure dimensions between implant-supported fixed dental prostheses (FDPs) and adjacent teeth. A total of 215 embrasures of 150 FDPs in 100 patients (55 males and 45 females, aged 27 to 83 years; mean age: 56 years) were included in the study. Clinical assessments of the periodontal/peri-implant mucosal conditions, radiographic assessments of embrasure dimensions, and overall patient satisfaction were used as explanatory variables for the food impaction and periodontal/peri-implant tissue conditions adjacent to implant-supported FDPs in the generalized estimating equation (GEE) analysis. Food impaction was reported in 96 (44.7%) of 215 embrasures between implant-supported FDPs and adjacent teeth. Food impaction was reported more frequently in the embrasures with proximal contact loss than in those with tight contact (P = 0.009). Overall patient satisfaction was influenced negatively by food impaction in the proximal embrasures (P = 0.01). Among embrasure dimensions, only the embrasure surface area (ESA) significantly influenced food impaction (P = 0.03). Significant influences of various embrasure dimensions on the periodontal/peri-implant mucosal conditions and bone level at the implant were found in the univariate and multivariate GEE analyses. Food impaction between implant-supported FDPs and adjacent teeth occurred more frequently when proximal contact was lost and ESA increased. Food impaction negatively affected overall patient satisfaction. Embrasure dimensions influenced the periodontal/peri-implant mucosal conditions and bone level at the implant.

Markers of fibrosis and epithelial to mesenchymal transition demonstrate field cancerization in histologically normal tissue adjacent to breast tumors

PubMed Central

Trujillo, Kristina A.; Heaphy, Christopher M.; Mai, Minh; Vargas, Keith M.; Jones, Anna C.; Vo, Phung; Butler, Kimberly S.; Joste, Nancy E.; Bisoffi, Marco; Griffith, Jeffrey K

2011-01-01

Previous studies have shown that a field of genetically altered but histologically normal tissue extends 1 cm or more from the margins of human breast tumors. The extent, composition and biological significance of this field are only partially understood, but the molecular alterations in affected cells could provide mechanisms for limitless replicative capacity, genomic instability and a microenvironment that supports tumor initiation and progression. We demonstrate by microarray, qRT-PCR and immunohistochemistry a signature of differential gene expression that discriminates between patient-matched, tumor-adjacent histologically normal breast tissues located 1 cm and 5 cm from the margins of breast adenocarcinomas (TAHN-1 and TAHN-5, respectively). The signature includes genes involved in extracellular matrix remodeling, wound healing, fibrosis and epithelial to mesenchymal transition (EMT). Myofibroblasts, which are mediators of wound healing and fibrosis, and intra-lobular fibroblasts expressing MMP2, SPARC, TGF-β3, which are inducers of EMT, were both prevalent in TAHN-1 tissues, sparse in TAHN-5 tissues, and absent in normal tissues from reduction mammoplasty. Accordingly, EMT markers S100A4 and vimentin were elevated in both luminal and myoepithelial cells, and EMT markers α-smooth muscle actin and SNAIL were elevated in luminal epithelial cells of TAHN-1 tissues. These results identify cellular processes that are differentially activated between TAHN-1 and TAHN-5 breast tissues, implicate myofibroblasts as likely mediators of these processes, provide evidence that EMT is occurring in histologically normal tissues within the affected field and identify candidate biomarkers to investigate whether or how field cancerization contributes to the development of primary or recurrent breast tumors. PMID:21105047

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

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.

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

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.

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.

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.

Increasing volume of vestibular soft tissues in flapless implant surgery through a modified connective punch technique: a controlled clinical trial

PubMed Central

BASSI, M. ANDREASI; ANDRISANI, C.; LICO, S.; SILVESTRE, F.; GARGARI, M.; ARCURI, C.

2016-01-01

SUMMARY Purpose The aim of this article is to make a comparative assessment between the modification of the soft-tissue profile, around the healing cap screws (HCSs), following both the traditional flapless surgery (TFS) and a new modified flapless surgery, named Modified Connective Tissue Punch (MCTP) technique. Materials and methods 8 patients (3M and 5F) (mean age 54.25±11.247 years) were enrolled in this study. Sixteen two-piece implants were placed on upper jaws, 2 for each patient, 8 with TFS and 8 with MCTP technique. In each patient the implants were placed in edentulous areas, of 2 or 3 adjacent teeth long. MCTP technique was performed on the front implant site (FIS) while the TFS was performed on the rear implant site (RIS). All implants were inserted and covered with healing cap screws (HCSs). Alginate impressions were carried out at the moment of the surgery, at 1 month and 4 months post-operative. Plaster models were poured and subsequently digitally scanned, in order to measure the distance between the gingival outline and the free margin of the HCS. The recorded values were analyzed with the ANOVA test. Results The use of MTCP technique, in comparison to TFS, showed a significative better outcome, in terms of vertical increments, of gingiva, on the VS toward the HCSs, during the entire observation period (p = 0.000 for all). Conclusion The Authors recommend the use of MCTP technique for a better vestibular soft tissue outcome in flapless implant surgery. PMID:28042442

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.

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

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.

Low dose of continuous – wave microwave irradiation did not cause temperature increase in muscles tissue adjacent to titanium alloy implants – an animal study

PubMed Central

2013-01-01

Background Research studies on the influence of radiofrequency electromagnetic radiation on implants in vitro have failed to investigate temperature changes in the tissues adjacent to the implants under microwave therapy. We therefore, used a rabbit model in an effort to determine the impact of microwave therapy on temperature changes in tissues adjacent to the titanium alloy implants and the safety profile thereof. Methods Titanium alloy internal fixation plates were implanted in New Zealand rabbits in the middle of femur. Microwave therapy was performed by a 2450 MHz microwave generator 3 days after the surgery. Temperature changes of muscles adjacent to the implants were recorded under exposure to dose-gradient microwave radiation from 20w to 60w. Results Significant difference between control and microwave treatment group at peak temperatures (Tpeak) and temperature gap (Tgap= Tpeak-Tvally) were observed in deep muscles (Tpeak, 41.63 ± 0.21°C vs. 44.40 ± 0.17°C, P < 0.01; Tgap, 5.33 ± 0.21°C vs. 8.10 ± 0.36°C, P < 0.01) and superficial muscles (Tpeak, 41.53 ± 0.15°C vs. 42.03 ± 0.23°C, P = 0.04; Tgap, 5.23 ± 0.21°C vs. 5.80 ± 0.17°C, P = 0.013) under 60 w, and deep muscles (Tpeak, 40.93 ± 0.25°C vs. 41.87 ± 0.23°C, P = 0.01; Tgap, 4.73 ± 0.20°C vs. 5.63 ± 0.35°C, P = 0.037) under 50w, but not under 20, 30 and 40w. Conclusion Our results suggest that low-dose (20w-40w) continuous-wave microwave irradiation delivered by a 2450 MHz microwave generator might be a promising treatment for patients with titanium alloy internal fixation, as it did not raise temperature in muscle tissues adjacent to the titanium alloy implant. PMID:24365389

Mechanics of biological networks: from the cell cytoskeleton to connective tissue.

PubMed

Pritchard, Robyn H; Huang, Yan Yan Shery; Terentjev, Eugene M

2014-03-28

From the cell cytoskeleton to connective tissues, fibrous networks are ubiquitous in metazoan life as the key promoters of mechanical strength, support and integrity. In recent decades, the application of physics to biological systems has made substantial strides in elucidating the striking mechanical phenomena observed in such networks, explaining strain stiffening, power law rheology and cytoskeletal fluidisation - all key to the biological function of individual cells and tissues. In this review we focus on the current progress in the field, with a primer into the basic physics of individual filaments and the networks they form. This is followed by a discussion of biological networks in the context of a broad spread of recent in vitro and in vivo experiments.

Non-invasive pH determination adjacent to degradable biomaterials in vivo.

PubMed

Bartsch, Ivonne; Willbold, Elmar; Rosenhahn, Bodo; Witte, Frank

2014-01-01

An appropriate pH level is an important prerequisite for the physiologal functioning of cells and tissues. Changes in the extracellular pH often lead to specific cellular reactions and an altered metabolism of cells and tissues influences the extracellular pH range. Thus a method to monitor the extracellular pH is a valuable tool to track specific tissue reactions. In this article we describe a method for the determination of the pH range adjacent to degradable biomaterials using wireless in vivo imaging. Using hairless but immunocompetent mice the fluorophor 5-(6)-carboxy SNARF-1 and the in vivo fluorescence and multispectral acquisition and analysis system Maestro it is possible to track shifts in pH in small living animals over a longer period of time. This method is especially suitable for studies which focus on the interaction of degrading biomaterials with their adjacent tissues. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Evaluation of collagen in connective tissue walls of odontogenic cysts--a histochemical study.

PubMed

Vij, Ruchieka; Vij, Hitesh; Rao, Nirmala N

2011-03-01

The purpose of this study was to evaluate the nature of collagen in the connective tissue walls of odontogenic cysts, like the odontogenic keratocyst (OKC), dentigerous cyst and radicular cyst using picrosirius red stained sections. Furthermore, it was intended to assess if the capsular connective tissue can affect the nature of overlying epithelium, thus emphasizing the role of epithelial-mesenchymal interactions in biological behaviour of the cysts. The material for the study included 51 formalin-fixed paraffin-embedded tissue blocks (15 odontogenic keratocyst, 15 dentigerous cysts, 15 radicular cysts and four normal mucosa and two dental follicular tissue as controls), retrieved from the Department of Oral Pathology and Microbiology, MCODS, Manipal. Tissue blocks were sectioned at 5-μm thickness, stained with picrosirius red stain and observed with polarization and light microscopy. Few sections of OKC and dentigerous cyst exhibited greenish-yellow birefringence in sub-epithelial region, whereas others showed a yellowish-orange birefringence under polarization microscopy. Most radicular cysts had yellowish-orange to orange birefringence. Shift in colour in case OKC and dentigerous cyst was attributed to the presence of inflammation in those sections. These regions also exhibited either a change in phenotype or thickness of overlying epithelium. This technique can be used to study the nature of collagen fibres in odontogenic cyst walls. Further studies with an increased sample size and using various epithelial and mesenchymal markers and ssDNA antibodies should be carried out to confirm the effect of epithelial-mesenchymal interactions on the nature of epithelium of odontogenic cysts. © 2010 John Wiley & Sons A/S.

LINE-1 methylation status in prostate cancer and non-neoplastic tissue adjacent to tumor in association with mortality.

PubMed

Fiano, Valentina; Zugna, Daniela; Grasso, Chiara; Trevisan, Morena; Delsedime, Luisa; Molinaro, Luca; Gillio-Tos, Anna; Merletti, Franco; Richiardi, Lorenzo

2017-01-02

Aberrant DNA methylation seems to be associated with prostate cancer behavior. We investigated LINE-1 methylation in prostate cancer and non-neoplastic tissue adjacent to tumor (NTAT) in association with mortality from prostate cancer. We selected 157 prostate cancer patients with available NTAT from 2 cohorts of patients diagnosed between 1982-1988 and 1993-1996, followed up until 2010. An association between LINE-1 hypomethylation and prostate cancer mortality in tumor was suggested [hazard ratio per 5% decrease in LINE-1 methylation levels: 1.40, 95% confidence interval (CI): 0.95-2.01]. After stratification of the patients for Gleason score, the association was present only for those with a Gleason score of at least 8. Among these, low (<75%) vs. high (>80%) LINE-1 methylation was associated with a hazard ratio of 4.68 (95% CI: 1.03-21.34). LINE-1 methylation in the NTAT was not associated with prostate cancer mortality. Our results are consistent with the hypothesis that tumor tissue global hypomethylation may be a late event in prostate cancerogenesis and is associated with tumor progression.

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

NASA Technical Reports Server (NTRS)

Vailas, Arthur C.; Martinez, Daniel A.

1999-01-01

Patients exhibiting changes in connective tissue and bone metabolism also show changes in urinary by-products of tissue metabolism. Furthermore, the changes in urinary connective tissue and bone metabolites precede alterations at the tissue macromolecular level. Astronauts and Cosmonauts have also shown suggestive increases in urinary by-products of mineralized and non-mineralized tissue degradation. Thus, the idea of assessing connective tissue and bone response in spaceflight monkeys by measurement of biomarkers in urine has merit. Other investigations of bone and connective histology, cytology and chemistry in the Bion 11 monkeys will allow for further validation of the relationship of urinary biomarkers and tissue response. In future flights the non-invasive procedure of urinary analysis may be useful in early detection of changes in these tissues. Purpose: The purpose of this grant investigation was to evaluate mineralized and non-mineralized connective tissue responses of non-human primates to microgravity by the non-invasive analysis of urinary biomarkers. Secondly, we also wanted to assess muscle connective tissue adaptive changes in three weight-bearing skeletal muscles: the soleus, medial gastrocnemius and tibialis anterior by obtaining pre-flight and post-flight small biopsy specimens in collaboration with Dr. V. Reggie Edgerton's laboratory at the University of California at Los Angeles.

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

NASA Technical Reports Server (NTRS)

Vailas, Arthur C.; Martinez, Daniel A.

1999-01-01

Patients exhibiting changes in connective tissue and bone metabolism also show changes in urinary by-products of tissue metabolism. Furthermore, the changes in urinary connective tissue and bone metabolites precede alterations at the tissue macromolecular level. Astronauts and Cosmonauts have also shown suggestive increases in urinary by-products of mineralized and non-mineralized tissue degradation. Thus, the idea of assessing connective tissue and bone response in spaceflight monkeys by measurement of biomarkers in urine has merit. Other investigations of bone and connective histology, cytology and chemistry in the Bion 11 monkeys will allow for further validation of the relationship of urinary biomarkers and tissue response. In future flights the non-invasive procedure of urinary analysis may be useful in early detection of changes in these tissues. The purpose of this grant investigation was to evaluate mineralized and non-mineralized connective tissue responses of non-human primates to microgravity by the non-invasive analysis of urinary biomarkers. Secondly, we also wanted to assess muscle connective tissue adaptive changes in three weight-bearing skeletal muscles: the soleus, media] gastrocnemius and tibialis anterior by obtaining pre-flight and post-flight small biopsy specimens in collaboration with Dr. V. Reggie Edgerton's laboratory at the University of California at Los Angeles.

[Kikuchi-Fujimoto's disease and connective tissue disease: a report of three cases].

PubMed

Frikha, F; Marzouk, S; Frigui, M; Jallouli, M; Kechaou, M; Kaddour, N; Boudawara, T; Jlidi, R; Bahloul, Z

2008-02-01

Kikuchi-Fujimoto's disease or histiocytic necrotizing lymphadenitis, clinicopathological entity of unknown aetiology, is a rare and benign cause of cervical lymphadenopathies. It can be associated with various auto-immune diseases especially systemic lupus erythematous (SLE) or with some infectious agents. This report describes a survey of three patients who developed Kikuchi's lymphadenitis occurring concomitantly with connective tissue disease: LES in two cases and non determined connective tissue disease in the other case. Comparing the clinical, histopathological and evolutionary findings to the literature allows to identify the main features of this self-limiting disorder: occurrence in young women; clinical presentation with cervical lymphadenopathy in a context of fever and asthenia. The definite diagnosis is usually made through histopathological examination of a lymph node biopsy. Disease course is generally favourable with spontaneous resolution within few weeks. It may be improved with corticosteroid treatment in patients with systemic involvement. Prognosis is related to the associated disease. Kikuchi-Fujimoto's disease is a rare and benign cause of cervical lymphadenopathy that could resemble lymphoma, tuberculosis and may be associated with a characterized systemic disease.

Desmosomes and Intermediate Filaments: Their Consequences for Tissue Mechanics.

PubMed

Hatzfeld, Mechthild; Keil, René; Magin, Thomas M

2017-06-01

Adherens junctions (AJs) and desmosomes connect the actin and keratin filament networks of adjacent cells into a mechanical unit. Whereas AJs function in mechanosensing and in transducing mechanical forces between the plasma membrane and the actomyosin cytoskeleton, desmosomes and intermediate filaments (IFs) provide mechanical stability required to maintain tissue architecture and integrity when the tissues are exposed to mechanical stress. Desmosomes are essential for stable intercellular cohesion, whereas keratins determine cell mechanics but are not involved in generating tension. Here, we summarize the current knowledge of the role of IFs and desmosomes in tissue mechanics and discuss whether the desmosome-keratin scaffold might be actively involved in mechanosensing and in the conversion of chemical signals into mechanical strength. Copyright © 2017 Cold Spring Harbor Laboratory Press; all rights reserved.

[Stomach cancer in patients with systemic non-differentiated connective tissue dysplasia].

PubMed

Zil'ber, V S

2014-01-01

The study was designed as a comparative analysis of clinical and anamnestic data and results of morphological studies of surgically obtained tissues from 61 patients with stomach cancer (SC) aged 29-78 yr with (group 1) and without (group 2) signs of connective tissue dysplasia (CTD). The groups had an identical structure of SC hystological types, but in group 1 the tumours were localized mainly in the stomach body (60.6%, p < 0.05) and in group 2 in the cardia (32.1%, p < 0.05). In group 1, SC was more frequently associated with chronic (sometimes multiple) ulcers outside the tumor (18.2 compared with 7.1% in group 2). Comparative analysis revealed the following features of SC in patients with CTD: predominance of stigmatization signs in the urogenital system (57.6%) and gastrointestinal tract (42.4%), cyst formation in different organs (75.8%) especially in kidneys (48.5%), high frequency of gastric problems in medical history (chronic gastritis, ulcer disease) (72.7 and 35.7% in groups 1 and 2 respectively, p < 0.05) and concomitant pathology of urogenital system (42.4%, p < 0.05). These peculiarities may be used as the marker for the inclusion of patients in the risk group for SC. Taking into account plastic, morphogenetic, and protective functions of connective tissue under physiological conditions, the above epithelial-stromal relationships and peculiarities of reparative processes in gastric mucosa one can not exclude effect of CTD on gastric cancerogenesis. This implies the necessity of further studies.

Expression and clinical significance of connective tissue growth factor in thyroid carcinomas.

PubMed

Wang, Guimin; Zhang, Wei; Meng, Wei; Liu, Jia; Wang, Peisong; Lin, Shan; Xu, Liyan; Li, Enmin; Chen, Guang

2013-08-01

To examine expression of the connective tissue growth factor (CTGF) gene in human thyroid cancer and establish whether a correlation exists between the presence of CTGF protein and clinicopathological parameters of the disease. CTGF protein expression was investigated retrospectively by immunohistochemical analysis of CTGF protein levels in thyroid tumour tissue. Associations between immunohistochemical score and several clinicopathological parameters were examined. In total, 131 thyroid tissue specimens were included. High levels of CTGF protein were observed in papillary thyroid carcinoma tissue; benign thyroid tumour tissue scored negatively for CTGF protein. In papillary thyroid carcinoma, there was a significant relationship between high CTGF protein levels and Union for International Cancer Control disease stage III-IV, and presence of lymph node metastasis. In papillary thyroid carcinomas, CTGF protein levels were not significantly associated with sex or age. These findings suggest that the CTGF protein level is increased in papillary thyroid carcinoma cells compared with benign thyroid tumours. CTGF expression might play a role in the development of malignant tumours in the thyroid.

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.

Ultrasound assessment of soft tissue augmentation around implants in the aesthetic zone using a connective tissue graft and xenogeneic collagen matrix - 1-year randomised follow-up.

PubMed

Puzio, Monika; Błaszczyszyn, Artur; Hadzik, Jakub; Dominiak, Marzena

2018-05-01

A comparative, ultrasound evaluation of the thickness of keratinized mucosa (TKT) around implants one year after gingival augmentation (GA) by means of a connective tissue graft (CTG) and the xenogeneic collagen matrix (CMX). A total of 75 bone level tapered implants (Conelog ® Camlog) were inserted in 57 patients in the aesthetic area of both jaws. The patients were divided into 3 groups: control group I- without GA; group II- GA 3 months before implantation, and group III- GA 3 months after implantation. Groups II and III were divided into two subgroups depends on type of material used for GA: (a) CMX (Mucograft ® , Geistlich Pharma AG) and (b) CTG. The patients underwent a clinical and ultrasound examination before, then after 3 and 12 months following GA respectively to evaluate TKT at two points using ultrasound equipment (Pirop ® , Echoson). Point 1 was considered to be in the middle of the line connecting the cemento-enamel junction (CEJ) to the adjacent teeth, and point 2 on the mucogingival junction (MGJ). Three months after GA, the highest increase in gingival thickness was noted in group IIIb (point 1 - 0.95mm, 2 - 1.01mm). However, 12 months after GA the highest gingival thickness was observed in group IIb (point 1 - 1.76mm, 2 - 1.36m) and next IIIb (point 1 - 1.52mm, 2 - 1.15mm). Both CTG and Geistlich Mucograft ® increased TKT, but higher values were noted using CTG augmentation before implantation. An ultrasonic device can be used as a non-invasive, reliable, and reproducible method for evaluating TKT. Copyright © 2017 Elsevier GmbH. All rights reserved.

Repair of Dense Connective Tissues via Biomaterial-Mediated Matrix Reprogramming of the Wound Interface

PubMed Central

Qu, Feini; Pintauro, Michael P.; Haughan, Joanne; Henning, Elizabeth A.; Esterhai, John L.; Schaer, Thomas P.; Mauck, Robert L.; Fisher, Matthew B.

2014-01-01

Repair of dense connective tissues in adults is limited by their intrinsic hypocellularity and is exacerbated by a dense extracellular matrix (ECM) that impedes cellular migration to and local proliferation at the wound site. Conversely, healing in fetal tissues occurs due in part to an environment conducive to cell mobility and division. Here, we investigated whether the application of a degradative enzyme, collagenase, could reprogram the adult wound margin to a more fetal-like state, and thus abrogate the biophysical impediments that hinder migration and proliferation. We tested this concept using the knee meniscus, a commonly injured structure for which few regenerative approaches exist. To focus delivery and degradation to the wound interface, we developed a system in which collagenase was stored inside poly(ethylene oxide) (PEO) electrospun nanofibers and released upon hydration. Through a series of in vitro and in vivo studies, our findings show that partial digestion of the wound interface improves repair by creating a more compliant and porous microenvironment that expedites cell migration to and/or proliferation at the wound margin. This innovative approach of targeted manipulation of the wound interface, focused on removing the naturally occurring barriers to adult tissue repair, may find widespread application in the treatment of injuries to a variety of dense connective tissues. PMID:25477175

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.

