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Sample records for increasing connective tissue

  1. [Connective tissue dysplasia].

    PubMed

    Piantkovskiĭ, A S

    2012-01-01

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

  2. Undifferentiated Connective Tissue Disease

    MedlinePlus

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

  3. Modified connective tissue punch technique to increase the vestibular/buccal keratinized tissue on flapless implant surgery: a case series.

    PubMed

    Andreasi Bassi, M; Andrisani, C; Lopez, M A; Gaudio, R M; Lombardo, L; Lauritano, D

    2016-01-01

    The aim of this article is to show a simple and predictable technique to enhance both the vestibular/buccal (V/B) gingival thickness (GT) and keratinized tissue width (KTW) improving the soft-tissue profile after flapless implant placement. The technique proposed was named Modified Connective Tissue Punch (MCTP). Fourteen patients (6 men and 8 women) aged between 35 and 69 years (mean value 48.07±13.023 years) were enrolled in this case series. Seventeen implant sites were submitted to flapless procedure. The connective punch (CP) was harvested with a motor-driven circular tissue punch and then a full-split dissection was executed, in order to create a deep pouch, beyond the mucogingival junction, on the V/B side. In this recipient site the CP was placed. The normal flapless surgical protocol was used; implants were inserted and covered with transgingival healing cap screws. GT and KTW were measured: both immediately before and after surgery; at the time of the prosthetic finalization (3-4months, respectively, for mandible and maxilla); 1 year post surgery follow-up. GT was measured at 1 mm, 2 mm and 5 mm on the V/B side, from the outline of the punch. Both KTW and GT at 1 and 2 mm can be effectively increased, while no significant effects for GT at 5 mm can be expected from this technique. Furthermore, the mean values of KTW and GT at 1 mm and 2 mm show significant increases at 3-4 months post-operative, while no further significant increments are shown at 1 year post-operative follow-up. The Authors recommend the use of the MCTP technique to reduce the number of aesthetic complications and soft tissue defects in flapless implant surgery. Longer follow-ups are needed to evaluate the stability of peri-implant tissues over time. PMID:27469545

  4. Modified connective tissue punch technique to increase the vestibular/buccal keratinized tissue on flapless implant surgery: a case series.

    PubMed

    Andreasi Bassi, M; Andrisani, C; Lopez, M A; Gaudio, R M; Lombardo, L; Lauritano, D

    2016-01-01

    The aim of this article is to show a simple and predictable technique to enhance both the vestibular/buccal (V/B) gingival thickness (GT) and keratinized tissue width (KTW) improving the soft-tissue profile after flapless implant placement. The technique proposed was named Modified Connective Tissue Punch (MCTP). Fourteen patients (6 men and 8 women) aged between 35 and 69 years (mean value 48.07±13.023 years) were enrolled in this case series. Seventeen implant sites were submitted to flapless procedure. The connective punch (CP) was harvested with a motor-driven circular tissue punch and then a full-split dissection was executed, in order to create a deep pouch, beyond the mucogingival junction, on the V/B side. In this recipient site the CP was placed. The normal flapless surgical protocol was used; implants were inserted and covered with transgingival healing cap screws. GT and KTW were measured: both immediately before and after surgery; at the time of the prosthetic finalization (3-4months, respectively, for mandible and maxilla); 1 year post surgery follow-up. GT was measured at 1 mm, 2 mm and 5 mm on the V/B side, from the outline of the punch. Both KTW and GT at 1 and 2 mm can be effectively increased, while no significant effects for GT at 5 mm can be expected from this technique. Furthermore, the mean values of KTW and GT at 1 mm and 2 mm show significant increases at 3-4 months post-operative, while no further significant increments are shown at 1 year post-operative follow-up. The Authors recommend the use of the MCTP technique to reduce the number of aesthetic complications and soft tissue defects in flapless implant surgery. Longer follow-ups are needed to evaluate the stability of peri-implant tissues over time.

  5. Could aging human skin use a connective tissue growth factor boost to increase collagen content?

    PubMed

    Oliver, Noelynn; Sternlicht, Mark; Gerritsen, Karin; Goldschmeding, Roel

    2010-02-01

    The roles of connective tissue growth factor (CTGF) and transforming growth factor-beta (TGF-beta), both well-known collagen production stimulators, were examined in skin aging. Aged skin and fibroblasts exhibited a coordinate decrease in CTGF, TGF-beta, and type I procollagen expression and content. CTGF knockdown and TGF-beta blockade in normal dermal fibroblasts reduced procollagen expression, whereas overexpressing CTGF increased procollagen by a TGF-beta/Smad signaling-dependent mechanism without involving Smad2/3.

  6. Connective Tissue Disorders

    MedlinePlus

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

  7. [Connective tissue and inflammation].

    PubMed

    Jakab, Lajos

    2014-03-23

    The author summarizes the structure of the connective tissues, the increasing motion of the constituents, which determine the role in establishing the structure and function of that. The structure and function of the connective tissue are related to each other in the resting as well as inflammatory states. It is emphasized that cellular events in the connective tissue are part of the defence of the organism, the localisation of the damage and, if possible, the maintenance of restitutio ad integrum. The organism responds to damage with inflammation, the non specific immune response, as well as specific, adaptive immunity. These processes are located in the connective tissue. Sterile and pathogenic inflammation are relatively similar processes, but inevitable differences are present, too. Sialic acids and glycoproteins containing sialic acids have important roles, and the role of Siglecs is also highlighted. Also, similarities and differences in damages caused by pathogens and sterile agents are briefly summarized. In addition, the roles of adhesion molecules linked to each other, and the whole event of inflammatory processes are presented. When considering practical consequences it is stressed that the structure (building up) of the organism and the defending function of inflammation both have fundamental importance. Inflammation has a crucial role in maintaining the integrity and the unimpaired somato-psychological state of the organism. Thus, inflammation serves as a tool of organism identical with the natural immune response, inseparably connected with the specific, adaptive immune response. The main events of the inflammatory processes take place in the connective tissue.

  8. 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

  9. Repetitive differential finger motion increases shear strain between the flexor tendon and subsynovial connective tissue.

    PubMed

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

    2013-10-01

    Non-inflammatory fibrosis and thickening of the subsynovial connective tissue (SSCT) are characteristic in carpal tunnel syndrome (CTS) patients. These pathological changes have been linked to repetitive hand tasks that create shear forces between the flexor tendons and SSCT. We measured the relative motion of the flexor digitorum superficialis tendon and SSCT during two repetitive finger tasks using color Doppler ultrasound. Twelve participants performed flexion-extension cycles for 30 min with the long finger alone (differential movement) and with all four fingers together (concurrent movement). Shear strain index (SSI, a relative measure of excursion in flexion and extension) and maximum velocity ratio (MVR, the ratio of SSCT versus tendon during flexion and extension) were used to represent shear. A linear effect of exertion time was significant and corresponded with larger tendon shear in differential motion. The flexion SSI increased 20.4% from the first to the 30th minute, while MVR decreased 8.9% in flexion and 8.7% in extension. No significant changes were found during concurrent motion. These results suggest that exposure to repetitive differential finger tasks may increase the risk of shear injury in the carpal tunnel.

  10. Connective Tissue Ulcers

    PubMed Central

    Dabiri, Ganary; Falanga, Vincent

    2013-01-01

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

  11. Radiotherapy in patients with connective tissue diseases.

    PubMed

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

    2016-03-01

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

  12. Mixed connective tissue disease.

    PubMed

    Gunnarsson, Ragnar; Hetlevik, Siri Opsahl; Lilleby, Vibke; Molberg, Øyvind

    2016-02-01

    The concept of mixed connective tissue disease (MCTD) as a separate connective tissue disease (CTD) has persisted for more than four decades. High titers of antibodies targeting the U1 small nuclear ribonucleoprotein particle (U1 snRNP) in peripheral blood are a sine qua non for the diagnosis of MCTD, in addition to distinct clinical features including Raynaud's phenomenon (RP), "puffy hands," arthritis, myositis, pleuritis, pericarditis, interstitial lung disease (ILD), and pulmonary hypertension (PH). Recently, population-based epidemiology data from Norway estimated the point prevalence of adult-onset MCTD to be 3.8 per 100,000 and the mean annual incidence to be 2.1 per million per year, supporting the notion that MCTD is the least common CTD. Little is known about the etiology of MCTD, but recent genetic studies have confirmed that MCTD is a strongly HLA (​human leukocyte antigen)-linked disease, as the HLA profiles of MCTD differ distinctly from the corresponding profiles of ethnically matched healthy controls and other CTDs. In the first section of this review, we provide an update on the clinical, immunological, and genetic features of MCTD and discuss the relationship between MCTD and the other CTDs. Then we proceed to discuss the recent advances in therapy and our current understanding of prognosis and prognostic factors, especially those that are associated with the more serious pulmonary and cardiovascular complications of the disease. In the final section, we discuss some of the key, unresolved questions related to anti-RNP-associated diseases and indicate how these questions may be approached in future studies. PMID:27421219

  13. [Muscles and connective tissue: histology].

    PubMed

    Delage, J-P

    2012-10-01

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

  14. [Connective tissue and prolapse genesis].

    PubMed

    Tremollieres, F

    2010-06-01

    The pathophysiology of pelvic floor disorders still remains not well understood. Increasing age as well as vaginal multiparity are the main commonly accepted factors. The hypothesis of a defect of connective tissues of the pelvic floor with aging due to collagen deficiency and/or elastic fiber degradation is often highlighted. The issue of a potential protective role of HRT is also discussed although the recent results from the WHI would suggest a negative impact of HRT on urinary incontinence, especially when HRT is initiated in elderly women, far from the menopause. Nevertheless, environmental factors cannot explain the full pathogenesis of pelvic organ prolapse (POP) and the contribution of genetic factors to the development of pelvic floor disorders is widely recognized. Support for a genetic influence on POP derives from reports suggesting that heritability is a strong contributing factor and a familial history of POP is considered as a classical risk factor. However, the characterization of the underlying molecular mechanisms remains limited, since POP may be considered the end result of a multifactorial process leading to destruction of vaginal wall connective tissue. Experimental studies in mice with null mutations in the genes encoding different putative factors involved in elastic fibers remodeling and homeostasis are crucial in the understanding of the pathogenesis of POP. Mice with null mutation in the gene encoding lysyl oxidase-like 1 (LOXL1) or fibulin-5, demonstrate signs of elastinopathy including the development of a POP in the postpartum. Likewise, homeobox genes such as HOXA11, which are essential in the embryonic development of the urogenital tract might also be involved in the pathogenesis of POP. The better understanding of the underlying determinants of pelvic floor disorders with a special focus on genetic factors may offer new therapeutic strategies, in addition to or replacement of surgical procedures.

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

    PubMed

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

    2014-01-01

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

  16. Increased Expression of Connective Tissue Growth Factor (CTGF) in Multiple Organs After Exposure of Non-Human Primates (NHP) to Lethal Doses of Radiation.

    PubMed

    Zhang, Pei; Cui, Wanchang; Hankey, Kim G; Gibbs, Allison M; Smith, Cassandra P; Taylor-Howell, Cheryl; Kearney, Sean R; MacVittie, Thomas J

    2015-11-01

    Exposure to sufficiently high doses of ionizing radiation is known to cause fibrosis in many different organs and tissues. Connective tissue growth factor (CTGF/CCN2), a member of the CCN family of matricellular proteins, plays an important role in the development of fibrosis in multiple organs. The aim of the present study was to quantify the gene and protein expression of CTGF in a variety of organs from non-human primates (NHP) that were previously exposed to potentially lethal doses of radiation. Tissues from non-irradiated NHP and NHP exposed to whole thoracic lung irradiation (WTLI) or partial-body irradiation with 5% bone marrow sparing (PBI/BM5) were examined by real-time quantitative reverse transcription PCR, western blot, and immunohistochemistry. Expression of CTGF was elevated in the lung tissues of NHP exposed to WTLI relative to the lung tissues of the non-irradiated NHP. Increased expression of CTGF was also observed in multiple organs from NHP exposed to PBI/BM5 compared to non-irradiated NHP; these included the lung, kidney, spleen, thymus, and liver. These irradiated organs also exhibited histological evidence of increased collagen deposition compared to the control tissues. There was significant correlation of CTGF expression with collagen deposition in the lung and spleen of NHP exposed to PBI/BM5. Significant correlations were observed between spleen and multiple organs on CTGF expression and collagen deposition, respectively, suggesting possible crosstalk between spleen and other organs. These data suggest that CTGF levels are increased in multiple organs after radiation exposure and that inflammatory cell infiltration may contribute to the elevated levels of CTGF in multiple organs.

  17. Transforming growth factor-β (TGF-β) expression is increased in the subsynovial connective tissue in a rabbit model of carpal tunnel syndrome.

    PubMed

    Chikenji, Takako; Gingery, Anne; Zhao, Chunfeng; Vanhees, Matthias; Moriya, Tamami; Reisdorf, Ramona; An, Kai-Nan; Amadio, Peter C

    2014-01-01

    Carpal tunnel syndrome (CTS) is an idiopathic disease that results from increased fibrosis of the subsynovial connective tissue (SSCT). A recent study found overexpression of both transforming growth factor-β (TGF-β) and connective tissue growth factor (CTGF) in the SSCT of CTS patients. This study investigated TGF-β and CTGF expression in a rabbit model of CTS, in which SSCT fibrosis is induced by a surgical injury. Levels of TGF-β1 and CTGF at 6, 12, 24 weeks after injury were determined by immunohistochemistry A significant increase in TGF-β1 and a concomitant significant increase in CTGF were found at 6 weeks, in addition to higher cell density compared to normal (all p<0.05), Interestingly, CTGF expression was reduced at 12 and 24 weeks, suggesting that an initial insult results in a time limited response. We conclude that this rabbit model mimics the fibrosis found in human CTS, and may be useful to study pathogenetic mechanisms of CTS in vivo.

  18. Hematopoietic stem cell origin of connective tissues.

    PubMed

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

    2010-07-01

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

  19. Stretching Impacts Inflammation Resolution in Connective Tissue.

    PubMed

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

    2016-07-01

    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 min twice daily reduced inflammation and improved pain, 2 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 versus no stretch for 48 h, 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.

  20. Stretching Impacts Inflammation Resolution in Connective Tissue.

    PubMed

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

    2016-07-01

    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 min twice daily reduced inflammation and improved pain, 2 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 versus no stretch for 48 h, 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

  1. [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.

  2. [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. PMID:27421127

  3. TGF-β1, in association with the increased expression of connective tissue growth factor, induce the hypertrophy of the ligamentum flavum through the p38 MAPK pathway

    PubMed Central

    Cao, Yan-Lin; Duan, Yang; Zhu, Li-Xin; Zhan, Ye-Nan; Min, Shao-Xiong; Jin, An-Min

    2016-01-01

    Hypertrophy of the ligamentum flavum (LF) is one of the key pathomechanisms of lumbar spinal stenosis (LSS). Transforming growth factor (TGF)-β1 is abundantly expressed in hypertrophied degenerative LF tissues from LSS. However, the molecular mechanisms underling the association between TGF-β1 and LF hypertrophy have not yet been fully elucidated. In this study, we investigated the important role of the mitogen-activated protein kinase (MAPK) pathway in the pathogenesis of LSS by analyzing the expression of connective tissue growth factor (CTGF) and extracellular matrix (ECM) components (collagen I and collagen III) in TGF-β1-treated LF cells. Cell growth assay revealed that TGF-β1, in association with CTGF, enhanced the the proliferation of LF cells, and we found that TGF-β1 also elevated CTGF expression and subsequently enhanced the mRNA expression of collagen I and collagen III. The increased mRNA expression levels of CTGF, collagen I and collagen III were abolished by p38 inhibitors. Both immunofluorescence imaging and western blot analysis of p38 and p-p38 revealed the increased expression and phosphorylation of p38. Silencing the expression of p38 by siRNA in LF cells decreased the protein expression of p38, p-p38 and CTGF, as well as the mRNA expression of CTGF, collagen I and collagen III. Taken together, our findings indicate that TGF-β1, in association with the increased expression of CTGF, contribute to the homeostasis of the ECM and to the hypertrophy of LF through the p38 MAPK pathway. PMID:27279555

  4. Connective tissue abnormalities in MRL/1 mice.

    PubMed Central

    Edwards, J C; Cooke, A; Moore, A R; Collins, C; Hay, F; Willoughby, D A

    1986-01-01

    Pathological changes in the connective tissue of the limbs of MRL/1 mice are described. Focal infiltrates of polymorphs or large mononuclear cells, or both, were seen both in synovial lining and subcutaneous tissue. Infiltrates were associated with vasculitis in some cases. Deposits of amorphous material were seen in and around joints and in foot pads. The material was more particulate and refractile than typical 'fibrinoid' and showed a positive Feulgen reaction. It was not surrounded by palisading cells and when seen in synovial tissue was not usually associated with changes in synovial lining cells. No obvious difference was seen between intra-articular and extra-articular lesions. Lesions in subcutaneous tissue occurred exclusively in the foot pads. Lymphocyte infiltration was not prominent at any site and no follicle formation was seen. Of two colonies studied, only one showed a significant increase in lining cell numbers in synovial tissue. Exercised animals had a similar distribution and severity of disease to those of matched controls. All lesions described were distinguishable from non-specific inflammatory lesions in normal control mice and MRL/++ mice on assessment of unmarked sections. The relation between these connective tissue lesions and the changes found in human chronic synovitis is discussed. Images PMID:3729576

  5. The Genetics of Soft Connective Tissue Disorders.

    PubMed

    Vanakker, Olivier; Callewaert, Bert; Malfait, Fransiska; Coucke, Paul

    2015-01-01

    Over the last few years, the field of hereditary connective tissue disorders has changed tremendously. This review highlights exciting insights into three prototypic disorders affecting the soft connective tissue: Ehlers-Danlos syndrome, pseudoxanthoma elasticum, and cutis laxa. For each of these disorders, the identification and characterization of several novel but related conditions or subtypes have widened the phenotypic spectrum. In parallel, the vast underlying molecular network connecting these phenotypes is progressively being uncovered. Identification and characterization (both clinical and molecular) of new phenotypes within the connective tissue disorder spectrum are often key to further unraveling the pathways involved in connective tissue biology and delineating the clinical spectrum and pathophysiology of the disorders. Although difficult challenges remain, recent findings have expanded our pathophysiological understanding and may lead to targeted therapies in the near future. PMID:26002060

  6. Strain hardening of fascia: static stretching of dense fibrous connective tissues can induce a temporary stiffness increase accompanied by enhanced matrix hydration.

    PubMed

    Schleip, Robert; Duerselen, Lutz; Vleeming, Andry; Naylor, Ian L; Lehmann-Horn, Frank; Zorn, Adjo; Jaeger, Heike; Klingler, Werner

    2012-01-01

    This study examined a potential cellular basis for strain hardening of fascial tissues: an increase in stiffness induced by stretch and subsequent rest. Mice lumbodorsal fascia were isometrically stretched for 15 min followed by 30 min rest (n=16). An increase in stiffness was observed in the majority of samples, including the nonviable control samples. Investigations with porcine lumbar fascia explored hydration changes as an explanation (n=24). Subject to similar loading procedures, tissues showed decreases in fluid content immediately post-stretch and increases during rest phases. When allowed sufficient resting time, a super-compensation phenomenon was observed, characterised by matrix hydration higher than initial levels and increases in tissue stiffness. Therefore, fascial strain hardening does not seem to rely on cellular contraction, but rather on this super-compensation. Given a comparable occurrence of this behaviour in vivo, clinical application of routines for injury prevention merit exploration. PMID:22196433

  7. Undifferentiated connective tissue disease with pulmonary involvement.

    PubMed

    Arjun, P; Ameer, K A; Sasikumar, S; Rajalakshmi, A; Hari, T A; Thomas, Mathew

    2011-03-01

    Pulmonary involvement in collagen vascular diseases is extremely common. It is usually seen in the well described dyscollagenoses and in mixed connective tissue diseases (MCTD). However, there is a lesser known entity called Undifferentiated Connective Tissue Disease (UCTD) which can also involve the lung. We herein present a case of a young man who was detected to have lung involvement secondary to UCTD. PMID:21751630

  8. Epidemiology of organic solvents and connective tissue disease

    PubMed Central

    Garabrant, David H; Dumas, Constantine

    2000-01-01

    Case reports suggest that solvents are associated with various connective tissue diseases (systemic sclerosis, scleroderma, undifferentiated connective tissue disease, systemic lupus erythematosis, and rheumatoid arthritis), particularly systemic sclerosis. A small number of epidemiological studies have shown statistically significant but weak associations between solvent exposure, systemic sclerosis, and undifferentiated connective tissue disease. However, the interpretation of these positive findings is tempered by a lack of replication, an inability to specify which solvents convey risk, and an absence of increasing risk with increasing exposure. Existing studies, on aggregate, do not show conclusively that solvents (either as a group of chemicals or individual chemicals) are causally associated with any connective tissue disease. Further investigations should be carried out to replicate the positive existing findings and to specify the solvents and circumstances of exposure that carry risk. PMID:11094414

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

    PubMed

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

    2015-06-01

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

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

    PubMed Central

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

    2015-01-01

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

  11. Connective tissue diseases, multimorbidity and the ageing lung.

    PubMed

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

    2016-05-01

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

  12. Chondroitin sulphate inhibits connective tissue mast cells

    PubMed Central

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

    2000-01-01

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

  13. 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.

  14. Microgravity Stress: Bone and Connective Tissue.

    PubMed

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

    2016-04-01

    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. PMID:27065165

  15. Fibroblast cytoskeletal remodeling contributes to connective tissue tension.

    PubMed

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

    2011-05-01

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

  16. FIBROBLAST CYTOSKELETAL REMODELING CONTRIBUTES TO CONNECTIVE TISSUE TENSION

    PubMed Central

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

    2011-01-01

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

  17. Undifferentiated Connective Tissue Disease, Mixed Connective Tissue Disease, and Overlap Syndromes in Rheumatology.

    PubMed

    Pepmueller, Peri Hickman

    2016-01-01

    Autoimmune diseases often have overlapping symptoms and laboratory somewhat unfamiliar to the non-rheumatologist. Characteristic signs, symptoms, and autoantibodies define specific connective tissue diseases. Some patients have some characteristic symptoms, but cannot be definitively classified. Still other patients meet criteria for more than one specific connective tissue disease. These patients can be confusing with regard to diagnosis and prognosis. Clarification of each patient's condition can lead to improved patient care.

  18. Connective tissue: Vascular and hematological (blood) support

    PubMed Central

    Calvino, Nick

    2003-01-01

    Abstract Connective Tissue (CT) is a ubiquitous component of all major tissues and structures of the body (50% of all body protein is CT), including that of the blood, vascular, muscle, tendon, ligament, fascia, bone, joint, IVD's (intervertebral discs) and skin. Because of its ubiquitous nature, CT is an often overlooked component of any essential nutritional program that may address the structure, and/or function of these tissues. The central role of CT in the health of a virtually all cells, tissues, organs, and organ systems, is discussed. General nutritional CT support strategies, as well as specific CT support strategies that focus on blood, vascular, structural system (eg, muscles, tendons, ligaments, fascia, bone, and joints), integument (skin) and inflammatory and immune mediation will be discussed here and will deal with connective tissue dynamics and dysfunction. An overview of the current scientific understanding and possible options for naturally enhancing the structure and function of CT through the application of these concepts will be discussed in this article, with specific attention on the vascular and hematological systems. PMID:19674592

  19. Liver abnormalities in connective tissue diseases.

    PubMed

    De Santis, Maria; Crotti, Chiara; Selmi, Carlo

    2013-08-01

    The liver is a lymphoid organ involved in the immune response and in the maintenance of tolerance to self molecules, but it is also a target of autoimmune reactions, as observed in primary liver autoimmune diseases (AILD) such as autoimmune hepatitis, primary biliary cirrhosis, and primary sclerosing cholangitis. Further, the liver is frequently involved in connective tissue diseases (CTD), most commonly in the form of liver function test biochemical changes with predominant cholestatic or hepatocellular patterns. CTD commonly affecting the liver include systemic lupus erythematosus, antiphospholypid syndrome, primary Sjögren's syndrome, systemic sclerosis, dermatomyositis, polimyositis, and anti-synthetase syndrome, while overlap syndromes between AILD and CTD may also be diagnosed. Although liver cirrhosis and failure are extremely rare in patients with CTD, unusual liver conditions such as nodular regenerative hyperplasia or Budd-Chiari syndrome have been reported with increasing frequency in patients with CTD. Acute or progressing liver involvement is generally related to viral hepatitis reactivation or to a concomitant AILD, so it appears to be fundamental to screen patients for HBV and HCV infection, in order to provide the ideal therapeutic regimen and avoid life-threatening reactivations. Finally, it is important to remember that the main cause of biochemical liver abnormalities in patients with CTD is a drug-induced alteration or coexisting viral hepatitis. The present article will provide a general overview of the liver involvement in CTD to allow rheumatologists to discriminate the most common clinical scenarios.

  20. [Autoimmune connective tissue diseases and vaccination].

    PubMed

    Więsik-Szewczyk, Ewa; Jahnz-Różyk, Karina

    2015-12-31

    The idea that infectious agents can induce autoimmune diseases in genetically susceptible subjects has been a matter of discussion for years. Moreover, increased incidence of autoimmune diseases and introduction of prophylactic vaccinations from early childhood suggest that these two trends are linked. In the medical literature and even non-professional media, case reports or events temporally related to vaccination are reported. It raises the issue of vaccination safety. In everyday practice medical professionals, physicians, rheumatologists and other specialists will be asked their opinion of vaccination safety. The decision should be made according to evidence-based medicine and the current state of knowledge. The purpose of this paper is to discuss a potential mechanism which links infections, vaccinations and autoimmunity. We present an overview of published case reports, especially of systemic connective tissue diseases temporally related to vaccination and results from case-nested studies. As yet, no conclusive evidence supports a causal relationship between vaccination and autoimmune diseases. It has to be determined whether the performed studies are sufficiently sensitive to detect the link. The debate is ongoing, and new data may be required to explain the pathogenesis of autoimmunity. We would like to underscore the need for prophylactic vaccination in patients with autoimmune rheumatic diseases and to break down the myth that the vaccines are contraindicated in this target group.

  1. Pregnancy and autoimmune connective tissue diseases.

    PubMed

    Marder, Wendy; Littlejohn, Emily A; Somers, Emily C

    2016-02-01

    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 pregnancy, during pregnancy, and in 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.

  2. Pregnancy and autoimmune connective tissue diseases.

    PubMed

    Marder, Wendy; Littlejohn, Emily A; Somers, Emily C

    2016-02-01

    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 pregnancy, during pregnancy, and in 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

  3. Patients with Encapsulating Peritoneal Sclerosis Have Increased Peritoneal Expression of Connective Tissue Growth Factor (CCN2), Transforming Growth Factor-β1, and Vascular Endothelial Growth Factor

    PubMed Central

    Abrahams, Alferso C.; Habib, Sayed M.; Dendooven, Amélie; Riser, Bruce L.; van der Veer, Jan Willem; Toorop, Raechel J.; Betjes, Michiel G. H.; Verhaar, Marianne C.; Watson, Christopher J. E.; Nguyen, Tri Q.; Boer, Walther H.

    2014-01-01

    Introduction Encapsulating peritoneal sclerosis (EPS) is a devastating complication of peritoneal dialysis (PD). The pathogenesis is not exactly known and no preventive strategy or targeted medical therapy is available. CCN2 has both pro-fibrotic and pro-angiogenic actions and appears an attractive target. Therefore, we studied peritoneal expression of CCN2, as well as TGFβ1 and VEGF, in different stages of peritoneal fibrosis. Materials and methods Sixteen PD patients were investigated and compared to 12 hemodialysis patients and four pre-emptively transplanted patients. Furthermore, expression was investigated in 12 EPS patients in comparison with 13 PD and 12 non-PD patients without EPS. Peritoneal tissue was taken during kidney transplantation procedure or during EPS surgery. In a subset of patients, CCN2 protein levels in peritoneal effluent and plasma were determined. Samples were examined by qPCR, histology, immunohistochemistry, and ELISA. Results Peritoneal CCN2 expression was 5-fold higher in PD patients compared to pre-emptively transplanted patients (P<0.05), but did not differ from hemodialysis patients. Peritoneal expression of TGFβ1 and VEGF were not different between the three groups; neither was peritoneal thickness. Peritoneum of EPS patients exhibited increased expression of CCN2 (35-fold, P<0.001), TGFβ1 (24-fold, P<0.05), and VEGF (77-fold, P<0.001) compared to PD patients without EPS. In EPS patients, CCN2 protein was mainly localized in peritoneal endothelial cells and fibroblasts. CCN2 protein levels were significantly higher in peritoneal effluent of EPS patients compared to levels in dialysate of PD patients (12.0±4.5 vs. 0.91±0.92 ng/ml, P<0.01), while plasma CCN2 levels were not increased. Conclusions Peritoneal expression of CCN2, TGFβ1, and VEGF are significantly increased in EPS patients. In early stages of peritoneal fibrosis, only CCN2 expression is slightly increased. Peritoneal CCN2 overexpression in EPS patients is a

  4. [Eye connective tissues: cornea and vitreous body].

    PubMed

    Labat-Robert, Jacqueline; Pouliquen, Yves; Robert, Ladislas

    2012-01-01

    The authors, ophtalmologist (Y.P.) and basic scientists (J.L.-R and L.R.), collaborated on eye-research since 1962 on normal and pathological aspects of eye tissues, considered as specialized forms of connective tissues, and on specific aspects of the physiology and pathology of the eye. This date coincides with the foundation of the French Society of Connective Tissues, which celebrates the 50th anniversary of its creation. We shall present here some of our work on the ontogenetic and phylogenetic aspects of the cornea, on its structure, function and regulation in normal and pathological states, taken from a large number of publications of our laboratories. Our work on cornea started with the study of the morphogenesis of its lamellar structure, made of collagen fibers and proteoglycans. This led us to the isolation and characterization of structural (or matrix) glycoproteins, a new class of matrix components, present also in all other connective tissues, and to the study of their biosynthesis by keratocytes. Corneal wounds and regeneration were also studied, as well as some corneal pathologies such as keratoconus. The confrontation of quantitative morphological methods with biochemical procedures were to yield important results on the mechanisms of the maintenance of corneal structure and function. Another series of studies concerned the vitreous where we detected, besides previously characterized components, such as hyaluronan and collagens, fibronectin which plays an important role in the adhesion of hyaluronan to the collagen network. Its age-dependent modifications were also studied, with a special focus on the role of reactive oxygen species (ROS)-mediated degradation of hyaluronan, especially important for the aging of the vitreous.

  5. Connective tissue response to periodontal dressing.

    PubMed

    Nezwek, R A; Caffesse, R G; Bergenholtz, A; Nasjleti, C E

    1980-09-01

    The effects of three periodontal dressings (Coe-Pak, PPC, Perio Putty) upon subcutaneous tissues in 26 Sprague-Dawley rats were investigated. The three dressings, and a control (Teflon), were placed into polyethylene tubes. Two tubes per animal were implanted on either side of the dorsal midline area. After 14 days the specimens were retrieved and prepared for histological examination. Three methods of scoring were utilized for evaluation. First, a system evaluating the overall number of inflammatory cells, connective tissue capsule thickness, and the vascular changes produced; second, an inflammatory cell count, the Inflammatory Index (I.I), computing the inflammatory cells in a particular field of view for each material; and third, a Reaction Spread Index (R.S.I.) comparing the distance of the spread of the inflammatory reaction into the connective tissues. Statistical analysis of the data was carried out utilizing the Chi-square test and analysis of variance. While the three scoring systems utilized did result in some comparative variation in reactions, the overall order of decreasing severity was always PPC, Coe-Pak, Perio Putty, and Teflon.

  6. [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

    , etc., have permitted a considerable increase of the knowledge in the field of connective tissue.

  7. Comparative Glycomics of Connective Tissue Glycosaminoglycans

    PubMed Central

    Hitchcock, Alicia M.; Yates, Karen E.; Costello, Catherine E.; Zaia, Joseph

    2008-01-01

    Homeostasis of connective joint tissues depends on the maintenance of an extracellular matrix, consisting of an integrated assembly of collagens, glycoproteins, proteoglycans and glycosaminoglycans (GAGs). Isomeric chondroitin sulfate (CS) glycoforms differing in position and degree of sulfation and uronic acid epimerization play specific and distinct functional roles during development and disease onset. This work profiles the CS epitopes expressed by different joint tissues as a function of age and osteoarthritis. Glycosaminoglycans were extracted from joint tissues (cartilage, tendon, ligment, muscle and synovium) and partially depolymerized using chondroitinase enzymes. The oligosaccharide products were differentially stable isotope labeled by reductive amination using 2-anthranilic acid- d0 or -d4 and subjected to amide-HILIC on-line liquid chromatography-tandem mass spectrometry. The analysis presented herein enables simultaneous profiling of the expression of non-reducing end, linker region, and Δ-unsaturated interior oligosaccharide domains of the CS chains among the different joint tissues. The results provide important new information on the changes to the expression of CS GAG chains during disease and development. PMID:18318007

  8. Adolescent impatience decreases with increased frontostriatal connectivity.

    PubMed

    van den Bos, Wouter; Rodriguez, Christian A; Schweitzer, Julie B; McClure, Samuel M

    2015-07-21

    Adolescence is a developmental period associated with an increase in impulsivity. Impulsivity is a multidimensional construct, and in this study we focus on one of the underlying components: impatience. Impatience can result from (i) disregard of future outcomes and/or (ii) oversensitivity to immediate rewards, but it is not known which of these evaluative processes underlie developmental changes. To distinguish between these two causes, we investigated developmental changes in the structural and functional connectivity of different frontostriatal tracts. We report that adolescents were more impatient on an intertemporal choice task and reported less future orientation, but not more present hedonism, than young adults. Developmental increases in structural connectivity strength in the right dorsolateral prefrontal tract were related to increased negative functional coupling with the striatum and an age-related decrease in discount rates. Our results suggest that mainly increased control, and the integration of future-oriented thought, drives the reduction in impatience across adolescence. PMID:26100897

  9. Adolescent impatience decreases with increased frontostriatal connectivity

    PubMed Central

    van den Bos, Wouter; Rodriguez, Christian A.; Schweitzer, Julie B.; McClure, Samuel M.

    2015-01-01

    Adolescence is a developmental period associated with an increase in impulsivity. Impulsivity is a multidimensional construct, and in this study we focus on one of the underlying components: impatience. Impatience can result from (i) disregard of future outcomes and/or (ii) oversensitivity to immediate rewards, but it is not known which of these evaluative processes underlie developmental changes. To distinguish between these two causes, we investigated developmental changes in the structural and functional connectivity of different frontostriatal tracts. We report that adolescents were more impatient on an intertemporal choice task and reported less future orientation, but not more present hedonism, than young adults. Developmental increases in structural connectivity strength in the right dorsolateral prefrontal tract were related to increased negative functional coupling with the striatum and an age-related decrease in discount rates. Our results suggest that mainly increased control, and the integration of future-oriented thought, drives the reduction in impatience across adolescence. PMID:26100897

  10. Vasculitis associated with connective tissue diseases.

    PubMed

    Cozzani, E; Gasparini, G; Papini, M; Burlando, M; Drago, F; Parodi, A

    2015-04-01

    Vasculitis in connective tissue disease (CTD) is quite rare, it is reported in approximately 10% of patients with CTD; systemic lupus erythematosus (SLE) shows the highest association rate. Vessels of any size may be involved, but mainly small vessels vasculitis is reported. At present the classification of these vasculitis is unsatisfactory. According to the 2012 revised International Chapel Hill Consensus Conference, vasculitides secondary to CTD are a well identified entity and are classified under the category of "vasculitis associated with systemic disease". However only lupus vasculitis and rheumatoid vasculitis are explicitly listed, while the remaining are generically included under the heading "others". Petechiae, purpura, gangrene and ulcers are the most frequent cutaneous manifestations that should investigated in order to rule out potentially dangerous systemic involvement, especially if cryoglobulinemic or necrotizing vasculitis are suspected. This review will focus on the cutaneous involvement in CTD associated vasculitis. PMID:25732106

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

    PubMed

    Dideriksen, Kasper

    2014-04-01

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

  12. [Peculiarities of the action of hyaluronidase of different origin to the connective tissue].

    PubMed

    Habriyev, R U; Kamayev, N O; Danilova, T I; Kakhoyan, E G

    2016-01-01

    The lecture is devoted to consideration of mechanism of therapeutic action of the enzyme hyaluronidase in hyperplastic connective tissue. Drugs based on hyaluronidase increase bioavailability of other drugs used in adjuvant therapy; they significantly increase effectiveness of treatment, and also provide targeted synthesis of hyaluronic acid, ths regulating the regeneration process of connective tissue.

  13. Role of PTPα in the destruction of periodontal connective tissues.

    PubMed

    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 PTPα(KO) 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.

  14. Connective tissue disorders in domestic animals.

    PubMed

    Halper, Jaroslava

    2014-01-01

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

  15. 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.

  16. Analgesic Drugs Alter Connective Tissue Remodeling and Mechanical Properties.

    PubMed

    Carroll, Chad C

    2016-01-01

    Exercising individuals commonly consume analgesics, but these medications alter tendon and skeletal muscle connective tissue properties, possibly limiting a person from realizing the full benefits of exercise training. I detail the novel hypothesis that analgesic medications alter connective tissue structure and mechanical properties by modifying fibroblast production of growth factors and matrix enzymes, which are responsible for extracellular matrix remodeling.

  17. 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

  18. Imaging of connective tissue diseases of the head and neck.

    PubMed

    Abdel Razek, Ahmed Abdel Khalek

    2016-06-01

    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.

  19. [Protein-energy malnutrition in patients with connective tissue dysplasia].

    PubMed

    Lialiukova, E A

    2013-01-01

    In the conditions of the specialized Center of a dysplasia of a connecting tissue the assessment of an protein--energy malnutrition at 121 patients with signs of a dysplasia of a connecting tissue is carried out. High frequency of an oligotrophy at patients with a dysplasia of a connecting tissue is registered. The I degree of a gipotorofiya is taped at 26.21% of the patients, II degree--at 18.44%, the III degree--at 3.88% of patients.

  20. 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. PMID:26807767

  1. 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.

  2. 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

  3. Cerebro-cerebellar connectivity is increased in primary lateral sclerosis

    PubMed Central

    Meoded, Avner; Morrissette, Arthur E.; Katipally, Rohan; Schanz, Olivia; Gotts, Stephen J.; Floeter, Mary Kay

    2014-01-01

    Increased functional connectivity in resting state networks was found in several studies of patients with motor neuron disorders, although diffusion tensor imaging studies consistently show loss of white matter integrity. To understand the relationship between structural connectivity and functional connectivity, we examined the structural connections between regions with altered functional connectivity in patients with primary lateral sclerosis (PLS), a long-lived motor neuron disease. Connectivity matrices were constructed from resting state fMRI in 16 PLS patients to identify areas of differing connectivity between patients and healthy controls. Probabilistic fiber tracking was used to examine structural connections between regions of differing connectivity. PLS patients had 12 regions with increased functional connectivity compared to controls, with a predominance of cerebro-cerebellar connections. Increased functional connectivity was strongest between the cerebellum and cortical motor areas and between the cerebellum and frontal and temporal cortex. Fiber tracking detected no difference in connections between regions with increased functional connectivity. We conclude that functional connectivity changes are not strongly based in structural connectivity. Increased functional connectivity may be caused by common inputs, or by reduced selectivity of cortical activation, which could result from loss of intracortical inhibition when cortical afferents are intact. PMID:25610792

  4. Cerebro-cerebellar connectivity is increased in primary lateral sclerosis.

    PubMed

    Meoded, Avner; Morrissette, Arthur E; Katipally, Rohan; Schanz, Olivia; Gotts, Stephen J; Floeter, Mary Kay

    2015-01-01

    Increased functional connectivity in resting state networks was found in several studies of patients with motor neuron disorders, although diffusion tensor imaging studies consistently show loss of white matter integrity. To understand the relationship between structural connectivity and functional connectivity, we examined the structural connections between regions with altered functional connectivity in patients with primary lateral sclerosis (PLS), a long-lived motor neuron disease. Connectivity matrices were constructed from resting state fMRI in 16 PLS patients to identify areas of differing connectivity between patients and healthy controls. Probabilistic fiber tracking was used to examine structural connections between regions of differing connectivity. PLS patients had 12 regions with increased functional connectivity compared to controls, with a predominance of cerebro-cerebellar connections. Increased functional connectivity was strongest between the cerebellum and cortical motor areas and between the cerebellum and frontal and temporal cortex. Fiber tracking detected no difference in connections between regions with increased functional connectivity. We conclude that functional connectivity changes are not strongly based in structural connectivity. Increased functional connectivity may be caused by common inputs, or by reduced selectivity of cortical activation, which could result from loss of intracortical inhibition when cortical afferents are intact.

  5. [CT imaging features of pulmonary involvement in connective tissue disorders].

    PubMed

    Brillet, P Y; Mama, N; Nunes, H; Uzunhan, Y; Abbad, S; Brauner, M W

    2009-11-01

    Connective tissue disorders correspond to a heterogeneous group of inflammatory diseases characterized by abnormal immune system activity leading to connective tissue alterations in multiple parts of the body. In adults, connective tissue disorders include rheumatoid arthritis, progressive systemic sclerosis, Sjögren syndrome, systemic lupus erythematosus, dermatomyositis and polymyositis, ankylosing spondylitis, and mixed connective tissue disease. Broncho-pulmonary involvement may be variable with involvement of all anatomical components of the lung. Involvement of other intrathoracic structures (pleura, respiratory muscles, heart, rib cage) is frequent. The most specific manifestations include interstitial lung diseases and pulmonary hypertension. During follow-up, progressive respiratory diseases may occur due to the treatment, infections, pulmonary embolism or neoplasms.

  6. Partial connectivity increases cultural accumulation within groups.

    PubMed

    Derex, Maxime; Boyd, Robert

    2016-03-15

    Complex technologies used in most human societies are beyond the inventive capacities of individuals. Instead, they result from a cumulative process in which innovations are gradually added to existing cultural traits across many generations. Recent work suggests that a population's ability to develop complex technologies is positively affected by its size and connectedness. Here, we present a simple computer-based experiment that compares the accumulation of innovations by fully and partially connected groups of the same size in a complex fitness landscape. We find that the propensity to learn from successful individuals drastically reduces cultural diversity within fully connected groups. In comparison, partially connected groups produce more diverse solutions, and this diversity allows them to develop complex solutions that are never produced in fully connected groups. These results suggest that explanations of ancestral patterns of cultural complexity may need to consider levels of population fragmentation and interaction patterns between partially isolated groups. PMID:26929364

  7. Partial connectivity increases cultural accumulation within groups

    PubMed Central

    Boyd, Robert

    2016-01-01

    Complex technologies used in most human societies are beyond the inventive capacities of individuals. Instead, they result from a cumulative process in which innovations are gradually added to existing cultural traits across many generations. Recent work suggests that a population’s ability to develop complex technologies is positively affected by its size and connectedness. Here, we present a simple computer-based experiment that compares the accumulation of innovations by fully and partially connected groups of the same size in a complex fitness landscape. We find that the propensity to learn from successful individuals drastically reduces cultural diversity within fully connected groups. In comparison, partially connected groups produce more diverse solutions, and this diversity allows them to develop complex solutions that are never produced in fully connected groups. These results suggest that explanations of ancestral patterns of cultural complexity may need to consider levels of population fragmentation and interaction patterns between partially isolated groups. PMID:26929364

  8. Partial connectivity increases cultural accumulation within groups.

    PubMed

    Derex, Maxime; Boyd, Robert

    2016-03-15

    Complex technologies used in most human societies are beyond the inventive capacities of individuals. Instead, they result from a cumulative process in which innovations are gradually added to existing cultural traits across many generations. Recent work suggests that a population's ability to develop complex technologies is positively affected by its size and connectedness. Here, we present a simple computer-based experiment that compares the accumulation of innovations by fully and partially connected groups of the same size in a complex fitness landscape. We find that the propensity to learn from successful individuals drastically reduces cultural diversity within fully connected groups. In comparison, partially connected groups produce more diverse solutions, and this diversity allows them to develop complex solutions that are never produced in fully connected groups. These results suggest that explanations of ancestral patterns of cultural complexity may need to consider levels of population fragmentation and interaction patterns between partially isolated groups.

  9. Connective tissue photodamage in the hairless mouse is partially reversible

    SciTech Connect

    Kligman, L.H.

    1987-03-01

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

  10. Hypericin-mediated selective photomodification of connective tissues

    SciTech Connect

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

    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.

  11. Hypericin-mediated selective photomodification of connective tissues

    NASA Astrophysics Data System (ADS)

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

    2014-12-01

    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.

  12. Oral manifestations of connective tissue disease and novel therapeutic approaches.

    PubMed

    Heath, Kenisha R; Rogers, Roy S; Fazel, Nasim

    2015-10-16

    Connective tissue diseases such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and Sjögren syndrome (SS) have presented many difficulties both in their diagnosis and treatment. Known causes for this difficulty include uncertainty of disease etiology, the multitude of clinical presentations, the unpredictable disease course, and the variable cell types, soluble mediators, and tissue factors that are believed to play a role in the pathogenesis of connective tissue diseases. The characteristic oral findings seen with these specific connective tissue diseases may assist with more swift diagnostic capability. Additionally, the recent use of biologics may redefine the success rate in the treatment and management of the disease. In this review we describe the oral manifestations associated with SLE, SSc, and SS and review the novel biologic drugs used to treat these conditions.

  13. 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

  14. 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.

  15. [Progress of Autoantibody Examinations for Connective Tissue Diseases].

    PubMed

    Akashi, Kengo; Saegusa, Jun; Morinobu, Akio

    2015-05-01

    Connective tissue diseases are chronic inflammatory diseases that can affect multiple organs and, thus, have a broad spectrum of clinical presentations. Various autoantibodies are detected in patients with connective tissue diseases, represented by anti-nuclear antibody for systemic lupus erythematosus (SLE), systemic sclerosis (SSc), polymyositis/dermatomyositis (PM/DM), Sjögren's syndrome, and mixed connective tissue disease. Assessment of the autoantibody profile is fundamental for the clinical management of patients with connective tissue diseases, providing important data for the diagnosis, clinical characterization, and disease activity evaluation. Anti-ribosomal P antibody and anti-NMDA receptor antibody are associated with neuropsychiatric SLE. Anti-synthetase syndrome comprises the association of myositis (PM/DM), interstitial lung disease, fever, Raynaud's phenomenon, mechanic's hands, and anti-aminoacyl tRNA synthetase antibodies. Anti-MDA5 antibody is detected in patients with clinically amyopathic DM, often complicated by rapidly progressive interstitial lung disease. Between 50 and 75% of malignancy-associated DM patients are positive for anti-TIF1-γ antibody. Anti-RNA polymerase III antibody is associated with diffuse cutaneous SSc and renal crisis. This review focuses on the importance and usefulness of these autoantibodies for the diagnosis and management of patients with connective tissue diseases in clinical practice.

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

    PubMed

    Kapandji, A-I

    2012-10-01

    The anatomical unity of the organism is realized by the connective tissue, which assumes five functions: the filling of the spaces between organs; the connexion between these organs; the driving of the vascular and nervous pedicles to these organs; the stocking of nutritive reserves in fat pads; an aesthetic role with hollows and bumps erasing. The space filling is done with jointed polyedric volumes, which are constituted, according to the theories of J.-C. Guimberteau, with microvacuoles, filled with under pressure fundamental substance. This is a status of preconstraint resulting in a form memory. So, the connective tissue under constraint get back its initial status after this constraint is over, according to the laws of a new science, the tensegrity. The explorations of the connective tissue with a 25× magnifying micro endoscopes are showing micro fibrillar structures, evoluting under constraint. Its arrangement, that seems chaotic, is in fractal disposition, in reality, and follows the "universal parcimony law" established by Williams of Ockham. The structure of the connective tissue can be integrated in a holistic conception of the organism. Many characteristics of this tissue have still to be discovered.

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

    PubMed

    Kapandji, A-I

    2012-10-01

    The anatomical unity of the organism is realized by the connective tissue, which assumes five functions: the filling of the spaces between organs; the connexion between these organs; the driving of the vascular and nervous pedicles to these organs; the stocking of nutritive reserves in fat pads; an aesthetic role with hollows and bumps erasing. The space filling is done with jointed polyedric volumes, which are constituted, according to the theories of J.-C. Guimberteau, with microvacuoles, filled with under pressure fundamental substance. This is a status of preconstraint resulting in a form memory. So, the connective tissue under constraint get back its initial status after this constraint is over, according to the laws of a new science, the tensegrity. The explorations of the connective tissue with a 25× magnifying micro endoscopes are showing micro fibrillar structures, evoluting under constraint. Its arrangement, that seems chaotic, is in fractal disposition, in reality, and follows the "universal parcimony law" established by Williams of Ockham. The structure of the connective tissue can be integrated in a holistic conception of the organism. Many characteristics of this tissue have still to be discovered. PMID:22884219

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

    PubMed

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

    2012-01-01

    The role played by nonspecialized connective tissues in chronic non-specific low back pain is not well understood. In a recent ultrasound study, human subjects with chronic low back pain had altered connective tissue structure compared to human subjects without low back pain, suggesting the presence of inflammation and/or fibrosis in the low back pain subjects. Mechanical input in the form of static tissue stretch has been shown in vitro and in vivo to have anti-inflammatory and anti-fibrotic effects. To better understand the pathophysiology of lumbar nonspecialized connective tissue as well as potential mechanisms underlying therapeutic effects of tissue stretch, we developed a carrageenan-induced inflammation model in the low back of a rodent. Induction of inflammation in the lumbar connective tissues resulted in altered gait, increased mechanical sensitivity of the tissues of the low back, and local macrophage infiltration. Mechanical input was then applied to this model as in vivo tissue stretch for 10 minutes twice a day for 12 days. In vivo tissue stretch mitigated the inflammation-induced changes leading to restored stride length and intrastep distance, decreased mechanical sensitivity of the back and reduced macrophage expression in the nonspecialized connective tissues of the low back. This study highlights the need for further investigation into the contribution of connective tissue to low back pain and the need for a better understanding of how interventions involving mechanical stretch could provide maximal therapeutic benefit. This tissue stretch research is relevant to body-based treatments such as yoga or massage, and to some stretch techniques used with physical therapy.

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

    PubMed Central

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

    2012-01-01

    The role played by nonspecialized connective tissues in chronic non-specific low back pain is not well understood. In a recent ultrasound study, human subjects with chronic low back pain had altered connective tissue structure compared to human subjects without low back pain, suggesting the presence of inflammation and/or fibrosis in the low back pain subjects. Mechanical input in the form of static tissue stretch has been shown in vitro and in vivo to have anti-inflammatory and anti-fibrotic effects. To better understand the pathophysiology of lumbar nonspecialized connective tissue as well as potential mechanisms underlying therapeutic effects of tissue stretch, we developed a carrageenan-induced inflammation model in the low back of a rodent. Induction of inflammation in the lumbar connective tissues resulted in altered gait, increased mechanical sensitivity of the tissues of the low back, and local macrophage infiltration. Mechanical input was then applied to this model as in vivo tissue stretch for 10 minutes twice a day for 12 days. In vivo tissue stretch mitigated the inflammation-induced changes leading to restored stride length and intrastep distance, decreased mechanical sensitivity of the back and reduced macrophage expression in the nonspecialized connective tissues of the low back. This study highlights the need for further investigation into the contribution of connective tissue to low back pain and the need for a better understanding of how interventions involving mechanical stretch could provide maximal therapeutic benefit. This tissue stretch research is relevant to body-based treatments such as yoga or massage, and to some stretch techniques used with physical therapy. PMID:22238664

  20. Electrical impedance along connective tissue planes associated with acupuncture meridians

    PubMed Central

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

    2005-01-01

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

  1. [Age changes of the connective tissue structures of human penis].

    PubMed

    Klimachev, V V; Neĭmark, A I; Gerval'd, V Ia; Bobrov, I P; Avdalian, A M; Muzalevskaia, N I; Gerval'd, I V; Aliev, R T; Cherdantseva, T M

    2011-01-01

    This investigation was aimed at the study of age changes of penis connective tissue structures. Tissue fragments of penis were obtained from 20 cadavers of men at the age of 20-38 years in group I, and from 20 cadavers of men at the age of 41-59 years in group II. The criteria for the exclusion of material from the research were arterial hypertension, diabetes mellitus, atherosclerosis of internal iliac arteries, Peyronie's disease, and anomalies of genital organ development. It was shown that in the cavernous body of penis, aging was associated with the increased amount and thickening of collagen and argyrophilic fibers, decreased content and thinning of elastic fibers, and the reduced amount of smooth muscle cells (SMC). The average area of fibroblast and SMC nucleolus was not different in both groups studied. The average area of endotheliocyte nucleolus was equal to 1.9+/-0.9 microm2 in group II, being lower than that one in group I, in which this index was equal to 2.1+/-0.9 microm2. No differences in the content of type III and IV collagen were found between the study groups. Age-associated decrease in the average area of endothelial cell nucleolus in the cavernous bodies may reflect the reduction of the activity of these cells and may indicate the development of endothelial dysfunction, which is one of the most important steps in the morphogenesis of age-related male erectile dysfunction.

  2. 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.

  3. Bioreactors for connective tissue engineering: design and monitoring innovations.

    PubMed

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

    2009-01-01

    The challenges for the tissue engineering of connective tissue lie in creating off-the-shelf tissue constructs which are capable of providing organs for transplantation. These strategies aim to grow a complex tissue with the appropriate mechanical integrity necessary for functional load bearing. Monolayer culture systems lack correlation with the in vivo environment and the naturally occur ring cell phenotypes. Part of the development of more recent models is to create growth environments or bioreactors which enable three-dimensional culture. Evidence suggests that in order to grow functional load-bearing tissues in a bioreactor, the cells must experience mechanical loading stimuli similar to that experienced in vivo which sets out the requirements for mechanical loading bioreactors. An essential part of developing new bioreactors for tissue growth is identifying ways of routinely and continuously measuring neo-tissue formation and in order to fully identify the successful generation of a tissue implant, the appropriate on-line monitoring must be developed. New technologies are being developed to advance our efforts to grow tissue ex vivo. The bioreactor is a critical part of these developments in supporting growth of biological implants and combining this with new advances in the detection of tissue formation allows us to refine our protocols and move nearer to off-the-shelf implants for clinical applications. PMID:19290498

  4. Bioreactors for Connective Tissue Engineering: Design and Monitoring Innovations

    NASA Astrophysics Data System (ADS)

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

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

  5. 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

  6. Connective tissue growth factor induces cardiac hypertrophy through Akt signaling

    SciTech Connect

    Hayata, Nozomi; Fujio, Yasushi; Yamamoto, Yasuhiro; Iwakura, Tomohiko; Obana, Masanori; Takai, Mika; Mohri, Tomomi; Nonen, Shinpei; Maeda, Makiko; Azuma, Junichi

    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, analyzed by Northern-blotting. CTGF treatment activated ERK1/2, p38 MAPK, JNK and Akt. The inhibition of Akt by transducing dominant-negative Akt abrogated CTGF-mediated increase in cell size, while the inhibition of MAP kinases did not affect the cardiac hypertrophy. These findings indicate that CTGF is a novel hypertrophic factor in cardiac myocytes.

