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Sample records for adjacent connective tissue

  1. 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

  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. 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 ...

  4. 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

  5. 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

  6. Laser ablation of human atherosclerotic plaque without adjacent tissue injury

    NASA Technical Reports Server (NTRS)

    Grundfest, W. S.; Litvack, F.; Forrester, J. S.; Goldenberg, T.; Swan, H. J. C.

    1985-01-01

    Seventy samples of human cadaver atherosclerotic aorta were irradiated in vitro using a 308 nm xenon chloride excimer laser. Energy per pulse, pulse duration and frequency were varied. For comparison, 60 segments were also irradiated with an argon ion and an Nd:YAG laser operated in the continuous mode. Tissue was fixed in formalin, sectioned and examined microscopically. The Nd:YAG and argon ion-irradiated tissue exhibited a central crater with irregular edges and concentric zones of thermal and blast injury. In contrast, the excimer laser-irradiated tissue had narrow deep incisions with minimal or no thermal injury. These preliminary experiments indicate that the excimer laser vaporizes tissue in a manner different from that of the continuous wave Nd:YAG or argon ion laser. The sharp incision margins and minimal damage to adjacent normal tissue suggest that the excimer laser is more desirable for general surgical and intravascular uses than are the conventionally used medical lasers.

  7. [Connective tissue diseases in adolescents].

    PubMed

    Peitz, J; Tantcheva-Poór, I

    2016-04-01

    In this article we provide a brief review of systemic lupus erythematosus, juvenile dermatomyositis, systemic scleroderma, and mixed connective tissue disease in adolescents. As skin manifestations often belong to the presenting symptoms and may have a significant impact on the quality of life, dermatologists play an important role in the management of patients with connective tissue diseases. Early diagnosis and therapy onset are crucial for the patients' long-term outcome. PMID:27000182

  8. Extraocular connective tissue architecture.

    PubMed

    Miller, Joel M; Demer, Joseph L; Poukens, Vadims; Pavlovski, Dmitri S; Nguyen, Hien N; Rossi, Ethan A

    2003-01-01

    Extraocular muscle pulleys, now well known to be kinematically significant extraocular structures, have been noted in passing and described in fragments several times over the past two centuries. They were late to be fully appreciated because biomechanical modeling of the orbit was not available to derive their kinematic consequences, and because pulleys are distributed condensations of collagen, elastin and smooth muscle (SM) that are not sharply delineated. Might other mechanically significant distributed extraocular structures still be awaiting description?An imaging approach is useful for describing distributed structures, but does not seem suitable for assessing mechanical properties. However, an image that distinguished types and densities of constituent tissues could give strong hints about mechanical properties. Thus, we have developed methods for producing three dimensional (3D) images of extraocular tissues based on thin histochemically processed slices, which distinguish collagen, elastin, striated muscle and SM. Overall tissue distortions caused by embedding for sectioning, and individual-slice distortions caused by thin sectioning and subsequent histologic processing were corrected by ordered image warping with intrinsic fiducials. We describe an extraocular structure, partly included in Lockwood's ligament, which contains dense elastin and SM bands, and which might refine horizontal eye alignment as a function of vertical gaze, and torsion in down-gaze. This active structure might therefore be a factor in strabismus and a target of therapeutic intervention. PMID:12723968

  9. Pediatric Mixed Connective Tissue Disease.

    PubMed

    Berard, Roberta A; Laxer, Ronald M

    2016-05-01

    Pediatric-onset mixed connective tissue disease is among the rare disease entities in pediatric rheumatology and includes features of arthritis, polymyositis/dermatomyositis, systemic lupus erythematosus, and systemic sclerosis. Accurate recognition and diagnosis of the disease is paramount to prevent long-term morbidity. Advances in the genetic and immunologic understanding of the factors involved in the etiopathogenesis provide an opportunity for improvements in prognostication and targeted therapy. The development of a multinational cohort of patients with mixed connective tissue disease would be invaluable to provide more updated data regarding the clinical presentation, to develop a standardized treatment approach, disease activity and outcome tools, and to provide data on long-term outcomes and comorbidities. PMID:27032791

  10. [Comparative proteomic analysis of cancerous and adjacent normal lung tissues].

    PubMed

    Lee, Ki Beom; Pi, Kyung Bae

    2010-01-01

    Lung cancer is the leading cause of cancer-related mortality in industrialized countries. Unfortunately, most lung cancers are found too late for a cure, therefore early detection and treatment is very important. We have applied proteomic analysis by using two-dimensional gel electrophoresis and peptide mass fingerprinting techniques for examination of cancerous and adjacent non-cancerous lung tissues from the same patient. The aim of the study was to find proteins, which could be used as biomarkers for diagnosis and monitoring of this disease. Indeed, we found differences in expression of several proteins, related to various cellular activities, such as, chaperoning (e.g., GRP96, GRP78, HSP27), metabolism and oxidation stress (e.g., L-fucose, GST), cytoskeleton (e.g., tubulin beta 2/3, beta actin), cell adhesion (e.g., annexin A5/3), binding proteins (e.g., 14-3-3 theta) and signal transduction. These changes may be important for progression of carcinogenesis; they may be used as the molecular-support for future diagnostic markers. PMID:21395069

  11. Divergent viral presentation among human tumors and adjacent normal tissues.

    PubMed

    Cao, Song; Wendl, Michael C; Wyczalkowski, Matthew A; Wylie, Kristine; Ye, Kai; Jayasinghe, Reyka; Xie, Mingchao; Wu, Song; Niu, Beifang; Grubb, Robert; Johnson, Kimberly J; Gay, Hiram; Chen, Ken; Rader, Janet S; Dipersio, John F; Chen, Feng; Ding, Li

    2016-01-01

    We applied a newly developed bioinformatics system called VirusScan to investigate the viral basis of 6,813 human tumors and 559 adjacent normal samples across 23 cancer types and identified 505 virus positive samples with distinctive, organ system- and cancer type-specific distributions. We found that herpes viruses (e.g., subtypes HHV4, HHV5, and HHV6) that are highly prevalent across cancers of the digestive tract showed significantly higher abundances in tumor versus adjacent normal samples, supporting their association with these cancers. We also found three HPV16-positive samples in brain lower grade glioma (LGG). Further, recurrent HBV integration at the KMT2B locus is present in three liver tumors, but absent in their matched adjacent normal samples, indicating that viral integration induced host driver genetic alterations are required on top of viral oncogene expression for initiation and progression of liver hepatocellular carcinoma. Notably, viral integrations were found in many genes, including novel recurrent HPV integrations at PTPN13 in cervical cancer. Finally, we observed a set of HHV4 and HBV variants strongly associated with ethnic groups, likely due to viral sequence evolution under environmental influences. These findings provide important new insights into viral roles of tumor initiation and progression and potential new therapeutic targets. PMID:27339696

  12. Divergent viral presentation among human tumors and adjacent normal tissues

    PubMed Central

    Cao, Song; Wendl, Michael C.; Wyczalkowski, Matthew A.; Wylie, Kristine; Ye, Kai; Jayasinghe, Reyka; Xie, Mingchao; Wu, Song; Niu, Beifang; Grubb, Robert; Johnson, Kimberly J.; Gay, Hiram; Chen, Ken; Rader, Janet S.; Dipersio, John F.; Chen, Feng; Ding, Li

    2016-01-01

    We applied a newly developed bioinformatics system called VirusScan to investigate the viral basis of 6,813 human tumors and 559 adjacent normal samples across 23 cancer types and identified 505 virus positive samples with distinctive, organ system- and cancer type-specific distributions. We found that herpes viruses (e.g., subtypes HHV4, HHV5, and HHV6) that are highly prevalent across cancers of the digestive tract showed significantly higher abundances in tumor versus adjacent normal samples, supporting their association with these cancers. We also found three HPV16-positive samples in brain lower grade glioma (LGG). Further, recurrent HBV integration at the KMT2B locus is present in three liver tumors, but absent in their matched adjacent normal samples, indicating that viral integration induced host driver genetic alterations are required on top of viral oncogene expression for initiation and progression of liver hepatocellular carcinoma. Notably, viral integrations were found in many genes, including novel recurrent HPV integrations at PTPN13 in cervical cancer. Finally, we observed a set of HHV4 and HBV variants strongly associated with ethnic groups, likely due to viral sequence evolution under environmental influences. These findings provide important new insights into viral roles of tumor initiation and progression and potential new therapeutic targets. PMID:27339696

  13. 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

  14. Tissue landscape alters adjacent cell fates during Drosophila egg development

    PubMed Central

    Manning, Lathiena; Weideman, Ann Marie; Peercy, Bradford; Starz-Gaiano, Michelle

    2015-01-01

    Extracellular signaling molecules control many biological processes, but the influence of tissue architecture on the local concentrations of these factors is unclear. Here we examine this issue in the Drosophila egg chamber, where two anterior cells secrete Unpaired (Upd) to activate Signal Transducer and Activator of Transcription (STAT) signaling in the epithelium. High STAT signaling promotes cell motility. Genetic analysis shows that all cells near the Upd source can respond. However, using upright imaging, we show surprising asymmetries in STAT activation patterns, suggesting that some cells experience different Upd levels than predicted by their location. We develop a three-dimensional mathematical model to characterize the spatio-temporal distribution of the activator. Simulations show that irregular tissue domains can produce asymmetric distributions of Upd, consistent with results in vivo. Mutant analysis substantiates this idea. We conclude that cellular landscape can heavily influence the effect of diffusible activators and should be more widely considered. PMID:26082073

  15. Influence of corticosteroids on connective tissue.

    PubMed

    Asboe-Hansen, G

    1976-01-01

    All glucocorticosteroids inhibit growth, regeneration and repair of cellular or intercellular components of dermal connective tissues, when penetrated through the skin barrier. The resulting atrophy is a logical manifestation of the action of these compounds. PMID:133835

  16. Testicular complications in connective tissue disease

    PubMed Central

    Tangney, N J

    1981-01-01

    Acute testicular symptoms are described in 2 patients with Schönlein-Henoch syndrome and in 1 with juvenile rheumatoid arthritis. The literature on testicular involvement in connective tissue disease of childhood is reviewed. PMID:7271306

  17. Effects of radiotherapy on uveal melanomas and adjacent tissues.

    PubMed

    Groenewald, C; Konstantinidis, L; Damato, B

    2013-02-01

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

  18. Effects of radiotherapy on uveal melanomas and adjacent tissues

    PubMed Central

    Groenewald, C; Konstantinidis, L; Damato, B

    2013-01-01

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

  19. Matrix metalloproteinase-1 expression in breast cancer and cancer-adjacent tissues by immunohistochemical staining

    PubMed Central

    XUAN, JIAJIA; ZHANG, YUNFENG; ZHANG, XIUJUN; HU, FEN

    2015-01-01

    Although matrix metalloproteinase-1 (MMP-1) has been considered a factor of crucial importance for breast cancer cells invasion and metastasis, the expression of MMP-1 in different breast cancer and cancer-adjacent tissues have not been fully examined. In the present study, immunohistochemical staining was used to detect the MMP-1 expression in non-specific invasive ductal carcinoma of the breast, cancer-adjacent normal breast tissue, lymph node metastatic non-specific invasive ductal carcinoma of the breast and normal lymph node tissue. The results showed that MMP-1 expression is different in the above tissues. MMP-1 had a positive expression in normal lymph node tissue and lymph node metastatic non-specific invasive ductal carcinoma. The MMP-1 negative expression rate was only 6.1% in non-specific invasive ductal carcinoma of the breast and 2.9% in cancer-adjacent normal breast tissue respectively. MMP-1 expression is higher in non-specific invasive ductal carcinoma and lymph node metastatic non-specific invasive ductal carcinoma compared to cancer-adjacent normal breast tissue and normal lymph node tissue. In conclusion, higher expression of MMP-1 in breast cancer may play a crucial role in promoting breast cancer metastasis. PMID:26137243

  20. Coexisiting adenoma and granuloma involving the right inferior parathyroid gland with adjacent ectopic thymic tissue

    PubMed Central

    Gupta, Mayank; Kandasamy, Subramaniam

    2014-01-01

    Inflammatory lesions, particularly granulomas, involving adenoma of the parathyroid gland are rare. Ectopic thymic tissue is commonly associated with the thyroid and/or parathyroid gland due to their close embryonic relationship. We report a rare case of coexisting adenoma and granuloma of the parathyroid gland with adjacent ectopic thymic tissue. PMID:24957592

  1. Telomere length in hepatocellular carcinoma and paired adjacent non-tumor tissues by quantitative PCR.

    PubMed

    Zhang, Yujing; Shen, Jing; Ming-Whei; Lee, Yu Po-Huang; Santella, Regina M

    2007-12-01

    Telomere shortening limits the proliferative capacity of human cells, restrains the regenerative capacity of organ systems during chronic diseases and aging and also induces chromosomal instability as well as initiation of cancer. Previous studies demonstrated that telomeres are often significantly shorter in tumor tissue, including hepatocellular carcinoma (HCC), compared to the surrounding tissue, but telomere length in HCC tissues was not correlated with several clinical parameters, such as age, sex, HBV or HCV infections and tumor size. In the present study, the telomere length ratio of 36 paired HCC, and their adjacent non-tumor tissues was measured by quantitative PCR (Q-PCR). The mean telomere lengths (SD) for HCC and adjacent non-tumor tissues were 0.26 (0.10) and 0.47 (0.20) respectively (t = 6.22, P < 0.0001). There was a large difference in the distribution of subjects based on telomere length in tumor and adjacent non-tumor tissues. The number of tumors with telomere length shorter than 0.50 was much higher than that of adjacent non-tumor tissues; more than 90% of the tissues with telomere length > or = 0.50 were adjacent non-tumor tissues. The correlations between telomere length and aflatoxin B1- and polycyclic aromatic hydrocarbon-DNA adducts level, p53 mutations and p16 hypermethylation status were also tested, but no significant associations were found. The relationship between telomere length shortening, chemical carcinogen exposure, and genetic and epigenetic changes in hepatocarcinogenesis needs further investigation. PMID:18058461

  2. Distinguishing epigenetic features of preneoplastic testis tissues adjacent to seminomas and nonseminomas

    PubMed Central

    Skvortsova, Yulia V.; Zinovyeva, Marina V.; Stukacheva, Elena A.; Klimov, Alexey; Tryakin, Alexey A.; Azhikina, Tatyana L.

    2016-01-01

    PIWI pathway proteins are expressed during spermatogenesis where they play a key role in germ cell development. Epigenetic loss of PIWI proteins expression was previously demonstrated in testicular germ cell tumors (TGCTs), implying their involvement in TGCT development. In this work, apart from studying only normal testis and TGCT samples, we also analyzed an intermediate stage, i.e. preneoplastic testis tissues adjacent to TGCTs. Importantly, in this study, we minimized the contribution of patient-to-patient heterogeneity by using matched preneoplastic/TGCT samples. Surprisingly, expression of germ cell marker DDX4 suggests that spermatogenesis is retained in premalignant testis tissues adjacent to nonseminoma, but not those adjacent to seminoma. Moreover, this pattern is followed by expression of PIWI pathway genes, which impacts one of their functions: DNA methylation level over LINE-1 promoters is higher in preneoplastic testis tissues adjacent to nonseminomas than those adjacent to seminomas. This finding might imply distinct routes for development of the two types of TGCTs and could be used as a novel diagnostic marker, possibly, noninvasively. Finally, we studied the role of CpG island methylation in expression of PIWI genes in patient samples and using in vitro experiments in cell line models: a more complex interrelation between DNA methylation and expression of the corresponding genes was revealed. PMID:26843623

  3. Distinguishing epigenetic features of preneoplastic testis tissues adjacent to seminomas and nonseminomas.

    PubMed

    Gainetdinov, Ildar V; Kondratieva, Sofia A; Skvortsova, Yulia V; Zinovyeva, Marina V; Stukacheva, Elena A; Klimov, Alexey; Tryakin, Alexey A; Azhikina, Tatyana L

    2016-04-19

    PIWI pathway proteins are expressed during spermatogenesis where they play a key role in germ cell development. Epigenetic loss of PIWI proteins expression was previously demonstrated in testicular germ cell tumors (TGCTs), implying their involvement in TGCT development. In this work, apart from studying only normal testis and TGCT samples, we also analyzed an intermediate stage, i.e. preneoplastic testis tissues adjacent to TGCTs. Importantly, in this study, we minimized the contribution of patient-to-patient heterogeneity by using matched preneoplastic/TGCT samples. Surprisingly, expression of germ cell marker DDX4 suggests that spermatogenesis is retained in premalignant testis tissues adjacent to nonseminoma, but not those adjacent to seminoma. Moreover, this pattern is followed by expression of PIWI pathway genes, which impacts one of their functions: DNA methylation level over LINE-1 promoters is higher in preneoplastic testis tissues adjacent to nonseminomas than those adjacent to seminomas. This finding might imply distinct routes for development of the two types of TGCTs and could be used as a novel diagnostic marker, possibly, noninvasively. Finally, we studied the role of CpG island methylation in expression of PIWI genes in patient samples and using in vitro experiments in cell line models: a more complex interrelation between DNA methylation and expression of the corresponding genes was revealed. PMID:26843623

  4. [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

  5. 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

  6. Hydrologic Connection Between Geysers and Adjacent Thermal Pools, Two Examples: El Tatio, Chile and Yellowstone, USA

    NASA Astrophysics Data System (ADS)

    Munoz Saez, C.; Fauria, K.; Manga, M.; Hurwitz, S.; Namiki, A.

    2014-12-01

    Geyser eruption cycles can be influenced by adjacent and distant thermals sources, suggesting a hydraulic connection through permeable pathways. Diffusion of fluid pressure can be responsible for the communication between geysers. In this study we examine the processes linking two different geysers with adjacent thermal pools. The first was Vega Rinconada, located at El Tatio geyser field, Chile, where we measured temperature inside the conduit between the ground surface and a depth of seven meters, at one-meter intervals. The second was Lone Star Geyser in Yellowstone National Park, where we measured temperature of the overflow water at the base of the cone. Concurrently, we measured temperature and the water level in pools adjacent to both geysers. We found common elements in both geyser - pool systems: First, water temperature in both adjacent pools was below the boiling point and cooler than water in the geysers. Second, changes in pool water levels were correlated with eruptions of the geysers. During the quiescent period of the geysers, the water level increased in adjacent pools, while water level in the pools deceased during eruptions. Additionally, measurements inside of the conduit in Vega Rinconada Geyser showed that water temperature increased in the deepest part of the conduit during eruptions, while water temperature decreased in the shallow part of the geyser conduit (~1 to 2 m). These drops in temperature in the shallow conduit were coincident with the drop in water level in the adjacent pool. This suggests that after the initiation of an eruption, water may drain from the pool to the geyser. Furthermore, we observed a temperature drop of 3oC in the shallow conduit immediately preceding the end of an eruption. This suggests that flow from the pool to geyser contributes to eruption shut off. Our observations of geyser-pool systems indicate a hydrologic connection between the geysers and their adjacent pools. In the case of Vega Rinconada, cold water

  7. 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

  8. 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. PMID:27311225

  9. [Pulmonary manifestations of connective tissue diseases].