Connective Tissue Nevi: A Review of the Literature.

PubMed

Arora, Harleen; Falto-Aizpurua, Leyre; Cortés-Fernandez, Andrea; Choudhary, Sonal; Romanelli, Paolo

2017-05-01

Connective tissue nevi (CTN) are hamartomas of the dermis, with the 3 main components being collagen, elastin, and proteoglycans. Each subtype can present as a solitary lesion or multiple lesions. They could present as part of systemic diseases or inherited disorders. This article provides a comprehensive literature review of the different types of CTN, their clinical presentations, associations, and treatment options. Treatment options for 56 lesions were reviewed. Fifty-two percent of lesions were present in males, and the age range at the time of presentation was wide (1.6-80 years). Management varied according to CTN subtypes. Most lesions (14) received topical or intralesional treatment with corticosteroids, followed by surgical removal of lesions (12), whereas the remaining lesions were clinically monitored.

Connective tissue growth factor (CTGF) and cancer progression.

PubMed

Chu, Chia-Yu; Chang, Cheng-Chi; Prakash, Ekambaranellore; Kuo, Min-Liang

2008-11-01

Connective tissue growth factor (CTGF) is a member of the CCN family of secreted, matrix-associated proteins encoded by immediate early genes that play various roles in angiogenesis and tumor growth. CCN family proteins share uniform modular structure which mediates various cellular functions such as regulation of cell division, chemotaxis, apoptosis, adhesion, motility, angiogenesis, neoplastic transformation, and ion transport. Recently, CTGF expression has been shown to be associated with tumor development and progression. There is growing body of evidence that CTGF may regulate cancer cell migration, invasion, angiogenesis, and anoikis. In this review, we will highlight the influence of CTGF expression on the biological behavior and progression of various cancer cells, as well as its regulation on various types of protein signals and their mechanisms.

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

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.

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

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

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

PubMed

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

2015-02-01

Few gene markers selectively identify mesenchymal progenitor cells inside the bone marrow. We have investigated a cell population located in the mouse bone marrow labeled by Connective Tissue Growth Factor reporter expression (CTGF-EGFP). Bone marrow flushed from CTGF reporter mice yielded an EGFP+ stromal cell population. Interestingly, the percentage of stromal cells retaining CTGF reporter expression decreased with age in vivo and was half the frequency in females compared to males. In culture, CTGF reporter expression and endogenous CTGF expression marked the same cell types as those labeled using Twist2-Cre and Osterix-Cre fate mapping approaches, which previously had been shown to identify mesenchymal progenitors in vitro. Consistent with this past work, sorted CTGF+ cells displayed an ability to differentiate into osteoblasts, chondrocytes, and adipocytes in vitro and into osteoblast, adipocyte, and stromal cell lineages after transplantation into a parietal bone defect. In vivo examination of CTGF reporter expression in bone tissue sections revealed that it marked cells highly localized to the trabecular bone region and was not expressed in the perichondrium or periosteum. Mesenchymal cells retaining high CTGF reporter expression were adjacent to, but distinct from mature osteoblasts lining bone surfaces and endothelial cells forming the vascular sinuses. Comparison of CTGF and Osterix reporter expression in bone tissue sections indicated an inverse correlation between the strength of CTGF expression and osteoblast maturation. Down-regulation of CTGF reporter expression also occurred during in vitro osteogenic differentiation. Collectively, our studies indicate that CTGF reporter mice selectively identify a subpopulation of bone marrow mesenchymal progenitor cells that reside in the trabecular bone region. Copyright © 2014 Elsevier Inc. All rights reserved.

Connective Tissue Growth Factor Reporter Mice Label a Subpopulation of Mesenchymal Progenitor Cells that Reside in the Trabecular Bone Region

PubMed Central

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

2014-01-01

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

New insights into the cellular makeup and progenitor potential of palatal connective tissues.

PubMed

Pall, Emoke; Cenariu, Mihai; Kasaj, Adrian; Florea, Adrian; Soancă, Andrada; Roman, Alexandra; Georgiu, Carmen

2017-12-01

The present study investigated the regenerative potential of connective tissues harvested from two palatal areas widely used as donor sites for muco-gingival surgical approaches. Connective tissue grafts (CTGs) were obtained by de-epithelialisation of a free gingival graft (deCTG) and by a split flap approach from a previous donor site (reCTG). Two types of mesenchymal stem cell (MSCs) were isolated and were named de-epithelialised MSCs (deMSCs) and re-entry MSCs (reMSCs). The cells were characterised and cellular functionality was investigated. CTGs were evaluated using immunohistochemical and ultrastructural approaches. No significant differences were observed regarding the frequency of colony-forming unit- fibroblasts, migration potential, and population doubling time between the two cell lines (p > 0.05). Both cell lines showed positivity for CD105, CD73, CD90, and CD44 and negative expression for CD34/45, CD14, CD79a, and HLA-DR. MSCs from both cell lines successfully differentiated into osteogenic, adipogenic, and chondrogenic lineages. Cells expressing antigens characteristic of CD34+ stromal cells (CD34+, αSMA-, CD31-) were traced in both CTGs. Ultrastructural analysis highlighted the presence of putative progenitors, namely fibroblasts,-in the pericapillary regions and in remote regions of the lamina propria- and pericytes-surrounding the capillaries. This study provides supplementary arguments for the use of CTG grafts in clinical practice due to the presence of putative progenitor cell. However, results were inconclusive regarding clinical decision-making to determine optimal harvesting area. Prior harvesting in the donor area did not appear to alter the regenerative capabilities of the connective tissue. © 2017 Wiley Periodicals, Inc.

Cyclophosphamide for connective tissue disease-associated interstitial lung disease.

PubMed

Barnes, Hayley; Holland, Anne E; Westall, Glen P; Goh, Nicole Sl; Glaspole, Ian N

2018-01-03

Approximately one-third of individuals with interstitial lung disease (ILD) have associated connective tissue disease (CTD). The connective tissue disorders most commonly associated with ILD include scleroderma/systemic sclerosis (SSc), rheumatoid arthritis, polymyositis/dermatomyositis, and Sjögren's syndrome. Although many people with CTD-ILD do not develop progressive lung disease, a significant proportion do progress, leading to reduced physical function, decreased quality of life, and death. ILD is now the major cause of death amongst individuals with systemic sclerosis.Cyclophosphamide is a highly potent immunosuppressant that has demonstrated efficacy in inducing and maintaining remission in autoimmune and inflammatory illnesses. However this comes with potential toxicities, including nausea, haemorrhagic cystitis, bladder cancer, bone marrow suppression, increased risk of opportunistic infections, and haematological and solid organ malignancies.Decision-making in the treatment of individuals with CTD-ILD is difficult; the clinician needs to identify those who will develop progressive disease, and to weigh up the balance between a high level of need for therapy in a severely unwell patient population against the potential for adverse effects from highly toxic therapy, for which only relatively limited data on efficacy can be found. Similarly, it is not clear whether histological subtype, disease duration, or disease extent can be used to predict treatment responsiveness. To assess the efficacy and adverse effects of cyclophosphamide in the treatment of individuals with CTD-ILD. We performed searches on CENTRAL, MEDLINE, Embase, CINAHL, and Web of Science up to May 2017. We handsearched review articles, clinical trial registries, and reference lists of retrieved articles. We included randomised controlled parallel-group trials that compared cyclophosphamide in any form, used individually or concomitantly with other immunomodulating therapies, versus non

Skin cancer risk in autoimmune connective tissue diseases.

PubMed

Kostaki, D; Antonini, A; Peris, K; Fargnoli, M C

2014-10-01

Cutaneous malignancies have been significantly associated with autoimmune connective tissue diseases (ACTDs). This review focuses on the current state of knowledge on skin cancer risk in the most prevalent ACTDs in dermatology including lupus erythematosus, scleroderma, dermatomyositis and Sjögren syndrome. Potential pathogenetic mechanisms for the association between ACTDs and malignancy involve disease-related impairment of immune system, sustained cutaneous inflammation, drug-associated immune suppression and increased susceptibility to acquired viral infections. An additional causal role might be played by environmental factors such as UV exposure and smoking. The occurrence of skin cancer can have a profound impact on the already compromised quality of life of ACTD patients. Therefore, effective screening and monitoring strategies are essential for ACTD patients as early detection and prompt therapeutic intervention can reduce morbidity and mortality in these patients.

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

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

Guillet, G.; Guillet, J.; Sanciaume, C.

1988-04-01

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

Repair of dense connective tissues via biomaterial-mediated matrix reprogramming of the wound interface.

PubMed

Qu, Feini; Pintauro, Michael P; Haughan, Joanne E; Henning, Elizabeth A; Esterhai, John L; Schaer, Thomas P; Mauck, Robert L; Fisher, Matthew B

2015-01-01

Repair of dense connective tissues in adults is limited by their intrinsic hypocellularity and is exacerbated by a dense extracellular matrix (ECM) that impedes cellular migration to and local proliferation at the wound site. Conversely, healing in fetal tissues occurs due in part to an environment conducive to cell mobility and division. Here, we investigated whether the application of a degradative enzyme, collagenase, could reprogram the adult wound margin to a more fetal-like state, and thus abrogate the biophysical impediments that hinder migration and proliferation. We tested this concept using the knee meniscus, a commonly injured structure for which few regenerative approaches exist. To focus delivery and degradation to the wound interface, we developed a system in which collagenase was stored inside poly(ethylene oxide) (PEO) electrospun nanofibers and released upon hydration. Through a series of in vitro and in vivo studies, our findings show that partial digestion of the wound interface improves repair by creating a more compliant and porous microenvironment that expedites cell migration to and/or proliferation at the wound margin. This innovative approach of targeted manipulation of the wound interface, focused on removing the naturally occurring barriers to adult tissue repair, may find widespread application in the treatment of injuries to a variety of dense connective tissues. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

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.

LINE-1 methylation status in prostate cancer and non-neoplastic tissue adjacent to tumor in association with mortality

PubMed Central

Delsedime, Luisa; Molinaro, Luca; Gillio-Tos, Anna

2017-01-01

ABSTRACT Aberrant DNA methylation seems to be associated with prostate cancer behavior. We investigated LINE-1 methylation in prostate cancer and non-neoplastic tissue adjacent to tumor (NTAT) in association with mortality from prostate cancer. We selected 157 prostate cancer patients with available NTAT from 2 cohorts of patients diagnosed between 1982–1988 and 1993–1996, followed up until 2010. An association between LINE-1 hypomethylation and prostate cancer mortality in tumor was suggested [hazard ratio per 5% decrease in LINE-1 methylation levels: 1.40, 95% confidence interval (CI): 0.95–2.01]. After stratification of the patients for Gleason score, the association was present only for those with a Gleason score of at least 8. Among these, low (<75%) vs. high (>80%) LINE-1 methylation was associated with a hazard ratio of 4.68 (95% CI: 1.03–21.34). LINE-1 methylation in the NTAT was not associated with prostate cancer mortality. Our results are consistent with the hypothesis that tumor tissue global hypomethylation may be a late event in prostate cancerogenesis and is associated with tumor progression. PMID:27892790

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

Enlarged Dural Sac in Idiopathic Bronchiectasis Implicates Heritable Connective Tissue Gene Variants

PubMed Central

Birchard, Katherine R.; Lowe, Jared R.; Patrone, Michael V.

2016-01-01

Rationale: Patients with idiopathic bronchiectasis are predominantly female and have an asthenic body morphotype and frequent nontuberculous mycobacterial respiratory infections. They also demonstrate phenotypic features (scoliosis, pectus deformity, mitral valve prolapse) that are commonly seen in individuals with heritable connective tissue disorders. Objectives: To determine whether lumbar dural sac size is increased in patients with idiopathic bronchiectasis as compared with control subjects, and to assess whether dural sac size is correlated with phenotypic characteristics seen in individuals with heritable connective tissue disorders. Methods: Two readers blinded to diagnosis measured anterior–posterior and transverse dural sac diameter using L1–L5 magnetic resonance images of 71 patients with idiopathic bronchiectasis, 72 control subjects without lung disease, 29 patients with cystic fibrosis, and 24 patients with Marfan syndrome. We compared groups by pairwise analysis of means, using Tukey’s method to adjust for multiple comparisons. Dural sac diameter association with phenotypic and clinical features was also tested. Measurements and Main Results: The L1–L5 (average) anterior–posterior dural sac diameter of the idiopathic bronchiectasis group was larger than those of the control group (P < 0.001) and the cystic fibrosis group (P = 0.002). There was a strong correlation between increased dural sac size and the presence of pulmonary nontuberculous mycobacterial infection (P = 0.007) and long fingers (P = 0.003). A trend toward larger dural sac diameter was seen in those with scoliosis (P = 0.130) and those with a family history of idiopathic bronchiectasis (P = 0.149). Conclusions: Individuals with idiopathic bronchiectasis have an enlarged dural sac diameter, which is associated with pulmonary nontuberculous mycobacterial infection, long fingers, and family history of idiopathic bronchiectasis. These findings support our

[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

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 ...

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.

Repair of full-thickness tendon injury using connective tissue progenitors efficiently derived from human embryonic stem cells and fetal tissues.

PubMed

Cohen, Shahar; Leshansky, Lucy; Zussman, Eyal; Burman, Michael; Srouji, Samer; Livne, Erella; Abramov, Natalie; Itskovitz-Eldor, Joseph

2010-10-01

The use of stem cells for tissue engineering (TE) encourages scientists to design new platforms in the field of regenerative and reconstructive medicine. Human embryonic stem cells (hESC) have been proposed to be an important cell source for cell-based TE applications as well as an exciting tool for investigating the fundamentals of human development. Here, we describe the efficient derivation of connective tissue progenitors (CTPs) from hESC lines and fetal tissues. The CTPs were significantly expanded and induced to generate tendon tissues in vitro, with ultrastructural characteristics and biomechanical properties typical of mature tendons. We describe a simple method for engineering tendon grafts that can successfully repair injured Achilles tendons and restore the ankle joint extension movement in mice. We also show the CTP's ability to differentiate into bone, cartilage, and fat both in vitro and in vivo. This study offers evidence for the possibility of using stem cell-derived engineered grafts to replace missing tissues, and sets a basic platform for future cell-based TE applications in the fields of orthopedics and reconstructive surgery.

Connective Tissue Disorders

MedlinePlus

... syndrome, and osteogenesis imperfecta Autoimmune disorders, such as lupus and scleroderma Cancers, like some types of soft tissue sarcoma Each disorder has its own symptoms and needs different treatment. NIH: National Institute of Arthritis and Musculoskeletal and Skin Diseases

[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.

Characterization of the anisotropic mechanical behavior of human abdominal wall connective tissues.

PubMed

Astruc, Laure; De Meulaere, Maurice; Witz, Jean-François; Nováček, Vit; Turquier, Frédéric; Hoc, Thierry; Brieu, Mathias

2018-06-01

Abdominal wall sheathing tissues are commonly involved in hernia formation. However, there is very limited work studying mechanics of all tissues from the same donor which prevents a complete understanding of the abdominal wall behavior and the differences in these tissues. The aim of this study was to investigate the differences between the mechanical properties of the linea alba and the anterior and posterior rectus sheaths from a macroscopic point of view. Eight full-thickness human anterior abdominal walls of both genders were collected and longitudinal and transverse samples were harvested from the three sheathing connective tissues. The total of 398 uniaxial tensile tests was conducted and the mechanical characteristics of the behavior (tangent rigidities for small and large deformations) were determined. Statistical comparisons highlighted heterogeneity and non-linearity in behavior of the three tissues under both small and large deformations. High anisotropy was observed under small and large deformations with higher stress in the transverse direction. Variabilities in the mechanical properties of the linea alba according to the gender and location were also identified. Finally, data dispersion correlated with microstructure revealed that macroscopic characterization is not sufficient to fully describe behavior. Microstructure consideration is needed. These results provide a better understanding of the mechanical behavior of the abdominal wall sheathing tissues as well as the directions for microstructure-based constitutive model. Copyright © 2018 Elsevier Ltd. All rights reserved.

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.

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

PubMed Central

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

1996-01-01

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

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.

STUDIES ON THE CHANGES PRODUCED BY ROENTGEN RAYS IN INFLAMED CONNECTIVE TISSUE.

PubMed

Maximow, A A

1923-02-28

The action of x-rays upon inflamed tissue manifests itself in the first place by a considerable depression of the usual reaction on the part of the fibroblasts. Under normal circumstances these elements begin to divide mitotically during the first 24 hours and soon form a layer of new connective tissue, surrounding the foreign body. After treatment with x-rays they remain idle, do not multiply at all, or start very late and often the division is abnormal. They undergo a high degree of pathological hypertrophy of protoplasm and nucleus. Instead of mitosis often amitotic constrictions appear in the nucleus. The capacity for collagen formation seems also to be lost. Simultaneously with these changes of the fibroblasts an intensive edema of the connective tissue surrounding the foreign body is to be noted and in the immediate neighborhood of the latter a thick layer of net-like clotted fibrinous exudate is formed. No distinctive qualitative changes could be found in the leucocytes and polyblasts. Degeneration was present here only to the same extent as in common aseptic inflammation. But first the rate and the duration of the emigration of all the cells coming from the blood were increased, and secondly there was always a distinct delay in the process of the common transformations usually undergone by the polyblasts on the field of inflammation. The transformation of the polyblasts into fixed resting forms seems above all to be delayed. Therefore, even in late stages, the tissue is overcrowded with granular special leucocytes and with mostly young, lymphocyte-like polyblasts, whereas in the early stages the local resting wandering cells only slowly undergo mobilization. Furthermore, in the blood vessels swelling of the endothelial cells with fragmentation of the nuclei and, in the striated muscles, degeneration of the fibers can be detected. In the latter there occur partly typical coagulation necrosis, partly atrophy, accompanied by loss of striation, separation of

Histologic evaluation of autogenous connective tissue and acellular dermal matrix grafts in humans.

PubMed

Cummings, Lewis C; Kaldahl, Wayne B; Allen, Edward P

2005-02-01

The clinical success of root coverage with autogenous connective tissue (CT) or acellular dermal matrix (ADM) has been well documented. However, limited histological results of CT grafts have been reported, and a case report of a human block section has been published documenting an ADM graft. The purpose of this study is to document the histological results of CT grafts, ADM grafts, and coronally advanced flaps to cover denuded roots in humans. This study included four patients previously treatment planned for extractions of three or more anterior teeth. Three teeth in each patient were selected and randomly designated to receive either a CT or ADM graft beneath a coronally advanced flap (tests) or coronally advanced flap alone (control). Six months postoperatively block section extractions were performed and the teeth processed for histologic evaluation with hematoxylin-eosin and Verhoeff's stains. Histologically, both the CT and ADM were well incorporated within the recipient tissues. New fibroblasts, vascular elements, and collagen were present throughout the ADM, while retention of the transplanted elastic fibers was apparent. No effect on the keratinization or connective tissue organization of the overlying alveolar mucosa was evident with either graft. For both materials, areas of cemental deposition were present within the root notches, the alveolar bone was essentially unaffected, and the attachments to the root surfaces were similar. Although CT and ADM have a slightly different histological appearance, both can successfully be used to cover denuded roots with similar attachments and no adverse healing.

[Connective tissue dysplasia in patients with celiac desease as a problem of violation of adaptation reserve islands of the body].

PubMed

Tkachenko, E; Oreshko, L S; Soloveva, E A; Shabanova, A A; Zhuravleva, M S

2015-01-01

Clinically significant dysplasia of connective tissue in patients with celiac disease is often responsible for various visceral disorders. Different disturbances of motor and evacuation functions are often determined in this patients (gastroesophageal reflux, duodenogastral reflux, spastic and hyperkinetic dyskinesia). The clinical course of the celiac disease, associated with connective tissue dysplasia, is characterized by asthenovegetative syndrome, reduced tolerance to physical activity, general weakness, fatigue and emotional instability. These data should be considered in choosing a treatment.

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.

Tumor-adjacent tissue co-expression profile analysis reveals pro-oncogenic ribosomal gene signature for prognosis of resectable hepatocellular carcinoma.

PubMed

Grinchuk, Oleg V; Yenamandra, Surya P; Iyer, Ramakrishnan; Singh, Malay; Lee, Hwee Kuan; Lim, Kiat Hon; Chow, Pierce Kah-Hoe; Kuznetsov, Vladamir A

2018-01-01

Currently, molecular markers are not used when determining the prognosis and treatment strategy for patients with hepatocellular carcinoma (HCC). In the present study, we proposed that the identification of common pro-oncogenic pathways in primary tumors (PT) and adjacent non-malignant tissues (AT) typically used to predict HCC patient risks may result in HCC biomarker discovery. We examined the genome-wide mRNA expression profiles of paired PT and AT samples from 321 HCC patients. The workflow integrated differentially expressed gene selection, gene ontology enrichment, computational classification, survival predictions, image analysis and experimental validation methods. We developed a 24-ribosomal gene-based HCC classifier (RGC), which is prognostically significant in both PT and AT. The RGC gene overexpression in PT was associated with a poor prognosis in the training (hazard ratio = 8.2, P = 9.4 × 10 -6 ) and cross-cohort validation (hazard ratio = 2.63, P = 0.004) datasets. The multivariate survival analysis demonstrated the significant and independent prognostic value of the RGC. The RGC displayed a significant prognostic value in AT of the training (hazard ratio = 5.0, P = 0.03) and cross-validation (hazard ratio = 1.9, P = 0.03) HCC groups, confirming the accuracy and robustness of the RGC. Our experimental and bioinformatics analyses suggested a key role for c-MYC in the pro-oncogenic pattern of ribosomal biogenesis co-regulation in PT and AT. Microarray, quantitative RT-PCR and quantitative immunohistochemical studies of the PT showed that DKK1 in PT is the perspective biomarker for poor HCC outcomes. The common co-transcriptional pattern of ribosome biogenesis genes in PT and AT from HCC patients suggests a new scalable prognostic system, as supported by the model of tumor-like metabolic redirection/assimilation in non-malignant AT. The RGC, comprising 24 ribosomal genes, is introduced as a robust and reproducible prognostic model for

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

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.

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

Xenogenic collagen matrix or autologous connective tissue graft as adjunct to coronally advanced flaps for coverage of multiple adjacent gingival recession: Randomized trial assessing non-inferiority in root coverage and superiority in oral health-related quality of life.