  7. Uniphasic Blanching of the Fingers, Abnormal Capillaroscopy in Nonsymptomatic Digits, and Autoantibodies: Expanding Options to Increase the Level of Suspicion of Connective Tissue Diseases beyond the Classification of Raynaud's Phenomenon.

    PubMed

    Ingegnoli, Francesca; Gualtierotti, Roberta; Orenti, Annalisa; Schioppo, Tommaso; Marfia, Giovanni; Campanella, Rolando; Mastaglio, Claudio; Meroni, Pier Luigi; Boracchi, Patrizia

    2015-01-01

    In patients with Raynaud's phenomenon (RP), the role of medical history, capillaroscopy, and autoantibodies in order to provide an early diagnosis of connective tissue disease (CTD) were examined. 115 consecutive adults with uni-, bi-, or triphasic colour changes of the fingers were studied. RP was bilateral in 92.7% of patients. The middle finger was significantly more affected. A lack of association between fingers affected by RP and fingers with capillary abnormalities was observed OR = 0.75 (0.34-1.66). RP with the cyanotic phase had a higher risk at capillaroscopy to have hemorrhages OR = 4.46 (1.50-13.30) and giant capillaries OR = 24.85 (1.48-417.44). The thumb and triphasic involvement have an OR of 1.477 and 1.845, respectively. RP secondary to systemic sclerosis (SSc) had greater value of VAS pain (p = 0.011). The presence of anti-centromere antibodies was significantly associated with a higher risk of SSc (p < 0.001). 44.3% of subjects had uniphasic blanching of the fingers, and among these, 27% was diagnosed as having an overt or suspected CTD. Markers of a potential development of CTDs include severe RP symptoms, positive autoantibodies, and capillary abnormalities. These data support the proposal to not discharge patients with uniphasic blanching of the fingers to avoid missing the opportunity of an early diagnosis.

  8. Uniphasic Blanching of the Fingers, Abnormal Capillaroscopy in Nonsymptomatic Digits, and Autoantibodies: Expanding Options to Increase the Level of Suspicion of Connective Tissue Diseases beyond the Classification of Raynaud's Phenomenon

    PubMed Central

    Gualtierotti, Roberta; Orenti, Annalisa; Schioppo, Tommaso; Marfia, Giovanni; Campanella, Rolando; Mastaglio, Claudio; Meroni, Pier Luigi; Boracchi, Patrizia

    2015-01-01

    In patients with Raynaud's phenomenon (RP), the role of medical history, capillaroscopy, and autoantibodies in order to provide an early diagnosis of connective tissue disease (CTD) were examined. 115 consecutive adults with uni-, bi-, or triphasic colour changes of the fingers were studied. RP was bilateral in 92.7% of patients. The middle finger was significantly more affected. A lack of association between fingers affected by RP and fingers with capillary abnormalities was observed OR = 0.75 (0.34–1.66). RP with the cyanotic phase had a higher risk at capillaroscopy to have hemorrhages OR = 4.46 (1.50–13.30) and giant capillaries OR = 24.85 (1.48–417.44). The thumb and triphasic involvement have an OR of 1.477 and 1.845, respectively. RP secondary to systemic sclerosis (SSc) had greater value of VAS pain (p = 0.011). The presence of anti-centromere antibodies was significantly associated with a higher risk of SSc (p < 0.001). 44.3% of subjects had uniphasic blanching of the fingers, and among these, 27% was diagnosed as having an overt or suspected CTD. Markers of a potential development of CTDs include severe RP symptoms, positive autoantibodies, and capillary abnormalities. These data support the proposal to not discharge patients with uniphasic blanching of the fingers to avoid missing the opportunity of an early diagnosis. PMID:26075287

  9. 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.

  10. Acquired disorders of elastic tissue: part I. Increased elastic tissue and solar elastotic syndromes.

    PubMed

    Lewis, Kevan G; Bercovitch, Lionel; Dill, Sara W; Robinson-Bostom, Leslie

    2004-07-01

    Elastic fibers in the extracellular matrix are an integral component of dermal connective tissue. The resilience and elasticity required for normal structure and function of the skin may be attributed to the network of elastic tissue. Advances in our understanding of elastic tissue physiology provide a foundation for studying the pathogenesis of elastic tissue disorders. Many acquired disorders are nevertheless poorly understood due to the paucity of reported cases. Several acquired disorders in which accumulation or elastotic degeneration of dermal elastic fibers produces prominent clinical and histopathologic features have recently been described. They include elastoderma, linear focal elastosis, and late-onset focal dermal elastosis and must be differentiated from better-known disorders, among them acquired pseudoxanthoma elasticum, elastosis perforans serpiginosa, and Favré-Racouchot syndrome. Learning objective At the conclusion of this learning activity, participants should understand the similarities and differences between acquired disorders of elastic tissue that are characterized by an increase in elastic tissue, as well as the spectrum of solar elastotic dermatoses.

  11. Extracellular matrix of connective tissues in the heads of teleosts.

    PubMed Central

    Benjamin, M; Ralphs, J R

    1991-01-01

    The distribution of extracellular matrix molecules (chondroitin and keratan sulphates, type II collagen) is described in cranial connective tissues of teleosts. Hyaline cartilage was similar to that in mammals and usually contained all 3 molecules. The more cellular cartilages that are not normally present in mammals were more variable in composition. Scleral cartilage closely resembled hyaline cartilage, Zellknorpel in the gill filaments resembled it in some species but not in others, and elastic/cell-rich and hyaline-cell cartilages were unlike hyaline cartilage. These variations may be related to functional or developmental differences between the tissues. Bone and chondroid bone also varied in composition between species. Whilst both tissues contained chondroitin sulphate, bone contained type II collagen in 5 of the 12 species examined. This suggests that cartilage components are more widespread in teleost bone than has previously been shown. Type II collagen also occurred in dense connective tissues of some species. Notably, where this molecule was present in one of these tissues, it was present in all. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:1817131

  12. The diagnosis and classification of undifferentiated connective tissue diseases.

    PubMed

    Mosca, Marta; Tani, Chiara; Vagnani, Sabrina; Carli, Linda; Bombardieri, Stefano

    2014-01-01

    The term undifferentiated connective tissue disease (UCTD) refers to unclassifiable systemic autoimmune diseases which share clinical and serological manifestations with definite connective tissue diseases (CTDs) but not fulfilling any of the existing classification criteria. In this review we will go through the more recent evidence on UCTD and we will discuss in what extent the availability of new criteria for the CTDs could interfere with the "UCTD concept". The development of criteria able to identify early phases of defined CTD, may help in the differentiation of stable UCTD form their early stages and may offer a valuable guide to the treating physician to set up appropriate follow up schedules as well as therapeutic protocols. This simplified subset of CTD could offer a model to study clinic pathological correlations as well as the role of possible environmental factors in the development of autoimmunity.

  13. Connective tissue disease-related pulmonary arterial hypertension.

    PubMed

    Thakkar, Vivek; Lau, Edmund M T

    2016-02-01

    Over the past two decades, there have been several advances in the assessment and management of connective tissue disease-related pulmonary arterial hypertension (CTD-PAH) that improved outcomes of the treatment of this lethal disease, and this will be the focus of this study. Systemic sclerosis is the leading cause of CTD-PAH, followed by systemic lupus erythematosus, mixed connective tissue disease, idiopathic inflammatory myositis, rheumatoid arthritis, and Sjogren's syndrome. Clinical registries have been invaluable in informing about the burden of disease, risk and prognostic factors, and temporal trends with respect to treatment and outcome in CTD-PAH. The major advances have centered on improved disease classification and diagnostic criteria, screening and early diagnosis, the emergence of evidence-based therapies including combination goal-orientated treatment strategies, and the establishment of centers with expertise in PAH.

  14. Connective tissue disease-related pulmonary arterial hypertension.

    PubMed

    Thakkar, Vivek; Lau, Edmund M T

    2016-02-01

    Over the past two decades, there have been several advances in the assessment and management of connective tissue disease-related pulmonary arterial hypertension (CTD-PAH) that improved outcomes of the treatment of this lethal disease, and this will be the focus of this study. Systemic sclerosis is the leading cause of CTD-PAH, followed by systemic lupus erythematosus, mixed connective tissue disease, idiopathic inflammatory myositis, rheumatoid arthritis, and Sjogren's syndrome. Clinical registries have been invaluable in informing about the burden of disease, risk and prognostic factors, and temporal trends with respect to treatment and outcome in CTD-PAH. The major advances have centered on improved disease classification and diagnostic criteria, screening and early diagnosis, the emergence of evidence-based therapies including combination goal-orientated treatment strategies, and the establishment of centers with expertise in PAH. PMID:27421214

  15. [A case report of undifferentiated connective tissue disease associated myelodysplastic].

    PubMed

    Zhang, Xiao-ying; Wen, Hong-yan; Chen, Jun-wei; Li, Xiao-feng; Wang, Li-xing

    2012-04-18

    A 58-year-old man exhibited polyarthritis, fever, thrombocytopenia and progressive anemia. Undifferentiated connective tissue diseases(UCTD) was diagnosed based on laboratory and radiographic findings. After diagnosis, the patient received glucocorticoid and blood-transfusion. The symptoms were improved notablely. However,the level of hemoglobin was lower than normal(between 57 g/L and 75 g/L). Thrombocytes were 19 000/microl to 32 000/microl. Bone marrow aspiration revealed highly abnormal cell morphology, indicating myelodysplastic syndrome(MDS). A diagnosis of UCTD with MDS was made. The patient was successfully treated by decitabine and thalidomide(an immunosuppressive regimen). It is necessary to promptly examine bone marrow cell morphology and chromosomal aberration in cases with connective tissue diseases complicated by sudden cytopenia and thrombocytopenia.

  16. Strategic Key Word Instruction: Increasing Fluency in Connected Expository Text

    ERIC Educational Resources Information Center

    Coulter, Gail; Lambert, Michael C.

    2015-01-01

    The effects of preteaching key words on fluency in connected text were examined with three third-grade general education participants. Researchers used a multiple base-line design (i.e., Baseline and Wordlist Intervention) and found that preteaching increased fluency in connected text written above the participant's instructional level of reading…

  17. Synaptic activity and connective tissue remodeling in denervated frog muscle

    PubMed Central

    1994-01-01

    Denervation of skeletal muscle results in dramatic remodeling of the cellular and molecular composition of the muscle connective tissue. This remodeling is concentrated in muscle near neuromuscular junctions and involves the accumulation of interstitial cells and several extracellular matrix molecules. Given the role of extracellular matrix in neurite outgrowth and synaptogenesis, we predict that this remodeling of the junctional connective tissue directly influences the regeneration of the neuromuscular junction. As one step toward understanding the role of this denervation-induced remodeling in synapse formation, we have begun to look for the signals that are involved in initiating the junctional accumulations of interstitial cells and matrix molecules. Here, the role of muscle inactivity as a signal was examined. The distributions of interstitial cells, fibronectin, and tenascin were determined in muscles inactivated by presynaptic blockade of muscle activity with tetrodotoxin. We found that blockade of muscle activity for up to 4 wk produced neither the junctional accumulation of interstitial cells nor the junctional concentrations of tenascin and fibronectin normally present in denervated frog muscle. In contrast, the muscle inactivity induced the extrajunctional appearance of two synapse-specific molecules, the acetylcholine receptor and a muscle fiber antigen, mAb 3B6. These results demonstrate that the remodeling of the junctional connective tissue in response to nerve injury is a unique response of muscle to denervation in that it is initiated by a mechanism that is independent of muscle activity. Thus connective tissue remodeling in denervated skeletal muscle may be induced by signals released from or associated with the nerve other than the evoked release of neurotransmitter. PMID:7525607

  18. Pauci-Immune Crescentic Glomerulonephritis in Connective Tissue Disease

    PubMed Central

    Cronin, Mary; Robin, Adam; Lorna, Campbell; Rosenthal, Ann K.

    2016-01-01

    Pauci-immune crescentic glomerulonephritis is commonly seen in ANCA-associated vasculitis but it is rarely seen during the course of other connective tissue diseases like lupus or Sjogren's syndrome or MCTD. We report 3 cases of pauci-immune crescentic glomerulonephritis in patients with connective tissue disease other than vasculitis. We reviewed literature and made summary of previously reported cases of this rare entity. Clinical and laboratory features of these patients varied widely, but most of patients have met criteria for lupus. In this small population of patients there is no correlation with ANCAs. Most of the patients were treated with aggressive immunosuppression and did well if they were treated early in the course of their disease. One of our patients required renal transplant, but she presented late in the course of her disease, as evidenced by chronicity on her renal biopsy. Whether these patients are overlap of vasculitis and other connective tissue diseases or to be considered as a separate entity is yet to be described. Clinicians must be aware of these presentations because initial presentation can be severe. PMID:27504208

  19. Accelerated aging phenotype in mice with conditional deficiency for mitochondrial superoxide dismutase in the connective tissue.

    PubMed

    Treiber, Nicolai; Maity, Pallab; Singh, Karmveer; Kohn, Matthias; Keist, Alexander F; Ferchiu, Florentina; Sante, Lea; Frese, Sebastian; Bloch, Wilhelm; Kreppel, Florian; Kochanek, Stefan; Sindrilaru, Anca; Iben, Sebastian; Högel, Josef; Ohnmacht, Michael; Claes, Lutz E; Ignatius, Anita; Chung, Jin H; Lee, Min J; Kamenisch, York; Berneburg, Mark; Nikolaus, Thorsten; Braunstein, Kerstin; Sperfeld, Anne-Dorte; Ludolph, Albert C; Briviba, Karlis; Wlaschek, Meinhard; Florin, Lore; Angel, Peter; Scharffetter-Kochanek, Karin

    2011-04-01

    The free radical theory of aging postulates that the production of mitochondrial reactive oxygen species is the major determinant of aging and lifespan. Its role in aging of the connective tissue has not yet been established, even though the incidence of aging-related disorders in connective tissue-rich organs is high, causing major disability in the elderly. We have now addressed this question experimentally by creating mice with conditional deficiency of the mitochondrial manganese superoxide dismutase in fibroblasts and other mesenchyme-derived cells of connective tissues in all organs. Here, we have shown for the first time that the connective tissue-specific lack of superoxide anion detoxification in the mitochondria results in reduced lifespan and premature onset of aging-related phenotypes such as weight loss, skin atrophy, kyphosis (curvature of the spine), osteoporosis and muscle degeneration in mutant mice. Increase in p16(INK4a) , a robust in vivo marker for fibroblast aging, may contribute to the observed phenotype. This novel model is particularly suited to decipher the underlying mechanisms and to develop hopefully novel connective tissue-specific anti-aging strategies.

  20. [The role of vitamin K in the metabolism of connective tissue biopolymers (review)].

    PubMed

    Sharaev, P N

    1984-01-01

    Metabolism of connective tissue biopolymers was studied under conditions of various content of vitamin K in the body. The data obtained suggest the existence of a new metabolic effect of vitamin K--its participation as an allosteric activator in regulation of glucosamine synthetase (EC 5.3.1.19). The anabolic effect of vitamin K on connective tissue is apparently related to an increase in the rate of biosynthesis of glucosamine-6-phosphate--general precursor of glycosaminoglycans, glycoproteins and hexosamine-containing glycolipids. PMID:6369774

  1. Tocilizumab in the treatment of mixed connective tissue disease and overlap syndrome in children

    PubMed Central

    Cabrera, Natalia; Duquesne, Agnes; Desjonquères, Marine; Larbre, Jean-Paul; Lega, Jean-Christophe; Fabien, Nicole; Belot, Alexandre

    2016-01-01

    Arthritis is one of the main manifestations of mixed connective tissue disease (MCTD) and overlap syndrome in children and can be responsible for functional disability. We report on 2 children with arthritis that were dramatically improved by a treatment with interleukin-6 (IL-6) blockers in the context of connective tissue disease. However, in both cases, other systemic autoimmune symptoms were not modified by the treatment and autoantibodies tend to increase, suggesting a differential effect of IL-6 inhibition on articular inflammation and systemic autoimmunity. PMID:27738519

  2. 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

  3. Electrospun nanofibrous scaffolds for engineering soft connective tissues.

    PubMed

    James, Roshan; Toti, Udaya S; Laurencin, Cato T; Kumbar, Sangamesh G

    2011-01-01

    Tissue-engineered medical implants, such as polymeric nanofiber scaffolds, are potential alternatives to autografts and allografts, which are short in supply and carry risks of disease transmission. These scaffolds have been used to engineer various soft connective tissues such as skin, ligament, muscle, and tendon, as well as vascular and neural tissue. Bioactive versions of these materials have been produced by encapsulating molecules such as drugs and growth factors during fabrication. The fibers comprising these scaffolds can be designed to match the structure of the native extracellular matrix (ECM) closely by mimicking the dimensions of the collagen fiber bundles evident in soft connective tissues. These nanostructured implants show improved biological performance over the bulk materials in aspects of cellular infiltration and in vivo integration, and the topography of such scaffolds has been shown to dictate cellular attachment, migration, proliferation, and differentiation, which are critical steps in engineering complex functional tissues and crucial to improved biocompatibility and functional performance. Nanofiber matrices can be fabricated using a variety of techniques, including drawing, molecular self-assembly, freeze-drying, phase separation, and electrospinning. Among these processes, electrospinning has emerged as a simple, elegant, scalable, continuous, and reproducible technique to produce polymeric nanofiber matrices from solutions and their melts. We have shown the ability of this technique to be used to fabricate matrices composed of fibers from a few hundred nanometers to several microns in diameter by simply altering the polymer solution concentration. This chapter will discuss the use of the electrospinning technique in the fabrication of ECM-mimicking scaffolds. Furthermore, selected scaffolds will be seeded with primary adipose-derived stromal cells, imaged using scanning electron microscopy and confocal microscopy, and evaluated in terms

  4. 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.

  5. [Peculiarities of the connective tissue metabolism in patients with hydronephrosis].

    PubMed

    Savenkov, V I; Pavlov, S B

    2014-10-01

    The connective tissue metabolism was investigated in patients, suffering hydronephrosis, caused by obstruction of various etiology of pelvio-ureteric segment (PUS) and ureter, which has a recurrent course. On the 21th day postoperatively the blood indices enhancement was revealed, what characterizes the disorder of collagen synthesis and degradation, including, free (FOP), proteinbinded (PRBOP) and peptidebinded (PEBOP) oxyproline. The changes noted are more pronounced in patients with the inborn obstruction of PUS and recurrent course of the disease. A new marker--the PRBOP to FOP levels ratio--was proposed for prognostication of stricture recurrence.

  6. Interstitial lung disease in the connective tissue diseases.

    PubMed

    Antin-Ozerkis, Danielle; Rubinowitz, Ami; Evans, Janine; Homer, Robert J; Matthay, Richard A

    2012-03-01

    The connective tissue diseases (CTDs) are inflammatory, immune-mediated disorders in which interstitial lung disease (ILD) is common and clinically important. Interstitial lung disease may be the first manifestation of a CTD in a previously healthy patient. CTD-associated ILD frequently presents with the gradual onset of cough and dyspnea, although rarely may present with fulminant respiratory failure. Infection and drug reaction should always be ruled out. A diagnosis of idiopathic ILD should never be made without a careful search for subtle evidence of underlying CTD. Treatment of CTD-ILD typically includes corticosteroids and immunosuppressive agents.

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

    PubMed

    Mérot, O; Le Goff, B

    2014-08-01

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

  8. Connective tissue diseases, arthritis require special patient counseling.

    PubMed

    Neinstein, L S; Katz, B

    1985-07-01

    Systemic lupus erythematous occurs most frequently in reproductive aged women, giving rise to concern about contraception and pregnancy. Most of the literature on contraceptive choices for patients with connective tissue diseases specifically considers oral contraceptives (OCs) with systemic lupus. A possible role of female sex hormones in systemic lupus disease activity is suggested by the constant female-male disease ratio of 9 to 1, the tendency for increased disease activity premenstrually and postpartum, and the report of a 54% prevalence of clinical or serological exacerbation during pregnancy compared with a 4% prevalence in the 6 months preceding pregnancy. Another study however failed to confirm increased prevalence of major nonrenal manifestations of systemic lupus with pregnancy, and the results of 3 studies showed permanent deterioration in 15 of 114 pregnancies. In most cases, therefore, renal function did not deteriorate with pregnancy. The effect of OCs on lupus patients is also unclear despite several reports of exacerbation of lupus by OCs or induction of serologic markers. Studies of women attending family planning clinics do not indicate either developing rheumatologic symptoms or developing positive serologic tests in healthy women on OCs. IUDs should be avoided in lupus patients with moderate or severe anemia or thrombocytopenia, and the possible decreased effectiveness of IUDs for patients on steroids should be considered. Lupus patients should avoid pregnancy until the disease is in clinical remission. Combined OCs should probably be avoided because of the possible exacerbation of symptoms in known lupus. The progestagen-only pill can be considered for lupus patients without renal or liver disease or hypertension if the patient is closely watched. Barrier methods are possible for patients who are reliable and will comply with directions. No absolute contraindications appear to exist for women with rheumatoid arthritis. Women using OCs are

  9. [Fiftieth anniversary of the French Society for Connective Tissue Research].

    PubMed

    Robert, Ladislas; Labat-Robert, Jacqueline; Michel Robert, Alexandre

    2012-01-01

    The Society was founded in 1962, at an international meeting organized at the Biomedical Institute rue des Saints-Pères, in Paris in the Department of Biochemistry headed at that time by Pr. Max F. Jayle, and published in the "Exposés Annuels de Biochimie Médicale" in 1963. At its beginnings a "Club", with a limited number of participants, it expanded rapidly into a Society, renamed recently "French Society of the Biology of Extracellular Matrix", with approximately 200 members working on a variety of subjects. Only six of these teams could present an oral report at the meeting of the Biological Society on January 18, 2012, celebrating this anniversary at the Curie Institute. A few more could send written contributions for this special issue of "Biologie Aujourd'hui". In this short introduction we shall recall some important stages of the developing connective tissue science. Besides such classical subjects, as the macromolecular components of connective tissue matrix, this discipline incorporated progressively receptors, integrins and other molecules, that mediate cell-matrix interactions.

  10. [Relation between autoimmune thyroid diseases and connective tissue diseases].

    PubMed

    Barragán-Garfias, Jorge Alberto; Zárate, Arturo

    2013-01-01

    The main physiological function of the immune system consists in the defense against infectious micro-organisms. Sometimes there is a loss of immunological tolerance with the consequence of ignorance of self-antibodies. Some thyroid diseases are related to autoimmune diseases associated with the most common exocrine glands between them. There are also the autoimmune thyroid organ specific diseases, such as Graves-Basedow and the Hashimoto thyroiditis. It has been shown that there is a higher prevalence of autoimmune thyroid diseases in patients with connective tissue diseases (systemic autoimmune) such as Sjögren syndrome, rheumatoid arthritis, systemic lupus erithmatosis and systemic myopathic diseases. In the same way a higher prevalence of antinuclear antibodies against antigens extracted from the nucleus in patients with a thyroid autoimmune disease has been identified. There is a high percentage of patients with subclinical thyroid diseases, and it is recommended for patients with connective tissue diseases with hypo- or hyperthyroidism to have thyroid globulin and peroxide antibodies measured.

  11. 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

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

    PubMed

    Stojanović, Vesna R; Jovanović, Ivan D; Ugrenović, Sladjana Z; Vasović, Ljiljana P; Živković, Vladimir S; Jocić, Miodrag V; Kundalić, Braca K; Pavlović, Miljana N

    2012-01-01

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

  13. Identification of human connective tissue in transplant of human oral mucosa in nude mice.

    PubMed

    Holmstrup, P; Hansen, I L; Harder, F; Dabelsteen, E

    1984-01-01

    The present study describes a method for identification of connective tissue of human oral mucosal transplants in nude mice. The method was based on the development of a murine antiserum to human fibroblasts. After absorption with murine fibroblasts the antiserum in an immunofluorescence method appeared to react specifically with human connective tissue of frozen sections, whereas the antiserum did not react with murine connective tissue. The antiserum, applied to frozen sections of human oral mucosal transplants in nude mice, could distinguish between human and murine connective tissue in the sections. The ability to distinguish between the two types of tissue was utilized to elucidate a possible relation between epithelial morphology and underlying type of connective tissue. It was found that the formation of rete ridges of transplanted human oral epithelium was dependent on the presence of subepithelial human connective tissue. The method described may be useful for the recognition of human tissue in experimental studies of human transplants to other species.

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

    PubMed

    Stafeev, A A

    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.

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

    PubMed

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

    2014-02-01

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

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

    PubMed

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

    2011-06-01

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

  17. Cutaneous Connective Tissue Diseases: Epidemiology, Diagnosis, and Treatment

    PubMed Central

    Reddy, Bobby Y.; Hantash, Basil M.

    2010-01-01

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

  18. Connective tissue disease-related interstitial lung disease.

    PubMed

    Demoruelle, M Kristen; Mittoo, Shikha; Solomon, Joshua J

    2016-02-01

    Interstitial lung disease (ILD) is commonly present in patients with an underlying connective tissue disease (CTD), particularly those with systemic sclerosis, rheumatoid arthritis, and inflammatory myositis. The clinical spectrum can range from asymptomatic findings on imaging to respiratory failure and death. Distinguishing features in the clinical, radiographic, and histopathologic characteristics of CTD-ILD subsets can predict prognosis and treatment response. Treatment often consists of combinations of immunosuppressive medications, but there is a paucity of guidance in the literature to help clinicians determine appropriate screening and management of CTD-ILD. As such, there is a critical need for studies that can elucidate the natural history of the CTD-ILD, as well as clarify optimal therapies for CTD patients with ILD. PMID:27421215

  19. Connective tissue representation for detection of microcalcifications in digital mammograms

    NASA Astrophysics Data System (ADS)

    McLoughlin, Kristin J.; Bones, Philip J.; Kovesi, Peter

    2002-05-01

    Microcalcification clusters appear as an early sign of breast cancer and play an important role in interpreting mammograms. Progress is reported towards an automated computer aided detection system for clustered microcalcifications utilizing two image feature parameters: local contrast and shape. The use of a shape parameter is necessary to distinguish thin patches of connective tissue from microcalcifications. Two shape parameter techniques are compared in the segmentation of 15 digital mammogram images. The first technique implements the linear Hough transform, while the second uses image phase information in the Fourier domain. In both cases labeling of the image is performed by a deterministic relaxation scheme, in which both image data dn prior beliefs are weighted simultaneously. Similar segmentation results are obtained for each shape parameter technique however the execution time for the phase method is approximately one quarter that for the Hough method. Both techniques offer an improvement over segmentation results obtained without the shape parameter.

  20. Pulmonary arterial hypertension among Filipino patients with connective tissue diseases.

    PubMed

    Santos Estrella, Paul V; Lin, Yih Chang; Navarra, Sandra V

    2007-01-01

    We describe the clinical features, therapies, and clinical course of pulmonary arterial hypertension (PAH) in a group of Filipinos with connective tissue diseases (CTDs). We retrospectively reviewed the records of patients diagnosed with PAH by a two-dimensional echocardiogram as a tricuspid regurgitant jet of more than 25 mmHg. All patients had underlying CTDs, defined by the American College of Rheumatology criteria, and were seen at the rheumatology clinics of the University of Santo Tomas Hospital and the St. Luke's Medical Center, Philippines. Of the 33 patients (32 women) included in the analysis, there were 14 patients with systemic lupus erythematosus (SLE), 12 with scleroderma, 5 with mixed connective tissue disease (MCTD), 1 with primary antiphospholipid syndrome (APS), and 1 with dermatomyositis. The average age at PAH diagnosis was 38 +/- 14 years (mean +/- SD), and the mean duration of illness from CTD to PAH diagnosis was 53 +/- 52 months. Twelve patients had died at the time of this report, with a median duration of 15 months (range 1-57 months) from PAH diagnosis to mortality: six of these had scleroderma, five with SLE, and one with APS. The following therapies were used in this group of patients: low molecular weight heparin, warfarin, calcium-channel blockers, aspirin, cyclophosphamide, bosentan, iloprost, and sildenafil. We have described the clinical profile of PAH in a group of Filipino patients with CTDs, most commonly SLE. Various forms of pharmacologic therapies were used among these patients. Mortality remains high, particularly among those with underlying scleroderma. Early recognition and treatment are crucial in order to provide a better outcome for these patients.

  1. EDTA separation and recombination of epithelium and connective tissue of human oral mucosa. Studies of tissue transplants in nude mice.

    PubMed

    Holmstrup, P; Dabelsteen, E; Harder, F

    1985-01-01

    A possible epithelial-mesenchymal interaction in determining epithelial histologic features of human oral mucosa was examined. The study comprised 74 biopsies of normal buccal mucosa and 54 biopsies of normal palatal mucosa. Epithelium was separated from connective tissue by the use of 1 mM ethylenediamine tetraacetate dihydrate. Self-recombined and cross-recombined epithelial and connective tissues and connective tissue sheets alone were transplanted to subcutaneous sites of nude mice. Histologic examination of cross-recombined palatal epithelium/buccal connective tissue transplants showed a change in keratinization pattern but no major change in number of epithelial cell layers as the result of connective tissue influence. Transplanted sheets of connective tissue after growth for 14 days showed that complete separation of biopsies from buccal mucosa had been obtained. However, palatal mucosa had been incompletely separated as evidenced by re-epithelialization of most of the connective tissue transplants. The consequences of the incomplete palatal epithelium-connective tissue separation are discussed.

  2. Aberrations of dermal connective tissue in patients with cervical artery dissection (sCAD).

    PubMed

    Uhlig, Phillip; Bruckner, Peter; Dittrich, Ralf; Ringelstein, E Bernd; Kuhlenbäumer, Gregor; Hansen, Uwe

    2008-03-01

    Spontaneous cervical artery dissection (sCAD) is a common cause of stroke in patients below 55 years of age. Hereditary connective tissue disorders, including Ehlers-Danlos syndrome type IV, have been associated with sCAD and suprastructural abnormalities of both collagen fibrils and elastic fibers have been found by transmission electron microscopy in the dermis of about 50% of sCAD patients. Here, we investigated dermal connective tissue abnormalities using a novel method. Transmission and immunogold electron microscopy were used to study mechanically generated fragments of dermal matrix suprastructures, in particular collagen fibrils. Analysis of dermal tissue of sCAD patients revealed structurally abnormal collagen fibrils with irregularly contoured surfaces and increased diameters, often associated with a faint or absent banding pattern. Interestingly, only a small number of fibrils displayed short abnormal sections along the length of the fibril. Collagens I and III were present in normal as well as abnormal sections of the fibrils.However, immunogold labeling for the two proteins was strongly increased in abnormal sections.A systematic blinded investigation of skin biopsies of 31 sCAD patients and 17 controls revealed abnormal collagen fibrils in 7 sCAD patients but none of the controls. We conclude that approximately 20% of sCAD patients show collagen fibril alterations, establishing a promising basis for further investigation of connective tissue aberrations in skin biopsies of sCAD patients.

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

    PubMed

    Sullivan, G A; Calkins, C R

    2010-08-01

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

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

    PubMed

    Sullivan, G A; Calkins, C R

    2010-08-01

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

  5. Low Pore Connectivity Increases Bacterial Diversity in Soil▿

    PubMed Central

    Carson, Jennifer K.; Gonzalez-Quiñones, Vanesa; Murphy, Daniel V.; Hinz, Christoph; Shaw, Jeremy A.; Gleeson, Deirdre B.

    2010-01-01

    One of soil microbiology's most intriguing puzzles is how so many different bacterial species can coexist in small volumes of soil when competition theory predicts that less competitive species should decline and eventually disappear. We provide evidence supporting the theory that low pore connectivity caused by low water potential (and therefore low water content) increases the diversity of a complex bacterial community in soil. We altered the pore connectivity of a soil by decreasing water potential and increasing the content of silt- and clay-sized particles. Two textures were created, without altering the chemical properties or mineral composition of the soil, by adding silt- and clay-sized particles of quartz to a quartz-based sandy soil at rates of 0% (sand) or 10% (silt+clay). Both textures were incubated at several water potentials, and the effect on the active bacterial communities was measured using terminal restriction fragment length polymorphism (TRFLP) of bacterial 16S rRNA. Bacterial richness and diversity increased as water potential decreased and soil became drier (P < 0.012), but they were not affected by texture (P > 0.553). Bacterial diversity increased at water potentials of ≤2.5 kPa in sand and ≤4.0 kPa in silt+clay, equivalent to ≤56% water-filled pore space (WFPS) in both textures. The bacterial community structure in soil was affected by both water potential and texture (P < 0.001) and was correlated with WFPS (sum of squared correlations [δ2] = 0.88, P < 0.001). These findings suggest that low pore connectivity is commonly experienced by soil bacteria under field conditions and that the theory of pore connectivity may provide a fundamental principle to explain the high diversity of bacteria in soil. PMID:20418420

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

    PubMed Central

    PAULSEN, FRIEDRICH; THALE, ANDREAS

    1998-01-01

    The papillary layer of the oral part of the human soft palate was studied in 31 subjects of different age by means of histological, immunohistochemical and scanning electron microscopical methods. For scanning electron microscopy a new maceration method was introduced. Results determine epithelial thickness, height and density of connective tissue papillae and their 3-dimensional architecture inside the lining epithelium as well as the collagenous arrangement of the openings of the glandular ducts. The individual connective tissue papillae of the soft palate are compared with the connective tissue boundary on the other side of the oral cavity. The connective tissue plateaux carrying a variable number of connective tissue papillae were found to be the basic structural units of the papillary body. The function of the epithelial-connective tissue interface and the extracellular matrix arrangement in the lamina propria are discussed in order to promote the comparability of normal with pathologically altered human soft palates. PMID:9877301

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

    PubMed

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

    2014-11-01

    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.

  8. Increased functional connectivity within mesocortical networks in open people.

    PubMed

    Passamonti, L; Terracciano, A; Riccelli, R; Donzuso, G; Cerasa, A; Vaccaro, Mg; Novellino, F; Fera, F; Quattrone, A

    2015-01-01

    Openness is a personality trait reflecting absorption in sensory experience, preference for novelty, and creativity, and is thus considered a driving force of human evolution. At the brain level, a relation between openness and dopaminergic circuits has been proposed, although evidence to support this hypothesis is lacking. Recent behavioral research has also found that people with mania, a psychopathological condition linked to dopaminergic dysfunctions, may display high levels of openness. However, whether openness is related to dopaminergic circuits has not been determined thus far. We addressed this issue via three functional magnetic resonance imaging (fMRI) experiments in n=46 healthy volunteers. In the first experiment participants lied at rest in the scanner while in the other two experiments they performed active tasks that included the presentation of pleasant odors and pictures of food. Individual differences in openness and other personality traits were assessed via the NEO-PI-R questionnaire (NEO-Personality Inventory-Revised), a widely employed measure of the five-factor model personality traits. Correlation between fMRI and personality data was analyzed via state-of-art methods assessing resting-state and task-related functional connectivity within specific brain networks. Openness was positively associated with the functional connectivity between the right substantia nigra/ventral tegmental area, the major source of dopaminergic inputs in the brain, and the ipsilateral dorsolateral prefrontal cortex (DLPFC), a key region in encoding, maintaining, and updating information that is relevant for adaptive behaviors. Of note, the same connectivity pattern was consistently found across all of the three fMRI experiments. Given the critical role of dopaminergic signal in gating information in DLPFC, the increased functional connectivity within mesocortical networks in open people may explain why these individuals display a wide "mental permeability" to

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

    PubMed Central

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

    2014-01-01

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

  10. 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.

  11. 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

  12. Connective tissue growth factor is a substrate of ADAM28

    SciTech Connect

    Mochizuki, Satsuki; Tanaka, Rena; Shimoda, Masayuki; Onuma, Junko; Fujii, Yutaka; Jinno, Hiromitsu; Okada, Yasunori

    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 carcinoma cells and the expression correlates with carcinoma cell proliferation and progression in human lung and breast carcinomas. However, information about substrates of ADAM28 is limited. We screened interacting molecules of ADAM28 in human lung cDNA library by yeast two-hybrid system and identified connective tissue growth factor (CTGF). Binding of CTGF to proADAM28 was demonstrated by yeast two-hybrid assay and protein binding assay. ADAM28 cleaved CTGF in dose- and time-dependent manners at the Ala{sup 181}-Tyr{sup 182} and Asp{sup 191}-Pro{sup 192} bonds in the hinge region of the molecule. ADAM28 selectively digested CTGF in the complex of CTGF and vascular endothelial growth factor{sub 165} (VEGF{sub 165}), releasing biologically active VEGF{sub 165} from the complex. RT-PCR and immunohistochemical analyses demonstrated that ADAM28, CTGF and VEGF are commonly co-expressed in the breast carcinoma tissues. These data provide the first evidence that CTGF is a novel substrate of ADAM28 and suggest that ADAM28 may promote VEGF{sub 165}-induced angiogenesis in the breast carcinomas by the CTGF digestion in the CTGF/VEGF{sub 165} complex.

  13. Idiopathic interstitial pneumonias with connective tissue diseases features: A review.

    PubMed

    Cottin, Vincent

    2016-02-01

    A systematic approach is recommended to search for clinical and biological features of connective tissue disease (CTD) in any patient with interstitial lung disease (ILD). In the diagnostic approach to ILD, a diagnosis of CTD should be considered particularly in women and subjects younger than 50 years, and in those with an imaging and/or pathological pattern of non-specific interstitial pneumonia. However, the diagnosis of CTD may be difficult when ILD is the presenting or the dominant manifestation of CTD. A proportion of patients with ILD present symptoms that belong to the spectrum of CTD and/or biological autoimmune features, but do not fulfil diagnostic criteria for a given CTD. Some imaging and histopathological patterns may also suggest the presence of an underlying CTD. Although studies published to date used heterogeneous definitions and terminology for this condition, evidence is accumulating that even limited CTD features are relevant regarding symptoms, imaging features, pathological pattern and possibly evolution to overt CTD, whereas the impact on prognosis needs confirmation. Conversely, autoantibodies alone do not seem to impact the prognosis or management in patients with otherwise typical idiopathic pulmonary fibrosis and no extra-pulmonary manifestation. A collective international multidisciplinary effort has proposed a uniform definition and criteria for 'interstitial pneumonia with autoimmune features', a condition characterized by limited CTD features occurring in the setting of ILD, with the aim of fostering future clinical studies. Referral of ILD patients suspect to have CTD to a rheumatologist and possibly multidisciplinary discussion may contribute to a better management.

  14. 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

  15. Aging of connective tissues: experimental facts and theoretical considerations.

    PubMed

    Labat-Robert, J; Robert, L

    2014-01-01

    In this chapter, we describe in detail the age-dependent modifications of connective tissues, separately for their cellular and extracellular compartments. Cell aging was studied by the in vitro method established by Hayflick as well as by ex vivo explant cultures, and results with both methods are discussed. Follows then the description of age changes of macromolecular components of extracellular matrix as well as the decline with age of receptor-mediated cell-matrix interactions. These interactions mediated by several types of receptors, as integrins, the elastin receptor and others, play a crucial role for the definition and regulation of the differentiated cell phenotype. Age-related modifications of both matrix components and receptors are discussed in order to explain the mechanisms of the age-dependent modulations of cell-matrix interactions. Finally, we discuss the relations between age changes of matrix components and the onset of age-related diseases, especially cardiovascular pathologies mostly involved in age-dependence of functions and limitation of longevity.

  16. [Morphological diagnosis of connective tissue dysplasia in patients, suffering postoperative abdominal hernia].

    PubMed

    Chetverikov, S H; Iashchenko, A M; Ier'omin, Iu V; Vododiuk, V Iu

    2012-05-01

    The results of treatment of 122 patients, to whom alloplasty for postoperative abdominal hernia (POAH) was performed, were analyzed. In 76 patients a connective tissue dysplasia (CTD) was diagnosed.Determination of a various types of collagen content in connective tissue of patients, suffering CTD, may confirm or exclude this diagnosis. Diagnostic significance has the enhancement of a collagen type III content in comparison with such of a type I by three times and more. The method of lectinohistochemical investigation of connective tissue was applied as a precision-enhancing method of a CTD diagnosis. Mosaic or diffuse loss of SNA, LABA, ConA receptors of lectins by collagen fascicles, which reflect carbohydrate determinants of dense and strong collagen fascicles, made of collagen type I, witness the CTD presence. Along with this, there was observed a lectin WGA receptors expression increase, which constitutes a marker of fascicular structures, made of collagen, predominantly type III and a lectin PNA receptors, which are revealed around vessels.

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

    PubMed Central

    Sayar, Ferena; Akhundi, Nasrin; Gholami, Sanaz

    2013-01-01

    Background: 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. Materials and Methods: 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. Results: 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). Conclusion: Enamel matrix protein derivative showed the same results as subepithelial connective tissue graft with relatively easy procedure to perform and low patient morbidity. PMID:23878562

  18. Fibrillin degradation by matrix metalloproteinases: implications for connective tissue remodelling.

    PubMed

    Ashworth, J L; Murphy, G; Rock, M J; Sherratt, M J; Shapiro, S D; Shuttleworth, C A; Kielty, C M

    1999-05-15

    Fibrillin is the principal structural component of the 10-12 nm diameter elastic microfibrils of the extracellular matrix. We have previously shown that both fibrillin molecules and assembled microfibrils are susceptible to degradation by serine proteases. In this study, we have investigated the potential catabolic effects of six matrix metalloproteinases (MMP-2, MMP-3, MMP-9, MMP-12, MMP-13 and MMP-14) on fibrillin molecules and on intact fibrillin-rich microfibrils isolated from ciliary zonules. Using newly synthesized recombinant fibrillin molecules, major cleavage sites within fibrillin-1 were identified. In particular, the six different MMPs generated a major degradation product of approximately 45 kDa from the N-terminal region of the molecule, whereas treatment of truncated, unprocessed and furin-processed C-termini also generated large degradation products. Introduction of a single ectopia lentis-causing amino acid substitution (E2447K; one-letter symbols for amino acids) in a calcium-binding epidermal growth factor-like domain, predicted to disrupt calcium binding, markedly altered the pattern of C-terminal fibrillin-1 degradation. However, the fragmentation pattern of a mutant fibrillin-1 with a comparable E-->K substitution in an upstream calcium-binding epidermal growth factor-like domain was indistinguishable from wild-type molecules. Ultrastructural examination highlighted that fibrillin-rich microfibrils isolated from ciliary zonules were grossly disrupted by MMPs. This is the first demonstration that fibrillin molecules and fibrillin-rich microfibrils are degraded by MMPs and that certain amino acid substitutions change the fragmentation patterns. These studies have important implications for physiological and pathological fibrillin catabolism and for loss of connective tissue elasticity in ageing and disease.

  19. Pulmonary manifestations of Sjögren syndrome, systemic lupus erythematosus, and mixed connective tissue disease.

    PubMed

    Mira-Avendano, Isabel C; Abril, Andy

    2015-05-01

    Interstitial lung disease is a common and often life-threatening manifestation of different connective tissue disorders, often affecting its overall prognosis. Systemic lupus erythematosus, Sjögren syndrome, and mixed connective tissue disease, although all unique diseases, can have lung manifestations as an important part of these conditions. This article reviews the different pulmonary manifestations seen in these 3 systemic rheumatologic conditions.

  20. 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

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

    PubMed

    Empson, Yvonne M; Ekwueme, Emmanuel C; Hong, Jung K; Paynter, Danielle M; Kwansa, Albert L; Brown, Chalmers; Pekkanen, Allison M; Roman, Maren; Rylander, Nichole M; Brolinson, Gunnar P; Freeman, Joseph W

    2014-09-01

    Subfailure matrix injuries such as sprains and strains account for a considerable portion of ligament and tendon pathologies. In addition to the lack of a robust biological healing response, these types of injuries are often characterized by seriously diminished matrix biomechanics. Recent work has shown nanosized particles, such as nanocarbons and nanocellulose, to be effective in modulating cell and biological matrix responses for biomedical applications. In this article, we investigate the feasibility and effect of using high stiffness nanostructures of varying size and shape as nanofillers to mechanically reinforce damaged soft tissue matrices. To this end, nanoparticles (NPs) were characterized using atomic force microscopy and dynamic light scattering techniques. Next, we used a uniaxial tensile injury model to test connective tissue (porcine skin and tendon) biomechanical response to NP injections. After injection into damaged skin and tendon specimens, the NPs, more notably nanocarbons in skin, led to an increase in elastic moduli and yield strength. Furthermore, rat primary patella tendon fibroblast cell activity evaluated using the metabolic water soluble tetrazolium salt assay showed no cytotoxicity of the NPs studied, instead after 21 days nanocellulose-treated tenocytes exhibited significantly higher cell activity when compared with nontreated control tenocytes. Dispersion of nanocarbons injected by solution into tendon tissue was investigated through histologic studies, revealing effective dispersion and infiltration in the treated region. Such results suggest that these high modulus NPs could be used as a tool for damaged connective tissue repair.

  2. [The effect of the biopolymer chondroitin sulfate on reparative regeneration of connective tissue].

    PubMed

    Belova, S V; Norkin, I A; Puchinyan, D M

    2015-01-01

    The research objective is a study of an intra-articular method of introduction of the preparation "mukosat" for stimulation of reparative regeneration of connective tissue of knee joints in rabbits with an experimental arthritis. It is ascertained that intra-articular maintenance of chondroitin sulfate (the preparation "mukosat") acts as a stimulus for reparative regeneration of connective tissue thus showing up positive changes in the status of connective tissue elements of joints: decrease in glycosaminoglycan content in blood serum and normalization of the composition of glycosaminoglycan carbohydrate component. It probably depends on stimulation of biosynthesis of autologous normal glycosaminoglycans in tissues of animal knee joints.

  3. 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.

  4. Connective tissue and bacterial deposits on rubber dam sheet and ePTFE barrier membranes in guided periodontal tissue regeneration.

    PubMed

    Apinhasmit, Wandee; Swasdison, Somporn; Tamsailom, Suphot; Suppipat, Nophadol

    2002-01-01

    The aim of this study was to compare the connective tissue and bacterial deposits on rubber dam sheets and expanded polytetrafluoroethylene membranes used as barrier membranes in guided tissue regeneration for periodontal treatment. Twenty patients having intrabony defects and/or furcation defects were surgically treated by guided tissue regeneration employing either rubber dam sheets (10 patients) or expanded polytetrafluoroethylene membranes (10 patients) as barrier membranes. Four to six weeks after the first operation, membranes were retrieved from the lesion sites and processed for scanning electron microscopy. The lesion-facing surfaces of membranes were examined for the presence of connective tissue and bacterial deposits. The differences between the numbers of fields and the distributions of connective tissue and bacteria on both types of membranes were analysed by the Chi-square test at the level of 0.05 significance. The results showed a lot of fibroblasts with their secreted extracellular matrices, known as components of the connective tissue on rubber dam sheets and expanded polytetrafluoroethylene membranes. There was no significant difference in the total number of connective tissue on both types of membranes (P = 0.456). Many bacterial forms including cocci, bacilli, filaments and spirochetes with the interbacterial matrices were identified. The total number of bacteria on rubber dam sheets was statistically less than that on expanded polytetrafluoroethylene membranes (P < 0.001). The comparable number of connective tissue on both types of membranes suggests that the healing process under both types of membranes was also comparable. Therefore, the rubber dam sheet might be used as a barrier membrane in guided tissue regeneration.

  5. SY 11-4 CONNECTIVE TISSUE DISEASE AND ITS ASSOCIATION WITH ARTERIAL HYPERTENSION.

    PubMed

    Ryan, Michael J

    2016-09-01

    Connective tissue diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis, and scleroderma, have a strong predilection for women and are associated with a marked increase in the prevalence of hypertension. The mechanisms leading to the increased risk of hypertension in these patients remain unclear; however, they are likely related to immune mediated changes in cardiovascular and renal function. Over the past several years, we have elucidated a number of factors that contribute to the development of hypertension during SLE using a widely established experimental model of SLE, the female NZBWF1 mouse. These factors include impaired systemic vascular function, altered renal hemodynamics, and increased oxidative stress and inflammatory cytokines. Recent work from our laboratory has focused on identifying fundamental immunological changes during SLE that ultimately lead to increased cardiovascular risk. This presentation will review clinical and basic evidence for the risk of hypertension during connective tissue diseases and provide experimental evidence that autoantibodies have a central mechanistic role in the pathogenesis of hypertension associated with SLE. PMID:27643119

  6. Connective tissue growth factor regulates cardiac function and tissue remodeling in a mouse model of dilated cardiomyopathy.

    PubMed

    Koshman, Yevgeniya E; Sternlicht, Mark D; Kim, Taehoon; O'Hara, Christopher P; Koczor, Christopher A; Lewis, William; Seeley, Todd W; Lipson, Kenneth E; Samarel, Allen M

    2015-12-01

    Cardiac structural changes associated with dilated cardiomyopathy (DCM) include cardiomyocyte hypertrophy and myocardial fibrosis. Connective tissue growth factor (CTGF) has been associated with tissue remodeling and is highly expressed in failing hearts. Our aim was to test if inhibition of CTGF would alter the course of cardiac remodeling and preserve cardiac function in the protein kinase Cε (PKCε) mouse model of DCM. Transgenic mice expressing constitutively active PKCε in cardiomyocytes develop cardiac dysfunction that was evident by 3 months of age, and that progressed to cardiac fibrosis, heart failure, and increased mortality. Beginning at 3 months of age, PKCε mice were treated with a neutralizing monoclonal antibody to CTGF (FG-3149) for an additional 3 months. CTGF inhibition significantly improved left ventricular (LV) systolic and diastolic functions in PKCε mice, and slowed the progression of LV dilatation. Using gene arrays and quantitative PCR, the expression of many genes associated with tissue remodeling was elevated in PKCε mice, but significantly decreased by CTGF inhibition. However total collagen deposition was not attenuated. The observation of significantly improved LV function by CTGF inhibition in PKCε mice suggests that CTGF inhibition may benefit patients with DCM. Additional studies to explore this potential are warranted.

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

    PubMed

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

    2007-09-22

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

  8. Leucine Supplementation Accelerates Connective Tissue Repair of Injured Tibialis Anterior Muscle

    PubMed Central

    Pereira, Marcelo G.; Silva, Meiricris T.; Carlassara, Eduardo O. C.; Gonçalves, Dawit A.; Abrahamsohn, Paulo A.; Kettelhut, Isis C.; Moriscot, Anselmo S.; Aoki, Marcelo S.; Miyabara, Elen H.

    2014-01-01

    This study investigated the effect of leucine supplementation on the skeletal muscle regenerative process, focusing on the remodeling of connective tissue of the fast twitch muscle tibialis anterior (TA). Young male Wistar rats were supplemented with leucine (1.35 g/kg per day); then, TA muscles from the left hind limb were cryolesioned and examined after 10 days. Although leucine supplementation induced increased protein synthesis, it was not sufficient to promote an increase in the cross-sectional area (CSA) of regenerating myofibers (p > 0.05) from TA muscles. However, leucine supplementation reduced the amount of collagen and the activation of phosphorylated transforming growth factor-β receptor type I (TβR-I) and Smad2/3 in regenerating muscles (p < 0.05). Leucine also reduced neonatal myosin heavy chain (MyHC-n) (p < 0.05), increased adult MyHC-II expression (p < 0.05) and prevented the decrease in maximum tetanic strength in regenerating TA muscles (p < 0.05). Our results suggest that leucine supplementation accelerates connective tissue repair and consequent function of regenerating TA through the attenuation of TβR-I and Smad2/3 activation. Therefore, future studies are warranted to investigate leucine supplementation as a nutritional strategy to prevent or attenuate muscle fibrosis in patients with several muscle diseases. PMID:25268835

  9. Clinical Features of Neuropsychiatric Syndromes in Systemic Lupus Erythematosus and Other Connective Tissue Diseases

    PubMed Central

    Kasama, Tsuyoshi; Maeoka, Airi; Oguro, Nao

    2016-01-01

    Systemic lupus erythematosus (SLE) and related disorders are chronic inflammatory diseases characterized by abnormalities and, in some cases, even complete failure of immune responses as the underlying pathology. Although almost all connective tissue diseases and related disorders can be complicated by various neuropsychiatric syndromes, SLE is a typical connective tissue disease that can cause neurological and psychiatric syndromes. In this review, neuropsychiatric syndromes complicating connective tissue diseases, especially SLE are outlined, and pathological and other conditions that should be considered in the differential diagnosis are also discussed. PMID:26819561

  10. Treatment of gingival recession in two surgical stages: Free gingival graft and connective tissue grafting.

    PubMed

    Henriques, Paulo Sergio Gomes; Nunes, Marcelo Pereira; Pelegrine, Andre Antonio

    2011-01-01

    This report describes a clinical case of severe Miller Class II gingival recession treated by two stages of surgery that combined a free gingival graft and connective tissue grafting. First, a free gingival graft (FGG) was performed to obtain an adequate keratinized tissue level. Three months later, a connective tissue graft (CTG) was performed to obtain root coverage. The results indicated that the FGG allows for a gain in the keratinized tissue level and the CTG allows for root coverage with decreased recession level after 16 months. Therefore, for this type of specific gingival recession, the combination of FGG and CTG can be used.

  11. Aortic tear and dissection related to connective tissues abnormalities resembling Marfan syndrome in a Great Dane.

    PubMed

    Lenz, Jennifer A; Bach, Jonathan F; Bell, Cynthia M; Stepien, Rebecca L

    2015-06-01

    Aortic tears and acute aortic dissection are rarely reported in dogs. This report describes a case of aortic dissection and probable sinus of Valsalva rupture in a young Great Dane with associated histopathologic findings suggestive of a connective tissue abnormality.

  12. [INFLUENCE OF QUINAPRIL IN COMBINATION WITH ANGIOLINE ON THE CONNECTIVE TISSUE COMPONENTS IN THE RATS SERUM WITH EXPERIMENTAL HYPERTENSION].