    PubMed

    Rehbock, B

    2015-03-01

    Systemic autoimmune diseases are responsible for about 25% of all deaths due to interstitial lung disease; therefore, an early identification of patients with pulmonary manifestation changes the management. Detection, differential diagnostic classification and staging of the pneumological pattern of findings are largely based on high-resolution computed tomography (HR-CT). The main differential diagnostic challenges are interstitial manifestations which present with radiological-histopathological phenotypes of interstitial pneumonia. The most common form of interstitial pulmonary reaction form of connective tissue diseases is the nonspecific interstitial pneumonia (NSIP) pattern. In rheumatoid arthritis, a usual interstitial pneumonia (UIP) pattern is dominant. Uncharacteristic reactions of airways and pleura can be the leading symptom or present as accompanying findings. A serious complication is pulmonary hypertension. Drug-induced lung lesions can present with similar HR-CT morphology as connective tissue diseases and can only be differentiated in the temporal and clinical context. PMID:25693496

  10. 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

  11. Differentially Expressed miRNAs in Tumor, Adjacent, and Normal Tissues of Lung Adenocarcinoma

    PubMed Central

    Tian, Fei; Li, Rui; Chen, Zhenzhu; Shen, Yanting; Lu, Jiafeng; Xie, Xueying; Ge, Qinyu

    2016-01-01

    Lung cancer is the leading cause of cancer deaths. Non-small-cell lung cancer (NSCLC) is the major type of lung cancer. The aim of this study was to characterize the expression profiles of miRNAs in adenocarcinoma (AC), one major subtype of NSCLC. In this study, the miRNAs were detected in normal, adjacent, and tumor tissues by next-generation sequencing. Then the expression levels of differential miRNAs were quantified by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). In the results, 259, 401, and 389 miRNAs were detected in tumor, adjacent, and normal tissues of pooled AC samples, respectively. In addition, for the first time we have found that miR-21-5p and miR-196a-5p were gradually upregulated from normal to adjacent to tumor tissues; miR-218-5p was gradually downregulated with 2-fold or greater change in AC tissues. These 3 miRNAs were validated by qRT-PCR. Lastly, we predicted target genes of these 3 miRNAs and enriched the potential functions and regulatory pathways. The aberrant miR-21-5p, miR-196a-5p, and miR-218-5p may become biomarkers for diagnosis and prognosis of lung adenocarcinoma. This research may be useful for lung adenocarcinoma diagnosis and the study of pathology in lung cancer. PMID:27247934

  12. Latest advances in connective tissue disorders

    PubMed Central

    Rao, Vijay

    2013-01-01

    The connective tissue disorders comprise a number of related conditions that include systemic lupus erythematosus (SLE) and the antiphospholipid (Hughes) syndrome, scleroderma, myositis and Sjögren’s syndrome. They are characterized by autoantibody production and other immune-mediated dysfunction. There are common clinical and serological features with some patients having multiple overlapping connective tissue disorders. The latest advances include new approaches to therapy, including more focused utilization of existing therapies and the introduction of biological therapies in SLE, more precise protocols for assessment of severe disease manifestations such as in interstitial lung disease and pulmonary artery hypertension in scleroderma, new antibodies for disease characterization in myositis and new approaches to patient assessment in Sjögren’s syndrome. B cells have a critical role in most, if not all of these disorders such that B-cell depletion or suppression of B-cell activating cytokines improves disease in many patients. In particular, the introduction of rituximab, a monoclonal antibody targeting the CD20 molecule on B cells, into clinical practice for rheumatoid arthritis and B-cell lymphoma has been a key driver of experimental approaches to therapy in connective tissue disorders. Genetic studies also suggest a role for the innate immune system in disease pathogenesis, suggesting further future targets for biological therapies over the next few years. PMID:23904866

  13. Spatiotemporal morphometry of adjacent tissue layers with application to the study of sulcal formation.

    PubMed

    Rajagopalan, Vidya; Scott, Julia; Habas, Piotr A; Kim, Kio; Rousseau, François; Glenn, Orit A; Barkovich, A James; Studholme, Colin

    2011-01-01

    The process of brain growth involves the expansion of tissue at different rates at different points within the brain. As the layers within the developing brain evolve they can thicken or increase in area as the brain surface begins to fold. In this work we propose a new spatiotemporal formulation of tensor based volume morphometry that is derived in relation to tissue boundaries. This allows the study of the directional properties of tissue growth by separately characterizing the changes in area and thickness of the adjacent layers. The approach uses temporally weighted, local regression across a population of anatomies with different ages to model changes in components of the growth radial and tangential to the boundary between tissue layers. The formulation is applied to the study of sulcal formation from in-utero MR imaging of human fetal brain anatomy. Results show that the method detects differential growth of tissue layers adjacent to the cortical surface, particularly at sulcal locations, as early as 22 gestational weeks. PMID:21995063

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

    PubMed Central

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

    2015-01-01

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

  15. Connective Tissue Disorder-Associated Vasculitis.

    PubMed

    Sharma, Aman; Dhooria, Aadhaar; Aggarwal, Ashish; Rathi, Manish; Chandran, Vinod

    2016-06-01

    Vasculitides secondary to connective tissue diseases are classified under the category of 'vasculitis associated with systemic disease' in the revised International Chapel Hill Consensus Conference (CHCC) nomenclature. These secondary vasculitides may affect any of the small, medium or large vessels and usually portend a poor prognosis. Any organ system can be involved and the presentation would vary depending upon that involvement. Treatment depends upon the type and severity of presentation. In this review, we describe secondary vasculitis associated with rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, relapsing polychondritis, systemic sclerosis, Sjogren's syndrome and idiopathic inflammatory myositis, focusing mainly on recent advances in the past 3 years. PMID:27097818

  16. CRLX101 nanoparticles localize in human tumors and not in adjacent, nonneoplastic tissue after intravenous dosing

    PubMed Central

    Clark, Andrew J.; Wiley, Devin T.; Zuckerman, Jonathan E.; Webster, Paul; Chao, Joseph; Lin, James; Yen, Yun; Davis, Mark E.

    2016-01-01

    Nanoparticle-based therapeutics are being used to treat patients with solid tumors. Whereas nanoparticles have been shown to preferentially accumulate in solid tumors of animal models, there is little evidence to prove that intact nanoparticles localize to solid tumors of humans when systemically administered. Here, tumor and adjacent, nonneoplastic tissue biopsies are obtained through endoscopic capture from patients with gastric, gastroesophageal, or esophageal cancer who are administered the nanoparticle CRLX101. Both the pre- and postdosing tissue samples adjacent to tumors show no definitive evidence of either the nanoparticle or its drug payload (camptothecin, CPT) contained within the nanoparticle. Similar results are obtained from the predosing tumor samples. However, in nine of nine patients that were evaluated, CPT is detected in the tumor tissue collected 24–48 h after CRLX101 administration. For five of these patients, evidence of the intact deposition of CRLX101 nanoparticles in the tumor tissue is obtained. Indications of CPT pharmacodynamics from tumor biomarkers such as carbonic anhydrase IX and topoisomerase I by immunohistochemistry show clear evidence of biological activity from the delivered CPT in the posttreatment tumors. PMID:27001839

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

    PubMed Central

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

    2015-01-01

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

  18. Generalized Connective Tissue Disease in Crtap-/- Mouse

    PubMed Central

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

    2010-01-01

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

  19. Connective tissue metabolism in chikungunya patients

    PubMed Central

    Lokireddy, Sudarsanareddy; Vemula, Sarojamma; Vadde, Ramakrishna

    2008-01-01

    Background Chikungunya (CHIK) fever is a viral disease transmitted to humans by the bite of Chikungunya virus (CHIK virus) infected Aedes mosquitoes. CHIK virus is a member of the Alphavirus genus of the family Togaviridae. Previous reports have indicated that infection with CHIK virus produces an acute arthritis in human hosts by large area of necrosis and collagenosis or fibrosis. Results We carried out the present study to determine the effect of chikungunya on the collagen and connective tissue metabolism in 75 chikungunya-affected people. First, we screened for mucopolysaccharides in urine by Cetyl Trimethyl Ammonium Bromide (CTAB) test. Appearance of heavy precipitate indicates the presence of higher levels of mucopolysaccharides and later quantified by DMB dye method. The urinary mucopolysaccharide in CHIK patients was 342 ± 45 mg/l compared to healthy controls (45 ± 5.6 mg/l). The collagen building blocks, proline and hydroxyproline were also measured in CHIK patients and observed higher excretion compared to healthy controls. Urinary excretions hydroxyproline was greater than the proline levels. Conclusion These results indicate that CHIK virus infection affects and damage the cartilage and connective metabolism and releases the degraded products from the tissue and responsible for increasing the levels of proline, hydroxyproline and mucopolysaccharides in CHIK affected patients. PMID:18302795

  20. Histopathological effects of intraoperative radiotherapy on pancreas and adjacent tissues: a postmortem analysis

    SciTech Connect

    Hoekstra, H.J.; Restrepo, C.; Kinsella, T.J.; Sindelar, W.F.

    1988-02-01

    Intraoperative radiotherapy (IORT) has been utilized in the treatment of resectable and unresectable pancreatic carcinoma at the National Cancer Institute. Detailed autopsy analyses of the radiation effects on the pancreas and adjacent tissues were performed on 13 patients dying at various times following therapy. IORT can induce a progressive retroperitoneal fibrosis and fibrosis of the porta hepatis in patients with resectable pancreatic carcinoma. In unresectable pancreatic carcinoma, the major expression of intraoperative irradiation with external beam irradiation is a progressive fibrosis of the pancreas with vascular sclerosis, nerve degeneration, atrophy of acinar cells, and atypical changes in the ducts of the pancreas, as well as degenerative changes of the pancreatic tumor.

  1. Pulmonary arterial hypertension in connective tissue diseases.

    PubMed

    Goldberg, Avram

    2010-01-01

    Pulmonary arterial hypertension (PAH) is an entity that is known to complicate connective tissue diseases (CTD). PAH in CTD is a very important diagnosis which greatly affects treatment and prognosis. The most commonly affected CTD is scleroderma, although lupus, inflammatory myopathies such as poly and dermatomyositis, and mixed CTD are also associated with PAH. The manifestations of PAH have both similarities and differences when occurring in the setting of CTD as compared with idiopathic PAH. These differences are most notable in scleroderma. In this section we will discuss the features of PAH as they appear in CTDs, and in particular, scleroderma. The focus of this article is an approach to the diagnosis and treatment of PAH in CTD, and how this setting might differ from idiopathic and other forms of PAH. PMID:20160534

  2. Pulmonary hypertension complicating connective tissue disease.

    PubMed

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

    2013-10-01

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

  3. Fibroblast involvement in soft connective tissue calcification

    PubMed Central

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

    2013-01-01

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

  4. Rare inflammatory and hereditary connective tissue diseases.

    PubMed

    Klipple, G L; Riordan, K K

    1989-05-01

    Polyarteritis nodosa developing during gestation has an extremely grave prognosis. To an uncertain extent, this results from a delay in recognition and therapy. The diagnosis of PAN is complicated by the expanded differential of common conditions associated with pregnancy such as pre-eclampsia and toxemia which can present with similar symptoms and signs. On the other hand, the pregnant woman with known, quiescent disease has a much better prognosis with only one of four women experiencing exacerbation. In women with Behcet's disease, convincing reports of both pregnancy-related flares and remissions involving primarily mucocutaneous manifestations are found in the literature. Gestational exacerbation of the more serious manifestations including chorioretinitis, vasculitis and CNS disease does not appear to be a problem. Also, a significant effect on fetal development or survival is not evident. The pregnant woman with the Marfan syndrome and pre-existing cardiovascular disease, particularly dilatation of the aortic root, has a substantially increased risk of developing a major complication during gestation most commonly aortic aneurysm, dissection, rupture or insufficiency. Echocardiographic determination of the aortic root diameter is prognostic with a decreased risk at a diameter of 40 mm or less. A diameter of greater than 40 to 45 mm constitutes a significant contraindication to pregnancy. All pregnancies in patients with the Marfan syndrome are considered high risk and frequent evaluations and echocardiograms are required. The EDS patient is subject to a wide range of gestational complications resulting from the basic connective tissue defect manifested clinically by hyperextensible skin, joint hypermobility, connective tissue and vascular fragility, and poor wound healing. The most serious complications occur in type I EDS (gravis) and type IV (ecchymotic) and include extensive perineal tears and hematoma after vaginal delivery, uterine prolapse and rupture

  5. Structure of the tendon connective tissue.

    PubMed

    Kannus, P

    2000-12-01

    Tendons consist of collagen (mostly type I collagen) and elastin embedded in a proteoglycan-water matrix with collagen accounting for 65-80% and elastin approximately 1-2% of the dry mass of the tendon. These elements are produced by tenoblasts and tenocytes, which are the elongated fibroblasts and fibrocytes that lie between the collagen fibers, and are organized in a complex hierarchical scheme to form the tendon proper. Soluble tropocollagen molecules form cross-links to create insoluble collagen molecules which then aggregate progressively into microfibrils and then into electronmicroscopically clearly visible units, the collagen fibrils. A bunch of collagen fibrils forms a collagen fiber, which is the basic unit of a tendon. A fine sheath of connective tissue called endotenon invests each collagen fiber and binds fibers together. A bunch of collagen fibers forms a primary fiber bundle, and a group of primary fiber bundles forms a secondary fiber bundle. A group of secondary fiber bundles, in turn, forms a tertiary bundle, and the tertiary bundles make up the tendon. The entire tendon is surrounded by a fine connective tissue sheath called epitenon. The three-dimensional ultrastructure of tendon fibers and fiber bundles is complex. Within one collagen fiber, the fibrils are oriented not only longitudinally but also transversely and horizontally. The longitudinal fibers do not run only parallel but also cross each other, forming spirals. Some of the individual fibrils and fibril groups form spiral-type plaits. The basic function of the tendon is to transmit the force created by the muscle to the bone, and, in this way, make joint movement possible. The complex macro- and microstructure of tendons and tendon fibers make this possible. During various phases of movements, the tendons are exposed not only to longitudinal but also to transversal and rotational forces. In addition, they must be prepared to withstand direct contusions and pressures. The above

  6. Early Growth Response1and Fatty Acid Synthase Expression is Altered in Tumor Adjacent Prostate Tissue and Indicates Field Cancerization

    PubMed Central

    Jones, Anna C.; Trujillo, Kristina A.; Phillips, Genevieve K.; Fleet, Trisha M.; Murton, Jaclyn K.; Severns, Virginia; Shah, Satyan K.; Davis, Michael S.; Smith, Anthony Y.; Griffith, Jeffrey K.; Fischer, Edgar G.; Bisoffi, Marco

    2011-01-01

    BACKGROUND Field cancerization denotes the occurrence of molecular alterations in histologically normal tissues adjacent to tumors. In prostate cancer, identification of field cancerization has several potential clinical applications. However, prostate field cancerization remains ill defined. Our previous work has shown up-regulated mRNA of the transcription factor early growth response 1 (EGR-1) and the lipogenic enzyme fatty acid synthase (FAS) in tissues adjacent to prostate cancer. METHODS Immunofluorescence data were analyzed quantitatively by spectral imaging and linear unmixing to determine the protein expression levels of EGR-1 and FAS in human cancerous, histologically normal adjacent, and disease-free prostate tissues. RESULTS EGR-1 expression was elevated in both structurally intact tumor adjacent (1.6× on average) and in tumor (3.0× on average) tissues compared to disease-free tissues. In addition, the ratio of cytoplasmic versus nuclear EGR-1 expression was elevated in both tumor adjacent and tumor tissues. Similarly, FAS expression was elevated in both tumor adjacent (2.7× on average) and in tumor (2.5× on average) compared to disease-free tissues. CONCLUSIONS EGR-1 and FAS expression is similarly deregulated in tumor and structurally intact adjacent prostate tissues and defines field cancerization. In cases with high suspicion of prostate cancer but negative biopsy, identification of field cancerization could help clinicians target areas for repeat biopsy. Field cancerization at surgical margins on prostatectomy specimen should also be looked at as a predictor of cancer recurrence. EGR-1 and FAS could also serve as molecular targets for chemoprevention. PMID:22127986

  7. 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

  8. [Autoimmune connective tissue diseases and vaccination].