PubMed

Tonetti, Maurizio S; Cortellini, Pierpaolo; Pellegrini, Gaia; Nieri, Michele; Bonaccini, Daniele; Allegri, Mario; Bouchard, Philippe; Cairo, Francesco; Conforti, Gianpaolo; Fourmousis, Ioannis; Graziani, Filippo; Guerrero, Adrian; Halben, Jan; Malet, Jacques; Rasperini, Giulio; Topoll, Heinz; Wachtel, Hannes; Wallkamm, Beat; Zabalegui, Ion; Zuhr, Otto

2018-01-01

To evaluate the non-inferiority of the adjunct of a xenogeneic collagen matrix (CMX) or connective tissue graft (CTG) to coronally advanced flaps (CAF) for coverage of multiple adjacent recessions and compare superiority in patient-reported outcomes (PROM). One hundred and eighty-seven subjects (92 CMX) with 485 recessions in 14 centres were randomized and followed up for 6 months. Patients filled daily diaries for 15 days to monitor patient-reported experience. The primary outcome was changed in position of the gingival margin. Multilevel analysis used centre, subject and tooth as levels and baseline parameters as covariates. Average baseline recession was 2.5 ± 1.0 mm. The surgery was 15.7 min shorter (95%CI from 11.9 to 19.6, p < .0001) and perceived lighter (11.9 VAS units, 95%CI from 4.6 to 19.1, p = .0014) in CMX subjects. Time to recovery was 1.8 days shorter in CMX. Six-month root coverage was 1.7 ± 1.1 mm for CMX and 2.1 ± 1.0 mm for CTG (difference of 0.44 mm, 95%CI from 0.25 to 0.63 mm). The upper limit of the confidence interval was over the non-inferiority margin of 0.25 mm. Odds of complete root coverage were significantly higher for CTG (OR = 4.0, 95% CI 1.8-8.8). Replacing CTG with CMX shortens time to recovery and decreases morbidity, but the tested generation of devices is probably inferior to autologous CTG in terms of root coverage. Significant variability in PROMs was observed among centres. © 2017 The Authors. Journal of Clinical Periodontology Published by John Wiley & Sons Ltd.

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.

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

PubMed Central

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

2013-01-01

Background Eosinophilic esophagitis (EoE) is an emerging chronic inflammatory disease mediated by immune hypersensitization to multiple foods and strongly associated with atopy and esophageal remodeling. Objective We provide clinical and molecular evidence indicating a high prevalence of EoE in patients with inherited connective tissue disorders (CTDs). Methods We examined the rate of EoE among patients with CTDs and subsequently analyzed esophageal mRNA transcript profiles in patients with EoE with or without CTD features. Results We report a cohort of 42 patients with EoE with a CTD-like syndrome, representing 0.8% of patients with CTDs and 1.3% of patients with EoE within our hospital-wide electronic medical record database and our EoE research registry, respectively. An 8-fold risk of EoE in patients with CTDs (relative risk, 8.1; 95% confidence limit, 5.1-12.9; χ21 = 112.0; P < 10−3) was present compared with the general population. Esophageal transcript profiling identified a distinct subset of genes, including COL8A2, in patients with EoE and CTDs. Conclusion There is a remarkable association of EoE with CTDs and evidence for a differential expression of genes involved in connective tissue repair in this cohort. Thus, we propose stratification of patients with EoE and CTDs into a subset referred to as EoE-CTD. PMID:23608731

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

Different alterations in brain functional networks according to direct and indirect topological connections in patients with schizophrenia.

PubMed

Park, Chang-Hyun; Lee, Seungyup; Kim, Taewon; Won, Wang Yeon; Lee, Kyoung-Uk

2017-10-01

Schizophrenia displays connectivity deficits in the brain, but the literature has shown inconsistent findings about alterations in global efficiency of brain functional networks. We supposed that such inconsistency at the whole brain level may be due to a mixture of different portions of global efficiency at sub-brain levels. Accordingly, we considered measuring portions of global efficiency in two aspects: spatial portions by considering sub-brain networks and topological portions by considering contributions to global efficiency according to direct and indirect topological connections. We proposed adjacency and indirect adjacency as new network parameters attributable to direct and indirect topological connections, respectively, and applied them to graph-theoretical analysis of brain functional networks constructed from resting state fMRI data of 22 patients with schizophrenia and 22 healthy controls. Group differences in the network parameters were observed not for whole brain and hemispheric networks, but for regional networks. Alterations in adjacency and indirect adjacency were in opposite directions, such that adjacency increased, but indirect adjacency decreased in patients with schizophrenia. Furthermore, over connections in frontal and parietal regions, increased adjacency was associated with more severe negative symptoms, while decreased adjacency was associated with more severe positive symptoms of schizophrenia. This finding indicates that connectivity deficits associated with positive and negative symptoms of schizophrenia may involve topologically different paths in the brain. In patients with schizophrenia, although changes in global efficiency may not be clearly shown, different alterations in brain functional networks according to direct and indirect topological connections could be revealed at the regional level. Copyright © 2017 Elsevier B.V. All rights reserved.

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

PubMed

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

2013-01-01

The objective of this review is to analyze in detail the microscopic structure and relations among muscular fibers, endomysium, perimysium, epimysium and deep fasciae. In particular, the multilayer organization and the collagen fiber orientation of these elements are reported. The endomysium, perimysium, epimysium and deep fasciae have not just a role of containment, limiting the expansion of the muscle with the disposition in concentric layers of the collagen tissue, but are fundamental elements for the transmission of muscular force, each one with a specific role. From this review it appears that the muscular fibers should not be studied as isolated elements, but as a complex inseparable from their fibrous components. The force expressed by a muscle depends not only on its anatomical structure, but also the angle at which its fibers are attached to the intramuscular connective tissue and the relation with the epimysium and deep fasciae. Copyright © 2012 Elsevier Ltd. All rights reserved.

Association of HLA-DRB1 alleles with susceptibility to mixed connective tissue disease in Polish patients.

PubMed

Paradowska-Gorycka, A; Stypińska, B; Olesińska, M; Felis-Giemza, A; Mańczak, M; Czuszynska, Z; Zdrojewski, Z; Wojciechowicz, J; Jurkowska, M

2016-01-01

Mixed connective tissue disease (MCTD) is a systemic autoimmune disease, originally defined as a connective tissue inflammatory syndrome with overlapping features of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), polymyositis/dermatomyositis (PM/DM) and systemic sclerosis (SSc), characterized by the presence of antibodies against components of the U1 small nuclear ribonucleoprotein (U1snRNP). The aim of the study was to assess the frequency of (high-resolution-typed) DRB1 alleles in a cohort of Polish patients with MCTD (n = 103). Identification of the variants potentially associated with risk and protection was carried out by comparison with the DKMS Polish Bone Marrow Donor Registry (41306 alleles). DRB1*15:01 (odds ratio (OR): 6.06; 95% confidence interval (CI) 4.55-8.06), DRB1*04 (OR: 3.69; 95% CI 2.69-5.01) and *09:01 (OR: 8.12; 95% CI 2.15-21.75) were identified as risk alleles for MCTD, while HLA-DRB1*07:01 allele was found to be protective (OR: 0.50; 95% CI 0.28-0.83). The carrier frequency of the DRB1*01 was higher in MCTD patients compared with controls, although the differences were not statistically significant. Our results confirm the modulating influence of HLA-DRB1 genotypes on development of connective tissue diseases such as MCTD. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Xenogeneic collagen matrix versus connective tissue graft for buccal soft tissue augmentation at implant site. A randomized, controlled clinical trial.

PubMed

Cairo, Francesco; Barbato, Luigi; Tonelli, Paolo; Batalocco, Guido; Pagavino, Gabriella; Nieri, Michele

2017-07-01

Peri-implant soft tissue may be critical to prevent inflammation and promote gingival margin stability. The purpose of this randomized clinical trial (RCT) is to compare xenogeneic collagen matrix (XCM) versus connective tissue graft (CTG) to increase buccal soft tissue thickness at implant site. Soft tissue augmentation with XCM (test) or CTG (control) was performed at 60 implants in 60 patients at the time of implant uncovering. Measurements were performed by a blinded examiner at baseline, 3 and 6 months. Outcome measures included buccal soft tissue thickness (GT), apico-coronal keratinized tissue (KT), chair time and post-operative discomfort. Visual Analogue Scale (VAS) was used to evaluate patient satisfaction. After 6 months, the final GT increase was 0.9 ± 0.2 in the XCM group and 1.2 ± 0.3 mm in the CTG group, with a significant difference favouring the control group (0.3 mm; p = .0001). Both procedures resulted in similar final KT amount with no significant difference between treatments. XCM was associated with significant less chair-time (p < .0001), less post-operative pain (p < .0001), painkillers intake (p < .0001) and higher final satisfaction than CTG (p = .0195). CTG was more effective than XCM to increase buccal peri-implant soft tissue thickness. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Biota: Providing Often-overlooked Connections among Freshwater Systems

EPA Science Inventory

When we think about connections in and among aquatic systems, we typically envision clear headwater streams flowing into downstream rivers, river floodwaters spilling out onto adjacent floodplains, or groundwater connecting wetlands to lakes to streams. However, there is another ...

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

Connections for solid oxide fuel cells

DOEpatents

Collie, Jeffrey C.

1999-01-01

A connection for fuel cell assemblies is disclosed. The connection includes compliant members connected to individual fuel cells and a rigid member connected to the compliant members. Adjacent bundles or modules of fuel cells are connected together by mechanically joining their rigid members. The compliant/rigid connection permits construction of generator fuel cell stacks from basic modular groups of cells of any desired size. The connections can be made prior to installation of the fuel cells in a generator, thereby eliminating the need for in-situ completion of the connections. In addition to allowing pre-fabrication, the compliant/rigid connections also simplify removal and replacement of sections of a generator fuel cell stack.

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.

Functional Connectivity in Islets of Langerhans from Mouse Pancreas Tissue Slices

PubMed Central

Stožer, Andraž; Gosak, Marko; Dolenšek, Jurij; Perc, Matjaž; Marhl, Marko; Rupnik, Marjan Slak; Korošak, Dean

2013-01-01

We propose a network representation of electrically coupled beta cells in islets of Langerhans. Beta cells are functionally connected on the basis of correlations between calcium dynamics of individual cells, obtained by means of confocal laser-scanning calcium imaging in islets from acute mouse pancreas tissue slices. Obtained functional networks are analyzed in the light of known structural and physiological properties of islets. Focusing on the temporal evolution of the network under stimulation with glucose, we show that the dynamics are more correlated under stimulation than under non-stimulated conditions and that the highest overall correlation, largely independent of Euclidean distances between cells, is observed in the activation and deactivation phases when cells are driven by the external stimulus. Moreover, we find that the range of interactions in networks during activity shows a clear dependence on the Euclidean distance, lending support to previous observations that beta cells are synchronized via calcium waves spreading throughout islets. Most interestingly, the functional connectivity patterns between beta cells exhibit small-world properties, suggesting that beta cells do not form a homogeneous geometric network but are connected in a functionally more efficient way. Presented results provide support for the existing knowledge of beta cell physiology from a network perspective and shed important new light on the functional organization of beta cell syncitia whose structural topology is probably not as trivial as believed so far. PMID:23468610

Satisfactory treatment of a large connective tissue nevus with intralesional steroid injection.

PubMed

Saki, Nasrin; Dorostkar, Azadeh; Heiran, Alireza; Aslani, Fatemeh Sari

2018-01-01

Collagenoma is a type of connective tissue nevi, a rare hamartomatous malformation characterized by the predominant proliferation of normal collagen fibers and normal, decreased, or increased elastic fibers. Collagenomas present as multiple or solitary, hereditary or sporadic, asymptomatic, skin-colored papules, nodules, and plaques with variable sizes, and are usually located on the trunk, arm, and back. Here, we report on a 14-year-old boy who presented with an isolated giant collagenoma of the frontal area that dramatically responded to intralesional triamcinolone acetonide.

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

Do Mangroves Subsidize Carbon to Adjacent Mudflat Fish Communities?

NASA Astrophysics Data System (ADS)

Henkel, S.; Kasten, S.; Hartmann, J.; Staubwasser, M.; Hernandez, M. F.; West, L.; Midway, S. R.; Polito, M. J.

2017-12-01

Mangroves are often implicated as energetic sources for fisheries productivity. However, the validity of this connection still remains in contention. Stable isotopes may provide answers by tracking the use of specific basal carbon sources in fish and invertebrates living in mangrove-mudflat habitat mosaics. We analyzed 307 consumer samples representing n=44 fish and invertebrate species collected from mangrove forest creeks and adjacent mudflats in coastal Tanzania using bulk carbon and nitrogen stable isotope analysis. Given the proposed high productivity of mangrove habitats, we hypothesize that mudflat communities will have carbon stable isotope values similar to mangrove communities either through the flux of mangrove carbon into adjacent mudflats and/or via the movement of mudflat fish communities into and out of mangrove habitats. Alternatively, mangrove carbon is often refractory, which may result in mudflat communities with isotopic values that differ from those found in adjacent mangrove communities. This scenario would suggest limited carbon flow between mudflat and mangrove food webs and that the movement of fish into and out of mangrove habitats is related to shelter from predation more than feeding. Data analysis is ongoing to test these competing hypotheses. By understanding the contribution of mangrove carbon to adjacent habitats, managers in Tanzania can make better informed decisions regarding the protection of mangroves and the local fisheries, which are a crucial source of income and food.

[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.

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.

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

PubMed Central

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

1980-01-01

The gross and microscopic connective tissue lesions in 12 goats with caprine arthritis-encephalitis (CAE) are described, including those from which a virus (CAEV) was isolated. Lesions were most often associated with synovial-lined structures including joints, tendon sheaths, and bursae, and were typified by synovial cell proliferations, subsynovial mononuclear cell infiltration, the presence of fibrin, fibrinous concretions, necrosis, and mineralization. Extrasynovial lesions were located in kidneys, vessels, and brain. The inflammatory infiltrates in these organs were predominantly mononuclear. Amyloid was also found in liver, spleen, and kidney. Microbiologic techniques failed to demonstrate any bacteria, mycoplasma, or chlamydia in the lesions. Images Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 1 Figure 2 Figure 3 Figure 4 PMID:7406019

[Involvement of the peripheral nervous system in systemic connective tissue diseases: report on clinical cases].

PubMed

Kujawska-Danecka, Hanna; Masiak, Anna; Smoleńska, Zaneta; Zdrojewski, Zbigniew

2011-01-01

The peripheral nervous system is usually involved in the majority of systemic connective tissue diseases, particularly in systemic lupus erythematosus, Sjögren's syndrome, vasculitis and systemic sclerosis. The pathogenesis of lesions in the peripheral nervous system associated with the autoimmune process is complex and it appears that two mechanisms, immunological and ischemic, are of greatest importance. Structures of the nervous system may be damaged by several autoantibodies (e.g. antineuronal, anti-nerve growth factor, anti-neurotrophins), by cytotoxic effects ofproinflammatory cytokines and by activated cells of the immune system. Local ischemia and hypoxia of neurons caused by inflammation of vasa nervosum represents the second significant mechanism leading to damage of nerve fibres in the peripheral nervous system. We present 3 cases with involvement of the peripheral nervous system as a dominant feature in the clinical picture of systemic connective tissue diseases. Clinical conditions in which the peripheral nervous system is involved include peripheral sensory and sensorimotor polyneuropathy, mononeuropathies, cranial neuropathies, acute inflammatory demyelinating polyneuropathy (Guillian-Barré syndrome), chronic inflammatory demyelinating polyneuropathy, plexopathy, myasthenia gravis, and dysfunctions of the autonomic nervous system. The diagnosis is based on clinical symptoms reported by the patient and disclosed during neurologic examination. The importance of electrophysiologic tests is advocated. Selection of treatment depends on the patient's clinical condition, as well as on the clinical form and type of disease. Treatment relies principally on glucocorticosteroids, intravenous immunoglobulins, cyclophosphamide, and other immunosuppressive drugs. Plasmapheresis and rituximab are administered in severe cases. Rehabilitation of the patient appears to be an important element of therapy. Cases with neurologic symptoms as the first and often the sole

[Lung involvement in systemic connective tissue diseases].

PubMed

Plavec, Goran; Tomić, Ilija; Bihorac, Sanela; Kovacević, Gordana; Pavlica, Ljiljana; Cvetković, Gordana; Sikimić, Stevan; Milić, Rade

2008-09-01

Systemic connective tissue diseases (SCTD) are chronic inflammatory autoimmune disorders of unknown cause that can involve different organs and systems. Their course and prognosis are different. All of them can, more or less, involve the respiratory sistem. The aim of this study was to find out the frequency of respiratory simptoms, lung function disorders, radiography and high-resolution computerized tomography (HRCT) abnormalities, and their correlation with the duration of the disease and the applied treatment. In 47 non-randomised consecutive patients standard chest radiography, HRCT, and lung function tests were done. Hypoxemia was present in nine of the patients with respiratory simptoms (20%). In all of them chest radiography was normal. In five of these patients lung fibrosis was established using HRCT. Half of all the patients with SCTD had simptoms of lung involment. Lung function tests disorders of various degrees were found in 40% of the patients. The outcome and the degree of lung functin disorders were neither in correlation with the duration of SCTD nor with therapy used (p > 0.05 Spearmans Ro). Pulmonary fibrosis occures in about 10% of the patients with SCTD, and possibly not due to the applied treatment regimens. Hypoxemia could be a sing of existing pulmonary fibrosis in the absence of disorders on standard chest radiography.

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.

[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.

Variation in primary and culture-expanded cells derived from connective tissue progenitors in human bone marrow space, bone trabecular surface and adipose tissue.

PubMed

Qadan, Maha A; Piuzzi, Nicolas S; Boehm, Cynthia; Bova, Wesley; Moos, Malcolm; Midura, Ronald J; Hascall, Vincent C; Malcuit, Christopher; Muschler, George F

2018-03-01

Connective tissue progenitors (CTPs) embody the heterogeneous stem and progenitor cell populations present in native tissue. CTPs are essential to the formation and remodeling of connective tissue and represent key targets for tissue-engineering and cell-based therapies. To better understand and characterize CTPs, we aimed to compare the (i) concentration and prevalence, (ii) early in vitro biological behavior and (iii) expression of surface-markers and transcription factors among cells derived from marrow space (MS), trabecular surface (TS), and adipose tissues (AT). Cancellous-bone and subcutaneous-adipose tissues were collected from 8 patients. Cells were isolated and cultured. Colony formation was assayed using Colonyze software based on ASTM standards. Cell concentration ([Cell]), CTP concentration ([CTP]) and CTP prevalence (P CTP ) were determined. Attributes of culture-expanded cells were compared based on (i) effective proliferation rate and (ii) expression of surface-markers CD73, CD90, CD105, SSEA-4, SSEA-3, SSEA-1/CD15, Cripto-1, E-Cadherin/CD324, Ep-CAM/CD326, CD146, hyaluronan and transcription factors Oct3/4, Sox-2 and Nanog using flow cytometry. Mean [Cell], [CTP] and P CTP were significantly different between MS and TS samples (P = 0.03, P = 0.008 and P= 0.0003), respectively. AT-derived cells generated the highest mean total cell yield at day 6 of culture-4-fold greater than TS and more than 40-fold greater than MS per million cells plated. TS colonies grew with higher mean density than MS colonies (290 ± 11 versus 150 ± 11 cell per mm 2 ; P = 0.0002). Expression of classical-mesenchymal stromal cell (MSC) markers was consistently recorded (>95%) from all tissue sources, whereas all the other markers were highly variable. The prevalence and biological potential of CTPs are different between patients and tissue sources and lack variation in classical MSC markers. Other markers are more likely to discriminate differences

Treatment of multiple adjacent Miller class I and II gingival recessions with a Modified Coronally Advanced Tunnel (MCAT) technique and a collagen matrix or palatal connective tissue graft: a randomized, controlled clinical trial.