    PubMed

    Nagornaya, A A; Magomedov, S; Gorchakova, N A; Belenichev, I F; Ghekman, I S; Kuzub, T A

    2015-01-01

    One of the most active inhibitors angiotensin-converting enzyme is quinapril that has a high affinity for tissue ACE, improves endothelial vasodilation, has a wide therapeutic range and beneficient influence on heart rate. A new biological active compound with antioxidant action that has endothelioprotective, cardioprotective, antiischemic action is angiolin. In experimental arterial hypertension in the animals blood serum the activity of collagenase, the content of free and protein connecting fractions of hydroxyproline and indicators that reflect the metabolism of glycosaminoglycans have been increased. Angiolin increases the activity of collagenase free and protein connecting fractions of hydroxyproline comparing to control. Concentration glycosoaminoglycan (GAG) also exceeds the standard data. Quinapril has similar to angiolin action directed effect to the connective tissue components, though losing as proteinconecting of hydroxiproline action. Cooperative application quinapril with angioline most effectively influence the metabolic processes stabilization in experimental animals.

  13. [INFLUENCE OF QUINAPRIL IN COMBINATION WITH ANGIOLINE ON THE CONNECTIVE TISSUE COMPONENTS IN THE RATS SERUM WITH EXPERIMENTAL HYPERTENSION].

    PubMed

    Nagornaya, A A; Magomedov, S; Gorchakova, N A; Belenichev, I F; Ghekman, I S; Kuzub, T A

    2015-01-01

    One of the most active inhibitors angiotensin-converting enzyme is quinapril that has a high affinity for tissue ACE, improves endothelial vasodilation, has a wide therapeutic range and beneficient influence on heart rate. A new biological active compound with antioxidant action that has endothelioprotective, cardioprotective, antiischemic action is angiolin. In experimental arterial hypertension in the animals blood serum the activity of collagenase, the content of free and protein connecting fractions of hydroxyproline and indicators that reflect the metabolism of glycosaminoglycans have been increased. Angiolin increases the activity of collagenase free and protein connecting fractions of hydroxyproline comparing to control. Concentration glycosoaminoglycan (GAG) also exceeds the standard data. Quinapril has similar to angiolin action directed effect to the connective tissue components, though losing as proteinconecting of hydroxiproline action. Cooperative application quinapril with angioline most effectively influence the metabolic processes stabilization in experimental animals. PMID:27089728

  14. Life-threatening acute pneumonitis in mixed connective tissue disease: a case report and literature review.

    PubMed

    Rath, Eva; Zandieh, Shahin; Löckinger, Alexander; Hirschl, Mirko; Klaushofer, Klaus; Zwerina, Jochen

    2015-10-01

    Mixed connective tissue disease (MCTD) is a rare connective tissue disease frequently involving the lungs. The main characteristic is a systemic sclerosis-like picture of slowly progressing interstitial lung disease consistent with lung fibrosis, while pulmonary arterial hypertension is rare. Herein, we present a case of a newly diagnosed MCTD patient developing life-threatening acute pneumonitis similar to lupus pneumonitis. Previous literature on this exceptionally rare complication of MCTD is reviewed and differential diagnosis and management discussed.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Increased default mode network connectivity associated with meditation.

    PubMed

    Jang, Joon Hwan; Jung, Wi Hoon; Kang, Do-Hyung; Byun, Min Soo; Kwon, Soo Jin; Choi, Chi-Hoon; Kwon, Jun Soo

    2011-01-10

    Areas associated with the default mode network (DMN) are substantially similar to those associated with meditation practice. However, no studies on DMN connectivity during resting states have been conducted on meditation practitioners. It was hypothesized that meditators would show heightened functional connectivity in areas of cortical midline activity. Thirty-five meditation practitioners and 33 healthy controls without meditation experience were included in this study. All subjects received 4.68-min resting state functional scanning runs. The posterior cingulate cortex and medial prefrontal cortex were chosen as seed regions for the DMN map. Meditation practitioners demonstrated greater functional connectivity within the DMN in the medial prefrontal cortex area (xyz=339-21) than did controls. These results suggest that the long-term practice of meditation may be associated with functional changes in regions related to internalized attention even when meditation is not being practiced.

  20. Effects of microgravity on rat bone, cartlage and connective tissues

    NASA Technical Reports Server (NTRS)

    Doty, S.

    1990-01-01

    The response to hypogravity by the skeletal system was originally thought to be the result of a reduction in weight bearing. Thus a reduced rate of new bone formation in the weight-bearing bones was accepted, when found, as an obvious result of hypogravity. However, data on non-weight-bearing tissues have begun to show that other physiological changes can be expected to occur to animals during spaceflight. This overview of the Cosmos 1887 data discusses these results as they pertain to individual bones or tissues because the response seems to depend on the architecture and metabolism of each tissue under study. Various effects were seen in different tissues from the rats flown on Cosmos 1887. The femur showed a reduced bone mineral content but only in the central region of the diaphysis. This same region in the tibia showed changes in the vascularity of bone as well as some osteocytic cell death. The humerus demonstrated reduced morphometric characteristics plus a decrease in mechanical stiffness. Bone mineral crystals did not mature normally as a result of flight, suggesting a defect in the matrix mineralization process. Note that these changes relate directly to the matrix portion of the bone or some function of bone which slowly responds to changes in the environment. However, most cellular functions of bone are rapid responders. The stimulation of osteoblast precursor cells, the osteoblast function in collagen synthesis, a change in the proliferation rate of cells in the epiphyseal growth plate, the synthesis and secretion of osteocalcin, and the movement of water into or out of tissues, are all processes which respond to environmental change. These rapidly responding events produced results from Cosmos 1887 which were frequently quite different from previous space flight data.

  1. Focal dermal hypoplasia: ultrastructural abnormalities of the connective tissue.

    PubMed

    del Carmen Boente, María; Asial, Raúl A; Winik, Beatriz C

    2007-02-01

    We followed over 10 years three girls with focal dermal hypoplasia syndrome. The histopathological changes demonstrated at the optical level an hypoplastic dermis with thin and scarce collagen bundles and a marked diminution of elastic fibers. Mature adipose tissue was found scattered within the papillary and reticular dermis. No alterations in the basal membrane were observed by immunocytochemical or ultrastructural techniques. Ultrastructurally, in the skin-affected areas, loosely arranged collagen bundles composed of few fibrils were seen scattered in the extracellular matrix. Scarce elastic fibers of normal morphology were also observed. Fibroblasts were smaller, oval-shaped, and diminished in number with a poorly developed cytoplasm. In these fibroblasts, the most conspicuous feature was a remarkable and irregular thickening of the nuclear fibrous lamina. Taking into account that a common link between all laminopaties may be a failure of stem cells to regenerate mesenchymal tissue, this failure would induce the dermal hypoplasia observed in our patients presenting Goltz syndrome.

  2. Cardiovascular risk and its modification in patients with connective tissue diseases.

    PubMed

    O'Sullivan, Miriam; Bruce, Ian N; Symmons, Deborah P M

    2016-02-01

    It is well documented that patients with systemic lupus erythematosus (SLE) are at an increased risk of atherosclerotic cardiovascular (CV) disease. There is evidence that traditional risk factors and disease-related factors are involved in this increased risk. Less is known about CV risk and outcomes in other connective tissue diseases (CTDs). Future longitudinal observational studies may help to answer these important questions; however, because CTDs are rare, collaboration between clinicians with similar research interests is needed to ensure sufficiently large cohorts are available to address these issues. Here, we review the evidence available for CV risk in CTDs and discuss the benefits of longitudinal observational studies in identifying CV outcomes. Structured care protocols for the management of CV risk in CTDs are lacking. We propose a target-based approach to assessing and managing CV risk in CTDs. PMID:27421218

  3. 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

  4. Conditional overexpression of connective tissue growth factor disrupts postnatal lung development.

    PubMed

    Wu, Shu; Platteau, Astrid; Chen, Shaoyi; McNamara, George; Whitsett, Jeffrey; Bancalari, Eduardo

    2010-05-01

    Connective tissue growth factor (CTGF) is a member of an emerging family of immediate-early gene products that coordinates complex biological processes during development, differentiation, and tissue repair. Overexpression of CTGF is associated with mechanical ventilation with high tidal volume and oxygen exposure in newborn lungs. However, the role of CTGF in postnatal lung development and remodeling is not well understood. In the present study, a double-transgenic mouse model was generated with doxycycline-inducible overexpression of CTGF in respiratory epithelial cells. Overexpression of CTGF from Postnatal Days 1-14 resulted in thicker alveolar septa and decreased secondary septal formation. This is correlated with increased myofibroblast differentiation and disorganized elastic fiber deposition in alveolar septa. Overexpression of CTGF also decreased alveolar capillary network formation. There were increased alpha-smooth muscle actin expression and collagen deposition, and dramatic thickening in the peribronchial/peribronchiolar and perivascular regions in the double-transgenic lungs. Furthermore, overexpression of CTGF increased integrin-linked kinase expression, activated its downstream signaling target, Akt, as well as increased mRNA expression of fibronectin. These data demonstrate that overexpression of CTGF disrupts alveologenesis and capillary formation, and induces fibrosis during the critical period of alveolar development. These histologic changes are similar to those observed in lungs of infants with bronchopulmonary dysplasia.

  5. Changes in connective tissue of M. semitendinosus as a response to different growth paths in steers.

    PubMed

    Harper, G S; Allingham, P G; Le Feuvre, R P

    1999-10-01

    The effect of growth path, as opposed to advancing age, on the biophysical and biochemical properties of muscle connective tissue was investigated. Nine-month old Brahman-cross steers were grown across either an uninterrupted path, or paths that incorporated weight-loss and then weight gain on two different diets: one group was realimented on pasture, whilst the other was realimented on a grain-based diet. Biophysical attributes of connective tissue toughness (Compression and Adhesion) in the semitendinosus muscle, were significantly reduced by treatment (P<0.05): weight loss with grain realimentation being the least tough in regard to the connective tissue component. Variance within the biophysical attributes was modelled statistically. Statistically significant models included terms for the post-slaughter connective tissue content as well as tissue contents of the enzymes lactate dehydrogenase and isocitrate dehydrogenase. The data suggest that biochemical measurements made up to 100 days prior to slaughter, may have value as indicators of final connective tissue toughness. PMID:22063087

  6. Lipid signaling in adipose tissue: Connecting inflammation & metabolism.

    PubMed

    Masoodi, Mojgan; Kuda, Ondrej; Rossmeisl, Martin; Flachs, Pavel; Kopecky, Jan

    2015-04-01

    Obesity-associated low-grade inflammation of white adipose tissue (WAT) contributes to development of insulin resistance and other disorders. Accumulation of immune cells, especially macrophages, and macrophage polarization from M2 to M1 state, affect intrinsic WAT signaling, namely anti-inflammatory and proinflammatory cytokines, fatty acids (FA), and lipid mediators derived from both n-6 and n-3 long-chain PUFA such as (i) arachidonic acid (AA)-derived eicosanoids and endocannabinoids, and (ii) specialized pro-resolving lipid mediators including resolvins derived from both eicosapentaenoic (EPA) and docosahexaenoic acid (DHA), lipoxins (AA metabolites), protectins and maresins (DHA metabolites). In this respect, potential differences in modulating adipocyte metabolism by various lipid mediators formed by inflammatory M1 macrophages typical of obese state, and non-inflammatory M2 macrophages typical of lean state remain to be established. Studies in mice suggest that (i) transient accumulation of M2 macrophages could be essential for the control of tissue FA levels during activation of lipolysis, (ii) currently unidentified M2 macrophage-borne signaling molecule(s) could inhibit lipolysis and re-esterification of lipolyzed FA back to triacylglycerols (TAG/FA cycle), and (iii) the egress of M2 macrophages from rebuilt WAT and removal of the negative feedback regulation could allow for a full unmasking of metabolic activities of adipocytes. Thus, M2 macrophages could support remodeling of WAT to a tissue containing metabolically flexible adipocytes endowed with a high capacity of both TAG/FA cycling and oxidative phosphorylation. This situation could be exemplified by a combined intervention using mild calorie restriction and dietary supplementation with EPA/DHA, which enhances the formation of "healthy" adipocytes. This article is part of a Special Issue entitled Oxygenated metabolism of PUFA: analysis and biological relevance." PMID:25311170

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

    Kemp, Anne

    2013-10-01

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

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

    PubMed

    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.

  10. 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

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

    PubMed Central

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

    2013-01-01

    Background Heart failure (HF) is associated with excessive extracellular matrix (ECM) deposition and abnormal ECM degradation leading to cardiac fibrosis. Connective Tissue Growth Factor (CTGF) modulates ECM production during inflammatory tissue injury, but available data on CTGF gene expression in failing human heart and its response to mechanical unloading are limited. Methods and Results LV tissue from patients undergoing cardiac transplantation for ischemic (ICM; n=20) and dilated (DCM; n=20) cardiomyopathies, and from nonfailing (NF; n=20) donor hearts were examined. Paired samples (n=15) from patients undergoing LV assist device (LVAD) implantation as “bridge to transplant” (34-1145 days) were also analyzed. There was more interstitial fibrosis in both ICM and DCM compared to NF hearts. Hydroxyproline concentration was also significantly increased in DCM relative to NF samples. The expression of CTGF,TGFB1, COL1-A1, COL3-A1, MMP2 and MMP9 mRNAs in ICM and DCM were also significantly elevated as compared to NF controls. Although TGFB1, CTGF, COL1-A1, and COL3-A1 mRNA levels were reduced by unloading, there was only a modest reduction in tissue fibrosis and no difference in protein-bound hydroxyproline concentration between pre- and post-LVAD tissue samples. The persistent fibrosis may be related to a concomitant reduction in MMP9 mRNA and protein levels following unloading. Conclusions CTGF may be a key regulator of fibrosis during maladaptive remodeling and progression to HF. Although mechanical unloading normalizes most genotypic and functional abnormalities, its effect on ECM remodeling during HF is incomplete. PMID:23582094

  12. Changes in pulmonary connective tissue proteins after a single intratracheal instillation of cadmium chloride in the rat

    SciTech Connect

    Kobrle, V.; Mirejovska, E.; Holusa, R.; Hurych, J.

    1986-06-01

    Changes of soluble and insoluble fractions of pulmonary connective tissue proteins were studied in rats for 2-84 days following a single intratracheal instillation of cadmium chloride (10 micrograms Cd/sup 2 +//lung). A transient decrease in body weight and an immediate increase in lung wet weight (200% of control value, P less than 0.01) were observed. Incorporation of (/sup 14/C)proline and its conversion to (/sup 14/C)hydroxyproline in vivo into different soluble and insoluble fractions of connective tissue revealed an increased metabolic turnover elicited by cadmium intoxication. A lag in the maturation of collagen into higher functional forms in the early phase of the process was demonstrated. A striking decrease in elastin was found in first 7 days (40-50%). However, this acute damage of pulmonary connective tissue was followed by a permanent increase of collagen and elastin concentration in the later phase of recovery. Histopathologic examination 14-84 days after cadmium instillation confirmed the presence of lesions in pulmonary tissue with an initial inflammation followed by reparatory changes.

  13. 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.

  14. Ultrastructural Changes Associated with Reversible Stiffening in Catch Connective Tissue of Sea Cucumbers.

    PubMed

    Tamori, Masaki; Ishida, Kinji; Matsuura, Eri; Ogasawara, Katsutoshi; Hanasaka, Tomohito; Takehana, Yasuhiro; Motokawa, Tatsuo; Osawa, Tokuji

    2016-01-01

    The dermis of sea cucumbers is a catch connective tissue or a mutable collagenous tissue that shows rapid, large and reversible stiffness changes in response to stimulation. The main component of the dermis is the extracellular material composed of collagen fibrils embedded in a hydrogel of proteoglycans. The stiffness of the extracellular material determines that of the dermis. The dermis has three mechanical states: soft (Sa), standard (Sb) and stiff (Sc). We studied the ultrastructural changes associated with the stiffness changes. Transverse sections of collagen fibrils in the dermis showed irregular perimeters with electron-dense protrusions or arms that cross-bridged between fibrils. The number of cross-bridges increased in stiffer dermis. The distance between the fibrils was shorter in Sc than that in other states, which was in accord with the previous report that water exuded from the tissue in the transition Sb→Sc. The ultrastructure of collagen fibrils that had been isolated from the dermis was also studied. Fibrils aggregated by tensilin, which causes the transition Sa→Sb possibly through an increase in cohesive forces between fibrils, had larger diameter than those dispersed by softenin, which antagonizes the effect of tensilin. No cross-bridges were found in isolated collagen fibrils. From the present ultrastructural study we propose that three different mechanisms work together to increase the dermal stiffness. 1.Tensilin makes collagen fibrils stronger and stiffer in Sa→Sb through an increase in cohesive forces between subfibrils that constituted fibrils; 2. Cross-bridging by arms caused the fibrils to be a continuous network of bundles both in Sa→Sb and in Sb→Sc; 3. The matrix embedding the fibril network became stiffer in Sb→Sc, which was produced by bonding associated with water exudation. PMID:27192546

  15. Ultrastructural Changes Associated with Reversible Stiffening in Catch Connective Tissue of Sea Cucumbers.

    PubMed

    Tamori, Masaki; Ishida, Kinji; Matsuura, Eri; Ogasawara, Katsutoshi; Hanasaka, Tomohito; Takehana, Yasuhiro; Motokawa, Tatsuo; Osawa, Tokuji

    2016-01-01

    The dermis of sea cucumbers is a catch connective tissue or a mutable collagenous tissue that shows rapid, large and reversible stiffness changes in response to stimulation. The main component of the dermis is the extracellular material composed of collagen fibrils embedded in a hydrogel of proteoglycans. The stiffness of the extracellular material determines that of the dermis. The dermis has three mechanical states: soft (Sa), standard (Sb) and stiff (Sc). We studied the ultrastructural changes associated with the stiffness changes. Transverse sections of collagen fibrils in the dermis showed irregular perimeters with electron-dense protrusions or arms that cross-bridged between fibrils. The number of cross-bridges increased in stiffer dermis. The distance between the fibrils was shorter in Sc than that in other states, which was in accord with the previous report that water exuded from the tissue in the transition Sb→Sc. The ultrastructure of collagen fibrils that had been isolated from the dermis was also studied. Fibrils aggregated by tensilin, which causes the transition Sa→Sb possibly through an increase in cohesive forces between fibrils, had larger diameter than those dispersed by softenin, which antagonizes the effect of tensilin. No cross-bridges were found in isolated collagen fibrils. From the present ultrastructural study we propose that three different mechanisms work together to increase the dermal stiffness. 1.Tensilin makes collagen fibrils stronger and stiffer in Sa→Sb through an increase in cohesive forces between subfibrils that constituted fibrils; 2. Cross-bridging by arms caused the fibrils to be a continuous network of bundles both in Sa→Sb and in Sb→Sc; 3. The matrix embedding the fibril network became stiffer in Sb→Sc, which was produced by bonding associated with water exudation.

  16. Ultrastructural Changes Associated with Reversible Stiffening in Catch Connective Tissue of Sea Cucumbers

    PubMed Central

    Tamori, Masaki; Ishida, Kinji; Matsuura, Eri; Ogasawara, Katsutoshi; Hanasaka, Tomohito; Takehana, Yasuhiro; Motokawa, Tatsuo; Osawa, Tokuji

    2016-01-01

    The dermis of sea cucumbers is a catch connective tissue or a mutable collagenous tissue that shows rapid, large and reversible stiffness changes in response to stimulation. The main component of the dermis is the extracellular material composed of collagen fibrils embedded in a hydrogel of proteoglycans. The stiffness of the extracellular material determines that of the dermis. The dermis has three mechanical states: soft (Sa), standard (Sb) and stiff (Sc). We studied the ultrastructural changes associated with the stiffness changes. Transverse sections of collagen fibrils in the dermis showed irregular perimeters with electron-dense protrusions or arms that cross-bridged between fibrils. The number of cross-bridges increased in stiffer dermis. The distance between the fibrils was shorter in Sc than that in other states, which was in accord with the previous report that water exuded from the tissue in the transition Sb→Sc. The ultrastructure of collagen fibrils that had been isolated from the dermis was also studied. Fibrils aggregated by tensilin, which causes the transition Sa→Sb possibly through an increase in cohesive forces between fibrils, had larger diameter than those dispersed by softenin, which antagonizes the effect of tensilin. No cross-bridges were found in isolated collagen fibrils. From the present ultrastructural study we propose that three different mechanisms work together to increase the dermal stiffness. 1.Tensilin makes collagen fibrils stronger and stiffer in Sa→Sb through an increase in cohesive forces between subfibrils that constituted fibrils; 2. Cross-bridging by arms caused the fibrils to be a continuous network of bundles both in Sa→Sb and in Sb→Sc; 3. The matrix embedding the fibril network became stiffer in Sb→Sc, which was produced by bonding associated with water exudation. PMID:27192546

  17. 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.

  18. Should Endovascular Therapy Be Considered for Patients With Connective Tissue Disorder?

    PubMed

    Gagné-Loranger, Maude; Voisine, Pierre; Dagenais, François

    2016-01-01

    Because of early diagnosis, strict imaging follow-up, and advances in medical and surgical management, life expectancy of Marfan patients has dramatically improved since the 1970s. Although disease of the root and ascending aorta are more frequent in patients with connective tissue disorders, a subset of patients present with diffuse disease that might involve any portion of the thoracoabdominal aorta. Thoracic endovascular aortic repair (TEVAR) has gained widespread acceptance for the treatment of different pathologies of the descending aorta. In contrast, TEVAR in patients with connective tissue disorders is associated with a high risk of early and mid-term complications and reinterventions. Currently, a consensus of experts recommend that an open approach should be reserved for use in acceptable risk candidates with connective tissue disorders. TEVAR should be considered solely in patients in a complex repeat surgical setting or in patients judged to have prohibitive open surgical risk. Finally, as a bridge to a definite open repair, TEVAR might be life-saving in patients with connective tissue disorders who present with exsanguination or severe malperfusion. Future developments in stent-graft technology might decrease stent-graft-related complications in patients with connective tissue disorders, although securing a device with radial force in a fragile aorta in the long-term will be challenging.

  19. Morphometric analysis of connective tissue sheaths of sural nerve in diabetic and nondiabetic patients.

    PubMed

    Kundalić, Braca; Ugrenović, Slađana; Jovanović, Ivan; Stefanović, Natalija; Petrović, Vladimir; Kundalić, Jasen; Stojanović, Vesna; Živković, Vladimir; Antić, Vladimir

    2014-01-01

    One of the most common complications of diabetes mellitus is diabetic neuropathy. It may be provoked by metabolic and/or vascular factors, and depending on duration of disease, various layers of nerve may be affected. Our aim was to investigate influence of diabetes on the epineurial, perineurial, and endoneurial connective tissue sheaths. The study included 15 samples of sural nerve divided into three groups: diabetic group, peripheral vascular disease group, and control group. After morphological analysis, morphometric parameters were determined for each case using ImageJ software. Compared to the control group, the diabetic cases had significantly higher perineurial index (P < 0.05) and endoneurial connective tissue percentage (P < 0.01). The diabetic group showed significantly higher epineurial area (P < 0.01), as well as percentage of endoneurial connective tissue (P < 0.01), in relation to the peripheral vascular disease group. It is obvious that hyperglycemia and ischemia present in diabetes lead to substantial changes in connective tissue sheaths of nerve, particularly in peri- and endoneurium. Perineurial thickening and significant endoneurial fibrosis may impair the balance of endoneurial homeostasis and regenerative ability of the nerve fibers. Future investigations should focus on studying the components of extracellular matrix of connective tissue sheaths in diabetic nerves.

  20. Morphometric analysis of connective tissue sheaths of sural nerve in diabetic and nondiabetic patients.

    PubMed

    Kundalić, Braca; Ugrenović, Slađana; Jovanović, Ivan; Stefanović, Natalija; Petrović, Vladimir; Kundalić, Jasen; Stojanović, Vesna; Živković, Vladimir; Antić, Vladimir

    2014-01-01

    One of the most common complications of diabetes mellitus is diabetic neuropathy. It may be provoked by metabolic and/or vascular factors, and depending on duration of disease, various layers of nerve may be affected. Our aim was to investigate influence of diabetes on the epineurial, perineurial, and endoneurial connective tissue sheaths. The study included 15 samples of sural nerve divided into three groups: diabetic group, peripheral vascular disease group, and control group. After morphological analysis, morphometric parameters were determined for each case using ImageJ software. Compared to the control group, the diabetic cases had significantly higher perineurial index (P < 0.05) and endoneurial connective tissue percentage (P < 0.01). The diabetic group showed significantly higher epineurial area (P < 0.01), as well as percentage of endoneurial connective tissue (P < 0.01), in relation to the peripheral vascular disease group. It is obvious that hyperglycemia and ischemia present in diabetes lead to substantial changes in connective tissue sheaths of nerve, particularly in peri- and endoneurium. Perineurial thickening and significant endoneurial fibrosis may impair the balance of endoneurial homeostasis and regenerative ability of the nerve fibers. Future investigations should focus on studying the components of extracellular matrix of connective tissue sheaths in diabetic nerves. PMID:25147820

  1. 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.

  2. Morphometric Analysis of Connective Tissue Sheaths of Sural Nerve in Diabetic and Nondiabetic Patients

    PubMed Central

    Kundalić, Braca; Ugrenović, Slađana; Jovanović, Ivan; Stefanović, Natalija; Petrović, Vladimir; Kundalić, Jasen; Stojanović, Vesna; Živković, Vladimir; Antić, Vladimir

    2014-01-01

    One of the most common complications of diabetes mellitus is diabetic neuropathy. It may be provoked by metabolic and/or vascular factors, and depending on duration of disease, various layers of nerve may be affected. Our aim was to investigate influence of diabetes on the epineurial, perineurial, and endoneurial connective tissue sheaths. The study included 15 samples of sural nerve divided into three groups: diabetic group, peripheral vascular disease group, and control group. After morphological analysis, morphometric parameters were determined for each case using ImageJ software. Compared to the control group, the diabetic cases had significantly higher perineurial index (P < 0.05) and endoneurial connective tissue percentage (P < 0.01). The diabetic group showed significantly higher epineurial area (P < 0.01), as well as percentage of endoneurial connective tissue (P < 0.01), in relation to the peripheral vascular disease group. It is obvious that hyperglycemia and ischemia present in diabetes lead to substantial changes in connective tissue sheaths of nerve, particularly in peri- and endoneurium. Perineurial thickening and significant endoneurial fibrosis may impair the balance of endoneurial homeostasis and regenerative ability of the nerve fibers. Future investigations should focus on studying the components of extracellular matrix of connective tissue sheaths in diabetic nerves. PMID:25147820

  3. Nonspecific interstitial pneumonia overlaps organizing pneumonia in lung-dominant connective tissue disease.

    PubMed

    Li, Xue-Ren; Peng, Shou-Chun; Wei, Lu-Qing

    2015-01-01

    Here, we reported two cases of nonspecific interstitial pneumonia overlap organizing pneumonia (NSIP/OP) with lung-dominant connective tissue disease (LD-ILD). The first case is a patient with hands of chapped skin, right-sided pleuritic chest discomfort, weakness, positive ANA and antibodies to Ro/SS-A (+++) and Ro-52 (++). In the second case, there were Reynaud's disease, and nucleolus-ANA increased (1:800). Chest high resolution CT scan in both cases showed ground-glass opacifications, predominantly in basal and subpleural region and the pathologic manifestation were correlated with NSIP/OP, which were previously discovered in Sjogren syndrome, PM/DM and other rheumatic diseases. The two cases of NSIP/OP with LD-CTD we reported expand disease spectrum of NSIP/OP pathological types in ILD. However, it is necessary to process large-scale studies.

  4. [Connective tissue growth factor (CTGF): a key factor in the onset and progression of kidney damage].

    PubMed

    Sánchez-López, E; Rodrigues Díez, R; Rodríguez Vita, J; Rayego Mateos, S; Rodrigues Díez, R R; Rodríguez García, E; Lavoz Barria, C; Mezzano, S; Egido, J; Ortiz, A; Ruiz-Ortega, M; Selgas, R

    2009-01-01

    Connective tissue growth factor (CTGF) is increased in several pathologies associated with fibrosis, including multiple renal diseases. CTGF is involved in biological processes such as cell cycle regulation, migration, adhesion and angiogenesis. Its expression is regulated by various factors involved in renal damage, such as transforming growth factor- , Angiotensin II, high concentrations of glucose and cellular stress. CTGF is involved in the initiation and progression of renal damage to be able to induce an inflammatory response and promote fibrosis, identified as a potential therapeutic target in the treatment of kidney diseases. In this paper we review the main actions of CTGF in renal disease, the intracellular action mechanisms and therapeutic strategies for its blocking.

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

    PubMed Central

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

    2009-01-01

    It has been more than 50 years since antinuclear antibodies were first discovered and found to be associated with connective tissue diseases. Since then different methods have been described and used for their detection or confirmation. For many decades immunofluorescent antinuclear antibody test has been the "gold standard" in the diagnosis of these disorders. However to increase the sensitivity and specificity of antinuclear antibody detection further approaches were explored. Today a battery of newer techniques are available some of which are now considered better and are competing with the older methods. This article provides an overview on advancement in antinuclear antibody detection methods, their future prospects, advantages, disadvantages and guidelines for use of these tests. PMID:19121207

  6. [Viscoelastic properties of isolated papillary muscle: contributions of connective tissue skeleton and intracellular matrix].

    PubMed

    Protsenko, Iu L; Kobelev, A V; Lukin, O N; Balakin, A A; Smoliuk, L T

    2009-07-01

    Peculiarities of viscoelastic behavior of rabbit papillary muscle in passive state are studied by transversal versus longitudinal deformation curves, stress-strain and hysteresis curves, and stress relaxation curves under ramp stretching. The papillary muscle was chosen because of mostly longitudinal orientation of fibers and its elongated shape, which both make it as an appropriate model for uniaxial tests. The problem of evaluation of connective tissue protein structures and intracellular matrix contribution into the properties under consideration is solved by using the maceration method to remove intracellular structures. The different contribution of intracellular and extracellular protein features into total properties of a papillary muscle leads to nonlinearity of myocardial viscoelastic properties, such as the increase of differential elastic module and relaxation time with deformation.

  7. Petroleum distillate solvents as risk factors for undifferentiated connective tissue disease (UCTD).

    PubMed

    Lacey, J V; Garabrant, D H; Laing, T J; Gillespie, B W; Mayes, M D; Cooper, B C; Schottenfeld, D

    1999-04-15

    Occupational solvent exposure may increase the risk of connective tissue disease (CTD). The objective of this case-control study was to investigate the relation between undifferentiated connective tissue disease (UCTD) and solvent exposure in Michigan and Ohio. Women were considered to have UCTD if they did not meet the American College of Rheumatology classification criteria for any CTD but had at least two documented signs, symptoms, or laboratory abnormalities suggestive of a CTD. Detailed information on solvent exposure was ascertained from 205 cases, diagnosed between 1980 and 1992, and 2,095 population-based controls. Age-adjusted odds ratios (OR) and 95 percent confidence intervals (CI) were calculated for all exposures. Among 16 self-reported occupational activities with potential solvent exposure, furniture refinishing (OR = 9.73, 95 percent CI 1.48-63.90), perfume, cosmetic, or drug manufacturing (OR = 7.71, 95 percent CI 2.24-26.56), rubber product manufacturing (OR = 4.70, 95 percent CI 1.75-12.61), work in a medical diagnostic or pathology laboratory (OR = 4.52, 95 percent CI 2.27-8.97), and painting or paint manufacturing (OR = 2.87, 95 percent CI 1.06-7.76) were significantly associated with UCTD. After expert review of self-reported exposure to ten specific solvents, paint thinners or removers (OR = 2.73, 95 percent CI 1.80-4.16) and mineral spirits (OR = 1.81, 95 percent CI 1.09-3.02) were associated with UCTD. These results suggest that exposure to petroleum distillates increases the risk of developing UCTD.

  8. Evidence for increased tissue androgen sensitivity in neurturin knockout mice.

    PubMed

    Simanainen, Ulla; Gao, Yan Ru Ellen; Desai, Reena; Jimenez, Mark; Spaliviero, Jennifer; Keast, Janet R; Handelsman, David J

    2013-01-01

    Neurturin (NTN) is a member of the glial cell line-derived neurotrophic factor (GDNF) family and signals through GDNF family receptor alpha 2 (GFRα2). We hypothesised that epithelial atrophy reported in the reproductive organs of Ntn (Nrtn)- and Gfrα2 (Gfra2)-deficient mice could be due to NTN affecting the hormonal environment. To investigate this, we compared the reproductive organs of Ntn- and Gfrα2-deficient male mice in parallel with an analysis of their circulating reproductive hormone levels. There were no significant structural changes within the organs of the knockout mice; however, serum and intratesticular testosterone and serum LH levels were very low. To reconcile these observations, we tested androgen sensitivity by creating a dihydrotestosterone (DHT) clamp (castration plus DHT implant) to create fixed circulating levels of androgens, allowing the evaluation of androgen-sensitive endpoints. At the same serum DHT levels, serum LH levels were lower and prostate and seminal vesicle weights were higher in the Ntn knockout (NTNKO) mice than in the wild-type mice, suggesting an increased response to androgens in the accessory glands and hypothalamus and pituitary of the NTNKO mice. Testicular and pituitary responsiveness was unaffected in the NTNKO males, as determined by the response to the human chorionic gonadotrophin or GNRH analogue, leuprolide, respectively. In conclusion, our results suggest that NTN inactivation enhances androgen sensitivity in reproductive and neuroendocrine tissues, revealing a novel mechanism to influence reproductive function and the activity of other androgen-dependent tissues.

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

    PubMed

    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.

  10. Muscle connective tissue controls development of the diaphragm and is a source of congenital diaphragmatic hernias.

    PubMed

    Merrell, Allyson J; Ellis, Benjamin J; Fox, Zachary D; Lawson, Jennifer A; Weiss, Jeffrey A; Kardon, Gabrielle

    2015-05-01

    The diaphragm is an essential mammalian skeletal muscle, and defects in diaphragm development are the cause of congenital diaphragmatic hernias (CDHs), a common and often lethal birth defect. The diaphragm is derived from multiple embryonic sources, but how these give rise to the diaphragm is unknown, and, despite the identification of many CDH-associated genes, the etiology of CDH is incompletely understood. Using mouse genetics, we show that the pleuroperitoneal folds (PPFs), which are transient embryonic structures, are the source of the diaphragm's muscle connective tissue and regulate muscle development, and we show that the striking migration of PPF cells controls diaphragm morphogenesis. Furthermore, Gata4 mosaic mutations in PPF-derived muscle connective tissue fibroblasts result in the development of localized amuscular regions that are biomechanically weaker and more compliant, leading to CDH. Thus, the PPFs and muscle connective tissue are critical for diaphragm development, and mutations in PPF-derived fibroblasts are a source of CDH.

  11. 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

  12. [The role of connective tissue nonspecific dysplasia in postoperative and recurrent abdominal hernias formation].

    PubMed

    Akhmedov, N I

    2011-04-01

    There were studied the rate of clinical indices diagnosis concerning nondifferentiated form of connective tissue dysplasia (NFCTD) as well as their significance in postoperative and recurrent abdominal hernias formation in 61 patients, ageing 20 - 78 years. It was established, that in 77% of patients the hernia have had formated on a NFCTD background, including in 16.4%--with a mild degree, in 27.8%--moderate degree and in 32.8%--a severe one. The authors recommend while abdominal hernia is present to study a characteristic phenotypical signs of a connective tissue dysplasia and, if more than 4 signs are diagnosed, to prefer the application of alloplastic methods.

  13. 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.

  14. Association of cervical artery dissection with connective tissue abnormalities in skin and arteries.

    PubMed

    Brandt, T; Morcher, M; Hausser, I

    2005-01-01

    Spontaneous cervical artery dissections (sCAD) often occur in otherwise healthy individuals without known risk factors for stroke and frequently develop spontaneously without relevant trauma. An underlying arteriopathy leading to a so-called 'weakness of the vessel wall' and predisposing certain individuals to dissection has often been postulated. Therefore, the morphology of connective tissue, a main component of vessel wall and environment, was investigated in carotids and skin. While the overall morphology of dermal connective tissue is normal, about half of patients with sCAD show mild ultrastructural connective tissue alterations. These ultrastructural morphological aberrations can be designated either as 'Ehlers-Danlos syndrome (EDS) III-like', resembling mild findings in patients with the hypermobility type of EDS (EDS III); or coined 'EDS IV-like' with collagen fibers containing fibrils with highly variable diameters resembling mild findings in vascular EDS; or the abnormalities are restricted to the elastic fibers (with fragmentation and minicalcifications) without significant alterations in the morphology of the collagen fibrils. These findings had some similarity with the morphology found in heterozygous carriers of pseudoxanthoma elasticum. A grading scale according to the severity of the findings has been introduced. Similar connective tissue abnormalities were detected in some first-degree relatives of patients with sCAD showing hereditary at least in a subgroup. They can serve as a phenotypic marker for further genetic studies in patients with sCAD and large families to possibly identify the underlying basic molecular defect(s). Very few of patients (<5%) with sCAD and connective tissue abnormalities have clinical manifestations of skin, joint, or skeletal abnormalities of a defined heritable connective tissue disorder. In specimens of arterial walls of carotid, aortic, and renal arteries of patients with sCAD, pronounced systemic, histopathological

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

    PubMed

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

    2009-03-01

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

  16. The connective tissue of the adductor canal – a morphological study in fetal and adult specimens

    PubMed Central

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

    2009-01-01

    The adductor canal is a conical or pyramid-shaped pathway that contains the femoral vessels, saphenous nerve and a varying amount of fibrous tissue. It is involved in adductor canal syndrome, a claudication syndrome involving young individuals. Our objective was to study modifications induced by aging on the connective tissue and to correlate them to the proposed pathophysiological mechanism. The bilateral adductor canals and femoral vessels of four adult and five fetal specimens were removed en bloc and analyzed. Sections 12 µm thick were obtained and the connective tissue studied with Sirius Red, Verhoeff, Weigert and Azo stains. Scanning electron microscopy (SEM) photomicrographs of the surfaces of each adductor canal were also analyzed. Findings were homogeneous inside each group. The connective tissue of the canal was continuous with the outer layer of the vessels in both groups. The pattern of concentric, thick collagen type I bundles in fetal specimens was replaced by a diffuse network of compact collagen bundles with several transversal fibers and an impressive content of collagen III fibers. Elastic fibers in adults were not concentrated in the thick bundles but dispersed in line with the transversal fiber system. A dynamic compression mechanism with or without an evident constricting fibrous band has been proposed previously for adductor canal syndrome, possibly involving the connective tissue inside the canal. The vessels may not slide freely during movement. These age-related modifications in normal individuals may represent necessary conditions for this syndrome to develop. PMID:19245505

  17. Esthetic Root Coverage with Double Papillary Subepithelial Connective Tissue Graft: A Case Report

    PubMed Central

    Mutthineni, Ramesh Babu; Dudala, Ram Babu; Ramisetty, Arpita

    2014-01-01

    Patients today have become excessively concerned about esthetics. These esthetic concerns of patients have become an integral part of periodontal practice. Gingival recession is an esthetic problem that can be successfully treated by means of several mucogingival surgical approaches, any of which can be used, provided that the biologic conditions for accomplishing root coverage are satisfied with no loss of soft and hard tissue height interdentally. There are currently different techniques for root coverage which include pedicle grafts, free gingival grafts, connective tissue grafts, and guided tissue regeneration (GTR). This paper reports a case in which a new double papillary connective tissue graft technique has been used in the treatment of gingival recession. PMID:24649378

  18. Smooth muscle myosin regulation by serum and cell density in cultured rat lung connective tissue cells.

    PubMed

    Babij, P; Zhao, J; White, S; Woodcock-Mitchell, J; Mitchell, J; Absher, M; Baldor, L; Periasamy, M; Low, R B

    1993-08-01

    RNA and protein analyses were used to detect expression of SM1 and SM2 smooth muscle myosin heavy chain (MHC) in cultured adult rat lung connective tissue cells (RL-90). Smooth muscle MHC mRNA expression in confluent cells grown in 10% serum was approximately 50% of the level in adult stomach. Similar results were obtained in cells cultured at low density (25% confluency) in 1% serum. However, in low-density cultures transferred to 10% serum for 24 h, the level of MHC mRNA decreased to approximately 20% of that in adult stomach. Smooth muscle alpha-actin showed a pattern of expression similar to that for smooth muscle MHC. Expression of nonmuscle MHC-A mRNA was higher in all culture conditions compared to stomach. MHC-A mRNA expression was less in low-density cultures in low serum and increased when low-density cultures were transferred to 10% serum for 24 h. MHC-B mRNA expression was less in low- vs. high-density cultures. In contrast to MHC-A, however, MHC-B mRNA expression in low-density cultures was higher in low serum. Immunofluorescence and immunoblotting with SM1-specific antibody demonstrated the presence of the SM1 protein isoform as well as reactivity to a protein band migrating slightly faster than SM2. These results demonstrate that cultured rat lung connective tissue cells express smooth muscle MHC and that expression is modulated by culture conditions.

  19. Higher maturity and connective tissue association distinguish resident from recently generated human tonsil plasma cells.

    PubMed

    Medina, Francisco; Segundo, Carmen; Jiménez-Gómez, Gema; González-García, Inés; Campos-Caro, Antonio; Brieva, José A

    2007-12-01

    Human plasma cells (PC) are present in cell suspensions obtained from the tonsil by mechanical disaggregation (PC(MECH)). The present study shows that a collagenase treatment of tonsillar debris remaining after mechanical disaggregation yielded similar proportions of PC (PC(COLL)). Moreover, PC(MECH) were present in suspensions highly enriched in germinal center cells whereas PC(COLL) contained most of the IgA-secreting cells, suggesting their predominant location in follicular and parafollicular areas and connective tissue-rich zones such as tonsil subepithelium, respectively. Tonsil PC(MECH) and PC(COLL) shared the phenotype CD38(high) CD19(+) CD20(low) CD45(high), expressed equivalent amounts of PRDI BF1/Blimp-1 transcription factor, and carried similarly mutated IgVH6 genes. However, they differed in several features. 1) PC(MECH) still expressed the early B cell transcription factor BSAP and were HLA-DR(high); in contrast, PC(COLL) were BSAP(-)and HLA-DR(low). 2) PC(MECH) were CD95(+) and Bcl-2(+/-) whereas PC(COLL) showed CD95(+/-) and Bcl-2(+) expression; in addition, PC(MECH) exhibited increased spontaneous apoptosis. 3) The two PC subsets exhibited distinctive adhesion molecule profiles, since PC(COLL) expressed higher levels of CD31, CD44, and CD49d, but a lower level of CD11a than PC(MECH). These results suggest that PC(MECH) are recently generated, short-living PC, and PC(COLL) constitutes a subset with higher maturity and survival, which resides in connective tissue-rich areas.

  20. 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.

  1. Substrate-protecting antiproteolytic agents for the prevention of pathological degradation of connective tissues. A review.

    PubMed

    Robert, A-M

    2012-02-01

    Connective tissues play an important role in the physiological functions of the organism. The integrity of the macromolecular components of these tissues, also called extracellular matrix, is necessary for their functional efficiency. A number of proteinases present in the organism, and the activity of which increases with age and with several pathologies, specifically degrade the components of the extracellular matrix. For a long time, tentatives for the protection of the matrix-components against degradation were made with low molecular weight inhibitors, not very efficient in vivo and not devoid of inconveniencies. We initiated a different approach for the preservation of the macromolecules of the extracellular matrix against proteolytic degradation with substances which exert an intense antiproteolytic activity not only in vitro, but also in vivo. The particularity of these substances is the fact that they do not act on the enzymes, but combine with the macromolecules. This is the type of combination of substances with the macromolecules of the matrix that prevents their degradation by the proteinases. Because of this affinity of such antiproteolytic agents not for the enzymes but for the substrates, we called them "substrate protectors" (Robert et al., 1979). The aim of the present review is to summarise the essential of our experiments which led to the description of substrate protectors.

  2. [Reparative regeneration of connective tissue structures of mammals under antioxidant therapy conditions].

    PubMed

    Belova, S V; Norkin, I A; Puchin'ian, D M

    2015-01-01

    The influence of administration of the antioxidant complexes consisting of nonenzymatic antioxidants (alpha-tocopherol acetate preparation) and enzymatic antioxidants (ceruloplasmin) has been studied in rabbits with experimental arthritis. The introduction of alpha-tocopherol acetate (at a daily dose of 4 mg) improved metabolic processes in the organism (decreased in the rate of erythrocyte precipitation, total leukocytes and their stub and segmental forms; increased in erythrocyte count; reduced the glycosaminoglycan content as determined from uronic acid and hexose level; decreased ceruloplasmin activity and malonic dialdehyde level ion blood serum, all at p < 0.05), thus favoring reduction in the total activity of the inflammatory process as judged from hematological and biochemical data. Intra-articular introduction of ceruloplasmin (1.5 mg/kg, once per week) positively influenced the state of joint structures in damaged knee joints of the animals: decreased the activity of ceruloplasmin (from 5.28 ± 0.06 to 3.94 ± 0.01 AU), and malonic dialdehyde level (0.18 ± 0.02 to 0.08 ± 0.01 μM) in the articular fluid (all at p < 0.05). These effects are probably related to the elimination of inefficiency of the antioxidant system in the synovial medium, thus preventing inflammatory destruction of articular tissues, hindering the development of pannus, and assisting the activation of reparative regeneration of connective tissue structures.

  3. [Reparative regeneration of connective tissue structures of mammals under antioxidant therapy conditions].

    PubMed

    Belova, S V; Norkin, I A; Puchin'ian, D M

    2015-01-01

    The influence of administration of the antioxidant complexes consisting of nonenzymatic antioxidants (alpha-tocopherol acetate preparation) and enzymatic antioxidants (ceruloplasmin) has been studied in rabbits with experimental arthritis. The introduction of alpha-tocopherol acetate (at a daily dose of 4 mg) improved metabolic processes in the organism (decreased in the rate of erythrocyte precipitation, total leukocytes and their stub and segmental forms; increased in erythrocyte count; reduced the glycosaminoglycan content as determined from uronic acid and hexose level; decreased ceruloplasmin activity and malonic dialdehyde level ion blood serum, all at p < 0.05), thus favoring reduction in the total activity of the inflammatory process as judged from hematological and biochemical data. Intra-articular introduction of ceruloplasmin (1.5 mg/kg, once per week) positively influenced the state of joint structures in damaged knee joints of the animals: decreased the activity of ceruloplasmin (from 5.28 ± 0.06 to 3.94 ± 0.01 AU), and malonic dialdehyde level (0.18 ± 0.02 to 0.08 ± 0.01 μM) in the articular fluid (all at p < 0.05). These effects are probably related to the elimination of inefficiency of the antioxidant system in the synovial medium, thus preventing inflammatory destruction of articular tissues, hindering the development of pannus, and assisting the activation of reparative regeneration of connective tissue structures. PMID:25826874

  4. [Normal connective tissue in penis and its changes in patients with erectile dysfunction and Peyronie's disease].

    PubMed

    Neĭmark, A I; Klimachev, V V; Gerval'd, V Ia; Bobrov, I P; Avdalian, A M; Muzalevskaia, N I; Gerval'd, I V; Aliev, R T; Kazymov, M A

    2009-01-01

    The aim of this study was to examine the connective tissue of penis in normal individuals and in patients with erectile dysfunction (ED) and Peyronie's disease (PD) using computer methods of image analysis. Penis tissues were obtained from 20 males aged 20-40 years who died in accidents, penis biopsies were taken from 23 patients with ED and 9 patients with PD (average age: 51 +/- 11.5 years). In both groups of patients, the volumetric fraction of collagen fibers in the tunica albuginea and corpora cavernosa was increased, while that one of elastic fibers was decreased. At the same time, the changes of elastic fibers were noted: the fibers become thinner and formed "rods". The reduction of the amplitude and the wavelength in the collagen fibers of the tunica albuginea in patients with ED and the presence of fibrous plaques in corpora cavernosa in in patients with PD were registered. The methods of computer image analysis may improve the morphologic diagnosis of ED and PD.

  5. Connective tissue growth factor is overexpressed in muscles of human muscular dystrophy.

    PubMed

    Sun, Guilian; Haginoya, Kazuhiro; Wu, Yanling; Chiba, Yoko; Nakanishi, Tohru; Onuma, Akira; Sato, Yuko; Takigawa, Masaharu; Iinuma, Kazuie; Tsuchiya, Shigeru

    2008-04-15

    The detailed process of how dystrophic muscles are replaced by fibrotic tissues is unknown. In the present study, the immunolocalization and mRNA expression of connective tissue growth factor (CTGF) in muscles from normal and dystrophic human muscles were examined with the goal of elucidating the pathophysiological function of CTGF in muscular dystrophy. Biopsies of frozen muscle from patients with Duchenne muscular dystrophy (DMD), Becker muscular dystrophy, congenital muscular dystrophy, spinal muscular atrophy, congenital myopathy were analyzed using anti-CTGF polyclonal antibody. Reverse transcription-polymerase chain reaction (RT-PCR) was also performed to evaluate the expression of CTGF mRNA in dystrophic muscles. In normal muscle, neuromuscular junctions and vessels were CTGF-immunopositive, which suggests a physiological role for CTGF in these sites. In dystrophic muscle, CTGF immunoreactivity was localized to muscle fiber basal lamina, regenerating fibers, and the interstitium. Triple immunolabeling revealed that activated fibroblasts were immunopositive for CTGF and transforming growth factor-beta1 (TGF-beta1). RT-PCR analysis revealed increased levels of CTGF mRNA in the muscles of DMD patients. Co-localization of TGF-beta1 and CTGF in activated fibroblasts suggests that CTGF expression is regulated by TGF-beta1 through a paracrine/autocrine mechanism. In conclusion, TGF-beta1-CTGF pathway may play a role in the fibrosis that is commonly observed in muscular dystrophy.

  6. Connective tissue growth factor production by activated pancreatic stellate cells in mouse alcoholic chronic pancreatitis

    PubMed Central

    Charrier, Alyssa; Brigstock, David R.

    2010-01-01

    Alcoholic chronic pancreatitis (ACP) is characterized by pancreatic necrosis, inflammation, and scarring, the latter of which is due to excessive collagen deposition by activated pancreatic stellate cells (PSC). The aim of this study was to establish a model of ACP in mice, a species that is usually resistant to the toxic effects of alcohol, and to identify the cell type(s) responsible for production of connective tissue growth factor (CTGF), a pro-fibrotic molecule. C57Bl/6 male mice received intraperitoneal ethanol injections for three weeks against a background of cerulein-induced acute pancreatitis. Peak blood alcohol levels remained consistently high in ethanol-treated mice as compared to control mice. In mice receiving ethanol plus cerulein, there was increased collagen deposition as compared to other treatment groups as well as increased frequency of α-smooth muscle actin and desmin-positive PSC which also demonstrated significantly enhanced CTGF protein production. Expression of mRNA for collagen α1(I), α-smooth muscle actin or CTGF were all increased and co-localized exclusively to activated PSC in ACP. Pancreatic expression of mRNA for key profibrotic markers were all increased in ACP. In conclusion, a mouse model of ACP has been developed that mimics key pathophysiological features of the disease in humans and which shows that activated PSC are the principal producers of collagen and CTGF. PSC-derived CTGF is thus a candidate therapeutic target in anti-fibrotic strategies for ACP. PMID:20368699

  7. Production of an optimized tissue-engineered pig connective tissue for the reconstruction of the urinary tract.

    PubMed

    Ouellet, Gabrielle; Dubé, Jean; Gauvin, Robert; Laterreur, Véronique; Bouhout, Sara; Bolduc, Stéphane

    2011-06-01

    Nonurological autologous tissues are used for urethral reconstruction to correct urinary tract disorders but are still leading to complications. Other substitutes have been studied on small animal models without great success. For preclinical tests, we selected the porcine model for its similarity to the human urinary tract. Up to now, porcine skin fibroblasts were not able to synthesize enough extracellular matrix under standard conditions to sustain the formation of an adequate tissue for transplantation purposes. Therefore, our goal was to optimize the harvesting site and culture conditions to obtain a thick and easy to handle porcine fibroblast tissue. The oral mucosa was found to be the ideal harvesting site, and a culture temperature of 39°C enabled the formation of a good porcine fibroblast sheet. We successfully superimpose three fibroblast sheets that merged into a thick and resistant tissue where physiological extracellular matrix was produced. Mechanical resistance evaluation by uniaxial traction on the three-layer fibroblast constructs also demonstrated its suitable properties. The production of this porcine connective tissue offers an interesting option in the field of urological tissue engineering. Autologous experiments on a larger animal model are now possible and accessible, allowing the performance of long-term in vivo studies.

  8. Decreasing latitude and increasing regulation in transplantable tissue programs.

    PubMed

    Humphries, Linda

    2005-11-01

    ADVANCED TECHNOLOGY and improved surgical techniques have led to new therapeutic uses for allografts. DISEASE TRANSMISSION via allograft tissue transplants has prompted federal intervention in the tissue banking industry and resulted in federal regulations. NEW STANDARDS from the Joint Commission on Accreditation of Healthcare Organizations became effective July 1, 2005, and apply to all hospitals that store or implant allograft tissues. These standards include mandatory policies on all aspects of hospital transplantation programs, including tissue ordering, receipt, storage, issuance, and record keeping. PMID:16355937

  9. Decreased receptivity of pathway connective tissue to sympathetic nerve ingrowth in the developing rat.

    PubMed

    Hiebert, J M; Fan, Q; Smith, P G

    1997-05-20

    Sympathetic axons can form atypical pathways to denervated orbital targets in neonatal rats but not in rats aged 30 or more days. The objective of this study was to determine if connective tissue pathways that carry sympathetic nerves lose their ability to sustain axonal sprouting during the early postnatal period. Regions of periorbital sheath known to contain large numbers of sympathetic axons that travel to distal orbital targets were excised from rats (sympathectomized 3 days previously) on postnatal days 6-7, 14-15, 30-31, and 48-49 and placed in anterior chambers of adult host rats. Tissues were removed 3, 6, or 10 days post-transplant and sympathetic ingrowth was analyzed by catecholamine histofluorescence in whole-mount or cryosectioned specimens. Connective tissue transplants from 6-15-day-old donors showed significant fiber ingrowth by 3 days in oculo, and innervation was maximal by 6 days. In contrast, sprouting into 30-49-day-old tissue was significantly slower, with most transplants lacking fibers at 3 days, and with small numbers of short fibers present at 6 days. We conclude that maturational changes occur in periorbital connective tissue pathways in the early postnatal period which make them less receptive to ingrowth by sympathetic nerves. The findings that connective tissue pathways are better substrates for sympathetic sprouting in the neonatal rat supports the view that developmental changes in these tissues are likely to contribute to the impaired reinnervation of orbital targets by contralateral neurons in juvenile and adult rats. PMID:9174244

  10. 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.