    PubMed

    Więsik-Szewczyk, Ewa; Jahnz-Różyk, Karina

    2015-01-01

    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. PMID:27259225

  9. Renal involvement in autoimmune connective tissue diseases

    PubMed Central

    2013-01-01

    Connective tissue diseases (CTDs) are a heterogeneous group of disorders that share certain clinical presentations and a disturbed immunoregulation, leading to autoantibody production. Subclinical or overt renal manifestations are frequently observed and complicate the clinical course of CTDs. Alterations of kidney function in Sjögren syndrome, systemic scleroderma (SSc), auto-immune myopathies (dermatomyositis and polymyositis), systemic lupus erythematosus (SLE), antiphospholipid syndrome nephropathy (APSN) as well as rheumatoid arthritis (RA) are frequently present and physicians should be aware of that. In SLE, renal prognosis significantly improved based on specific classification and treatment strategies adjusted to kidney biopsy findings. Patients with scleroderma renal crisis (SRC), which is usually characterized by severe hypertension, progressive decline of renal function and thrombotic microangiopathy, show a significant benefit of early angiotensin-converting-enzyme (ACE) inhibitor use in particular and strict blood pressure control in general. Treatment of the underlying autoimmune disorder or discontinuation of specific therapeutic agents improves kidney function in most patients with Sjögren syndrome, auto-immune myopathies, APSN and RA. In this review we focus on impairment of renal function in relation to underlying disease or adverse drug effects and implications on treatment decisions. PMID:23557013

  10. Connective tissue growth factor in tumor pathogenesis

    PubMed Central

    2012-01-01

    Key roles for connective tissue growth factor (CTGF/CCN2) are demonstrated in the wound repair process where it promotes myofibroblast differentiation and angiogenesis. Similar mechanisms are active in tumor-reactive stroma where CTGF is expressed. Other potential roles include prevention of hypoxia-induced apoptosis and promoting epithelial-mesenchymal transistion (EMT). CTGF expression in tumors has been associated to both tumor suppression and progression. For example, CTGF expression in acute lymphoblastic leukemia, breast, pancreas and gastric cancer correlates to worse prognosis whereas the opposite is true for colorectal, lung and ovarian cancer. This discrepancy is not yet understood. High expression of CTGF is a hallmark of ileal carcinoids, which are well-differentiated endocrine carcinomas with serotonin production originating from the small intestine and proximal colon. These tumors maintain a high grade of differentiation and low proliferation. Despite this, they are malignant and most patients have metastatic disease at diagnosis. These tumors demonstrate several phenotypes potentially related to CTGF function namely: cell migration, absent tumor cell apoptosis, as well as, reactive and well vascularised myofibroblast rich stroma and fibrosis development locally and in distal organs. The presence of CTGF in other endocrine tumors indicates a role in the progression of well-differentiated tumors. PMID:23259759

  11. Comparative connective tissue structure-function relationships in biologic pumps.

    PubMed

    Factor, S M; Robinson, T F

    1988-02-01

    A complex connective tissue framework exists in mammalian hearts that surrounds and interconnects individual myocytes and fascicles of cells. Recent evidence suggests that this connective tissue plays a role in maintaining shape, modulating contractile forces, and mediating elastic recoil during cavity filling and contraction. In order to analyze the involvement of connective tissue in pump contraction and recoil, we examined silver impregnated connective tissue in rat hearts which spontaneously jet through fluid ex vivo by contracting their cavities forcefully and then sucking fluid for the next cycle, and compared them to frog hearts which beat actively under the same conditions, but do not demonstrate jet propulsion. A further analysis was carried out in unrelated but analogous models: the squid and octopus. The former jets rapidly through the ocean, while the latter moves sinuously along the seabed. We observed highly interconnected myocytes in the rat heart, whereas frog myocytes are individually wrapped by connective tissue but are not interconnected. The squid mantle muscle is surrounded by a complex connective tissue grid that is tethered to each muscle cell, whereas the octopus mantle muscle cells are surrounded by connective tissue but are not tethered. These observations suggest that myocyte connective tissue tethering may be necessary for muscle cavities to generate forceful and coordinated contractions sufficient for rapid ejection and suction of fluid. PMID:2448546

  12. 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

  13. 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

  14. 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. PMID:26988082

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

    NASA Astrophysics Data System (ADS)

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

    2011-08-01

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

  16. A Rodent Model to Evaluate the Tissue Response to a Biological Scaffold When Adjacent to a Synthetic Material.

    PubMed

    Dearth, Christopher L; Keane, Timothy J; Scott, Jeffrey R; Daly, Kerry A; Badylak, Stephen F

    2015-10-01

    The use of biologic scaffold materials adjacent to synthetic meshes is commonplace. A prevalent clinical example is two-staged breast reconstruction, where biologic scaffolds are used to provide support and coverage for the inferior aspect of the synthetic expander. However, limited data exist regarding either the kinetics of biologic scaffold integration or the host tissue response to the biologic scaffold materials used for this application or other applications in which such scaffold materials are used. The present study evaluated the temporal host response to a biological scaffold when placed adjacent to a synthetic material. Evaluation criteria included quantification of material contracture and characterization of the host cell response and tissue remodeling events. Results show a decreased thickness of the collagenous tissue layer at biologic scaffold/silicone interface compared to the abdominal wall/silicone interface during the 12-week experimental time course. All test materials were readily incorporated into surrounding host tissue. PMID:26176992

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

    NASA Astrophysics Data System (ADS)

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

    2005-04-01

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

  18. 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

  19. Cytoarchitecture and Cortical Connections of the Anterior Cingulate and Adjacent Somatomotor Fields in the Rhesus Monkey

    PubMed Central

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

    2012-01-01

    The cytoarchitecture and cortical connections of the anterior cingulate, medial and dorsal premotor, and precentral region are investigated using the Nissl and NeuN staining method and the fluorescent retrodgrade tract tracing technique. There is a gradual stepwise laminar change in the cytoarchitectonic organization from the proisocortical anterior cingulate region, through the lower and upper banks of the cingulate sulcus, to the dorsolateral isocortical premotor and precentral motor regions of the frontal lobe. These changes are characterized by a gradational emphasis on the lower stratum layers (V and VI) in the proisocortical cingulate region to the upper stratum layers (II and III) in the premotor and precentral motor region. This is accompanied by a progressive widening of layers III and VI, a poorly delineated border between layers III and V and a sequential increase in the size of layer V neurons culminating in the presense of giant Betz cells in the precentral motor region. The overall patterns of corticocortical connections paralleled the sequential changes in cytoarchitectonic organization. The proisocortical areas have connections with cingulate motor, supplementary motor, premotor and precentral motor areas on the one hand and have widespread connections with the frontal, parietal, temporal and multimodal association cortex and limbic regions on the other. The dorsal premotor areas have connections with the proisocortical areas including cingulate motor areas and supplementary motor area on the one hand, and premotor and precentral motor cortex on the other. Additionally, this region has significant connections with posterior parietal cortex and limited connections with prefrontal, limbic and multimodal regions. The precentral motor cortex also has connections with the proisocortical areas and premotor areas. Its other connections are limited to the somatosensory regions of the parietal lobe. Since the isocortical motor areas on the dorsal convexity

  20. Silica associated mixed connective tissue disorder in a stone crusher.

    PubMed

    Khanna, Arjun; Suri, Jagdish Chander; Ray, Animesh; Sharma, Rahul Kumar

    2013-05-01

    Silica exposure has been implicated with the development of various connective tissue diseases. We report a case of 32-year-old stone crusher who developed silicosis with mixed connective tissue disorder (MCTD) 6 years after exposure to silica. This association of silicosis with MCTD has never been reported from the Indian subcontinent, although the problem of this pneumoconiosis remains rampant. This rare association urges us to report this case. PMID:24421595

  1. Silica associated mixed connective tissue disorder in a stone crusher

    PubMed Central

    Khanna, Arjun; Suri, Jagdish Chander; Ray, Animesh; Sharma, Rahul Kumar

    2013-01-01

    Silica exposure has been implicated with the development of various connective tissue diseases. We report a case of 32-year-old stone crusher who developed silicosis with mixed connective tissue disorder (MCTD) 6 years after exposure to silica. This association of silicosis with MCTD has never been reported from the Indian subcontinent, although the problem of this pneumoconiosis remains rampant. This rare association urges us to report this case. PMID:24421595

  2. Mechanical properties of orbital fat and its encapsulating connective tissue.

    PubMed

    Chen, Kinon; Weiland, James D

    2011-06-01

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

  3. 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

  4. 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.

  5. 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.

  6. [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. PMID:26524895

  7. Connective tissue fibroblasts and Tcf4 regulate myogenesis

    PubMed Central

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

    2011-01-01

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

  8. Connective tissue anomalies in patients with spontaneous cervical artery dissection

    PubMed Central

    Giossi, Alessia; Ritelli, Marco; Costa, Paolo; Morotti, Andrea; Poli, Loris; Del Zotto, Elisabetta; Volonghi, Irene; Chiarelli, Nicola; Gamba, Massimo; Bovi, Paolo; Tomelleri, Giampaolo; Carletti, Monica; Checcarelli, Nicoletta; Meneghetti, Giorgio; Morra, Michele; Chinaglia, Mauro; De Giuli, Valeria; Colombi, Marina; Padovani, Alessandro

    2014-01-01

    Objective: To investigate the prevalence of connective tissue abnormalities in patients with spontaneous cervical artery dissections (sCeAD). Methods: We systematically assessed clinically detectable signs of connective tissue aberration in a series of consecutive patients with sCeAD and of age- and sex-matched patients with ischemic stroke unrelated to CeAD (non-CeAD IS) by a standard examination protocol including 68 items, and performed extensive molecular investigation for hereditary connective tissue disorders in all patients with sCeAD. Results: The study group included 84 patients with sCeAD (mean age, 44.5 ± 7.8 years; 66.7% men) and 84 patients with non-CeAD IS. None of the patients with sCeAD met clinical or molecular diagnostic criteria for established hereditary connective tissue disorder. Connective tissue abnormalities were detected more frequently in the group of patients with sCeAD than in the group of those with non-CeAD IS (mean number of pathologic findings, 4.5 ± 3.5 vs 1.9 ± 2.3; p < 0.001). Eighty-one patients (96.4%) in the sCeAD group had at least one detectable sign compared with 55 patients (66.7%) in the group with non-CeAD IS (p < 0.001). Skeletal, ocular, and skin abnormalities, as well as craniofacial dysmorphisms, were the clinical signs more strongly associated with sCeAD. Signs suggesting connective tissue abnormality were also more frequently represented in patients with sCeAD than in patients with traumatic CeAD (28.6%, p < 0.001; mean number of pathologic findings, 1.7 ± 3.7, p = 0.045). Conclusions: Connective tissue abnormalities are frequent in patients with sCeAD. This reinforces the hypothesis that systemic aberrations of the connective tissue might be implicated in the pathogenesis of the disease. PMID:25355826

  9. Histopathology of lung disease in the connective tissue diseases.

    PubMed

    Vivero, Marina; Padera, Robert F

    2015-05-01

    The pathologic correlates of interstitial lung disease (ILD) secondary to connective tissue disease (CTD) comprise a diverse group of histologic patterns. Lung biopsies in patients with CTD-associated ILD tend to demonstrate simultaneous involvement of multiple anatomic compartments of the lung. Certain histologic patterns tend to predominate in each defined CTD, and it is possible in many cases to confirm connective tissue-associated lung disease and guide patient management using surgical lung biopsy. This article will cover the pulmonary pathologies seen in rheumatoid arthritis, systemic sclerosis, myositis, systemic lupus erythematosus, Sjögren syndrome, and mixed CTD. PMID:25836637

  10. Connective tissue disease-associated pulmonary arterial hypertension.

    PubMed

    Sung, Yon K; Chung, Lorinda

    2015-05-01

    Pulmonary arterial hypertension (PAH) is characterized by vascular remodeling of pulmonary arterioles that leads to increased pulmonary vascular resistance, right heart failure, and death. It is associated with connective tissue diseases, including systemic sclerosis, systemic lupus erythematosus, and mixed connective tissue disease. PAH is characterized by dyspnea on exertion and fatigue. Syncopal events suggest severe disease. Patients may present with signs of right heart failure. One- and 3-year survival rates are approximately 81% and 52%, respectively. Given the high prevalence and mortality, algorithms for screening are currently under investigation and will hopefully lead to earlier diagnosis and improved survival. PMID:25836644

  11. [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

  12. A thermal monitoring sheet with low influence from adjacent waterbolus for tissue surface thermometry during clinical hyperthermia.

    PubMed

    Arunachalam, Kavitha; Maccarini, Paolo F; Stauffer, Paul R

    2008-10-01

    This paper presents a complete thermal analysis of a novel conformal surface thermometer design with directional sensitivity for real-time temperature monitoring during hyperthermia treatments of large superficial cancer. The thermal monitoring sheet (TMS) discussed in this paper consists of a 2-D array of fiberoptic sensors embedded between two layers of flexible, low-loss, and thermally conductive printed circuit board (PCB) film. Heat transfer across all interfaces from the tissue surface through multiple layers of insulating dielectrics surrounding the small buried temperature sensor and into an adjacent temperature-regulated water coupling bolus was studied using 3-D thermal simulation software. Theoretical analyses were carried out to identify the most effective differential TMS probe configuration possible with commercially available flexible PCB materials and to compare their thermal responses with omnidirectional probes commonly used in clinical hyperthermia. A TMS sensor design that employs 0.0508-mm Kapton MTB and 0.2032-mm Kapton HN flexible polyimide films is proposed for tissue surface thermometry with low influence from the adjacent waterbolus. Comparison of the thermal simulations with clinical probes indicates the new differential TMS probe design to outperform in terms of both transient response and steady-state accuracy in selectively reading the tissue surface temperature, while decreasing the overall thermal barrier of the probe between the coupling waterbolus and tissue surface. PMID:18838365

  13. A Thermal Monitoring Sheet with Low Influence from Adjacent Waterbolus for Tissue Surface Thermometry during Clinical Hyperthermia

    PubMed Central

    Arunachalam, K.; Maccarini, P.F.; Stauffer, P. R.

    2009-01-01

    This paper presents a complete thermal analysis of a novel conformal surface thermometer design with directional sensitivity for real time temperature monitoring during hyperthermia treatments of large superficial cancer. The thermal monitoring sheet (TMS) discussed in this paper consists of a two-dimensional array of fiberoptic sensors embedded between two layers of flexible, low loss and thermally conductive printed circuit board (PCB) film. Heat transfer across all interfaces from the tissue surface through multiple layers of insulating dielectrics surrounding the small buried temperature sensor and into an adjacent temperature regulated water coupling bolus was studied using 3D thermal simulation software. Theoretical analyses were carried out to identify the most effective differential TMS probe configuration possible with commercially available flexible PCB materials, and to compare their thermal responses with omni-directional probes commonly used in clinical hyperthermia. A TMS sensor design that employs 0.0508m Kapton MTB® and 0.2032 mm Kapton HN® flexible polyimide films is proposed for tissue surface thermometry with low influence from the adjacent waterbolus. Comparison of the thermal simulations with clinical probes indicate the new differential TMS probe design to outperform in terms of both transient response and steady state accuracy in selectively reading the tissue surface temperature, while decreasing the overall thermal barrier of the probe between the coupling waterbolus and tissue surface. PMID:18838365

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

    PubMed Central

    Agarwal, Ashish; Gupta, Narinder Dev

    2015-01-01

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

  15. 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

  16. 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.

  17. [The Marfan syndrome and related connective tissue disorders].

    PubMed

    Siepe, Matthias; Löffelbein, Florian

    2009-06-01

    The Marfan syndrome is an inherited disorder of the connective tissue which is mainly caused by a mutation in the fibrillin-1 gene. The defect in the connective tissue protein can lead to several organ dysfunctions. For the life expectancy, the cardiovascular aspect is of paramount importance. Patients with Marfan syndrome may develop aortic aneurysms and valvular heart defects. The risk of aortic aneurysms consists in the development of aortic dissection or rupture with their fatal consequences. Besides the cardiovascular manifestation, the skeletal and ocular system can also be affected. The skeletal manifestation is often characterised by long limbs, arachnodactyly, and abnormal joint flexibility along with other signs. Patients may also have dislocated lenses, ectasia of the dural sac, stretch marks, spontaneous pneumothorax, recurrent hernia, or a family history suspicious for Marfan. During the past years, other related connective tissue disorders with analogous organ manifestation have been described (e.g., Loeys-Dietz syndrome). In this article we present the basic knowledge about these connective tissue disorders, and we mention new insights in the recently explored pathophysiology of the disorder which is a possible target for future medical treatment options. Furthermore, recent new concepts for the prophylactic treatment of the aortic manifestation are explained. PMID:19554831

  18. Mechanical behavior of carpal tunnel subsynovial connective tissue under compression.

    PubMed

    Goetz, Jessica E; Baer, Thomas E

    2011-01-01

    Subsynovial connective tissue (SSCT) is a fluid-permeated loose connective tissue that occupies the majority of the space in the carpal tunnel not occupied by the digital flexor tendons or the median nerve. It is arranged in layers around these more discrete structures, presumably to assist with tendon gliding. As a result of this arrangement, the compressive behavior and the fluid permeability of this tissue may substantially affect the stresses in the median nerve resulting from contact with its neighboring tendons or with the walls of the tunnel itself. These stresses may contribute to damage of the median nerve and the development of carpal tunnel syndrome. In this study, the fluid permeability and the compressive behavior of the SSCT were investigated to better understand the mechanics of this tissue and how it may mediate mechanical insult to the median nerve. A custom experimental apparatus was built to allow simultaneous measurement of tissue compression and fluid flow. Using Darcy's law, the average SSCT fluid permeability was 8.78×10(15) m(4)/Ns. The compressive behavior of the SSCT demonstrated time dependence, with an initial modulus of 395kPa gradually decreasing to a value of 285kPa. These baseline tissue data may serve as a mechanical norm (toward which pathological tissue might be returned, therapeutically) and may serve as essential properties to include in future mechanical models of the carpal tunnel. PMID:22096431

  19. MECHANICAL BEHAVIOR OF CARPAL TUNNEL SUBSYNOVIAL CONNECTIVE TISSUE UNDER COMPRESSION

    PubMed Central

    Goetz, Jessica E; Baer, Thomas E

    2011-01-01

    Subsynovial connective tissue (SSCT) is a fluid-permeated loose connective tissue that occupies the majority of the space in the carpal tunnel not occupied by the digital flexor tendons or the median nerve. It is arranged in layers around these more discrete structures, presumably to assist with tendon gliding. As a result of this arrangement, the compressive behavior and the fluid permeability of this tissue may substantially affect the stresses in the median nerve resulting from contact with its neighboring tendons or with the walls of the tunnel itself. These stresses may contribute to damage of the median nerve and the development of carpal tunnel syndrome. In this study, the fluid permeability and the compressive behavior of the SSCT were investigated to better understand the mechanics of this tissue and how it may mediate mechanical insult to the median nerve. A custom experimental apparatus was built to allow simultaneous measurement of tissue compression and fluid flow. Using Darcy’s law, the average SSCT fluid permeability was 8.78×1015 m4/Ns. The compressive behavior of the SSCT demonstrated time dependence, with an initial modulus of 395kPa gradually decreasing to a value of 285kPa. These baseline tissue data may serve as a mechanical norm (toward which pathological tissue might be returned, therapeutically) and may serve as essential properties to include in future mechanical models of the carpal tunnel. PMID:22096431

  20. Anisotropic Tissue Motion Induced by Acupuncture Needling Along Intermuscular Connective Tissue Planes

    PubMed Central

    Fox, James R.; Gray, Weili; Koptiuch, Cathryn; Badger, Gary J.

    2014-01-01

    Abstract Objectives: Acupuncture needle manipulation causes mechanical deformation of connective tissue, which in turn results in mechanical stimulation of fibroblasts, with active changes in cell shape and autocrine purinergic signaling. We have previously shown using ultrasound elastography in humans that acupuncture needle manipulation causes measurable movement of tissue up to several centimeters away from the needle. The goal of this study was to quantify the spatial pattern of tissue displacement and deformation (shear strain) in response to acupuncture needling along an intermuscular connective tissue plane compared with needling over the belly of a muscle. Design: Eleven (11) healthy human subjects underwent a single testing session during which robotic acupuncture needling was performed while recording tissue displacement using ultrasound. Outcome measures were axial and lateral tissue displacement as well as lateral shear strain calculated using ultrasound elastography postprocessing. Results: Tissue displacement and strain extended further in the longitudinal direction when needling between muscles, and in the transverse direction when needling over the belly of a muscle. Conclusions: The anisotropic tissue motion observed in this study may influence the spatial distribution of local connective tissue cellular responses following acupuncture needle manipulation. PMID:24593827

  1. 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. PMID:26156071

  2. [Basement membranes as the regulatory system between epithelial cell connections and connective tissue].