PubMed

Aroca, Sofia; Molnár, Bálint; Windisch, Péter; Gera, István; Salvi, Giovanni E; Nikolidakis, Dimitris; Sculean, Anton

2013-07-01

A newly developed collagen matrix (CM) of porcine origin has been shown to represent a potential alternative to palatal connective tissue grafts (CTG) for the treatment of single Miller Class I and II gingival recessions when used in conjunction with a coronally advanced flap (CAF). However, at present it remains unknown to what extent CM may represent a valuable alternative to CTG in the treatment of Miller Class I and II multiple adjacent gingival recessions (MAGR). The aim of this study was to compare the clinical outcomes following treatment of Miller Class I and II MAGR using the modified coronally advanced tunnel technique (MCAT) in conjunction with either CM or CTG. Twenty-two patients with a total of 156 Miller Class I and II gingival recessions were included in this study. Recessions were randomly treated according to a split-mouth design by means of MCAT + CM (test) or MCAT + CTG (control). The following measurements were recorded at baseline (i.e. prior to surgery) and at 12 months: Gingival Recession Depth (GRD), Probing Pocket Depth (PD), Clinical Attachment Level (CAL), Keratinized Tissue Width (KTW), Gingival Recession Width (GRW) and Gingival Thickness (GT). GT was measured 3-mm apical to the gingival margin. Patient acceptance was recorded using a Visual Analogue Scale (VAS). The primary outcome variable was Complete Root Coverage (CRC), secondary outcomes were Mean Root Coverage (MRC), change in KTW, GT, patient acceptance and duration of surgery. Healing was uneventful in both groups. No adverse reactions at any of the sites were observed. At 12 months, both treatments resulted in statistically significant improvements of CRC, MRC, KTW and GT compared with baseline (p < 0.05). CRC was found at 42% of test sites and at 85% of control sites respectively (p < 0.05). MRC measured 71 ± 21% mm at test sites versus 90 ± 18% mm at control sites (p < 0.05). Mean KTW measured 2.4 ± 0.7 mm at test sites versus 2.7 ± 0.8 mm at

Aberrant gene expression in mucosa adjacent to tumor reveals a molecular crosstalk in colon cancer

PubMed Central

2014-01-01

Background A colorectal tumor is not an isolated entity growing in a restricted location of the body. The patient’s gut environment constitutes the framework where the tumor evolves and this relationship promotes and includes a complex and tight correlation of the tumor with inflammation, blood vessels formation, nutrition, and gut microbiome composition. The tumor influence in the environment could both promote an anti-tumor or a pro-tumor response. Methods A set of 98 paired adjacent mucosa and tumor tissues from colorectal cancer (CRC) patients and 50 colon mucosa from healthy donors (246 samples in total) were included in this work. RNA extracted from each sample was hybridized in Affymetrix chips Human Genome U219. Functional relationships between genes were inferred by means of systems biology using both transcriptional regulation networks (ARACNe algorithm) and protein-protein interaction networks (BIANA software). Results Here we report a transcriptomic analysis revealing a number of genes activated in adjacent mucosa from CRC patients, not activated in mucosa from healthy donors. A functional analysis of these genes suggested that this active reaction of the adjacent mucosa was related to the presence of the tumor. Transcriptional and protein-interaction networks were used to further elucidate this response of normal gut in front of the tumor, revealing a crosstalk between proteins secreted by the tumor and receptors activated in the adjacent colon tissue; and vice versa. Remarkably, Slit family of proteins activated ROBO receptors in tumor whereas tumor-secreted proteins transduced a cellular signal finally activating AP-1 in adjacent tissue. Conclusions The systems-level approach provides new insights into the micro-ecology of colorectal tumorogenesis. Disrupting this intricate molecular network of cell-cell communication and pro-inflammatory microenvironment could be a therapeutic target in CRC patients. PMID:24597571

Modulating Intrinsic Connectivity: Adjacent Subregions within Supplementary Motor Cortex, Dorsolateral Prefrontal Cortex, and Parietal Cortex Connect to Separate Functional Networks during Task and Also Connect during Rest

PubMed Central

Roth, Jennifer K.; Johnson, Marcia K.; Tokoglu, Fuyuze; Murphy, Isabella; Constable, R. Todd

2014-01-01

Supplementary motor area (SMA), the inferior frontal junction (IFJ), superior frontal junction (SFJ) and parietal cortex are active in many cognitive tasks. In a previous study, we found that subregions of each of these major areas were differentially active in component processes of executive function during working memory tasks. In the present study, each of these subregions was used as a seed in a whole brain functional connectivity analysis of working memory and resting state data. These regions show functional connectivity to different networks, thus supporting the parcellation of these major regions into functional subregions. Many regions showing significant connectivity during the working memory residual data (with task events regressed from the data) were also significantly connected during rest suggesting that these network connections to subregions within major regions of cortex are intrinsic. For some of these connections, task demands modulate activity in these intrinsic networks. Approximately half of the connections significant during task were significant during rest, indicating that some of the connections are intrinsic while others are recruited only in the service of the task. Furthermore, the network connections to traditional ‘task positive’ and ‘task negative’ (a.k.a ‘default mode’) regions shift from positive connectivity to negative connectivity depending on task demands. These findings demonstrate that such task-identified subregions are part of distinct networks, and that these networks have different patterns of connectivity for task as they do during rest, engaging connections both to task positive and task negative regions. These results have implications for understanding the parcellation of commonly active regions into more specific functional networks. PMID:24637793

Proteolytic processing of connective tissue growth factor in normal ocular tissues and during corneal wound healing.

PubMed

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

2012-12-13

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

Prognosis after surgical excision of canine fibrous connective tissue sarcomas.

PubMed

Bostock, D E; Dye, M T

1980-09-01

One hundred eighty seven dogs from which fibrous connective tissue sarcomas had been excised were studied until death or for at least 3 years after surgery. Dogs with a skin fibrosarcoma had a median survival time of 80 weeks, compared with 140 weeks for animals with haemangiopericytoma in similar sites, this difference being statistically significant. However, the difference in survival time between the two histologic types disappeared when tumours with a similar mitotic index were compared. Dogs with a tumour of mitotic index 9 or more had a median survival time of 49 weeks, compared with 118 weeks for those with a tumour of mitotic index less than 9, regardless of tumour morphology. Tumour recurrence rates of 62% and 25% respectively for the two groups were also significantly different.

Effects of rituximab in connective tissue disorders related interstitial lung disease.

PubMed

Lepri, Gemma; Avouac, Jerome; Airò, Paolo; Anguita Santos, Francisco; Bellando-Randone, Silvia; Blagojevic, Jelena; Garcia Hernàndez, Francisco; Gonzalez Nieto, Jose Antonio; Guiducci, Serena; Jordan, Suzana; Limaye, Vidya; Maurer, Britta; Selva-O'Callaghan, Albert; Riccieri, Valeria; Distler, Oliver; Matucci-Cerinic, Marco; Allanore, Yannick

2016-01-01

Interstitial lung disease (ILD) is a key prognostic factor in connective tissue disorders (CTDs). The aim of our study was to assess the changes in pulmonary functional tests (PFTs) in various CTDs, including anti-synthetase syndrome (SYN), systemic sclerosis (SSc) and mixed connective tissue disorder (MCTD), following the use of rituximab therapy. A multicentre retrospective analysis of patients with ILD secondary to SYN (n=15), MCTD (n=6) and SSc (n=23). PFTs were performed at baseline and at 1 and 2 years of follow-up. The primary outcome was the change in forced vital capacity (FVC) at 1 year. In the SYN population, median FVC changed from 53.0% (42.0-90.0) at baseline to 51.4% (45.6-85.0) at 1 year and 63.0 (50-88) (p=0.6) at 2 years (p=0.14). In SSc, FVC changed from 81.0% (66.0-104.0) at baseline to 89.0% (65.0-113.0) at 1 year (p=0.1) and 74.5 (50-91) at 2 years (p=0.07). In the MCTD population, FVC changed from 64.5% (63.0-68.0) at baseline to 63.0% (59.0-71.0) at 1 year (p=0.6) and 61 (59-71) after 2 years (p=0.8). DLCO showed a trend for improvement in the SYN population (p=0.06 at 1 year and 0.2 at years) while changes remain non-significant in the SSc and MCTD patients. In SYN patients, the percentage of responders at 1 year for FVC (33.3%) was greater than in SSc (9.5%) (p=0.07) and MCTD (17%) (p=0.45). RTX showed a satisfactory safety profile. A trend of improvement of PFTs was observed in SYN patients although not reaching significance, while SSc and MCTD patients were stabilised.

An overview of inverted colloidal crystal systems for tissue engineering.

PubMed

João, Carlos Filipe C; Vasconcelos, Joana Marta; Silva, Jorge Carvalho; Borges, João Paulo

2014-10-01

Scaffolding is at the heart of tissue engineering but the number of techniques available for turning biomaterials into scaffolds displaying the features required for a tissue engineering application is somewhat limited. Inverted colloidal crystals (ICCs) are inverse replicas of an ordered array of monodisperse colloidal particles, which organize themselves in packed long-range crystals. The literature on ICC systems has grown enormously in the past 20 years, driven by the need to find organized macroporous structures. Although replicating the structure of packed colloidal crystals (CCs) into solid structures has produced a wide range of advanced materials (e.g., photonic crystals, catalysts, and membranes) only in recent years have ICCs been evaluated as devices for medical/pharmaceutical and tissue engineering applications. The geometry, size, pore density, and interconnectivity are features of the scaffold that strongly affect the cell environment with consequences on cell adhesion, proliferation, and differentiation. ICC scaffolds are highly geometrically ordered structures with increased porosity and connectivity, which enhances oxygen and nutrient diffusion, providing optimum cellular development. In comparison to other types of scaffolds, ICCs have three major unique features: the isotropic three-dimensional environment, comprising highly uniform and size-controllable pores, and the presence of windows connecting adjacent pores. Thus far, this is the only technique that guarantees these features with a long-range order, between a few nanometers and thousands of micrometers. In this review, we present the current development status of ICC scaffolds for tissue engineering applications.

[The connective tissues, from the origin of the concept to its "Maturation" to extracellular matrix. Application to ocular tissues. Contribution to the history of medical sciences].

PubMed

Labat-Robert, J; Robert, L; Pouliquen, Y

2011-06-01

The "Tissue" concept emerged apparently in the medical literature at about the French revolution, during the second half of the 18(th) century. It was found in the texts written by the physicians of Béarn and Montpellier, the Bordeu-s and also by the famous physician, Felix Vicq d'Azyr, the last attending physician of the queen Marie-Antoinette, "Bordeu et al. (1775) et Pouliquen (2009)". It was elaborated into a coherent doctrine somewhat later by Xavier Bichat, considered as the founder of modern pathological anatomy, Bichat. With the advent of histochemistry, from the beginning of the 20(th) century, several of the principal macromolecular components of connective tissues, collagens, elastin, "acid mucopolysaccharides" (later glycosaminoglycans and proteoglycans) and finally structural glycoproteins were characterized. These constituents of connective tissues were then designated as components of the extracellular matrix (ECM), closely associated to the cellular components of these tissues by adhesive (structural) glycoproteins as fibronectin, several others and cell receptors, "recognising" ECM-components as integrins, the elastin-receptor and others. This molecular arrangement fastens cells to the ECM-components they synthesize and mediates the exchange of informations between the cells to the ECM (inside-out) and also from the ECM-components to the cells (outside-in). This macromolecular arrangement is specific for each tissue as a result of the differentiation of their cellular components. It is also the basis and condition of the fulfillment of the specific functions of differentiated tissues. This is a short description of the passage of the "tissue" concept from its vague origin towards its precise identification at the cellular and molecular level up to the recognition of its functional importance and its establishment as an autonomous science. This can be considered as a new example of the importance of metaphors for the progress of science, Keller

Endovascular Repair of Thoracoabdominal and Arch Aneurysms in Patients with Connective Tissue Disease Using Branched and Fenestrated Devices.

PubMed

Clough, Rachel E; Martin-Gonzalez, Teresa; Van Calster, Katrien; Hertault, Adrien; Spear, Rafaëlle; Azzaoui, Richard; Sobocinski, Jonathan; Haulon, Stéphan

2017-10-01

Prophylactic open surgery is the standard practice in patients with connective tissue and thoracoabdominal aortic aneurysm (TAAA) and aortic arch disease. Branched and fenestrated devices offer a less invasive alternative but there are concerns regarding the durability of the repair and the effect of the stent graft on the fragile aortic wall. The aim of this study is to evaluate mid-term outcomes of fenestrated and/or branched endografting in patients with connective tissue disease. All patients with connective tissue disease who underwent TAAA or arch aneurysm repair using a fenestrated and/or branched endograft in a single, high-volume center between 2004 and 2015 were included. Ruptured aneurysms and acute aortic dissections were excluded from this study, but not chronic aortic dissections. In total, 427 (403 pararenal and TAAAs, and 24 arch aneurysms) endovascular interventions were performed during the study period. Of these, 17 patients (4%) (16 TAAAs, 1 arch) had connective tissue disease. All patients were classified as unfit for open repair. The mean age was 51 ± 8 years. Thirteen patients with TAAA were treated with a fenestrated, 1 with a branched, and 2 with a combined fenestrated/branch device. A double inner branch device was used to treat the arch aneurysm. The technical success rate was 100% with no incidence of early mortality, spinal cord ischemia, stroke, or further dissection. Postoperative deterioration in renal function was seen in 3 patients (18.8%) and no hemodialysis was required. The mean follow-up was 3.4 years (0.3-7.4). Aneurysm sac shrinkage was seen in 35% of patients (6/17) and the sac diameter remained stable in 65% of patients (11/17). No sac or sealing zone enlargement was observed in any of the patients and there were no conversions to open repair. Reintervention was required in 1 patient at 2 years for bilateral renal artery occlusion (successful fibrinolysis). One type II endoleak (lumbar) is under surveillance and 1 type

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

Aberrant immune response with consequent vascular and connective tissue remodeling - causal to scleroderma and associated syndromes such as Raynaud phenomenon and other fibrosing syndromes?

PubMed

Durmus, Nedim; Park, Sung-Hyun; Reibman, Joan; Grunig, Gabriele

2016-11-01

Scleroderma and other autoimmune-induced connective tissue diseases are characterized by dysfunctions in the immune system, connective tissue and the vasculature. We are focusing on systemic sclerosis (SSc)-associated pulmonary hypertension, which remains a leading cause of death with only a 50-60% of 2-year survival rate. Much research and translational efforts have been directed at understanding the immune response that causes SSc and the networked interactions with the connective tissue and the vasculature. One of the unexpected findings was that in some cases the pathogenic immune response in SSc resembles the immune response to helminth parasites. During coevolution, means of communication were developed which protect the host from over-colonization with parasites and which protect the parasite from excessive host responses. One explanation for the geographically clustered occurrence of SSc is that environmental exposures combined with genetic predisposition turn on triggers of molecular and cellular modules that were once initiated by parasites. Future research is needed to further understand the parasite-derived signals that dampen the host response. Therapeutic helminth infection or treatment with parasite-derived response modifiers could be promising new management tools for autoimmune connective tissue diseases.

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

Metamorphosis of mesothelial cells with active horizontal motility in tissue culture.

PubMed

Nagai, Hirotaka; Chew, Shan Hwu; Okazaki, Yasumasa; Funahashi, Satomi; Namba, Takashi; Kato, Takuya; Enomoto, Atsushi; Jiang, Li; Akatsuka, Shinya; Toyokuni, Shinya

2013-01-01

Mesothelial cells, which have diverse roles in physiology and pathology, constitute the mesothelium along with connective tissue and the basement membrane; the mesothelium serves to shield the somatic cavities. After mesothelial injury, mesothelial cells undergo tissue recovery. However, the mechanism of mesothelial regeneration remains poorly understood. In this study, we used confocal time-lapse microscopy to demonstrate that transformed mesothelial cells (MeT5A) and mouse peritoneal mesothelial cells can randomly migrate between cells in cell culture and in ex vivo tissue culture, respectively. Moreover, peritoneal mesothelial cells changed their morphology from a flattened shape to a cuboidal one prior to the migration. Conversely, MDCKII epithelial cells forming tight cell-cell contacts with one another do not alter the arrangement of adjacent cells during movement. Our evidence complements the current hypotheses of mesothelial regeneration and suggests that certain types of differentiated mesothelial cells undergo morphological changes before initiating migration to repair injured sites.

Addison's disease secondary to connective tissue diseases: a report of six cases.

PubMed

Zhang, Zhuo-li; Wang, Yu; Zhou, Wei; Hao, Yan-jie

2009-04-01

Addison's disease is an autoimmune process. However, Addison's disease associated with connective tissue diseases (CTD) is only occasionally reported. Here, we report six cases of Addison's disease secondary to a variety of CTD, which include systemic lupus erythematosus, Takayasu arteritis, systemic sclerosis, ankylosing spondylitis (AS) and antiphospholipid antibody syndrome. The association of Addison's disease with Takayasu arteritis and AS is reported for the first time. We also found high prevalence of hypothyroidism as concomitant autoimmune disorder. Our case series highlight the autoimmune features of Addison's disease. Therefore, we suggest considering adrenal dysfunction in patients with CTD.

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

PubMed

Franco, Alexandre R; Ling, Josef; Caprihan, Arvind; Calhoun, Vince D; Jung, Rex E; Heileman, Gregory L; Mayer, Andrew R

2008-12-01

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

Adjacency Matrix-Based Transmit Power Allocation Strategies in Wireless Sensor Networks

PubMed Central

Consolini, Luca; Medagliani, Paolo; Ferrari, Gianluigi

2009-01-01

In this paper, we present an innovative transmit power control scheme, based on optimization theory, for wireless sensor networks (WSNs) which use carrier sense multiple access (CSMA) with collision avoidance (CA) as medium access control (MAC) protocol. In particular, we focus on schemes where several remote nodes send data directly to a common access point (AP). Under the assumption of finite overall network transmit power and low traffic load, we derive the optimal transmit power allocation strategy that minimizes the packet error rate (PER) at the AP. This approach is based on modeling the CSMA/CA MAC protocol through a finite state machine and takes into account the network adjacency matrix, depending on the transmit power distribution and determining the network connectivity. It will be then shown that the transmit power allocation problem reduces to a convex constrained minimization problem. Our results show that, under the assumption of low traffic load, the power allocation strategy, which guarantees minimal delay, requires the maximization of network connectivity, which can be equivalently interpreted as the maximization of the number of non-zero entries of the adjacency matrix. The obtained theoretical results are confirmed by simulations for unslotted Zigbee WSNs. PMID:22346705

Randomized controlled clinical study evaluating effectiveness and safety of a volume-stable collagen matrix compared to autogenous connective tissue grafts for soft tissue augmentation at implant sites.

PubMed

Thoma, Daniel S; Zeltner, Marco; Hilbe, Monika; Hämmerle, Christoph H F; Hüsler, Jürg; Jung, Ronald E

2016-10-01

To test whether or not the use of a collagen matrix (VCMX) results in short-term soft tissue volume increase at implant sites non-inferior to an autogenous subepithelial connective tissue graft (SCTG), and to evaluate safety and tissue integration of VCMX and SCTG. In 20 patients with a volume deficiency at single-tooth implant sites, soft tissue volume augmentation was performed randomly allocating VCMX or SCTG. Soft tissue thickness, patient-reported outcome measures (PROMs), and safety were assessed up to 90 days (FU-90). At FU-90 (abutment connection), tissue samples were obtained for histological analysis. Descriptive analysis was computed for both groups. Non-parametric tests were applied to test non-inferiority for the gain in soft tissue thickness at the occlusal site. Median soft tissue thickness increased between BL and FU-90 by 1.8 mm (Q1:0.5; Q3:2.0) (VCMX) (p = 0.018) and 0.5 mm (-1.0; 2.0) (SCTG) (p = 0.395) (occlusal) and by 1.0 mm (0.5; 2.0) (VCMX) (p = 0.074) and 1.5 mm (-2.0; 2.0) (SCTG) (p = 0.563) (buccal). Non-inferiority with a non-inferiority margin of 1 mm could be demonstrated (p = 0.020); the difference between the two group medians (1.3 mm) for occlusal sites indicated no relevant, but not significant superiority of VCMX versus SCTG (primary endpoint). Pain medication consumption and pain perceived were non-significantly higher in group SCTG up to day 3. Median physical pain (OHIP-14) at day 7 was 100% higher for SCTG than for VCMX. The histological analysis revealed well-integrated grafts. Soft tissue augmentation at implant sites resulted in a similar or higher soft tissue volume increase after 90 days for VCMX versus SCTG. PROMs did not reveal relevant differences between the two groups. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons 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

Connectivity algorithm with depth first search (DFS) on simple graphs

NASA Astrophysics Data System (ADS)

Riansanti, O.; Ihsan, M.; Suhaimi, D.

2018-01-01

This paper discusses an algorithm to detect connectivity of a simple graph using Depth First Search (DFS). The DFS implementation in this paper differs than other research, that is, on counting the number of visited vertices. The algorithm obtains s from the number of vertices and visits source vertex, following by its adjacent vertices until the last vertex adjacent to the previous source vertex. Any simple graph is connected if s equals 0 and disconnected if s is greater than 0. The complexity of the algorithm is O(n2).

Optimization of Soft Tissue Management, Spacer Design, and Grafting Strategies For Large Segmental Bone Defects Using The Chronic Caprine Tibial Defect Model

DTIC Science & Technology

2014-10-01

spacer placed at the time of the “Pre-Procedure”. Autogenous Cancellous Bone Graft (ACBG harvested from the sternum at the time of the treatment...will receive more specialized training and orientation to microCT analysis, both on a theoretical and practical level. He will work with raw CT...adjacent to the PMMA) composed of mononuclear cells and exhibited extensive, diffuse fibrous connective tissue.  Performed histology on goat autogenous

Molecular regulation of CCN2 in the intervertebral disc: lessons learned from other connective tissues.

PubMed

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

2013-08-08

Connective tissue growth factor (CCN2/CTGF) plays an important role in extracellular matrix synthesis, especially in skeletal tissues such as cartilage, bone, and the intervertebral disc. As a result there is a growing interest in examining the function and regulation of this important molecule in the disc. This review discusses the regulation of CCN2 by TGF-β and hypoxia, two critical determinants that characterize the disc microenvironment, and discusses known functions of CCN2 in the disc. The almost ubiquitous regulation of CCN2 by TGF-β, including that seen in the disc, emphasizes the importance of the TGF-β-CCN2 relationship, especially in terms of extracellular matrix synthesis. Likewise, the unique cross-talk between CCN2 and HIF-1 in the disc highlights the tissue and niche specific mode of regulation. Taken together the current literature supports an anabolic role for CCN2 in the disc and its involvement in the maintenance of tissue homeostasis during both health and disease. Further studies of CCN2 in this tissue may reveal valuable targets for the biological therapy of disc degeneration. © 2013 Elsevier B.V. All rights reserved.

Connective tissue growth factor and bone morphogenetic protein 2 are induced following myocardial ischemia in mice and humans.

PubMed

Rutkovskiy, Arkady; Sagave, Julia; Czibik, Gabor; Baysa, Anton; Zihlavnikova Enayati, Katarina; Hillestad, Vigdis; Dahl, Christen Peder; Fiane, Arnt; Gullestad, Lars; Gravning, Jørgen; Ahmed, Shakil; Attramadal, Håvard; Valen, Guro; Vaage, Jarle

2017-09-01

We aimed to study the cardiac expression of bone morphogenetic protein 2, its receptor 1 b, and connective tissue growth factor, factors implicated in cardiac embryogenesis, following ischemia/hypoxia, heart failure, and in remodeling hearts from humans and mice. Biopsies from the left ventricle of patients with end-stage heart failure due to dilated cardiomyopathy or coronary artery disease were compared with donor hearts and biopsies from patients with normal heart function undergoing coronary artery bypass grafting. Mouse model of post-infarction remodeling was made by permanent ligation of the left coronary artery. Hearts were analyzed by real-time polymerase chain reaction and Western blotting after 24 hours and after 2 and 4 weeks. Patients with dilated cardiomyopathy and mice post-infarction had increased cardiac expression of connective tissue growth factor. Bone morphogenetic protein 2 was increased in human hearts failing due to coronary artery disease and in mice post-infarction. Gene expression of bone morphogenetic protein receptor 1 beta was reduced in hearts of patients with failure, but increased two weeks following permanent ligation of the left coronary artery in mice. In conclusion, connective tissue growth factor is upregulated in hearts of humans with dilated cardiomyopathy, bone morphogenetic protein 2 is upregulated in remodeling due to myocardial infarction while its receptor 1 b in human failing hearts is downregulated. A potential explanation might be an attempt to engage regenerative processes, which should be addressed by further, mechanistic studies.

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.

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.