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

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

    PubMed

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

    2013-11-01

    Scanning electron microscopy (SEM) was utilized to evaluate microstructural changes in intramuscular connective tissue of beef semimembranosus muscle subjected to hydrodynamic pressure processing (HDP). Samples were HDP treated in a plastic container (HDP-PC) or a steel commercial unit (HDP-CU). Control and HDP samples were obtained immediately post-treatment and after 14days of aging for SEM and Warner-Bratzler shear force (WBSF) analysis. Immediately post-treatment, HDP treated samples exhibited lower (P<0.01) WBSF than did controls. After aging, HDP-PC samples had lower (P<0.01) WBSF than that of aged controls. SEM analysis indicated that HDP-PC treatment disrupted the integrity of the collagen fibril network of the endomysium in both the non-aged and aged samples. Aging effects on the intramuscular connective tissue were observed in the HDP-PC and control samples. Both WBSF and connective tissue changes were greater in the HDP-PC than in the HDP-CU treated samples. Data suggest that shockwave alterations to connective tissue contribute to the meat tenderization of HDP.

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

    SciTech Connect

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

    1982-02-01

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

  14. Structure of the rat subcutaneous connective tissue in relation to its sliding mechanism.

    PubMed

    Kawamata, Seiichi; Ozawa, Junya; Hashimoto, Masakazu; Kurose, Tomoyuki; Shinohara, Harumichi

    2003-08-01

    Mammalian skin can extensively slide over most parts of the body. To study the mechanism of this mobility of the skin, the structure of the subcutaneous connective tissue was examined by light microscopy. The subcutaneous connective tissue was observed to be composed of multiple layers of thin collagen sheets containing elastic fibers. These piled-up collagen sheets were loosely interconnected with each other, while the outer and inner sheets were respectively anchored to the dermis and epimysium by elastic fibers. Collagen fibers in each sheet were variable in diameter and oriented in different directions to form a thin, loose meshwork under conditions without mechanical stretching. When a weak shear force was loaded between the skin and the underlying abdominal muscles, each collagen sheet slid considerably, resulting in a stretching of the elastic fibers which anchor these sheets. When a further shear force was loaded, collagen fibers in each sheet seemed to align in a more parallel manner to the direction of the tension. With the reduction or removal of the force, the arrangement of collagen fibers in each sheet was reversed and the collagen sheets returned to their original shapes and positions, probably with the stabilizing effect of elastic fibers. Blood vessels and nerves in the subcutaneous connective tissue ran in tortuous routes in planes parallel to the unloaded skin, which seemed very adaptable for the movement of collagen sheets. These findings indicate that the subcutaneous connective tissue is extensively mobile due to the presence of multilayered collagen sheets which are maintained by elastic fibers.

  15. 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.

  16. Dynamic Vibration Cooperates with Connective Tissue Growth Factor to Modulate Stem Cell Behaviors

    PubMed Central

    Tong, Zhixiang; Zerdoum, Aidan B.; Duncan, Randall L.

    2014-01-01

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

  17. Differences in HLA antigens between patients with mixed connective tissue disease and systemic lupus erythematosus.

    PubMed Central

    Ruuska, P; Hämeenkorpi, R; Forsberg, S; Julkunen, H; Mäkitalo, R; Ilonen, J; Tiilikainen, A

    1992-01-01

    Patients with mixed connective tissue disease (MCTD, n = 32) or systemic lupus erythematosus (SLE, n = 60) were typed for HLA-A, B, C, Dw, and DR antigens. All patients with SLE fulfilled at least four criteria of SLE and the patients with MCTD met the criteria proposed by Alarcon-Segovia (1989). The presence of antibodies to Sm was not considered as an exclusion for MCTD. In the patients with SLE, Dw3, DR3, and the associated B8 and A1 antigens were increased, whereas in the patients with MCTD an increased frequency of Dw4 was found (45 v 18% in controls v 14% in SLE). Of the subtypes of DR4, Dw4 was present in all but one of the DR4 positive patients. The frequency of DR4 in patients with MCTD (52%) differed significantly from that of controls (28%). The strong association of MCTD to one DR4 subtype was further seen in the significantly increased frequency of the B15, DR4 combination. Thus the genetic background seems to be different in patients with MCTD from that in patients with SLE. This could partly explain the clinical differences between these diseases. PMID:1540038

  18. Connective Tissue Growth Factor Is Required for Normal Follicle Development and Ovulation

    PubMed Central

    Nagashima, Takashi; Kim, Jaeyeon; Li, Qinglei; Lydon, John P.; DeMayo, Francesco J.; Lyons, Karen M.

    2011-01-01

    Connective tissue growth factor (CTGF) is a cysteine-rich protein the synthesis and secretion of which are hypothesized to be selectively regulated by activins and other members of the TGF-β superfamily. To investigate the in vivo roles of CTGF in female reproduction, we generated Ctgf ovarian and uterine conditional knockout (cKO) mice. Ctgf cKO mice exhibit severe subfertility and multiple reproductive defects including disrupted follicle development, decreased ovulation rates, increased numbers of corpus luteum, and smaller but functionally normal uterine horns. Steroidogenesis is disrupted in the Ctgf cKO mice, leading to increased levels of serum progesterone. We show that disrupted follicle development is accompanied by a significant increase in granulosa cell apoptosis. Moreover, despite normal cumulus expansion, Ctgf cKO mice exhibit a significant decrease in oocytes ovulated, likely due to impaired ovulatory process. During analyses of mRNA expression, we discovered that Ctgf cKO granulosa cells show gene expression changes similar to our previously reported granulosa cell-specific knockouts of activin and Smad4, the common TGF-β family intracellular signaling protein. We also discovered a significant down-regulation of Adamts1, a progesterone-regulated gene that is critical for the remodeling of extracellular matrix surrounding granulosa cells of preovulatory follicles. These findings demonstrate that CTGF is a downstream mediator in TGF-β and progesterone signaling cascades and is necessary for normal follicle development and ovulation. PMID:21868453

  19. Increased Plasminogen Activator (Urokinase) in Tissue Culture After Fibrin Deposition

    PubMed Central

    Bernik, Maria B.

    1973-01-01

    Lysis of fibrin in tissue culture has been shown to be due to plasminogen activator identified immunologically as urokinase. The present study examines fibrinolytic events in culture, particularly mechanisms leading to increased urokinase levels and accelerated fibrinolysis. Deposition of fibrin on cells in culture was followed by a two- to six-fold increase in urokinase in the supernates and rapid disappearance of the fibrin. Investigation of factors that might be responsible for these events (including fibrin, fibrinogen, vasoactive stimuli, and the enzymes thrombin and plasmin) indicated that the enhanced urokinase yields were mediated through plasmin and thrombin. Study of the possible modes of action of thrombin and plasmin indicated that these enzymes are capable of acting on the cells themselves as well as on cell-produced material. The effect on cells was manifested by mitotic activity or, occasionally, cell injury and death. Although these effects influenced urokinase levels, enhanced yields were explained best by the action of enzymes on cellproduced material. Studies with plasmin and thrombin, and also trypsin, indicated that proteolytic enzymes may act in various ways—affect the stability of urokinase, interfere with inhibition of urokinase by naturally occurring inhibitor(s), and induce urokinase activity from inactive material. Plasma and thrombin appeared to act primarily through the latter mechanism. Inactive material, which gave rise to urokinase upon exposure to proteolytic enzymes and which may represent urokinase precursor, was found in cultures of kidney, lung, spleen, and thyroid. Urokinase in such inactive state appears to be readily accessible to activation by enzymes, particularly plasmin and thrombin, thus facilitating removal of fibrin and possibly also providing pathways to excessive fibrinolysis. PMID:4266421

  20. Expanding the clinical and genetic heterogeneity of hereditary disorders of connective tissue.

    PubMed

    Alazami, Anas M; Al-Qattan, Sarah M; Faqeih, Eissa; Alhashem, Amal; Alshammari, Muneera; Alzahrani, Fatema; Al-Dosari, Mohammed S; Patel, Nisha; Alsagheir, Afaf; Binabbas, Bassam; Alzaidan, Hamad; Alsiddiky, Abdulmonem; Alharbi, Nasser; Alfadhel, Majid; Kentab, Amal; Daza, Riza M; Kircher, Martin; Shendure, Jay; Hashem, Mais; Alshahrani, Saif; Rahbeeni, Zuhair; Khalifa, Ola; Shaheen, Ranad; Alkuraya, Fowzan S

    2016-05-01

    Ehlers-Danlos syndrome (EDS) describes a group of clinical entities in which the connective tissue, primarily that of the skin, joint and vessels, is abnormal, although the resulting clinical manifestations can vary widely between the different historical subtypes. Many cases of hereditary disorders of connective tissue that do not seem to fit these historical subtypes exist. The aim of this study is to describe a large series of patients with inherited connective tissue disorders evaluated by our clinical genetics service and for whom a likely causal variant was identified. In addition to clinical phenotyping, patients underwent various genetic tests including molecular karyotyping, candidate gene analysis, autozygome analysis, and whole-exome and whole-genome sequencing as appropriate. We describe a cohort of 69 individuals representing 40 families, all referred because of suspicion of an inherited connective tissue disorder by their primary physician. Molecular lesions included variants in the previously published disease genes B3GALT6, GORAB, ZNF469, B3GAT3, ALDH18A1, FKBP14, PYCR1, CHST14 and SPARC with interesting variations on the published clinical phenotypes. We also describe the first recessive EDS-like condition to be caused by a recessive COL1A1 variant. In addition, exome capture in a familial case identified a homozygous truncating variant in a novel and compelling candidate gene, AEBP1. Finally, we also describe a distinct novel clinical syndrome of cutis laxa and marked facial features and propose ATP6V1E1 and ATP6V0D2 (two subunits of vacuolar ATPase) as likely candidate genes based on whole-genome and whole-exome sequencing of the two families with this new clinical entity. Our study expands the clinical spectrum of hereditary disorders of connective tissue and adds three novel candidate genes including two that are associated with a highly distinct syndrome.

  1. Expanding the clinical and genetic heterogeneity of hereditary disorders of connective tissue.

    PubMed

    Alazami, Anas M; Al-Qattan, Sarah M; Faqeih, Eissa; Alhashem, Amal; Alshammari, Muneera; Alzahrani, Fatema; Al-Dosari, Mohammed S; Patel, Nisha; Alsagheir, Afaf; Binabbas, Bassam; Alzaidan, Hamad; Alsiddiky, Abdulmonem; Alharbi, Nasser; Alfadhel, Majid; Kentab, Amal; Daza, Riza M; Kircher, Martin; Shendure, Jay; Hashem, Mais; Alshahrani, Saif; Rahbeeni, Zuhair; Khalifa, Ola; Shaheen, Ranad; Alkuraya, Fowzan S

    2016-05-01

    Ehlers-Danlos syndrome (EDS) describes a group of clinical entities in which the connective tissue, primarily that of the skin, joint and vessels, is abnormal, although the resulting clinical manifestations can vary widely between the different historical subtypes. Many cases of hereditary disorders of connective tissue that do not seem to fit these historical subtypes exist. The aim of this study is to describe a large series of patients with inherited connective tissue disorders evaluated by our clinical genetics service and for whom a likely causal variant was identified. In addition to clinical phenotyping, patients underwent various genetic tests including molecular karyotyping, candidate gene analysis, autozygome analysis, and whole-exome and whole-genome sequencing as appropriate. We describe a cohort of 69 individuals representing 40 families, all referred because of suspicion of an inherited connective tissue disorder by their primary physician. Molecular lesions included variants in the previously published disease genes B3GALT6, GORAB, ZNF469, B3GAT3, ALDH18A1, FKBP14, PYCR1, CHST14 and SPARC with interesting variations on the published clinical phenotypes. We also describe the first recessive EDS-like condition to be caused by a recessive COL1A1 variant. In addition, exome capture in a familial case identified a homozygous truncating variant in a novel and compelling candidate gene, AEBP1. Finally, we also describe a distinct novel clinical syndrome of cutis laxa and marked facial features and propose ATP6V1E1 and ATP6V0D2 (two subunits of vacuolar ATPase) as likely candidate genes based on whole-genome and whole-exome sequencing of the two families with this new clinical entity. Our study expands the clinical spectrum of hereditary disorders of connective tissue and adds three novel candidate genes including two that are associated with a highly distinct syndrome. PMID:27023906

  2. Mechanisms of bradykinin-induced expression of connective tissue growth factor and nephrin in podocytes.

    PubMed

    Abou Msallem, J; Chalhoub, H; Al-Hariri, M; Saad, L; Jaffa, M A; Ziyadeh, F N; Jaffa, A A

    2015-12-01

    Diabetic nephropathy (DN) is the main cause of morbidity and mortality in diabetes and is characterized by mesangial matrix deposition and podocytopathy, including podocyte loss. The risk factors and mechanisms involved in the pathogenesis of DN are still not completely defined. In the present study, we aimed to understand the cellular mechanisms through which activation of B2 kinin receptors contribute to the initiation and progression of DN. Stimulation of cultured rat podocytes with bradykinin (BK) resulted in a significant increase in ROS generation, and this was associated with a significant increase in NADPH oxidase (NOX)1 and NOX4 protein and mRNA levels. BK stimulation also resulted in a signicant increase in the phosphorylation of ERK1/2 and Akt, and this effect was inhibited in the presence of NOX1 and Nox4 small interfering (si)RNA. Furthermore, podocytes stimulated with BK resulted in a significant increase in protein and mRNA levels of connective tissue growth factor (CTGF) and, at the same time, a significant decrease in protein and mRNA levels of nephrin. siRNA targeted against NOX1 and NOX4 significantly inhibited the BK-induced increase in CTGF. Nephrin expression was increased in response to BK in the presence of NOX1 and NOX4 siRNA, thus implicating a role for NOXs in modulating the BK response in podocytes. Moreover, nephrin expression in response to BK was also significantly increased in the presence of siRNA targeted against CTGF. These findings provide novel aspects of BK signal transduction pathways in pathogenesis of DN and identify novel targets for interventional strategies.

  3. Influence of maturation and aging on mechanical and biochemical properties of connective tissue in rats.

    PubMed

    Vogel, H G

    1980-01-01

    The influence of maturation and age on the physical and chemical properties of various organs of connective tissue has been studied in rats at ages of 4 weeks, 8 weeks, 4 monhs, 1 year and 2 years. The changes between young (4 weeks old) and adult (4 months to 1 year old) animals were considered as the effects of maturation, whereas the changes between adult and senescent (2 years old) rats were regarded as the effects of aging. Ultimate values, such as ultimate load, tensile strength and breaking strength, or ultimate modulus of elasticity, showed a sharp rise during maturation and a smaller but significant decrease during aging in all organs, such as skin strips, tail tendons, shaft bones, epiphyseal cartilage and aorta rings. Ultimate strain showed a similar pattern, but the maximum occurred earlier. These changes were parallel with the content of insoluble collagen. Other chemical parameters such as soluble collagen or glycosaminoglycans, showed a continuous decrease during the life span, whereas elastin rose continuously. More detailed analysis of mechanical properties in rat skin gave insight into the viscoelastic behaviour of skin. In creep experiments time until break under constant load rose continuously during the life span, whereas ultimate extension rate showed a sharp fall during maturation and a slow decrease during senescence. Stress at low extension degree and moduli of elasticity at low extension degree were decreased by maturation and increased by senescence, exactly the opposite of the changes at high extension degrees. The so-called step phenomenon was increased due to maturation and decreased due to aging. Relaxation and mechanical recovery were changed in the same direction by maturation and aging. Relative viscoelastic parameters, such as the hysteresis phenomenon and relative decrease of stress under cyclic strain, were barely influenced by the aging process. Changes of most of the mechanical parameters at high extension degrees during

  4. Increased Functional Connectivity between Prefrontal Cortex and Reward System in Pathological Gambling

    PubMed Central

    Koehler, Saskia; Ovadia-Caro, Smadar; van der Meer, Elke; Villringer, Arno; Heinz, Andreas

    2013-01-01

    Pathological gambling (PG) shares clinical characteristics with substance-use disorders and is thus discussed as a behavioral addiction. Recent neuroimaging studies on PG report functional changes in prefrontal structures and the mesolimbic reward system. While an imbalance between these structures has been related to addictive behavior, whether their dysfunction in PG is reflected in the interaction between them remains unclear. We addressed this question using functional connectivity resting-state fMRI in male subjects with PG and controls. Seed-based functional connectivity was computed using two regions-of-interest, based on the results of a previous voxel-based morphometry study, located in the prefrontal cortex and the mesolimbic reward system (right middle frontal gyrus and right ventral striatum). PG patients demonstrated increased connectivity from the right middle frontal gyrus to the right striatum as compared to controls, which was also positively correlated with nonplanning aspect of impulsiveness, smoking and craving scores in the PG group. Moreover, PG patients demonstrated decreased connectivity from the right middle frontal gyrus to other prefrontal areas as compared to controls. The right ventral striatum demonstrated increased connectivity to the right superior and middle frontal gyrus and left cerebellum in PG patients as compared to controls. The increased connectivity to the cerebellum was positively correlated with smoking in the PG group. Our results provide further evidence for alterations in functional connectivity in PG with increased connectivity between prefrontal regions and the reward system, similar to connectivity changes reported in substance use disorder. PMID:24367675

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

    PubMed Central

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

    2009-01-01

    INTRODUCTION: The purpose of this study was to compare the histocompatibility of white (WMTA) and gray (GMTA) mineral trioxide aggregate mixed with 0.12% chlorhexidine (CHX) and distilled water (DW) in subcutaneous connective tissues of rats. MATERIALS AND METHODS: The freshly mixed WMTA and GMTA with CHX or DW were inserted in polyethylene tubes and implanted into dorsal subcutaneous connective tissue of 50 Wistar Albino rats; tissue biopsies were collected and were then examined histologically 7, 15, 30, 60 and 90 days after the implantation procedure. The histology results were scored from 1-4; score 4 was considered as the worst finding. Data were analyzed using one-way ANOVA tests. RESULTS: All experimented materials were tolerated well by the connective tissues after 90-day evaluation, except for the WMTA/CHX group that had significantly more mean inflammatory scores (P<0.001). There was a statistically significant difference in the mean inflammation grades between experimental groups in each interval (P<0.001). After 90 days, GMTA/CHX group had the lowest inflammatory score. CONCLUSION: Although adding CHX to WMTA produces significantly higher inflammatory response, it seems a suitable substitute for DW in combination with GMTA. Further research is necessary to recommend this mixture for clinical use. PMID:23864873

  6. 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.

  7. 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.

  8. 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

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

    PubMed Central

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

    2014-01-01

    Cerebral palsy (CP) of the spastic type is a neurological disorder characterized by a velocity-dependent increase in tonic stretch reflexes with exaggerated tendon jerks. Secondary to the spasticity, muscle adaptation is presumed to contribute to limitations in the passive range of joint motion. However, the mechanisms underlying these limitations are unknown. Using biopsies, we compared mechanical as well as histological properties of flexor carpi ulnaris muscle (FCU) from CP patients (n = 29) and healthy controls (n = 10). The sarcomere slack length (mean 2.5 µm, SEM 0.05) and slope of the normalized sarcomere length-tension characteristics of spastic fascicle segments and single myofibre segments were not different from those of control muscle. Fibre type distribution also showed no significant differences. Fibre size was significantly smaller (1933 µm2, SEM 190) in spastic muscle than in controls (2572 µm2, SEM 322). However, our statistical analyses indicate that the latter difference is likely to be explained by age, rather than by the affliction. Quantities of endomysial and perimysial networks within biopsies of control and spastic muscle were unchanged with one exception: a significant thickening of the tertiary perimysium (3-fold), i.e. the connective tissue reinforcement of neurovascular tissues penetrating the muscle. Note that this thickening in tertiary perimysium was shown in the majority of CP patients, however a small number of patients (n = 4 out of 23) did not have this feature. These results are taken as indications that enhanced myofascial loads on FCU is one among several factors contributing in a major way to the aetiology of limitation of movement at the wrist in CP and the characteristic wrist position of such patients. PMID:24977410

  10. Intramuscular connective tissue differences in spastic and control muscle: a mechanical and histological study.

    PubMed

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

    2014-01-01

    Cerebral palsy (CP) of the spastic type is a neurological disorder characterized by a velocity-dependent increase in tonic stretch reflexes with exaggerated tendon jerks. Secondary to the spasticity, muscle adaptation is presumed to contribute to limitations in the passive range of joint motion. However, the mechanisms underlying these limitations are unknown. Using biopsies, we compared mechanical as well as histological properties of flexor carpi ulnaris muscle (FCU) from CP patients (n = 29) and healthy controls (n = 10). The sarcomere slack length (mean 2.5 µm, SEM 0.05) and slope of the normalized sarcomere length-tension characteristics of spastic fascicle segments and single myofibre segments were not different from those of control muscle. Fibre type distribution also showed no significant differences. Fibre size was significantly smaller (1933 µm2, SEM 190) in spastic muscle than in controls (2572 µm2, SEM 322). However, our statistical analyses indicate that the latter difference is likely to be explained by age, rather than by the affliction. Quantities of endomysial and perimysial networks within biopsies of control and spastic muscle were unchanged with one exception: a significant thickening of the tertiary perimysium (3-fold), i.e. the connective tissue reinforcement of neurovascular tissues penetrating the muscle. Note that this thickening in tertiary perimysium was shown in the majority of CP patients, however a small number of patients (n = 4 out of 23) did not have this feature. These results are taken as indications that enhanced myofascial loads on FCU is one among several factors contributing in a major way to the aetiology of limitation of movement at the wrist in CP and the characteristic wrist position of such patients.

  11. Alteration of Connective Tissue Growth Factor (CTGF) Expression in Orbital Fibroblasts from Patients with Graves’ Ophthalmopathy

    PubMed Central

    Chang, Pei-Chen; Wei, Yau-Huei

    2015-01-01

    Graves’ ophthalmopathy (GO) is a disfiguring and sometimes blinding disease, which is characterized by inflammation and swelling of orbital tissues, with fibrosis and adipogenesis being predominant features. The aim of this study is to investigate whether the expression levels of fibrosis-related genes, especially that of connective tissue growth factor (CTGF), are altered in orbital fibroblasts of patients with GO. The role of oxidative stress in the regulation of CTGF expression in GO orbital fibroblasts is also examined. By a SYBR Green-based real time quantitative PCR (RT-QPCR), we demonstrated that the mRNA expression levels of fibronectin, apolipoprotein J, and CTGF in cultured orbital fibroblasts from patients with GO were significantly higher than those of age-matched normal controls (p = 0.007, 0.037, and 0.002, respectively). In addition, the protein expression levels of fibronectin, apolipoprotein J, and CTGF analyzed by Western blot were also significantly higher in GO orbital fibroblasts (p = 0.046, 0.032, and 0.008, respectively) as compared with the control. Furthermore, after treatment of orbital fibroblasts with a sub-lethal dose of hydrogen peroxide (200 μM H2O2), we found that the H2O2-induced increase of CTGF expression was more pronounced in the GO orbital fibroblasts as compared with those in normal controls (20% vs. 7%, p = 0.007). Importantly, pre-incubation with antioxidants including N-acetylcysteine (NAC) and vitamin C, respectively, resulted in significant attenuation of the induction of CTGF in GO orbital fibroblasts in response to H2O2 (p = 0.004 and 0.015, respectively). Taken together, we suggest that oxidative stress plays a role in the alteration of the expression of CTGF in GO orbital fibroblasts that may contribute to the pathogenesis and progression of GO. Antioxidants may be used in combination with the therapeutic agents for effective treatment of GO. PMID:26599235

  12. Connective tissue and its growth factor CTGF distinguish the morphometric and molecular remodeling of the bladder in a model of neurogenic bladder.

    PubMed

    Altuntas, Cengiz Z; Daneshgari, Firouz; Izgi, Kenan; Bicer, Fuat; Ozer, Ahmet; Sakalar, Cagri; Grimberg, Kerry O; Sayin, Ismail; Tuohy, Vincent K

    2012-11-01

    We previously reported that mice with experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), develop profound urinary bladder dysfunction. Because neurogenic bladder in MS patients causes marked bladder remodeling, we next examined morphometric and molecular alterations of the bladder in EAE mice. EAE was created in female SJL/J mice by immunization with the p139-151 encephalitogenic peptide of myelin proteolipid protein in complete Freund's adjuvant, along with intraperitoneal injections of Bordetella pertussis toxin. Seventy days after immunization, mice were scored for the level of neurological impairment and then killed. Spinal cord sections were assessed for demyelination, inflammation, and T cell infiltration; the composition of the bladder tissue was measured quantitatively; and gene expression of markers of tissue remodeling and fibrosis was assessed. A significant increase in the bladder weight-to-body weight ratio was observed with increasing neurological impairment, and morphometric analysis showed marked bladder remodeling with increased luminal area and tissue hypertrophy. Despite increased amounts of all tissue components (urothelium, smooth muscle, and connective tissue), the ratio of connective tissue to muscle increased significantly in EAE mice compared with control mice. Marked increases in mRNA expression of collagen type I α(2), tropoelastin, transforming growth factor-β3, and connective tissue growth factor (CTGF) were observed in EAE mice, as were decreased levels of mRNAs for smooth muscle myosin heavy chain, nerve growth factors, and muscarinic and purinergic receptors. Our results suggest that bladder remodeling corresponding to EAE severity may be due to enhanced expression of CTGF and increased growth of connective tissue.

  13. Connective tissue and its growth factor CTGF distinguish the morphometric and molecular remodeling of the bladder in a model of neurogenic bladder

    PubMed Central

    Altuntas, Cengiz Z.; Izgi, Kenan; Bicer, Fuat; Ozer, Ahmet; Sakalar, Cagri; Grimberg, Kerry O.; Sayin, Ismail; Tuohy, Vincent K.

    2012-01-01

    We previously reported that mice with experimental autoimmune encephalomyelitis (EAE), a model of multiple sclerosis (MS), develop profound urinary bladder dysfunction. Because neurogenic bladder in MS patients causes marked bladder remodeling, we next examined morphometric and molecular alterations of the bladder in EAE mice. EAE was created in female SJL/J mice by immunization with the p139–151 encephalitogenic peptide of myelin proteolipid protein in complete Freund's adjuvant, along with intraperitoneal injections of Bordetella pertussis toxin. Seventy days after immunization, mice were scored for the level of neurological impairment and then killed. Spinal cord sections were assessed for demyelination, inflammation, and T cell infiltration; the composition of the bladder tissue was measured quantitatively; and gene expression of markers of tissue remodeling and fibrosis was assessed. A significant increase in the bladder weight-to-body weight ratio was observed with increasing neurological impairment, and morphometric analysis showed marked bladder remodeling with increased luminal area and tissue hypertrophy. Despite increased amounts of all tissue components (urothelium, smooth muscle, and connective tissue), the ratio of connective tissue to muscle increased significantly in EAE mice compared with control mice. Marked increases in mRNA expression of collagen type I α2, tropoelastin, transforming growth factor-β3, and connective tissue growth factor (CTGF) were observed in EAE mice, as were decreased levels of mRNAs for smooth muscle myosin heavy chain, nerve growth factors, and muscarinic and purinergic receptors. Our results suggest that bladder remodeling corresponding to EAE severity may be due to enhanced expression of CTGF and increased growth of connective tissue. PMID:22993071

  14. Undifferentiated connective tissue disease-associated interstitial lung disease: changes in lung function.

    PubMed

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

    2010-04-01

    Undifferentiated connective tissue disease (UCTD) is a distinct clinical entity that may be accompanied by interstitial lung disease (ILD). The natural history of UCTD-ILD is unknown. We hypothesized that patients with UCTD-ILD would be more likely to have improvement in lung function than those with idiopathic pulmonary fibrosis (IPF) during longitudinal follow-up. We identified subjects enrolled in the UCSF ILD cohort study with a diagnosis of IPF or UCTD. The primary outcome compared the presence or absence of a > or = 5% increase in percent predicted forced vital capacity (FVC) in IPF and UCTD. Regression models were used to account for potential confounding variables. Ninety subjects were identified; 59 subjects (30 IPF, 29 UCTD) had longitudinal pulmonary function data for inclusion in the analysis. After accounting for baseline pulmonary function tests, treatment, and duration between studies, UCTD was associated with substantial improvement in FVC (odds ratio = 8.23, 95% confidence interval, 1.27-53.2; p = 0.03) during follow-up (median, 8 months) compared with IPF. Patients with UCTD-ILD are more likely to have improved pulmonary function during follow-up than those with IPF. These findings demonstrate the clinical importance of identifying UCTD in patients presenting with an "idiopathic" interstitial pneumonia.

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

    PubMed

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

    2015-01-01

    Fatty acids are a valuable tool in ecological studies because of the large number of unique structures synthesized. They provide versatile signatures that are being increasingly employed to delineate the transfer of dietary material through marine and terrestrial food webs. The standard procedure for determining fatty acids generally involves lipid extraction followed by methanolysis to produce methyl esters for analysis by gas chromatography. By directly transmethylating ~50 mg wet samples and adding an internal standard it was possible to greatly simplify the analytical methodology to enable rapid throughput of 20-40 fish tissue fatty acid analyses a day including instrumental analysis. This method was verified against the more traditional lipid methods using albacore tuna and great white shark muscle and liver samples, and it was shown to provide an estimate of sample dry mass, total lipid content, and a condition index. When large fatty acid data sets are generated in this way, multidimensional scaling, analysis of similarities, and similarity of percentages analysis can be used to define trophic connections among samples and to quantify them. These routines were used on albacore and skipjack tuna fatty acid data obtained by direct methylation coupled with literature values for krill. There were clear differences in fatty acid profiles among the species as well as spatial differences among albacore tuna sampled from different locations. PMID:25376156

  16. Second cancer following cutaneous melanoma and cancers of the brain, thyroid, connective tissue, bone, and eye in Connecticut, 1935-82.

    PubMed

    Tucker, M A; Boice, J D; Hoffman, D A

    1985-12-01

    The risk of second primary cancers developing was evaluated in individuals with 6 rare tumors in Connecticut between 1935 and 1982. Small but significant excesses of all second cancers occurred in patients with cutaneous melanoma (42%), and cancers of the brain (59%), thyroid (49%), connective tissue (23%), bone (66%), and eye (40%). In individuals with cutaneous melanoma, the highest risks were for subsequent cutaneous melanomas [relative risk (RR) = 8.5] that persisted throughout all intervals of observation. The risk for second melanomas was higher in persons under age 40, consistent with a heritable component. Connective tissue tumors and breast cancers also occurred in excess. Among patients with brain cancer, an increase of melanoma was observed that may represent an underlying neural crest abnormality, although no excess of brain cancer was seen after melanoma. Reciprocal increases of bone cancer after connective tissue cancer and connective tissue cancer after bone cancer point to shared risk factors, such as high dose radiotherapy or genetic susceptibility states. An anticipated high risk of osteogenic sarcoma following Ewing's sarcoma was not seen. An excess of breast cancer (RR = 1.9) after thyroid cancer indicates common etiologic factors. Expected excesses of bilateral retinoblastoma and bone cancer after retinoblastoma were seen. Tumors commonly treated with alkylating agents or nitrosoureas (melanoma, brain, connective tissue) showed slightly elevated risks of acute nonlymphocytic leukemia. Prostate cancer was frequently found to be in excess, but this is likely an artifact due to ascertainment bias.

  17. A Winding Road: Alzheimer’s Disease Increases Circuitous Functional Connectivity Pathways

    PubMed Central

    Suckling, John; Simas, Tiago; Chattopadhyay, Shayanti; Tait, Roger; Su, Li; Williams, Guy; Rowe, James B.; O’Brien, John T.

    2015-01-01

    Neuroimaging has been successful in characterizing the pattern of cerebral atrophy that accompanies the progression of Alzheimer’s disease (AD). Examination of functional connectivity, the strength of signal synchronicity between brain regions, has gathered pace as another way of understanding changes to the brain that are associated with AD. It appears to have good sensitivity and detect effects that precede cognitive decline, and thus offers the possibility to understand the neurobiology of the disease in its earliest phases. However, functional connectivity analyzes to date generally consider only the strongest connections, with weaker links ignored. This proof-of-concept study compared patients with mild-to-moderate AD (N = 11) and matched control individuals (N = 12) based on functional connectivities derived from blood-oxygenation level dependent (BOLD) sensitive functional MRI acquired during resting wakefulness. All positive connectivities irrespective of their strength were included. Transitive closures of the resulting connectome were calculated that classified connections as either direct or indirect. Between-group differences in the proportion of indirect paths were observed. In AD, there was broadly increased indirect connectivity across greater spatial distances. Furthermore, the indirect pathways in AD had greater between-subject topological variance than controls. The prevailing characterization of AD as being a disconnection syndrome is refined by the observation that direct links between regions that are impaired are perhaps replaced by an increase in indirect functional pathways that is only detectable through inclusion of connections across the entire range of connection strengths. PMID:26635593

  18. 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.

  19. Pulmonary vascular reactivity in severe pulmonary hypertension associated with mixed connective tissue disease.

    PubMed Central

    Jolliet, P.; Thorens, J. B.; Chevrolet, J. C.

    1995-01-01

    Pulmonary vascular reactivity tests were performed in a young woman with mixed connective tissue disease and severe pulmonary hypertension. Vasoreactivity was documented in response to intravenous prostacyclin (PGI2), oral nifedipine, and inhaled nitric oxide, with quantitative differences. Nitric oxide produced a moderate lowering of pulmonary arterial pressure and resistance without any deleterious systemic effect. The use of nitric oxide in testing for pulmonary vasoreactivity merits further evaluation. Images PMID:7886662

  20. Anti-Ku antibodies in connective tissue diseases. Report of three cases.

    PubMed

    Parodi, A; Rebora, A

    1989-08-01

    Three patients are described with clinical features of connective tissue diseases, namely, dermatomyositis, progressive systemic scleroderma, and systemic lupus erythematosus. In two patients the symptoms of disease overlapped. The rare anti-Ku antibody was found in all of them. Anti-Ku antibody characterizes those patients, with polymyositis-scleroderma overlap syndromes who have a good prognosis. One of our patients, who also had severe anti-Sm-positive systemic lupus erythematosus, seems to be an exception.

  1. Tissue microchimerism is increased during pregnancy: a human autopsy study.

    PubMed

    Rijnink, Emilie C; Penning, Marlies E; Wolterbeek, Ron; Wilhelmus, Suzanne; Zandbergen, Malu; van Duinen, Sjoerd G; Schutte, Joke; Bruijn, Jan A; Bajema, Ingeborg M

    2015-11-01

    Microchimerism is the occurrence of small populations of cells with a different genetic background within an individual. Tissue microchimerism is considered to be primarily pregnancy-derived and is often studied relative to female-dominant autoimmune diseases, pregnancy complications, malignancies, response to injury, and transplantation outcomes. A particular distribution pattern of chimeric cells across various organs was recently described in a model of murine pregnancies. Our aim was to determine the frequency and distribution of tissue microchimerism across organs during and after pregnancy in humans. We performed in situ hybridization of the Y chromosome on paraffin-embedded autopsy samples of kidneys, livers, spleens, lungs, hearts and brains that were collected from 26 women who died while pregnant or within 1 month after delivery of a son. Frequencies of chimeric cells in various tissues were compared with those of a control group of non-pregnant women who had delivered sons. Tissue microchimerism occurred significantly more frequently in the lungs, spleens, livers, kidneys and hearts of pregnant women compared with non-pregnant women (all P < 0.01). We showed that some of the chimeric cells were CD3+ or CD34+. After correction for cell density, the lung was most chimeric (470 Y chromosome-positive nuclei per million nuclei scored), followed by the spleen (208 Y+/10(6) nuclei), liver (192 Y+/10(6) nuclei), kidney (135 Y+/10(6) nuclei), brain (85 Y+/10(6) nuclei) and heart (40 Y+/10(6) nuclei). Data from this unique study group of women who died while pregnant or shortly after delivery provide information about the number and physiologic distribution of chimeric cells in organs of pregnant women. We demonstrate that during pregnancy, a boost of chimeric cells is observed in women, with a distribution across organs, that parallels findings in mouse models. PMID:26307194

  2. Connective tissue growth factor and its regulation: a new element in diabetic glomerulosclerosis.

    PubMed

    Riser, B L; Cortes, P

    2001-01-01

    Connective tissue growth factor (CTGF), a member of the closely related CCN family of cytokines appears to be fibrotic in skin. To determine whether CTGF is implicated in diabetic glomerulosclerosis we studied cultured rat mesangial cells (MC) as well as kidney cortex and microdissected glomeruli from obese, diabetic db/db mice and their normal counterparts. Exposure of MC to rhCTGF significantly increased fibronectin and collagen type I secretion. Further, unstimulated MC expressed low levels of CTGF message and secreted minimal amounts of CTGF protein (36-38 kDa). However, exposure to TGF-beta, increased glucose concentrations, or cyclic mechanical strain, all causal factors in glomerulosclerosis, markedly induced the expression of CTGF transcripts. With all but mechanical strain there was a concomitant stimulation of CTGF protein secretion. TGF-beta also induced abundant quantities of a small molecular weight form of CTGF (18 kDa). The induction of CTGF protein by a high glucose concentration was mediated by TGF-beta, since a TGF-beta neutralizing antibody blocked this stimulation. In vivo studies using quantitative RT-PCR demonstrated that while CTGF transcripts were low in the glomeruli of control mice, expression was increased 27-fold after approximately 3.5 months of diabetes. These changes occurred early in diabetic nephropathy when mesangial expansion was mild, and interstitial disease and proteinuria were absent. A substantially reduced elevation of CTGF mRNA (2-fold) observed in whole kidney cortices indicted that the primary alteration of CTGF expression was in the glomerulus. These results suggest that CTGF upregulation is an important factor in the pathogenesis of mesangial matrix accumulation in both diabetic and non-diabetic glomerulosclerosis, acting downstream of TGF-beta. PMID:11499561

  3. Connective tissue growth factor hammerhead ribozyme attenuates human hepatic stellate cell function

    PubMed Central

    Gao, Run-Ping; Brigstock, David R

    2009-01-01

    AIM: To determine the effect of hammerhead ribozyme targeting connective tissue growth factor (CCN2) on human hepatic stellate cell (HSC) function. METHODS: CCN2 hammerhead ribozyme cDNA plus two self-cleaving sequences were inserted into pTriEx2 to produce pTriCCN2-Rz. Each vector was individually transfected into cultured LX-2 human HSCs, which were then stimulated by addition of transforming growth factor (TGF)-β1 to the culture medium. Semi-quantitative RT-PCR was used to determine mRNA levels for CCN2 or collagen I, while protein levels of each molecule in cell lysates and conditioned medium were measured by ELISA. Cell-cycle progression of the transfected cells was assessed by flow cytometry. RESULTS: In pTriEx2-transfected LX-2 cells, TGF-β1 treatment caused an increase in the mRNA level for CCN2 or collagen I, and an increase in produced and secreted CCN2 or extracellular collagen I protein levels. pTriCCN2-Rz-transfected LX-2 cells showed decreased basal CCN2 or collagen mRNA levels, as well as produced and secreted CCN2 or collagen I protein. Furthermore, the TGF-β1-induced increase in mRNA or protein for CCN2 or collagen I was inhibited partially in pTriCCN2-Rz-transfected LX-2 cells. Inhibition of CCN2 using hammerhead ribozyme cDNA resulted in fewer of the cells transitioning into S phase. CONCLUSION: Endogenous CCN2 is a mediator of basal or TGF-β1-induced collagen I production in human HSCs and regulates entry of the cells into S phase. PMID:19673024

  4. [Clinical and serologic course of patients with mixed connective tissue disease].

    PubMed

    López-Longo, F J; Fernández, J; Monteagudo, I; Rodríguez-Mahou, M; Sánchez-Atrio, A I; Pérez, T; Escalona, M; González, C M; Lapointe, N; Carreño, L

    1994-09-01

    The so called mixed connective tissue disease (MCTD), continues to be a controversial entity, while some authors considered it a good characterized disease, others think that is an undifferentiated connective tissue disease. OBJECTIVE. To analyse the clinical and serological evolution of a group of patients diagnosed of MCTD, with particular consideration to the meaning of anti-nRNP and anti-Sm antibodies. METHOD. We have studied 20 patients diagnosed of MCTD and 112 with systemic lupus erythematosus (SLE). Anti-nRNP and anti-Sm antibodies were detected through counter immunoelectrophoresis, immunoblotting and ELISA. RESULTS. After an average time of evolution of 10 years, 70% (14/20) of the patients diagnosed of MCTD fulfill criteria for SLE (6 cases), scleroderma (6 cases) or polymyositis (2 cases). Anti-nRNP response is persistent, directed mainly against the 70 Kd and A-nRNP polypeptides and qualitatively higher in MCTD in SLE (absorbencies 2.64 vs 1.25. The immunoblotting test detected anti-Sm antibodies in 5 patients (25%) and ELISA test in 14 (70%). CONCLUSIONS. Clinical and serological evolution suggest that MCTD is an undifferentiated connective tissue disease. Anti-nRNP antibodies are characteristic, although anti-Sm antibodies can be detected with ELISA regardless whether on not patients fulfill SLE criteria.

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

    PubMed Central

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

    2013-01-01

    The initial evaluation of patients with interstitial lung disease (ILD) primarily involves a comprehensive, active search for the cause. Autoantibody assays, which can suggest the presence of a rheumatic disease, are routinely performed at various referral centers. When interstitial lung involvement is the condition that allows the definitive diagnosis of connective tissue disease and the classical criteria are met, there is little debate. However, there is still debate regarding the significance, relevance, specificity, and pathophysiological role of autoimmunity in patients with predominant pulmonary involvement and only mild symptoms or formes frustes of connective tissue disease. The purpose of this article was to review the current knowledge of autoantibody positivity and to discuss its possible interpretations in patients with ILD and without clear etiologic associations, as well as to enhance the understanding of the natural history of an allegedly new disease and to describe the possible prognostic implications. We also discuss the proposition of a new term to be used in the classification of ILDs: lung-dominant connective tissue disease. PMID:24473767

  6. Different types of connective tissue alterations associated with cervical artery dissections.

    PubMed

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

    2004-06-01

    This study describes the technical handling and the diagnostic evaluation of skin biopsies in order to standardize the assessment of the delicate morphologic abnormalities that are found in patients with spontaneous cervical artery dissections (sCAD). Skin biopsies from 126 patients with sCAD and from 29 healthy relatives were analyzed. The morphology of the connective tissue was normal in 54 patients with sCAD (43%) and aberrant in 72 patients with sCAD (57%). These latter patients were classified into three groups: in 43 patients, we repeatedly observed composite collagen fibrils and elastic fibers with fragmentation and minicalcifications. In 13 further patients, the dermis was significantly thinner than in healthy subjects. The collagen fibers contained fibrils with highly variable diameters. In a third group of 16 sCAD patients, the abnormalities were restricted to the elastic fibers (with fragmentation and minicalcifications) without significant alterations in the morphology of the collagen fibrils. The finding of different morphologic classes of aberrations among patients suggests that the connective tissue defects are genetically heterogeneous. The segregation of the connective tissue phenotype in three families suggested an autosomal dominant pattern of inheritance.

  7. Irbesartan increased PPAR{gamma} activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction

    SciTech Connect

    Iwai, Masaru; Kanno, Harumi; Senba, Izumi; Nakaoka, Hirotomo; Moritani, Tomozo; Horiuchi, Masatsugu

    2011-03-04

    Research highlights: {yields} Atherosclerotic apolipoprotein E-deficient (ApoEKO) mice were treated with irbesartan. {yields} Irbesartan decreased white adipose tissue weight without affecting body weight. {yields} DNA-binding for PPAR{gamma} was increased in white adipose tissue in vivo by irbesartan. {yields} Irbesartan increased adipocyte number in white adipose tissue. {yields} Irbesatan increased the expression of adiponectin and leptin in white adipose tissue. -- Abstract: The effect of the PPAR{gamma} agonistic action of an AT{sub 1} receptor blocker, irbesartan, on adipose tissue dysfunction was explored using atherosclerotic model mice. Adult male apolipoprotein E-deficient (ApoEKO) mice at 9 weeks of age were treated with a high-cholesterol diet (HCD) with or without irbesartan at a dose of 50 mg/kg/day for 4 weeks. The weight of epididymal and retroperitoneal adipose tissue was decreased by irbesartan without changing food intake or body weight. Treatment with irbesartan increased the expression of PPAR{gamma} in white adipose tissue and the DNA-binding activity of PPAR{gamma} in nuclear extract prepared from adipose tissue. The expression of adiponectin, leptin and insulin receptor was also increased by irbesartan. These results suggest that irbesartan induced activation of PPAR{gamma} and improved adipose tissue dysfunction including insulin resistance.

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

    PubMed

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

    2015-07-01

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

  9. 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.

  10. 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

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

    PubMed

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

    2013-12-01

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

  12. 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. PMID:25477175

  13. Development of mixed connective tissue disease and Sjögren's syndrome in a patient with trisomy X.

    PubMed

    Fujimoto, M; Ikeda, K; Nakamura, T; Iwamoto, T; Furuta, S; Nakajima, H

    2015-10-01

    Increased risk of developing systemic lupus erythematosus (SLE) has been reported in patients with Klinefelter syndrome. Here, we describe a 16-year-old Japanese patient with trisomy X (47,XXX) who developed mixed connective tissue disease (MCTD) and Sjögren's syndrome. She had polyarthritis, edematous fingers with Raynaud's phenomenon, sicca syndrome, interstitial lung disease, possible myositis, and was positive for anti-nuclear antibody, anti-nRNP antibody and rheumatoid factor. This is the first report in the literature of a case of MCTD with female polysomy X, which further supports the link between the presence of extra X chromosome(s) and the development of autoimmune diseases.

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

    PubMed Central

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

    2015-01-01

    ABSTRACT 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. PMID:26462740

  15. 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.

  16. Efficacy and Safety of Grapefruit Juice Intake Accompanying Tacrolimus Treatment in Connective Tissue Disease Patients.

    PubMed

    Tsuji, Hideaki; Ohmura, Koichiro; Nakashima, Ran; Hashimoto, Motomu; Imura, Yoshitaka; Yukawa, Naoichiro; Yoshifuji, Hajime; Fujii, Takao; Mimori, Tsuneyo

    2016-01-01

    Objective It is well known that grapefruit juice (GFJ) elevates the blood tacrolimus (TAC) concentration. We investigated the efficacy and safety of GFJ intake with TAC in cases of connective tissue diseases in which the TAC blood concentration was insufficiently high for clinical improvement, even when 3 mg/day or more of TAC was administered. Methods Seven patients took 200 mL of GFJ every day. The trough levels of the TAC blood concentration were measured before and after GFJ intake and the clinical courses were monitored thereafter. Results First, we surveyed the blood TAC trough levels of 30 recent patients who took 3 mg/day of TAC, and found that 21 patients (70%) did not achieve the minimum target TAC concentration (>5 ng/mL). Seven patients took GFJ due to a lack of efficacy and a relatively low TAC blood concentration. GFJ increased the TAC level from 4.3±2.4 ng/mL to 13.8±6.9 ng/mL (average increase: 3.3-fold). GFJ was also effective in achieving a clinical improvement in most cases without causing any severe adverse events, and it helped to decrease the dosages of glucocorticoid and TAC. In some cases, the blood TAC concentration fluctuated for no apparent reason. Conclusion GFJ intake was effective for the elevation of TAC concentration by approximately three fold and clinical improvement, but special care is required for monitoring its influence on concomitantly used drugs as well as TAC concentration. The addition of GFJ to TAC treatment could be an efficacious treatment option, when the plasma TAC concentration does not reach the minimal target concentration. PMID:27301503

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

    PubMed Central

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

    2012-01-01

    Although variability in connective tissue parameters is widely reported and recognized, systematic examination of the effect of such parametric uncertainties on predictions derived from a full anatomical joint model is lacking. As such, a sensitivity analysis was performed to consider the behavior of a three-dimensional, non-linear, finite element knee model with connective tissue material parameters that varied within a given interval. The model included the coupled mechanics of the tibio-femoral and patellofemoral degrees of freedom. Seven primary connective tissues modeled as nonlinear continua, articular cartilages described by a linear elastic model, and menisci modeled as transverse isotropic elastic materials were included. In this study, a multi-factorial global sensitivity analysis is proposed, which can detect the contribution of influential material parameters while maintaining the potential effect of parametric interactions. To illustrate the effect of material uncertainties on model predictions, exemplar loading conditions reported in a number of isolated experimental paradigms were used. Our findings illustrated that the inclusion of material uncertainties in a coupled tibio-femoral and patello-femoral model reveals biomechanical interactions that otherwise would remain unknown. For example, our analysis revealed that the effect of anterior cruciate ligament parameter variations on the patello-femoral kinematic and kinetic response sensitivities were significantly larger, over a range of flexion angles, when compared to variations associated with material parameters of tissues intrinsic to the patello-femoral joint. We argue that the systematic sensitivity framework presented herein will help identify key material uncertainties that merit further research, as well as provide insight on those uncertainties that may not be as relative to a given response. PMID:20810114

  18. The effect of connective tissue material uncertainties on knee joint mechanics under isolated loading conditions.

    PubMed

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

    2010-12-01

    Although variability in connective tissue parameters is widely reported and recognized, systematic examination of the effect of such parametric uncertainties on predictions derived from a full anatomical joint model is lacking. As such, a sensitivity analysis was performed to consider the behavior of a three-dimensional, non-linear, finite element knee model with connective tissue material parameters that varied within a given interval. The model included the coupled mechanics of the tibio-femoral and patello-femoral degrees of freedom. Seven primary connective tissues modeled as non-linear continua, articular cartilages described by a linear elastic model, and menisci modeled as transverse isotropic elastic materials were included. In this study, a multi-factorial global sensitivity analysis is proposed, which can detect the contribution of influential material parameters while maintaining the potential effect of parametric interactions. To illustrate the effect of material uncertainties on model predictions, exemplar loading conditions reported in a number of isolated experimental paradigms were used. Our findings illustrated that the inclusion of material uncertainties in a coupled tibio-femoral and patello-femoral model reveals biomechanical interactions that otherwise would remain unknown. For example, our analysis revealed that the effect of anterior cruciate ligament parameter variations on the patello-femoral kinematic and kinetic response sensitivities was significantly larger, over a range of flexion angles, when compared to variations associated with material parameters of tissues intrinsic to the patello-femoral joint. We argue that the systematic sensitivity framework presented herein will help identify key material uncertainties that merit further research and provide insight on those uncertainties that may not be as relative to a given response.

  19. Fourier transform infrared imaging and infrared fiber optic probe spectroscopy identify collagen type in connective tissues.

    PubMed

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

    2013-01-01

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

  20. Optimum scratch assay condition to evaluate connective tissue growth factor expression for anti-scar therapy.

    PubMed

    Moon, Heekyung; Yong, Hyeyoung; Lee, Ae-Ri Cho

    2012-02-01

    To evaluate a potential anti-scar therapy, we first need to have a reliable in vitro wound model to understand dermal fibroblast response upon cell injury and how cytokine levels are changed upon different wound heal phases. An in vitro wound model with different scratch assay conditions on primary human foreskin fibroblast monolayer cultures was prepared and cytokine levels and growth properties were evaluated with the aim of determining optimum injury conditions and observation time. Morphological characteristics of differently scratched fibroblasts from 0 to 36 h post injury (1 line, 2 lines and 3 lines) were investigated. The expression of connective tissue growth factor, CTGF, which is a key mediator in hyper-tropic scarring, and relative intensity of CTGF as a function of time were determined by western blot and gelatin Zymography. After injury (1 line), CTGF level was increased more than 2-fold within 1 h and continuously increased up to 3-fold at 6 h and was leveled down to reach normal value at 36 h, at which cell migration was complete. In more serious injury (2 lines), higher expression of CTGF was observed. The down regulation of CTGF expression after CTGF siRNA/lipofectamine transfection in control, 1 line and 2 lines scratch conditions were 40%, 75% and 55%, respectively. As a model anti-CTGF based therapy, CTGF siRNA with different ratios of linear polyethyleneimine (PEI) complexes (1:1, 1:5, 1:10, 1:20 and 1:30) were prepared and down-regulation efficacy of CTGF was evaluated with our optimized scratch assay, which is 1 line injury at 6 h post injury observation time. As the cationic linear PEI ratio increased, the down regulation efficacy was increased from 20% (1:20) to 55% (1:30). As CTGF level was increased to the highest at 6 h and leveled down afterwards, CTGF level at 6 h could provide the most sensitive response upon CTGF siRNA transfection. The scratch assay in the present study can be employed as a useful experimental tool to differentiate

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

    PubMed

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

    2013-08-01

    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.

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

    PubMed

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

    2013-05-24

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

  3. State-of-the-Art Imaging of the Lung for Connective Tissue Disease (CTD).

    PubMed

    Ohno, Yoshiharu; Koyama, Hisanobu; Yoshikawa, Takeshi; Seki, Shinichiro

    2015-12-01

    Involvement of the respiratory system is common in connective tissue diseases (CTDs), and the resultant lung injury can affect every part of the lung: the pleura, alveoli, interstitium, vasculature, lymphatic tissue, and large and/or small airways. Most of the parenchymal manifestations of CTD are similar to those found in interstitial lung diseases (ILDs), especially idiopathic interstitial pneumonias, and can be classified using the same system. Although there is some overlap, each CTD is associated with a characteristic pattern of pulmonary involvement. For this reason, thin-section CT as well as pulmonary function tests and serum markers are utilized for diagnosis, disease severity assessment, and therapeutic efficacy evaluation of ILD associated with CTD. In addition, newly developed pulmonary magnetic resonance imaging (MRI) procedures have been recommended as useful alternative imaging options for patients with CTD. This review article will (1) address radiological findings for chest radiography and conventional or thin-section CT currently used for six major types of CTD, rheumatoid arthritis, scleroderma (progressive systemic sclerosis), polymyositis/dermatomyositis, systemic lupus erythematosus, Sjögren syndrome and mixed connective tissue disease; (2) briefly deal with radiation dose reduction for thin-section CT examination; and (3) discuss clinically applicable or state-of-the-art MR imaging for CTD patients.

  4. 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

  5. The action of vitamin E on the ageing of connective tissues in the mouse.

    PubMed

    Blackett, A D; Hall, D A

    1980-01-01

    In an attempt to determine the relevance of the free radical theory of ageing to age changes discernible in connective tissue parameters, a small colony of C3H/He and LAF1 mice was set up, with sample culled at intervals throughout the lifespan to provide experimental samples. To half of the stock a dietary supplement of vitamin E, a naturally occurring antioxidant, was given at a level of 2500 mg/kg of diet. Tests were carried out on culled samples to provide data on the total collagen levels of bone and skin, on thermal shrinkage temperature and maximal degree of shrinkage of tendon fibres, and on the recovery of skin from stress. Vitamin E was found to have no effect on any of the parameters measured on C3H/He mice but to exert an influence on the parameters of LAF1 mice around the age of 10 months. This influence, however, is not regarded as being relevant to the ageing of the tissues and thus no evidence can be derived for a free-radical mechanism playing a role in the ageing of connective tissues.