    PubMed

    Heine, H

    1986-01-01

    Basement membranes develop by an interaction between epithelium and underlying mesenchymal. Basement membranes are to an great extend involved in the metabolic induced informational exchange between these 2 compartments. Informational selectivity is not only given with the construction of basement membranes. By redox systems like ascorbic acid/dehydroascorbic acid, preferentially located in basement membranes, the capability exists of scavenging free oxygen radicals on the border line between epithelia and connective tissue. This seems to be a very important factor in coupling the biorhythms between epithelia and connective tissue. PMID:3743995

  3. Clinical Evaluation of Papilla Reconstruction Using Subepithelial Connective Tissue Graft

    PubMed Central

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

    2014-01-01

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

  4. Smooth Muscle-Mediated Connective Tissue Remodeling in Pulmonary Hypertension

    NASA Astrophysics Data System (ADS)

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

    1987-07-01

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

  5. 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.

  6. Embryonic expression of endogenous retroviral RNAs in somatic tissues adjacent to the Oikopleura germline

    PubMed Central

    Henriet, Simon; Sumic, Sara; Doufoundou-Guilengui, Carlette; Jensen, Marit Flo; Grandmougin, Camille; Fal, Kateryna; Thompson, Eric; Volff, Jean-Nicolas; Chourrout, Daniel

    2015-01-01

    Selective pressure to maintain small genome size implies control of transposable elements, and most old classes of retrotransposons are indeed absent from the very compact genome of the tunicate Oikopleura dioica. Nonetheless, two families of retrotransposons are present, including the Tor elements. The gene organization within Tor elements is similar to that of LTR retrotransposons and retroviruses. In addition to gag and pol, many Tor elements carry a third gene encoding viral envelope-like proteins (Env) that may mediate infection. We show that the Tor family contains distinct classes of elements. In some classes, env mRNA is transcribed from the 5′LTR as in retroviruses. In others, env is transcribed from an additional promoter located downstream of the 5′LTR. Tor Env proteins are membrane-associated glycoproteins which exhibit some features of viral membrane fusion proteins. Whereas some elements are expressed in the adult testis, many others are specifically expressed in embryonic somatic cells adjacent to primordial germ cells. Such embryonic expression depends on determinants present in the Tor elements and not on their surrounding genomic environment. Our study shows that unusual modes of transcription and expression close to the germline may contribute to the proliferation of Tor elements. PMID:25779047

  7. Connective Tissue Disease-Associated Interstitial Lung Diseases: Unresolved Issues.

    PubMed

    Aparicio, Irene Jarana; Lee, Joyce S

    2016-06-01

    Interstitial lung disease (ILD) complicating connective tissue disorders, such as scleroderma and rheumatoid arthritis, is associated with significant morbidity and mortality. Progress has been made in our understanding of these collective diseases; however, there are still many unanswered questions. In this review, we describe the current views on epidemiology, clinical presentation, treatment, and prognosis in patients with connective tissue disease (CTD)-associated ILD. We also highlight several areas that remain unresolved and in need of further investigation, including interstitial pneumonia with autoimmune features, histopathologic phenotype, and pharmacologic management. A multidisciplinary and multidimensional approach to diagnosis, management, and investigation of CTD-associated ILD patients is essential to advance our understanding of the epidemiology and pathobiology of this challenging group of diseases. PMID:27231868

  8. New perspectives on rare connective tissue calcifying diseases.

    PubMed

    Rashdan, Nabil A; Rutsch, Frank; Kempf, Hervé; Váradi, András; Lefthériotis, Georges; MacRae, Vicky E

    2016-06-01

    Connective tissue calcifying diseases (CTCs) are characterized by abnormal calcium deposition in connective tissues. CTCs are caused by multiple factors including chronic diseases (Type II diabetes mellitus, chronic kidney disease), the use of pharmaceuticals (e.g. warfarin, glucocorticoids) and inherited rare genetic diseases such as pseudoxanthoma elasticum (PXE), generalized arterial calcification in infancy (GACI) and Keutel syndrome (KTLS). This review explores our current knowledge of these rare inherited CTCs, and highlights the most promising avenues for pharmaceutical intervention. Advancing our understanding of rare inherited forms of CTC is not only essential for the development of therapeutic strategies for patients suffering from these diseases, but also fundamental to delineating the mechanisms underpinning acquired chronic forms of CTC. PMID:26930168

  9. 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

  10. 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

  11. [Connective tissue diseases in hospital practice in Ouagadougou (Burkina Faso)].

    PubMed

    Ouédraogo, D D; Korsaga-Somé, N; Zabsonné Tiendrébéogo, J; Tiéno, H; Kaboré, H; Niamba, P; Drabo, J

    2014-01-01

    To describe the semiological and immunological features of connective tissue diseases seen at the Yalgado Ouédraogo University Hospital in Ouagadougou. A retrospective study reviewed the records of patients seen in the hospital dermatology and internal medicine departments from January 1, 2004, through December 31, 2009 and diagnosed with systemic lupus erythematosus (SLE), systemic sclerosis (ScS), dermatopolymyositis (DPM), primary Gougerot-Sjögren disease (GS), polymyositis (PM) or indeterminate connective tissue disease (ICTD) meeting the criteria of the American College of Rheumatology. The study included 42 patients, 36 women and 6 men. Their mean age was 41.2 years ±11.97 (range: 15-75). SLE was the diagnosis for 10 patients, ScS for 14, DPM for 7, primary GS for 1, PM for 1, and ICTD for 9. Hematologic (93%), cutaneous (88%), and rheumatologic (81%) abnormalities were the most frequent manifestations. The specific auto-antibodies associated with SLE patients were: anti-native DNA (3/6), anti-Sm (3/6), anti-RNP (3/6), and anti-SSA (4/6); anti-Scl 70 antibodies were present in 5 patients with ScS. Connective tissue diseases seem to be rare in Africa, south of the Sahara. However, the very fragmentary studies and the weak healthcare coverage do not allow any definitive conclusions. PMID:24921183

  12. Pauci-Immune Crescentic Glomerulonephritis in Connective Tissue Disease.

    PubMed

    Yeturi, Supraja; 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

  13. [Wounds in autoimmune bullous dermatoses and systemic connective tissue diseases].

    PubMed

    Marinović, Branka; Jukić, Ines Lakos; Lipozencić, Jasna

    2012-10-01

    Autoimmune bullous dermatoses are a group of skin and/or mucous membrane diseases characterized by blisters and erosions, which are the results of autoantibodies directed to structural components of desmosomes and structural proteins of the basement membrane zone. In this group of diseases, the diagnosis is based on history, clinical presentation, histopathologic findings, findings of direct and indirect immunofluorescence, and specific evidence of circulating antibodies by the enzyme linked immunosorbent assay (ELISA) method. Connective tissue diseases are a heterogeneous group of diseases with some common pathogenetic mechanisms and frequent involvement of the skin. This group of diseases commonly includes lupus erythematosus, dermatomyositis/polymyositis, localized and systemic scleroderma. As most of the diseases in this group have positive one of the antinuclear antibodies, in clinical practice these diseases are often called autoimmune connective tissue diseases. In the group of autoimmune bullous dermatoses, wounds occur as the result of breaking of blisters, and consequently affect the epidermis alone or epidermis and upper dermis, while in the group of systemic diseases of connective tissue, wounds occur in advanced stages of disease as a result of vascular tissue damage, causing necrosis of tissue and wounds. When wounds in these diseases last for a longer period (longer than 3 months), they are considered as chronic wounds and in these cases it is necessary to determine the reason for slow healing. In patients with wounds as a symptom of disease, besides systemic therapy, special attention should be paid to local therapy in order to prevent superinfection and accelerate epithelialization and wound healing. PMID:23193815

  14. Lead in tissues of woodchucks fed crown vetch growing adjacent to a highway

    SciTech Connect

    Young, R.W.; Ridgely, S.L.; Blue, J.T.; Bache, C.A.; Lisk, D.J.

    1986-01-01

    Woodchucks (Marmota monax) were fed crown vetch (Coronilla varia) growing along a major highway that was harvested in 1979, before unleaded gas was widely used, and again in 1985. Crown vetch, harvested 300 m from the nearest road, was fed as the control. The crops were fed as 50% dry weight of the diet for 58 d. The concentrations of lead in the control, 1979 crop, and 1985 crop were, respectively, 0.74, 50.65, and 6.78 ppm dry weight. The average +/- SE) concentrations (ppm, dry weight) of lead found in the tissues of the control, 1979, and 1985 dietary-treatment animals were, respectively, kidney, 0.36 +/- 0.05, 5.78 +/- 0.72, and 0.79 +/- 0.09; liver, 0.09 +/- 0.01, 4.71 +/- 0.17, and 0.46 +/- 0.06; muscle, 0.07 +/- 0.01, 0.14 +/- 0.02, and 0.07 +/- 0.00; blood, 0.09 +/- 0.02, 2.17 +/- 0.13, and 0.31 +/- 0.05; and bone, 1.27 +/- 0.25, 47.52 +/- 7.05, and 3.71 +/- 0.65. No significant differences (p greater than 0.05) between dietary treatments were found in the general hematological analyses of the woodchucks. The ecological significance of these findings is discussed.

  15. Connective tissue alterations in Fkbp10−/− mice

    PubMed Central

    Lietman, Caressa D.; Rajagopal, Abbhirami; Homan, Erica P.; Munivez, Elda; Jiang, Ming-Ming; Bertin, Terry K.; Chen, Yuqing; Hicks, John; Weis, MaryAnn; Eyre, David; Lee, Brendan; Krakow, Deborah

    2014-01-01

    Osteogenesis imperfecta (OI) is an inherited brittle bone disorder characterized by bone fragility and low bone mass. Loss of function mutations in FK506-binding protein 10 (FKBP10), encoding the FKBP65 protein, result in recessive OI and Bruck syndrome, of which the latter is additionally characterized by joint contractures. FKBP65 is thought to act as a collagen chaperone, but it is unknown how loss of FKBP65 affects collagen synthesis and extracellular matrix formation. We evaluated the developmental and postnatal expression of Fkbp10 and analyzed the consequences of its generalized loss of function. Fkbp10 is expressed at low levels in E13.5 mouse embryos, particularly in skeletal tissues, and steadily increases through E17.5 with expression in not only skeletal tissues, but also in visceral tissues. Postnatally, expression is limited to developing bone and ligaments. In contrast to humans, with complete loss of function mutations, Fkbp10−/− mice do not survive birth, and embryos present with growth delay and tissue fragility. Type I calvarial collagen isolated from these mice showed reduced stable crosslink formation at telopeptide lysines. Furthermore, Fkbp10−/− mouse embryonic fibroblasts show retention of procollagen in the cell layer and associated dilated endoplasmic reticulum. These data suggest a requirement for FKBP65 function during embryonic connective tissue development in mice, but the restricted expression postnatally in bone, ligaments and tendons correlates with the bone fragility and contracture phenotype in humans. PMID:24777781

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

    ERIC Educational Resources Information Center

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

    2014-01-01

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

  17. 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. PMID:27162076

  18. Ibuprofen-induced meningitis in mixed connective tissue disease.

    PubMed

    Hoffman, M; Gray, R G

    1982-06-01

    A young Black woman with mixed connective tissue disease (MCTD) developed an aseptic meningitis after receiving ibuprofen. The meningeal reaction, reported infrequently in systemic lupus erythematosus (SLE) and only once previously in MCTD, was characterized by a predominantly polymorphonuclear cerebrospinal fluid (CSF) pleocytosis and depression of CSF glucose. Reversible renal insufficiency also occurred. Features suggestive of a hypersensitivity reaction included pruritus, conjunctivitis, facial oedema, desquamation of the palms and soles, and subsequent near total alopecia. Meningeal signs responded rapidly to systemic corticosteroid therapy. Patients with MCTD as well as those with SLE may be at peculiar risk of developing this uncommon reaction to ibuprofen. PMID:6985377

  19. [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. PMID:24439720

  20. Microvascular filtration in subjects with connective tissue disorders.

    PubMed Central

    Edwards, J C; Snaith, M L

    1984-01-01

    A simple non-invasive method for studying microvascular filtration in the non-articular tissues of the forearm is described. Rates of filtration under a standard hydrostatic pressure were measured in 20 normal female subjects and 44 female subjects with connective tissue disorders. An increased mean filtration rate was found in 14 subjects with rheumatoid arthritis. In 20 subjects with systemic lupus erythematosus and 10 subjects with scleroderma no such generalised increase in filtration rates was seen, but isolated cases had very high filtration rates, suggesting a more heterogeneous physiological disturbance. Increased filtration was not associated with the presence of oedema. This confirms doubts raised by other workers about the importance of filtration in the genesis of clinical oedema. Images PMID:6476914

  1. Gut microbiome compositional and functional differences between tumor and non-tumor adjacent tissues from cohorts from the US and Spain

    PubMed Central

    Allali, Imane; Delgado, Susana; Marron, Pablo Isidro; Astudillo, Aurora; Yeh, Jen Jen; Ghazal, Hassan; Amzazi, Saaïd; Keku, Temitope; Azcarate-Peril, M Andrea

    2015-01-01

    Colorectal cancer (CRC) is the third most common cancer in the world and the second leading cause of cancer deaths in the US and Spain. The molecular mechanisms involved in the etiology of CRC are not yet elucidated due in part to the complexity of the human gut microbiota. In this study, we compared the microbiome composition of 90 tumor and matching adjacent tissue (adjacent) from cohorts from the US and Spain by 16S rRNA amplicon sequencing in order to determine the impact of the geographic origin on the CRC microbiome. Data showed a significantly (P < 0.05) higher Phylogenetic Diversity (PD) for the US (PD Adjacent = 26.3 ± 5.3, PD Tumor = 23.3 ± 6.2) compared to the Spanish cohort (PD Adjacent = 18.9 ± 5.9, PD Tumor = 18.7 ± 6.6) while no significant differences in bacterial diversity were observed between tumor and adjacent tissues for individuals from the same country. Adjacent tissues from the Spanish cohort were enriched in Firmicutes (SP = 43.9% and US = 22.2%, P = 0.0001) and Actinobacteria (SP = 1.6% and US = 0.5%, P = 0.0018) compared to US adjacent tissues, while adjacent tissues from the US had significantly higher abundances of Fusobacteria (US = 8.1% and SP = 1.5%, P = 0.0023) and Sinergistetes (US = 0.3% and SP = 0.1%, P = 0.0097). Comparisons between tumor and adjacent tissues in each cohort identified the genus Eikenella significantly over represented in US tumors (T = 0.024% and A = 0%, P = 0.03), and the genera Fusobacterium (T = 10.4% and A = 1.5%, P = <0.0001), Bulleida (T = 0.36% and A = 0.09%, P = 0.02), Gemella (T = 1.46% and A = 0.19%, P = 0.03), Parvimonas (T = 3.14% and A = 0.86%, P = 0.03), Campylobacter (T = 0.15% and A = 0.008%, P = 0.047), and Streptococcus (T = 2.84% and A = 2.19%, P = 0.05) significantly over represented in Spanish tumors. Predicted metagenome functional content from 16S rRNA surveys showed that bacterial motility proteins and proteins involved in flagellar assembly were over represented in adjacent tissues

  2. 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.

  3. 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

  4. Can Breast Tumors Affect the Oxidative Status of the Surrounding Environment? A Comparative Analysis among Cancerous Breast, Mammary Adjacent Tissue, and Plasma

    PubMed Central

    Panis, C.; Victorino, V. J.; Herrera, A. C. S. A.; Cecchini, A. L.; Simão, A. N. C.; Tomita, L. Y.; Cecchini, R.

    2016-01-01

    In this paper, we investigated the oxidative profile of breast tumors in comparison with their normal adjacent breast tissue. Our study indicates that breast tumors present enhanced oxidative/nitrosative stress, with concomitant augmented antioxidant capacity when compared to the adjacent normal breast. These data indicate that breast cancers may be responsible for the induction of a prooxidant environment in the mammary gland, in association with enhanced TNF-α and nitric oxide. PMID:26697139

  5. 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

  6. Discovery and verification of protein differences between Er positive/Her2/neu negative breast tumor tissue and matched adjacent normal breast tissue.

    PubMed

    Weitzel, Lindsay-Rae B; Byers, Tim; Allen, Jenna; Finlayson, Christina; Helmke, Steve M; Hokanson, John E; Hunsucker, Stephen W; Murphy, James R; Newell, Keri; Queensland, Kelly M; Singh, Meenakshi; Wischmeyer, Paul E; Duncan, Mark W; Elias, Anthony

    2010-11-01

    This study was designed to quantify and identify differences in protein levels between tumor and adjacent normal breast tissue from the same breast in 18 women with stage I/II ER positive/Her2/neu negative invasive breast cancer. Eighteen separate difference gel electrophoresis (DIGE) gels were run (1 gel per patient). Relative quantification was based on DIGE analysis. After excision and tryptic digestion, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and peptide mass mapping were used to identify protein spots. Two hundred and forty-three spots were differentially abundant between normal and cancer tissues. Fifty spots were identified: 41 were over abundant and nine were less abundant in cancers than in normal breast tissue. Western blotting provided independent confirmation for three of the most biologically and statistically interesting proteins. All 18 gels were replicated by another technician and 32% of the differentially abundant proteins were verified by the duplicate analysis. Follow-up studies are now examining these proteins as biomarkers in blood. PMID:20087651

  7. Prostaglandins of the E-series inhibit connective tissue proliferation in the liver wound of the rat.

    PubMed

    Arend, A; Aunapuu, M; Masso, R; Selstam, G

    2005-03-01

    The present study was undertaken to relate wound healing of an internal organ to prostaglandins of the E and F series. A small liver wound was induced by a galvanic cauter via the abdominal route under general anesthesia and prostaglandin E1, E2 and F2alpha were injected twice daily at a dose of 250 microg/kg. Proliferation of the connective tissue in the liver wound was estimated morphometrically 6 days after liver wound infliction. Levels of prostaglandins E2 and F2alpha were measured in the liver wound as well as in normal liver tissue from adjacent lobes using radioimmunoassay. The results show that exogenous prostaglandins of the E-series suppress connective tissue proliferation. Three minutes after the last prostaglandin E2 injection, high prostaglandin concentrations were measured both in the liver wound and in the liver tissue of the adjacent lobe. Prostaglandin F2alpha injections had no effect on wound healing. We believe that the rat thermic liver wound model can be used for different studies on wound healing mechanisms and that prostaglandins of the E-series are involved in wound healing in the specific time period studied. PMID:15835401

  8. Higher FOXP3-TSDR demethylation rates in adjacent normal tissues in patients with colon cancer were associated with worse survival

    PubMed Central

    2014-01-01

    Background The influence of natural regulatory T cells (nTregs) on the patients with colon cancer is unclear. Demethylated status of the Treg-specific demethylated region (TSDR) of the FOXP3 gene was reported to be a potential biomarker for the identification of nTregs. Methods The demethylation rate of the TSDR (TSDR-DMR) was calculated by using methylation-specific quantitative polymerase chain reaction (MS-qPCR) assay. The expression of TSDR-DMR and FOXP3 mRNA was investigated in various colorectal cancer cell lines. A total of 130 colon carcinoma samples were utilized to study the DMR at tumor sites (DMRT) and adjacent normal tissue (DMRN). The correlations between DMRs and clinicopathological variables of patients with colon cancer were studied. Results The TSDR-DMRs varied dramatically among nTregs (97.920 ± 0.466%) and iTregs (3.917 ± 0.750%). Significantly, DMRT (3.296 ± 0.213%) was higher than DMRN (1.605 ± 0.146%) (n = 130, p = 0.000). Higher DMRN levels were found in female patients (p = 0.001) and those with distant metastases (p = 0.017), and were also associated with worse recurrence-free survival in non-stage IV patients (low vs. high, p = 0.022). However, further Cox multivariate analysis revealed that the FOXP3-TSDR status does not have prognostic value. Conclusion MS-qPCR assays of FOXP3-TSDR can efficiently distinguish nTregs from non-nTregs. Abnormal recruitment of nTregs occurs in the local tumor microenvironment. Infiltration of tissue-resident nTregs may have a negative role in anti-tumor effects in patients with colon cancer; however, this role is limited and complicated. PMID:24938080

  9. [Microflora in patients with systemic connective tissue diseases].