The Connective Tissue Components of Optic Nerve Head Cupping in Monkey Experimental Glaucoma Part 1: Global Change

PubMed Central

Yang, Hongli; Ren, Ruojin; Lockwood, Howard; Williams, Galen; Libertiaux, Vincent; Downs, Crawford; Gardiner, Stuart K.; Burgoyne, Claude F.

2015-01-01

Purpose To characterize optic nerve head (ONH) connective tissue change within 21 monkey experimental glaucoma (EG) eyes, so as to identify its principal components. Methods Animals were imaged three to five times at baseline then every 2 weeks following chronic unilateral IOP elevation, and euthanized early through end-stage confocal scanning laser tomographic change. Optic nerve heads were serial-sectioned, three-dimensionally (3D) reconstructed, delineated, and quantified. Overall EG versus control eye differences were assessed by general estimating equations (GEE). Significant, animal-specific, EG eye change was required to exceed the maximum physiologic intereye differences in six healthy animals. Results Overall EG eye change was significant (P < 0.0026) and animal-specific EG eye change most frequent, for five phenomena (number of EG eyes and range of animal-specific change): posterior laminar deformation (21, −29 to −437 μm), laminar thickening (11, 20–73 μm) and thinning (3, −23 to −31 μm), scleral canal expansion (17, 20–139 μm), outward anterior (16, −16 to −124 μm) and posterior (17, −22 to −279 μm) laminar insertion migration, and peripapillary scleral bowing (11, 21–77 μm). Experimental glaucoma versus control eye laminar thickness differences were bimodal in behavior, being thickened in most EG eyes demonstrating the least deformation and less thickened or thinned in most EG eyes demonstrating the greatest deformation. Conclusions Our postmortem studies retrospectively identify five connective tissue components of ONH “cupping” in monkey EG which serve as targets for longitudinally staging and phenotyping ONH connective tissue alteration within all forms of monkey and human optic neuropathy. PMID:26641545

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.

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.

Inflammatory process induced by carrageenan in adjacent tissue triggers the acute inflammation in deep digital flexor tendon of rats.

PubMed

Vieira, Cristiano Pedrozo; De Aro, Andrea Aparecida; Da Ré Guerra, Flávia; De Oliveira, Letícia Prado; De Almeida, Marcos Dos Santos; Pimentel, Edson Rosa

2013-08-01

Tendinopathy is a pathology found mainly in the rotator cuff, patellar, Achilles and flexor tendons. Tendinopathy is a significant impediment to performance in athletes and in workers in the labor market. Some studies have indicated that inflammation in adjacent tissues may affect the rotator cuff and Achilles tendon. In this study alterations were verified in the extracellular matrix (ECM) of the deep digital flexor tendon after two periods (12 and 24 hr) of induction inflammation in rat paw. Wistar rats were divided into three groups: those that received injection of 1% carrageenan; those that received 0.9% NaCl; and those that received no application. The tendon was divided into distal (d), proximal (p), and intermediate (i) regions. Biochemical analyses were performed and included non-collagenous proteins (NCP), glycosaminoglycans (GAGs), hydroxyproline (HoPro) and metalloproteinases 2 and 9. Tissue sections were stained with toluidine blue, hematoxylin-eosin, and Ponceau SS and observed under polarization microscopy. Remarkable results were detected that included the presence of MMP-9, degradation of NCP and GAG and the presence of cellular infiltrate closer to digits in d region. The different concentrations of HoPro, as well as alterations in the organization of the collagen fibers showed the collagenous matrix undergoing some alterations. The results indicated that the induced inflammation in rat paw exhibited characteristics similar to the typical acute inflammatory process observed in tendons. Copyright © 2013 Wiley Periodicals, Inc.

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.

Cancer testis antigen OY-TES-1: analysis of protein expression in ovarian cancer with tissue microarrays.

PubMed

Fan, R; Huang, W; Luo, B; Zhang, Q M; Xiao, S W; Xie, X X

2015-01-01

Revised manuscript accepted for publication March 5, Objectives: The purpose of this study was to determine the potential of cancer testis antigen OY-TES-1 as a vaccine for ovarian cancer (OC). A tissue microarray (TMA) containing 107 samples from OC tissues and 48 samples from OC adjacent tissues was analyzed by immunohistochemistry with the OY-TES-1 polyclonal antibody. The correlation between OY-TES-1 and clinic pathological traits of OC was statistically analyzed. The expression of OY-TES-1 protein was found in 81% (87/107) of OC tissues and 56% (27/48) of OC adjacent tissues. The immunostaining intensity of OY-TES-1 in OC tissues was significantly higher than that in OC adjacent tissues tested (p = 0.040). OC adjacent tissues only demonstrated lower immunostaining intensity, whereas some of OC tissues presented higher immunostaining intensity and majority showed the heterogeneity of protein distribution. There was no statistically significant correlation found between OY-TES-1 expression and any other clinicopathological traits such as age, FIGO stage, pathological grade, and histological type. OY-TES-1 was expressed in OC tissues with a high proportion, and some of OC tissues presented OY-TES-1 expression in high level vs OC adjacent tissues. OY-TES-1 could be an attractive target for immunotherapy for OC in the future.

Proteomic Analysis of Human Tendon and Ligament: Solubilization and Analysis of Insoluble Extracellular Matrix in Connective Tissues.

PubMed

Sato, Nori; Taniguchi, Takako; Goda, Yuichiro; Kosaka, Hirofumi; Higashino, Kosaku; Sakai, Toshinori; Katoh, Shinsuke; Yasui, Natsuo; Sairyo, Koichi; Taniguchi, Hisaaki

2016-12-02

Connective tissues such as tendon, ligament and cartilage are mostly composed of extracellular matrix (ECM). These tissues are insoluble, mainly due to the highly cross-linked ECM proteins such as collagens. Difficulties obtaining suitable samples for mass spectrometric analysis render the application of modern proteomic technologies difficult. Complete solubilization of them would not only elucidate protein composition of normal tissues but also reveal pathophysiology of pathological tissues. Here we report complete solubilization of human Achilles tendon and yellow ligament, which is achieved by chemical digestion combined with successive protease treatment including elastase. The digestion mixture was subjected to liquid chromatography-mass spectrometry. The low specificity of elastase was overcome by accurate mass analysis achieved using FT-ICR-MS. In addition to the detailed proteome of both tissues, we also quantitatively determine the major protein composition of samples, by measuring peak area of some characteristic peptides detected in tissue samples and in purified proteins. As a result, differences between human Achilles tendon and yellow ligament were elucidated at molecular level.

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.

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.

Subpedicle connective tissue graft versus guided tissue regeneration with bioabsorbable membrane in the treatment of human gingival recession defects.

PubMed

Trombelli, L; Scabbia, A; Tatakis, D N; Calura, G

1998-11-01

The purpose of the present clinical study was to evaluate the effect of guided tissue regeneration (GTR) in comparison to subpedicle connective tissue graft (SCTG) in the treatment of gingival recession defects. A total of 12 patients, each contributing a pair of Miller's Class I or II buccal gingival recessions, was treated. According to a randomization list, one defect in each patient received a polyglycolide/lactide bioabsorbable membrane, while the paired defect received a SCTG. Treatment effect was evaluated 6 months postsurgery. Clinical recordings included full-mouth and defect-specific oral hygiene standards and gingival health, recession depth (RD), recession width (RW), probing depth (PD), clinical attachment level (CAL), and keratinized tissue width (KT). Mean RD significantly decreased from 3.1 mm presurgery to 1.5 mm at 6 months postsurgery for the GTR group (48% root coverage), and from 3.0 mm to 0.5 mm for the SCTG group (81% root coverage). RD reduction and root coverage were significantly greater in SCTG group compared to GTR group. Mean CAL gain amounted to 1.7 mm for the GTR group, and 2.3 mm in the SCTG group. No significant differences in PD changes were observed within and between groups. KT increased significantly from presurgery for both treatment groups, however gingival augmentation was significantly greater in the SCTG group compared to GTR group. Results indicate that: 1) treatment of human gingival recession defects by means of both GTR and SCTG procedures results in clinically and statistically significant improvement of the soft tissue conditions of the defect; and 2) treatment outcome was significantly better following SCTG compared to GTR in terms of recession depth reduction, root coverage, and keratinized tissue increase.

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.

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

PubMed

Halper, Jaroslava; Kjaer, Michael

2014-01-01

Collagens are the most abundant components of the extracellular matrix and many types of soft tissues. Elastin is another major component of certain soft tissues, such as arterial walls and ligaments. Many other molecules, though lower in quantity, function as essential components of the extracellular matrix in soft tissues. Some of these are reviewed in this chapter. Besides their basic structure, biochemistry and physiology, their roles in disorders of soft tissues are discussed only briefly as most chapters in this volume deal with relevant individual compounds. Fibronectin with its muldomain structure plays a role of "master organizer" in matrix assembly as it forms a bridge between cell surface receptors, e.g., integrins, and compounds such collagen, proteoglycans and other focal adhesion molecules. It also plays an essential role in the assembly of fibrillin-1 into a structured network. Laminins contribute to the structure of the extracellular matrix (ECM) and modulate cellular functions such as adhesion, differentiation, migration, stability of phenotype, and resistance towards apoptosis. Though the primary role of fibrinogen is in clot formation, after conversion to fibrin by thrombin, it also binds to a variety of compounds, particularly to various growth factors, and as such fibrinogen is a player in cardiovascular and extracellular matrix physiology. Elastin, an insoluble polymer of the monomeric soluble precursor tropoelastin, is the main component of elastic fibers in matrix tissue where it provides elastic recoil and resilience to a variety of connective tissues, e.g., aorta and ligaments. Elastic fibers regulate activity of TGFβs through their association with fibrillin microfibrils. Elastin also plays a role in cell adhesion, cell migration, and has the ability to participate in cell signaling. Mutations in the elastin gene lead to cutis laxa. Fibrillins represent the predominant core of the microfibrils in elastic as well as non

Variability in physical and biological exchange among coastal wetlands and their adjacent Great Lakes

EPA Science Inventory

Hydrology is a major governor of physically-driven exchange among coastal wetlands and the adjacent Great Lake, whereas fish movement is a major governor of biologically-driven exchange. We use data describing coastal wetland morphology, hydrology, water quality, and fish tissue...

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

PubMed Central

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

2014-01-01

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

Neutrophilic Skin Lesions in Autoimmune Connective Tissue Diseases

PubMed Central

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

2014-01-01

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

Undifferentiated connective tissue disease and interstitial lung disease: Trying to define patterns.

PubMed

Alberti, María Laura; Paulin, Francisco; Toledo, Heidegger Mateos; Fernández, Martín Eduardo; Caro, Fabián Matías; Rojas-Serrano, Jorge; Mejía, Mayra Edith

To identify clinical or immunological features in patients with undifferentiated connective tissue disease (UCTD) associated interstitial lung disease (ILD), in order to group them and recognize different functional and high resolution computed tomography (HRCT) behavior. Retrospective cohort study. Patients meeting Kinder criteria for UCTD were included. We defined the following predictive variables: 'highly specific' connective tissue disease (CTD) manifestations (Raynaud's phenomenon, dry eyes or arthritis), high antinuclear antibody (ANA) titer (above 1: 320), and 'specific' ANA staining patterns (centromere, cytoplasmic and nucleolar patterns). We evaluated the following outcomes: change in the percentage of the predicted forced vital capacity (FVC%) during the follow-up period, and HRCT pattern. Sixty-six patients were included. Twenty-nine (43.94%) showed at least one 'highly specific' CTD manifestation, 16 (28.57%) had a 'specific' ANA staining pattern and 29 (43.94%) high ANA titer. Patients with 'highly specific' CTD manifestations were younger (mean [SD] 52 years [14.58] vs 62.08 years [9.46], P<.001), were more likely men (10.34% vs 48.65%, P<.001) and showed a smaller decline of the FVC% (median [interquartile range] 1% [-1 to 10] vs -6% [-16 to -4], P<.006). In the multivariate analysis, the presence of highly specific manifestations was associated with improvement in the FVC% (B coefficient of 13.25 [95% confidence interval, 2.41 to 24.09]). No association was observed in relation to the HRCT pattern. The presence of 'highly specific' CTD manifestations was associated with female sex, younger age and better functional behavior. These findings highlight the impact of the clinical features in the outcome of patients with UCTD ILD. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

Small cell lung cancer presenting as dermatomyositis: mistaken for single connective tissue disease.

PubMed

Chao, Guanqun; Fang, Lizheng; Lu, Chongrong; Chen, Zhouwen

2012-06-01

Dermatomyositis (DM) is well-known to be associated with several types of malignancy. This case emphasizes the importance of a thorough examination for an underlying cancer, in patients with the symptoms of dermatomyositis. We report the case of a 62-year-old Chinese man who presented with a two-month history of edema of face and neck, together with erythema of the eyelids diagnosed of small cell lung cancer. Initially, it was thought to be single connective tissue disease such as DM. This study highlights the importance of a thorough physical examination when visiting a patient.

Diagnostic Exome Sequencing Identifies a Novel Gene, EMILIN1, Associated with Autosomal-Dominant Hereditary Connective Tissue Disease.

PubMed

Capuano, Alessandra; Bucciotti, Francesco; Farwell, Kelly D; Tippin Davis, Brigette; Mroske, Cameron; Hulick, Peter J; Weissman, Scott M; Gao, Qingshen; Spessotto, Paola; Colombatti, Alfonso; Doliana, Roberto

2016-01-01

Heritable connective tissue diseases are a highly heterogeneous family of over 200 disorders that affect the extracellular matrix. While the genetic basis of several disorders is established, the etiology has not been discovered for a large portion of patients, likely due to rare yet undiscovered disease genes. By performing trio-exome sequencing of a 55-year-old male proband presenting with multiple symptoms indicative of a connective disorder, we identified a heterozygous missense alteration in exon 1 of the Elastin Microfibril Interfacer 1 (EMILIN1) gene, c.64G>A (p.A22T). The proband presented with ascending and descending aortic aneurysms, bilateral lower leg and foot sensorimotor peripheral neuropathy, arthropathy, and increased skin elasticity. Sanger sequencing confirmed that the EMILIN1 alteration, which maps around the signal peptide cleavage site, segregated with disease in the affected proband, mother, and son. The impaired secretion of EMILIN-1 in cells transfected with the mutant p.A22T coincided with abnormal protein accumulation within the endoplasmic reticulum. In skin biopsy of the proband, we detected less EMILIN-1 with disorganized and abnormal coarse fibrils, aggregated deposits underneath the epidermis basal lamina, and dermal cells apoptosis. These findings collectively suggest that EMILIN1 may represent a new disease gene associated with an autosomal-dominant connective tissue disorder. © 2015 The Authors. **Human Mutation published by Wiley Periodicals, Inc.

A case of mixed connective tissue disease with pseudo-pseudo Meigs' syndrome (PPMS)-like features.

PubMed

Cheah, C K; Ramanujam, S; Mohd Noor, N; Gandhi, C; D Souza, Beryl A; Gun, S C

2016-02-01

Pseudo-pseudo Meigs' syndrome (PPMS) has been reported to be a rare presentation of patients with systemic lupus erythematosus (SLE). However, such a presentation is not common in other forms of connective tissue disease. We presented a case of gross ascites, pleural effusion, and marked elevation of CA-125 level (PPMS-like features) that led to a diagnosis of MCTD. The patient responded to systemic steroid therapy. © The Author(s) 2015.

Complications of harvesting a connective tissue graft from the palate. A retrospective study and description of a new technique

PubMed Central

Aguirre-Zorzano, Luis-Antonio; Estefanía-Fresco, Ruth; Marichalar-Mendía, Xabier

2017-01-01

Background Connective tissue graft (CTG) is considered as the gold standard for the treatment of gingival recessions (GR). There are few studies assessing the complications that can arise in the donor site when harvesting a connective tissue graft (CTG) and how the harvesting technique can influence those complications. Material and Methods A retrospective clinical study was carried out in order to compare the complications observed in 40 patients with Miller class I, II and III GR ≥ 3 mm, after using the trap-door technique (TD) in the control group and a newly described technique, the “UPV/EHU technique”, in the test group. Patients were consecutively allocated to each treatment group. Patients were monitored 14 days after surgery in order to evaluate post-operative complications in the donor site: presence of pain (P), bleeding (B), infection (I) and necrosis > 30%. Results Although morbidity was observed in both groups, it was less important in the test group (no pain and minimal pain in 30% and 35% of the cases, respectively, and absence of bleeding or infection and necrosis >30% in only 5% of the cases). Conclusions Within the limits of this study, this newly described “UPV/EHU technique” should be considered as a treatment option when harvesting a CTG, with minimal morbidity for patients. Key words:Connective tissue graft, pain, gingival recessions, wound healing, cosmetic periodontal plastic surgery, trap-door technique, “UPV/EHU technique”. PMID:29410760

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.

Connective Tissue Growth Factor Is Involved in Structural Retinal Vascular Changes in Long-Term Experimental Diabetes

PubMed Central

Van Geest, Rob J.; Leeuwis, Jan Willem; Dendooven, Amélie; Pfister, Frederick; Bosch, Klazien; Hoeben, Kees A.; Vogels, Ilse M.C.; Van der Giezen, Dionne M.; Dietrich, Nadine; Hammes, Hans-Peter; Goldschmeding, Roel; Klaassen, Ingeborg; Van Noorden, Cornelis J.F.

2014-01-01

Early retinal vascular changes in the development of diabetic retinopathy (DR) include capillary basal lamina (BL) thickening, pericyte loss and the development of acellular capillaries. Expression of the CCN (connective tissue growth factor/cysteine-rich 61/nephroblastoma overexpressed) family member CCN2 or connective tissue growth factor (CTGF), a potent inducer of the expression of BL components, is upregulated early in diabetes. Diabetic mice lacking one functional CTGF allele (CTGF+/−) do not show this BL thickening. As early events in DR may be interrelated, we hypothesized that CTGF plays a role in the pathological changes of retinal capillaries other than BL thickening. We studied the effects of long-term (6-8 months) streptozotocin-induced diabetes on retinal capillary BL thickness, numbers of pericytes and the development of acellular capillaries in wild type and CTGF+/− mice. Our results show that an absence of BL thickening of retinal capillaries in long-term diabetic CTGF+/− mice is associated with reduced pericyte dropout and reduced formation of acellular capillaries. We conclude that CTGF is involved in structural retinal vascular changes in diabetic rodents. Inhibition of CTGF in the eye may therefore be protective against the development of DR. PMID:24217924

Laboratory and in vivo transport characterization of hollow fiber membranes and adjacent scar tissue that forms following their implantation in the central nervous system

NASA Astrophysics Data System (ADS)

Bridge, Michael John

Hollow fiber membrane (HFM) cell encapsulation devices use a semipermeable membrane to physically immunoisolate transplanted secretory cells from host tissues and high molecular weight solutes. Advantages inherent to macroencapsulation technology have led to extensive research towards their utilization for treating a wide range of disorders including a number of neurodegenerative diseases and diabetes. Although feasibility studies have already established the therapeutic potential of macroencapsulation technology, a common observation among these and later studies is diminishing therapeutic efficacy over a span of a few weeks following implantation of devices. Progress towards fulfilling the therapeutic potential of this technology initially recognized by investigators has potentially been hampered by inadequate diffusive transport characterization of membranes employed in studies. In addition, the potential effects of host tissue responses following central nervous system (CNS) implantation of these devices is completely unknown. To address these issues a membrane characterization instrument capable of efficiently characterizing the diffusive and convective transport properties of individual HFM segments, such as they are used in devices, was developed. The instrument was then employed to study the effects of ethanol exposure, a common sterilization method, on PAN-PVC membranes commonly used in CNS implantation macro encapsulation device studies. Lastly, the solute diffusivity properties of tissue that forms adjacent to the membranes of brain implanted transcranial access devices were investigated. Coinciding with this investigation was the development of a novel technique for examining the solute diffusivity properties in the extracellular spaces of CNS tissue.

LRP1 protects the vasculature by regulating levels of connective tissue growth factor and HtrA1.

PubMed

Muratoglu, Selen C; Belgrave, Shani; Hampton, Brian; Migliorini, Mary; Coksaygan, Turhan; Chen, Ling; Mikhailenko, Irina; Strickland, Dudley K

2013-09-01

Low-density lipoprotein receptor-related protein 1 (LRP1) is a large endocytic and signaling receptor that is abundant in vascular smooth muscle cells. Mice in which the lrp1 gene is deleted in smooth muscle cells (smLRP1(-/-)) on a low-density lipoprotein receptor-deficient background display excessive platelet derived growth factor-signaling, smooth muscle cell proliferation, aneurysm formation, and increased susceptibility to atherosclerosis. The objectives of the current study were to examine the potential of LRP1 to modulate vascular physiology under nonatherogenic conditions. We found smLRP1(-/-) mice to have extensive in vivo aortic dilatation accompanied by disorganized and degraded elastic lamina along with medial thickening of the arterial vessels resulting from excess matrix deposition. Surprisingly, this was not attributable to excessive platelet derived growth factor-signaling. Rather, quantitative differential proteomic analysis revealed that smLRP1(-/-) vessels contain a 4-fold increase in protein levels of high-temperature requirement factor A1 (HtrA1), which is a secreted serine protease that is known to degrade matrix components and to impair elastogenesis, resulting in fragmentation of elastic fibers. Importantly, our study discovered that HtrA1 is a novel LRP1 ligand. Proteomics analysis also identified excessive accumulation of connective tissue growth factor, an LRP1 ligand and a key mediator of fibrosis. Our findings suggest a critical role for LRP1 in maintaining the integrity of vessels by regulating protease activity as well as matrix deposition by modulating HtrA1 and connective tissue growth factor protein levels. This study highlights 2 new molecules, connective tissue growth factor and HtrA1, which contribute to detrimental changes in the vasculature and, therefore, represent new target molecules for potential therapeutic intervention to maintain vessel wall homeostasis.

Connective tissue growth factor induces cardiac hypertrophy through Akt signaling

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

Hayata, Nozomi; Fujio, Yasushi; Yamamoto, Yasuhiro

2008-05-30

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

[Expression of connective tissue growth factor in colorectal cancer and its association with prognosis].