  6. Resorption of elastic fibers in monkey gingival connective tissue: ultrastructural and immunocytochemical evidence.

    PubMed

    Sawada, Takashi

    2011-04-01

    Little is known about the remodeling of elastic fibers in gingival connective tissue. In this study, elastic fibers in the lamina propria of monkey gingiva were examined by transmission electron microscopy and immunocytochemistry. Some elastic fibers were localized at invagination on the surface of the narrow processes of fibroblasts distributed among dense assemblies of collagen fibrils, and also within coated pits, which were pinching off as coated vesicles. At a higher magnification, the coated vesicles contained filamentous structures, as well as pentagonal structures similar those previously reported in elastic fibers. Immunoelectron microscopy demonstrated positive staining for fibrillin, one of the main components of microfibril, localized either in the coated pits or vesicles. These observations indicate that at least some elastic fibers were resorbed by fibroblasts, and that, in spite of the general belief that little remodeling of elastic fibers occurs under normal conditions, resorption of elastic fibers does occur in monkey gingival connective tissue. The functional significance of this is not yet clear, but it may be involved in facilitating the delicate and efficient adaptation of tissue to physical requirements during mastication.

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

    PubMed Central

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

    2009-01-01

    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

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

    PubMed Central

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

    2010-01-01

    Epithelial ovarian carcinoma (EOC) is a leading cause of death from gynecologic malignancy, due mainly to the prevalence of undetected metastatic disease. The process of cell invasion during intra-peritoneal anchoring of metastatic lesions requires concerted regulation of many processes, including modulation of adhesion to the extracellular matrix and localized invasion. Exploratory cDNA microarray analysis of early response genes (altered after 4 hours of 3-dimensional collagen culture) coupled with confirmatory real-time RT-PCR, multiple three-dimensional cell culture matrices, Western blot, immunostaining, adhesion, migration, and invasion assays were used to identify modulators of adhesion pertinent to EOC progression and metastasis. cDNA microarray analysis indicated a dramatic downregulation of connective tissue growth factor (CTGF) in EOC cells placed in invasion-mimicking conditions (3-dimensional type I collagen). Examination of human EOC specimens revealed that CTGF expression was absent in 46% of the tested samples (n=41), but was present in 100% of normal ovarian epithelium samples (n=7). Reduced CTGF expression occurs in many types of cells and may be a general phenomenon displayed by cells encountering a 3D environment. CTGF levels were inversely correlated with invasion such that downregulation of CTGF increased, while its upregulation reduced, collagen invasion. Cells adhered preferentially to a surface comprised of both collagen I and CTGF relative to either component alone using α6β1 and α3β1 integrins. Together these data suggest that downregulation of CTGF in EOC cells may be important for cell invasion through modulation of cell-matrix adhesion. PMID:19382180

  9. [Antinuclear antibodies without connective tissue disease : Antibodies against LEDGF/DSF70].

    PubMed

    Mierau, R

    2016-05-01

    Testing for antinuclear antibodies (ANA) by the indirect immunofluorescence test (IFT) is regarded as a fundamental serological screening method for diagnosing connective tissue diseases (CTD). In the case of a negative result exclusion of certain CTDs is indicated, especially systemic lupus erythematosus, and a positive ANA result is the starting point for further tests aimed at finding disease-specific autoantibodies. The recently discovered antibodies against lens epithelium-derived growth factor (LEDGF/DSF70) deviate from the normal interpretation pattern in ANA diagnostics. These antibodies give rise to a characteristic dense fine speckled (DSF) immunofluorescence pattern in IFT and target the ubiquitously expressed nuclear stress protector protein LEDGFp75. They can be detected, sometimes in high titers, not only in patients with diverse disorders of the skin or eyes and with neoplasms but also in persons with relatively mild or unspecific complaints and even in apparently healthy individuals; however, they are less frequent in CTD. These anti-LEDGF antibodies can be found in all age groups with a tendency to a higher prevalence in younger people and the frequency does not increase in advanced age. The vast majority of anti-LEDGF carriers are female. The CTDs with isolated anti-LEDGF antibodies, i. e. unaccompanied by autoantibodies typical for the respective CTD, are extremely rare. Detection of ANA exclusively with a DSF immunofluorescence pattern and confirmed by a specific anti-LEDGF binding assay, does not therefore indicate the presence of CTD but is indicative of exclusion of systemic lupus erythematosus, systemic sclerosis and an ANA-associated overlap syndrome, similar to a completely negative ANA result.

  10. Brachial Neuritis With Phrenic Nerve Involvement in a Patient With a Possible Connective Tissue Disease

    PubMed Central

    Subash, Meera; Patel, Gaurav; Welker, John

    2014-01-01

    Background. Brachial neuritis (BN) is a rare inflammatory condition of peripheral nerves, usually involving the cervicobrachial plexus. These patients present with sudden onset of shoulder and arm pain that evolves into muscle weakness and atrophy.. Case Report. A 33-year-old woman presented with a 1-month history of diffuse pain in her thorax. She had no trauma or inciting incident prior to the onset of this pain and was initially treated for muscle spasms. The patient was seen in the emergency room multiple times and was treated with several courses of antibiotics for pneumonia on the basis of clinical symptoms and abnormal x-rays. The pleuritic chest pain persisted for at least 4 months, and the patient was eventually admitted for worsening pain and dyspnea. On physical examination, crackles were heard at both lung bases, and chest inspection revealed increased expansion in the upper thorax but poor expansion of the lower thorax and mild paradoxical respiration. “Sniff” test revealed no motion of the left hemidiaphragm and reduced motion on the right hemidiaphragm. Her computed tomography scan revealed bilateral atelectasis, more severe at the left base. She reported no symptoms involving her joints or skin or abdomen. Her presentation and clinical course are best explained by BN with a bilateral diaphragmatic weakness. However, she had a positive ANA, RF, anti-RNP antibody, and anti SS-A. Conclusion. Patients with BN can present with diffuse thoracic pain, pleuritic chest pain, and diaphragmatic weakness. Our patient may represent a case of connective tissue disease presenting with brachial plexus neuritis. PMID:26425609

  11. [Three dimensional structure of the connective tissue papillae of the tongue in Suncus murinus].

    PubMed

    Kobayashi, K; Miyata, K; Iwasaki, S; Takahashi, K

    1989-08-01

    The surface structure of the connective tissue papillae (CP) of Suncus murinus tongue was observed by SEM after fixing with Karnovsky's fixative and removal of the epithelial cell layer with 3N or 8N HCl. On the surface of the slender conical tongue, there are densely distributed filiform papillae among which fungiform papillae are seen sporadically. A pair of vallate papillae are situated in the posterior region of the tongue. Filiform papillae appear somewhat different externally depending on the dorsal surface of the anterior tongue. At the tip of the tongue, filiform papillae are of a slender conical shape and have a slight depression in the anterior basal portion. The CP of these is seen as a spherical protrusion on which a shallow groove runs in the anteroposterior direction. In the middle region, somewhat large filiform papillae contain CP having one or two small round head-like structures on each spherical protrusion. These head-like structures are increased in number in the posterior region. In the most posterior region of the anterior tongue, there are distributed large filiform papillae having several slender protrusions that surround a basal anterior depression. These large branched filiform papillae have a glove finger like CP. Small conical filiform papillae are distributed in the posterior marginal region of the anterior tongue which have CP of a horse-shoe like protrusion that opens in the anterior direction. Spherical fungiform papillae have CP which are thick columnar in shape with many lateral thin folds running vertically and having a round depression on the top of each. CP of the vallate papillae appear as a beehive like structure.(ABSTRACT TRUNCATED AT 250 WORDS)

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

    PubMed

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

    2014-10-01

    positive change in [Formula: see text] and [Formula: see text] with increases in [Formula: see text]-the findings lend support to the hypotheses, implicating the implicit dependence of UV-induced cross-links on [Formula: see text] and [Formula: see text] for directing tissue stiffness and resilience. From a practical perspective, the study is a step in the direction to establish a UV irradiation treatment protocol for effective control of exogenous cross-linking in connective tissues.

  13. Familial occurrence and heritable connective tissue disorders in cervical artery dissection

    PubMed Central

    Goeggel Simonetti, Barbara; Schilling, Sabrina; Martin, Juan José; Kloss, Manja; Sarikaya, Hakan; Hausser, Ingrid; Engelter, Stefan; Metso, Tiina M.; Pezzini, Alessandro; Thijs, Vincent; Touzé, Emmanuel; Paolucci, Stefano; Costa, Paolo; Sessa, Maria; Samson, Yves; Béjot, Yannick; Altintas, Ayse; Metso, Antti J.; Hervé, Dominique; Lichy, Christoph; Jung, Simon; Fischer, Urs; Lamy, Chantal; Grau, Armin; Chabriat, Hugues; Caso, Valeria; Lyrer, Philippe A.; Stapf, Christian; Tatlisumak, Turgut; Brandt, Tobias; Tournier-Lasserve, Elisabeth; Germain, Dominique P.; Frank, Michael; Baumgartner, Ralf W.; Grond-Ginsbach, Caspar; Bousser, Marie-Germaine; Leys, Didier; Dallongeville, Jean; Bersano, Anna

    2014-01-01

    Objective: In a large series of patients with cervical artery dissection (CeAD), a major cause of ischemic stroke in young and middle-aged adults, we aimed to examine frequencies and correlates of family history of CeAD and of inherited connective tissue disorders. Methods: We combined data from 2 large international multicenter cohorts of consecutive patients with CeAD in 23 neurologic departments participating in the CADISP-plus consortium, following a standardized protocol. Frequency of reported family history of CeAD and of inherited connective tissue disorders was assessed. Putative risk factors, baseline features, and 3-month outcome were compared between groups. Results: Among 1,934 consecutive patients with CeAD, 20 patients (1.0%, 95% confidence interval: 0.6%–1.5%) from 17 families (0.9%, 0.5%–1.3%) had a family history of CeAD. Family history of CeAD was significantly more frequent in patients with carotid location of the dissection and elevated cholesterol levels. Two patients without a family history of CeAD had vascular Ehlers-Danlos syndrome with a mutation in COL3A1. This diagnosis was suspected in 2 additional patients, but COL3A1 sequencing was negative. Two patients were diagnosed with classic and hypermobile Ehlers-Danlos syndrome, one patient with Marfan syndrome, and one with osteogenesis imperfecta, based on clinical criteria only. Conclusions: In this largest series of patients with CeAD to date, family history of symptomatic CeAD was rare and inherited connective tissue disorders seemed exceptional. This finding supports the notion that CeAD is a multifactorial disease in the vast majority of cases. PMID:25355833

  14. Microwave irradiation increases recovery of neuropeptides from brain tissues

    SciTech Connect

    Theodorsson, E.; Stenfors, C.; Mathe, A.A. )

    1990-11-01

    The effect of focused high energy microwave treatment (MW) on brain concentrations and molecular forms of substance P, neurokinin A, neuropeptide Y, neurotensin, galanin and calcitonin gene-related peptide was investigated. Groups of rats were treated as follows: (1) MW, storage for 60 min at 22 degrees C, (2) Decapitation, storage for 60 min at 22 degrees C, (3) Decapitation, storage for 60 min at 22 degrees C, MW treatment, (4) MW, decapitation, storage for 2 min at 22 degrees C and 5. Decapitation, storage for 2 min at 22 degrees C. Peptide concentrations were in all instances highest in the MW sacrificed groups. MW increased the concentration of intact peptides by rapid inhibition of peptidase activity and increase in peptide solubility/extractability.

  15. Antinuclear antibodies in scleroderma, mixed connective tissue disease and "primary" Raynaud's phenomenon.

    PubMed

    Cruz, M; Mejia, G; Lavalle, C; Cortes, J J; Reyes, P A

    1988-03-01

    The diversity of antibodies in patients with scleroderma, mixed connective tissue disease or "primary" Raynaud's phenomenon could be used as a laboratory aid in the clinical diagnosis. In serum samples of 75 patients we screened for antinuclear antibodies (HEp 2 cells), anti DNA, soluble nucleoprotein and extractable nuclear antigens (Sm, rRNP, U1-nRNP, SSA/Ro, SSB/La and Scl-70). Distinctive antinuclear antibodies pattern was identified in each group of patients. This immunologic profile is valuable for clinical diagnosis and the preferential association of certain autoantibodies with some diseases and not with others, suggest an antigen-driven stimulus for its production.

  16. Biological effects of hyaluronan in connective tissues, eye, skin, venous wall. Role in aging.

    PubMed

    Robert, L; Robert, A-M; Renard, G

    2010-06-01

    Hyaluronan, as most macromolecules of the extracellular matrix, are produced by the differentiated mesenchymal cells. These cells produce also enzymes degrading hyaluronan. This results in the presence of several hyaluronan pools of different molecular weights, all capable of interacting with surrounding cells, mediated by hyaluronan binding proteins and receptors. These interactions modulate cell phenotype and produce a variety of effects conditioning the specific functions of tissues. We shall discuss here several examples studied in our laboratory, concerning skin, cornea and the venous wall. Some of these actions might even be harmful, and could play an important role in aging of connective tissues with loss of function. Some of these age-dependent modifications mediated by hyaluronan will be reviewed and commented, especially the upregulation of matrix degrading enzymes as MMP-2 and MMP-9. We shall also mention some of our experiments for finding molecules capable of counteracting the harmful effects mediated by hyaluronan.

  17. 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.

  18. Mutation of fibulin-1 causes a novel syndrome involving the central nervous system and connective tissues.

    PubMed

    Bohlega, Saeed; Al-Ajlan, Huda; Al-Saif, Amr

    2014-05-01

    Fibulin-1 is an extracellular matrix protein that has an important role in the structure of elastic fibers and basement membranes of various tissues. Using homozygosity mapping and exome sequencing, we discovered a missense mutation, p.(Cys397Phe), in fibulin-1 in three patients from a consanguineous family presented with a novel syndrome of syndactyly, undescended testes, delayed motor milestones, mental retardation and signs of brain atrophy. The mutation discovered segregated with the phenotype and was not found in 374 population-matched alleles. The affected cysteine is highly conserved across vertebrates and its mutation is predicted to abolish a disulfide bond that defines the tertiary structure of fibulin-1. Our findings emphasize the crucial role fibulin-1 has in development of the central nervous system and various connective tissues.

  19. [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. PMID:25993866

  20. In the beginning there were soft collagen-cell gels: towards better 3D connective tissue models?

    PubMed

    Brown, Robert A

    2013-10-01

    In the 40 years since Elsdale and Bard's analysis of fibroblast culture in collagen gels we have moved far beyond the concept that such 3D fibril network systems are better models than monolayer cultures. This review analyses key aspects of that progression of models, against a background of what exactly each model system tries to mimic. This story tracks our increasing understanding of fibroblast responses to soft collagen gels, in particularly their cytoskeletal contraction, migration and integrin attachment. The focus on fibroblast mechano-function has generated models designed to directly measure the overall force generated by fibroblast populations, their reaction to external loads and the role of the matrix structure. Key steps along this evolution of 3D collagen models have been designed to mimic normal skin, wound repair, tissue morphogenesis and remodelling, growth and contracture during scarring/fibrosis. As new models are developed to understand cell-mechanical function in connective tissues the collagen material has become progressively more important, now being engineered to mimic more complex aspects of native extracellular matrix structure. These have included collagen fibril density, alignment and hierarchical structure, controlling material stiffness and anisotropy. But of these, tissue-like collagen density is key in that it contributes to control of the others. It is concluded that across this 40 year window major progress has been made towards establishing a family of 3D experimental collagen tissue-models, suitable to investigate normal and pathological fibroblast mechano-functions.

  1. Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution.

    PubMed

    Tagliazucchi, Enzo; Roseman, Leor; Kaelen, Mendel; Orban, Csaba; Muthukumaraswamy, Suresh D; Murphy, Kevin; Laufs, Helmut; Leech, Robert; McGonigle, John; Crossley, Nicolas; Bullmore, Edward; Williams, Tim; Bolstridge, Mark; Feilding, Amanda; Nutt, David J; Carhart-Harris, Robin

    2016-04-25

    Lysergic acid diethylamide (LSD) is a non-selective serotonin-receptor agonist that was first synthesized in 1938 and identified as (potently) psychoactive in 1943. Psychedelics have been used by indigenous cultures for millennia [1]; however, because of LSD's unique potency and the timing of its discovery (coinciding with a period of major discovery in psychopharmacology), it is generally regarded as the quintessential contemporary psychedelic [2]. LSD has profound modulatory effects on consciousness and was used extensively in psychological research and psychiatric practice in the 1950s and 1960s [3]. In spite of this, however, there have been no modern human imaging studies of its acute effects on the brain. Here we studied the effects of LSD on intrinsic functional connectivity within the human brain using fMRI. High-level association cortices (partially overlapping with the default-mode, salience, and frontoparietal attention networks) and the thalamus showed increased global connectivity under the drug. The cortical areas showing increased global connectivity overlapped significantly with a map of serotonin 2A (5-HT2A) receptor densities (the key site of action of psychedelic drugs [4]). LSD also increased global integration by inflating the level of communication between normally distinct brain networks. The increase in global connectivity observed under LSD correlated with subjective reports of "ego dissolution." The present results provide the first evidence that LSD selectively expands global connectivity in the brain, compromising the brain's modular and "rich-club" organization and, simultaneously, the perceptual boundaries between the self and the environment.

  2. β2-Adrenoceptor is involved in connective tissue remodeling in regenerating muscles by decreasing the activity of MMP-9.

    PubMed

    Silva, Meiricris T; Nascimento, Tábata L; Pereira, Marcelo G; Siqueira, Adriane S; Brum, Patrícia C; Jaeger, Ruy G; Miyabara, Elen H

    2016-07-01

    We investigated the role of β2-adrenoceptors in the connective tissue remodeling of regenerating muscles from β2-adrenoceptor knockout (β2KO) mice. Tibialis anterior muscles from β2KO mice were cryolesioned and analyzed after 3, 10, and 21 days. Regenerating muscles from β2KO mice showed a significant increase in the area density of the connective tissue and in the amount of collagen at 10 days compared with wild-type (WT) mice. A greater increase occurred in the expression levels of collagen I, III, and IV in regenerating muscles from β2KO mice evaluated at 10 days compared with WT mice; this increase continued at 21 days, except for collagen III. Matrix metalloproteinase (MMP-2) activity increased to a similar extent in regenerating muscles from both β2KO and WT mice at 3 and 10 days. This was also the case for MMP-9 activity in regenerating muscles from both β2KO and WT mice at 3 days; however, at 10 days post-cryolesion, this activity returned to baseline levels only in WT mice. MMP-3 activity was unaltered in regenerating muscles at 10 days. mRNA levels of tumor necrosis factor-α increased in regenerating muscles from WT and β2KO mice at 3 days and, at 10 days post-cryolesion, returned to baseline only in WT mice. mRNA levels of interleukin-6 increased in muscles from WT mice at 3 days post-cryolesion and returned to baseline at 10 days post-cryolesion but were unchanged in β2KO mice. Our results suggest that the β2-adrenoceptor contributes to collagen remodeling during muscle regeneration by decreasing MMP-9 activity. PMID:26896238

  3. β2-Adrenoceptor is involved in connective tissue remodeling in regenerating muscles by decreasing the activity of MMP-9.

    PubMed

    Silva, Meiricris T; Nascimento, Tábata L; Pereira, Marcelo G; Siqueira, Adriane S; Brum, Patrícia C; Jaeger, Ruy G; Miyabara, Elen H

    2016-07-01

    We investigated the role of β2-adrenoceptors in the connective tissue remodeling of regenerating muscles from β2-adrenoceptor knockout (β2KO) mice. Tibialis anterior muscles from β2KO mice were cryolesioned and analyzed after 3, 10, and 21 days. Regenerating muscles from β2KO mice showed a significant increase in the area density of the connective tissue and in the amount of collagen at 10 days compared with wild-type (WT) mice. A greater increase occurred in the expression levels of collagen I, III, and IV in regenerating muscles from β2KO mice evaluated at 10 days compared with WT mice; this increase continued at 21 days, except for collagen III. Matrix metalloproteinase (MMP-2) activity increased to a similar extent in regenerating muscles from both β2KO and WT mice at 3 and 10 days. This was also the case for MMP-9 activity in regenerating muscles from both β2KO and WT mice at 3 days; however, at 10 days post-cryolesion, this activity returned to baseline levels only in WT mice. MMP-3 activity was unaltered in regenerating muscles at 10 days. mRNA levels of tumor necrosis factor-α increased in regenerating muscles from WT and β2KO mice at 3 days and, at 10 days post-cryolesion, returned to baseline only in WT mice. mRNA levels of interleukin-6 increased in muscles from WT mice at 3 days post-cryolesion and returned to baseline at 10 days post-cryolesion but were unchanged in β2KO mice. Our results suggest that the β2-adrenoceptor contributes to collagen remodeling during muscle regeneration by decreasing MMP-9 activity.

  4. Factors affecting uptake and retention of technetium-99m-diphosphonate and 99m-pertechnetate in osseous, connective and soft tissues.

    PubMed

    Francis, M D; Slough, C L; Tofe, A J

    1976-06-14

    The bone scanning complex, 99mTc-Sn-EHDP, consisting of the nuclide technetium-99m, stannous ion and ethane-1-hydroxy-1,1-diphosphonate, administered intravenously is retained in soft tissues in proportion to increasing calcium content of the tissues. Within bone tissue, the retention is proportional to vascularity and to surface area of calcium phosphate in bones and not necessarily to calcium and phosphate concentration. The nuclidic agent 99mTcO4-BUT NOT THE 99MTc-diphosphonate is selectively taken up by the thyroid and this uptake can be blocked by administering sodium perchlorate. Among the connective tissues studied, the tracheal cartilage seems to have the greatest potential to calcify with increasing age of the animal and man. Soft tissue does not retain the bone scanning complex 99mTc-Sn-EHDP but does retain 99mTcO4-. PMID:182328

  5. Clinical ultrashort echo time imaging of bone and other connective tissues.

    PubMed

    Robson, Matthew D; Bydder, Graeme M

    2006-11-01

    The background underpinning the clinical use of ultrashort echo time, SPRITE and other pulse sequences for imaging bone and other connective tissues with short T2 is reviewed. Features of the basic physics relevant to UTE imaging are described, including the consequences when the radiofrequency pulse duration is of the order of T2 so that rotation of tissue magnetization into the transverse plane is incomplete. Consequences of the broad linewidth of short T2 components are also discussed, including partial saturation by off-resonance fat suppression pulses as well as those used in multislice and multiecho imaging. The need for rapid data acquisition of the order of T2 is explained. The basic two-dimensional UTE pulse sequence with its half excitation pulse and radial imaging from the centre of k-space is described, together with options that suppress fat and/or reduce the signal from long T2 components. The basic features of SPRITE and other sequences with very short TE are described. Image interpretation is discussed. Clinical features of the imaging of cortical bone, tendons, ligaments, menisci, periosteum and the spine are illustrated. The source of the short T2 signal in these tissues is predominantly collagen and water tightly bound to collagen. Short T2 components in all of these tissues are detectible and may show high signals. Possible future developments are outlined, as are technical limitations of clinical magnetic resonance systems. PMID:17075960

  6. Targeted ablation of the abcc6 gene results in ectopic mineralization of connective tissues.

    PubMed

    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

    2005-09-01

    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.

  7. 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

    -elastic extracellular matrixes, and interact closely with tropoelastin and integrins. Not only do microfibrils provide structural integrity of specific organ systems, but they also provide a scaffold for elastogenesis in elastic tissues. Fibrillin is important for the assembly of elastin into elastic fibers. Mutations in the fibrillin-1 gene are closely associated with Marfan syndrome. Fibulins are tightly connected with basement membranes, elastic fibers and other components of extracellular matrix and participate in formation of elastic fibers. Tenascins are ECM polymorphic glycoproteins found in many connective tissues in the body. Their expression is regulated by mechanical stress both during development and in adulthood. Tenascins mediate both inflammatory and fibrotic processes to enable effective tissue repair and play roles in pathogenesis of Ehlers-Danlos, heart disease, and regeneration and recovery of musculo-tendinous tissue. One of the roles of thrombospondin 1 is activation of TGFβ. Increased expression of thrombospondin and TGFβ activity was observed in fibrotic skin disorders such as keloids and scleroderma. Cartilage oligomeric matrix protein (COMP) or thrombospondin-5 is primarily present in the cartilage. High levels of COMP are present in fibrotic scars and systemic sclerosis of the skin, and in tendon, especially with physical activity, loading and post-injury. It plays a role in vascular wall remodeling and has been found in atherosclerotic plaques as well.

  8. Connective tissue, Ehlers-Danlos syndrome(s), and head and cervical pain.

    PubMed

    Castori, Marco; Morlino, Silvia; Ghibellini, Giulia; Celletti, Claudia; Camerota, Filippo; Grammatico, Paola

    2015-03-01

    Ehlers-Danlos syndrome (EDS) is an umbrella term for a growing group of hereditary disorders of the connective tissue mainly manifesting with generalized joint hypermobility, skin hyperextensibility, and vascular and internal organ fragility. In contrast with other well known heritable connective tissue disorders with severe cardiovascular involvement (e.g., Marfan syndrome), most EDS patients share a nearly normal life span, but are severely limited by disabling features, such as pain, fatigue and headache. In this work, pertinent literature is reviewed with focus on prevalence, features and possible pathogenic mechanisms of headache in EDSs. Gathered data are fragmented and generally have a low level of evidence. Headache is reported in no less than 1/3 of the patients. Migraine results the most common type in the hypermobility type of EDS. Other possibly related headache disorders include tension-type headache, new daily persistent headache, headache attributed to spontaneous cerebrospinal fluid leakage, headache secondary to Chiari malformation, cervicogenic headache and neck-tongue syndrome, whose association still lacks of reliable prevalence studies. The underlying pathogenesis seems complex and variably associated with cardiovascular dysautonomia, cervical spine and temporomandibular joint instability/dysfunction, meningeal fragility, poor sleep quality, pain-killer drugs overuse and central sensitization. Particular attention is posed on a presumed subclinical cervical spine dysfunction. Standard treatment is always symptomatic and usually unsuccessful. Assessment and management procedures are discussed in order to put some basis for ameliorating the actual patients' needs and nurturing future research. PMID:25655119

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

    SciTech Connect

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

    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 muscle enzymes levels. Thallium 201 scans showed abnormal findings in 32 patients and revealed subclinical lesions in 18 patients, while electromyography findings were abnormal in 25 of these 32 patients. Serum enzyme levels were raised in only 8 patients. Thallium 201 scanning proved to be a useful guide for modifying therapy when laboratory data were conflicting. It was useful to evaluate treatment efficacy. Because our data indicate a 100% positive predictive value, we believe that thallium 201 scanning should be advised for severe systemic connective tissue diseases with discordant test results.

  10. The integrin-collagen connection--a glue for tissue repair?

    PubMed

    Zeltz, Cédric; Gullberg, Donald

    2016-02-15

    The α1β1, α2β1, α10β1 and α11β1 integrins constitute a subset of the integrin family with affinity for GFOGER-like sequences in collagens. Integrins α1β1 and α2β1 were originally identified on a subset of activated T-cells, and have since been found to be expressed on a number of cell types including platelets (α2β1), vascular cells (α1β1, α2β1), epithelial cells (α1β1, α2β1) and fibroblasts (α1β1, α2β1). Integrin α10β1 shows a distribution that is restricted to mesenchymal stem cells and chondrocytes, whereas integrin α11β1 appears restricted to mesenchymal stem cells and subsets of fibroblasts. The bulk of the current literature suggests that collagen-binding integrins only have a limited role in adult connective tissue homeostasis, partly due to a limited availability of cell-binding sites in the mature fibrillar collagen matrices. However, some recent data suggest that, instead, they are more crucial for dynamic connective tissue remodeling events--such as wound healing--where they might act specifically to remodel and restore the tissue architecture. This Commentary discusses the recent development in the field of collagen-binding integrins, their roles in physiological and pathological settings with special emphasis on wound healing, fibrosis and tumor-stroma interactions, and include a discussion of the most recently identified newcomers to this subfamily--integrins α10β1 and α11β1. PMID:26857815

  11. Mechanical properties of human autologous tubular connective tissues (human biotubes) obtained from patients undergoing peritoneal dialysis.

    PubMed

    Nakayama, Yasuhide; Kaneko, Yoshiyuki; Takewa, Yoshiaki; Okumura, Noriko

    2016-10-01

    Completely autologous in vivo tissue-engineered connective tissue tubes (Biotubes) have promise as arterial vascular grafts in animal implantation studies. In this clinical study of patients undergoing peritoneal dialysis (PD) (n = 11; age: 39-83 years), we evaluated human Biotubes' (h-Biotubes) mechanical properties to determine whether Biotubes with feasibility as vascular grafts could be formed in human bodies. We extracted PD catheters, embedded for 4-47 months, and obtained tubular connective tissues as h-Biotubes (internal diameter: 5 mm) from around the catheter' silicone tubular parts. h-Biotubes were composed mainly of collagen with smooth luminal surfaces. The average wall thickness was 278 ± 178 μm. No relationship was founded between the tubes' mechanical properties and patients' ages or PD catheter embedding periods statistically. However, the elastic modulus (2459 ± 970 kPa) and tensile strength (623 ± 314 g) of h-Biotubes were more than twice as great as those from animal Biotubes, formed from the same PD catheters by embedding in the beagle subcutaneous pouches for 1 month, or beagle arteries. The burst strength (6338 ± 1106 mmHg) of h-Biotubes was almost the same as that of the beagle thoracic or abdominal aorta. h-Biotubes could be formed in humans over a 4-month embedding period, and they satisfied the mechanical requirements for application as vascular grafts. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 104B: 1431-1437, 2016.

  12. [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.

  13. The integrin-collagen connection--a glue for tissue repair?

    PubMed

    Zeltz, Cédric; Gullberg, Donald

    2016-02-15

    The α1β1, α2β1, α10β1 and α11β1 integrins constitute a subset of the integrin family with affinity for GFOGER-like sequences in collagens. Integrins α1β1 and α2β1 were originally identified on a subset of activated T-cells, and have since been found to be expressed on a number of cell types including platelets (α2β1), vascular cells (α1β1, α2β1), epithelial cells (α1β1, α2β1) and fibroblasts (α1β1, α2β1). Integrin α10β1 shows a distribution that is restricted to mesenchymal stem cells and chondrocytes, whereas integrin α11β1 appears restricted to mesenchymal stem cells and subsets of fibroblasts. The bulk of the current literature suggests that collagen-binding integrins only have a limited role in adult connective tissue homeostasis, partly due to a limited availability of cell-binding sites in the mature fibrillar collagen matrices. However, some recent data suggest that, instead, they are more crucial for dynamic connective tissue remodeling events--such as wound healing--where they might act specifically to remodel and restore the tissue architecture. This Commentary discusses the recent development in the field of collagen-binding integrins, their roles in physiological and pathological settings with special emphasis on wound healing, fibrosis and tumor-stroma interactions, and include a discussion of the most recently identified newcomers to this subfamily--integrins α10β1 and α11β1.

  14. Connecting and Collaborating: How Content-Related Instruction Increases Students' Speaking Abilities

    ERIC Educational Resources Information Center

    Harkins, Sherri

    2010-01-01

    Young students come to world language classrooms with genuine excitement about the possibility of being able to speak a language other than their own. When world language teachers connect second language instruction to students' general education curriculum content, the opportunity presents itself to potentially increase students' ability to speak…

  15. Effect of Cues to Increase Sound Pressure Level on Respiratory Kinematic Patterns during Connected Speech

    ERIC Educational Resources Information Center

    Huber, Jessica E.

    2007-01-01

    Purpose: This study examined the response of the respiratory system to 3 cues used to elicit increased vocal loudness to determine whether the effects of cueing, shown previously in sentence tasks, were present in connected speech tasks and to describe differences among tasks. Method: Fifteen young men and 15 young women produced a 2-paragraph…

  16. Increasing the penetration depth for ultrafast laser tissue ablation using glycerol based optical clearing

    NASA Astrophysics Data System (ADS)

    Gabay, Ilan; Subramanian, Kaushik G.; Martin, Chris; Yildirim, Murat; Tuchin, Valery V.; Ben-Yakar, Adela

    2016-03-01

    Background: Deep tissue ablation is the next challenge in ultrafast laser microsurgery. By focusing ultrafast pulses below the tissue surface one can create an ablation void confined to the focal volume. However, as the ablation depth increases in a scattering tissue, increase in the required power can trigger undesired nonlinear phenomena out of focus that restricts our ability to ablate beyond a maximum ablation depth of few scattering lengths. Optical clearing (OC) might reduce the intensity and increase the maximal ablation depth by lowering the refractive index mismatch, and therefore reducing scattering. Some efforts to ablate deeper showed out of focus damage, while others used brutal mechanical methods for clearing. Our clinical goal is to create voids in the scarred vocal folds and inject a biomaterial to bring back the tissue elasticity and restore phonation. Materials and methods: Fresh porcine vocal folds were excised and applied a biocompatible OC agent (75% glycerol). Collimated transmittance was monitored. The tissue was optically cleared and put under the microscope for ablation threshold measurements at different depths. Results: The time after which the tissue was optically cleared was roughly two hours. Fitting the threshold measurements to an exponential decay graph indicated that the scattering length of the tissue increased to 83+/-16 μm, which is more than doubling the known scattering length for normal tissue. Conclusion: Optical clearing with Glycerol increases the tissue scattering length and therefore reduces the energy for ablation and increases the maximal ablation depth. This technique can potentially improve clinical microsurgery.

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

    PubMed Central

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

    2015-01-01

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

  18. 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.

  19. 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. PMID:27053177

  20. Increased functional connectivity with puberty in the mentalising network involved in social emotion processing

    PubMed Central

    Klapwijk, Eduard T.; Goddings, Anne-Lise; Heyes, Stephanie Burnett; Bird, Geoffrey; Viner, Russell M.; Blakemore, Sarah-Jayne

    2015-01-01

    There is increasing evidence that puberty plays an important role in the structural and functional brain development seen in adolescence, but little is known of the pubertal influence on changes in functional connectivity. We explored how pubertal indicators (salivary concentrations of testosterone, oestradiol and DHEA; pubertal stage; menarcheal status) relate to functional connectivity between components of a mentalising network identified to be engaged in social emotion processing by our prior work, using psychophysiological interaction (PPI) analysis. Female adolescents aged 11 to 13 years were scanned whilst silently reading scenarios designed to evoke either social emotions (guilt and embarrassment) or basic emotions (disgust and fear), of which only social compared to basic emotions require the representation of another person’s mental states. Pubertal stage and menarcheal status were used to assign participants to pre/early or mid/late puberty groups. We found increased functional connectivity between the dorsomedial prefrontal cortex (DMPFC) and the right posterior superior temporal sulcus (pSTS) and right temporo-parietal junction (TPJ) during social relative to basic emotion processing. Moreover, increasing oestradiol concentrations were associated with increased functional connectivity between the DMPFC and the right TPJ during social relative to basic emotion processing, independent of age. Our analysis of the PPI data by phenotypic pubertal status showed that more advanced puberty stage was associated with enhanced functional connectivity between the DMPFC and the left anterior temporal cortex (ATC) during social relative to basic emotion processing, also independent of age. Our results suggest increased functional maturation of the social brain network with the advancement of puberty in girls. PMID:23998674

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

    PubMed Central

    Tong, Zhixiang; Sant, Shilpa

    2011-01-01

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

  2. The rate of synthesis and decomposition of tissue proteins in hypokinesia and increased muscular activity

    NASA Technical Reports Server (NTRS)

    Fedorov, I. V.; Chernyy, A. V.; Fedorov, A. I.

    1978-01-01

    During hypokinesia and physical loading (swimming) of rats, the radioactivity of skeletal muscle, liver, kidney, heart, and blood proteins was determined after administration of radioactive amino acids. Tissue protein synthesis decreased during hypokinesia, and decomposition increased. Both synthesis and decomposition increased during physical loading, but anabolic processes predominated in the total tissue balance. The weights of the animals decreased in hypokinesia and increased during increased muscle activity.

  3. Increased cortical-limbic anatomical network connectivity in major depression revealed by diffusion tensor imaging.

    PubMed

    Fang, Peng; Zeng, Ling-Li; Shen, Hui; Wang, Lubin; Li, Baojuan; Liu, Li; Hu, Dewen

    2012-01-01

    Magnetic resonance imaging studies have reported significant functional and structural differences between depressed patients and controls. Little attention has been given, however, to the abnormalities in anatomical connectivity in depressed patients. In the present study, we aim to investigate the alterations in connectivity of whole-brain anatomical networks in those suffering from major depression by using machine learning approaches. Brain anatomical networks were extracted from diffusion magnetic resonance images obtained from both 22 first-episode, treatment-naive adults with major depressive disorder and 26 matched healthy controls. Using machine learning approaches, we differentiated depressed patients from healthy controls based on their whole-brain anatomical connectivity patterns and identified the most discriminating features that represent between-group differences. Classification results showed that 91.7% (patients=86.4%, controls=96.2%; permutation test, p<0.0001) of subjects were correctly classified via leave-one-out cross-validation. Moreover, the strengths of all the most discriminating connections were increased in depressed patients relative to the controls, and these connections were primarily located within the cortical-limbic network, especially the frontal-limbic network. These results not only provide initial steps toward the development of neurobiological diagnostic markers for major depressive disorder, but also suggest that abnormal cortical-limbic anatomical networks may contribute to the anatomical basis of emotional dysregulation and cognitive impairments associated with this disease. PMID:23049910

  4. Increasing functional connectivity of the anterior cingulate cortex during the course of recovery from Bell's palsy.

    PubMed

    Hu, Sheng; Wu, Yuanyuan; Li, Chuanfu; Park, Kyungmo; Lu, Guangming; Mohamed, Abdalla Z; Wu, Hongli; Xu, Chunsheng; Zhang, Wei; Wang, Linying; Yang, Jun; Qiu, Bensheng

    2015-01-01

    Bell's palsy (BP), a unilateral and idiopathic palsy of the facial nerve, is a common disorder generally followed by a good natural recovery. The aim of this study was to investigate the relationship between the functional connectivity of the anterior cingulate cortex (ACC) and the recovery process of BP. Thirty-seven healthy volunteers and 67 patients were studied by functional MRI (fMRI). The seed regions of bilateral ACC were first extracted from the task-state fMRI data of healthy participants performing the task of mouth opening and closing. The connectivity of bilateral ACC was calculated from resting-state fMRI data of patients in whom only resting-state fMRI data were collected. The correlation between the strength of ACC's connectivity with the duration (time course of disease) was computed by analysis of covariance. It was found that the functional connectivity of the ACC ipsilateral to the lesioned side was enforced as the duration increased. The enforced brain areas included the sensorimotor areas and the ACC contralateral to the palsy. It was suggested that enforced functional connectivity of ACC might be related to cortical reorganization, which is important in the process of BP recovery. PMID:25426823

  5. 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. PMID:27114461

  6. Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution.

    PubMed

    Tagliazucchi, Enzo; Roseman, Leor; Kaelen, Mendel; Orban, Csaba; Muthukumaraswamy, Suresh D; Murphy, Kevin; Laufs, Helmut; Leech, Robert; McGonigle, John; Crossley, Nicolas; Bullmore, Edward; Williams, Tim; Bolstridge, Mark; Feilding, Amanda; Nutt, David J; Carhart-Harris, Robin

    2016-04-25

    Lysergic acid diethylamide (LSD) is a non-selective serotonin-receptor agonist that was first synthesized in 1938 and identified as (potently) psychoactive in 1943. Psychedelics have been used by indigenous cultures for millennia [1]; however, because of LSD's unique potency and the timing of its discovery (coinciding with a period of major discovery in psychopharmacology), it is generally regarded as the quintessential contemporary psychedelic [2]. LSD has profound modulatory effects on consciousness and was used extensively in psychological research and psychiatric practice in the 1950s and 1960s [3]. In spite of this, however, there have been no modern human imaging studies of its acute effects on the brain. Here we studied the effects of LSD on intrinsic functional connectivity within the human brain using fMRI. High-level association cortices (partially overlapping with the default-mode, salience, and frontoparietal attention networks) and the thalamus showed increased global connectivity under the drug. The cortical areas showing increased global connectivity overlapped significantly with a map of serotonin 2A (5-HT2A) receptor densities (the key site of action of psychedelic drugs [4]). LSD also increased global integration by inflating the level of communication between normally distinct brain networks. The increase in global connectivity observed under LSD correlated with subjective reports of "ego dissolution." The present results provide the first evidence that LSD selectively expands global connectivity in the brain, compromising the brain's modular and "rich-club" organization and, simultaneously, the perceptual boundaries between the self and the environment. PMID:27085214

  7. Microdissection specimens of connective, chondrous, or Bone Tissue of human osteosarcomas and chondrosarcomas transplanted to athymic nude mice.

    PubMed

    Nilsson, O S; Lindholm, T S; Nilsonne, U

    1982-01-01

    Five osteosarcomas and two chondrosarcomas were microdissected to separate tumor compartments of calcified, chondrous, and connective tissue. The compartments were lyophilized separately and transplanted subcutaneously or intramuscularly into nude mice for three, four, and five weeks, respectively. In three of the osteosarcomas and in one of the chrondrosarcomas, calcified tissue induced ectopic bone formation by the host, while cartilaginous tissue induced ectopic bone formation in one of the osteosarcomas and in one of the chondrosarcomas. The tumor-derived connective tissue did not induce osteogenic response in the host tissue. Thus, the ability to develop an osteoinductive response and to produce bone morphogenetic protein seems to be restricted to the population of cells that eventually will, or have, differentiated into bone or cartilage.

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

    PubMed

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

    2014-09-01

    The authors report a rare case of a female patient with mixed connective tissue disease (MCTD) with coexisting antiphospholipid syndrome (APS). Five years after the diagnosis of MCTD high concentrations of anticardiolipin (anti-CL) and anti-β2-glycoprotein (anti-β2GPI) autoantibodies were present in the patient's serum without thrombotic events. Epstein-Barr virus (EBV) reactivation provoked APS, with the clinical manifestations of livedo reticularis, digital gangrene and leg ulcers. Skin biopsy from the necrotic area showed multiple fibrin microthrombi in the superficial vessels. Corticosteroid pulse therapy, and plasma exchange in combination with synchronized cyclophosphamide was administered, which led to improvement of the digital gangrenes, while no new lesions developed. The number of CD27high plasma cells decreased, and the previous high levels of autoantibodies also normalized in the peripheral blood. In the case of MCTD with coexisting APS combination therapy, including plasmapheresis has beneficial effects.

  9. Treatment of noncarious cervical lesions by a subepithelial connective tissue graft versus a composite resin restoration.

    PubMed

    Leybovich, Martin; Bissada, Nabil F; Teich, Sorin; Demko, Catherine A; Ricchetti, Paul A

    2014-01-01

    This study compared two treatments for mild noncarious cervical lesions (NCCLs): a subepithelial connective tissue graft (CTG) versus a Class V composite resin restoration (CRR). Twenty-six sites with NCCLs were randomly assigned to be treated by CTG or CRR. Periodontal health parameters and dentinal hypersensitivity (DH) were recorded at baseline and 3 months postoperatively. Esthetics was also evaluated at 3 months. Results showed a significant improvement in all periodontal health parameters in the CTG treatment. The CTG treatment attained a mean 82% defect coverage with 75% of sites achieving complete coverage. Patients rated the CTG treatment to be significantly more esthetic (P = .03), while a clinician panel did not see an esthetic difference (P = .86). There was no difference in DH reduction between the two treatments (P = .81). In conclusion, the CTG treatment is superior to the CRR treatment for NCCLs based on periodontal health parameters. From a patient point of view, the CTG is the more esthetic treatment.

  10. Ischemic Colitis Due to a Mesenteric Arteriovenous Malformation in a Patient with a Connective Tissue Disorder

    PubMed Central

    Poullos, Peter D.; Thompson, Atalie C.; Holz, Grant; Edelman, Lauren A.; Jeffrey, R. Brooke

    2014-01-01

    Ischemic colitis is a rare, life-threatening, consequence of mesenteric arteriovenous malformations. Ischemia ensues from a steal phenomenon through shunting, and may be compounded by the resulting portal hypertension. Computed tomographic angiography is the most common first-line test because it is quick, non-invasive, and allows for accurate anatomic characterization. Also, high-resolution three-dimensional images can be created for treatment planning. Magnetic resonance angiography is similarly sensitive for vascular mapping. Conventional angiography remains the gold standard for diagnosis and also allows for therapeutic endovascular embolization. Our patient underwent testing using all three of these modalities. We present the first reported case of this entity in a patient with a vascular connective tissue disorder. PMID:25926912

  11. [THE ROLE OF TRANSFORMING GROWTH FACTOR-B IN IMMUNOPATHOGENESIS OF DISEASES OF CONNECTIVE TISSUE].

    PubMed

    Rudoi, A S; Moskalev, A V; Sboitchakov, V B

    2016-02-01

    The recent studies of molecular physiology of fibrillin and pathophysiology of inherent disorders of structure and function of connective tissue such as dissection and aneurysm of aorta, myxomatously altered cusps and prolapses of mitral valve, syndrome of hyper-mobility of joints, demonstrated that important role in development of these malformations play alterations of transfer of signals by growth factors and matrix cellular interaction. These conditions under manifesting Marfan's syndrome can be a consequence of anomalies of fibrillin-1 which deficiency unbrakes process of activation of transforming growth factor-β (TGFβ). The involvement of TGFβ in pathogenesis of Marfan's syndrome permits consider antagonists of angiotensin-transforming enzymes as potential pharmaceuticals in therapy of this disease. The article presents analysis of publications' data related to this problem.

  12. 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

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

    PubMed

    Leask, Andrew

    2013-08-01

    Tensegrity (tensional integrity) is an emerging concept governing the structure of the body. Integrin-mediated mechanical tension is essential for connective tissue function in vivo. For example, in adult skin fibroblasts, the integrin β1 subunit mediates adhesion to collagen and fibronectin. Moreover, integrin β1, through its abilities to activate latent TGFβ1 and promote collagen production through focal adhesion kinase/rac1/nicotinamide adenine dinucleotide phosphate oxidase (NOX)/reactive oxygen species (ROS), is essential for dermal homeostasis, repair and fibrosis. The integrin β1-interacting protein CCN2, a member of the CCN family of proteins, is induced by TGFβ1; yet, CCN2 is not a simple downstream mediator of TGFβ1, but instead synergistically promote TGFβ1-induced adhesive signaling and fibrosis. Due to its selective ability to sense mechanical forces in the microenvironment, CCN2 may represent an exquisitely precise target for therapeutic intervention. PMID:23729366

  14. Cyclical cell stretching of skin-derived fibroblasts downregulates connective tissue growth factor (CTGF) production.

    PubMed

    Kanazawa, Yuichiro; Nomura, Jun; Yoshimoto, Shinya; Suzuki, Toshikazu; Kita, Kazuko; Suzuki, Nobuo; Ichinose, Masaharu

    2009-01-01

    Delayed healing of skin wounds can be caused by wound instability, whereas appropriate massage or exercise prevents sclerosis and scar contracture. However, the mechanism by which wound healing is related to mechanical stress has not been fully elucidated. The present study aimed to identify whether mechanical stretching of fibroblasts reduces their production of extracellular matrix. We transferred skin fibroblasts into collagen-coated elastic silicone chambers, cultured them on a stretching apparatus, and used RT-PCR to examine the effects of mechanical stretching on the expression levels of 17 genes related to extracellular matrix production and growth factor secretion. We found that connective tissue growth factor (CTGF) was downregulated after 24 hr of cell stretching. Specifically, the CTGF mRNA and protein levels were 50% and 48% of the control levels, respectively. These findings suggest that cyclic stretching of fibroblasts contributes to anti-fibrotic processes by reducing CTGF production.

  15. [THE ROLE OF TRANSFORMING GROWTH FACTOR-B IN IMMUNOPATHOGENESIS OF DISEASES OF CONNECTIVE TISSUE].

    PubMed

    Rudoi, A S; Moskalev, A V; Sboitchakov, V B

    2016-02-01

    The recent studies of molecular physiology of fibrillin and pathophysiology of inherent disorders of structure and function of connective tissue such as dissection and aneurysm of aorta, myxomatously altered cusps and prolapses of mitral valve, syndrome of hyper-mobility of joints, demonstrated that important role in development of these malformations play alterations of transfer of signals by growth factors and matrix cellular interaction. These conditions under manifesting Marfan's syndrome can be a consequence of anomalies of fibrillin-1 which deficiency unbrakes process of activation of transforming growth factor-β (TGFβ). The involvement of TGFβ in pathogenesis of Marfan's syndrome permits consider antagonists of angiotensin-transforming enzymes as potential pharmaceuticals in therapy of this disease. The article presents analysis of publications' data related to this problem. PMID:27455564

  16. Spontaneous Esophageal Perforation in a Patient with Mixed Connective Tissue Disease

    PubMed Central

    Lyman, David

    2011-01-01

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

  17. Treatment of noncarious cervical lesions by a subepithelial connective tissue graft versus a composite resin restoration.

    PubMed

    Leybovich, Martin; Bissada, Nabil F; Teich, Sorin; Demko, Catherine A; Ricchetti, Paul A

    2014-01-01

    This study compared two treatments for mild noncarious cervical lesions (NCCLs): a subepithelial connective tissue graft (CTG) versus a Class V composite resin restoration (CRR). Twenty-six sites with NCCLs were randomly assigned to be treated by CTG or CRR. Periodontal health parameters and dentinal hypersensitivity (DH) were recorded at baseline and 3 months postoperatively. Esthetics was also evaluated at 3 months. Results showed a significant improvement in all periodontal health parameters in the CTG treatment. The CTG treatment attained a mean 82% defect coverage with 75% of sites achieving complete coverage. Patients rated the CTG treatment to be significantly more esthetic (P = .03), while a clinician panel did not see an esthetic difference (P = .86). There was no difference in DH reduction between the two treatments (P = .81). In conclusion, the CTG treatment is superior to the CRR treatment for NCCLs based on periodontal health parameters. From a patient point of view, the CTG is the more esthetic treatment. PMID:25171035

  18. Effect of increase in intraperitoneal pressure on fluid distribution in tissue using finite difference method

    NASA Astrophysics Data System (ADS)

    Putri, Selmi; Arif, Idam; Khotimah, Siti Nurul

    2015-04-01

    In this study, peritoneal dialysis transport system was numerically simulated using finite difference method. The increase in the intraperitoneal pressure due to coughing has a high value outside the working area of the void volume fraction of the hydrostatic pressure θ(P). Therefore to illustrate the effects of the pressure increment, the pressure of working area is chosen between 1 and 3 mmHg. The effects of increased pressure in peritoneal tissue cause more fluid to flow into the blood vessels and lymph. Furthermore, the increased pressure in peritoneal tissue makes the volumetric flux jv and solute flux js across the tissue also increase. The more fluid flow into the blood vessels and lymph causes the fluid to flow into tissue qv and the glucose flow qs to have more negative value and also decreases the glucose concentration CG in the tissue.

  19. [Lower limb varicose veins as a manifestation of undifferentiated connective tissue dysplasia].

    PubMed

    Potapov, M P; Potapov, P P; Staver, E V; Mazepina, L S

    2016-01-01

    Analysed herein are the data of 737 patients (a total of 745 lower limbs) suffering from lower-limb varicose veins (LLVV) and subjected to treatment at the Surgical Department consisting of crossectomy, truncal and tributary phlebectomy, dissection of perforant veins exclusively in the basin of the great saphenous vein. Relapses during five-year follow up occurred in 13.8% (102/745) of cases. Based on clinical signs and laboratory findings we studied the effect of the factor of undifferentiated connective tissue dysplasia (UDCTD) on the development of lower-limb varicosity. We carried out comparative analysis in the groups with relapsing LLVV (n=43), without relapses (n=39) and control group comprising volunteers not suffering from LLVV (n=37). The median of blood serum total oxiprolin concentration in LLVV patients both with and without relapses was elevated and amounted to 18.4 (IR 14.9-19.65) and 14.3 (IR 13.1-16.5) versus 8.35 (5.75-9.75) μmol/l, respectively. The mode of the clinical parameter of UDCTD degree in accordance with the rating scale of Smolnova T.Yu. (2003) in the group of patients with LLVV relapses turned out to be higher (Mo=19) than in the group of patients without relapses (Mo=10, p=0.003). The lowest score was in the control group. In patients having immediate relatives with LLVV the level of blood serum total oxiprolin and clinical scores of LLVV turned out to be statistically significantly higher. Hence, based on the obtained during the study clinical and laboratory findings it may be supposed that undifferentiated connective tissue dysplasia plays an important part in the development of both lower limb varicosity and relapses thereof. PMID:27100544

  20. Epithelial-connective tissue cross-talk is essential for regeneration of intestinal epithelium.

    PubMed

    Ishizuya-Oka, Atsuko

    2005-02-01

    Epithelial cells of the gastrointestine undergo a rapid cell-renewal and originate from stem cells throughout the life of the organisms. Previous studies have provided a solid body of evidence to show that the epithelial cell-renewal is under the strict control of cell-cell and cell-extracellular matrix (ECM) interactions between the epithelium and the connective tissue. Especially, the microenvironment around the stem cells called "niche" is thought to play important roles in this control, and its disruption leads to diseases or disorders such as cancer in the human gastrointestine. Although understanding how the niche affects the stem cells is clinically important, its mechanisms still remain mostly unknown at the molecular level, possibly due to difficulties in the identification of the stem cells in the gastrointestine. Recent progress in cell and molecular biology is gradually beginning to shed light on some of the key signaling pathways in the cell-renewal of the intestinal epithelium, such as Wnt/T-cell factor (TCF)/beta-catenin, Notch, Sonic hedgehog (Shh)/bone morphogenetic protein (BMP) signaling pathways, which are also involved in embryonic organogenesis and/or adult carcinogenesis. At present, only fragmentary information is available on their precise functions in the intestine. Nevertheless, there is a growing body of evidence that such signaling pathways have conservative functions in the intestine throughout terrestrial vertebrates, suggesting the usefulness of experimental animals to clarify molecular mechanisms regulating epithelial cell-renewal. In this article, I review some recent findings in this field, with particular focus on our studies using the Xenopus laevis intestine, where the stem cells form the mammalian-type intestinal epithelium under the control of connective tissue during metamorphosis. This Xenopus experimental system will certainly serve as a useful model for the study of the intestinal niche, whose clarification is urgently

  1. [Lower limb varicose veins as a manifestation of undifferentiated connective tissue dysplasia].