    PubMed

    Romanov, V A; Shilkina, N P; Gul'neva, M Iu; Ivanov, D V

    2008-01-01

    The study of microflora of skin, mucous tunic of nose and mouth, and the quantitative and qualitative structure of the intestinal and urinal microflora in cases of systemic connective tissues diseases, are reproduced. The decrease of the dominant state of typical representatives, and the increase of the role of pseudopathogenic bacteria in various biotypes, were observed. The frequency of S. aureus detection increased in skin, mucous tunic of nose and mouth. Pseudopathogenic microbes acquired greater significance in the forming of microbiocenosis of intestine, while the number of E. coli, Bifidobacterium and Lactobacterium decreased. The frequency of detection of microbes in urine decreased. The comparative analyses of the microflora in patients with systemic lupus erythromatosis and progressive systemic sclerosis demonstrated the common peculiarities for microflora character change. PMID:18488449

  10. 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

  11. The effect of Tookad-mediated photodynamic ablation of the prostate gland on adjacent tissues - in vivo study in a canine model

    PubMed Central

    Huang, Zheng; Chen, Qun; Dole, Kenneth C.; Barqawi, Al B.; Chen, Yang K.; Blanc, Dominique; Wilson, Brian C.; Hetzel, Fred W.

    2008-01-01

    Summary Photodynamic therapy (PDT) mediated with vascular acting photosensitizer Tookad (pd-bacteriopheophorbide) was investigated as an alternative modality for treating prostate cancer. Photodynamic effects on the prostate gland and its adjacent tissues were evaluated in a canine model. Interstitial prostate PDT was performed by irradiating individual lobes with a cylindrical diffuser fiber at various drug/light doses. The sensitivity of the adjacent tissues to Tookad PDT was determined by directly irradiating the surface of the bladder, colon, abdominal muscle and pelvic plexus with a microlens fiber at various drug/light doses. The prostate and adjacent tissues were harvested one-week after the treatment and subjected to histopathological examination. PDT-induced prostate lesions were characterized by marked hemorrhagic necrosis. The bladder, colon, abdominal muscle and pelvic plexus appeared to be sensitive to PDT although the Tookad PDT-induced responses in these tissues were minimal compared to that of the prostate gland at the same dose levels. Nevertheless, the protection of the adjacent tissues should be taken into consideration during the total prostate ablation process due to their sensitivity to PDT. The sensitivity of the prostatic urethra is worth further investigation. Direct intraurethral irradiation might provide an ideal means to determine the sensitivity of the prostatic urethra and might lead to transurethral PDT protocols for the management of benign prostatic hyperplasia. PMID:18046488

  12. Connective tissue adaptations in the fingers of performance sport climbers.

    PubMed

    Schreiber, Tonja; Allenspach, Philippe; Seifert, Burkhardt; Schweizer, Andreas

    2015-01-01

    This study investigates the changes of the connective tissue in the fingers of performance sport climbers resulting after a minimum of 15 years of climbing. Evaluation was performed by ultrasonography on the palmar side of the fingers (Dig) II-V to measure the thickness of the A2 and A4 annular pulleys, the flexor digitorum superficialis (FDS) and profundus (FDP) tendons and the palmar plates (PP's) of the proximal interphalangeal (PIP) as well as distal interphalangeal (DIP) joint in sagittal and axial direction. Totally, 31 experienced male sport climbers (mean age 37y, 30-48y grade French scale median 8b, range 7b+ to 9a+) participated in the study. The control-group consisted of 20 male non-climbers (age 37y, 30-51y). The A2 and A4 pulleys in climbers were all significantly thicker (A2 Dig III 62%, Dig IV 69%; A4 Dig III 69%, Dig IV 76%) as compared to non-climbers pulleys. All PP's of the DIP joints were also significantly thicker, particularly at Dig III and IV (76 and 67%), whereas the PP's at PIP joints were only scarce significant for three joints. Differences of the diameter of the flexor tendons were less distinct (1-21%) being significant only over the middle phalanx. High load to the fingers of rock climbers after a minimum of 15 years of climbing years induced considerable connective tissue adaptions in the fingers, most distinct at the flexor tendon pulleys and joint capsule (PP) of the DIP joints and well detectable by ultrasound. PMID:26267120

  13. Management of interstitial lung disease associated with connective tissue disease.

    PubMed

    Mathai, Stephen C; Danoff, Sonye K

    2016-01-01

    The lung is a common site of complications of systemic connective tissue disease (CTD), and lung involvement can present in several ways. Interstitial lung disease (ILD) and pulmonary hypertension are the most common lung manifestations in CTD. Although it is generally thought that interstitial lung disease develops later on in CTD it is often the initial presentation ("lung dominant" CTD). ILD can be present in most types of CTD, including rheumatoid arthritis, scleroderma, systemic lupus erythematosus, polymyositis or dermatomyositis, Sjögren's syndrome, and mixed connective tissue disease. Despite similarities in clinical and pathologic presentation, the prognosis and treatment of CTD associated ILD (CTD-ILD) can differ greatly from that of other forms of ILD, such as idiopathic pulmonary fibrosis. Pulmonary hypertension (PH) can present as a primary vasculopathy in pulmonary arterial hypertension or in association with ILD (PH-ILD). Therefore, detailed history, physical examination, targeted serologic testing, and, occasionally, lung biopsy are needed to diagnose CTD-ILD, whereas both non-invasive and invasive assessments of pulmonary hemodynamics are needed to diagnose pulmonary hypertension. Immunosuppression is the mainstay of treatment for ILD, although data from randomized controlled trials (RCTs) to support specific treatments are lacking. Furthermore, treatment strategies vary according to the clinical situation-for example, the treatment of a patient newly diagnosed as having CTD-ILD differs from that of someone with an acute exacerbation of the disease. Immunosuppression is indicated only in select cases of pulmonary arterial hypertension related to CTD; more commonly, selective pulmonary vasodilators are used. For both diseases, comorbidities such as sleep disordered breathing, symptoms of dyspnea, and cough should be evaluated and treated. Lung transplantation should be considered in patients with advanced disease but is not always feasible because

  14. Connective tissue progenitor cell growth characteristics on textured substrates.

    PubMed

    Mata, Alvaro; Boehm, Cynthia; Fleischman, Aaron J; Muschler, George F; Roy, Shuvo

    2007-01-01

    Growth characteristics of human connective tissue progenitor (CTP) cells were investigated on smooth and textured substrates, which were produced using MEMS (microelectromechanical systems) fabrication technology. Human bone marrow derived cells were cultured for 9 days under conditions promoting osteoblastic differentiation on polydimethylsiloxane (PDMS) substrates comprising smooth (non-patterned) surfaces (SMOOTH), 4 different cylindrical post micro-textures (POSTS) that were 7-10 microm high and 5, 10, 20, and 40 microm diameter, respectively, and channel micro-textures (CHANNELS) with curved cross-sections that were 11 microm high, 45 microm wide, and separated by 5 microm wide ridges. Standard glass-tissue culture surfaces were used as controls. Micro-textures resulted in the modification of CTP morphology, attachment, migration, and proliferation characteristics. Specifically, cells on POSTS exhibited more contoured morphology with closely packed cytoskeletal actin microfilaments compared to the more random orientation in cells grown on SMOOTH. CTP colonies on 10 gm-diameter POSTS exhibited higher cell number than any other POSTS, and a significant increase in cell number (442%) compared to colonies on SMOOTH (71%). On CHANNELS, colonies tended to be denser (229%) than on POSTS (up to 140% on 10 microm POSTS), and significantly more so compared to those on SMOOTH (104%). PMID:18019838

  15. Anatomy of the Visual Word form Area: Adjacent Cortical Circuits and Long-Range White Matter Connections

    ERIC Educational Resources Information Center

    Yeatman, Jason D.; Rauschecker, Andreas M.; Wandell, Brian A.

    2013-01-01

    Circuitry in ventral occipital-temporal cortex is essential for seeing words. We analyze the circuitry within a specific ventral-occipital region, the visual word form area (VWFA). The VWFA is immediately adjacent to the retinotopically organized VO-1 and VO-2 visual field maps and lies medial and inferior to visual field maps within motion…

  16. Biomarkers in connective tissue disease-associated interstitial lung disease.

    PubMed

    Bonella, Francesco; Costabel, Ulrich

    2014-04-01

    This article reviews major biomarkers in serum and bronchoalveolar lavage fluid (BALF) with respect to their diagnostic and prognostic value in connective tissue disease-associated interstitial lung disease (CTD-ILD). In some CTD such as systemic sclerosis (SSc), the incidence of ILD is up to two-third of patients, and currently ILD represents the leading cause of death in SSc. Because of the extremely variable incidence and outcome of ILD in CTD, progress in the discovery and validation of biomarkers for diagnosis, prognosis, patients' subtyping, response to treatment, or as surrogate endpoints in clinical trials is extremely important. In contrast to idiopathic interstitial pneumonias, autoantibodies play a crucial role as biomarkers in CTD-ILD because their presence is strictly linked to the pathogenesis and tissue damage. Patterns of autoantibodies, for instance, anticitrullinated peptide antibodies in rheumatoid arthritis or aminoacyl-tRNA synthetases (ARS) in polymyositis/dermatomyositis, have been found to correlate with the presence and occasionally with the course of ILD in CTD. Besides autoantibodies, an increase in serum or BALF of a biomarker of pulmonary origin may be able to predict or reflect the development of fibrosis, the impairment of lung function, and ideally also the prognosis. Promising biomarkers are lung epithelium-derived proteins such as KL-6 (Krebs von den Lungen-6), SP-D (surfactant protein-D), SP-A (surfactant protein-A), YKL-40 (chitinase-3-like protein 1 [CHI3L1] or cytokines such as CCL18 [chemokine (C-C) motif ligand 18]). In the future, genetic/epigenetic markers, such as human leukocyte antigen (HLA) haplotypes, single nucleotide polymorphisms, and micro-RNA, may help to identify subtypes of patients with different needs of management and treatment strategies. PMID:24668534

  17. Prostate Field Cancerization: Deregulated Expression of Macrophage Inhibitory Cytokine 1 (MIC-1) and Platelet Derived Growth Factor A (PDGF-A) in Tumor Adjacent Tissue

    PubMed Central

    Jones, Anna C.; Shoshan, Dor S.; Fischer, Edgar G.; Trujillo, Kristina A.; Bisoffi, Marco

    2015-01-01

    Prostate field cancerization denotes molecular alterations in histologically normal tissues adjacent to tumors. Such alterations include deregulated protein expression, as we have previously shown for the key transcription factor early growth response 1 (EGR-1) and the lipogenic enzyme fatty acid synthase (FAS). Here we add the two secreted factors macrophage inhibitory cytokine 1 (MIC-1) and platelet derived growth factor A (PDGF-A) to the growing list of protein markers of prostate field cancerization. Expression of MIC-1 and PDGF-A was measured quantitatively by immunofluorescence and comprehensively analyzed using two methods of signal capture and several groupings of data generated in human cancerous (n = 25), histologically normal adjacent (n = 22), and disease-free (n = 6) prostate tissues. A total of 208 digitized images were analyzed. MIC-1 and PDGF-A expression in tumor tissues were elevated 7.1x to 23.4x and 1.7x to 3.7x compared to disease-free tissues, respectively (p<0.0001 to p = 0.08 and p<0.01 to p = 0.23, respectively). In support of field cancerization, MIC-1 and PDGF-A expression in adjacent tissues were elevated 7.4x to 38.4x and 1.4x to 2.7x, respectively (p<0.0001 to p<0.05 and p<0.05 to p = 0.51, respectively). Also, MIC-1 and PDGF-A expression were similar in tumor and adjacent tissues (0.3x to 1.0x; p<0.001 to p = 0.98 for MIC-1; 0.9x to 2.6x; p<0.01 to p = 1.00 for PDGF-A). All analyses indicated a high level of inter- and intra-tissue heterogeneity across all types of tissues (mean coefficient of variation of 86.0%). Our data shows that MIC-1 and PDGF-A expression is elevated in both prostate tumors and structurally intact adjacent tissues when compared to disease-free specimens, defining field cancerization. These secreted factors could promote tumorigenesis in histologically normal tissues and lead to tumor multifocality. Among several clinical applications, they could also be exploited as indicators of disease in false negative

  18. Anatomy of the visual word form area: adjacent cortical circuits and long-range white matter connections

    PubMed Central

    Yeatman, Jason D.; Rauschecker, Andreas M.; Wandell, Brian A.

    2012-01-01

    Circuitry in ventral occipital-temporal cortex is essential for seeing words. We analyze the circuitry within a specific ventral-occipital region, the visual word form area (VWFA). The VWFA is immediately adjacent to the retinotopically organized VO-1 and VO-2 visual field maps and lies medial and inferior to visual field maps within motion selective human cortex. Three distinct white matter fascicles pass within close proximity to the VWFA: (1) the inferior longitudinal fasciculus, (2) the inferior frontal occipital fasciculus and (3) the vertical occipital fasciculus. The vertical occipital fasciculus terminates in or adjacent to the functionally defined VWFA voxels in every individual. The vertical occipital fasciculus projects dorsally to language and reading related cortex. The combination of functional responses from cortex and anatomical measures in the white matter provides an overview of how the written word is encoded and communicated along the ventral occipital-temporal circuitry for seeing words. PMID:22632810

  19. 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.

  20. The diagnosis and classification of mixed connective tissue disease.

    PubMed

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

    2014-01-01

    The term "mixed connective tissue disease" (MCTD) concerns a systemic autoimmune disease typified by overlapping features between two or more systemic autoimmune diseases and the presence of antibodies against the U1 small nuclear ribonucleoprotein autoantigen (U1snRNP). Since the first description of this condition in 1972, the understanding of clinical manifestations and long-term outcome of MCTD have significantly advanced. Polyarthritis, Raynaud's phenomenon, puffy fingers, lung involvement and esophageal dysmotility are the most frequently reported symptoms among the different cohorts during the course of the disease. Moreover, in recent years a growing interest has been focused on severe organ involvement such as pulmonary arterial hypertension and interstitial lung disease which can accrue during the long-term follow-up and can still significantly influence disease prognosis. Over the last years, significant advances have been made also in disease pathogenesis understanding and a central pathogenetic role of anti-U1RNP autoantibodies has clearly emerged. Although controversies on disease definition and classification still persist, MCTD identifies a group of patients in whom increased surveillance for specific manifestations and prognostic stratification became mandatory to improve patient's outcomes. PMID:24461387

  1. 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

  2. The role of intramuscular connective tissue in meat texture.

    PubMed

    Nishimura, Takanori

    2010-02-01

    The structure, composition and amount of intramuscular connective tissue (IMCT) vary tremendously between muscles, species and breeds, and certainly contribute to meat texture. With animal growth, collagen crosslinks become more stable, and the structural integrity of IMCT increases. These changes increase the mechanical properties of IMCT, contributing to the toughening of meat. Intramuscular fat deposits, mainly in the perimysium between muscle fiber bundles, result in marbling. This causes the remodeling of IMCT structures and reduces the mechanical strength of IMCT, contributing to the tenderization of beef. The IMCT has been thought to be rather immutable compared to myofibrils during postmortem ageing of meat. However, recent studies have shown the disintegration of IMCT during postmortem ageing of meat and its relationship to tenderization of raw meat, although its contribution to cooked meat is still controversial. Given the large influence of IMCT on meat texture, further elucidations of molecular mechanisms which change the structural integrity of IMCT during chronological ageing of animals and postmortem ageing of meat are needed. PMID:20163668

  3. 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.

  4. Treatment of pulmonary arterial hypertension in connective tissue disease.

    PubMed

    Grünig, Ekkehard

    2012-05-28

    Pulmonary arterial hypertension (PAH) is a group of distinct disorders that includes idiopathic PAH (IPAH), familial PAH and PAH associated with other conditions (APAH) such as connective tissue disease (CTD-APAH) or congenital heart disease. PAH is characterized by increased pulmonary arterial pressure and pulmonary vascular resistance. If left untreated, PAH can lead to right heart failure and premature death. CTD-APAH represents an important clinical subgroup of APAH that has a higher risk of death than IPAH. The European treatment guidelines advocate the use of PAH-targeted therapies including bosentan, ambrisentan, sildenafil, inhaled iloprost, intravenous epoprostenol (I-A recommendations), tadalafil or treprostinil (I-B recommendations) for patients in WHO functional class II-III. Not all randomized clinical studies of the approved PAH-targeted therapies have included patients with CTD-APAH. The purpose of this review is to describe the clinical characteristics of CTD-APAH and discuss the approved pharmacological treatments, with a focus on data specific to this subgroup where possible. PMID:22621693

  5. Laparoscopic Antireflux Surgery in Patients with Connective Tissue Diseases.

    PubMed

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

    2016-04-01

    Different connective tissue diseases (CTDs), such as dermatomyositis, mixed CTD, rheumatoid arthritis, polymyositis, lupus, and Behçet's, may affect the esophagus, impairing its motor function. The muscular atrophy and fibrosis caused by the autoimmune vasculitis and neuronal dysfunction affect the esophageal body and the lower esophageal sphincter, leading to a clinical presentation of dysphagia and gastroesophageal reflux disease (GERD). The belief that the impaired esophageal motility may negatively affect surgical outcome has led to the common recommendation of avoiding laparoscopic antireflux surgery (LARS) for fear of creating or worsening dysphagia. This review focuses on the evaluation of the outcome of LARS in patients with CTD. Specifically, this review shows that the literature on LARS and CTDs is scarce and most studies have a small number of patients and a short follow-up. Furthermore, a subanalysis of the outcome based on the type of CTD or the manometric profile is still elusive. In the setting of these limitations, it appears that results are good and comparable to those of patients with GERD and without a CTD. Morbidity and mortality are insignificant even considering the systemic manifestations of the CTD. LARS should not be denied to patients with CTD and GERD. PMID:27027697

  6. 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

  7. Identification of reliable reference genes for quantitative gene expression studies in oral squamous cell carcinomas compared to adjacent normal tissues in the F344 rat model.