PubMed

Sun, Zheng; Yang, Ping; Liang, Li-yuan; Zhang, Tong; Zhang, Wei-jian; Cao, Jie

2012-11-01

To investigate the expression of connective tissue growth factor (CTGF) in colorectal cancer(CRC) and its association with clinicopathologic parameters and overall survival rate. Fresh tumor tissues and matched distal normal colon tissues were collected from 92 patients diagnosed as CRC by surgical operation. The expression level of CTGF mRNA was quantified by quantitative reverse transcription PCR. Thirty out of 92 pairs of tissue specimens were selected randomly to detect CTGF protein by immunohistochemistry. All the cases were followed up to identify prognostic factors for survival. CTGF mRNA expression was up-regulated in CRC. The positive rate of CTGF protein expression tissues (73.3%) was significantly higher than that in the corresponding normal tissues (23.3%, P<0.01). CTGF expression was lower in patients with lymphatic metastasis or stage III/IIII disease (all P<0.05). A negative association was also observed between the CTGF protein positive rate and tumor infiltration depth (P<0.05). The relative expression of CTGF mRNA in tumor tissues was classified into high and low expression groups. The 5-year cumulative survival rate was lower in patients with low CTGF expression (29.3%) as compared to those with high CTGF expressions (68.3%) (P<0.01). Cox regression analysis revealed that the relative expression level of CTGF was independent factor of overall survival (RR=2.960, 95%CI:1.491-1.587, P<0.01). ROC curve analysis showed that sensitivity and specificity of CTGF mRNA expression for prediction of 5-year survival were 64.9% and 74.5%, respectively. The aberrant expression of CTGF is associated with the malignant biological behaviors of CRC. Low expression of CTGF is associated with worse prognosis of CRC.

Adipocytes in both brown and white adipose tissue of adult mice are functionally connected via gap junctions: implications for Chagas disease.

PubMed

Burke, Shoshana; Nagajyothi, Fnu; Thi, Mia M; Hanani, Menachem; Scherer, Philipp E; Tanowitz, Herbert B; Spray, David C

2014-11-01

Adipose tissue serves as a host reservoir for the protozoan Trypanosoma cruzi, the causative organism in Chagas disease. Gap junctions interconnect cells of most tissues, serving to synchronize cell activities including secretion in glandular tissue, and we have previously demonstrated that gap junctions are altered in various tissues and cells infected with T. cruzi. Herein, we examined the gap junction protein connexin 43 (Cx43) expression in infected adipose tissues. Adipose tissue is the largest endocrine organ of the body and is also involved in other physiological functions. In mammals, it is primarily composed of white adipocytes. Although gap junctions are a prominent feature of brown adipocytes, they have not been explored extensively in white adipocytes, especially in the setting of infection. Thus, we examined functional coupling in both white and brown adipocytes in mice. Injection of electrical current or the dye Lucifer Yellow into adipocytes within fat tissue spread to adjacent cells, which was reduced by treatment with agents known to block gap junctions. Moreover, Cx43 was detected in both brown and white fat tissue. At thirty and ninety days post-infection, Cx43 was downregulated in brown adipocytes and upregulated in white adipocytes. Gap junction-mediated intercellular communication likely contributes to hormone secretion and other functions in white adipose tissue and to nonshivering thermogenesis in brown fat, and modulation of the coupling by T. cruzi infection is expected to impact these functions. Copyright © 2014. Published by Elsevier Masson SAS.

Development and evaluation of a connective tissue phantom model for subsurface visualization of cancers requiring wide local excision

NASA Astrophysics Data System (ADS)

Samkoe, Kimberley S.; Bates, Brent D.; Tselepidakis, Niki N.; DSouza, Alisha V.; Gunn, Jason R.; Ramkumar, Dipak B.; Paulsen, Keith D.; Pogue, Brian W.; Henderson, Eric R.

2017-12-01

Wide local excision (WLE) of tumors with negative margins remains a challenge because surgeons cannot directly visualize the mass. Fluorescence-guided surgery (FGS) may improve surgical accuracy; however, conventional methods with direct surface tumor visualization are not immediately applicable, and properties of tissues surrounding the cancer must be considered. We developed a phantom model for sarcoma resection with the near-infrared fluorophore IRDye 800CW and used it to iteratively define the properties of connective tissues that typically surround sarcoma tumors. We then tested the ability of a blinded surgeon to resect fluorescent tumor-simulating inclusions with ˜1-cm margins using predetermined target fluorescence intensities and a Solaris open-air fluorescence imaging system. In connective tissue-simulating phantoms, fluorescence intensity decreased with increasing blood concentration and increased with increasing intralipid concentrations. Fluorescent inclusions could be resolved at ≥1-cm depth in all inclusion concentrations and sizes tested. When inclusion depth was held constant, fluorescence intensity decreased with decreasing volume. Using targeted fluorescence intensities, a blinded surgeon was able to successfully excise inclusions with ˜1-cm margins from fat- and muscle-simulating phantoms with inclusion-to-background contrast ratios as low as 2∶1. Indirect, subsurface FGS is a promising tool for surgical resection of cancers requiring WLE.

Intracranial phosphaturic mesenchymal tumor, mixed connective tissue variant presenting without oncogenic osteomalacia.

PubMed

Bower, Regina S; Daugherty, Wilson P; Giannini, Caterina; Parney, Ian F

2012-01-01

Phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT) is a rare tumor typically occurring in soft tissues and bone, causing oncogenic (tumor-induced) osteomalacia (TIO) through secretion of the phosphaturic hormone, fibroblast growth factor-23 (FGF-23). Rare tumors identical to PMTMCT occur without known TIO. Intracranial localization of PMTMCT is extremely rare, with only two cases reported in the literature. We present a very unusual case of a patient with an intracranial PMTMCT that presented with neurologic changes without osteomalacia. A 67-year-old woman presented with progressive incontinence, apathy, and abulia after having undergone a total knee replacement 1 month earlier. Imaging disclosed a large left frontal anterior fossa mass. She underwent uncomplicated surgical resection of this tumor. Surprisingly, histopathology suggested PMTMCT. Reverse transcription polymerase chain reaction (RT-PCR) assay demonstrating FGF-23 expression in the tumor confirmed the diagnosis. Serum FGF-23 levels postoperatively were normal and she had no clinical or laboratory evidence of osteomalacia or phosphaturia. This report should serve to alert clinicians to the possibility that PMTMCT can be included in the differential diagnosis of intracranial masses even in the absence of tumor-induced osteomalacia.

Marginal bone and soft tissue behavior following platform switching abutment connection/disconnection--a dog model study.

PubMed

Alves, Célia C; Muñoz, Fernando; Cantalapiedra, António; Ramos, Isabel; Neves, Manuel; Blanco, Juan

2015-09-01

The effect on the marginal peri-implant tissues following repeated platform switching abutment removal and subsequent reconnection was studied. Six adult female Beagle dogs were selected, and Pm3 and Pm4 teeth, both left and right sides, were extracted and the sites healed for 3 months. At this time, 24 bone level (BL) (Straumann, Basel, Switzerland) Ø 3.3/8 mm implants were placed, 2 in each side on Pm3 and Pm4 regions. In one side (control group), 12 bone level conical Ø 3.6 mm healing abutments and, on the other side (test group), 12 Narrow CrossFit (NC) multibase abutments (Straumann) , Basel, Switzerland) were connected at time of implant surgery. On test group, all prosthetic procedures were carried out direct to multibase abutment without disconnecting it, where in the control group, the multibase abutment was connected/disconnected five times (at 6/8/10/12/14 weeks) during prosthetic procedures. Twelve fixed metal bridges were delivered 14 weeks after implant placement. A cleaning/control appointment was scheduled 6 months after implant placement. The animals were sacrificed at 9 months of the study. Clinical parameters and peri-apical x-rays were registered in every visit. Histomorphometric analysis was carried out for the 24 implants. The distance from multibase abutment shoulder to the first bone implant contact (S-BIC) was defined as the primary histomorphometric parameter. Wilcoxon comparison paired test (n = 6) found no statistically significant differences (buccal P = 0.917; Lingual P = 0.463) between test and control groups both lingually and buccally for S-BIC distance. Only Pm3 buccal aBE-BC (distance from the apical end of the barrier epithelium to the first bone implant contact) (P = 0.046) parameter presented statistically significant differences between test and control groups. Control group presented 0.57 mm more recession than test group, being this difference statistically significant between the two groups (P < 0.001). It can be conclude

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

PubMed Central

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

2005-01-01

Pseudoxanthoma elasticum (PXE), characterized by connective tissue mineralization of the skin, eyes, and cardiovascular system, is caused by mutations in the ABCC6 gene. ABCC6 encodes multidrug resistance-associated protein 6 (MRP6), which is expressed primarily in the liver and kidneys. Mechanisms producing ectopic mineralization as a result of these mutations remain unclear. To elucidate this complex disease, a transgenic mouse was generated by targeted ablation of the mouse Abcc6 gene. Abcc6 null mice were negative for Mrp6 expression in the liver, and complete necropsies revealed profound mineralization of several tissues, including skin, arterial blood vessels, and retina, while heterozygous animals were indistinguishable from the wild-type mice. Particularly striking was the mineralization of vibrissae, as confirmed by von Kossa and alizarin red stains. Electron microscopy revealed mineralization affecting both elastic structures and collagen fibers. Mineralization of vibrissae was noted as early as 5 weeks of age and was progressive with age in Abcc6−/− mice but was not observed in Abcc6+/− or Abcc6+/+ mice up to 2 years of age. A total body computerized tomography scan of Abcc6−/− mice revealed mineralization in skin and subcutaneous tissue as well as in the kidneys. These data demonstrate aberrant mineralization of soft tissues in PXE-affected organs, and, consequently, these mice recapitulate features of this complex disease. PMID:16135817

Regulatory mechanisms of anthrax toxin receptor 1-dependent vascular and connective tissue homeostasis.

PubMed

Besschetnova, Tatiana Y; Ichimura, Takaharu; Katebi, Negin; St Croix, Brad; Bonventre, Joseph V; Olsen, Bjorn R

2015-03-01

It is well known that angiogenesis is linked to fibrotic processes in fibroproliferative diseases, but insights into pathophysiological processes are limited, due to lack of understanding of molecular mechanisms controlling endothelial and fibroblastic homeostasis. We demonstrate here that the matrix receptor anthrax toxin receptor 1 (ANTXR1), also known as tumor endothelial marker 8 (TEM8), is an essential component of these mechanisms. Loss of TEM8 function in mice causes reduced synthesis of endothelial basement membrane components and hyperproliferative and leaky blood vessels in skin. In addition, endothelial cell alterations in mutants are almost identical to those of endothelial cells in infantile hemangioma lesions, including activated VEGF receptor signaling in endothelial cells, increased expression of the downstream targets VEGF and CXCL12, and increased numbers of macrophages and mast cells. In contrast, loss of TEM8 in fibroblasts leads to increased rates of synthesis of fiber-forming collagens, resulting in progressive fibrosis in skin and other organs. Compromised interactions between TEM8-deficient endothelial and fibroblastic cells cause dramatic reduction in the activity of the matrix-degrading enzyme MMP2. In addition to insights into mechanisms of connective tissue homeostasis, our data provide molecular explanations for vascular and connective tissue abnormalities in GAPO syndrome, caused by loss-of-function mutations in ANTXR1. Furthermore, the loss of MMP2 activity suggests that fibrotic skin abnormalities in GAPO syndrome are, in part, the consequence of pathophysiological mechanisms underlying syndromes (NAO, Torg and Winchester) with multicentric skin nodulosis and osteolysis caused by homozygous loss-of-function mutations in MMP2. Copyright © 2014 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

Matriptase activation connects tissue factor-dependent coagulation initiation to epithelial proteolysis and signaling.

PubMed

Le Gall, Sylvain M; Szabo, Roman; Lee, Melody; Kirchhofer, Daniel; Craik, Charles S; Bugge, Thomas H; Camerer, Eric

2016-06-23

The coagulation cascade is designed to sense tissue injury by physical separation of the membrane-anchored cofactor tissue factor (TF) from inactive precursors of coagulation proteases circulating in plasma. Once TF on epithelial and other extravascular cells is exposed to plasma, sequential activation of coagulation proteases coordinates hemostasis and contributes to host defense and tissue repair. Membrane-anchored serine proteases (MASPs) play critical roles in the development and homeostasis of epithelial barrier tissues; how MASPs are activated in mature epithelia is unknown. We here report that proteases of the extrinsic pathway of blood coagulation transactivate the MASP matriptase, thus connecting coagulation initiation to epithelial proteolysis and signaling. Exposure of TF-expressing cells to factors (F) VIIa and Xa triggered the conversion of latent pro-matriptase to an active protease, which in turn cleaved the pericellular substrates protease-activated receptor-2 (PAR2) and pro-urokinase. An activation pathway-selective PAR2 mutant resistant to direct cleavage by TF:FVIIa and FXa was activated by these proteases when cells co-expressed pro-matriptase, and matriptase transactivation was necessary for efficient cleavage and activation of wild-type PAR2 by physiological concentrations of TF:FVIIa and FXa. The coagulation initiation complex induced rapid and prolonged enhancement of the barrier function of epithelial monolayers that was dependent on matriptase transactivation and PAR2 signaling. These observations suggest that the coagulation cascade engages matriptase to help coordinate epithelial defense and repair programs after injury or infection, and that matriptase may contribute to TF-driven pathogenesis in cancer and inflammation.

33 CFR 148.217 - How can a State be designated as an adjacent coastal State?

Code of Federal Regulations, 2010 CFR

2010-07-01

..., DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DEEPWATER PORTS DEEPWATER PORTS: GENERAL Processing Applications... as an adjacent coastal State in the notice may request to be designated as one if the environmental risks to it are equal to or greater than the risks posed to a State directly connected by pipeline to...

Co-expression networks reveal the tissue-specific regulation of transcription and splicing

PubMed Central

Saha, Ashis; Kim, Yungil; Gewirtz, Ariel D.H.; Jo, Brian; Gao, Chuan; McDowell, Ian C.; Engelhardt, Barbara E.

2017-01-01

Gene co-expression networks capture biologically important patterns in gene expression data, enabling functional analyses of genes, discovery of biomarkers, and interpretation of genetic variants. Most network analyses to date have been limited to assessing correlation between total gene expression levels in a single tissue or small sets of tissues. Here, we built networks that additionally capture the regulation of relative isoform abundance and splicing, along with tissue-specific connections unique to each of a diverse set of tissues. We used the Genotype-Tissue Expression (GTEx) project v6 RNA sequencing data across 50 tissues and 449 individuals. First, we developed a framework called Transcriptome-Wide Networks (TWNs) for combining total expression and relative isoform levels into a single sparse network, capturing the interplay between the regulation of splicing and transcription. We built TWNs for 16 tissues and found that hubs in these networks were strongly enriched for splicing and RNA binding genes, demonstrating their utility in unraveling regulation of splicing in the human transcriptome. Next, we used a Bayesian biclustering model that identifies network edges unique to a single tissue to reconstruct Tissue-Specific Networks (TSNs) for 26 distinct tissues and 10 groups of related tissues. Finally, we found genetic variants associated with pairs of adjacent nodes in our networks, supporting the estimated network structures and identifying 20 genetic variants with distant regulatory impact on transcription and splicing. Our networks provide an improved understanding of the complex relationships of the human transcriptome across tissues. PMID:29021288

Connective tissue growth factor is a substrate of ADAM28

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

Mochizuki, Satsuki; Tanaka, Rena; Shimoda, Masayuki

2010-11-26

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

Prostate tissue metal levels and prostate cancer recurrence in smokers.

PubMed

Neslund-Dudas, Christine; Kandegedara, Ashoka; Kryvenko, Oleksandr N; Gupta, Nilesh; Rogers, Craig; Rybicki, Benjamin A; Dou, Q Ping; Mitra, Bharati

2014-02-01

Although smoking is not associated with prostate cancer risk overall, smoking is associated with prostate cancer recurrence and mortality. Increased cadmium (Cd) exposure from smoking may play a role in progression of the disease. In this study, inductively coupled plasma mass spectrometry was used to determine Cd, arsenic (As), lead (Pb), and zinc (Zn) levels in formalin-fixed paraffin embedded tumor and tumor-adjacent non-neoplastic tissue of never- and ever-smokers with prostate cancer. In smokers, metal levels were also evaluated with regard to biochemical and distant recurrence of disease. Smokers (N = 25) had significantly higher Cd (median ppb, p = 0.03) and lower Zn (p = 0.002) in non-neoplastic tissue than never-smokers (N = 21). Metal levels were not significantly different in tumor tissue of smokers and non-smokers. Among smokers, Cd level did not differ by recurrence status. However, the ratio of Cd ppb to Pb ppb was significantly higher in both tumor and adjacent tissue of cases with distant recurrence when compared with cases without distant recurrence (tumor tissue Cd/Pb, 6.36 vs. 1.19, p = 0.009, adjacent non-neoplastic tissue Cd/Pb, 6.36 vs. 1.02, p = 0.038). Tissue Zn levels were also higher in smokers with distant recurrence (tumor, p = 0.039 and adjacent non-neoplastic, p = 0.028). These initial findings suggest that prostate tissue metal levels may differ in smokers with and without recurrence. If these findings are confirmed in larger studies, additional work will be needed to determine whether variations in metal levels are drivers of disease progression or are simply passengers of the disease process.

Cystic adventitial degeneration: ectopic ganglia from adjacent joint capsules.

PubMed

Ortmann, J; Widmer, M K; Gretener, S; Do, D D; Willenberg, T; Daliri, A; Baumgartner, I

2009-11-01

Cystic adventitial degeneration is a rare non-atherosclerotic cause of peripheral arterial occlusive disease, mainly seen in young men without other evidence of vascular disease. Diagnosis will be established by clinical findings and by ultrasound or angiography and can be treated by excision or enucleation of the affected arterial segment or by percutaneous ultrasound-guided aspiration. However, the etiology of adventitial cysts remains unknown. We report a case of cystic adventitial degeneration showing a connection between the joint capsule and the adventitial cyst, supporting the theory that cystic adventitial degeneration may represent ectopic ganglia from adjacent joint capsules.

[Morphological features of the myometrium in connective tissue dysplasia in women with uterine inertia].

PubMed

Konovalov, P V; Mitrofanova, L B; Gorshkov, A N; Ovsyannikov, F A

2015-01-01

to reveal the morphological features of the lower uterine segment myometrium in connective tissue dysplasia (CTD) in women with uterine inertia. Histological, immunohistochemical (with antibodies against collagen types I and III, matrix metalloproteinases 1 and 9 (MMR-1, MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), fibronectin; fibulin-5, connexin-43), electron microscopic, and electron immunocytochemical studies with morphometry of myometrial fragments from 15 parturient women with CTD and uterine inertia (a study group) and those from 10 women without CTD (a control group). The myometrium in CTD exhibited the decreased expression of connextin-43, fibulin-5, TIMP-1, collagens types I and III with collagen type III predominance and the unchanged levels of fibronectin and MMP-1 and MMP-9. Electron microscopy and immunocytochemistry showed fewer intercellular contacts and the dramatically lower expression of connexin-43 than in the control. A set of found myometrial changes in women with uterine inertia is a manifestation of CTD.

Behavioral connectivity among bighorn sheep suggests potential for disease spread

USGS Publications Warehouse

Borg, Nathan J.; Mitchell, Michael S.; Lukacs, Paul M.; Mack, Curt M.; Waits, Lisette P.; Krausman, Paul R.

2017-01-01

Connectivity is important for population persistence and can reduce the potential for inbreeding depression. Connectivity between populations can also facilitate disease transmission; respiratory diseases are one of the most important factors affecting populations of bighorn sheep (Ovis canadensis). The mechanisms of connectivity in populations of bighorn sheep likely have implications for spread of disease, but the behaviors leading to connectivity between bighorn sheep groups are not well understood. From 2007–2012, we radio-collared and monitored 56 bighorn sheep in the Salmon River canyon in central Idaho. We used cluster analysis to define social groups of bighorn sheep and then estimated connectivity between these groups using a multi-state mark-recapture model. Social groups of bighorn sheep were spatially segregated and linearly distributed along the Salmon River canyon. Monthly probabilities of movement between adjacent male and female groups ranged from 0.08 (±0.004 SE) to 0.76 (±0.068) for males and 0.05 (±0.132) to 0.24 (±0.034) for females. Movements of males were extensive and probabilities of movement were considerably higher during the rut. Probabilities of movement for females were typically smaller than those of males and did not change seasonally. Whereas adjacent groups of bighorn sheep along the Salmon River canyon were well connected, connectivity between groups north and south of the Salmon River was limited. The novel application of a multi-state model to a population of bighorn sheep allowed us to estimate the probability of movement between adjacent social groups and approximate the level of connectivity across the population. Our results suggest high movement rates of males during the rut are the most likely to result in transmission of pathogens among both male and female groups. Potential for disease spread among female groups was smaller but non-trivial. Land managers can plan grazing of domestic sheep for spring and summer

Investigating the optimal passive and active vibration controls of adjacent buildings based on performance indices using genetic algorithms

NASA Astrophysics Data System (ADS)

Hadi, Muhammad N. S.; Uz, Mehmet E.

2015-02-01

This study proposes the optimal passive and active damper parameters for achieving the best results in seismic response mitigation of coupled buildings connected to each other by dampers. The optimization to minimize the H2 and H∞ norms in the performance indices is carried out by genetic algorithms (GAs). The final passive and active damper parameters are checked for adjacent buildings connected to each other under El Centro NS 1940 and Kobe NS 1995 excitations. Using real coded GA in H∞ norm, the optimal controller gain is obtained by different combinations of the measurement as the feedback for designing the control force between the buildings. The proposed method is more effective than other metaheuristic methods and more feasible, although the control force increased. The results in the active control system show that the response of adjacent buildings is reduced in an efficient manner.

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

PubMed Central

Castori, Marco

2012-01-01

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

Characterization of human breast cancer tissues by infrared imaging.