    PubMed

    Potapov, M P; Potapov, P P; Staver, E V; Mazepina, L S

    2016-01-01

    Analysed herein are the data of 737 patients (a total of 745 lower limbs) suffering from lower-limb varicose veins (LLVV) and subjected to treatment at the Surgical Department consisting of crossectomy, truncal and tributary phlebectomy, dissection of perforant veins exclusively in the basin of the great saphenous vein. Relapses during five-year follow up occurred in 13.8% (102/745) of cases. Based on clinical signs and laboratory findings we studied the effect of the factor of undifferentiated connective tissue dysplasia (UDCTD) on the development of lower-limb varicosity. We carried out comparative analysis in the groups with relapsing LLVV (n=43), without relapses (n=39) and control group comprising volunteers not suffering from LLVV (n=37). The median of blood serum total oxiprolin concentration in LLVV patients both with and without relapses was elevated and amounted to 18.4 (IR 14.9-19.65) and 14.3 (IR 13.1-16.5) versus 8.35 (5.75-9.75) μmol/l, respectively. The mode of the clinical parameter of UDCTD degree in accordance with the rating scale of Smolnova T.Yu. (2003) in the group of patients with LLVV relapses turned out to be higher (Mo=19) than in the group of patients without relapses (Mo=10, p=0.003). The lowest score was in the control group. In patients having immediate relatives with LLVV the level of blood serum total oxiprolin and clinical scores of LLVV turned out to be statistically significantly higher. Hence, based on the obtained during the study clinical and laboratory findings it may be supposed that undifferentiated connective tissue dysplasia plays an important part in the development of both lower limb varicosity and relapses thereof.

  2. Contribution of Underlying Connective Tissue Cells to Taste Buds in Mouse Tongue and Soft Palate

    PubMed Central

    Mederacke, Ingmar; Komatsu, Yoshihiro; Stice, Steve; Schwabe, Robert F.; Mistretta, Charlotte M.; Mishina, Yuji; Liu, Hong-Xiang

    2016-01-01

    Taste buds, the sensory organs for taste, have been described as arising solely from the surrounding epithelium, which is in distinction from other sensory receptors that are known to originate from neural precursors, i.e., neural ectoderm that includes neural crest (NC). Our previous study suggested a potential contribution of NC derived cells to early immature fungiform taste buds in late embryonic (E18.5) and young postnatal (P1-10) mice. In the present study we demonstrated the contribution of the underlying connective tissue (CT) to mature taste buds in mouse tongue and soft palate. Three independent mouse models were used for fate mapping of NC and NC derived connective tissue cells: (1) P0-Cre/R26-tdTomato (RFP) to label NC, NC derived Schwann cells and derivatives; (2) Dermo1-Cre/RFP to label mesenchymal cells and derivatives; and (3) Vimentin-CreER/mGFP to label Vimentin-expressing CT cells and derivatives upon tamoxifen treatment. Both P0-Cre/RFP and Dermo1-Cre/RFP labeled cells were abundant in mature taste buds in lingual taste papillae and soft palate, but not in the surrounding epithelial cells. Concurrently, labeled cells were extensively distributed in the underlying CT. RFP signals were seen in the majority of taste buds and all three types (I, II, III) of differentiated taste bud cells, with the neuronal-like type III cells labeled at a greater proportion. Further, Vimentin-CreER labeled cells were found in the taste buds of 3-month-old mice whereas Vimentin immunoreactivity was only seen in the CT. Taken together, our data demonstrate a previously unrecognized origin of taste bud cells from the underlying CT, a conceptually new finding in our knowledge of taste bud cell derivation, i.e., from both the surrounding epithelium and the underlying CT that is primarily derived from NC. PMID:26741369

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

    PubMed Central

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

    2011-01-01

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

  4. Connective tissue reflex massage for type 2 diabetic patients with peripheral arterial disease: randomized controlled trial.

    PubMed

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

    2011-01-01

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

  5. CCN1 contributes to skin connective tissue aging by inducing age-associated secretory phenotype in human skin dermal fibroblasts.

    PubMed

    Quan, Taihao; Qin, Zhaoping; Robichaud, Patrick; Voorhees, John J; Fisher, Gary J

    2011-08-01

    Dermal connective tissue collagen is the major structural protein in skin. Fibroblasts within the dermis are largely responsible for collagen production and turnover. We have previously reported that dermal fibroblasts, in aged human skin in vivo, express elevated levels of CCN1, and that CCN1 negatively regulates collagen homeostasis by suppressing collagen synthesis and increasing collagen degradation (Quan et al. Am J Pathol 169:482-90, 2006, J Invest Dermatol 130:1697-706, 2010). In further investigations of CCN1 actions, we find that CCN1 alters collagen homeostasis by promoting expression of specific secreted proteins, which include matrix metalloproteinases and proinflammatory cytokines. We also find that CCN1-induced secretory proteins are elevated in aged human skin in vivo. We propose that CCN1 induces an "Age-Associated Secretory Phenotype", in dermal fibroblasts, which mediates collagen reduction and fragmentation in aged human skin.

  6. Laminar structure of the heart: ventricular myocyte arrangement and connective tissue architecture in the dog.

    PubMed

    LeGrice, I J; Smaill, B H; Chai, L Z; Edgar, S G; Gavin, J B; Hunter, P J

    1995-08-01

    We have studied the three-dimensional arrangement of ventricular muscle cells and the associated extracellular connective tissue matrix in dog hearts. Four hearts were potassium-arrested, excised, and perfusion-fixed at zero transmural pressure. Full-thickness segments were cut from the right and left ventricular walls at a series of precisely located sites. Morphology was visualized macroscopically and with scanning electron microscopy in 1) transmural planes of section and 2) planes tangential to the epicardial surface. The appearance of all specimens was consistent with an ordered laminar arrangement of myocytes with extensive cleavage planes between muscle layers. These planes ran radially from endocardium toward epicardium in transmural section and coincided with the local muscle fiber orientation in tangential section. Stereological techniques were used to quantify aspects of this organization. There was no consistent variation in the cellular organization of muscle layers (48.4 +/- 20.4 microns thick and 4 +/- 2 myocytes across) transmurally or in different ventricular regions (23 sites in 6 segments), but there was significant transmural variation in the coupling between adjacent layers. The number of branches between layers decreased twofold from subepicardium to midwall, whereas the length distribution of perimysial collagen fibers connecting muscle layers was greatest in the midwall. We conclude that ventricular myocardium is not a uniformly branching continuum but a laminar hierarchy in which it is possible to identify three axes of material symmetry at any point.

  7. Immunohistochemical identification of myoepithelial, epithelial, and connective tissue cells in canine mammary tumors.

    PubMed

    Destexhe, E; Lespagnard, L; Degeyter, M; Heymann, R; Coignoul, F

    1993-03-01

    Fifty-eight formalin-fixed paraffin-embedded canine mammary tumors, 19 malignant and 39 benign, were used in this study. Tumors were obtained from dogs submitted for surgical resection of lesions at private veterinary practices in Brussels or from the surgery unit of the Faculty of Veterinary Medicine, University of Liège. Immunohistochemical evaluation was performed, using monoclonal antibodies directed against keratins 8-18 and 19, vimentin, desmin, and alpha-actin and polyclonal antibodies directed against high-molecular-weight keratins and S-100 protein. The main cell types, epithelial, myoepithelial, and connective, were identified, and myoepithelial cells represented the major component of most tumors, both benign and malignant. Myoepithelial cells had five patterns: resting and proliferative suprabasal cells, spindle and star-shaped interstitial cells, and cartilage. Reactivity to keratin 19, vimentin, alpha-actin, and S-100 protein suggested a progressive transformation from resting cells to cartilage. Epithelial cell reactivities were limited to keratins; only keratinized cells were positive for polyclonal keratins. Myofibroblasts were positive for both vimentin and alpha-actin, and connective tissue cells were positive for vimentin. Myoepithelial cells appeared to be the major component of carcinomas, justifying reevaluation and simplification of histomorphologic classifications, with a "pleomorphic carcinoma" group including all carcinomas except squamous, mucinous, and comedo carcinomas. Immunohistochemical evaluation, in addition to routine hematoxylin and eosin histopathologic evaluation is recommended for precise classification of canine mammary tumors. PMID:7682367

  8. Tissue types (image)

    MedlinePlus

    There are 4 basic types of tissue: connective tissue, epithelial tissue, muscle tissue, and nervous tissue. Connective tissue supports other tissues and binds them together (bone, blood, and lymph tissues). Epithelial tissue ...

  9. Tensilin-like stiffening protein from Holothuria leucospilota does not induce the stiffest state of catch connective tissue.

    PubMed

    Tamori, Masaki; Yamada, Akira; Nishida, Naoto; Motobayashi, Yumiko; Oiwa, Kazuhiro; Motokawa, Tatsuo

    2006-05-01

    The dermis of sea cucumbers is a catch connective tissue or mutable connective tissue that exhibits large changes in mechanical properties. A stiffening protein, tensilin, has been isolated from the sea cucumber Cucumaria frondosa. We purified a similar protein, H-tensilin, from Holothuria leucospilota, which belongs to a different family to C. frondosa. H-tensilin appeared as a single band with an apparent molecular mass of 34 kDa on SDS-PAGE. No sugar chain was detected. Tryptic fragments of the protein had homology to known tensilin. H-tensilin aggregated isolated collagen fibrils in vitro in a buffer containing 0.5 mol l(-1) NaCl with or without 10 mmol l(-1) Ca(2+). The activity of H-tensilin was quantitatively studied by dynamic mechanical tests on the isolated dermis. H-tensilin increased stiffness of the dermis in the soft state, induced by Ca(2+)-free artificial seawater, to a level comparable to that of the standard state, which was the state found in the dermis rested in artificial seawater with normal ionic condition. H-tensilin decreased the energy dissipation ratio of the soft dermis to a level comparable to that of the standard state. When H-tensilin was applied on the dermis in the standard state, it did not alter stiffness nor dissipation ratio. The subsequent application of artificial seawater in which the potassium concentration was raised to 100 mmol l(-1) increased stiffness by one order of magnitude. These findings suggest that H-tensilin is involved in the changes from the soft state to the standard state and that some stiffening factors other than tensilin are necessary for the changes from the standard to the stiff state.

  10. Physical activity associated with increased resting-state functional connectivity in multiple sclerosis.

    PubMed

    Prakash, Ruchika Shaurya; Patterson, Beth; Janssen, Alisha; Abduljalil, Amir; Boster, Aaron

    2011-11-01

    Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, resulting in physical, cognitive and affective disturbances, with notable declines in the ability to learn and retain new information. In this study, we examined if higher levels of physical activity in MS individuals were associated with an increased resting-state connectivity of the hippocampus and cortex, resulting in better performance on a task of episodic memory. Forty-five individuals with a clinically definite diagnosis of MS were recruited for the study. Consistent with previous reports, hippocampus was functionally connected to the posteromedial cortex, parahippocampal gyrus, superior frontal gyrus, and the medial frontal cortex. Higher levels of physical activity in MS patients were associated with an increased coherence between the hippocampus and the posteromedial cortex (PMC). The increased connectivity between these two regions, in turn, was predictive of better relational memory, such that MS patients who showed an increased coherence between the left (not right) hippocampus and the PMC also showed better relational memory. Results of the study are interpreted in light of the challenge of disentangling effects of physical activity from effects of disease severity and its neuropathological correlates.

  11. Ovariectomy in mature mice does not increase food intake, but increases adiposity and adipose tissue inflammation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Menopause, characterized by reduced estrogen (E2), is associated with increased adiposity and metabolic pathology. Molecular mechanisms underlying this association between low E2 status and metabolic disease are not fully elucidated. When mice are fed a high fat diet (HFD) to induce obesity and diab...

  12. Arecoline-stimulated connective tissue growth factor production in human buccal mucosal fibroblasts: Modulation by curcumin.

    PubMed

    Deng, Yi-Ting; Chen, Hsin-Ming; Cheng, Shih-Jung; Chiang, Chun-Pin; Kuo, Mark Yen-Ping

    2009-09-01

    Connective tissue growth factor (CTGF) is associated with the onset and progression of fibrosis in many human tissues. Areca nut (AN) chewing is the most important etiological factor in the pathogenesis of oral submucous fibrosis (OSF). We immunohistochemically examined the expression of CTGF protein in 20 cases of OSF and found positive CTGF staining in fibroblasts and endothelial cells in all cases. Western blot analysis showed that arecoline, a main alkaloid found in AN, stimulated CTGF synthesis in a dose- and time-dependent manner in buccal mucosal fibroblasts. Constitutive overexpression of CTGF during AN chewing may enhance the fibrotic activity in OSF and play a role in the pathogenesis of OSF. Pretreatment with NF-kappaB inhibitor Bay 11-7082, JNK inhibitor SP600125, p38 MAPK inhibitor SB203580 and antioxidant N-acetyl-l-cysteine, but not ERK inhibitor PD98059, significantly reduced arecoline-induced CTGF synthesis. Furthermore, curcumin completely inhibited arecoline-induced CTGF synthesis and the inhibition is dose-dependent. These results indicated that arecoline-induced CTGF synthesis was mediated by ROS, NF-kappaB, JNK, P38 MAPK pathways and curcumin could be a useful agent in controlling OSF.

  13. Recombinant Expression, Purification, and Functional Characterisation of Connective Tissue Growth Factor and Nephroblastoma-Overexpressed Protein

    PubMed Central

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

    2010-01-01

    The CCN family of proteins, especially its prominent member, the Connective tissue growth factor (CTGF/CCN2) has been identified as a possible biomarker for the diagnosis of fibrotic diseases. As a downstream mediator of TGF-β1 signalling, it is involved in tissue scarring, stimulates interstitial deposition of extracellular matrix proteins, and promotes proliferation of several cell types. Another member of this family, the Nephroblastoma-Overexpressed protein (NOV/CCN3), has growth-inhibiting properties. First reports further suggest that these two CCN family members act opposite to each other in regulating extracellular matrix protein expression and reciprocally influence their own expression when over-expressed. We have established stable HEK and Flp-In-293 clones as productive sources for recombinant human CCN2/CTGF. In addition, we generated an adenoviral vector for recombinant expression of rat NOV and established protocols to purify large quantities of these CCN proteins. The identity of purified human CCN2/CTGF and rat CCN3/NOV was proven by In-gel digest followed by ESI-TOF/MS mass spectrometry. The biological activity of purified proteins was demonstrated using a Smad3-sensitive reporter gene and BrdU proliferation assay in permanent cell line EA•hy 926 cells. We further demonstrate for the first time that both recombinant CCN proteins are N-glycosylated. PMID:21209863

  14. Connective tissue-bone onlay graft with enamel matrix derivative for treatment of gingival recession: a case report.

    PubMed

    Nozawa, Takeshi; Sugiyama, Takahiko; Satoh, Tohru; Tanaka, Koji; Enomoto, Hiroaki; Ito, Koichi

    2002-12-01

    We describe a case of gingival recession in which root coverage and coronal bone regrowth were achieved after treatment with a connective tissue-bone graft and enamel matrix derivative. The connective tissue-bone graft was harvested from a maxillary edentulous area and then curved to fit the root surfaces of the maxillary left central and lateral incisors. Enamel matrix derivative was applied to the root surfaces, and the connective tissue-bone graft was fixed to the interdental bone by a titanium screw. Six months later, the exposed roots were covered with thick gingiva, and coronal regrowth of thick bone was evident at reentry surgery. This technique is useful for esthetic restoration placement with an intracrevicular margin on teeth with a thin, receding gingiva.

  15. Increased functional connectivity and brain atrophy in elderly with subjective memory complaints.

    PubMed

    Hafkemeijer, Anne; Altmann-Schneider, Irmhild; Oleksik, Anna M; van de Wiel, Lotte; Middelkoop, Huub A M; van Buchem, Mark A; van der Grond, Jeroen; Rombouts, Serge A R B

    2013-01-01

    Subjective memory complaints (SMC) are common among elderly. Although subtle changes in memory functioning can hardly be determined using neuropsychological evaluation, neuroimaging studies indicate regionally smaller brain structures in elderly with SMC. Imaging of resting-state functional connectivity is sensitive to detect changes in neurodegenerative diseases, but is currently underexplored in SMC. Here, we investigate resting-state functional connectivity and brain structure in SMC. We analyzed magnetic resonance imaging data of 25 elderly with SMC and 29 age-matched controls (mean age of 71 years). Voxel-based morphometry and volume measurements of subcortical structures were employed on the structural scans using FSL. The dual regression method was used to analyze voxel-wise functional connectivity in relation to eight well-characterized resting-state networks. Group differences were studied with two-sample t-tests (p<0.05, Family-Wise Error corrected). In addition to gray matter volume reductions (hippocampus, anterior cingulate cortex (ACC), medial prefrontal cortex, cuneus, precuneus, and precentral gyrus), elderly with SMC showed increased functional connectivity in the default mode network (hippocampus, thalamus, posterior cingulate cortex (PCC), cuneus, precuneus, and superior temporal gyrus) and the medial visual network (ACC, PCC, cuneus, and precuneus). This study is the first which demonstrates that, in addition to smaller regional brain volumes, increases in functional connectivity are present in elderly with SMC. This suggests that self-reported SMC is a reflection of objective alterations in brain function. Furthermore, our results indicate that functional imaging, in addition to structural imaging, can be a useful tool to objectively determine a difference in brain integrity in SMC.

  16. Company, country, connections: counterfactual origins increase organizational commitment, patriotism, and social investment.

    PubMed

    Ersner-Hershfield, Hal; Galinsky, Adam D; Kray, Laura J; King, Brayden G

    2010-10-01

    Four studies examined the relationship between counterfactual origins--thoughts about how the beginning of organizations, countries, and social connections might have turned out differently--and increased feelings of commitment to those institutions and connections. Study 1 found that counterfactually reflecting on the origins of one's country increases patriotism. Study 2 extended this finding to organizational commitment and examined the mediating role of poignancy. Study 3 found that counterfactual reflection boosts organizational commitment even beyond the effects of other commitment-enhancing appeals and that perceptions of fate mediate the positive effect of counterfactual origins on commitment. Finally, Study 4 temporally separated the counterfactual manipulation from a behavioral measure of commitment and found that counterfactual reflection predicted whether participants e-mailed social contacts 2 weeks later. The robust relationship between counterfactual origins and commitment was found across a wide range of companies and countries, with undergraduates and M.B.A. students, and for attitudes and behaviors.

  17. Connectivity

    ERIC Educational Resources Information Center

    Grush, Mary, Ed.

    2006-01-01

    Connectivity has dramatically changed the landscape of higher education IT. From "on-demand" services for net-gen students and advanced eLearning systems for faculty, to high-performance computing grid resources for researchers, IT now provides more networked services than ever to connect campus constituents to each other and to the world.…

  18. Prevalence of increases in functional connectivity in visual, somatosensory and language areas in congenital blindness

    PubMed Central

    Heine, Lizette; Bahri, Mohamed A.; Cavaliere, Carlo; Soddu, Andrea; Laureys, Steven; Ptito, Maurice; Kupers, Ron

    2015-01-01

    There is ample evidence that congenitally blind individuals rely more strongly on non-visual information compared to sighted controls when interacting with the outside world. Although brain imaging studies indicate that congenitally blind individuals recruit occipital areas when performing various non-visual and cognitive tasks, it remains unclear through which pathways this is accomplished. To address this question, we compared resting state functional connectivity in a group of congenital blind and matched sighted control subjects. We used a seed-based analysis with a priori specified regions-of-interest (ROIs) within visual, somato-sensory, auditory and language areas. Between-group comparisons revealed increased functional connectivity within both the ventral and the dorsal visual streams in blind participants, whereas connectivity between the two streams was reduced. In addition, our data revealed stronger functional connectivity in blind participants between the visual ROIs and areas implicated in language and tactile (Braille) processing such as the inferior frontal gyrus (Broca's area), thalamus, supramarginal gyrus and cerebellum. The observed group differences underscore the extent of the cross-modal reorganization in the brain and the supra-modal function of the occipital cortex in congenitally blind individuals. PMID:26190978

  19. Prevalence of increases in functional connectivity in visual, somatosensory and language areas in congenital blindness.

    PubMed

    Heine, Lizette; Bahri, Mohamed A; Cavaliere, Carlo; Soddu, Andrea; Laureys, Steven; Ptito, Maurice; Kupers, Ron

    2015-01-01

    There is ample evidence that congenitally blind individuals rely more strongly on non-visual information compared to sighted controls when interacting with the outside world. Although brain imaging studies indicate that congenitally blind individuals recruit occipital areas when performing various non-visual and cognitive tasks, it remains unclear through which pathways this is accomplished. To address this question, we compared resting state functional connectivity in a group of congenital blind and matched sighted control subjects. We used a seed-based analysis with a priori specified regions-of-interest (ROIs) within visual, somato-sensory, auditory and language areas. Between-group comparisons revealed increased functional connectivity within both the ventral and the dorsal visual streams in blind participants, whereas connectivity between the two streams was reduced. In addition, our data revealed stronger functional connectivity in blind participants between the visual ROIs and areas implicated in language and tactile (Braille) processing such as the inferior frontal gyrus (Broca's area), thalamus, supramarginal gyrus and cerebellum. The observed group differences underscore the extent of the cross-modal reorganization in the brain and the supra-modal function of the occipital cortex in congenitally blind individuals. PMID:26190978

  20. Dynamics of connective-tissue localization during chronic Borrelia burgdorferi infection.

    PubMed

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

    2013-08-01

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

  1. Hierarchical mechanics of connective tissues: integrating insights from nano to macroscopic studies.

    PubMed

    Gohl, Kheng Lim; Listrat, Anne; Béchet, Daniel

    2014-10-01

    As the key component of the musculoskeletal system, the extracellular matrix of soft connective tissues such as ligaments and tendons is a biological example of fibre-reinforced composite but with a complex hierarchical architecture. To establish a comprehensive structure-function relationship at the respective levels (i.e., from molecule to tissue) of the hierarchical architecture is challenging and requires a multidisciplinary approach, involving the integration of findings from the fields of molecular biology, biochemistry, structural biology, materials science and biophysics. Accordingly, in recent years, some of these fields, namely structural biology, materials science and biophysics, have made significant progress in the microscale and nanoscale studies of extracellular matrix using new tools, such as microelectromechanical systems, optical tweezers and atomic force microscopy, complemented by new techniques in simultaneous imaging and mechanical testing and computer modelling. The intent of this paper is to review the key findings on the mechanical response of extracellular matrix at the respective levels of the hierarchical architecture. The main focus is on the structure and function--the findings are compared across the different levels to provide insights that support the goal of establishing a comprehensive structure-function relationship of extracellular matrix. For this purpose, the review is divided into two parts. The first part explores the features of key structural units of extracellular matrix, namely tropocollagen molecule (the lowest level), microfibril, collagen fibril, collagen fibre and fascicle. The second part examines the mechanics of the structural units at the respective levels. Finally a framework for extracellular matrix mechanics is proposed to support the goal to establish a comprehensive structure-function relationship. The framework describes the integration of the mechanisms of reinforcement by the structural units at the

  2. Hierarchical mechanics of connective tissues: integrating insights from nano to macroscopic studies.

    PubMed

    Gohl, Kheng Lim; Listrat, Anne; Béchet, Daniel

    2014-10-01

    As the key component of the musculoskeletal system, the extracellular matrix of soft connective tissues such as ligaments and tendons is a biological example of fibre-reinforced composite but with a complex hierarchical architecture. To establish a comprehensive structure-function relationship at the respective levels (i.e., from molecule to tissue) of the hierarchical architecture is challenging and requires a multidisciplinary approach, involving the integration of findings from the fields of molecular biology, biochemistry, structural biology, materials science and biophysics. Accordingly, in recent years, some of these fields, namely structural biology, materials science and biophysics, have made significant progress in the microscale and nanoscale studies of extracellular matrix using new tools, such as microelectromechanical systems, optical tweezers and atomic force microscopy, complemented by new techniques in simultaneous imaging and mechanical testing and computer modelling. The intent of this paper is to review the key findings on the mechanical response of extracellular matrix at the respective levels of the hierarchical architecture. The main focus is on the structure and function--the findings are compared across the different levels to provide insights that support the goal of establishing a comprehensive structure-function relationship of extracellular matrix. For this purpose, the review is divided into two parts. The first part explores the features of key structural units of extracellular matrix, namely tropocollagen molecule (the lowest level), microfibril, collagen fibril, collagen fibre and fascicle. The second part examines the mechanics of the structural units at the respective levels. Finally a framework for extracellular matrix mechanics is proposed to support the goal to establish a comprehensive structure-function relationship. The framework describes the integration of the mechanisms of reinforcement by the structural units at the

  3. Magnetoencephalography Reveals a Widespread Increase in Network Connectivity in Idiopathic/Genetic Generalized Epilepsy.

    PubMed

    Elshahabi, Adham; Klamer, Silke; Sahib, Ashish Kaul; Lerche, Holger; Braun, Christoph; Focke, Niels K

    2015-01-01

    Idiopathic/genetic generalized epilepsy (IGE/GGE) is characterized by seizures, which start and rapidly engage widely distributed networks, and result in symptoms such as absences, generalized myoclonic and primary generalized tonic-clonic seizures. Although routine magnetic resonance imaging is apparently normal, many studies have reported structural alterations in IGE/GGE patients using diffusion tensor imaging and voxel-based morphometry. Changes have also been reported in functional networks during generalized spike wave discharges. However, network function in the resting-state without epileptiforme discharges has been less well studied. We hypothesize that resting-state networks are more representative of the underlying pathophysiology and abnormal network synchrony. We studied functional network connectivity derived from whole-brain magnetoencephalography recordings in thirteen IGE/GGE and nineteen healthy controls. Using graph theoretical network analysis, we found a widespread increase in connectivity in patients compared to controls. These changes were most pronounced in the motor network, the mesio-frontal and temporal cortex. We did not, however, find any significant difference between the normalized clustering coefficients, indicating preserved gross network architecture. Our findings suggest that increased resting state connectivity could be an important factor for seizure spread and/or generation in IGE/GGE, and could serve as a biomarker for the disease.

  4. Magnetoencephalography Reveals a Widespread Increase in Network Connectivity in Idiopathic/Genetic Generalized Epilepsy

    PubMed Central

    Elshahabi, Adham; Klamer, Silke; Sahib, Ashish Kaul; Lerche, Holger; Braun, Christoph; Focke, Niels K.

    2015-01-01

    Idiopathic/genetic generalized epilepsy (IGE/GGE) is characterized by seizures, which start and rapidly engage widely distributed networks, and result in symptoms such as absences, generalized myoclonic and primary generalized tonic-clonic seizures. Although routine magnetic resonance imaging is apparently normal, many studies have reported structural alterations in IGE/GGE patients using diffusion tensor imaging and voxel-based morphometry. Changes have also been reported in functional networks during generalized spike wave discharges. However, network function in the resting-state without epileptiforme discharges has been less well studied. We hypothesize that resting-state networks are more representative of the underlying pathophysiology and abnormal network synchrony. We studied functional network connectivity derived from whole-brain magnetoencephalography recordings in thirteen IGE/GGE and nineteen healthy controls. Using graph theoretical network analysis, we found a widespread increase in connectivity in patients compared to controls. These changes were most pronounced in the motor network, the mesio-frontal and temporal cortex. We did not, however, find any significant difference between the normalized clustering coefficients, indicating preserved gross network architecture. Our findings suggest that increased resting state connectivity could be an important factor for seizure spread and/or generation in IGE/GGE, and could serve as a biomarker for the disease. PMID:26368933

  5. Increased Causal Connectivity Related to Anatomical Alterations as Potential Endophenotypes for Schizophrenia

    PubMed Central

    Guo, Wenbin; Liu, Feng; Xiao, Changqing; Yu, Miaoyu; Zhang, Zhikun; Liu, Jianrong; Zhang, Jian; Zhao, Jingping

    2015-01-01

    Abstract Anatomical and functional abnormalities in the cortico-cerebellar-thalamo-cortical circuit have been observed in schizophrenia patients and their unaffected siblings. However, it remains unclear to the relationship between anatomical and functional abnormalities within this circuit in schizophrenia patients and their unaffected siblings, which may serve as potential endophenotypes for schizophrenia. Anatomical and resting-state functional magnetic resonance imaging data were acquired from 49 first-episode, drug-naive schizophrenia patients, 46 unaffected siblings, and 46 healthy controls. Data were analyzed by using voxel-based morphometry and Granger causality analysis. The patients and the siblings shared anatomical deficits in the left middle temporal gyrus (MTG) and increased left MTG–left angular gyrus (AG) connectivity. Moreover, the left MTG–left AG connectivity negatively correlates to the duration of untreated psychosis in the patients. The findings indicate that anatomical deficits in the left MTG and its increased causal connectivity with the left AG may serve as potential endophenotypes for schizophrenia with clinical implications. PMID:26496253

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

    PubMed

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

    2014-03-19

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

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

    PubMed Central

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

    2010-01-01

    Background: REVEAL (the Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management) is the largest US cohort of patients with pulmonary arterial hypertension (PAH) confirmed by right-sided heart catheterization (RHC), providing a more comprehensive subgroup characterization than previously possible. We used REVEAL to analyze the clinical features of patients with connective tissue disease-associated PAH (CTD-APAH). Methods: All newly and previously diagnosed patients with World Health Organization (WHO) group 1 PAH meeting RHC criteria at 54 US centers were consecutively enrolled. Cross-sectional and 1-year mortality and hospitalization analyses from time of enrollment compared CTD-APAH to idiopathic disease and systemic sclerosis (SSc) to systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), and rheumatoid arthritis (RA). Results: Compared with patients with idiopathic disease (n = 1,251), patients with CTD-APAH (n = 641) had better hemodynamics and favorable right ventricular echocardiographic findings but a higher prevalence of pericardial effusions, lower 6-min walk distance (300.5 ± 118.0 vs 329.4 ± 134.7 m, P = .01), higher B-type natriuretic peptide (BNP) levels (432.8 ± 789.1 vs 245.6 ± 427.2 pg/mL, P < .0001), and lower diffusing capacity of carbon monoxide (Dlco) (44.9% ± 18.0% vs 63.6% ± 22.1% predicted, P < .0001). One-year survival and freedom from hospitalization were lower in the CTD-APAH group (86% vs 93%, P < .0001; 67% vs 73%, P = .03). Compared with patients with SSc-APAH (n = 399), those with other CTDs (SLE, n = 110; MCTD, n = 52; RA, n = 28) had similar hemodynamics; however, patients with SSc-APAH had the highest BNP levels (552.2 ± 977.8 pg/mL), lowest Dlco (41.2% ± 16.3% predicted), and poorest 1-year survival (82% vs 94% in SLE-APAH, 88% in MCTD-APAH, and 96% in RA-APAH). Conclusions: Patients with SSc-APAH demonstrate a unique phenotype with the highest BNP levels, lowest Dlco

  8. 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.

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

    PubMed Central

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

    2013-01-01

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

  10. Oral administration of lithium increases tissue magnesium contents but not plasma magnesium level in rats.

    PubMed

    Kiełczykowska, Małgorzata; Musik, Irena; Hordyjewska, Anna; Boguszewska, Anna; Lewandowska, Anna; Pasternak, Kazimierz

    2007-01-01

    The aim of this work was to determine the influence of different doses of lithium on magnesium concentration in plasma and tissues of rats. For a period of eight weeks rats had been provided with aqueous solutions of Li(2)CO(3) whose concentrations were established as follows: 0.7; 1.4; 2.6; 3.6; 7.1; 10.7 mmol Li(+)/l. Magnesium concentration was determined in plasma and tissue supernatants. Lithium caused no changes in magnesium concentration in plasma, whereas Mg concentration in tissues was found to be enhanced, although the degree of the increment depended on the studied tissue. In the liver, brain and heart muscle, the increase was statistically insignificant vs. control. In the kidney, the higher Li doses were required to result in the significant Mg enhancement, whereas in femoral muscle all the used doses caused well-marked Mg increase vs. control. Positive correlations between average daily Li intake and tissue Mg concentration in the kidney (r = 0.650) and femoral muscle (r = 0.696) were found. In conclusion, the present study indicates that the different Li doses disturbed tissue homeostasis of magnesium. The increase in Mg tissue concentration, observed in groups receiving higher Li doses can influence nervous-muscular excitability.

  11. Exogenous methyl jasmonate treatment increases glucosinolate biosynthesis and quinone reductase activity in kale leaf tissue.

    PubMed

    Ku, Kang-Mo; Jeffery, Elizabeth H; Juvik, John A

    2014-01-01

    Methyl jasmonate (MeJA) spray treatments were applied to the kale varieties 'Dwarf Blue Curled Vates' and 'Red Winter' in replicated field plantings in 2010 and 2011 to investigate alteration of glucosinolate (GS) composition in harvested leaf tissue. Aqueous solutions of 250 µM MeJA were sprayed to saturation on aerial plant tissues four days prior to harvest at commercial maturity. The MeJA treatment significantly increased gluconasturtiin (56%), glucobrassicin (98%), and neoglucobrassicin (150%) concentrations in the apical leaf tissue of these genotypes over two seasons. Induction of quinone reductase (QR) activity, a biomarker for anti-carcinogenesis, was significantly increased by the extracts from the leaf tissue of these two cultivars. Extracts of apical leaf tissues had greater MeJA mediated increases in phenolics, glucosinolate concentrations, GS hydrolysis products, and QR activity than extracts from basal leaf tissue samples. The concentration of the hydrolysis product of glucoraphanin, sulforphane was significantly increased in apical leaf tissue of the cultivar 'Red Winter' in both 2010 and 2011. There was interaction between exogenous MeJA treatment and environmental conditions to induce endogenous JA. Correlation analysis revealed that indole-3-carbanol (I3C) generated from the hydrolysis of glucobrassicin significantly correlated with QR activity (r = 0.800, P<0.001). Concentrations required to double the specific QR activity (CD values) of I3C was calculated at 230 µM, which is considerably weaker at induction than other isothiocyanates like sulforphane. To confirm relationships between GS hydrolysis products and QR activity, a range of concentrations of MeJA sprays were applied to kale leaf tissues of both cultivars in 2011. Correlation analysis of these results indicated that sulforaphane, NI3C, neoascorbigen, I3C, and diindolylmethane were all significantly correlated with QR activity. Thus, increased QR activity may be due to combined

  12. The subepithelial connective tissue pedicle graft combined with the coronally advanced flap for restoring missing papilla: a report of two cases.

    PubMed

    De Castro Pinto, Rodrigo Carlos Nahas; Colombini, Bella Luna; Ishikiriama, Sérgio Kiyoshi; Chambrone, Leandro; Pustiglioni, Francisco Emílio; Romito, Giuseppe Alexandre

    2010-03-01

    This case report describes the clinical application of the coronally advanced flap procedure associated with the subepithelial connective tissue pedicle graft in the reconstruction of interdental papilla. This procedure was used in two distinct situations: to reconstruct missing papilla and cover two Miller Class IV gingival recessions between the maxillary right lateral incisor and canine (case 1) and to improve esthetics and restore missing papilla between the maxillary left central and lateral incisors (case 2). In case 1, there was a clinical attachment level gain, complete root coverage (canine), and an increase in papillary height. Case 2 showed similar improvements for the interdental papilla, ie, significant reduction of the black triangle. Subepithelial connective tissue pedicle graft associated with a coronally advanced flap yielded satisfactory esthetics and may be considered a viable approach for the treatment of missing papilla associated or not with recession-type defects. However, further investigation is required.

  13. 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.

  14. 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.

  15. [Features of fluor intoxication development in patients with nondifferentiated connective tissue dysplasia and physical therapy methods for these patients].

    PubMed

    Tereshina, L G; Budkar', L N; Obukhova, T Iu; Bugaeva, I V; Karpova, E A

    2013-01-01

    The article covers results of studies concerning time of fluorosis development in patients with signs of connective tissue dysplasia syndrome (CTDS). if compared with patients without CTDS, and of studies concerning hyperostosis coefficient in accordance with presence or absence of CTDS. Efficiency of physical therapy and balneotherapy for these patients are also reported by the authors.

  16. [Adaptive increase of serotonergic system activity in tissues of half-migratory and migratory fish at increased water salinity].

    PubMed

    2013-01-01

    The article deals with studies of the serotoninergic system activity in different tissues of half-migratory fish--the Caspian roach (Rutilus rutilus caspicus) and carpbream (Abramis brama orientalis)--and migratory fish--shemaya (Chalcalburnus chalcoides) caught in fresh and brackish waters, as well as in the common carp (Cyprinus carpio L.) tissues under effect of brackish water in model experiments. Using indirect solid-phase ELISA-test, the serotoninergic system activity was evaluated by measuring in the tissues of the studied fish the serotonin-modulated anticonsolidation protein (SMAP) which is in linear relationship with serotonin level. There was found a significant elevation of the SMAP levels in the brain of the Caspian roach, carpbream, shemaya, and the common carp under effect of increased water sainity. The revealed increase of the SMAP content in brains of the Caspian roach, carpbream, shemaya, and the common carp under action of increased water salinity reflects the corresponding elevated activity of the serotoninergic system and indicates involvement of adaptive readjustments in the animals' body. PMID:25509051

  17. [Adaptive increase of serotonergic system activity in tissues of half-migratory and migratory fish at increased water salinity].

    PubMed

    Mustafaev, N J; Mekhtiev, A A

    2013-01-01

    The article deals with studies of the serotoninergic system activity in different tissues of half-migratory fish--the Caspian roach (Rutilus rutilus caspicus) and carpbream (Abramis brama orientalis)--and migratory fish--shemaya (Chalcalburnus chalcoides) caught in fresh and brackish waters, as well as in the common carp (Cyprinus carpio L.) tissues under effect of brackish water in model experiments. Using indirect solid-phase ELISA-test, the serotoninergic system activity was evaluated by measuring in the tissues of the studied fish the serotonin-modulated anticonsolidation protein (SMAP) which is in linear relationship with serotonin level. There was found a significant elevation of the SMAP levels in the brain of the Caspian roach, carpbream, shemaya, and the common carp under effect of increased water sainity. The revealed increase of the SMAP content in brains of the Caspian roach, carpbream, shemaya, and the common carp under action of increased water salinity reflects the corresponding elevated activity of the serotoninergic system and indicates involvement of adaptive readjustments in the animals' body. PMID:25490850

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

    PubMed

    Jiang, Qiujie; Uitto, Jouni

    2012-09-01

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

  19. Transmucosal Implant Placement with Submarginal Connective Tissue Graft in Area of Shallow Buccal Bone Dehiscence: A Three-Year Follow-Up Case Series.

    PubMed

    Stefanini, Martina; Felice, Pietro; Mazzotti, Claudio; Marzadori, Matteo; Gherlone, Enrico F; Zucchelli, Giovanni

    2016-01-01

    The aim of the present case series study was to evaluate the short- and long-term (3 years) soft tissue stability of a surgical technique combining transmucosal implant placement with submarginal connective tissue graft (CTG) in an area of shallow buccal bone dehiscence. A sample of 20 patients were treated by positioning a transmucosal implant in an intercalated edentulous area. A CTG sutured to the inner aspect of the buccal flap was used to cover the shallow buccal bone dehiscence. Clinical evaluations were made at 6 months (T₁) and 1 (T₂) and 3 (T₃) years after the surgery. Statistically significant increases in buccal soft tissue thickness and improvement of vertical soft tissue level were achieved at the T₁, T₂, and T₃ follow-ups. A significant increase in keratinized tissue height was also found at T₃. No significant marginal bone loss was recorded. The submarginal CTG technique was able to provide simultaneous vertical and horizontal soft tissue increases around single implants with shallow buccal bone dehiscence and no buccal mucosal recession or clinical signs of mucositis or peri-implantitis at 1 and 3 years. PMID:27560667

  20. Localized increase of tissue oxygen tension by magnetic targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Liong, Celine; Ortiz, Daniel; Ao-ieong, Eilleen; Navati, Mahantesh S.; Friedman, Joel M.; Cabrales, Pedro

    2014-07-01

    Hypoxia is the major hindrance to successful radiation therapy of tumors. Attempts to increase the oxygen (O2) tension (PO2) of tissue by delivering more O2 have been clinically disappointing, largely due to the way O2 is transported and released by the hemoglobin (Hb) within the red blood cells (RBCs). Systemic manipulation of O2 transport increases vascular resistance due to metabolic autoregulation of blood flow to prevent over oxygenation. This study investigates a new technology to increase O2 delivery to a target tissue by decreasing the Hb-O2 affinity of the blood circulating within the targeted tissue. As the Hb-O2 affinity decreases, the tissue PO2 to satisfy tissue O2 metabolic needs increases without increasing O2 delivery or extraction. Paramagnetic nanoparticles (PMNPs), synthetized using gadolinium oxide, were coated with the cell permeable Hb allosteric effector L35 (3,5-trichlorophenylureido-phenoxy-methylpropionic acid). L35 decreases Hb affinity for O2 and favors the release of O2. The L35-coated PMNPs (L35-PMNPs) were intravenously infused (10 mg kg-1) to hamsters instrumented with the dorsal window chamber model. A magnetic field of 3 mT was applied to localize the effects of the L35-PMNPs to the window chamber. Systemic O2 transport characteristics and microvascular tissue oxygenation were measured after administration of L35-PMNPs with and without magnetic field. The tissue PO2 in untreated control animals was 25.2 mmHg. L35-PMNPs without magnetic field decreased tissue PO2 to 23.4 mmHg, increased blood pressure, and reduced blood flow, largely due to systemic modification of Hb-O2 affinity. L35-PMNPs with magnetic field increased tissue PO2 to 27.9 mmHg, without systemic or microhemodynamic changes. These results indicate that localized modification of Hb-O2 affinity can increase PO2 of target tissue without affecting systemic O2 delivery or triggering O2 autoregulation mechanisms. This technology can be used to treat local hypoxia and to

  1. Connective tissue growth factor as a novel therapeutic target in high grade serous ovarian cancer

    PubMed Central

    Moran-Jones, Kim; Gloss, Brian S.; Murali, Rajmohan; Chang, David K.; Colvin, Emily K.; Jones, Marc D.; Yuen, Samuel; Howell, Viive M.; Brown, Laura M.; Wong, Carol W.; Spong, Suzanne M.; Scarlett, Christopher J.; Hacker, Neville F.; Ghosh, Sue; Mok, Samuel C.; Birrer, Michael J.; Samimi, Goli

    2015-01-01

    Ovarian cancer is the most common cause of death among women with gynecologic cancer. We examined molecular profiles of fibroblasts from normal ovary and high-grade serous ovarian tumors to identify novel therapeutic targets involved in tumor progression. We identified 2,300 genes that are significantly differentially expressed in tumor-associated fibroblasts. Fibroblast expression of one of these genes, connective tissue growth factor (CTGF), was confirmed by immunohistochemistry. CTGF protein expression in ovarian tumor fibroblasts significantly correlated with gene expression levels. CTGF is a secreted component of the tumor microenvironment and is being pursued as a therapeutic target in pancreatic cancer. We examined its effect in in vitro and ex vivo ovarian cancer models, and examined associations between CTGF expression and clinico-pathologic characteristics in patients. CTGF promotes migration and peritoneal adhesion of ovarian cancer cells. These effects are abrogated by FG-3019, a human monoclonal antibody against CTGF, currently under clinical investigation as a therapeutic agent. Immunohistochemical analyses of high-grade serous ovarian tumors reveal that the highest level of tumor stromal CTGF expression was correlated with the poorest prognosis. Our findings identify CTGF as a promoter of peritoneal adhesion, likely to mediate metastasis, and a potential therapeutic target in high-grade serous ovarian cancer. These results warrant further studies into the therapeutic efficacy of FG-3019 in high-grade serous ovarian cancer. PMID:26575166

  2. Connective tissue growth factor as a novel therapeutic target in high grade serous ovarian cancer.

    PubMed

    Moran-Jones, Kim; Gloss, Brian S; Murali, Rajmohan; Chang, David K; Colvin, Emily K; Jones, Marc D; Yuen, Samuel; Howell, Viive M; Brown, Laura M; Wong, Carol W; Spong, Suzanne M; Scarlett, Christopher J; Hacker, Neville F; Ghosh, Sue; Mok, Samuel C; Birrer, Michael J; Samimi, Goli

    2015-12-29

    Ovarian cancer is the most common cause of death among women with gynecologic cancer. We examined molecular profiles of fibroblasts from normal ovary and high-grade serous ovarian tumors to identify novel therapeutic targets involved in tumor progression. We identified 2,300 genes that are significantly differentially expressed in tumor-associated fibroblasts. Fibroblast expression of one of these genes, connective tissue growth factor (CTGF), was confirmed by immunohistochemistry. CTGF protein expression in ovarian tumor fibroblasts significantly correlated with gene expression levels. CTGF is a secreted component of the tumor microenvironment and is being pursued as a therapeutic target in pancreatic cancer. We examined its effect in in vitro and ex vivo ovarian cancer models, and examined associations between CTGF expression and clinico-pathologic characteristics in patients. CTGF promotes migration and peritoneal adhesion of ovarian cancer cells. These effects are abrogated by FG-3019, a human monoclonal antibody against CTGF, currently under clinical investigation as a therapeutic agent. Immunohistochemical analyses of high-grade serous ovarian tumors reveal that the highest level of tumor stromal CTGF expression was correlated with the poorest prognosis. Our findings identify CTGF as a promoter of peritoneal adhesion, likely to mediate metastasis, and a potential therapeutic target in high-grade serous ovarian cancer. These results warrant further studies into the therapeutic efficacy of FG-3019 in high-grade serous ovarian cancer.

  3. Relationships between physical and structural properties of intramuscular connective tissue and toughness of raw pork.

    PubMed

    Nishimura, Takanori; Fang, Suhong; Wakamatsu, Jun-ichi; Takahashi, Koui

    2009-02-01

    We studied the relationships between the shear-force value and physical and structural properties of the intramuscular connective tissue (IMCT) in six classes of porcine skeletal muscle to elucidate the contribution of IMCT to toughness of raw pork. The shear-force value of raw pork correlated significantly with that of the IMCT model prepared from each class of skeletal muscle (P < 0.05). The correlation suggested that the variable toughness of pork was caused by the mechanical strength of the endomysium and perimysium. The thickness of the secondary perimysium correlated significantly with the shear-force value of raw pork (P < 0.05) and with that of the IMCT model (P < 0.05). The shear-force value of raw pork correlated significantly with the total amount of collagen (P < 0.05) but not with the heat-solubility of collagen. We concluded therefore that the thickness of the secondary perimysium determines the mechanical strength of IMCT and contributes to toughness in raw pork.

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

    PubMed

    Wells, Athol U; Denton, Christopher P

    2014-12-01

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

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

    PubMed

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

    2014-10-01

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

  6. Lung involvement in connective tissue diseases: a comprehensive review and a focus on rheumatoid arthritis.

    PubMed

    Marigliano, Benedetta; Soriano, Alessandra; Margiotta, Domenico; Vadacca, Marta; Afeltra, Antonella

    2013-09-01

    The lungs are frequently involved in Connective Tissue Diseases (CTDs). Interstitial lung disease (ILD) is one of the most common pleuropulmonary manifestations that affects prognosis significantly. In practice, rheumatologists and other physicians tend to underestimate the impact of CTD-ILDs and diagnose respiratory impairment when it has reached an irreversible fibrotic stage. Early investigation, through clinical evidence, imaging and - in certain cases - lung biopsy, is therefore warranted in order to detect a possible ILD at a reversible initial inflammatory stage. In this review, we focus on lung injury during CTDs, with particular attention to ILDs, and examine their prevalence, clinical manifestations and histological patterns, as well as therapeutic approaches and known complications till date. Although several therapeutic agents have been approved, the best treatment is still not certain and additional trials are required, which demand more knowledge of pulmonary involvement in CTDs. Our central aim is therefore to document the impact that lung damage has on CTDs. We will mainly focus on Rheumatoid Arthritis (RA), which - unlike other rheumatic disorders - resembles Idiopathic Pulmonary Fibrosis (IPF) in numerous aspects.

  7. Invasive pulmonary fungal infections in patients with connective tissue disease: a retrospective study from northern China

    PubMed Central

    Ge, H.F.; Liu, X.Q.; Zhu, Y.Q.; Chen, H.Q.; Chen, G.Z.

    2016-01-01

    Invasive pulmonary fungal infection (IPFI) is a potentially fatal complication in patients with connective tissue disease (CTD). The current study aimed to uncover the clinical characteristics and risk factors of patients with IPFI-CTD. The files of 2186 CTD patients admitted to a single center in northern China between January 2011 and December 2013 were retrospectively reviewed. A total of 47 CTD patients with IPFI were enrolled into this study and assigned to the CTD-IPFI group, while 47 uninfected CTD patients were assigned to the control group. Clinical manifestations were recorded, and risk factors of IPFI were calculated by stepwise logistical regression analysis. Forty-seven (2.15%) CTD patients developed IPFI. Systemic lupus erythematosus patients were responsible for the highest proportion (36.17%) of cases with IPFI. Candida albicans (72.3%) accounted for the most common fungal species. CTD-IPFI patients had significantly elevated white blood cell count, erythrocyte sedimentation rate, C-reactive protein and fasting glucose values compared to controls (P<0.05). Cough, sputum and blood in phlegm were the most common symptoms. Risk factors of IPFI in CTD included maximum prednisone dose ≥30 mg/day within 3 months prior to infection, anti-microbial drug therapy, and interstitial pneumonia. CTD patients who have underlying interstitial pneumonia, prior prednisone or multiple antibiotics, were more likely to develop IPFI. PMID:27683823

  8. An immunological study of glycosaminoglycans in the connective tissue of bovine and cod skeletal muscle.

    PubMed

    Hannesson, Kirsten O; Tingbø, Monica G; Olsen, Ragnar L; Enersen, Grethe; Baevre, Anne Birgit; Ofstad, Ragni

    2007-04-01

    The presence of sulfated glycosaminoglycans (GAGs) was demonstrated in the connective tissue of bovine and cod skeletal muscle by histochemical staining using Alcian blue added MgCl(2) (0.06 M and 0.4 M, respectively). For further identification of the sulfated GAGs, a panel of monoclonal antibodies, 1B5, 2B6, 3B3 and 5D4 was used that recognizes epitopes in chondroitin-0-sulfate (C0S), chondroitin-4-sulfate/dermatan sulfate (C4S/DS), chondroitin-6-sulfate (C6S) and keratan sulfate (KS), respectively. Light microscopy and Western blotting techniques showed that in bovine and cod muscle C0S and C6S were primarily localized pericellularly, whereas cod exhibited a more intermittent staining. C4S was expressed around the separate cells and also in the perimysium and myocommata. In contrast to bovine muscle, which hardly expressed highly sulfated KS, cod exhibited a very strong and consistent staining. Western blotting showed that C0S and C6S were mainly associated with proteoglycans (PGs) of high molecular sizes in both species. Contrary to bovine muscle, C4S in cod was associated with molecules of various sizes. Both cod and bovine muscle contained KSPGs of similar sizes as C4S. KSPGs of different sizes and buoyant densities, sensitive to keratanase I and II were found expressed in cod. PMID:17270478

  9. Development of a novel gene silencer pyrrole-imidazole polyamide targeting human connective tissue growth factor.

    PubMed

    Wan, Jian-Xin; Fukuda, Noboru; Ueno, Takahiro; Watanabe, Takayoshi; Matsuda, Hiroyuki; Saito, Kosuke; Nagase, Hiroki; Matsumoto, Yoshiaki; Matsumoto, Koichi

    2011-01-01

    Pyrrole-imidazole (PI) polyamide can bind to specific sequences in the minor groove of double-helical DNA and inhibit transcription of the genes. We designed and synthesized a PI polyamide to target the human connective tissue growth factor (hCTGF) promoter region adjacent to the Smads binding site. Among coupling activators that yield PI polyamides, 1-[bis(dimethylamino)methylene]-5-chloro-1H-benzotriazolium 3-oxide hexafluorophosphate (HCTU) was most effective in total yields of PI polyamides. A gel shift assay showed that a PI polyamide designed specifically for hCTGF (PI polyamide to hCTGF) bound the appropriate double-stranded oligonucleotide. A fluorescein isothiocyanate (FITC)-conjugated PI polyamide to CTGF permeated cell membranes and accumulated in the nuclei of cultured human mesangial cells (HMCs) and remained there for 48 h. The PI polyamide to hCTGF significantly decreased phorbol 12-myristate acetate (PMA)- or transforming growth factor-β1 (TGF-β1)-stimulated luciferase activity of the hCTGF promoter in cultured HMCs. The PI polyamide to hCTGF significantly decreased PMA- or TGF-β1-stimulated expression of hCTGF mRNA in a dose-dependent manner. The PI polyamide to hCTGF significantly decreased PMA- or TGF-β1-stimulated levels of hCTGF protein in HMCs. These results indicate that the developed synthetic PI polyamide to hCTGF could be a novel gene silencer for fibrotic diseases.

  10. Assessment and management of connective tissue disease-associated interstitial lung disease.

    PubMed

    Fischer, Aryeh; Chartrand, Sandra

    2015-01-01

    The intersection of the connective tissue diseases (CTD) and the interstitial lung diseases (ILD) is complex. Although often considered as a single entity, "CTD-ILD" actually reflects a heterogeneous spectrum of diverse CTDs and a variety of patterns of interstitial pneumonia. The evaluation of patients with CTD that develop ILD, or the assessment for underlying CTD in those presenting with presumed "idiopathic" ILD can be challenging and these evaluations can be optimized by effective multidisciplinary collaboration. When a diagnosis of CTD-ILD is confirmed, careful and thorough assessments to determine extra- versus intra-thoracic disease activity, and degrees of impairment are needed. Pharmacologic intervention with immunosuppression is the mainstay of therapy for all forms of CTD-ILD, but should be reserved only for those that demonstrate clinically significant and/or progressive disease. The management of CTD-ILD is not yet evidence based and there is a desperate need for controlled trials across the spectrum of CTD-ILD. Non-pharmacologic management strategies and addressing comorbidities or aggravating factors should be part of a comprehensive treatment plan for individuals with CTD-ILD.

  11. Clinical features and outcome of acute exacerbation of interstitial pneumonia associated with connective tissue disease.