    PubMed

    Peng, Xinjian; McCormick, David L

    2016-08-01

    Oral squamous cell carcinomas (OSCCs) induced in F344 rats by 4-nitroquinoline-1-oxide (4-NQO) demonstrate considerable phenotypic similarity to human oral cancers and the model has been widely used for carcinogenesis and chemoprevention studies. Molecular characterization of this model needs reliable reference genes (RGs) to avoid false- positive and -negative results for proper interpretation of gene expression data between tumor and adjacent normal tissues. Microarray analysis of 11 pairs of OSCC and site-matched phenotypically normal oral tissues from 4-NQO-treated rats identified 10 stably expressed genes in OSCC compared to adjacent normal tissues (p>0.5, CV<15%) that could serve as potential RGs in this model. The commonly used 27 RGs in the rat were also analyzed based on microarray data and most of them were found unsuitable for RGs in this model. Traditional RGs such as ACTB and GAPDH were significantly altered in OSCC compared to adjacent normal tissues (p<0.01, n=11); however, the Hsp90ab1 was ranked as the best RG candidate and the combination of Hsp90ab1 and HPRT1 was identified by NormFinder to be a superior reference for gene normalization among the commonly used RGs. This result was also validated by RT-PCR based on the selected top RG candidate pool. These data suggest that there are no common RGs suitable for different models and RG(s) should be identified before gene expression analysis. We successfully identified Hsp90ab1 as a stable RG in 4-NQO-induced OSCC compared to adjacent normal tissues in F344 rats. The combination of two stably expressed genes may be a better option for gene normalization in tissue samples. PMID:27375172

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

    PubMed Central

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

    2015-01-01

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

  9. [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. PMID:26973193

  10. 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.

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

    PubMed Central

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

    2009-01-01

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

  12. 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

  13. 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. PMID:25836642

  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. PMID:26142172

  15. The saddle connective tissue graft: a periodontal plastic surgery technique to obtain soft tissue coronal gain on immediate implants. A case report.

    PubMed

    González, David; Cabello, Gustavo; Olmos, Gema; Niñoles, Carlos L

    2015-01-01

    Based on recent studies regarding the advantages of flapless immediate implants on the maintenance of the soft tissue architecture (especially at papillae level) in those situations where it is necessary to extract an anterior tooth, this case report describes a clinical procedure designed to replace a hopeless central incisor (2.1) showing root resorption adjacent to an implant-supported crown (1.1), whose gingival margin is 2 mm coronal regarding the hopeless tooth to be replaced. After the extraction of the hopeless tooth (2.1), a flapless immediate implant was placed. The implant-bone gap was then filled with bone substitute and a palatal connective tissue graft was placed ad modum saddle extending at buccal level from apical to the mucogingival line, sealing the socket and extending until 6 mm at palatal level ad modum saddle. This procedure allowed symmetry of the soft tissue margins between the two implants (1.1 and 2.1) to be obtained as well as the preservation of the inter-implant papillae (1.1). PMID:26171446

  16. 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.

  17. 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

  18. Metal debris concentrations in soft tissues adjacent to loosened femoral stems is higher in uncemented than cemented implants

    PubMed Central

    2014-01-01

    Background There are still many questions related to aseptic femoral stem loosening. Systemic and local immune responses to the implanted “foreign body” is one of the reasons for loosening. The purpose of the study was to measure metal ion concentration (Ti, Co, Cr, Mo, Ni, Al) around loosened femoral stems and compare their levels around uncemented and cemented implants. Methods This paper reports 50 hips operated for isolated stem loosening, in 50 patients at the mean age of 57 years (from 21 to 87). There were 25 cemented (Co,Cr29,Mo,Ni) and 25 uncemented (Ti, Al) stems. The mean follow-up from primary hip replacement to revision was 10.1 years (from 0.5 to 17). During the procedure, scar tissue around the stem was taken for analysis of metal ions. Results The concentrations of titanium and aluminium in soft tissues around uncemented loosened stems were higher than cemented ones (p < 0.001, p < 0.001 respectively). However, no statistically significant differences were observed between both types of stems in terms of ions of the metal of which cemented implants had been made of (Co, Cr, Mo, Ni). Conclusions In soft tissue around a loosened stem, the concentrations of metal ions from implants are much higher in case of uncemented stems than of cemented ones. Metal ions from vitalium femoral heads were found around uncemented stems in similar values to cemented streams. PMID:25098913

  19. 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

  20. 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

  1. 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. PMID:23801584

  2. 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

  3. Quantitative analysis of the reconstruction errors of the currently popular algorithm of magnetic resonance electrical property tomography at the interfaces of adjacent tissues.

    PubMed

    Duan, Song; Xu, Chao; Deng, Guanhua; Wang, Jiajia; Liu, Feng; Xin, Sherman Xuegang

    2016-06-01

    This work quantitatively analyzed the reconstruction errors (REs) of electrical property (EP) images using a currently popular algorithm of magnetic resonance electrical property tomography (MREPT), which occurred along the tissue interfaces. Transmitted magnetic fields B1+ were acquired at 3 T using a birdcage coil loaded with a phantom consisting of various adjacent tissues. Homogeneous Helmholtz was employed to calculate the EP maps by Laplacian computation of central differences. The maps of absolute REs (aREs) and relative REs (rREs) were calculated. The maximum and mean rREs, in addition to rRE distributions at the interfaces, were presented. Reconstructed EP maps showed various REs along different interface boundaries. Among all the investigated tissue interfaces, the kidney-fat interface presented the maximum mean rREs for both conductivity and relative permittivity. The minimum mean rRE of conductivity was observed at the spleen-muscle interface, and the minimum mean rRE of relative permittivity was detected along the lung-heart interface. The mean rREs ranged from 0.3986 to 36.11 for conductivity and 0.2218 to 11.96 for relative permittivity. Overall, this research indicates that different REs occur at various tissue boundaries, as shown by the currently popular algorithm of MREPT. Thus, REs should be considered when applying MREPT to reconstruct the EP distributions inside the human body. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27037715

  4. Adipose tissue and sustainable development: a connection that needs protection

    PubMed Central

    Tremblay, Angelo; Picard-Deland, Éliane; Panahi, Shirin; Marette, André

    2015-01-01

    Obesity is generally considered as an excess body fat that increases the risk to develop ergonomic, metabolic, and psychosocial problems. As suggested in this paper, body fat gain is also a protective adaptation that prevents body lipotoxicity, contributes to the secretion of molecules involved in metabolic regulation, and dilutes lipid soluble persistent organic pollutants. Recent literature shows that this protective role of adipose tissue is more solicited in a modern context in which unsuspected factors can affect energy balance to a much greater extent than what is generally perceived by health care professionals. These factors include short sleep duration, demanding mental work, and chemical pollution whose impact is more detectable in a context dominated by economic productivity and competitiveness. Since these factors might also include the increase in atmospheric CO2, it is likely that obesity prevention will need the support of a promotion in sustainable development, whether it is for human health, and well-being or global ecological protection. PMID:26074821

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

    PubMed Central

    2008-01-01

    Integrity of the extracellular matrix (ECM) is essential for maintaining the normal structure and function of connective tissues. ECM is secreted locally by cells and organized into a complex meshwork providing physical support to cells, tissues, and organs. Initially thought to act only as a scaffold, the ECM is now known to provide a myriad of signals to cells regulating all aspects of their phenotype from morphology to differentiation. Matricellular proteins are a class of ECM related molecules defined through their ability to modulate cell–matrix interactions. Matricellular proteins are expressed at high levels during development, but typically only appear in postnatal tissue in wound repair or disease, where their levels increase substantially. Members of the CCN family, tenascin-C, osteopontin, secreted protein acidic rich in cysteine (SPARC), bone sialoprotein, thrombospondins, and galectins have all been classed as matricellular proteins. Periostin, a 90 kDa secreted homophilic cell adhesion protein, was recently added to matricellular class of proteins based on its expression pattern and function during development as well as in wound repair. Periostin is expressed in connective tissues including the periodontal ligament, tendons, skin and bone, and is also prominent in neoplastic tissues, cardiovascular disease, as well as in connective tissue wound repair. This review will focus on the functional role of periostin in tissue physiology. Fundamentally, it appears that periostin influences cell behaviour as well as collagen fibrillogenesis, and therefore exerts control over the structural and functional properties of connective tissues in both health and disease. Periostin is a novel matricellular protein with close homology to Drosophila fasciclin 1. In this review, the functional role of periostin is discussed in the context of connective tissue physiology, in development, disease, and wound repair. PMID:18642132

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

    PubMed

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

    2016-06-17

    Connective tissue growth factor (CTGF) has been reported in gastric adenocarcinoma and in carcinoid tumors. The aim of this study was to explore a possible link between CTGF and gastrin in gastric epithelial cells and to study the role of CTGF in gastrin induced migration and invasion of AGS-GR cells. The effects of gastrin were studied using RT-qPCR, Western blot and assays for migration and invasion. We report an association between serum gastrin concentrations and CTGF abundancy in the gastric corpus mucosa of hypergastrinemic subjects and mice. We found a higher expression of CTGF in gastric mucosa tissue adjacent to tumor compared to normal control tissue. We showed that gastrin induced expression of CTGF in gastric epithelial AGS-GR cells via MEK, PKC and PKB/AKT pathways. CTGF inhibited gastrin induced migration and invasion of AGS-GR cells. We conclude that CTGF expression is stimulated by gastrin and involved in remodeling of the gastric epithelium. PMID:27179776

  7. 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

  8. 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

  9. 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.

  10. Phototherapy, photodynamic therapy and photophoresis in the treatment of connective-tissue diseases: a review.

    PubMed

    Gordon Spratt, E A; Gorcey, L V; Soter, N A; Brauer, J A

    2015-07-01

    Connective-tissue disorders, which include lupus erythematosus, morphoea/scleroderma and dermatomyositis, are characterized by cutaneous manifestations that are sometimes resistant to conventional therapy. Light treatments, which include phototherapy, photodynamic therapy (PDT) and photopheresis, are routinely utilized in the treatment of dermatological conditions and may provide unique mechanisms of action in the treatment of these connective-tissue disorders. The objective of this study is to conduct a review of the literature that describes the use of phototherapy, PDT and photopheresis in the treatment of lupus erythematosus, morphoea/scleroderma and dermatomyositis. A MEDLINE search was conducted to find articles that discuss treatment of connective-tissue diseases with light therapies and more than 30 publications that discuss light therapy for these diseases were identified. These range in design from case reports to randomized, prospective trials. Study outcomes and details were summarized and presented within each connective-tissue disease by light therapy modality, which includes phototherapy, PDT and photopheresis. Although there is a known association between photosensitivity and connective-tissue diseases, light therapies, when used appropriately, may be legitimate therapeutic options for recalcitrant cutaneous manifestations in lupus erythematosus, morphoea/scleroderma and dermatomyositis. PMID:25400115

  11. 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. PMID:26577892

  12. 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

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

    PubMed Central

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

    2015-01-01

    The diaphragm is an essential mammalian skeletal muscle, and defects in diaphragm development are the cause of congenital diaphragmatic hernias (CDH), 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), transient embryonic structures, are the source of the diaphragm’s muscle connective tissue, regulate muscle development, and their striking migration 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 and lead 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. PMID:25807280

  14. Comparison of heavy metal concentrations in tissues of red foxes from adjacent urban, suburban, and rural areas.

    PubMed

    Dip, R; Stieger, C; Deplazes, P; Hegglin, D; Müller, U; Dafflon, O; Koch, H; Naegeli, H

    2001-05-01

    The red fox (Vulpes vulpes) is a representative of the canid family with wide distribution in the Northern Hemisphere and Australia. The increasing utilization of urbanized habitats by red foxes prompted us to test whether this species may be used to monitor the presence of anthropogenic pollutants in cities or suburbs. For that purpose, we compared the concentrations of heavy metals (Cd, Pb, Cu, Zn) in foxes from urban, suburban, and rural areas within the municipality of Zürich (Switzerland). The kidney and liver of suburban and rural foxes contained the highest Cd concentrations, whereas urban foxes contained the highest Pb levels. In the kidney of suburban foxes, Cd concentrations increased from a median value of 0.73 mg/kg in juvenile animals to 1.82 mg/kg in adults. Similarly, the liver of suburban foxes contained increasing Cd levels from a median of 0.21 mg/kg in juvenile animals to 0.94 mg/kg in adults. An age-dependent storage of Cd was also found in foxes from the rural surroundings, but no such accumulation occurred in urban foxes from the city center, where even adult animals contained very low Cd levels. Conversely, foxes from the urban center were characterized by elevated Pb concentrations during the first 2 years of life, but this transient Pb accumulation was absent in suburban or rural animals. The liver of juvenile foxes contained a median Pb concentration of 0.99 mg/kg in the city compared to only 0.47 and 0.37 mg/kg in the suburban and rural area, respectively. Thus, we found that animals from separate environmental compartments contain different patterns of tissue residues, implying that red foxes may serve as a bioindicator species to detect certain toxic hazards in urbanized habitats. PMID:11525499

  15. Human lung and bladder carcinoma tumors as compared to their adjacent normal tissue have elevated AP-1 activity associated with the retinoblastoma gene promoter.

    PubMed

    Linardopoulos, S; Papadakis, E; Delakas, D; Theodosiou, V; Cranidis, A; Spandidos, D A

    1993-01-01

    Examination of the nucleotide sequence of the retinoblastoma (Rb) promoter revealed the presence of a DNA region highly homologous to the recognition site for the cellular transcription factor AP-1. A pair of complementary oligonucleotides containing the AP-1 site was synthesized and used in gel retardation assays to determine the role of the AP-1 protein in the regulation of the Rb gene expression. Using nuclear extracts from Hela cells as well as from lung and bladder tumors, we found specific binding of the AP-1 protein to this oligonucleotide. This binding is elevated in Hela cells, in 10/13 lung and 3/8 bladder tumors as compared to adjacent normal tissue. These results suggest that AP-1 could be implicated in Rb gene transcriptional regulation through its interaction with the AP-1 binding site of the Rb gene promoter. PMID:8476221

  16. 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.

  17. The cauliflower mosaic virus (CaMV) 35S promoter sequence alters the level and patterns of activity of adjacent tissue- and organ-specific gene promoters.

    PubMed

    Zheng, Xuelian; Deng, Wei; Luo, Keming; Duan, Hui; Chen, Yongqin; McAvoy, Richard; Song, Shuiqing; Pei, Yan; Li, Yi

    2007-08-01

    Here we report the effect of the 35S promoter sequence on activities of the tissue- and organ-specific gene promoters in tobacco plants. In the absence of the 35S promoter sequence the AAP2 promoter is active only in vascular tissues as indicated by expression of the AAP2:GUS gene. With the 35S promoter sequence in the same T-plasmid, transgenic plants exhibit twofold to fivefold increase in AAP2 promoter activity and the promoter becomes active in all tissue types. Transgenic plants hosting the ovary-specific AGL5:iaaM gene (iaaM coding an auxin biosynthetic gene) showed a wild-type phenotype except production of seedless fruits, whereas plants hosting the AGL5:iaaM gene along with the 35S promoter sequence showed drastic morphological alterations. RT-PCR analysis confirms that the phenotype was caused by activation of the AGL5:iaaM gene in non-ovary organs including roots, stems and flowers. When the pollen-, ovule- and early embryo-specific PAB5:barnase gene (barnase coding a RNase gene) was transformed, the presence of 35S promoter sequence drastically reduced transformation efficiencies. However, the transformation efficiencies were restored in the absence of 35S promoter, indicating that the 35S promoter might activate the expression of PAB5:barnase in non-reproductive organs such as calli and shoot primordia. Furthermore, if the 35S promoter sequence was replaced with the NOS promoter sequence, no alteration in AAP2, AGL5 or PAB5 promoter activities was observed. Our results demonstrate that the 35S promoter sequence can convert an adjacent tissue- and organ-specific gene promoter into a globally active promoter. PMID:17340093

  18. 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

  19. Evidence that cyclosporin A administration induces the formation of new cementum-like islets inside the gingival connective tissue.

    PubMed

    Ayanoglou, C M

    1998-04-01

    Two groups of 3 male Sprague-Dawley rats were given orally 30 mg/kg/d of vehicle (control group) or cyclosporin-A (experimental group) solution for 14 wk. The rats were anesthetized, tissues fixed by intracardiac perfusion of fixative solution and jaws dissected, demineralized, processed for Epon inclusion and cut by semi-thin serial sections. Histological examination revealed the presence of several islets located paravascularly inside the gingival connective tissue in the proximity of the root surfaces. The structure of these new cementum-like islets (NCLIs) was either compact and homogeneous or heterogeneous, but identical to that of the adjacent new cementum (NC) deposits. Histomorphometric evaluation indicated that the volume and the external surface of the NCLIs varied from 2354 to 679,497 micron 3 and from 465 to 47,517 micron 2, respectively. These observations (a) suggest that CsA stimulates possibly paravascular progenitor cells which secrete in situ a NC-like material and (b) provides further evidence about the high potential of CsA to induce NC formation. PMID:9651878

  20. Connective tissue disorders associated with vasculitis and vaso-occlusive disease of the hand.

    PubMed

    Michelotti, Brett; Rizzo, Marco; Moran, Steven L

    2015-02-01

    Hand ischemia caused by vasculitis is a secondary finding in many autoimmune processes. Many of these autoimmune diseases are managed primarily with medications that can prevent the development of occlusive disease, tissue ischemia, and tissue loss. Unfortunately several disease conditions can be recalcitrant to medical management and can result in ischemic changes within the hand, which may require operative intervention. This article briefly reviews the major connective tissue disorders associated with vasculitis and vaso-occlusive disease of the hand, including scleroderma, lupus, and Buerger disease, and their surgical treatment. PMID:25455357

  1. Elevated expression levels of androgen receptors and matrix metalloproteinase-2 and -9 in 30 cases of hepatocellular carcinoma compared with adjacent tissues as predictors of cancer invasion and staging

    PubMed Central

    ZHANG, YAN; SHEN, YUCHENG; CAO, BIN; YAN, AITING; JI, HAOMING

    2015-01-01

    The aim of the present study was to investigate the potential roles of the androgen receptor (AR) and matrix metalloproteinase (MMP)-2 and MMP-9 in hepatocellular carcinoma (HCC) tissues and whether their expression could be used as a predictor of the invasion and stage of cancer. The expression levels of AR, MMP-2 and MMP-9 in HCC tissues and tissues adjacent to the tumor were measured by immunohistochemical staining assay. The expression rates of AR, MMP-2 and MMP-9 in the HCC tissue were 76.67, 73.33 and 76.67%, respectively, all of which were significantly higher than those in the tissues adjacent to the tumor. The expression of these proteins represents the local invasion and stage. AR, MMP-2 and MMP-9 expression levels in HCC tissues have the potential to be employed as predictors of the progression of local cancer invasion and the tumor stage. PMID:25667651

  2. 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...