PubMed

Verdonck, M; Denayer, A; Delvaux, B; Garaud, S; De Wind, R; Desmedt, C; Sotiriou, C; Willard-Gallo, K; Goormaghtigh, E

2016-01-21

Fourier Transform InfraRed (FTIR) spectroscopy coupled to microscopy (IR imaging) has shown unique advantages in detecting morphological and molecular pathologic alterations in biological tissues. The aim of this study was to evaluate the potential of IR imaging as a diagnostic tool to identify characteristics of breast epithelial cells and the stroma. In this study a total of 19 breast tissue samples were obtained from 13 patients. For 6 of the patients, we also obtained Non-Adjacent Non-Tumor tissue samples. Infrared images were recorded on the main cell/tissue types identified in all breast tissue samples. Unsupervised Principal Component Analyses and supervised Partial Least Square Discriminant Analyses (PLS-DA) were used to discriminate spectra. Leave-one-out cross-validation was used to evaluate the performance of PLS-DA models. Our results show that IR imaging coupled with PLS-DA can efficiently identify the main cell types present in FFPE breast tissue sections, i.e. epithelial cells, lymphocytes, connective tissue, vascular tissue and erythrocytes. A second PLS-DA model could distinguish normal and tumor breast epithelial cells in the breast tissue sections. A patient-specific model reached particularly high sensitivity, specificity and MCC rates. Finally, we showed that the stroma located close or at distance from the tumor exhibits distinct spectral characteristics. In conclusion FTIR imaging combined with computational algorithms could be an accurate, rapid and objective tool to identify/quantify breast epithelial cells and differentiate tumor from normal breast tissue as well as normal from tumor-associated stroma, paving the way to the establishment of a potential complementary tool to ensure safe tumor margins.

Development and evaluation of a connective tissue phantom model for subsurface visualization of cancers requiring wide local excision.

PubMed

Samkoe, Kimberley S; Bates, Brent D; Tselepidakis, Niki N; DSouza, Alisha V; Gunn, Jason R; Ramkumar, Dipak B; Paulsen, Keith D; Pogue, Brian W; Henderson, Eric R

2017-12-01

Wide local excision (WLE) of tumors with negative margins remains a challenge because surgeons cannot directly visualize the mass. Fluorescence-guided surgery (FGS) may improve surgical accuracy; however, conventional methods with direct surface tumor visualization are not immediately applicable, and properties of tissues surrounding the cancer must be considered. We developed a phantom model for sarcoma resection with the near-infrared fluorophore IRDye 800CW and used it to iteratively define the properties of connective tissues that typically surround sarcoma tumors. We then tested the ability of a blinded surgeon to resect fluorescent tumor-simulating inclusions with ∼1-cm margins using predetermined target fluorescence intensities and a Solaris open-air fluorescence imaging system. In connective tissue-simulating phantoms, fluorescence intensity decreased with increasing blood concentration and increased with increasing intralipid concentrations. Fluorescent inclusions could be resolved at ≥1-cm depth in all inclusion concentrations and sizes tested. When inclusion depth was held constant, fluorescence intensity decreased with decreasing volume. Using targeted fluorescence intensities, a blinded surgeon was able to successfully excise inclusions with ∼1-cm margins from fat- and muscle-simulating phantoms with inclusion-to-background contrast ratios as low as 2∶1. Indirect, subsurface FGS is a promising tool for surgical resection of cancers requiring WLE. (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

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

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

PubMed Central

Hagiwara, Shinya; Tsuboi, Hiroto; Hagiya, Chihiro; Yokosawa, Masahiro; Hirota, Tomoya; Ebe, Hiroshi; Takahashi, Hiroyuki; Ogishima, Hiroshi; Asashima, Hiromitsu; Kondo, Yuya; Umeda, Naoto; Suzuki, Takeshi; Hitomi, Shigemi; Matsumoto, Isao; Sumida, Takayuki

2014-01-01

Summary Reported here are 2 patients with connective tissue disease who developed pulmonary nocardiosis. Case 1 involved a 73-year-old man with malignant rheumatoid arthritis treated with prednisolone 25 mg/day. Chest X-rays revealed a pulmonary cavity and bronchoscopy detected Nocardia species. The patient was successfully treated with trimethoprim/sulfamethoxazole. Case 2 involved a 41-year-old woman with systemic lupus erythematosus. The patient received remission induction therapy with 50 mg/day of prednisolone and tacrolimus. Six weeks later, a chest CT scan revealed a pulmonary cavity; bronchoscopy resulted in a diagnosis of pulmonary nocardiosis. The patient had difficulty tolerating trimethoprim/sulfamethoxazole, so she was switched to and successfully treated with imipenem/cilastatin and amikacin. PMID:25343123

Predictive Genes in Adjacent Normal Tissue Are Preferentially Altered by sCNV during Tumorigenesis in Liver Cancer and May Rate Limiting

PubMed Central

Lamb, John R.; Zhang, Chunsheng; Xie, Tao; Wang, Kai; Zhang, Bin; Hao, Ke; Chudin, Eugene; Fraser, Hunter B.; Millstein, Joshua; Ferguson, Mark; Suver, Christine; Ivanovska, Irena; Scott, Martin; Philippar, Ulrike; Bansal, Dimple; Zhang, Zhan; Burchard, Julja; Smith, Ryan; Greenawalt, Danielle; Cleary, Michele; Derry, Jonathan; Loboda, Andrey; Watters, James; Poon, Ronnie T. P.; Fan, Sheung T.; Yeung, Chun; Lee, Nikki P. Y.; Guinney, Justin; Molony, Cliona; Emilsson, Valur; Buser-Doepner, Carolyn; Zhu, Jun; Friend, Stephen; Mao, Mao; Shaw, Peter M.; Dai, Hongyue; Luk, John M.; Schadt, Eric E.

2011-01-01

Background In hepatocellular carcinoma (HCC) genes predictive of survival have been found in both adjacent normal (AN) and tumor (TU) tissues. The relationships between these two sets of predictive genes and the general process of tumorigenesis and disease progression remains unclear. Methodology/Principal Findings Here we have investigated HCC tumorigenesis by comparing gene expression, DNA copy number variation and survival using ∼250 AN and TU samples representing, respectively, the pre-cancer state, and the result of tumorigenesis. Genes that participate in tumorigenesis were defined using a gene-gene correlation meta-analysis procedure that compared AN versus TU tissues. Genes predictive of survival in AN (AN-survival genes) were found to be enriched in the differential gene-gene correlation gene set indicating that they directly participate in the process of tumorigenesis. Additionally the AN-survival genes were mostly not predictive after tumorigenesis in TU tissue and this transition was associated with and could largely be explained by the effect of somatic DNA copy number variation (sCNV) in cis and in trans. The data was consistent with the variance of AN-survival genes being rate-limiting steps in tumorigenesis and this was confirmed using a treatment that promotes HCC tumorigenesis that selectively altered AN-survival genes and genes differentially correlated between AN and TU. Conclusions/Significance This suggests that the process of tumor evolution involves rate-limiting steps related to the background from which the tumor evolved where these were frequently predictive of clinical outcome. Additionally treatments that alter the likelihood of tumorigenesis occurring may act by altering AN-survival genes, suggesting that the process can be manipulated. Further sCNV explains a substantial fraction of tumor specific expression and may therefore be a causal driver of tumor evolution in HCC and perhaps many solid tumor types. PMID:21750698

Laparoscopic Antireflux Surgery in Patients with Connective Tissue Diseases.

PubMed

Menezes, Mariano A; Herbella, Fernando A M; Patti, Marco G

2016-04-01

Different connective tissue diseases (CTDs), such as dermatomyositis, mixed CTD, rheumatoid arthritis, polymyositis, lupus, and Behçet's, may affect the esophagus, impairing its motor function. The muscular atrophy and fibrosis caused by the autoimmune vasculitis and neuronal dysfunction affect the esophageal body and the lower esophageal sphincter, leading to a clinical presentation of dysphagia and gastroesophageal reflux disease (GERD). The belief that the impaired esophageal motility may negatively affect surgical outcome has led to the common recommendation of avoiding laparoscopic antireflux surgery (LARS) for fear of creating or worsening dysphagia. This review focuses on the evaluation of the outcome of LARS in patients with CTD. Specifically, this review shows that the literature on LARS and CTDs is scarce and most studies have a small number of patients and a short follow-up. Furthermore, a subanalysis of the outcome based on the type of CTD or the manometric profile is still elusive. In the setting of these limitations, it appears that results are good and comparable to those of patients with GERD and without a CTD. Morbidity and mortality are insignificant even considering the systemic manifestations of the CTD. LARS should not be denied to patients with CTD and GERD.

Biomaterials for tissue engineering applications.

PubMed

Keane, Timothy J; Badylak, Stephen F

2014-06-01

With advancements in biological and engineering sciences, the definition of an ideal biomaterial has evolved over the past 50 years from a substance that is inert to one that has select bioinductive properties and integrates well with adjacent host tissue. Biomaterials are a fundamental component of tissue engineering, which aims to replace diseased, damaged, or missing tissue with reconstructed functional tissue. Most biomaterials are less than satisfactory for pediatric patients because the scaffold must adapt to the growth and development of the surrounding tissues and organs over time. The pediatric community, therefore, provides a distinct challenge for the tissue engineering community. Copyright © 2014. Published by Elsevier Inc.

Expression analysis of URI/RMP gene in endometrioid adenocarcinoma by tissue microarray immunohistochemistry.

PubMed

Gu, Junxia; Liang, Yuting; Qiao, Longwei; Li, Xiaoyun; Li, Xingang; Lu, Yaojuan; Zheng, Qiping

2013-01-01

Multiple studies have recently demonstrated the oncogenic property of URI (or RMP, a member of the prefoldin family of molecular chaperones) during progression of hepatocellular carcinoma, ovarian cancer, and possibly prostate cancer. Most recently, we have shown that URI/RMP is up-regulated in cervical cancer, another reproductive system tumor beside ovarian and prostate cancers. To investigate if URI/RMP also plays a role in other reproductive system tumors, especially in endometrioid adenocarcinoma, we analyzed URI/RMP expression in a TMA (tissue microarray) containing tissues from 30 cases of endometrioid adenocarcinoma (which covers tumor tissues from Grade I through Grade III) and adjacent endometrium by immunohistochemistry (IHC) and densitometry analysis using image-pro plus 6.0 software. Our results showed that the mean density of URI/RMP expression in cancerous tissue is slightly higher than that of the adjacent endometrial tissue, though not statistically significant (p>0.05). There is no significant difference either between the mean density of Grade III cancerous tissue and that of Grade I and II cancers. Notably, we detected significantly higher signal intensity in cancerous tissue of all 7 Grade III cases than that of their adjacent endometrial tissue (p<0.05), suggesting a correlation of URI/RMP expression with the differentiation and pathological classification of endometrioid adenocarcinoma. Together, our results demonstrate the heterogeneous expression of URI/RMP in endometrioid adenocarcinoma. The higher level of URI/RMP expression in high-grade endometrioid adenocarcinomas compared to tissues of adjacent endometrium or gland suggests a diagnostic and possibly, a prognostic value of URI/RMP in endometrioid adenocarcinoma.

Expression analysis of URI/RMP gene in endometrioid adenocarcinoma by tissue microarray immunohistochemistry

PubMed Central

Gu, Junxia; Liang, Yuting; Qiao, Longwei; Li, Xiaoyun; Li, Xingang; Lu, Yaojuan; Zheng, Qiping

2013-01-01

Multiple studies have recently demonstrated the oncogenic property of URI (or RMP, a member of the prefoldin family of molecular chaperones) during progression of hepatocellular carcinoma, ovarian cancer, and possibly prostate cancer. Most recently, we have shown that URI/RMP is up-regulated in cervical cancer, another reproductive system tumor beside ovarian and prostate cancers. To investigate if URI/RMP also plays a role in other reproductive system tumors, especially in endometrioid adenocarcinoma, we analyzed URI/RMP expression in a TMA (tissue microarray) containing tissues from 30 cases of endometrioid adenocarcinoma (which covers tumor tissues from Grade I through Grade III) and adjacent endometrium by immunohistochemistry (IHC) and densitometry analysis using image-pro plus 6.0 software. Our results showed that the mean density of URI/RMP expression in cancerous tissue is slightly higher than that of the adjacent endometrial tissue, though not statistically significant (p>0.05). There is no significant difference either between the mean density of Grade III cancerous tissue and that of Grade I and II cancers. Notably, we detected significantly higher signal intensity in cancerous tissue of all 7 Grade III cases than that of their adjacent endometrial tissue (p<0.05), suggesting a correlation of URI/RMP expression with the differentiation and pathological classification of endometrioid adenocarcinoma. Together, our results demonstrate the heterogeneous expression of URI/RMP in endometrioid adenocarcinoma. The higher level of URI/RMP expression in high-grade endometrioid adenocarcinomas compared to tissues of adjacent endometrium or gland suggests a diagnostic and possibly, a prognostic value of URI/RMP in endometrioid adenocarcinoma. PMID:24228101

Co-expression networks reveal the tissue-specific regulation of transcription and splicing.

PubMed

Saha, Ashis; Kim, Yungil; Gewirtz, Ariel D H; Jo, Brian; Gao, Chuan; McDowell, Ian C; Engelhardt, Barbara E; Battle, Alexis

2017-11-01

Gene co-expression networks capture biologically important patterns in gene expression data, enabling functional analyses of genes, discovery of biomarkers, and interpretation of genetic variants. Most network analyses to date have been limited to assessing correlation between total gene expression levels in a single tissue or small sets of tissues. Here, we built networks that additionally capture the regulation of relative isoform abundance and splicing, along with tissue-specific connections unique to each of a diverse set of tissues. We used the Genotype-Tissue Expression (GTEx) project v6 RNA sequencing data across 50 tissues and 449 individuals. First, we developed a framework called Transcriptome-Wide Networks (TWNs) for combining total expression and relative isoform levels into a single sparse network, capturing the interplay between the regulation of splicing and transcription. We built TWNs for 16 tissues and found that hubs in these networks were strongly enriched for splicing and RNA binding genes, demonstrating their utility in unraveling regulation of splicing in the human transcriptome. Next, we used a Bayesian biclustering model that identifies network edges unique to a single tissue to reconstruct Tissue-Specific Networks (TSNs) for 26 distinct tissues and 10 groups of related tissues. Finally, we found genetic variants associated with pairs of adjacent nodes in our networks, supporting the estimated network structures and identifying 20 genetic variants with distant regulatory impact on transcription and splicing. Our networks provide an improved understanding of the complex relationships of the human transcriptome across tissues. © 2017 Saha et al.; Published by Cold Spring Harbor Laboratory Press.

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.

Size cues and the adjacency principle.

DOT National Transportation Integrated Search

1963-11-01

The purpose of the present study was to apply the adjacency principle to the perception of relative depth from size cues. In agreement with the adjacency principle, it was found that the size cue between adjacent objects was more effective than the s...

Effects of radiotherapy on uveal melanomas and adjacent tissues

PubMed Central

Groenewald, C; Konstantinidis, L; Damato, B

2013-01-01

Most uveal melanomas are treated with radiotherapy. An adequate understanding of the effects of radiation on the tumour and the healthy ocular tissues is necessary. Ionizing radiation damages cell membranes, organelles, and DNA. Irradiated cells are lysed or undergo apoptosis, necrosis, and senescence. These effects occur in tumour cells and vascular endothelial cells, resulting in tumour shrinkage, ischaemia, infarction, exudation, and fibrosis, which can cause exudative maculopathy, serous retinal detachment, rubeosis, and neovascular glaucoma (ie, ‘toxic tumour syndrome'). Such abnormalities must be distinguished from collateral damage to healthy ocular tissues that receive high doses of radiation, and these include radiation-induced retinopathy, optic neuropathy, choroidopathy, cataract, and scleral necrosis. Radiation retinopathy can be treated effectively with photodynamic therapy, anti-angiogenic agents, and intravitreal steroid injections. In some patients, optic neuropathy may improve with intravitreal steroids or anti-angiogenic agents. Neovascular glaucoma resolves with intra-cameral bevacizumab. Exudative retinal detachment can regress with intra-vitreal steroid injections. Cataract is treated in the usual manner. Scleral necrosis, if severe, may require grafting, possibly using a lamellar flap from the same eye. Depending on the bulk of the residual toxic tumour, treatment can consist of intra-vitreal steroids and/or anti-angiogenic agents, transpupillary thermotherapy or photodynamic therapy to the tumour, or surgical removal of the tumour by endo- or exo-resection. Measures aimed at preventing collateral damage include eccentric placement of ruthenium plaques or iodine seeds and delivery of a notched proton beam. The decision to treat a uveal melanoma with radiotherapy requires the ability to manage iatrogenic side effects and complications. PMID:23196647

Hypericin-mediated selective photomodification of connective tissues

NASA Astrophysics Data System (ADS)

Hovhannisyan, V.; Hovhannisyan, A.; Ghukasyan, V.; Guo, H. W.; Lin, Hung-Ming; Chen, S. J.; Chen, Yang-Fang; Dong, Chen-Yuan

2017-02-01

Hypericin (Hyp) has received attention due to its high phototoxicity against viruses and anti-tumor photoactivity. Using two-photon imaging, we demonstrated that Hyp induced photosensitized modification of collagen fibers in native tissues. Dynamics of photo-processes was monitored by time-lapse multiphoton imaging. We showed that Hyp-mediated processes in collagen tissues may be used for the selective modification of collagen fibers.

Soft tissue remodeling technique as a non-invasive alternative to second implant surgery.

PubMed

Vela, Xavier; Méndez, Víctor; Rodríguez, Xavier; Segalà, Maribel; Gil, Jaime A

2012-01-01

It is currently accepted that success in implant-supported restorations is based not only on osseointegration, but also on achieving the esthetic outcome of natural teeth and healthy soft tissues. The socalled "pink esthetic" has become the main challenge with implant-supported rehabilitations in the anterior area. This is especially difficult in the cases with two adjacent implants. Two components affect the final periimplant gingiva: a correct bone support, and a sufficient quantity and quality of soft tissues. Several papers have emphasized the need to regenerate and preserve the bone after extractions, or after the exposure of the implants to the oral environment. The classical implantation protocol entails entering the working area several times and always involves the surgical manipulation of peri-implant tissues. Careful surgical handling of the soft tissues when exposing the implants and placing the healing abutments (second surgery) helps the clinician to obtain the best possible results, but even so there is a loss of volume of the tissues as they become weaker and more rigid after each procedure. The present study proposes a new protocol that includes the connective tissue graft placement and the soft tissues remodeling technique, which is based on the use of the ovoid pontics. This technique may help to minimize the logical scar reaction after the second surgery and to improve the final emergence profile.

Is the stripping technique a tissue-sparing procedure in large simple ovarian cysts in children?

PubMed

Arena, Francesco; Romeo, Carmelo; Castagnetti, Marco; Scalfari, GianFranco; Cimador, Marcello; Impellizzeri, Pietro; Villari, Daniela; Zimbaro, Fabrizio; DeGrazia, Enrico

2008-07-01

Stripping of the cystic wall is performed by gynecologists to treat large ovarian cysts. Information in the pediatric population is poor. We prospectively evaluated the pathologic specimens of large ovarian cyst to determine whether the stripping technique is a tissue-sparing procedure even in this age. We evaluated 5 patients. Samples were taken from the intermediate part of the cystic wall and from the layer covering the cyst during excision. The presence of ovarian tissue adjacent to the cyst wall, and the morphological features of the surrounding tissue were both evaluated. Pelvic ultrasound follow-up was also performed. Patients' mean age was 4.5 years (7 days to 12 years). All cysts were removed because all were symptomatic. The mean diameter was 86.6 mm (74-100 mm). Cysts were follicular in 2 cases, serous in other two, and endometriotic in 1 case. Adjacent ovarian tissue was present in 1 of 5 specimens and was approximately 1 to 2 mm in thickness. The layer adjacent to the cystic wall always appeared as normal ovarian tissue. Ultrasound scans at follow-up revealed presence of ovarian tissue. The stripping procedure for large ovarian cyst excision allows to spare the adjacent normal ovarian tissue even in pediatric age because ovarian tissue is rarely excised with the cyst wall during the procedure.

Brain connectivity associated with cascading levels of language.

PubMed

Richards, Todd; Nagy, William; Abbott, Robert; Berninger, Virginia

2016-01-01

Typical oral and written language learners (controls) (5 girls, 4 boys) completed fMRI reading judgment tasks (sub-word grapheme-phoneme, word spelling, sentences with and without spelling foils, affixed words, sentences with and without affix foils, and multi-sentence). Analyses identified connectivity within and across adjacent levels (units) of language in reading: from subword to word to syntax in Set I and from word to syntax to multi-sentence in Set II). Typicals were compared to (a) students with dyslexia (6 girls, 10 boys) on the subword and word tasks in Set I related to levels of language impaired in dyslexia, and (b) students with oral and written language learning disability (OWL LD) (3 girls, 2 boys) on the morphology and syntax tasks in Set II, related to levels of language impaired in OWL LD. Results for typical language learners showed that adjacent levels of language in the reading brain share common and unique connectivity. The dyslexia group showed over-connectivity to a greater degree on the imaging tasks related to their levels of language impairments than the OWL LD group who showed under-connectivity to a greater degree than did the dyslexia group on the imaging tasks related to their levels of language impairment. Results for these students in grades 4 to 9 (ages 9 to 14) are discussed in reference to the contribution of patterns of connectivity across levels of language to understanding the nature of persisting dyslexia and dysgraphia despite early intervention.

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

PubMed Central

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

2013-01-01

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

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

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.

Tissue engineering human small-caliber autologous vessels using a xenogenous decellularized connective tissue matrix approach: preclinical comparative biomechanical studies.