    PubMed

    Toyoda, Yuko; Hanibuchi, Masaki; Kishi, Jun; Kawano, Hiroshi; Morizumi, Shun; Sato, Seidai; Kondo, Mayo; Takikura, Terumi; Tezuka, Toshifumi; Goto, Hisatsugu; Nishioka, Yasuhiko

    2016-01-01

    Acute exacerbation (AE) of interstitial lung disease is reported to be developed in not only idiopathic pulmonary fibrosis but also connective tissue disease-associated interstitial pneumonia (CTD-IP). As the significance of AE of CTD-IP has not been so widely recognized, its clinical feature is not fully elucidated. In the present study, we investigated the incidence, clinical features and outcome of AE of CTD-IP. We retrospectively reviewed admitted cases in our department with medical record from 2011 to 2015. Among 155 patients with CTD-IP, 10 (6.5%) cases developed AE (6 rheumatoid arthritis, 2 polymyositis/dermatomyositis, 1 systemic lupus erythematosus, 1 Sjögren syndrome), and one died of AE within 30 days. Median survival time after the onset of AE was 169 days in all 10 patients. The treatment with immunosuppressant just before AE onset might improve the prognosis of AE. The median survival time after the onset of AE was significantly longer in patients showing good response to corticosteroid compared with those with poor response to corticosteroid (805 days and 45 days, respectively) (p <0.05), suggesting that there are some cases in CTD-IP, showing the good response to corticosteroid even when AE was complicated. J. Med. Invest. 63: 294-299, August, 2016. PMID:27644575

  12. Increased variability in ApcMin/+ intestinal tissue can be measured with microultrasound

    PubMed Central

    Fatehullah, A.; Sharma, S.; Newton, I. P.; Langlands, A. J.; Lay, H.; Nelson, S. A.; McMahon, R. K.; McIlvenny, N.; Appleton, P. L.; Cochran, S.; Näthke, I. S.

    2016-01-01

    Altered tissue structure is a feature of many disease states and is usually measured by microscopic methods, limiting analysis to small areas. Means to rapidly and quantitatively measure the structure and organisation of large tissue areas would represent a major advance not just for research but also in the clinic. Here, changes in tissue organisation that result from heterozygosity in Apc, a precancerous situation, are comprehensively measured using microultrasound and three-dimensional high-resolution microscopy. Despite its normal appearance in conventionally examined cross-sections, both approaches revealed a significant increase in the variability of tissue organisation in Apc heterozygous tissue. These changes preceded the formation of aberrant crypt foci or adenoma. Measuring these premalignant changes using microultrasound provides a potential means to detect microscopically abnormal regions in large tissue samples, independent of visual examination or biopsies. Not only does this provide a powerful tool for studying tissue structure in experimental settings, the ability to detect and monitor tissue changes by microultrasound could be developed into a powerful adjunct to screening endoscopy in the clinic. PMID:27406832

  13. Increased variability in ApcMin/+ intestinal tissue can be measured with microultrasound

    NASA Astrophysics Data System (ADS)

    Fatehullah, A.; Sharma, S.; Newton, I. P.; Langlands, A. J.; Lay, H.; Nelson, S. A.; McMahon, R. K.; McIlvenny, N.; Appleton, P. L.; Cochran, S.; Näthke, I. S.

    2016-07-01

    Altered tissue structure is a feature of many disease states and is usually measured by microscopic methods, limiting analysis to small areas. Means to rapidly and quantitatively measure the structure and organisation of large tissue areas would represent a major advance not just for research but also in the clinic. Here, changes in tissue organisation that result from heterozygosity in Apc, a precancerous situation, are comprehensively measured using microultrasound and three-dimensional high-resolution microscopy. Despite its normal appearance in conventionally examined cross-sections, both approaches revealed a significant increase in the variability of tissue organisation in Apc heterozygous tissue. These changes preceded the formation of aberrant crypt foci or adenoma. Measuring these premalignant changes using microultrasound provides a potential means to detect microscopically abnormal regions in large tissue samples, independent of visual examination or biopsies. Not only does this provide a powerful tool for studying tissue structure in experimental settings, the ability to detect and monitor tissue changes by microultrasound could be developed into a powerful adjunct to screening endoscopy in the clinic.

  14. Lysophosphatidic acid upregulates connective tissue growth factor expression in osteoblasts through the GPCR/PKC and PKA pathways.

    PubMed

    Yu, Zi-Li; Li, Dian-Qi; Huang, Xiang-Yu; Xing, Xin; Yu, Ru-Qing; Li, Zhi; Li, Zu-Bing

    2016-02-01

    Lysophosphatidic acid (LPA) is an efficient, bioactive phospholipid involved in various biological processes. In this study, LPA-induced connective tissue growth factor (CTGF/CCN2) expression and the underlying mechanisms were investigated using the MC3T3-E1 cell line. The MC3T3-E1 cells were stimulated with an inhibitor of LPA receptors, an activator and inhibitor of protein kinase C (PKC) and protein kinase A (PKA) for indicated periods of time. RT-qPCR and western blot analyses were used to measure the expression levels of CCN2. Immunofluorescence staining was used to observe the translocation of PKC. The mRNA expression level of CCN2 was increased following stimulation of the cells with LPA; LPA transiently induced the mRNA expression of CCN2; maximum expression levels were observed 2 h following stimulation with LPA. This increase was accompanied by CCN2 protein synthesis. LPA receptor1/3 was inhibited by Ki16425, a specific inhibitor of LPA1/3; as a result, the LPA-induced increase in CCN2 expression was abrogated. LPA also induced the membrane translocation of PKC and enhanced PKC activity in the osteoblasts. Pre-treatment of the osteoblasts with staurosporine prevented the increase in CCN2 expression by induced by LPA, and the activation of PKC by phorbol 12-myristate 13-acetate (PMA) enhanced CCN2 expression, indicating that the PKC pathway is involved in the LPA-induced increase in CCN2 expression. The interference of PKA signaling also led to the induction of CCN2 expresion by LPA. These data indicate that LPA increases CCN2 expression through the activation of PKC and PKA. Thus, the regulatory functions of the PKC and PKA pathways are implicated in the LPA-induced increase in CCN2 expression.

  15. Increased Functional Connectivity between Dorsal Posterior Parietal and Ventral Occipitotemporal Cortex during Uncertain Memory Decisions

    PubMed Central

    Hutchinson, J. Benjamin; Uncapher, Melina R.; Wagner, Anthony D.

    2014-01-01

    Retrieval of episodic memories is a multi-component act that relies on numerous operations ranging from processing the retrieval cue, evaluating retrieved information, and selecting the appropriate response given the demands of the task. Motivated by a rich functional neuroimaging literature, recent theorizing about various computations at retrieval has focused on the role of posterior parietal cortex (PPC). In a potentially promising line of research, recent neuroimaging findings suggest that different subregions of dorsal PPC respond distinctly to different aspects of retrieval decisions, suggesting that better understanding of their contributions might shed light on the component processes of retrieval. In an attempt to understand the basic operations performed by dorsal PPC, we used functional MRI and functional connectivity analyses to examine how activation in, and connectivity between, dorsal PPC and ventral temporal regions representing retrieval cues varies as a function of retrieval decision uncertainty. Specifically, participants made a five-point recognition confidence judgment for a series of old and new visually presented words. Consistent with prior studies, memory-related activity patterns dissociated across left dorsal PPC subregions, with activity in the lateral IPS tracking the degree to which participants perceived an item to be old, whereas activity in the SPL increased as a function of decision uncertainty. Importantly, whole-brain functional connectivity analyses further revealed that SPL activity was more strongly correlated with that in the visual word-form area during uncertain relative to certain decisions. These data suggest that the involvement of SPL during episodic retrieval reflects, at least in part, the processing of the retrieval cue, perhaps in service of attempts to increase the mnemonic evidence elicited by the cue. PMID:24825621

  16. [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

  17. Compensation through increased functional connectivity: neural correlates of inhibition in old and young.

    PubMed

    Geerligs, Linda; Saliasi, Emi; Maurits, Natasha M; Lorist, Monicque M

    2012-10-01

    With increasing age, people experience more difficulties with suppressing irrelevant information, which may have a major impact on cognitive functioning. The extent of decline of inhibitory functions with age is highly variable between individuals. In this study, we used ERPs and phase locking analyses to investigate neural correlates of this variability in inhibition between individuals. Older and younger participants performed a selective attention task in which relevant and irrelevant information was presented simultaneously. The participants were split into high and low performers based on their level of inhibition inefficiency, that is, the slowing of RTs induced by information that participants were instructed to ignore. P1 peak amplitudes were larger in low performers than in high performers, indicating that low performers were less able to suppress the processing of irrelevant stimuli. Phase locking analyses were used as a measure of functional connectivity. Efficient inhibition in both age groups was related to the increased functional connectivity in the alpha band between frontal and occipito-parietal ROIs in the prestimulus interval. In addition, increased power in the alpha band in occipito-parietal ROIs was related to better inhibition both before and after stimulus onset. Phase locking in the upper beta band before and during stimulus presentation between frontal and occipito-parietal ROIs was related to a better performance in older participants only, suggesting that this is an active compensation mechanism employed to maintain adequate performance. In addition, increased top-down modulation and increased power in the alpha band appears to be a general mechanism facilitating inhibition in both age groups.

  18. The Role of Tumor Cell-Derived Connective Tissue Growth Factor (CTGF/CCN2) in Pancreatic Tumor Growth

    PubMed Central

    Bennewith, Kevin L.; Huang, Xin; Ham, Christine M.; Graves, Edward E.; Erler, Janine T.; Kambham, Neeraja; Feazell, Jonathan; Yang, George P.; Koong, Albert

    2009-01-01

    Pancreatic cancer is highly aggressive and refractory to existing therapies. Connective tissue growth factor (CTGF/CCN2) is a fibrosis-related gene that is thought to play a role in pancreatic tumor progression. However, CCN2 can be expressed in a variety of cell types, and the contribution of CCN2 derived from either tumor cells or stromal cells as it affects the growth of pancreatic tumors is unknown. Using genetic inhibition of CCN2, we have discovered that CCN2 derived from tumor cells is a critical regulator of pancreatic tumor growth. Pancreatic tumor cells derived from CCN2 shRNA-expressing clones showed dramatically reduced growth in soft agar and when implanted subcutaneously. We also observed a role for CCN2 in the growth of pancreatic tumors implanted orthotopically, with tumor volume measurements obtained by PET imaging. Mechanistically, CCN2 protects cells from hypoxia-mediated apoptosis, providing an in vivo selection for tumor cells that express high levels of CCN2. We found that CCN2 expression and secretion was increased in hypoxic pancreatic tumor cells in vitro, and we observed co-localization of CCN2 and hypoxia in pancreatic tumor xenografts and clinical pancreatic adenocarcinomas. Furthermore, we found increased CCN2 staining in clinical pancreatic tumor tissue relative to stromal cells surrounding the tumor, supporting our assertion that tumor cell-derived CCN2 is important for pancreatic tumor growth. Taken together, these data improve our understanding of the mechanisms responsible for pancreatic tumor growth and progression, and also indicate that CCN2 produced by tumor cells represents a viable therapeutic target for the treatment of pancreatic cancer. PMID:19179545

  19. Clinical evaluation of expanded mesh connective tissue graft in the treatment for multiple adjacent gingival recessions in the esthetic zone

    PubMed Central

    Shanmugam, M.; Shivakumar, B.; Meenapriya, B.; Anitha, V.; Ashwath, B.

    2015-01-01

    Background: Multiple approaches have been used to replace lost, damaged or diseased gingival tissues. The connective tissue graft (CTG) procedure is the golden standard method for root coverage. Although multiple sites often need grafting, the palatal mucosa supplies only a limited area of grafting material. To overcome this limitation, expanded mesh graft provides a method whereby a graft can be stretched to cover a large area. The aim of this study was to evaluate the effectiveness and the predictability of expanded mesh CTG (e-MCTG) in the treatment of adjacent multiple gingival recessions. Materials and Methods: Sixteen patients aged 20–50 years contributed to 55 sites, each site falling into at least three adjacent Miller's Class 1 or Class 2 gingival recession. The CTG obtained from the palatal mucosa was expanded to cover the recipient bed, which was 1.5 times larger than the graft. Clinical measurements were recorded at baseline and 3 months, 12 months postoperatively. Results: A mean coverage of 1.96 mm ± 0.66 mm and 2.22 mm ± 0.68 mm was obtained at the end of 3rd and 12th month, respectively. Twelve months after surgery a statistically significant increase in CAL (2.2 mm ± 0.68 mm, P < 0.001) and increasing WKT (1.75 ± 0.78, P < 0.001) were obtained. In 80% of the treated sites, 100% root coverage was achieved (mean 93.5%). Conclusions: The results of this study demonstrated that multiple adjacent recessions were treated by using e-MCTG technique can be applied and highly predictable root coverage can be achieved. PMID:26321829

  20. Increased functional connectivity between language and visually deprived areas in late and partial blindness.

    PubMed

    Sabbah, Norman; Authié, Colas N; Sanda, Nicolae; Mohand-Saïd, Saddek; Sahel, José-Alain; Safran, Avinoam B; Habas, Christophe; Amedi, Amir

    2016-08-01

    In the congenitally blind, language processing involves visual areas. In the case of normal visual development however, it remains unclear whether later visual loss induces interactions between the language and visual areas. This study compared the resting-state functional connectivity (FC) of retinotopic and language areas in two unique groups of late visually deprived subjects: (1) blind individuals suffering from retinitis pigmentosa (RP), (2) RP subjects without a visual periphery but with preserved central "tunnel vision", both of whom were contrasted with sighted controls. The results showed increased FC between Broca's area and the visually deprived areas in the peripheral V1 for individuals with tunnel vision, and both the peripheral and central V1 for blind individuals. These findings suggest that FC can develop in the adult brain between the visual and language systems in the completely and partially blind. These changes start in the deprived areas and increase in size (involving both foveal and peripheral V1) and strength (from negative to positive FC) as the disease and sensory deprivation progress. These observations support the claim that functional connectivity between remote systems that perform completely different tasks can change in the adult brain in cases of total and even partial visual deprivation. PMID:27143090

  1. Increased functional connectivity between language and visually deprived areas in late and partial blindness.

    PubMed

    Sabbah, Norman; Authié, Colas N; Sanda, Nicolae; Mohand-Saïd, Saddek; Sahel, José-Alain; Safran, Avinoam B; Habas, Christophe; Amedi, Amir

    2016-08-01

    In the congenitally blind, language processing involves visual areas. In the case of normal visual development however, it remains unclear whether later visual loss induces interactions between the language and visual areas. This study compared the resting-state functional connectivity (FC) of retinotopic and language areas in two unique groups of late visually deprived subjects: (1) blind individuals suffering from retinitis pigmentosa (RP), (2) RP subjects without a visual periphery but with preserved central "tunnel vision", both of whom were contrasted with sighted controls. The results showed increased FC between Broca's area and the visually deprived areas in the peripheral V1 for individuals with tunnel vision, and both the peripheral and central V1 for blind individuals. These findings suggest that FC can develop in the adult brain between the visual and language systems in the completely and partially blind. These changes start in the deprived areas and increase in size (involving both foveal and peripheral V1) and strength (from negative to positive FC) as the disease and sensory deprivation progress. These observations support the claim that functional connectivity between remote systems that perform completely different tasks can change in the adult brain in cases of total and even partial visual deprivation.

  2. Elevated Urinary Connective Tissue Growth Factor in Diabetic Nephropathy Is Caused by Local Production and Tubular Dysfunction

    PubMed Central

    Gerritsen, Karin G. F.; Leeuwis, Jan Willem; Koeners, Maarten P.; Bakker, Stephan J. L.; van Oeveren, Willem; Aten, Jan; Tarnow, Lise; Rossing, Peter; Wetzels, Jack F. M.; Joles, Jaap A.; Kok, Robbert Jan; Goldschmeding, Roel; Nguyen, Tri Q.

    2015-01-01

    Connective tissue growth factor (CTGF; CCN2) plays a role in the development of diabetic nephropathy (DN). Urinary CTGF (uCTGF) is elevated in DN patients and has been proposed as a biomarker for disease progression, but it is unknown which pathophysiological factors contribute to elevated uCTGF. We studied renal handling of CTGF by infusion of recombinant CTGF in diabetic mice. In addition, uCTGF was measured in type 1 DN patients and compared with glomerular and tubular dysfunction and damage markers. In diabetic mice, uCTGF was increased and fractional excretion (FE) of recombinant CTGF was substantially elevated indicating reduced tubular reabsorption. FE of recombinant CTGF correlated with excretion of endogenous CTGF. CTGF mRNA was mainly localized in glomeruli and medullary tubules. Comparison of FE of endogenous and recombinant CTGF indicated that 60% of uCTGF had a direct renal source, while 40% originated from plasma CTGF. In DN patients, uCTGF was independently associated with markers of proximal and distal tubular dysfunction and damage. In conclusion, uCTGF in DN is elevated as a result of both increased local production and reduced reabsorption due to tubular dysfunction. We submit that uCTGF is a biomarker reflecting both glomerular and tubulointerstitial hallmarks of diabetic kidney disease. PMID:26171399

  3. Dexamethasone Induces Connective Tissue Growth Factor Expression in Renal Tubular Epithelial Cells in a Mouse Strain-Specific Manner

    PubMed Central

    Okada, Hirokazu; Kikuta, Tomohiro; Inoue, Tsutomu; Kanno, Yoshihiko; Ban, Shinichi; Sugaya, Takeshi; Takigawa, Masaharu; Suzuki, Hiromichi

    2006-01-01

    Connective tissue growth factor (CTGF), a downstream mediator of transforming growth factor-β1, mediates mesangial cell/fibroblast proliferation and extracellular matrix production by renal cells. Here, we show that renal tubular epithelial cells from patients with minimal change nephritic syndrome produced CTGF after glucocorticoid treatment. In addition, the glucocorticoid dexamethasone (DEX) increased CTGF mRNA levels in the kidneys of C57B6 but not SJL mice and produced intermediate CTGF mRNA levels in the kidneys of F1 (C57B6 × SJL) mice, midway between the levels found for parental strains. DEX also increased CTGF mRNA levels in cultured tubular epithelial cells derived from C57B6 (mProx24) but not SJL (MCT) mice via transcriptional up-regulation of CTGF mRNA. Transient transfection experiments using luciferase reporter constructs bearing CTGF promoter fragments revealed that the −897- to −628-bp fragment contained DEX-responsive positive regulatory elements, which were active in mProx24 but not MCT cells. Long-term DEX treatment resulted in fibronectin deposition in the kidneys of C57B6 but not SJL mice, and this effect was inhibited by co-administration of CTGF anti-sense oligodeoxynucleotides. Thus, glucocorticoid-induced renal fibrogenesis seems to be influenced by genetic background, with the critical DEX-responsive elements in the −897- to −628-bp region of the CTGF promoter. PMID:16507889

  4. Factors promoting increased rate of tissue regeneration: the zebrafish fin as a tool for examining tissue engineering design concepts.

    PubMed

    Boominathan, Vijay P; Ferreira, Tracie L

    2012-12-01

    Student interest in topics of tissue engineering is increasing exponentially as the number of universities offering programs in bioengineering are on the rise. Bioengineering encompasses all of the STEM categories: Science, Technology, Engineering, and Math. Inquiry-based learning is one of the most effective techniques for promoting student learning and has been demonstrated to have a high impact on learning outcomes. We have designed program outcomes for our bioengineering program that require tiered activities to develop problem solving skills, peer evaluation techniques, and promote team work. While it is ideal to allow students to ask unique questions and design their own experiments, this can be difficult for instructors to have reagents and supplies available for a variety of activities. Zebrafish can be easily housed, and multiple variables can be tested on a large enough group to provide statistical value, lending them well to inquiry-based learning modules. We have designed a laboratory activity that takes observation of fin regeneration to the next level: analyzing conditions that may impact regeneration. Tissue engineers seek to define the optimum conditions to grow tissue for replacement parts. The field of tissue engineering is likely to benefit from understanding natural mechanisms of regeneration and the factors that influence the rate of regeneration. We have outlined the results of varying temperature on fin regeneration and propose other inquiry modules such as the role of pH in fin regeneration. Furthermore, we have provided useful tools for developing critical thinking and peer review of research ideas, assessment guidelines, and grading rubrics for the activities associated with this exercise. PMID:23244692

  5. Factors promoting increased rate of tissue regeneration: the zebrafish fin as a tool for examining tissue engineering design concepts.

    PubMed

    Boominathan, Vijay P; Ferreira, Tracie L

    2012-12-01

    Student interest in topics of tissue engineering is increasing exponentially as the number of universities offering programs in bioengineering are on the rise. Bioengineering encompasses all of the STEM categories: Science, Technology, Engineering, and Math. Inquiry-based learning is one of the most effective techniques for promoting student learning and has been demonstrated to have a high impact on learning outcomes. We have designed program outcomes for our bioengineering program that require tiered activities to develop problem solving skills, peer evaluation techniques, and promote team work. While it is ideal to allow students to ask unique questions and design their own experiments, this can be difficult for instructors to have reagents and supplies available for a variety of activities. Zebrafish can be easily housed, and multiple variables can be tested on a large enough group to provide statistical value, lending them well to inquiry-based learning modules. We have designed a laboratory activity that takes observation of fin regeneration to the next level: analyzing conditions that may impact regeneration. Tissue engineers seek to define the optimum conditions to grow tissue for replacement parts. The field of tissue engineering is likely to benefit from understanding natural mechanisms of regeneration and the factors that influence the rate of regeneration. We have outlined the results of varying temperature on fin regeneration and propose other inquiry modules such as the role of pH in fin regeneration. Furthermore, we have provided useful tools for developing critical thinking and peer review of research ideas, assessment guidelines, and grading rubrics for the activities associated with this exercise.

  6. Increased regional gray matter atrophy and enhanced functional connectivity in male multiple sclerosis patients.

    PubMed

    Sanchis-Segura, C; Cruz-Gómez, A J; Belenguer, A; Fittipaldi Márquez, M S; Ávila, C; Forn, C

    2016-09-01

    Evidence suggests that sex/gender is an important factor for understanding multiple sclerosis (MS) and that some of its neuropathological consequences might manifest earlier in males. In the present study, we assessed gray matter (GM) volume and functional connectivity (FC) in a sample of female and male MS patients (MSp) and female and male healthy controls (HCs). As compared to female MSp, male MSp showed decreased GM volume in the bilateral frontal areas and increased FC between different brain regions. Because both sets of changes correlated significantly and no differences in cognitive performance were observed, we suggest that the FC increase observed in male MSp acts as a compensatory mechanism for their more extensive GM loss and that it promotes a functional convergence between male- and female-MSp.

  7. Increased regional gray matter atrophy and enhanced functional connectivity in male multiple sclerosis patients.

    PubMed

    Sanchis-Segura, C; Cruz-Gómez, A J; Belenguer, A; Fittipaldi Márquez, M S; Ávila, C; Forn, C

    2016-09-01

    Evidence suggests that sex/gender is an important factor for understanding multiple sclerosis (MS) and that some of its neuropathological consequences might manifest earlier in males. In the present study, we assessed gray matter (GM) volume and functional connectivity (FC) in a sample of female and male MS patients (MSp) and female and male healthy controls (HCs). As compared to female MSp, male MSp showed decreased GM volume in the bilateral frontal areas and increased FC between different brain regions. Because both sets of changes correlated significantly and no differences in cognitive performance were observed, we suggest that the FC increase observed in male MSp acts as a compensatory mechanism for their more extensive GM loss and that it promotes a functional convergence between male- and female-MSp. PMID:27436479

  8. Comparison of different test systems for simultaneous autoantibody detection in connective tissue diseases.

    PubMed

    Eissfeller, Petra; Sticherling, Michael; Scholz, Dietmar; Hennig, Kirsten; Lüttich, Tanja; Motz, Manfred; Kromminga, Arno

    2005-06-01

    The serological diagnosis of connective tissue diseases (CTDs) is based on the analysis of circulating autoantibodies to cytoplasmic and nuclear proteins (extractable nuclear antigens [ENAs]). The determination of autoantibody specificities supports the clinical diagnosis of the type of CTD and also often the prognosis of the disease. The former indirect immunofluorescence (IIF) technique still provides a useful screening method that currently is supplemented by a range of different techniques allowing the exact determination of single autoantibody specificities. These ENA profiling techniques include ELISA, immunoblotting, line-blot assays, and flow cytometric bead-based multiplex assays. The novel line immunoassay (LIA) from Mikrogen has been introduced in a recent study as a suitable technique for the simultaneous detection of autoantibodies in a routine clinical laboratory, providing comparable results as ELISA and ELiA (both from Pharmacia Diagnostics) (see Damoiseaux et al., this volume). In this study, LIAs from three different manufacturers were performed in 30 serum samples from patients with dermatological manifestations and 27 samples from SLE patients with renal involvement. The line assays from Mikrogen (recomLine ANA/ENA), Innogenetics (Inno-Lia ANA Update), and Imtec (ANA-LIA) were compared for antigen composition, handling, and statistical analysis including sensitivity and concordance. Autoantibody frequencies detected by the Mikrogen, Innogenetics, and Imtec line assays were 14.0%, 19.3%, and 15.8% for RNP; 14.0%, 22.8%, and 14.0% for Sm; 26.3%, 31.6%, and 40.3% for SSA; 3.5%, 12.3%, and 14.0% for SSB; and 3.5%, 14.0%, and 10.5% for histones. Our studies show that the line assay format is an easy-to-use, sensitive, and specific method for ENA antibody detection in human sera.

  9. [The clinical immunology laboratory in diagnosis and monitoring of systemic lupus erythematosus and connective tissue diseases].

    PubMed

    Sinico, R A; Radice, A

    2005-01-01

    The laboratory and particularly clinical immunology laboratories have an essential role in diagnosing and monitoring systemic lupus erythematosus (SLE), as well as other connective tissue diseases. The role of the clinical immunology laboratory in these diseases is to confirm or exclude diagnosis, to monitor disease activity, and to identify subgroup of patients. To obtain the best results in terms of diagnostic performance and clinical usefulness, the following recommendations should be fulfilled: anti-nuclear antibodies (ANA) determination by indirect immunofluorescence on Hep-2 cells is an effective screening assay in patients with clinical features of SLE. A negative ANA test makes the diagnosis of SLE unlikely. Anti-dsDNA antibodies are highly specific for SLE and are associated with renal involvement. The method of choice for anti-dsDNA is the Farr assay; however, the necessity of using radioactive materials reduces its applicability. As an alternative, immunofluorescence on Crithidia Luciliae can be used in the diagnostic phase due to its high specificity. The detection of antibodies to extractable nuclear antigens (ENA) and to phospholipids (lupus anticoagulant and anti-cardiolipin antibodies) is useful in identifying subgroups of patients at risk for some clinical manifestations. Anti-dsDNA measurement with a quantitative assay (the Farr assay or ELISA) is currently the best method to monitor disease activity along with complement levels. New assays (anti-C1q and anti-nucleosome antibodies) have been recently proposed for the diagnosis (anti-nucleosome) and monitoring of SLE patients (anti-C1q and anti-nucleosome antibodies), with promising results.

  10. Connective tissue growth factor is secreted through the Golgi and is degraded in the endosome.

    PubMed

    Chen, Y; Segarini, P; Raoufi, F; Bradham, D; Leask, A

    2001-11-15

    Connective tissue growth factor (CTGF) is a cysteine-rich heparin-binding polypeptide that promotes proliferation, collagen synthesis, and chemotaxis in mesanchymal cells. When coinjected subcutaneously with transforming growth factor beta (TGFbeta), CTGF promotes sustained fibrosis in rats. However, little is known about the cell biology and structure/functional relationship of CTGF. In particular, no detailed characterization of the subcellular localization of CTGF has occurred, nor have sequences been identified within this protein required for this localization. In this report, using immunofluorescence and Western blot analysis, we show that CTGF is localized to the Golgi apparatus both in dermal fibroblasts and activated hepatic stellate cells. Using these methods, no CTGF was detected in endosomal, plasma membrane, cytosolic or nuclear fractions. Addition of brefeldin A, a drug that disrupts the Golgi, blocks the secretion of CTGF. We further show that the amino-terminal 37 amino acids of CTGF are sufficient to localize a heterologous protein (red fluorescent protein, RFP) to the Golgi. Although within this region of human CTGF is a N-glycosylation site, tunicamycin, which blocks N-linked glycosylation, has no significant effect on CTGF secretion. Surprisingly, mutation of a single amino acid residue, CYS-34, to alanine prevents localization of a CTGF-RFP fusion protein to the Golgi. These results are the first proof that endogenous CTGF is localized to the Golgi apparatus. Furthermore, using exogenously added (125)I-labeled CTGF, we show that CTGF is internalized and rapidly degraded in the endosome. That is, CTGF is quantitatively secreted through the golgi and is degraded in the endosome.

  11. Reduced-fat bologna manufactured with poultry skin connective tissue gel.

    PubMed

    Osburn, W N; Mandigo, R W

    1998-10-01

    The objectives of this study were to determine temperature (50, 60, 70, and 80 C) and time (0.5, 1.0, 1.5, and 2.0 h) effects on the water binding ability of chicken skin connective tissue (CCT) and its ability to form model gels; to develop and determine the functionality of added water (AW, 100, 200, and 300%) CCT gels; and to evaluate the attributes of reduced-fat bologna containing 10 to 30% addition of 100 to 300% AW CCT gels. Determination of water binding and holding capacities, and objective textural and color attributes provided data suggesting the practicality of developing and incorporating AW CCT gels as water binders in reduced-fat bologna. Processing qualities, and textural and sensory attributes were analyzed to assess the feasibility of manufacturing a reduced-fat processed poultry product containing a modified poultry by-product. Heating (60 C) CCT for 0.5 h allowed the formation of model CCT gels containing 100 to 300% AW. Added water decreased CCT gel fat, protein, collagen content, and hardness due to a protein (collagen) dilution. Hydration values were sufficient to allow CCT to bind up to 300% AW. Gel fragility and syneresis were observed in higher AW CCT gels due to protein dilution, a result of the high fat content of raw CCT (approximately 40%) and added water. Percentage gel addition and AW decreased (P < 0.05) the hardness of reduced-fat CCT gel bologna. All bologna treatments exhibited acceptable sensory attributes. This study indicated the feasibility of using lower AW CCT gels as texture-modifying agents in reduced-fat comminuted meat products.

  12. Volumetric imaging of oral epithelial neoplasia by MPM-SHGM: epithelial connective tissue interface (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Pal, Rahul; Yang, Jinping; Qiu, Suimin; Resto, Vicente; McCammon, Susan; Vargas, Gracie

    2016-03-01

    The majority of oral cancers are comprised of oral squamous cell carcinoma in which neoplastic epithelial cells invade across the epithelial connective tissue interface (ECTI). Invasion is preceded by a multi-component process including epithelial hyperproliferation, loss of cell polarity, and remodeling of the extracellular matrix. Multiphoton Autofluorescence Microscopy (MPAM) and Second Harmonic Generation Microscopy (SHGM) show promise for revealing indicators of neoplasia. In particular, volumetric imaging by these methods can reveal aspects of the 3D microstructure that are not possible by other methods and which could both further our understanding of neoplastic transformation and be explored for development of diagnostic approaches in this disease having only 55% 5-year survival rate. MPAM-SHG were applied to reveal the 3D structure of the critical ECTI interface that plays an integral part toward invasion. Epithelial dysplasia was induced in an established hamster model. MPAM-SHGM was applied to lesion sites, using 780 nm excitation (450-600nm emission) for autofluroescence of cellular and extracellular components; 840 nm using 420 nm bandpass filter for SHG. The ECTI surface was identified as the interface at which SHG signal began following the epithelium and was modeled as a 3D surface using Matlab. ECTI surface area and cell features at sites of epithelial expansion where ECTI was altered were measured; Imaged sites were biopsied and processed for histology. ROC analysis using ECTI image metrics indicated the ability to delineate normal from neoplasia with high sensitivity and specificity and it is noteworthy that inflammation did not significantly alter diagnostic potential of MPAM-SHGM .

  13. Undiagnosed connective tissue diseases: High prevalence in pulmonary arterial hypertension patients.

    PubMed

    Cavagna, Lorenzo; Codullo, Veronica; Ghio, Stefano; Scirè, Carlo Alberto; Guzzafame, Eleonora; Scelsi, Laura; Rossi, Silvia; Montecucco, Carlomaurizio; Caporali, Roberto

    2016-09-01

    Among different subgroups of pulmonary arterial hypertension (PAH), those associated with connective tissue diseases (CTDs) have distinct hemodynamic and prognostic features; a correct etiologic diagnosis is thus mandatory.To estimate frequency and prognosis of previously undiagnosed CTDs in a suspect idiopathic (i) PAH cohort.Consecutive patients with PAH confirmed by right heart catheterization referred at the Cardiology Division of our Hospital without a previous rheumatological assessment or the occurrence of other conditions explaining PAH were checked for CTD by a clinical, laboratory, and instrumental evaluation. Survival in each group has also been analyzed.In our study 17 of 49 patients were classified as CTD-PAH, corresponding to a prevalence (95% CI) of 34.7% (21.7-49.6%). ANA positivity had 94% (71.3-99.9%) sensitivity and 78.1% (60-90.7%) specificity for a diagnosis of CTD-PAH; Raynaud phenomenon (RP) showed 83.3% (51.6-97.9%) sensitivity and 100% (90.5-100%) specificity for the diagnosis of Systemic Sclerosis (SSc)-PAH. At diagnosis, SSc patients were older and had a lower creatinine clearance compared with iPAH and other CTD-PAH. After a median follow-up of 44 (2-132) months, 18 of 49 (36.7%) patients died: 31.2% in the iPAH group, 20% in the CTD-, and 58.3% in the SSc-PAH group. Mortality was significantly higher in SSc-PAH (HR 3.32, 1.11-9.95, P <0.05) versus iPAH.We show a high prevalence of undiagnosed CTDs in patients with iPAH without a previous rheumatological assessment. All patients with RP were diagnosed with SSc. Our data stress the importance of a rheumatological assessment in PAH, especially because of the unfavorable prognostic impact of an associated SSc. PMID:27684814

  14. Comparative morphological study on the lingual papillae and their connective tissue cores in rabbits.

    PubMed

    Nonaka, Kouji; Zheng, Jin Hua; Kobayashi, Kan

    2008-08-01

    The morphological structure of the lingual papillae and their connective tissue cores (CTC) in a rabbit were studied using LM and SEM and were compared to that of other animal species. Externally, the filiform papillae distributed on the anterior surface of the dorsal tongue were short and conical with a round base and had a flat area on their anterior upper half. The CTC of the conical filiform papillae had a roughly triangular plate-like structure with a round top. Several small round protrusions were found on both inclined planes of the triangle. Spearhead-like filiform papillae were distributed on the anterior edge of the lingual prominence and branched filiform papillae were on the posteriorly wide area of the prominence. These papillae on the prominence had a slightly ramified CTC that differed from that of the CTC of the conical filiform papillae distributed on the anterior tongue. Dome-like fungiform papillae were distributed among the conical filiform papillae of the anterior tongue and had a CTC with a roundish structure that was almost but, not quite spherical in appearance with 1 to 10 small round concave indentations for taste buds on their upper surface. The foliate papillae had approximately 15 parallel ridges separated by grooves. These ridges contained a parallel thin plate-like CTC exhibited after removal of the epithelium. The vallate papilla was comprised of a spherical central papilla and had a circular wall with a flower-like CTC almost resembling a carnation. The stereostructure of the rabbit's filiform CTC are comparatively described as being morphologically in between those of rodents and those of the guinea pig and Japanese serow. Such evolution has probably occurred due to the species unique masticatory and gustatory needs and functions. PMID:18975613

  15. Basement membrane and connective tissue proteins in intestinal mucosa of patients with coeliac disease

    PubMed Central

    Verbeke, S; Gotteland, M; Fernández, M; Bremer, J; Ríos, G; Brunser, O

    2002-01-01

    Aims: Gluten ingestion in coeliac disease is associated with alterations of the intestinal mucosa, especially the expansion of the lamina propria. Antiendomysium and antireticulin antibodies may result from interactions between gliadin and extracellular matrix components. By behaving as autoantigens, connective tissue proteins could initiate mucosal damage. This study evaluates changes in the distribution of laminin, type IV collagen, and fibronectin in the mucosa of patients with coeliac disease in an attempt to explain the alterations of mucosal morphology. Methods: Intestinal biopsies were obtained from patients with coeliac disease on admission and while on a gluten free diet. The distribution of type IV collagen, laminin, fibronectin, and α-smooth muscle actin was evaluated by immunofluorescence and by immunogold labelling and electron microscopy. Results: In patients with coeliac disease, the intensity of type IV collagen, laminin, and fibronectin immunofluorescent staining was decreased and less well defined than in controls, with frequent breaches in the basement membrane; fibronectin staining was weak in the distal third of the elongated crypts and absent under the flat surface. The distribution of smooth muscle fibre in the distal lamina propria of flat mucosae was altered. The distribution of these proteins was normal as assessed by immunoelectron microscopy. Conclusions: The intensity of staining of some components of the basement membrane is decreased in coeliac disease and the distribution of smooth muscle fibres is altered. These changes may result from interactions between gliadin and components of the extracellular matrix and may play a role in the genesis of mucosal lesions and in the damage to the epithelium. PMID:12037027

  16. Myocardial Connective Tissue Growth Factor (CCN2/CTGF) Attenuates Left Ventricular Remodeling after Myocardial Infarction

    PubMed Central

    Gravning, Jørgen; Ørn, Stein; Kaasbøll, Ole Jørgen; Martinov, Vladimir N.; Manhenke, Cord; Dickstein, Kenneth; Edvardsen, Thor; Attramadal, Håvard; Ahmed, Mohammed Shakil

    2012-01-01

    Aims Myocardial CCN2/CTGF is induced in heart failure of various etiologies. However, its role in the pathophysiology of left ventricular (LV) remodeling after myocardial infarction (MI) remains unresolved. The current study explores the role of CTGF in infarct healing and LV remodeling in an animal model and in patients admitted for acute ST-elevation MI. Methods and Results Transgenic mice with cardiac-restricted overexpression of CTGF (Tg-CTGF) and non-transgenic littermate controls (NLC) were subjected to permanent ligation of the left anterior descending coronary artery. Despite similar infarct size (area of infarction relative to area at risk) 24 hours after ligation of the coronary artery in Tg-CTGF and NLC mice, Tg-CTGF mice disclosed smaller area of scar tissue, smaller increase of cardiac hypertrophy, and less LV dilatation and deterioration of LV function 4 weeks after MI. Tg-CTGF mice also revealed substantially reduced mortality after MI. Remote/peri-infarct tissue of Tg-CTGF mice contained reduced numbers of leucocytes, macrophages, and cells undergoing apoptosis as compared with NLC mice. In a cohort of patients with acute ST-elevation MI (n = 42) admitted to hospital for percutaneous coronary intervention (PCI) serum-CTGF levels (s-CTGF) were monitored and related to infarct size and LV function assessed by cardiac MRI. Increase in s-CTGF levels after MI was associated with reduced infarct size and improved LV ejection fraction one year after MI, as well as attenuated levels of CRP and GDF-15. Conclusion Increased myocardial CTGF activities after MI are associated with attenuation of LV remodeling and improved LV function mediated by attenuation of inflammatory responses and inhibition of apoptosis. PMID:23284892

  17. Identification of tissue sites for increased albumin degradation in sarcoma-bearing mice

    SciTech Connect

    Andersson, C.; Iresjoe, B.M.L.; Lundholm, K. )

    1991-02-01

    Plasma albumin concentration declines in both experimental and clinical cancer. Previous investigations have demonstrated that this is partly explained by increased breakdown of albumin. The present study has identified the tissue sites for increased albumin degradation in a nonmetastasizing sarcoma mouse (C57/BL6J) model. Results have been compared to nontumor-bearing animals either freely fed or food restricted (pair-weighed) so that their body composition was similar to tumor-bearing animals. Tumor-bearing mice had increased albumin degradation (0.13 +/- 0.02 mg/hr/g bw) compared to both freely fed (0.09 +/- 0.007) and pair-weighed control animals (0.05 +/- 0.008). Radioactivity from circulating (3H)raffine aldehyde labeled albumin appeared with maximum peak values in lysosomes isolated from both tumor and nontumor tissues at 48 hr following iv injection. The intralysosomal accumulation of radioactivity was two- to threefold higher in tumor tissue compared to liver tissue, although the specific activity of protease(s) for albumin degradation measured in vitro was not higher in tumor tissue (30.4 +/- 3.6 mg/hr/g tissue) compared to normal liver tissue (36.9 +/- 1.7). Accounting for the entire tumor the proteolytic capacity for albumin breakdown was however much larger in the tumor (161.6 +/- 32.6 mg/organ) compared to both normal liver (37.5 +/- 2.3) and tumor-host liver (56.4 +/- 2.8). Pepstatin inhibited 78 +/- 6% of the proteolytic activity in the tumor measured by 125I-labeled undenatured mouse albumin as the substrate. Leupeptin inhibited 49 +/- 6%. There was a significantly decreased breakdown of albumin in both skeletal muscles and the gastrointestinal tract from tumor-bearing animals.

  18. Increase of Microcirculatory Blood Flow Enhances Penetration of Ciprofloxacin into Soft Tissue

    PubMed Central

    Joukhadar, Christian; Dehghanyar, Pejman; Traunmüller, Friederike; Sauermann, Robert; Mayer-Helm, Bernhard; Georgopoulos, Apostolos; Müller, Markus

    2005-01-01

    The present study addressed the effect of microcirculatory blood flow on the ability of ciprofloxacin to penetrate soft tissues. Twelve healthy male volunteers were enrolled in an analyst-blinded, clinical pharmacokinetic study. A single intravenous dose of 200 mg of ciprofloxacin was administered over a period of approximately 20 min. The concentrations of ciprofloxacin were measured in plasma and in the warmed and contralateral nonwarmed lower extremities. The microdialysis technique was used for the assessment of unbound ciprofloxacin concentrations in subcutaneous adipose tissue. Microcirculatory blood flow was measured by use of laser Doppler flowmetry. Warming of the extremity resulted in an increase of microcirculatory blood flow by approximately three- to fourfold compared to that at the baseline (P < 0.05) in subcutaneous adipose tissue. The ratio of the maximum concentration (Cmax) of ciprofloxacin for the warmed thigh to the Cmax for the nonwarmed thigh was 2.10 ± 0.90 (mean ± standard deviation; P < 0.05). A combined in vivo pharmacokinetic (PK)-in vitro pharmacodynamic (PD) simulation based on tissue concentration data indicated that killing of Pseudomonas aeruginosa (ATCC 27853 and two clinical isolates) was more effective by about 2 log10 CFU/ml under the warmed conditions than under the nonwarmed conditions (P < 0.05). The improvement of microcirculatory blood flow due to the warming of the extremity was paralleled by an increased ability of ciprofloxacin to penetrate soft tissue. Subsequent PK-PD simulations based on tissue PK data indicated that this increase in tissue penetration was linked to an improved antimicrobial effect at the target site. PMID:16189092

  19. Increased functional connectivity in the resting-state basal ganglia network after acute heroin substitution

    PubMed Central

    Schmidt, A; Denier, N; Magon, S; Radue, E-W; Huber, C G; Riecher-Rossler, A; Wiesbeck, G A; Lang, U E; Borgwardt, S; Walter, M

    2015-01-01

    Reinforcement signals in the striatum are known to be crucial for mediating the subjective rewarding effects of acute drug intake. It is proposed that these effects may be more involved in early phases of drug addiction, whereas negative reinforcement effects may occur more in later stages of the illness. This study used resting-state functional magnetic resonance imaging to explore whether acute heroin substitution also induced positive reinforcement effects in striatal brain regions of protracted heroin-maintained patients. Using independent component analysis and a dual regression approach, we compared resting-state functional connectivity (rsFC) strengths within the basal ganglia/limbic network across a group of heroin-dependent patients receiving both an acute infusion of heroin and placebo and 20 healthy subjects who received placebo only. Subsequent correlation analyses were performed to test whether the rsFC strength under heroin exposure correlated with the subjective rewarding effect and with plasma concentrations of heroin and its main metabolites morphine. Relative to the placebo treatment in patients, heroin significantly increased rsFC of the left putamen within the basal ganglia/limbic network, the extent of which correlated positively with patients' feelings of rush and with the plasma level of morphine. Furthermore, healthy controls revealed increased rsFC of the posterior cingulate cortex/precuneus in this network relative to the placebo treatment in patients. Our results indicate that acute heroin substitution induces a subjective rewarding effect via increased striatal connectivity in heroin-dependent patients, suggesting that positive reinforcement effects in the striatum still occur after protracted maintenance therapy. PMID:25803496

  20. Increased functional connectivity in the resting-state basal ganglia network after acute heroin substitution.

    PubMed

    Schmidt, A; Denier, N; Magon, S; Radue, E-W; Huber, C G; Riecher-Rossler, A; Wiesbeck, G A; Lang, U E; Borgwardt, S; Walter, M

    2015-03-24

    Reinforcement signals in the striatum are known to be crucial for mediating the subjective rewarding effects of acute drug intake. It is proposed that these effects may be more involved in early phases of drug addiction, whereas negative reinforcement effects may occur more in later stages of the illness. This study used resting-state functional magnetic resonance imaging to explore whether acute heroin substitution also induced positive reinforcement effects in striatal brain regions of protracted heroin-maintained patients. Using independent component analysis and a dual regression approach, we compared resting-state functional connectivity (rsFC) strengths within the basal ganglia/limbic network across a group of heroin-dependent patients receiving both an acute infusion of heroin and placebo and 20 healthy subjects who received placebo only. Subsequent correlation analyses were performed to test whether the rsFC strength under heroin exposure correlated with the subjective rewarding effect and with plasma concentrations of heroin and its main metabolites morphine. Relative to the placebo treatment in patients, heroin significantly increased rsFC of the left putamen within the basal ganglia/limbic network, the extent of which correlated positively with patients' feelings of rush and with the plasma level of morphine. Furthermore, healthy controls revealed increased rsFC of the posterior cingulate cortex/precuneus in this network relative to the placebo treatment in patients. Our results indicate that acute heroin substitution induces a subjective rewarding effect via increased striatal connectivity in heroin-dependent patients, suggesting that positive reinforcement effects in the striatum still occur after protracted maintenance therapy.

  1. Contribution of collagen and elastin fibers to the mechanical behavior of an abdominal connective tissue.

    PubMed

    Levillain, A; Orhant, M; Turquier, F; Hoc, T

    2016-08-01

    The linea alba is a complex structure commonly involved in hernia formation. Knowledge of its mechanical behavior is essential to design suitable meshes and reduce the risk of recurrence. The aim of this study was to investigate the relationships between the mechanical properties of the linea alba and the organization of collagen and elastin fibers. For that purpose, longitudinal and transversal samples were removed from four porcine and three human linea alba, to perform tensile tests under a biphotonic confocal microscope, in each direction. Microscopic observation revealed a tissue composed of two layers, made of transversal collagen fibers in the dorsal side and oblique collagen fibers in the ventral side. This particular architecture led to an anisotropic mechanical behavior, with higher stress in the transversal direction. During loading, oblique fibers of the ventral layer reoriented toward the tensile axis in both directions, while fibers of the dorsal layer remained in the transversal direction. This rotation of oblique fibers progressively increased the stiffness of the tissue and induced a non-linear stress-stretch relation. Elastin fibers formed a layer covering the collagen fibers and followed their movement, suggesting that they ensure their elastic recoil. All of these results demonstrated the strong relationships between the microstructure and the mechanical behavior of the linea alba.

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

    PubMed Central

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

    2013-01-01

    Varying geometry and layout of microposts on a cell culture substrate provides an effective technique for applying mechanical stimuli to living cells. In the current study, the optimal geometry and arrangement of microposts on the polydimethylsiloxane (PDMS) surfaces to enhance cell growth behavior were investigated. Human bone marrow derived connective tissue progenitor cells were cultured on PDMS substrates comprising unpatterned smooth surfaces and cylindrical post microtextures that were 10 µm in diameter, 4 heights (5, 10, 20 and 40 µm) and 3 pitches (10, 20, and 40 µm). With the same 10 µm diameter, post heights ranging from 5 to 40 µm resulted in a more than 535000 fold range of rigidity from 0.011 nNµm−1 (40 µm height) up to 5888 nNµm−1(5 µm height). Even though shorter microposts result in higher effective stiffness, decreasing post heights below the optimal value, 5 µm height micropost in this study decreased cell growth behavior. The maximum number of cells was observed on the post microtextures with 20 µm height and 10 µm inter-space, which exhibited a 675% increase relative to the smooth surfaces. The cells on all heights of post microtextures with 10 µm and 20 µm inter-spaces exhibited highly contoured morphology. Elucidating the cellular response to various external geometry cues enables us to better predict and control cellular behavior. In addition, knowledge of cell response to surface stimuli could lead to the incorporation of specific size post microtextures into surfaces of implants to achieve surface-textured scaffold materials for tissue engineering applications. PMID:23378044

  3. Exogenous Methyl Jasmonate Treatment Increases Glucosinolate Biosynthesis and Quinone Reductase Activity in Kale Leaf Tissue

    PubMed Central

    Ku, Kang-Mo; Jeffery, Elizabeth H.; Juvik, John A.

    2014-01-01

    Methyl jasmonate (MeJA) spray treatments were applied to the kale varieties ‘Dwarf Blue Curled Vates’ and ‘Red Winter’ in replicated field plantings in 2010 and 2011 to investigate alteration of glucosinolate (GS) composition in harvested leaf tissue. Aqueous solutions of 250 µM MeJA were sprayed to saturation on aerial plant tissues four days prior to harvest at commercial maturity. The MeJA treatment significantly increased gluconasturtiin (56%), glucobrassicin (98%), and neoglucobrassicin (150%) concentrations in the apical leaf tissue of these genotypes over two seasons. Induction of quinone reductase (QR) activity, a biomarker for anti-carcinogenesis, was significantly increased by the extracts from the leaf tissue of these two cultivars. Extracts of apical leaf tissues had greater MeJA mediated increases in phenolics, glucosinolate concentrations, GS hydrolysis products, and QR activity than extracts from basal leaf tissue samples. The concentration of the hydrolysis product of glucoraphanin, sulforphane was significantly increased in apical leaf tissue of the cultivar ‘Red Winter’ in both 2010 and 2011. There was interaction between exogenous MeJA treatment and environmental conditions to induce endogenous JA. Correlation analysis revealed that indole-3-carbanol (I3C) generated from the hydrolysis of glucobrassicin significantly correlated with QR activity (r = 0.800, P<0.001). Concentrations required to double the specific QR activity (CD values) of I3C was calculated at 230 µM, which is considerably weaker at induction than other isothiocyanates like sulforphane. To confirm relationships between GS hydrolysis products and QR activity, a range of concentrations of MeJA sprays were applied to kale leaf tissues of both cultivars in 2011. Correlation analysis of these results indicated that sulforaphane, NI3C, neoascorbigen, I3C, and diindolylmethane were all significantly correlated with QR activity. Thus, increased QR activity may be due to

  4. DUOX2 Expression Is Increased in Barrett Esophagus and Cancerous Tissues of Stomach and Colon

    PubMed Central

    Qi, Ran; Zhou, Yunfeng; Li, Xiaozhen; Guo, Hong; Gao, Lei; Wu, Lijuan; Wang, Yufeng; Gao, Qiang

    2016-01-01

    Aim. To detect the expression of dual oxidase (DUOX) 2 in Barrett esophagus, gastric cancer, and colorectal cancer (CRC). Materials and Methods. The endoscopic biopsies were collected from patients with Barrett esophagus, while the curative resection tissues were obtained from patients with gastric cancer, CRC, or hepatic carcinoma. The DUOX2 protein and mRNA levels were detected with immunohistochemistry (IHC) and real-time quantitative PCR (qPCR). The correlation of DUOX2 expression with clinicopathological parameters of tumors was identified. Results. Low levels of DUOX2 mRNA were detected in Barrett esophagus and the adjacent normal tissues, and there was no difference between these two groups. DUOX2 protein was found in Barrett esophagus and undetectable in the normal epithelium. The DUOX2 mRNA and protein levels in the gastric cancer and CRC were increased compared to the adjacent nonmalignant tissues. The elevated DUOX2 in the gastric cancer was significantly associated with smoking history. In CRC tissues, the DUOX2 protein expression level in stages II–IV was significantly higher than that in stage I. In both hepatic carcinoma and the adjacent nonmalignant tissue, the DUOX2 was virtually undetectable. Conclusion. DUOX2 in Barrett esophagus, gastric cancer, and CRC may be involved in the tumorigenesis of these tissues. PMID:26839536

  5. The neuroimmune connection interferes with tissue regeneration and chronic inflammatory disease in the skin.

    PubMed

    Peters, Eva M J; Liezmann, Christiane; Klapp, Burghard F; Kruse, Johannes

    2012-07-01

    Research over the past decades has revealed close interactions between the nervous and immune systems that regulate peripheral inflammation and link psychosocial stress with chronic somatic disease. Besides activation of the sympathetic and the hypothalamus-pituitary-adrenal axis, stress leads to increased neurotrophin and neuropeptide production in organs at the self-environment interface. The scope of this short review is to discuss key functions of these stress mediators in the skin, an exemplary stress-targeted and stress-sensitive organ. We will focus on the skin's response to acute and chronic stress in tissue regeneration and pathogenesis of allergic inflammation, psoriasis, and skin cancer to illustrate the impact of local stress-induced neuroimmune interaction on chronic inflammation. PMID:22823443

  6. The neuroimmune connection interferes with tissue regeneration and chronic inflammatory disease in the skin.

    PubMed

    Peters, Eva M J; Liezmann, Christiane; Klapp, Burghard F; Kruse, Johannes

    2012-07-01

    Research over the past decades has revealed close interactions between the nervous and immune systems that regulate peripheral inflammation and link psychosocial stress with chronic somatic disease. Besides activation of the sympathetic and the hypothalamus-pituitary-adrenal axis, stress leads to increased neurotrophin and neuropeptide production in organs at the self-environment interface. The scope of this short review is to discuss key functions of these stress mediators in the skin, an exemplary stress-targeted and stress-sensitive organ. We will focus on the skin's response to acute and chronic stress in tissue regeneration and pathogenesis of allergic inflammation, psoriasis, and skin cancer to illustrate the impact of local stress-induced neuroimmune interaction on chronic inflammation.

  7. Magnetic stimulation at Neiguan (PC6) acupoint increases connections between cerebral cortex regions

    PubMed Central

    Yu, Hong-li; Xu, Gui-zhi; Guo, Lei; Fu, Ling-di; Yang, Shuo; Shi, Shuo; Lv, Hua

    2016-01-01

    Stimulation at specific acupoints can activate cortical regions in human subjects. Previous studies have mainly focused on a single brain region. However, the brain is a network and many brain regions participate in the same task. The study of a single brain region alone cannot clearly explain any brain-related issues. Therefore, for the present study, magnetic stimulation was used to stimulate the Neiguan (PC6) acupoint, and 32-channel electroencephalography data were recorded before and after stimulation. Brain functional networks were constructed based on electroencephalography data to determine the relationship between magnetic stimulation at the PC6 acupoint and cortical excitability. Results indicated that magnetic stimulation at the PC6 acupoint increased connections between cerebral cortex regions.