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

    PubMed Central

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

    2004-01-01

    Skeletal muscle includes satellite cells, which reside beneath the muscle fiber basal lamina and mainly represent committed myogenic precursor cells, and multipotent stem cells of unknown origin that are present in muscle connective tissue, express the stem cell markers Sca-1 and CD34, and can differentiate into different cell types. We tracked bone marrow (BM)-derived stem cells in both muscle connective tissue and satellite cell niches of irradiated mice transplanted with green fluorescent protein (GFP)-expressing BM cells. An increasing number of GFP+ mononucleated cells, located both inside and outside of the muscle fiber basal lamina, were observed 1, 3, and 6 months after transplantation. Sublaminal cells expressed unambiguous satellite cell markers (M-cadherin, Pax7, NCAM) and fused into scattered GFP+ muscle fibers. In muscle connective tissue there were GFP+ cells located close to blood vessels that expressed the ScaI or CD34 stem-cell antigens. The rate of settlement of extra- and intralaminal compartments by BM-derived cells was compatible with the view that extralaminal cells constitute a reservoir of satellite cells. We conclude that both muscle satellite cells and stem cell marker-expressing cells located in muscle connective tissue can derive from BM in adulthood. PMID:14982831

  4. Membranous glomerulonephritis in rheumatoid arthritis unrelated to gold, D-penicillamine or other connective tissue disease.

    PubMed

    Zarza, L P; Sanchez, E N; Acin, P A; Ara, J M; Baños, J G

    1996-07-01

    We report a 58-year-old woman with classical rheumatoid arthritis (RA) who developed a membranous glomerulonephritis (MGN). She had never been treated with gold or D-penicillamine; other connective tissue diseases as well as hepatitis B were excluded. We suggest that the responsible cause of MGN is RA. PMID:8853174

  5. 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. PMID:23803280

  6. 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.

  7. Mediastinal lymphadenopathy and pulmonary arterial hypertension in mixed connective tissue disease

    SciTech Connect

    Guit, G.L.; Shaw, P.C.; Ehrlich, J.; Kroon, H.M.; Oudkerk, M.

    1985-02-01

    A case of mixed connective tissue disease (MCTD) is presented in which mediastinal lymphadenopathy was the most prominent radiological finding detected by plain chest radiographs and computed tomography. Pulmonary arterial hypertension, which is a rare and often fatal complication of MCTD, also developed in this patient.

  8. 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.

  9. Extracellular Wound Matrices:A Novel Regenerative Tissue Matrix (RTM) Technology for Connective Tissue Reconstruction.

    PubMed

    Harper, John R; McQuillan, David J

    2007-06-01

    The restoration of structure, function, and physiology to damaged or missing tissue through the use of a regenerative tissue matrix (RTM) leads to regenerative healing rather than reparative scarring. While many processes exist to transform biologic materials into an extracellular matrix (ECM), only those that maintain the required structural and biochemical properties necessary to capture the intrinsic regenerative abilities of the body are suitable to produce an RTM. Histological examination using differential staining with hematoxylin and eosin stain or Verhoeff von Geisen stain of human biopsies of RTM obtained from 2 different abdominal surgery patients taken at 8- and 12 months were consistent with RTM remodeling into fascia-like tissue. A synopsis of recent studies on the use of the RTM GraftJacket® (Wright Medical Technologies, Memphis, Tenn) in successful closure of diabetic foot wounds is presented. Collectively, these reports indicate that LifeCell produced ECMs exemplified by GraftJacket exhibit the required clinical outcomes associated with an RTM. PMID:26110325

  10. 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

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

    PubMed Central

    2009-01-01

    Background Although the connective tissues forming the fascial planes of the back have been hypothesized to play a role in the pathogenesis of chronic low back pain (LBP), there have been no previous studies quantitatively evaluating connective tissue structure in this condition. The goal of this study was to perform an ultrasound-based comparison of perimuscular connective tissue structure in the lumbar region in a group of human subjects with chronic or recurrent LBP for more than 12 months, compared with a group of subjects without LBP. Methods In each of 107 human subjects (60 with LBP and 47 without LBP), parasagittal ultrasound images were acquired bilaterally centered on a point 2 cm lateral to the midpoint of the L2-3 interspinous ligament. The outcome measures based on these images were subcutaneous and perimuscular connective tissue thickness and echogenicity measured by ultrasound. Results There were no significant differences in age, sex, body mass index (BMI) or activity levels between LBP and No-LBP groups. Perimuscular thickness and echogenicity were not correlated with age but were positively correlated with BMI. The LBP group had ~25% greater perimuscular thickness and echogenicity compared with the No-LBP group (ANCOVA adjusted for BMI, p < 0.01 and p < 0.001 respectively). Conclusion This is the first report of abnormal connective tissue structure in the lumbar region in a group of subjects with chronic or recurrent LBP. This finding was not attributable to differences in age, sex, BMI or activity level between groups. Possible causes include genetic factors, abnormal movement patterns and chronic inflammation. PMID:19958536

  12. 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

  13. 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

  14. 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

  15. 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. PMID:25545833

  16. Gingival Cyst of the Adult as Early Sequela of Connective Tissue Grafting

    PubMed Central

    Gil Escalante, Mariana; Tatakis, Dimitris N.

    2015-01-01

    The subepithelial connective tissue graft (SCTG) is a highly predictable procedure with low complication rate. The reported early complications consist of typical postsurgical sequelae, such as pain and swelling. This case report describes the development and management of a gingival cyst following SCTG to obtain root coverage. Three weeks after SCTG procedure, a slightly raised, indurated, ~5 mm diameter asymptomatic lesion was evident. Excisional biopsy was performed and the histopathological evaluation confirmed the gingival cyst diagnosis. At the 1-year follow-up, the site had complete root coverage and normal tissue appearance and the patient remained asymptomatic. PMID:26236510

  17. Temporomandibular joint dysfunction. Connective tissue variations in skin biopsy and mitral valve function.

    PubMed

    Westling, L; Holm, S; Wallentin, I

    1992-12-01

    Ten women with temporomandibular joint dysfunction and general joint hypermobility (score, 4 to 8) and 10 symptom-free female volunteers without systemic laxity (score, 0 to 2) were selected for the study. A biopsy of connective tissue from arm skin found that the total collagen concentrations were lower and the proteoglycan values were higher in the hypermobile TMJ patients than in the control subjects. The mitral region of the heart was inspected by echocardiography. Eight patients and four controls had slightly abnormal echocardiographic findings. Two patients fulfilled the criteria for mitral valve prolapse. The patients had significantly more musculoskeletal complaints than did the controls. The study suggests an association between joint hypermobility, abnormal skin connective tissue composition, mitral valve malfunction, and musculoskeletal disorders in young women with TMJ dysfunction, especially internal derangement. PMID:1488224

  18. 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

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

    PubMed

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

    1998-11-01

    The purpose of the present clinical study was to evaluate the effect of guided tissue regeneration (GTR) in comparison to subpedicle connective tissue graft (SCTG) in the treatment of gingival recession defects. A total of 12 patients, each contributing a pair of Miller's Class I or II buccal gingival recessions, was treated. According to a randomization list, one defect in each patient received a polyglycolide/lactide bioabsorbable membrane, while the paired defect received a SCTG. Treatment effect was evaluated 6 months postsurgery. Clinical recordings included full-mouth and defect-specific oral hygiene standards and gingival health, recession depth (RD), recession width (RW), probing depth (PD), clinical attachment level (CAL), and keratinized tissue width (KT). Mean RD significantly decreased from 3.1 mm presurgery to 1.5 mm at 6 months postsurgery for the GTR group (48% root coverage), and from 3.0 mm to 0.5 mm for the SCTG group (81% root coverage). RD reduction and root coverage were significantly greater in SCTG group compared to GTR group. Mean CAL gain amounted to 1.7 mm for the GTR group, and 2.3 mm in the SCTG group. No significant differences in PD changes were observed within and between groups. KT increased significantly from presurgery for both treatment groups, however gingival augmentation was significantly greater in the SCTG group compared to GTR group. Results indicate that: 1) treatment of human gingival recession defects by means of both GTR and SCTG procedures results in clinically and statistically significant improvement of the soft tissue conditions of the defect; and 2) treatment outcome was significantly better following SCTG compared to GTR in terms of recession depth reduction, root coverage, and keratinized tissue increase. PMID:9848537

  20. Remodeling of the Epithelial-Connective Tissue Interface in Oral Epithelial Dysplasia as Visualized by Noninvasive 3D Imaging.

    PubMed

    Pal, Rahul; Shilagard, Tuya; Yang, Jinping; Villarreal, Paula; Brown, Tyra; Qiu, Suimin; McCammon, Susan; Resto, Vicente; Vargas, Gracie

    2016-08-15

    Early neoplastic features in oral epithelial dysplasia are first evident at the basal epithelium positioned at the epithelial-connective tissue interface (ECTI), separating the basal epithelium from the underlying lamina propria. The ECTI undergoes significant deformation in early neoplasia due to focal epithelial expansion and proteolytic remodeling of the lamina propria, but few studies have examined these changes. In the present study, we quantitated alterations in ECTI topography in dysplasia using in vivo volumetric multiphoton autofluorescence microscopy and second harmonic generation microscopy. The label-free method allows direct noninvasive visualization of the ECTI surface without perturbing the epithelium. An image-based parameter, "ECTI contour," is described that indicates deformation of the ECTI surface. ECTI contour was higher in dysplasia than control or inflamed specimens, indicating transition from flat to a deformed surface. Cellular parameters of nuclear area, nuclear density, coefficient of variation in nuclear area in the basal epithelium and collagen density in areas adjacent to ECTI were measured. ECTI contour differentiated dysplasia from control/benign mucosa with higher sensitivity and specificity than basal nuclear density or basal nuclear area, comparable with coefficient of variation in nuclear area and collagen density. The presented method offers a unique opportunity to study ECTI in intact mucosa with simultaneous assessment of cellular and extracellular matrix features, expanding opportunities for studies of early neoplastic events near this critical interface and potentially leading to development of new approaches for detecting neoplasia in vivo Cancer Res; 76(16); 4637-47. ©2016 AACR. PMID:27302162

  1. Elevated dietary magnesium prevents connective tissue mineralization in a mouse model of pseudoxanthoma elasticum (Abcc6(-/-)).

    PubMed

    LaRusso, Jennifer; Li, Qiaoli; Jiang, Qiujie; Uitto, Jouni

    2009-06-01

    Pseudoxanthoma elasticum (PXE) is an autosomal recessive multisystem disorder characterized by ectopic connective tissue mineralization, with clinical manifestations primarily in the skin, eyes, and cardiovascular system. There is considerable, both intra- and interfamilial, variability in the spectrum of phenotypic presentation. Previous studies have suggested that mineral content of the diet may modify the severity of the clinical phenotype in PXE. In this study, we utilized a targeted mutant mouse (Abcc6(-/-)) as a model system for PXE. We examined the effects of changes in dietary phosphate and magnesium on the mineralization process using calcification of the connective tissue capsule surrounding the vibrissae as an early phenotypic biomarker. Mice placed on custom-designed diets either high or low in phosphate did not show changes in mineralization, which was similar to that noted in Abcc6(-/-) mice on control diet. However, mice placed on diet enriched in magnesium (fivefold) showed no evidence of connective tissue mineralization in this mouse model of PXE. The inhibitory capacity of magnesium was confirmed in a cell-based mineralization assay system in vitro. Collectively, our observations suggest that assessment of dietary magnesium in patients with PXE may be warranted. PMID:19122649

  2. 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

  3. 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

  4. 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

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

    PubMed Central

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

    2007-01-01

    Background In humans, connective tissue forms a complex, interconnected network throughout the body that may have mechanosensory, regulatory and signaling functions. Understanding these potentially important phenomena requires non-invasive measurements of collagen network structure that can be performed in live animals or humans. The goal of this study was to show that ultrasound can be used to quantify dynamic changes in local connective tissue structure in vivo. We first performed combined ultrasound and histology examinations of the same tissue in two subjects undergoing surgery: in one subject, we examined the relationship of ultrasound to histological images in three dimensions; in the other, we examined the effect of a localized tissue perturbation using a previously developed robotic acupuncture needling technique. In ten additional non-surgical subjects, we quantified changes in tissue spatial organization over time during needle rotation vs. no rotation using ultrasound and semi-variogram analyses. Results 3-D renditions of ultrasound images showed longitudinal echogenic sheets that matched with collagenous sheets seen in histological preparations. Rank correlations between serial 2-D ultrasound and corresponding histology images resulted in high positive correlations for semi-variogram ranges computed parallel (r = 0.79, p < 0.001) and perpendicular (r = 0.63, p < 0.001) to the surface of the skin, indicating concordance in spatial structure between the two data sets. Needle rotation caused tissue displacement in the area surrounding the needle that was mapped spatially with ultrasound elastography and corresponded to collagen bundles winding around the needle on histological sections. In semi-variograms computed for each ultrasound frame, there was a greater change in the area under the semi-variogram curve across successive frames during needle rotation compared with no rotation. The direction of this change was heterogeneous across subjects. The frame

  6. [Scanning electron microscopic study of films of the loose connective tissue of mice exposed to DMBA].

    PubMed

    Ol'shevskaia, L V

    1979-01-01

    Under examination by scanning electron microscopy were film samples of the subcutaneous connective tissue. The surface of the films from intact mice was even and smooth, fibroblasts have a spread pattern. Following the saline injection the film was even, collagen fibres, differing in the character of surface and the size of diameter, were readily seen. The collagen fibres formed a multilayer system with a definite orientation inside the layer. After DMBA injection the film surface would get uneven and tuberous, the fibroblast body rising over the film surface, thus the orientation of fibres and all strata was disturbed. There was a spacial rearrangement of all tissue components. It is suggested that carcinogenic agents affecting the relationship between tissue components could interfere the contact inhibition of cell division and result in the development of focal cell proliferates. PMID:113934

  7. 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

  8. An opioid system in connective tissue: a study of achilles tendon in the rat.

    PubMed

    Ackermann, P W; Spetea, M; Nylander, I; Ploj, K; Ahmed, M; Kreicbergs, A

    2001-11-01

    The occurrence of endogenous opioids and their receptors in rat achilles tendon was analyzed by immunohistochemistry (IHC), radioimmunoassay (RIA), and in vitro binding assays. The investigation focused on four enkephalins, dynorphin B, and nociceptin/orphanin FQ. Nerve fibers immunoreactive to all enkephalins (Met-enkephalin, Leu-enkephalin, Met-enkephalin-Arg-Gly-Lys, Met-enkephalin-Arg-Phe) were consistently found in the loose connective tissue and the paratenon, whereas dynorphin B and nociceptin/orphanin FQ could not be detected. The majority of enkephalin-positive nerve fibers exhibited varicosities predominantly seen in blood vessel walls. Measurable levels of Met-enkephalin-Arg-Phe and nociceptin/orphanin FQ were found in tendon tissue using RIA, whereas dynorphin B could not be detected. In addition to the endogenous opioids identified, delta-opioid receptors on nerve fibers were also detected by IHC. Binding assays to characterize the opioid binding sites showed that they were specific and saturable for [3H]-naloxone (Kd 7.01 +/- 0.98 nM; Bmax 23.52 +/- 2.23 fmol/mg protein). Our study demonstrates the occurrence of an opioid system in rat achilles tendon, which may be assumed to be present also in other connective tissues of the locomotor apparatus. This system may prove to be a useful target for pharmacological therapy in painful and inflammatory conditions by new drugs acting selectively in the periphery. PMID:11668192

  9. Histological changes in connective tissue of rat tails after bipolar radiofrequency treatment.

    PubMed

    Beltrán-Frutos, E; Bernal-Mañas, C M; Navarro, S; Zuasti, A; Ferrer, C; Canteras, M; Seco-Rovira, V; García-Collado, A J; Pastor, L M

    2012-09-01

    Radiofrequency (RF) has been included in the techniques used in aesthetic surgery/medicine. To date, no studies have performed a histological assessment of changes in the tissue after application of bipolar radiofrequency (BRF) with low energy and frequency. The aim of this study was to examine changes that are produced in connective tissue, principally in the fibroblasts, following BRF treatment. Four groups of rats received a different number of RF sessions (1, 2, 3 and 5). The following parameters were determined: the number of fibroblasts/unit area (FA), the proliferation index (PI), the Heat shock Protein 47 index (HSPI) and the percentage of connective tissue (PC). For statistical analysis, two subgroups (A and B) were made for the variables FA, PI and PC, and another two subgroups (C and D) for the variable HSPI. Significant differences for FA, PI and PC were observed between subgroups A and B, FA and PI having higher values in A, while PC had higher values in B. The HSPI in subgroup C showed significantly higher values than in D. Low energy and frequency BRF led to an increase in the number, proliferation and biosynthetic activity of fibroblasts. The resulting stress suffered by fibroblasts as a result of heat may be associated with the phenomenon of hormesis. PMID:22806911

  10. 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. PMID:26483318

  11. Satellite cells, connective tissue fibroblasts and their interactions are crucial for muscle regeneration

    PubMed Central

    Murphy, Malea M.; Lawson, Jennifer A.; Mathew, Sam J.; Hutcheson, David A.; Kardon, Gabrielle

    2011-01-01

    Muscle regeneration requires the coordinated interaction of multiple cell types. Satellite cells have been implicated as the primary stem cell responsible for regenerating muscle, yet the necessity of these cells for regeneration has not been tested. Connective tissue fibroblasts also are likely to play a role in regeneration, as connective tissue fibrosis is a hallmark of regenerating muscle. However, the lack of molecular markers for these fibroblasts has precluded an investigation of their role. Using Tcf4, a newly identified fibroblast marker, and Pax7, a satellite cell marker, we found that after injury satellite cells and fibroblasts rapidly proliferate in close proximity to one another. To test the role of satellite cells and fibroblasts in muscle regeneration in vivo, we created Pax7CreERT2 and Tcf4CreERT2 mice and crossed these to R26RDTA mice to genetically ablate satellite cells and fibroblasts. Ablation of satellite cells resulted in a complete loss of regenerated muscle, as well as misregulation of fibroblasts and a dramatic increase in connective tissue. Ablation of fibroblasts altered the dynamics of satellite cells, leading to premature satellite cell differentiation, depletion of the early pool of satellite cells, and smaller regenerated myofibers. Thus, we provide direct, genetic evidence that satellite cells are required for muscle regeneration and also identify resident fibroblasts as a novel and vital component of the niche regulating satellite cell expansion during regeneration. Furthermore, we demonstrate that reciprocal interactions between fibroblasts and satellite cells contribute significantly to efficient, effective muscle regeneration. PMID:21828091

  12. Vertical and Horizontal Genetic Connectivity in Chromis verater, an Endemic Damselfish Found on Shallow and Mesophotic Reefs in the Hawaiian Archipelago and Adjacent Johnston Atoll

    PubMed Central

    Tenggardjaja, Kimberly A.; Bowen, Brian W.; Bernardi, Giacomo

    2014-01-01

    Understanding vertical and horizontal connectivity is a major priority in research on mesophotic coral ecosystems (30–150 m). However, horizontal connectivity has been the focus of few studies, and data on vertical connectivity are limited to sessile benthic mesophotic organisms. Here we present patterns of vertical and horizontal connectivity in the Hawaiian Islands-Johnston Atoll endemic threespot damselfish, Chromis verater, based on 319 shallow specimens and 153 deep specimens. The mtDNA markers cytochrome b and control region were sequenced to analyze genetic structure: 1) between shallow (<30 m) and mesophotic (30–150 m) populations and 2) across the species' geographic range. Additionally, the nuclear markers rhodopsin and internal transcribed spacer 2 of ribosomal DNA were sequenced to assess connectivity between shallow and mesophotic populations. There was no significant genetic differentiation by depth, indicating high levels of vertical connectivity between shallow and deep aggregates of C. verater. Consequently, shallow and deep samples were combined by location for analyses of horizontal connectivity. We detected low but significant population structure across the Hawaiian Archipelago (overall cytochrome b: ΦST = 0.009, P = 0.020; control region: ΦST = 0.012, P = 0.009) and a larger break between the archipelago and Johnston Atoll (cytochrome b: ΦST = 0.068, P<0.001; control region: ΦST = 0.116, P<0.001). The population structure within the archipelago was driven by samples from the island of Hawaii at the southeast end of the chain and Lisianski in the middle of the archipelago. The lack of vertical genetic structure supports the refugia hypothesis that deep reefs may constitute a population reservoir for species depleted in shallow reef habitats. These findings represent the first connectivity study on a mobile organism that spans shallow and mesophotic depths and provide a reference point for future connectivity

  13. Vertical and horizontal genetic connectivity in Chromis verater, an endemic damselfish found on shallow and mesophotic reefs in the Hawaiian Archipelago and adjacent Johnston Atoll.