PubMed

Heine, Jörg; Schmiedl, Andreas; Cebotari, Serghei; Karck, Matthias; Mertsching, Heike; Haverich, Axel; Kallenbach, Klaus

2011-10-01

Suggesting that bioartificial vascular scaffolds cannot but tissue-engineered vessels can withstand biomechanical stress, we developed in vitro methods for preclinical biological material testings. The aim of the study was to evaluate the influence of revitalization of xenogenous scaffolds on biomechanical stability of tissue-engineered vessels. For measurement of radial distensibility, a salt-solution inflation method was used. The longitudinal tensile strength test (DIN 50145) was applied on bone-shaped specimen: tensile/tear strength (SigmaB/R), elongation at maximum yield stress/rupture (DeltaB/R), and modulus of elasticity were determined of native (NAs; n = 6), decellularized (DAs; n = 6), and decellularized carotid arteries reseeded with human vascular smooth muscle cells and human vascular endothelial cells (RAs; n = 7). Radial distensibility of DAs was significantly lower (113%) than for NAs (135%) (P < 0.001) or RAs (127%) (P = 0.018). At levels of 120 mm Hg and more, decellularized matrices burst (120, 160 [n = 2] and 200 mm Hg). Although RAs withstood levels up to 300 mm Hg, ANOVA revealed a significant difference from NA (P = 0.018). Compared with native vessels (NAs), SigmaB/R values were lower in DAs (44%; 57%) (P = 0.014 and P = 0.002, respectively) and were significantly higher in RAs (71%; 83%) (both P < 0.001). Similarly, DeltaB/R values were much higher in DAs compared with NAs (94%; 88%) (P < 0.001) and RAs (87%; 103%) (P < 0.001), but equivalent in NAs and RAs. Modulus of elasticity (2.6/1.1/3.7 to 16.6 N/mm(2)) of NAs, DAs, RAs was comparable (P = 0.088). Using newly developed in vitro methods for small-caliber vascular graft testing, this study proved that revitalization of decellularized connective tissue scaffolds led to vascular graft stability able to withstand biomechanical stress mimicking the human circulation. This tissue engineering approach provides a sufficiently stable autologized graft. © 2011, Copyright the Authors. Artificial

46 CFR 148.445 - Adjacent spaces.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 5 2011-10-01 2011-10-01 false Adjacent spaces. 148.445 Section 148.445 Shipping COAST... THAT REQUIRE SPECIAL HANDLING Additional Special Requirements § 148.445 Adjacent spaces. When... following requirements must be met: (a) Each space adjacent to a cargo hold must be ventilated by natural...

46 CFR 148.445 - Adjacent spaces.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 5 2014-10-01 2014-10-01 false Adjacent spaces. 148.445 Section 148.445 Shipping COAST... THAT REQUIRE SPECIAL HANDLING Additional Special Requirements § 148.445 Adjacent spaces. When... following requirements must be met: (a) Each space adjacent to a cargo hold must be ventilated by natural...

46 CFR 148.445 - Adjacent spaces.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 5 2013-10-01 2013-10-01 false Adjacent spaces. 148.445 Section 148.445 Shipping COAST... THAT REQUIRE SPECIAL HANDLING Additional Special Requirements § 148.445 Adjacent spaces. When... following requirements must be met: (a) Each space adjacent to a cargo hold must be ventilated by natural...

46 CFR 148.445 - Adjacent spaces.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 5 2012-10-01 2012-10-01 false Adjacent spaces. 148.445 Section 148.445 Shipping COAST... THAT REQUIRE SPECIAL HANDLING Additional Special Requirements § 148.445 Adjacent spaces. When... following requirements must be met: (a) Each space adjacent to a cargo hold must be ventilated by natural...

Growth and maturational changes in dense fibrous connective tissue following 14 days of rhGH supplementation in the dwarf rat

NASA Technical Reports Server (NTRS)

Kyparos, Antonios; Orth, Michael W.; Vailas, Arthur C.; Martinez, Daniel A.

2002-01-01

The purpose of this study was to investigate the impact of recombinant human growth hormone (rhGH) on patella tendon (PT), medial collateral ligament (MCL), and lateral collateral ligament (LCL) on collagen growth and maturational changes in dwarf GH-deficient rats. Twenty male Lewis mutant dwarf rats, 37 days of age, were randomly assigned to Dwarf + rhGH (n = 10) and Dwarf + vehicle (n = 10) groups. The GH group received 1.25 mg rhGH/kg body wt twice daily for 14 days. rhGH administration stimulated dense fibrous connective tissue growth, as demonstrated by significant increases in hydroxyproline specific activity and significant decreases in the non-reducible hydroxylysylpyridinoline (HP) collagen cross-link contents. The increase in the accumulation of newly accreted collagen was 114, 67, and 117% for PT, MCL, and LCL, respectively, in 72 h. These findings suggest that a short course rhGH treatment can affect the rate of new collagen production. However, the maturation of the tendon and ligament tissues decreased 18-25% during the rapid accumulation of de novo collagen. We conclude that acute rhGH administration in a dwarf rat can up-regulate new collagen accretion in dense fibrous connective tissues, while causing a reduction in collagen maturation. Copyright 2002 Elsevier Science Ltd.

Autoantibodies Associated With Connective Tissue Diseases: What Meaning for Clinicians?

PubMed Central

Didier, Kevin; Bolko, Loïs; Giusti, Delphine; Toquet, Segolene; Robbins, Ailsa; Antonicelli, Frank; Servettaz, Amelie

2018-01-01

Connective tissue diseases (CTDs) such as systemic lupus erythematosus, systemic sclerosis, myositis, Sjögren’s syndrome, and rheumatoid arthritis are systemic diseases which are often associated with a challenge in diagnosis. Autoantibodies (AAbs) can be detected in these diseases and help clinicians in their diagnosis. Actually, pathophysiology of these diseases is associated with the presence of antinuclear antibodies. In the last decades, many new antibodies were discovered, but their implication in pathogenesis of CTDs remains unclear. Furthermore, the classification of these AAbs is nowadays misused, as their targets can be localized outside of the nuclear compartment. Interestingly, in most cases, each antibody is associated with a specific phenotype in CTDs and therefore help in better defining either the disease subtypes or diseases activity and outcome. Because of recent progresses in their detection and in the comprehension of their pathogenesis implication in CTD-associated antibodies, clinicians should pay attention to the presence of these different AAbs to improve patient’s management. In this review, we propose to focus on the different phenotypes and features associated with each autoantibody used in clinical practice in those CTDs. PMID:29632529

How are cancer and connective tissue diseases related to sarcoidosis?

PubMed

Chopra, Amit; Judson, Marc A

2015-09-01

Several studies have suggested an association between sarcoidosis and cancer, and between sarcoidosis and connective tissue diseases (CTDs). In this review, we discuss the evidence supporting and refuting these associations. In terms of a cancer risk in sarcoidosis patients, the data are somewhat conflicting but generally show a very small increased risk. The data supporting an association between sarcoidosis and CTD are not as robust as for cancer. However, it appears that scleroderma is the CTD most strongly associated with sarcoidosis. There are several important clinical and research-related implications of the association of sarcoidosis and CTDs. First, rigorous efforts should be made to exclude alternative causes for granulomatous inflammation before establishing a diagnosis of sarcoidosis. Second, the association between sarcoidosis and both cancer and CTDs may yield important insights into the immunopathogenesis of all three diseases. Finally, these data provide insight in answering a common question asked by sarcoidosis patients, 'Am I at an increased risk of developing cancer?' We believe that although there is an increased (relative) risk of cancer in sarcoidosis patients compared with the general population, that increased risk is quite small (low absolute risk).

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

Increased and correlated expression of connective tissue growth factor and transforming growth factor beta 1 in surgically removed periodontal tissues with chronic periodontitis.

PubMed

Mize, T W; Sundararaj, K P; Leite, R S; Huang, Y

2015-06-01

Both gingival tissue destruction and regeneration are associated with chronic periodontitis, although the former overwhelms the latter. Studies have shown that transforming growth factor beta 1 (TGF-β1), a growth factor largely involved in tissue regeneration and remodeling, is upregulated in chronic periodontitis. However, the gingival expression of connective tissue growth factor (CTGF or CCN2), a TGF-β1-upregulated gene, in patients with periodontitis remains undetermined. Although both CTGF/CCN2 and TGF-b1 increase the production of extracellular matrix, they have many different biological functions. Therefore, it is important to delineate the impact of periodontitis on gingival CTGF/CCN2 expression. Periodontal tissue specimens were collected from seven individuals without periodontitis (group 1) and from 14 with periodontitis (group 2). The expression of CTGF and TGFβ1 mRNAs were quantified using real-time PCR. Analysis using the nonparametric Mann-Whitney U-test showed that the levels of expression of both CTGF/CCN2 and TGFβ1 mRNAs were significantly increased in individuals with periodontitis compared with individuals without periodontitis. Furthermore, analysis using a nonparametric correlation (Spearman r) test showed a positive correlation between TGFβ1 and CTGF/CCN2 mRNAs. The gingival expression levels of CTGF/CCN2 and TGFβ1 mRNAs in individuals with periodontitis are upregulated and correlated. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Cytoarchitecture and Cortical Connections of the Anterior Insula and Adjacent Frontal Motor Fields in the Rhesus Monkey

PubMed Central

Morecraft, RJ; Stilwell-Morecraft, KS; Ge, J; Cipolloni, PB; Pandya, DN

2015-01-01

The cytoarchitecture and cortical connections of the ventral motor region are investigated using Nissl, and NeuN staining methods and the fluorescent retrograde tract tracing technique in the rhesus monkey. On the basis of gradual laminar differentiation, it is shown that the ventral motor region stems from the ventral proisocortical area (anterior insula and dorsal Sylvian opercular region). The cytoarchitecture of the ventral motor region is shown to progress in three lines, as we have recently shown for the dorsal motor region. Namely, root (anterior insular and dorsal Sylvian opercular area ProM), belt (ventral premotor cortex) and core (precentral motor cortex) lines. This stepwise architectonic organization is supported by the overall patterns of corticocortical connections. Areas in each line are sequentially interconnected (intralineal connections) and all lines are interconnected (interlinear connections). Moreover, root areas, as well as some of the belt areas of the ventral and dorsal trend are interconnected. The ventral motor region is also connected with the ventral somatosensory areas in a topographic manner. The root and belt areas of ventral motor region are connected with paralimbic, multimodal and prefrontal (outer belt) areas. In contrast, the core area has a comparatively more restricted pattern of corticocortical connections. This architectonic and connectional organization is consistent in part, with the functional organization of the ventral motor region as reported in behavioral and neuroimaging studies which include the mediation of facial expression and emotion, communication, phonic articulation, and language in human. PMID:26496798

Best Merge Region Growing Segmentation with Integrated Non-Adjacent Region Object Aggregation

NASA Technical Reports Server (NTRS)

Tilton, James C.; Tarabalka, Yuliya; Montesano, Paul M.; Gofman, Emanuel

2012-01-01

Best merge region growing normally produces segmentations with closed connected region objects. Recognizing that spectrally similar objects often appear in spatially separate locations, we present an approach for tightly integrating best merge region growing with non-adjacent region object aggregation, which we call Hierarchical Segmentation or HSeg. However, the original implementation of non-adjacent region object aggregation in HSeg required excessive computing time even for moderately sized images because of the required intercomparison of each region with all other regions. This problem was previously addressed by a recursive approximation of HSeg, called RHSeg. In this paper we introduce a refined implementation of non-adjacent region object aggregation in HSeg that reduces the computational requirements of HSeg without resorting to the recursive approximation. In this refinement, HSeg s region inter-comparisons among non-adjacent regions are limited to regions of a dynamically determined minimum size. We show that this refined version of HSeg can process moderately sized images in about the same amount of time as RHSeg incorporating the original HSeg. Nonetheless, RHSeg is still required for processing very large images due to its lower computer memory requirements and amenability to parallel processing. We then note a limitation of RHSeg with the original HSeg for high spatial resolution images, and show how incorporating the refined HSeg into RHSeg overcomes this limitation. The quality of the image segmentations produced by the refined HSeg is then compared with other available best merge segmentation approaches. Finally, we comment on the unique nature of the hierarchical segmentations produced by HSeg.

Magnesium carbonate-containing phosphate binder prevents connective tissue mineralization in Abcc6(-/-) mice-potential for treatment of pseudoxanthoma elasticum.

PubMed

Li, Qiaoli; Larusso, Jennifer; Grand-Pierre, Alix E; Uitto, Jouni

2009-12-01

Pseudoxanthoma elasticum (PXE) is a heritable disorder characterized by ectopic mineralization of connective tissues primarily in the skin, eyes, and the cardiovascular system. PXE is caused by mutations in the ABCC6 gene. While PXE is associated with considerable morbidity and mortality, there is currently no effective or specific treatment. In this study, we tested oral phosphate binders for treatment of a mouse model of PXE which we have developed by targeted ablation of the corresponding mouse gene (Abcc6(-/-)). This "knock-out" (KO) mouse model recapitulates features of PXE and demonstrates mineralization of a number of tissues, including the connective tissue capsule surrounding vibrissae in the muzzle skin which serves as an early biomarker of the mineralization process. Treatment of these mice with a magnesium carbonate-enriched diet (magnesium concentration being 5-fold higher than in the control diet) completely prevented mineralization of the vibrissae up to 6 months of age, as demonstrated by computerized morphometric analysis of histopathology as well as by calcium and phosphate chemical assays. The magnesium carbonate-enriched diet also prevented the progression of mineralization when the mice were placed on that experimental diet at 3 months of age and followed up to 6 months of age. Treatment with magnesium carbonate was associated with a slight increase in the serum concentration of magnesium, with no effect on serum calcium and phosphorus levels. In contrast, concentration of calcium in the urine was increased over 10-fold while the concentration of phosphorus was markedly decreased, being essentially undetectable after long-term (> 4 month) treatment. No significant changes were noted in the serum parathyroid hormone levels. Computerized axial tomography scan of bones in mice placed on magnesium carbonate-enriched diet showed no differences in the bone density compared to mice on the control diet, and chemical assays showed a small increase in

Evaluation of an automated connective tissue disease screening assay in Korean patients with systemic rheumatic diseases

PubMed Central

Jeong, Seri; Yang, Heeyoung; Hwang, Hyunyong

2017-01-01

This study aimed to evaluate the diagnostic utilities of the automated connective tissues disease screening assay, CTD screen, in patients with systemic rheumatic diseases. A total of 1093 serum samples were assayed using CTD screen and indirect immunofluorescent (IIF) methods. Among them, 162 were diagnosed with systemic rheumatic disease, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCT). The remaining 931 with non-systemic rheumatic disease were assigned to the control group. The median ratios of CTD screen tests were significantly higher in the systemic rheumatic disease group than in the control group. The positive likelihood ratios of the CTD screen were higher than those of IIF in patients with total rheumatic diseases (4.1 vs. 1.6), including SLE (24.3 vs. 10.7). The areas under the receiver operating characteristic curves (ROC-AUCs) of the CTD screen for discriminating total rheumatic diseases, RA, SLE, and MCT from controls were 0.68, 0.56, 0.92 and 0.80, respectively. The ROC-AUCs of the combinations with IIF were significantly higher in patients with total rheumatic diseases (0.72) and MCT (0.85) than in those of the CTD screen alone. Multivariate analysis indicated that both the CTD screen and IIF were independent variables for predicting systemic rheumatic disease. CTD screen alone and in combination with IIF were a valuable diagnostic tool for predicting systemic rheumatic diseases, particularly for SLE. PMID:28273146

Evaluation of an automated connective tissue disease screening assay in Korean patients with systemic rheumatic diseases.

PubMed

Jeong, Seri; Yang, Heeyoung; Hwang, Hyunyong

2017-01-01

This study aimed to evaluate the diagnostic utilities of the automated connective tissues disease screening assay, CTD screen, in patients with systemic rheumatic diseases. A total of 1093 serum samples were assayed using CTD screen and indirect immunofluorescent (IIF) methods. Among them, 162 were diagnosed with systemic rheumatic disease, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCT). The remaining 931 with non-systemic rheumatic disease were assigned to the control group. The median ratios of CTD screen tests were significantly higher in the systemic rheumatic disease group than in the control group. The positive likelihood ratios of the CTD screen were higher than those of IIF in patients with total rheumatic diseases (4.1 vs. 1.6), including SLE (24.3 vs. 10.7). The areas under the receiver operating characteristic curves (ROC-AUCs) of the CTD screen for discriminating total rheumatic diseases, RA, SLE, and MCT from controls were 0.68, 0.56, 0.92 and 0.80, respectively. The ROC-AUCs of the combinations with IIF were significantly higher in patients with total rheumatic diseases (0.72) and MCT (0.85) than in those of the CTD screen alone. Multivariate analysis indicated that both the CTD screen and IIF were independent variables for predicting systemic rheumatic disease. CTD screen alone and in combination with IIF were a valuable diagnostic tool for predicting systemic rheumatic diseases, particularly for SLE.

Cardiovascular magnetic resonance imaging: clinical implications in the evaluation of connective tissue diseases

PubMed Central

Mavrogeni, Sophie; Markousis-Mavrogenis, George; Koutsogeorgopoulou, Loukia; Kolovou, Genovefa

2017-01-01

Cardiovascular magnetic resonance imaging is a recently developed noninvasive, nonradiating, operator-independent technique that has been successfully used for the evaluation of congenital heart disease, valvular and pericardial diseases, iron overload, cardiomyopathies, great and coronary vessel diseases, cardiac inflammation, stress–rest myocardial perfusion, and fibrosis. Rheumatoid arthritis and other spondyloarthropathies, systemic lupus erythematosus, inflammatory myopathies, mixed connective tissue diseases (CTDs), systemic sclerosis, vasculitis, and sarcoidosis are among CTDs with serious cardiovascular involvement; this is due to multiple causative factors such as myopericarditis, micro/macrovascular disease, coronary artery disease, myocardial fibrosis, pulmonary hypertension, and finally heart failure. The complicated pathophysiology and the high cardiovascular morbidity and mortality of CTDs demand a versatile, noninvasive, nonradiative diagnostic tool for early cardiovascular diagnosis, risk stratification, and treatment follow-up. Cardiovascular magnetic resonance imaging can detect early silent cardiovascular lesions, assess disease acuteness, and reliably evaluate the effect of both cardiac and rheumatic medication in the cardiovascular system, due to its capability to perform tissue characterization and its high spatial resolution. However, until now, high cost; lack of interaction between cardiologists, radiologists, and rheumatologists; lack of availability; and lack of experts in the field have limited its wider adoption in the clinical practice. PMID:28546762

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

PubMed Central

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

2009-01-01

Extensive gingival recessions associated with cervical abrasions are common among the population. Several different surgical and/or restorative therapies have been proposed to correct these lesions. This manuscript reports the treatment of multiple gingival recessions associated to cervical abrasions. The procedure involved the utilization of subepithelial connective tissue graft (SCTG) combined with coronally advanced flap onto a previously restored root surface. At the postoperative follow-up visits, the success of the restorative/surgical approach was confirmed by the absence of bleeding to probing and periodontal pockets as well as presence of gingival tissue with normal color, texture and contouring. After 18 months of follow-up, the clinical conditions are stable with satisfactory root coverage and periodontal health. An excellent esthetical outcome was achieved and the patient is satisfied with case resolution. PMID:19826605

Collecting lymphatic vessel permeability facilitates adipose tissue inflammation and distribution of antigen to lymph node-homing adipose tissue dendritic cells.

PubMed

Kuan, Emma L; Ivanov, Stoyan; Bridenbaugh, Eric A; Victora, Gabriel; Wang, Wei; Childs, Ed W; Platt, Andrew M; Jakubzick, Claudia V; Mason, Robert J; Gashev, Anatoliy A; Nussenzweig, Michel; Swartz, Melody A; Dustin, Michael L; Zawieja, David C; Randolph, Gwendalyn J

2015-06-01

Collecting lymphatic vessels (CLVs), surrounded by fat and endowed with contractile muscle and valves, transport lymph from tissues after it is absorbed into lymphatic capillaries. CLVs are not known to participate in immune responses. In this study, we observed that the inherent permeability of CLVs allowed broad distribution of lymph components within surrounding fat for uptake by adjacent macrophages and dendritic cells (DCs) that actively interacted with CLVs. Endocytosis of lymph-derived Ags by these cells supported recall T cell responses in the fat and also generated Ag-bearing DCs for emigration into adjacent lymph nodes (LNs). Enhanced recruitment of DCs to inflammation-reactive LNs significantly relied on adipose tissue DCs to maintain sufficient numbers of Ag-bearing DCs as the LN expanded. Thus, CLVs coordinate inflammation and immunity within adipose depots and foster the generation of an unexpected pool of APCs for Ag transport into the adjacent LN. Copyright © 2015 by The American Association of Immunologists, Inc.

Exercise and Regulation of Bone and Collagen Tissue Biology.

PubMed

Kjaer, Michael; Jørgensen, Niklas Rye; Heinemeier, Katja; Magnusson, S Peter

2015-01-01

The musculoskeletal system and its connective tissue include the intramuscular connective tissue, the myotendinous junction, the tendon, the joints with their cartilage and ligaments, and the bone; they all together play a crucial role in maintaining the architecture of the skeletal muscle, ensuring force transmission, storing energy, protecting joint surface and stability, and ensuring the transfer of muscular forces into resulting limb movement. The musculoskeletal connective tissue structure is relatively stable, but mechanical loading and subsequent mechanotransduction and molecular anabolic signaling can result in some adaptation of the connective tissue, its size, its strength, and its mechanical properties, whereby it can improve its capacity by 5-20% with regular physical activity. For several of the mechanically loaded connective tissues, only limited information regarding molecular and cellular signaling pathways and their adaptation to exercise is available. In contrast to tissue responses with exercise, lack of mechanical tissue loading through inactivity or immobilization of the human body will result in a dramatic loss of connective tissue content, structure, and tolerable load within weeks, to a degree (30-40%) that mimics that of contractile skeletal musculature. This illustrates the importance of regular mechanical load in order to preserve the stabilizing role of the connective tissue for the overall function of the musculoskeletal system in both daily activity and exercise. © 2015 Elsevier Inc. All rights reserved.

Adjacent slice prostate cancer prediction to inform MALDI imaging biomarker analysis

NASA Astrophysics Data System (ADS)

Chuang, Shao-Hui; Sun, Xiaoyan; Cazares, Lisa; Nyalwidhe, Julius; Troyer, Dean; Semmes, O. John; Li, Jiang; McKenzie, Frederic D.

2010-03-01

Prostate cancer is the second most common type of cancer among men in US [1]. Traditionally, prostate cancer diagnosis is made by the analysis of prostate-specific antigen (PSA) levels and histopathological images of biopsy samples under microscopes. Proteomic biomarkers can improve upon these methods. MALDI molecular spectra imaging is used to visualize protein/peptide concentrations across biopsy samples to search for biomarker candidates. Unfortunately, traditional processing methods require histopathological examination on one slice of a biopsy sample while the adjacent slice is subjected to the tissue destroying desorption and ionization processes of MALDI. The highest confidence tumor regions gained from the histopathological analysis are then mapped to the MALDI spectra data to estimate the regions for biomarker identification from the MALDI imaging. This paper describes a process to provide a significantly better estimate of the cancer tumor to be mapped onto the MALDI imaging spectra coordinates using the high confidence region to predict the true area of the tumor on the adjacent MALDI imaged slice.

Healing of localized gingival recessions treated with coronally advanced flap alone or combined with either a resorbable collagen matrix or subepithelial connective tissue graft. A preclinical study.