  8. Magnetic stimulation at Neiguan (PC6) acupoint increases connections between cerebral cortex regions.

    PubMed

    Yu, Hong-Li; Xu, Gui-Zhi; Guo, Lei; Fu, Ling-di; Yang, Shuo; Shi, Shuo; Lv, Hua

    2016-07-01

    Stimulation at specific acupoints can activate cortical regions in human subjects. Previous studies have mainly focused on a single brain region. However, the brain is a network and many brain regions participate in the same task. The study of a single brain region alone cannot clearly explain any brain-related issues. Therefore, for the present study, magnetic stimulation was used to stimulate the Neiguan (PC6) acupoint, and 32-channel electroencephalography data were recorded before and after stimulation. Brain functional networks were constructed based on electroencephalography data to determine the relationship between magnetic stimulation at the PC6 acupoint and cortical excitability. Results indicated that magnetic stimulation at the PC6 acupoint increased connections between cerebral cortex regions. PMID:27630699

  9. Magnetic stimulation at Neiguan (PC6) acupoint increases connections between cerebral cortex regions

    PubMed Central

    Yu, Hong-li; Xu, Gui-zhi; Guo, Lei; Fu, Ling-di; Yang, Shuo; Shi, Shuo; Lv, Hua

    2016-01-01

    Stimulation at specific acupoints can activate cortical regions in human subjects. Previous studies have mainly focused on a single brain region. However, the brain is a network and many brain regions participate in the same task. The study of a single brain region alone cannot clearly explain any brain-related issues. Therefore, for the present study, magnetic stimulation was used to stimulate the Neiguan (PC6) acupoint, and 32-channel electroencephalography data were recorded before and after stimulation. Brain functional networks were constructed based on electroencephalography data to determine the relationship between magnetic stimulation at the PC6 acupoint and cortical excitability. Results indicated that magnetic stimulation at the PC6 acupoint increased connections between cerebral cortex regions. PMID:27630699

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

    PubMed Central

    Boueiz, Adel; Hassoun, Paul M.

    2014-01-01

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

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

    PubMed

    Lamond, Rebecca; Barnett, Susan C

    2013-11-20

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

  12. The effect of low- and high-velocity tendon excursion on the mechanical properties of human cadaver subsynovial connective tissue.

    PubMed

    Filius, Anika; Thoreson, Andrew R; Yang, Tai-Hua; Vanhees, Matthias; An, Kai-Nan; Zhao, Chunfeng; Amadio, Peter C

    2014-01-01

    Fibrosis of the subsynovial connective tissue (SSCT) in the carpal tunnel is the most common histological finding in carpal tunnel syndrome (CTS). Fibrosis may result from damaged SSCT. Previous studies found that with low-velocity (2 mm/s), tendon excursions can irreversibly damage the SSCT. We investigated the effect of tendon excursion velocity in the generation of SSCT damage. Nine human cadaver wrists were used. Three repeated cycles of ramp-stretch testing were performed simulating 40%, 60%, 90%, and 120% of the middle finger flexor tendon superficialis physiological excursion with an excursion velocity of 60 mm/s. Energy and force were calculated and normalized by values obtained in the first cycle for each excursion level. Data were compared with low-velocity excursion data. For high-velocity excursions, a significant drop in the excursion energy ratio was first observed at an excursion level of 60% physiological excursion (p < 0.024) and that for low-velocity excursions was first observed at 90% physiological excursion (p < 0.038). Furthermore, the energy ratio was lower at 60% for high velocities (p ≤ 0.039). Increasing velocity lowers the SSCT damage threshold. This finding may be relevant for understanding the pathogenesis of SSCT fibrosis, such as that accompanying CTS, and a relationship with occupational factors.

  13. The Clinical Value of Soluble Urokinase Plasminogen Activator Receptor (suPAR) Levels in Autoimmune Connective Tissue Disorders

    PubMed Central

    Toldi, Gergely; Balog, Attila

    2016-01-01

    The assessment of the general inflammatory condition of patients with autoimmune connective tissue disorders (ACTD) is a major challenge. The use of traditional inflammatory markers including CRP-levels and erythrocyte sedimentation rate (ESR) is limited by several preanalytical factors and their low specificities. Soluble urokinase plasminogen activator receptor (suPAR) is one of the novel candidate markers that is increasingly used in immune mediated disorders. In our studies we compared suPAR levels of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and ankylosing spondylitis with those of healthy controls. suPAR provided valuable clinical information on disease activity in RA, SLE and SSc. We identified a subgroup of remitted RA patients, who presented still clinical symptoms of inflammatory activity which correlated to high plasma suPAR (while ESR and CRP were normal). In SLE we established specific suPAR cut-off values that support the discrimination between patients with high and those with moderate SLE activity. In patients with SSc suPAR correlated with objective measures of lung and other complications. In the majority of ACTDs including SLE, SSc or RA, suPAR is seemingly a good biomarker that would provide valuable clinical information. However, before the introduction of this novel parameter in laboratory repertoire important issues should be elucidated. These include the establishment of appropriate and disease specific cutoff values, clarification of interfering preanalytical values and underlying conditions and declaration of age- and gender-specific reference ranges. PMID:27683525

  14. The Clinical Value of Soluble Urokinase Plasminogen Activator Receptor (suPAR) Levels in Autoimmune Connective Tissue Disorders.

    PubMed

    Vasarhelyi, Barna; Toldi, Gergely; Balog, Attila

    2016-04-01

    The assessment of the general inflammatory condition of patients with autoimmune connective tissue disorders (ACTD) is a major challenge. The use of traditional inflammatory markers including CRP-levels and erythrocyte sedimentation rate (ESR) is limited by several preanalytical factors and their low specificities. Soluble urokinase plasminogen activator receptor (suPAR) is one of the novel candidate markers that is increasingly used in immune mediated disorders. In our studies we compared suPAR levels of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and ankylosing spondylitis with those of healthy controls. suPAR provided valuable clinical information on disease activity in RA, SLE and SSc. We identified a subgroup of remitted RA patients, who presented still clinical symptoms of inflammatory activity which correlated to high plasma suPAR (while ESR and CRP were normal). In SLE we established specific suPAR cut-off values that support the discrimination between patients with high and those with moderate SLE activity. In patients with SSc suPAR correlated with objective measures of lung and other complications. In the majority of ACTDs including SLE, SSc or RA, suPAR is seemingly a good biomarker that would provide valuable clinical information. However, before the introduction of this novel parameter in laboratory repertoire important issues should be elucidated. These include the establishment of appropriate and disease specific cutoff values, clarification of interfering preanalytical values and underlying conditions and declaration of age- and gender-specific reference ranges. PMID:27683525

  15. The Prevalence of Atherosclerosis in Those with Inflammatory Connective Tissue Disease by Race, Age, and Traditional Risk Factors

    PubMed Central

    Alenghat, Francis J.

    2016-01-01

    Systemic inflammation promotes cardiovascular disease. Inflammatory connective tissue diseases (CTD) like lupus and rheumatoid arthritis associate with cardiovascular risk, but it is unknown whether particular groups of patients have enhanced propensity for atherosclerotic cardiovascular disease (ASCVD) associated with their CTD. Analysis of aggregate health record data at a large U.S. academic center identified CTD and ASCVD status for 287,467 African American and white adults. ASCVD prevalence in those with CTD was 29.7% for African Americans and 14.7% for white patients with prevalence ratios, compared to those without CTD, of 3.1 and 1.8, respectively. When different types of CTD were analyzed individually (rheumatoid arthritis; lupus; scleroderma; Sjögren Syndrome; dermatomyositis/polymyositis; unspecified/mixed CTD; other inflammatory arthropathy), increased ASCVD rates were found in nearly all subsets, always with higher prevalence ratios in African Americans. The prevalence ratio of ASCVD was particularly high in young African Americans. Furthermore, individuals lacking traditional cardiovascular risk factors had more ASCVD if they had CTD (prevalence ratio 2.9). Multivariate analysis confirmed a positive interaction between CTD and African-American race and a negative interaction between CTD and age. The factors driving the observed disproportionate CTD-associated ASCVD in African Americans, young adults, and those without traditional risk factors warrant further study. PMID:26842423

  16. "Project ACTS": An Intervention to Increase Organ and Tissue Donation Intentions among African Americans

    ERIC Educational Resources Information Center

    Arriola, Kimberly; Robinson, Dana H.; Thompson, Nancy J.; Perryman, Jennie P.

    2010-01-01

    This study sought to evaluate the effectiveness of "Project ACTS: About Choices in Transplantation and Sharing," which was developed to increase readiness for organ and tissue donation among African American adults. Nine churches (N = 425 participants) were randomly assigned to receive donation education materials currently available to consumers…

  17. Inflammation and increased aromatase expression occur in the breast tissue of obese women with breast cancer

    PubMed Central

    Morris, Patrick G.; Hudis, Clifford A.; Giri, Dilip; Morrow, Monica; Falcone, Domenick J.; Zhou, Xi Kathy; Du, Baoheng; Brogi, Edi; Crawford, Carolyn B.; Kopelovich, Levy; Subbaramaiah, Kotha; Dannenberg, Andrew J.

    2011-01-01

    Obesity is a risk factor for the development of hormone receptor-positive breast cancer in postmenopausal women and has been associated with an increased risk of recurrence and reduced survival. In humans, obesity causes subclinical inflammation in visceral and subcutaneous adipose tissue, characterized by necrotic adipocytes surrounded by macrophages forming crown-like structures (CLS). Recently, we found increased numbers of CLS, activation of the NF-κB transcription factor and elevated aromatase levels and activity in the mammary glands of obese mice. These preclinical findings raised the possibility that the obesity→inflammation axis is important for the development and progression of breast cancer. Here, our main objective was to determine if the findings in mouse models of obesity translated to women. Breast tissue was obtained from 30 women who underwent breast surgery. CLS of the breast (CLS-B) were found in nearly 50% (14 of 30) of patient samples. The severity of breast inflammation, defined as the CLS-B index, correlated with both body mass index (P<0.001) and adipocyte size (P=0.01). Increased NF-κB binding activity and elevated aromatase expression and activity were found in the inflamed breast tissue of overweight and obese women. Collectively, our results suggest that the obesity→inflammation→aromatase axis is present in the breast tissue of most overweight and obese women. The presence of CLS-B may be a biomarker of increased breast cancer risk or poor prognosis. PMID:21622727

  18. 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.

  19. Structural changes in connective tissues caused by a moderate laser heating

    SciTech Connect

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

    2002-10-31

    The structural changes in adipose and fibrous tissues caused by 2- and 3-W IR laser irradiation are studied by the methods of IR and Raman spectroscopy and differential scanning calorimetry. It is shown that heating of fibrous tissue samples to 50 {sup 0}C and adipose tissue samples to 75 {sup 0}C by IR laser radiation changes the supramolecular structure of their proteins and triacylglycerides, respectively, without the intramolecular bond breaking. Heating of fibrous tissue to 70 {sup 0}C and adipose tissue to 90 - 110 {sup 0}C leads to a partial reversible denaturation of proteins and to oxidation of fats.

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

    PubMed

    Motokawa, Tatsuo; Fuchigami, Yoshiro

    2015-03-01

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

  1. 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.

  2. Surgical treatment of localized gingival recessions using coronally advanced flaps with or without subepithelial connective tissue graft

    PubMed Central

    Bellver-Fernández, Ricardo; Martínez-Rodriguez, Ana-María; Gioia-Palavecino, Claudio; Caffesse, Raul-Guillermo

    2016-01-01

    Background A coronally advanced flap with subepithelial connective tissue graft is the gold standard surgical treatment of gingival recessions, since it offers a higher probability of achieving complete root coverage compared with other techniques. However, optimum short- and middle-term clinical results have also been obtained with coronally advanced flaps alone. The aim of the present study was to evaluate the results obtained by the surgical treatment of localized gingival recessions using coronally advanced flaps with or without subepithelial connective tissue graft. Material and Methods The reduction of recession height was assessed, together with the gain in gingival attachment apical to the recession, and total reduction of recession, in a comparative study of two techniques. Twenty-two gingival recessions were operated upon: 13 in the control group (coronally advanced flap) and 9 in the test group (coronally advanced flap associated to subepithelial connective tissue graft). Results After 18 months, the mean reduction of recession height was 2.2 ± 0.8 mm in the control group and 2.3 ± 0.7 mm in the test group, with a mean gain in gingival attachment of 1.3 ± 0.9 mm and 2.3 ± 1.3 mm, respectively. In percentage terms, the mean reduction of recession height was 84.6 ± 19.6% in the control group and 81.7 ± 17.8% in the test group, with a mean gain in gingival attachment of 20.5 ± 37.4% and 184.4 ± 135.5%, respectively. Conclusions Significant reduction of gingival recession was achieved with both techniques, though the mean gain in gingival attachment (in mm and as a %) was greater in test group. Key words:Gingival recession, coronally advanced flap, subepthelial connective tissue graft. PMID:26595836

  3. 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.

  4. 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.

  5. Adverse Events in Connective Tissue Disease–Associated Pulmonary Arterial Hypertension

    PubMed Central

    Rhee, Rennie L.; Gabler, Nicole B.; Praestgaard, Amy; Merkel, Peter A.; Kawut, Steven M.

    2016-01-01

    Objective Patients with connective tissue disease (CTD)–associated pulmonary arterial hypertension (PAH) have a poorer prognosis compared to those with idiopathic PAH, but little is known about the differences in treatment-related adverse events (AEs) and serious adverse events (SAEs) between these groups. This study was undertaken to characterize these differences. Methods Individual patient-level data from 10 randomized controlled trials of therapies for PAH were obtained from the US Food and Drug Administration. Patients diagnosed as having either CTD-associated PAH or idiopathic PAH were included. A treatment-by-diagnosis interaction term was used to examine whether the effect of treatment on occurrence of AEs differed between patients with CTD-associated PAH and those with idiopathic PAH. Studies were pooled using fixed-effect models. Results The study sample included 2,370 participants: 716 with CTD-associated PAH and 1,654 with idiopathic PAH. In the active treatment group compared to the placebo group, the risk of AEs was higher among patients with CTD-associated PAH than among those with idiopathic PAH (odds ratio [OR] 1.57, 95% confidence interval [95% CI] 1.00–2.47 versus OR 0.94, 95% CI 0.69–1.26; P for interaction = 0.061), but there was no difference in the risk of SAEs in analyses adjusted for age, race, sex, hemodynamic findings, and laboratory values. Despite the higher occurrence of AEs in patients with CTD-associated PAH assigned to active therapy compared to those receiving placebo, the risk of drug discontinuation due to an AE was similar to that in patients with idiopathic PAH assigned to active therapy (P for interaction = 0.27). Conclusion Patients with CTD-associated PAH experienced more treatment-related AEs compared to those with idiopathic PAH in therapeutic clinical trials. These findings suggest that the overall benefit of advanced therapies for PAH may be attenuated by the greater frequency of AEs. PMID:26016953

  6. Silica-associated connective tissue disease. A study of 24 cases.

    PubMed

    Koeger, A C; Lang, T; Alcaix, D; Milleron, B; Rozenberg, S; Chaibi, P; Arnaud, J; Mayaud, C; Camus, J P; Bourgeois, P

    1995-09-01

    We prospectively studied all patients hospitalized for connective tissue disease (CTD) in our French rheumatology clinic from January 1979 to December 1989. Our aims were 1) to determine if CTDs associated with occupational exposure to silica (Si) are currently observed in a rheumatology clinic, and, if so, 2) to describe the major features of Si-associated CTD, and 3) to specify which individuals are affected by Si-associated CTD. Patients were divided into 2 groups based on their responses to a questionnaire: those who had been exposed to Si, and those who had no occupational exposure to Si. Among the 764 patients with CTD studied, 24 (3%) were patients with Si-associated CTD and 740 (97%) were patients with non-Si-associated CTD. The sex ratio between the 2 groups was significantly different with a high frequency of men and of immigrants in the Si-associated CTD group. Two thirds of the patients exposed to Si were male miners or sandblasters, but the other third had more unusual exposures to Si, which may involve members of all socio-economics sectors and both sexes, such as sculpture or exposure to abrasive powders. Progressive systemic sclerosis (PSS) was significantly more prevalent in the Si-associated CTD group. This group also consisted of patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), dermatomyositis (DM), and other autoimmune diseases. Si-associated CTD was characterized by the frequency of radiologic lung fibrosis, impaired pulmonary function tests, secondary Sjögren syndrome, and antinuclear antibodies. The number of mineral particles and crystalline Si content were raised in all the bronchoalveolar lavage specimens of Si-exposed patients but in none of those of nonexposed patients. In some cases of Si-associated CTD, the disease was reversible after early cessation of Si exposure. Epidemiologic studies are required to confirm our hypothesis that not only PSS and RA but also SLE and DM are associated with occupational

  7. Per2-Mediated Vascular Dysfunction Is Caused by the Upregulation of the Connective Tissue Growth Factor (CTGF)

    PubMed Central

    Jadhav, Vaishnavi; Luo, Qianyi; M. Dominguez, James; Al-Sabah, Jude; Chaqour, Brahim; Grant, Maria B.; Bhatwadekar, Ashay D.

    2016-01-01

    Period 2-mutant mice (Per2m/m), which possess a circadian dysfunction, recapitulate the retinal vascular phenotype similar to diabetic retinopathy (DR). The vascular dysfunction in Per2m/m is associated with an increase in connective tissue growth factor (CTGF/CCN2). At the molecular level, CTGF gene expression is dependent on the canonical Wnt/β-catenin pathway. The nuclear binding of β-catenin to a transcription factor, lymphoid enhancer binding protein (Lef)/ T-cell factor (TCF/LEF), leads to downstream activation of CTGF. For this study, we hypothesized that the silencing of Per2 results in nuclear translocation and subsequent transactivation of the CTGF gene. To test this hypothesis, we performed immunofluorescence labeling for CTGF in retinal sections from wild-type (WT) and Per2m/m mice. Human retinal endothelial cells (HRECs) were transfected with siRNA for Per2, and the protein expression of CTGF and β-catenin was evaluated. The TCF/LEF luciferase reporter (TOPflash) assay was performed to validate the involvement of β-catenin in the activation of CTGF. Per2m/m retinas exhibited an increased CTGF immunostaining in ganglion cell layer and retinal endothelium. Silencing of Per2 using siRNA resulted in an upregulation of CTGF and β-catenin. The TOPflash assay revealed an increase in luminescence for HRECs transfected with Per2 siRNA. Our studies show that loss of Per2 results in an activation of CTGF via nuclear entry of β-catenin. Our study provides novel insight into the understanding of microvascular dysfunction in Per2m/m mice. PMID:27662578

  8. 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.

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

    PubMed Central

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

    1994-01-01

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

  10. 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. PMID:26818120

  11. Purification and characterization of pepsin-solubilized collagen from skin and connective tissue of giant red sea cucumber (Parastichopus californicus).

    PubMed

    Liu, Zunying; Oliveira, Alexandra C M; Su, Yi-Cheng

    2010-01-27

    Pepsin-solubilized collagen (PSC) was extracted from giant red sea cucumbers ( Parastichopus californicus ) and characterized for denaturation temperature (T(d)), maximum transition temperature (T(m)), enzyme-digested peptide maps, and gel-forming capability. SDS-PAGE showed that PSCs from giant red sea cucumber skin and connective tissue were both type I collagens, consisting of three alpha(1) chains of approximately 138 kDa each. The amino acid composition and peptide maps of PSCs digested by V8 protease were different from those of calf skin type I collagen. The T(d) and T(m) are 18.5 and 33.2 degrees C, respectively, for skin PSC and are 17.9 and 32.7 degrees C, respectively, for connective tissue PSC. Both skin and connective tissue PSCs exhibited good gel-forming capability at pH 6.5 and at an ionic strength of 300 mM salt (NaCl). Collagen isolated from giant red sea cucumbers might be used as an alternative to mammalian collagen in the food and pharmaceutical industries.

  12. Increased Functional Connectivity Between Subcortical and Cortical Resting-State Networks in Autism Spectrum Disorder

    PubMed Central

    Cerliani, Leonardo; Mennes, Maarten; Thomas, Rajat M.; Di Martino, Adriana; Thioux, Marc; Keysers, Christian

    2016-01-01

    Importance Individuals with autism spectrum disorder (ASD) exhibit severe difficulties in social interaction, motor coordination, behavioral flexibility, and atypical sensory processing, with considerable interindividual variability. This heterogeneous set of symptoms recently led to investigating the presence of abnormalities in the interaction across large-scale brain networks. To date, studies have focused either on constrained sets of brain regions or whole-brain analysis, rather than focusing on the interaction between brain networks. Objectives To compare the intrinsic functional connectivity between brain networks in a large sample of individuals with ASD and typically developing control subjects and to estimate to what extent group differences would predict autistic traits and reflect different developmental trajectories. Design, Setting, and Participants We studied 166 male individuals (mean age, 17.6 years; age range, 7-50 years) diagnosed as having DSM-IV-TR autism or Asperger syndrome and 193 typical developing male individuals (mean age, 16.9 years; age range, 6.5-39.4 years) using resting-state functional magnetic resonance imaging (MRI). Participants were matched for age, IQ, head motion, and eye status (open or closed) in the MRI scanner. We analyzed data from the Autism Brain Imaging Data Exchange (ABIDE), an aggregated MRI data set from 17 centers, made public in August 2012. Main Outcomes and Measures We estimated correlations between time courses of brain networks extracted using a data-driven method (independent component analysis). Subsequently, we associated estimates of interaction strength between networks with age and autistic traits indexed by the Social Responsiveness Scale. Results Relative to typically developing control participants, individuals with ASD showed increased functional connectivity between primary sensory networks and subcortical networks (thalamus and basal ganglia) (all t ≥ 3.13, P < .001 corrected). The strength of

  13. Influence of laser photobiomodulation upon connective tissue remodeling during wound healing.

    PubMed

    Medrado, Alena P; Soares, Ana Prates; Santos, Elisângela T; Reis, Sílvia Regina A; Andrade, Zilton A

    2008-09-18

    The modulation of collagen fibers during experimental skin wound healing was studied in 112 Wistar rats submitted to laser photobiomodulation treatment. A standardized 8mm-diameter wound was made on the dorsal skin of all animals. In half of them, 0.2ml of a silica suspension was injected along the border of the wound in order to enhance collagen deposition and facilitate observation. The others received saline as vehicle. The treatment was carried out by means of laser rays from an aluminum-gallium arsenide diode semiconductor with 9mW applied every other day (total dose=4J/cm2) on the borders of the wound. Tissue sections obtained from four experimental groups representing sham-irradiated animals, laser, silica and the association of both, were studied after 3, 7, 10, 15, 20, 30 and 60 days from the laser application. The wounded skin area was surgically removed and submitted to histological, immunohistochemical, ultrastructural, and immunofluorescent studies. Besides the degree and arrangement of collagen fibers and of their isotypes, the degree of edema, the presence of several cell types especially pericytes and myofibroblasts, were described and measured. The observation of Sirius-red stained slides under polarized microscopy revealed to be of great help during the morphological analysis of the collagen tissue dynamic changes. It was demonstrated that laser application was responsible for edema regression and a diminution in the number of inflammatory cells (p<0.05). An evident increase in the number of actin-positive cells was observed in the laser-treated wounds. Collagen deposition was less than expected in silica-treated wounds, and laser treatment contributed to its better differentiation and modulation in all irradiated groups. Thus, laser photobiomodulation was able to induce several modifications during the cutaneous healing process, especially in favoring newly-formed collagen fibers to be better organized and compactedly disposed.

  14. Increased Dapivirine Tissue Accumulation through Vaginal Film Codelivery of Dapivirine and Tenofovir

    PubMed Central

    2015-01-01

    The HIV-1 replication inhibitor dapivirine (DPV) is one of the most promising drug candidates being used in topical microbicide products for prevention of HIV-1 sexual transmission. To be able to block HIV-1 replication, DPV must have access to the viral reverse transcriptase enzyme. The window for DPV to access the enzyme happens during the HIV-1 cellular infection cycle. Thus, in order for DPV to exert its anti-HIV activity, it must be present in the mucosal tissue or cells where HIV-1 infection occurs. A dosage form containing DPV must be able to deliver the drug to the tissue site of action. Polymeric films are solid dosage forms that dissolve and release their payload upon contact with fluids. Films have been used as vaginal delivery systems of topical microbicide drug candidates including DPV. For use in topical microbicide products containing DPV, polymeric films must prove their ability to deliver DPV to the target tissue site of action. Ex vivo exposure studies of human ectocervical tissue to DPV film revealed that DPV was released from the film and did diffuse into the tissue in a concentration dependent manner indicating a process of passive diffusion. Analysis of drug distribution in the tissue revealed that DPV accumulated mostly at the basal layer of the epithelium infiltrating the upper part of the stroma. Furthermore, as a combination microbicide product, codelivery of DPV and TFV from a polymeric film resulted in a significant increase in DPV tissue concentration [14.21 (single entity film) and 31.03 μg/g (combination film)], whereas no impact on TFV tissue concentration was found. In vitro release experiments showed that this observation was due to a more rapid DPV release from the combination film as compared to the single entity film. In conclusion, the findings of this study confirm the ability of polymeric films to deliver DPV and TFV to human ectocervical tissue and show that codelivery of the two agents has a significant impact on DPV

  15. Cellular and Matrix Contributions to Tissue Construct Stiffness Increase with Cellular Concentration

    PubMed Central

    Marquez, J. Pablo; Genin, Guy M.; Pryse, Kenneth M.; Elson, Elliot L.

    2013-01-01

    The mechanics of bio-artificial tissue constructs result from active and passive contributions of cells and extracellular matrix (ECM). We delineated these for a fibroblast-populated matrix (FPM) consisting of chick embryo fibroblast cells in a type I collagen ECM through mechanical testing, mechanical modeling, and selective biochemical elimination of tissue components. From a series of relaxation tests, we found that contributions to overall tissue mechanics from both cells and ECM increase exponentially with the cell concentration. The force responses in these relaxation tests exhibited a logarithmic decay over the 3600 second test duration. The amplitudes of these responses were nearly linear with the amplitude of the applied stretch. The active component of cellular forces rose dramatically for FPMs containing higher cell concentrations. PMID:16874557

  16. Free-ranging domestic cats are characterized by increased metal content in reproductive tissues.

    PubMed

    Rzymski, Piotr; Niedzielski, Przemysław; Poniedziałek, Barbara; Rzymski, Paweł; Pacyńska, Joanna; Kozak, Lidia; Dąbrowski, Piotr

    2015-12-01

    Trace metals may be supportive to mammalian reproduction but also reveal certain toxicities. The present study investigated the content of selected metals (Ca, Cd, Cu, Mn, Mg, Ni, Pb, Zn) in uterine and testicular tissue of free-ranging and household cats and its relation with hair metal status, cats' age, weight, physical activity, diet and inhabited environment. Free-rangers and cats not fed by humans were characterized by higher concentrations of essential metals in their reproductive tissues as well as increased levels of toxic elements, particularly Cd and Ni. No difference in metal status was found for household individuals fed on different varieties of commercial food. Cats inhabiting urbanized areas were characterized by higher Pb levels in their reproductive system. Feline hair was found to be less, if at all, susceptible to environmental, lifestyle and dietary variables and most importantly, did not reflect a metal burden in reproductive tissues.

  17. Increase of AKR-specific sequences in tumor tissues of leukemic AKR mice.

    PubMed Central

    Berns, A; Jaenisch, R

    1976-01-01

    AKR mice produce, from shortly after birth, high titers of their endogenous Gross type murine leukemia virus, and develop a thymus-derived leukemia at 7-9 months of age. We show that this oncogenesis is accompanied by an increase in the number of AKR-specific DNA sequences in the tumor tissues, whereas the "non-target" organs are not affected. Sequence increase was determined by kinetic analysis of DNA reassociation using an AKR-murine leukemia virus (MuLV)-specific cDNA and also by hybridization with excess AKR cDNA. The AKR cDNA was selected to recognize AKR sequences without significant crossreaction with DNA sequences of other endogenous viruses. The results show that during the development of the leukemia, the number of AKR-MuLV-specific genes increases in tumor tissues by a factor of 1 1/2 to 2. PMID:181752

  18. Troponin I Assessment of Cardiac Involvement in Patients With Connective Tissue Disease and an Elevated Creatine Kinase MB Isoform Report of Four Cases and Review of the Literature.

    PubMed

    Badsha, H; Gunes, B; Grossman, J; Brahn, E

    1997-06-01

    Levels of creatine kinase MB isoform (CKMB) can be elevated in patients with myopathy, neuropathy, skeletal muscle injury, or renal failure in the absence of myocardial injury. These elevated CKMB levels make it difficult to identify cardiac involvement in conditions that can be associated with a variety of cardiac abnormalities or with symptoms that mimic them. Cardiac troponin I (cTnI), a myocardial regulatory protein, has a high specificity for cardiac muscle and can be used to clarify the etiology of CKMB elevations in such patients. In this report, four patients with diverse causes for increased CKMB levels are discussed with respect to cill.The first three patients, with tentative diagnoses of mixed connective tissue disease, amyotrophic lateral sclerosis, and polymyositis presented with increasing shortness of breath, tachycardia, nonspecific electrocardiogram changes, high creative kinase, and CKMB levels. A normal cTnI helped exclude a diagnosis of a cardiac cause of their symptoms. Patient 4 had a scleroderma variant and experienced sudden, fatal, cardiac decompensation caused by a dilated cardiomyopathy, accompanied by an increased cTnl.The cTnI is a reliable, specific, and quick wav of excluding or determining cardiac involvement in patients with connective tissue disease. As this test is inexpensive and becoming increasingly available, it could become the test of choice, especially in scenarios in which urgent management decisions are needed.

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

    PubMed

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

    2006-11-01

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

  20. Hydrologic connectivity increases denitrification in the hyporheic zone and restored floodplains of an agricultural stream

    NASA Astrophysics Data System (ADS)

    Roley, Sarah S.; Tank, Jennifer L.; Williams, Maureen A.

    2012-09-01

    Stream ecotones, specifically the lateral floodplain and subsurface hyporheic zone, can be important sites for nitrogen (N) removal via denitrification, but their role in streams with constructed floodplains has not been examined. We studied denitrification in the hyporheic zone and floodplains of an agriculturally influenced headwater stream in Indiana, USA, that had floodplains added as part of a "two-stage ditch" restoration project. To examine the potential for N removal in the hyporheic zone, we seasonally measured denitrification rates and nitrate concentrations by depth into the stream sediments. We found that nitrate concentration and denitrification rates declined with depth into the hyporheic zone, but denitrification was still measureable to a depth of at least 20 cm. We also measured denitrification rates on the restored floodplains over the course of a flood (pre, during, and post-inundation), and also compared denitrification rates between vegetated and non-vegetated areas of the floodplain. We found that floodplain denitrification rates increased over the course of a floodplain inundation event, and that the presence of surface water increased denitrification rates when vegetation was present. Stream ecotones in midwestern, agriculturally influenced streams have substantial potential for N removal via denitrification, particularly when they are hydrologically connected with high-nitrate surface water.

  1. The periprosthetic capsule and connective tissue diseases: a piece in the puzzle of autoimmune/autoinflammatory syndrome induced by adjuvants.

    PubMed

    Bassetto, Franco; Scarpa, Carlotta; Vindigni, Vincenzo; Doria, Andrea

    2012-10-01

    Breast prostheses have been criticized for being responsible for triggering systemic autoimmune disease. The presence of breast implants causes a natural foreign body reaction characterized by the infiltration of macrophages and T-cells. Using PubMed, Medline and eMedicine, we performed a systematic literature review on the stages of periprosthetic capsule formation and cells involved in order to understand which immunological pathways could be responsible for giving rise to, and the development of, connective tissue disease such as systemic sclerosis. We focused on the relationship between tissue growth factor-β, interleukin (IL)-1, IL-6 and T helper 17 or T regulatory cells, as well as on their effects on the different steps of capsular tissue formation. A disturbance in the modulation of these key cytokines may be responsible, in susceptible individuals, for a perpetuation of the inflammatory reaction which can locally lead to capsular contracture and at the systemic level may contribute to triggering autoimmune diseases.

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

    PubMed

    Hodges, G M; Melcher, A H

    1976-06-01

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

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

    NASA Technical Reports Server (NTRS)

    Vailas, A. C.; Grindeland, R.; Ashman, R.; Choy, V.; Durnova, G.; Graf, B.; Griffith, P.; Kaplansky, A. S.; Kolis, S.; Martinez, D.; Rao, J. S.; Rayford, A. R.; Reddy, B. R.; Sears, J.; Thielke, R.; Ulm, M.; Vanderby, R.

    1994-01-01

    The skin repair studies started to be problematic for the following reasons: (1) It was very difficult to locate the wound and many lesions were not of the same dimensions. A considerable amount of time was devoted to the identification of the wound using polarized light. We understand that this experiment was added on to the overall project. Marking of the wound site and standard dimensions should be recommended for the next flight experiment. (2) The tissue was frozen, therefore thawing and fixation caused problems with some of the immunocytochemical staining for obtaining better special resolution with light microscopy image processing. Despite these problems, we were unable to detect any significant qualitative differences for the following wound markers: (1) Collagen Type 3, (2) Hematotoxylin and Eosin, and (3) Macrophage Factor 13. All protein markers were isolated from rat sources and antibodies prepared and tested for cross reactivity with other molecules at the University of Wisconsin Hybridoma Facility. However, rat skin from the non lesioned site 'normal' showed interesting biochemical results. Skin was prepared for the following measurements: (1) DNA content, (2) Collagen content by hydroxyproline, and (3) uronic acid content and estimation of ground substance. The results indicated there was a non-significant increase (10%) in the DNA concentration of skin from flight animals. However, the data expressed as a ratio DNA/Collagen estimates the cell or nuclear density that supports a given quantity of collagen showed a dramatic increase in the flight group (33%). This means flight conditions may have slowed down collagen secretion and/or increased cell proliferation in adult rat skin. Further biochemical tests are being done to determine the crosslinking of elastin which will enhance the insight to assessing changes in skin turnover.

  4. Regulation of lysyl oxidase mRNA in dermal fibroblasts from normal donors and patients with inherited connective tissue disorders.

    PubMed

    Yeowell, H N; Marshall, M K; Walker, L C; Ha, V; Pinnell, S R

    1994-01-01

    Lysyl oxidase (LO) is an extracellular copper-dependent enzyme that catalyzes the initial reaction in the formation of lysine or hydroxylysine-derived crosslinks during collagen biosynthesis. We have isolated a cDNA for human LO from skin fibroblast poly(A+)RNA by PCR using primers based on the recently published sequence of human LO. This cDNA probe detects a major mRNA of 4.2 kb on Northern blots of RNA from normal fibroblasts. The level of LO mRNA was not significantly affected by cell density or by ascorbate treatment. Treatment of skin fibroblasts with hydralazine (50 microM), which increases the mRNAs for both the alpha and the beta subunits of prolyl hydroxylase (PH) and the mRNAs for lysyl hydroxylase, also increased LO mRNA by fourfold over a 72-h time course. In contrast, hydralazine dramatically decreased the mRNAs for alpha 1(I) collagen. Administration of minoxidil (500 microM), which specifically decreases LH activity without affecting PH activity or collagen biosynthesis in skin fibroblasts, stimulated the level of LO mRNA. Neither the administration of penicillamine (100 microM), which interferes with collagen cross-linking, nor the administration of beta-aminopropionitrile, which is a strong irreversible inhibitor of LO, to fibroblasts significantly changed the levels of LO mRNA over a 72-h time course. However, bleomycin (0.6 microgram/ml) significantly decreased the 4.2-kb LO mRNA in contrast to the levels of the alpha 1(I) collagen mRNAs, which were unchanged. No significant change was observed in the steady-state levels of LO mRNAs in fibroblasts isolated from patients with certain connective tissue disorders, including Marfan syndrome, Menkes disease, cutis laxa, and pseudoxanthoma elasticum. PMID:7508709

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

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

    PubMed

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

    2014-01-01

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

  8. Increased IMP dehydrogenase gene expression in solid tumor tissues and tumor cell lines

    SciTech Connect

    Collart, F.R.; Chubb, C.B.; Mirkin, B.L.; Huberman, E.

    1992-07-10

    IMP dehydrogenase, a regulatory enzyme of guanine nucleotide biosynthesis, may play a role in cell proliferation and malignancy. To assess this possibility, we examined IMP dehydrogenase expression in a series of human solid tumor tissues and tumor cell lines in comparison with their normal counterparts. Increased IMP dehydrogenase gene expression was observed in brain tumors relative to normal brain tissue and in sarcoma cells relative to normal fibroblasts. Similarly, in several B- and T-lymphoid leukemia cell lines, elevated levels of IMP dehydrogenase mRNA and cellular enzyme were observed in comparison with the levels in peripheral blood lymphocytes. These results are consistent with an association between increased IMP dehydrogenase expression and either enhanced cell proliferation or malignant transformation.

  9. 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

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

    PubMed Central

    2010-01-01

    Introduction The aim of the present study was to investigate the association between cardiovascular risk factors and endothelial dysfunction in patients with mixed connective tissue disease (MCTD) and to determine which biomarkers are associated with atherosclerotic complications, such as cardiovascular disease. Methods Fifty MCTD patients and 38 healthy age-matched and sex-matched controls were enrolled in this study. In order to describe endothelial dysfunction, we assessed flow-mediated dilation (FMD), nitrate-mediated dilation (NMD) and carotid artery intima-media thickness (IMT). We investigated FMD of the brachial artery after reactive hyperemia and NMD after sublingual nitroglycerin administration, while the IMT of the common carotid artery was determined by ultrasound. Anti-U1 ribonucleoprotein (anti-U1RNP) antibodies, anti-cardiolipin (anti-CL) antibodies, anti-endothelial cell antibody (AECA) and endothelial cell markers, such as soluble thrombomodulin (TM) and von Willebrand factor antigen (vWFAg), were assessed. Results The endothelium-dependent vasodilation (FMD) was significantly impaired in patients with MCTD, as compared with controls (%FMD: 4.7 ± 4.2% vs. 8.7 ± 5.0%; P < 0.001), while the percentage NMD did not differ (%NMD: 14.3 ± 6.6% vs. 17.1 ± 6.7%; P = 0.073). Mean carotid IMT values were higher in patients than in controls (IMT: MCTD, 0.64 ± 0.13 mm vs. controls, 0.53 ± 0.14 mm; P < 0.001). FMD negatively correlated with disease duration, the levels of apolipoprotein A1, the paraoxonase-1 activity, and systolic blood pressure in MCTD patients. The percentage FMD was significantly lower in MCTD patients with cardiovascular diseases (CVD), than in those without CVD (%FMD: 3.5 ± 2.9 vs. 5.8 ± 4.8, P < 0.0002), while percentage NMD did not differ between patients with and without CVDs. Serum levels of autoantibodies (anti-U1RNP, AECA and anti-CL) were significantly higher in MCTD patients and differed between MCTD patients with and

  11. Increased functional connectivity common to symptomatic amyotrophic lateral sclerosis and those at genetic risk

    PubMed Central

    Menke, Ricarda A L; Proudfoot, Malcolm; Wuu, Joanne; Andersen, Peter M; Talbot, Kevin; Benatar, Michael; Turner, Martin R

    2016-01-01

    Objective To discern presymptomatic changes in brain structure or function using advanced MRI in carriers of mutations predisposing to amyotrophic lateral sclerosis (ALS). Methods T1-weighted, diffusion weighted and resting state functional MRI data were acquired at 3 T for 12 asymptomatic mutation carriers (psALS), 12 age-matched controls and affected patients with ALS. Cortical thickness analysis, voxel-based morphometry, volumetric and shape analyses of subcortical structures, tract-based spatial statistics of metrics derived from the diffusion tensor, and resting state functional connectivity (FC) analyses were performed. Results Grey matter cortical thickness and shape analysis revealed significant atrophy in patients with ALS (but not psALS) compared with controls in the right primary motor cortex and right caudate. Comparison of diffusion tensor metrics showed widespread fractional anisotropy and radial diffusivity differences in patients with ALS compared to controls and the psALS group, encompassing parts of the corpus callosum, corticospinal tracts and superior longitudinal fasciculus. While FC in the resting-state sensorimotor network was similar in psALS and controls, FC between the cerebellum and a network comprising the precuneus, cingulate & middle frontal lobe was significantly higher in psALS and affected ALS compared to controls. Conclusions Rather than structural brain changes, increased FC may be among the earliest detectable brain abnormalities in asymptomatic carriers of ALS-causing gene mutations. With replication and significant refinement, this technique has potential in the future assessment of neuroprotective strategies. PMID:26733601

  12. Motor cortex maturation is associated with reductions in recurrent connectivity among functional subpopulations and increases in intrinsic excitability.

    PubMed

    Biane, Jeremy S; Scanziani, Massimo; Tuszynski, Mark H; Conner, James M

    2015-03-18

    Behavior is derived from the configuration of synaptic connectivity among functionally diverse neurons. Fine motor behavior is absent at birth in most mammals but gradually emerges during subsequent postnatal corticospinal system maturation; the nature of circuit development and reorganization during this period has been largely unexplored. We investigated connectivity and synaptic signaling among functionally distinct corticospinal populations in Fischer 344 rats from postnatal day 18 through 75 using retrograde tracer injections into specific spinal cord segments associated with distinct aspects of forelimb function. Primary motor cortex slices were prepared enabling simultaneous patch-clamp recordings of up to four labeled corticospinal neurons and testing of 3489 potential synaptic connections. We find that, in immature animals, local connectivity is biased toward corticospinal neurons projecting to the same spinal cord segment; this within-population connectivity significantly decreases through maturation until connection frequency is similar between neurons projecting to the same (within-population) or different (across-population) spinal segments. Concomitantly, postnatal maturation is associated with a significant reduction in synaptic efficacy over time and an increase in intrinsic neuronal excitability, altering how excitation is effectively transmitted across recurrent corticospinal networks. Collectively, the postnatal emergence of fine motor control is associated with a relative broadening of connectivity between functionally diverse cortical motor neurons and changes in synaptic properties that could enable the emergence of smaller independent networks, enabling fine motor movement. These changes in synaptic patterning and physiological function provide a basis for the increased capabilities of the mature versus developing brain.

  13. Werner's syndrome: a review of recent research with an analysis of connective tissue metabolism, growth control of cultured cells, and chromosomal aberrations.

    PubMed

    Salk, D

    1982-01-01

    Werner's syndrome is a rare, autosomal recessive condition with multiple progeroid features, but it is an imitation of aging rather than accelerated or premature senescence. Somatic chromosome aberrations occur in multiple tissues in vivo and in vitro, and there is an increased incidence of neoplasia. Thus. Werner's syndrome can be classified in the group of chromosome instability syndromes. Recent findings provide additional support for the concept that there is an aberration of connective tissue metabolism in Werner's syndrome, but it is unclear whether this is a primary or secondary manifestation of the underlying genetic defect. Abnormal growth characteristics are observed in cultured skin fibroblast-like cells and this provides another avenue for current research. Identification of the basic genetic defect in Werner's syndrome might clarify our understanding of the normal aging process in general, or might elucidate specific aspects such as the development of neoplasia, atherosclerosis, diabetes, or osteoporosis.

  14. Quantification of the global and local complexity of the epithelial-connective tissue interface of normal, dysplastic, and neoplastic oral mucosae using digital imaging.

    PubMed

    Abu Eid, Rasha; Landini, Gabriel

    2003-01-01

    This study aimed at quantifying the complexity of the epithelial-connective tissue interface (ECTI) in human normal mucosa, premalignant, and malignant lesions using fractal geometry. Two approaches were used to describe the complexity of 377 oral mucosa ECTI profiles. The box counting method was used to estimate their global fractal dimension, while local fractal dimensions were estimated using the mass radius relation at various local scales. The ECTI complexity significantly increased from normal through premalignant to malignant profiles in both global and local (over 283 microm) scales. Normal mucosa samples from different sites of the oral cavity also had different degrees of global complexity. Fractal geometry is a useful morphological marker of tissue complexity changes taking place during epithelial malignancy and premalignancy, and we propose it as a quantitative marker of epithelial complexity. PMID:14521264

  15. Subepithelial Connective Tissue Graft in Combination with a Tunnel Technique for the Treatment of Miller Class II and III Gingival Recessions in Mandibular Incisors: Clinical and Esthetic Results.

    PubMed

    Nart, Jose; Valles, Cristina

    2016-01-01

    There is limited evidence regarding the effect of the subepithelial connective tissue graft (SCTG) on root coverage in the mandibular anterior region. A sample of 15 Miller Class II and III recessions were treated in 15 patients using a SCTG with a tunnel technique. After a mean follow-up of 20.53 months, the mean percentage of root coverage was 83.25% for all treated recessions. Furthermore, a statistically significant increase of keratinized tissue was observed at the end of the evaluation period (2.66 mm; P = .001). The combination of tunnel technique and SCTG should be considered a treatment option to obtain root coverage in mandibular incisors with Class II and III recession defects. PMID:27333018

  16. Downregulation of metabolic activity increases cell survival under hypoxic conditions: potential applications for tissue engineering.

    PubMed

    Kim, Jaehyun; Andersson, Karl-Erik; Jackson, John D; Lee, Sang Jin; Atala, Anthony; Yoo, James J

    2014-08-01

    A major challenge to the success of cell-based implants for tissue regeneration is an insufficient supply of oxygen before host vasculature is integrated into the implants, resulting in premature cell death and dysfunction. Whereas increasing oxygenation to the implants has been a major focus in the field, our strategy is aimed at lowering oxygen consumption by downregulating cellular metabolism of cell-based implants. Adenosine, which is a purine nucleoside that functions as an energy transferring molecule, has been reported to increase under hypoxia, resulting in reducing the adenosine triphosphate (ATP) demands of the Na(+)/K(+) ATPase. In the present study, we investigated whether adenosine could be used to downregulate cellular metabolism to achieve prolonged survival under hypoxic conditions. Murine myoblasts (C2C12) lacking a self-survival mechanism were treated with adenosine under 0.1% hypoxic stress. The cells, cultured in the presence of 5 mM adenosine, maintained their viability under hypoxia, and regained their normal growth and function of forming myotubes when transferred to normoxic conditions at day 11 without further supply of adenosine, whereas nontreated cells failed to survive. An increase in adenosine concentrations shortened the onset of reproliferation after transfer to normoxic conditions. This increase correlated with an increase in metabolic downregulation during the early phase of hypoxia. A higher intracellular ATP level was observed in adenosine-treated cells throughout the duration of hypoxia. This strategy of increasing cell survival under hypoxic conditions through downregulating cellular metabolism may be utilized for cell-based tissue regeneration applications as well as protecting tissues against hypoxic injuries.

  17. The bronze baby syndrome: evidence of increased tissue concentration of copper porphyrins.

    PubMed

    Rubaltelli, F F; Da Riol, R; D'Amore, E S; Jori, G

    1996-03-01

    A case regarding a newborn infant with severe Rh haemolytic disease, who presented with the bronze baby syndrome and eventually died, is reported. The postmortem examination showed marked extramedullary haematopoiesis in the liver and spleen, heavy hepatic haemosiderosis and mild intralobular cholestasis. The porphyrin content, which was assayed in different tissues, was very high in the liver, suggesting that the increased erythropoiesis seen in Rh haemolytic disease leads to an increased synthesis of porphyrins as by-products of haem synthesis. Phototherapy causes photodestruction, sensitized by bilirubin, of porphyrins (mainly copper porphyrins), yielding brown photoproducts.

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

    PubMed

    deBotton, Gal; Oren, Tal

    2013-01-01

    State of the art research and treatment of biological tissues require accurate and efficient methods for describing their mechanical properties. Indeed, micromechanics-motivated approaches provide a systematic method for elevating relevant data from the microscopic level to the macroscopic one. In this work, the mechanical responses of hyperelastic tissues with one and two families of collagen fibers are analyzed by application of a new variational estimate accounting for their histology and the behaviors of their constituents. The resulting close-form expressions are used to determine the overall response of the wall of a healthy human coronary artery. To demonstrate the accuracy of the proposed method, these predictions are compared with corresponding 3D finite element simulations of a periodic unit cell of the tissue with two families of fibers. Throughout, the analytical predictions for the highly nonlinear and anisotropic tissue are in agreement with the numerical simulations.

  19. Increased Risk of Revision after ACL Reconstruction with Soft Tissue Allograft Compared to Autograft

    PubMed Central

    Maletis, Gregory; Chen, Jason; Inacio, Maria Carolina Secorun; Love, Rebecca; Funahashi, Tadashi Ted

    2016-01-01

    Objectives: The use of allograft tissue for anterior cruciate ligament reconstruction (ACLR) remains controversial. Numerous meta-analysis and systematic reviews of small clinical studies have not found differences between autograft and allograft outcomes but large registry studies have shown an increased risk of revision with allografts. The purpose of this study was to compare the risk of aseptic revision between bone-patellar tendon-bone (BPTB) autografts, hamstring tendon autografts and soft tissue allografts. Methods: A retrospective cohort study of prospectively collected data was conducted using an US ACLR Registry. A cohort of primary unilateral ACLR cases reconstructed with BPTB autografts, hamstring autografts and soft tissue allografts (from any site) was identified. Aseptic revision was the end point of the study. Type of graft and allograft processing methods (non-processed, <1.8Mrads with and without chemical processing (Allowash or AlloTrue methods), >1.8 Mrads irradiation with and without chemical processing, and chemical processing alone (BioCleanse)) were the exposures of interest evaluated. Time from surgery was evaluated as an effect modifier. All analyses were adjusted for age, gender, and race. Kaplan-Meier curves and Cox proportional hazard models were employed. Hazard ratios (HR), 95% confidence intervals (CI) are provided. Results: The cohort had 14015 cases, 8924 (63.7%) were male, 6397 (45.6%) were White, 4557 (32.5%) cases used BPTB autograft, 3751 (26.8%) cases used soft tissue allograft and 5707 (40.7%) cases used hamstring autograft. The median age was 34.6 years-old (IQR 24.1-43.2) for allograft cases and 24.3 years-old (IQR 17.7-33.8) for hamstring autograft cases, and 22.0 years-old (IQR 17.6-30.0) for BPTB autograft cases. Compared to hamstring tendon autografts, an increased risk of revision was found in allografts processed with >1.8Mrads without chemical processing after 2.5 years (HR: 3.88 95%CI 1.48-10.12), and >1.8Mrads with

  20. Adaptive tolerance in mice upon subchronic exposure to chloroform: Increased exhalation and target tissue regeneration

    SciTech Connect

    Anand, Sathanandam S. . E-mail: sanand@rx.uga.edu; Philip, Binu K.; Palkar, Prajakta S.; Mumtaz, Moiz M.; Latendresse, John R.; Mehendale, Harihara M. . E-mail: mehendale@ulm.edu

    2006-06-15

    The aims of the present study were to characterize the subchronic toxicity of chloroform by measuring tissue injury, repair, and distribution of chloroform and to assess the reasons for the development of tolerance to subchronic chloroform toxicity. Male Swiss Webster (SW) mice were given three dose levels of chloroform (150, 225, and 300 mg/kg/day) by gavage in aqueous vehicle for 30 days. Liver and kidney injury were measured by plasma ALT and BUN, respectively, and by histopathology. Tissue regeneration was assessed by {sup 3}H-thymidine incorporation into hepato- and nephro-nuclear DNA and by proliferating cell nuclear antigen staining. In addition, GSH and CYP2E1 in liver and kidney were assessed at selected time points. The levels of chloroform were measured in blood, liver, and kidney during the dosing regimen (1, 7, 14, and 30 days). Kidney injury was evident after 1 day with all three doses and sustained until 7 days followed by complete recovery. Mild to moderate liver injury was observed from 1 to 14 days with all three dose levels followed by gradual decrease. Significantly higher regenerative response was evident in liver and kidney at 7 days, but the response was robust in kidney, preventing progression of injury beyond first week of exposure. While the kidney regeneration reached basal levels by 21 days, moderate liver regeneration with two higher doses sustained through the end of the dosing regimen and 3 days after that. Following repeated exposure for 7, 14, and 30 days, the blood and tissue levels of chloroform were substantially lower with all three dose levels compared to the levels observed with single exposure. Increased exhalation of {sup 14}C-chloroform after repeated exposures explains the decreased chloroform levels in circulation and tissues. These results suggest that toxicokinetics and toxicodynamics (tissue regeneration) contribute to the tolerance observed in SW mice to subchronic chloroform toxicity. Neither bioactivation nor

  1. MicroRNA-145 Is Downregulated in Glial Tumors and Regulates Glioma Cell Migration by Targeting Connective Tissue Growth Factor

    PubMed Central

    Cazacu, Simona; Finniss, Susan; Xiang, Cunli; Twito, Hodaya; Poisson, Laila M.; Mikkelsen, Tom; Slavin, Shimon; Jacoby, Elad; Yalon, Michal; Toren, Amos; Rempel, Sandra A.; Brodie, Chaya

    2013-01-01

    Glioblastomas (GBM), the most common and aggressive type of malignant glioma, are characterized by increased invasion into the surrounding brain tissues. Despite intensive therapeutic strategies, the median survival of GBM patients has remained dismal over the last decades. In this study we examined the expression of miR-145 in glial tumors and its function in glioma cells. Using TCGA analysis and real-time PCR we found that the expression of miR-145/143 cluster was downregulated in astrocytic tumors compared to normal brain specimens and in glioma cells and glioma stem cells (GSCs) compared to normal astrocytes and neural stem cells. Moreover, the low expression of both miR-145 and miR-143 in GBM was correlated with poor patient prognosis. Transfection of glioma cells with miR-145 mimic or transduction with a lentivirus vector expressing pre-miR 145 significantly decreased the migration and invasion of glioma cells. We identified connective tissue growth factor (CTGF) as a novel target of miR-145 in glioma cells; transfection of the cells with this miRNA decreased the expression of CTGF as determined by Western blot analysis and the expression of its 3′-UTR fused to luciferase. Overexpression of a CTGF plasmid lacking the 3′-UTR and administration of recombinant CTGF protein abrogated the inhibitory effect of miR-145 on glioma cell migration. Similarly, we found that silencing of CTGF decreased the migration of glioma cells. CTGF silencing also decreased the expression of SPARC, phospho-FAK and FAK and overexpression of SPARC abrogated the inhibitory effect of CTGF silencing on cell migration. These results demonstrate that miR-145 is downregulated in glial tumors and its low expression in GBM predicts poor patient prognosis. In addition miR-145 regulates glioma cell migration by targeting CTGF which downregulates SPARC expression. Therefore, miR-145 is an attractive therapeutic target for anti-invasive treatment of astrocytic tumors. PMID:23390502

  2. Increased Functional Connectivity in an Insula-Based Network is Associated with Improved Smoking Cessation Outcomes.