    PubMed

    Tenggardjaja, Kimberly A; Bowen, Brian W; Bernardi, Giacomo

    2014-01-01

    Understanding vertical and horizontal connectivity is a major priority in research on mesophotic coral ecosystems (30-150 m). However, horizontal connectivity has been the focus of few studies, and data on vertical connectivity are limited to sessile benthic mesophotic organisms. Here we present patterns of vertical and horizontal connectivity in the Hawaiian Islands-Johnston Atoll endemic threespot damselfish, Chromis verater, based on 319 shallow specimens and 153 deep specimens. The mtDNA markers cytochrome b and control region were sequenced to analyze genetic structure: 1) between shallow (< 30 m) and mesophotic (30-150 m) populations and 2) across the species' geographic range. Additionally, the nuclear markers rhodopsin and internal transcribed spacer 2 of ribosomal DNA were sequenced to assess connectivity between shallow and mesophotic populations. There was no significant genetic differentiation by depth, indicating high levels of vertical connectivity between shallow and deep aggregates of C. verater. Consequently, shallow and deep samples were combined by location for analyses of horizontal connectivity. We detected low but significant population structure across the Hawaiian Archipelago (overall cytochrome b: ΦST = 0.009, P = 0.020; control region: ΦST = 0.012, P = 0.009) and a larger break between the archipelago and Johnston Atoll (cytochrome b: ΦST = 0.068, P < 0.001; control region: ΦST = 0.116, P < 0.001). The population structure within the archipelago was driven by samples from the island of Hawaii at the southeast end of the chain and Lisianski in the middle of the archipelago. The lack of vertical genetic structure supports the refugia hypothesis that deep reefs may constitute a population reservoir for species depleted in shallow reef habitats. These findings represent the first connectivity study on a mobile organism that spans shallow and mesophotic depths and provide a reference point for future connectivity studies on mesophotic

  14. Depression and seizures as the main neuropsychiatric manifestation of mixed connective tissue disorder.

    PubMed

    Kiani, Ismaa Ghazanfar; Qureshi, Safina Hameed; Shah, Faridullah

    2014-05-01

    A 38 years female presented with arthralgia, dyspnoea, progressive proximal muscle weakness, seizures, weight loss, dysphagia, alopecia, and dryness of the eyes and mouth with tightening of the skin. Psychiatric evaluation revealed major depression. She had oral ulcers, tightening of the skin of the hands with restricted mouth opening, and proximal muscle weakness. Mixed connective tissue disorder (MCTD) with predominant polymyositis and neuropsychiatric manifestations was diagnosed as the patient had anti-RNP positive with significantly raised muscle enzymes. This case is unique because major depression in MCTD is rarely documented, severe polymyositis is a rarity and ANA was negative but characteristic anti-RNP antibody was positive. PMID:24906270

  15. Local delivery of nitric oxide: targeted delivery of therapeutics to bone and connective tissues

    PubMed Central

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

    2012-01-01

    Non-invasive treatment of injuries and disorders affecting bones and connective tissue is a significant challenge facing the medical community. A treatment route that has recently been proposed is nitric oxide (NO) therapy. Nitric oxide plays several roles in physiology with many conditions lacking adequate levels of NO. As NO is a radical, localized delivery via NO donors is essential to promoting biological activity. Herein, we review current literature related to therapeutic NO delivery in the treatment of bone, skin and tendon repair. PMID:22433782

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

    PubMed Central

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

    2013-01-01

    Eosinophilic pleural effusion (EPE) is defined as a pleural effusion that contains at least 10% eosinophils. EPE occurs due to a variety of causes such as blood or air in the pleural space, infection, malignancy, or an autoimmune disease. Undifferentiated connective tissue disease (UCTD) associated with eosinophilic pleural effusion is a rare condition generally characterized by the presence of the signs and symptoms but not fulfilling the existing classification criteria. We report a case involving a 67-year-old man with UCTD and EPE, who has been successfully treated with a single intrapleural corticosteroid injection. PMID:24265645

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

    PubMed Central

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

    2014-01-01

    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. PMID:24084572

  18. [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

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

    PubMed Central

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

    2005-01-01

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

  20. Genome-Wide Transcriptional Profiling Reveals Connective Tissue Mast Cell Accumulation in Bronchopulmonary Dysplasia

    PubMed Central

    Bhattacharya, Soumyaroop; Go, Diana; Krenitsky, Daria L.; Huyck, Heidi L.; Solleti, Siva Kumar; Lunger, Valerie A.; Metlay, Leon; Srisuma, Sorachai; Wert, Susan E.; Pryhuber, Gloria S.

    2012-01-01

    Rationale: Bronchopulmonary dysplasia (BPD) is a major complication of premature birth. Risk factors for BPD are complex and include prenatal infection and O2 toxicity. BPD pathology is equally complex and characterized by inflammation and dysmorphic airspaces and vasculature. Due to the limited availability of clinical samples, an understanding of the molecular pathogenesis of this disease and its causal mechanisms and associated biomarkers is limited. Objectives: Apply genome-wide expression profiling to define pathways affected in BPD lungs. Methods: Lung tissue was obtained at autopsy from 11 BPD cases and 17 age-matched control subjects without BPD. RNA isolated from these tissue samples was interrogated using microarrays. Standard gene selection and pathway analysis methods were applied to the data set. Abnormal expression patterns were validated by quantitative reverse transcriptase–polymerase chain reaction and immunohistochemistry. Measurements and Main Results: We identified 159 genes differentially expressed in BPD tissues. Pathway analysis indicated previously appreciated (e.g., DNA damage regulation of cell cycle) as well as novel (e.g., B-cell development) biological functions were affected. Three of the five most highly induced genes were mast cell (MC)-specific markers. We confirmed an increased accumulation of connective tissue MCTC (chymase expressing) mast cells in BPD tissues. Increased expression of MCTC markers was also demonstrated in an animal model of BPD-like pathology. Conclusions: We present a unique genome-wide expression data set from human BPD lung tissue. Our data provide information on gene expression patterns associated with BPD and facilitated the discovery that MCTC accumulation is a prominent feature of this disease. These observations have significant clinical and mechanistic implications. PMID:22723293

  1. 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.

  2. 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

  3. Leucine supplementation accelerates connective tissue repair of injured tibialis anterior muscle.

    PubMed

    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

    2014-10-01

    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

  4. Development of human connective tissue mast cells from purified blood monocytes.

    PubMed Central

    Czarnetzki, B M; Figdor, C G; Kolde, G; Vroom, T; Aalberse, R; de Vries, J E

    1984-01-01

    Highly purified subfractions of human peripheral blood monocytes, when cultured in the presence of 30% L cell supernatant and 30% horse serum, assumed all the characteristics that define human connective tissue mast cells. After three weeks of culture, 75% of the cells developed metachromasia and granular chloroacetate esterase staining, and their intracellular histamine levels increased from 0.0 to 50.5 ng/10(6) cells. On electron microscopy, the cells developed intracytoplasmic granules with all the features typical for mature and immature mast cells. Cultured cells bound 55 pg 125I-IgE/10(6) cells, while labelling was negligible with cells prior to culture and with heat-denatured 125I-IgE. Fluorescent staining with anti-IgE increased slightly as well, while staining with monoclonal anti-monocyte and anti-HLA-Dr markers decreased. Purified lymphocytes did not assume mast cell characteristics, and lymphokines did not induce or enhance in vitro mast cell development or IgE binding. The data therefore further support the concept that connective tissue mast cells arise from the monocytoid lineage. Images Figure 1 PMID:6698581

  5. Development of an autologous connective tissue tube as a small caliber vascular substitute.

    PubMed

    Satoh, S; Niu, S; Shirakata, S; Oka, T; Noishiki, Y

    1988-01-01

    A small-caliber vascular graft with good healing properties was developed using an autologous connective tissue tube (ACTT) and in situ heparinization. ACTT is the best material for implantable grafts, but as a small-caliber vascular graft, both the high thrombogenicity and requirement for time to preparation in situ were serious problems. To overcome these difficulties, an ultrafine polyester fiber (UFPF) mesh was used for the framework of the graft. it has been shown that UFPF provides a good framework for fibroblast migration and proliferation both in vivo and in vitro. The granulomatous connective tissue tube could be constructed very rapidly and had numerous capillary blood vessels, which opened onto the luminal surface of the graft when it was implanted as a vascular substitute and provided colonies of endothelial cells. These colonies spread rapidly all over the luminal surface, and the graft developed permanent antithrombogenicity by endothelialization. The next problem was attainment of temporary antithrombogenicity of the graft before complete endothelialization. Since collagen fibrils are highly thrombogenic, the fact that ACTT collagen fibrils face the luminal surface requires greater antithrombogenicity. A new technique for binding heparin to collagen fibrils in situ was also developed. This was proved to be useful in maintaining the antithrombogenicity of the grafts (3 mm in inner diameter, 6 to 7 cm in length) in the animal studies. The graft showed rapid healing of the neonintima with endothelialization and long-term stability of the graft wall. PMID:3196580

  6. Massage-induced morphological changes of dense connective tissue in rat's tendon.

    PubMed

    Kassolik, Krzysztof; Andrzejewski, Waldemar; Dziegiel, Piotr; Jelen, Michal; Fulawka, Lukasz; Brzozowski, Marcin; Kurpas, Donata; Gworys, Bohdan; Podhorska-Okolow, Marzenna

    2013-01-01

    The aim of the experiment was to determine if possible changes in connective tissue induced by massage could have a positive effect justifing the use of massage in all post-traumatic connective tissue conditions, e.g. tendon injuries. The investigations were performed in a group of 18 Buffalo rats. The rats were divided into two groups (experimental and control). To standardize the massage procedure, it was performed with an algometer probe of 0.5 cm2 with constant pressure force of 1 kG (9,81 N). To analyse the number and diameter of collagen fibrils, two electron micrographs were performed for each rat of the collected segments of tendons of rat tail lateral extensor muscle. After image digitalization and calibration, the measurements were carried out using iTEM 5.0 software. The number of fibrils, their diameter and area were measured in a cross-sectional area. An increase of the number of collagen fibrils was observed in the tendons of massaged animals compared to the control group. Our study demonstrated that massage may cause a beneficial effect on metabolic activity of tendon's fibroblasts and, in consequence, may be applied for more effective use of massage for the prevention of tendon injury as well as after the injury has occurred. (Folia Histochemica et Cytobiologica 2013, Vol. 51, No. 1, 103-106). PMID:23690224

  7. 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

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

    PubMed Central

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

    2014-01-01

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

  9. Mapping the hydraulic connection between a coalbed and adjacent aquifer: example of the coal-seam gas resource area, north Galilee Basin, Australia

    NASA Astrophysics Data System (ADS)

    Jiang, Zhenjiao; Mariethoz, Gregoire; Schrank, Christoph; Cox, Malcolm; Timms, Wendy

    2016-07-01

    Coal-seam gas production requires groundwater extraction from coal-bearing formations to reduce the hydraulic pressure and improve gas recovery. In layered sedimentary basins, the coalbeds are often separated from freshwater aquifers by low-permeability aquitards. However, hydraulic connection between the coalbed and aquifers is possible due to the heterogeneity in the aquitard such as the existence of conductive faults or sandy channel deposits. For coal-seam gas extraction operations, it is desirable to identify areas in a basin where the probability of hydraulic connection between the coalbed and aquifers is low in order to avoid unnecessary loss of groundwater from aquifers and gas production problems. A connection indicator, the groundwater age indictor (GAI), is proposed, to quantify the degree of hydraulic connection. The spatial distribution of GAI can indicate the optimum positions for gas/water extraction in the coalbed. Depressurizing the coalbed at locations with a low GAI would result in little or no interaction with the aquifer when compared to the other positions. The concept of GAI is validated on synthetic cases and is then applied to the north Galilee Basin, Australia, to assess the degree of hydraulic connection between the Aramac Coal Measure and the water-bearing formations in the Great Artesian Basin, which are separated by an aquitard, the Betts Creek Beds. It is found that the GAI is higher in the western part of the basin, indicating a higher risk to depressurization of the coalbed in this region due to the strong hydraulic connection between the coalbed and the overlying aquifer.

  10. 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

  11. A novel stiffening factor inducing the stiffest state of holothurian catch connective tissue.

    PubMed

    Yamada, Akira; Tamori, Masaki; Iketani, Tomoaki; Oiwa, Kazuhiro; Motokawa, Tatsuo

    2010-10-15

    The dermis of sea cucumbers is a catch connective tissue or mutable collagenous tissue that shows large changes in stiffness. Extensive studies on the dermis revealed that it can adopt three different states having different mechanical properties that can be reversibly converted. These are the stiff, standard and soft states. The standard state is readily produced when a dermal piece is immersed in the sea water containing Ca²+, whereas the soft state can be produced by removal of Ca²+. A stiffening protein, tensilin, has been isolated from some sea cucumbers (Cucumaria frondosa and Holothuria leucospilota). Although tensilin converts the state of the dermis from soft to standard, it cannot convert from standard to stiff. In this study, we isolated and partially purified a novel stiffening factor from the dermis of Holothuria leucospilota. The factor stiffened the dermis in normal artificial sea water (ASW) but did not stiffen the soft dermis in Ca²+-free ASW. It also stiffened the dermis that had been converted to the standard state in Ca²+-free ASW by the action of tensilin. These results suggest that the factor produces the stiff dermis from the standard state but cannot work as a stiffener on the soft dermis. Its addition to longitudinal muscles of the sea cucumber produced no effects, suggesting that its effect is specific to the catch connective tissue. Its stiffening activity was susceptible to trypsin, meaning that it is a polypeptide, and its molecular mass estimated from gel filtration chromatography was 2.4 kDa. PMID:20889821

  12. Characterization of connective tissue progenitors through phase contrast and multicolor fluorescence time-lapse microscopy

    NASA Astrophysics Data System (ADS)

    Kwee, Edward; Powell, Kimerly; Muschler, George

    2015-03-01

    Connective tissue progenitors (CTPs) are defined as the heterogeneous population of tissue resident stem and progenitor cells capable of proliferating and differentiating into connective tissue phenotypes. The prevalence and variation in clonal progeny of CTPs can be characterized using a colony formation assay. However, colony assays do not directly assess the characteristics of the colony founding CTP. We developed a large field of view, time lapse microscopy system with phase contrast and fluorescence capabilities that enables tracking from seeding through colony formation. Cells derived from the trabecular surface of bone were prepared and seeded in an Ibidi-Ph+ chamber slide. Phase contrast images of the slide were obtained every hour using a DMI6000 Leica microscope, 10X objective, and Retiga 2000R camera. Cells were stained using fluorescent antibodies for multiple markers at the time of plating to determine marker expression on seeded cells and re-stained to determine expression on their progeny. Colonies were identified and characterized using automated image processing and quantitative analysis methods. Following colony identification, the time lapse was reversed to identify and characterize the colony founding CTP according to morphology and marker expression. As a representative example, a CD73+/CD90-/CD105- and a CD73+/CD90+/CD105- CTP resulted in a colony with an area of 3720826 microns2 and percent area expression of 2.98%, 3.62%, and 1.13% for CD73, CD90, and CD105, respectively. This method can be used to study CTPs and other stem and progenitor cell populations to benefit point-of-care methods for assay and isolation in cell based therapies.

  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. PMID:26857815

  14. Phosphaturic mesenchymal tumour mixed connective tissue variant: report of three cases with unusual histological findings.

    PubMed

    Shustik, David A; Ng, David Ce; Sittampalam, Kesavan

    2015-01-01

    Phosphaturic mesenchymal tumour mixed connective tissue variant (PMTMCT) is a rare tumour occurring in bone and soft tissue that usually behaves in a benign manner. Elaboration of biologically active substances by this tumour gives rise to a paraneoplastic syndrome known as oncogenic osteomalacia, manifesting clinically as bone pain, generalized weakness and pathological fractures. Recognition of PMTMCT and its associated syndrome is important, as resection of the tumour in most instances results in prompt resolution of symptoms. Previously reported cases of this tumour have emphasized the consistent presence of certain histological features that are considered prerequisite for making the diagnosis of PMTMCT. We describe three cases of PMTMCT, of which two first presented with progressive symptoms of osteomalacia and one remained clinically silent aside from the symptom of a palpable lump. Our cases highlight the wide-ranging histological patterns displayed by these tumours, and draw attention to certain microscopic findings that until now have been given little if any mention. Tentacular growth pattern and satellite nodules appear to be common findings in PMTMCTs, and can make complete surgical excision of these tumours challenging. The ability of this otherwise histologically benign tumour to permeate vascular spaces has to our knowledge never been described previously. One tumour lacked the characteristic calcifying matrix of PMTMCT, suggesting that in some tumours this defining feature may be focal if not entirely absent. PMTMCT shares features with and can resemble a variety of bone and soft tissue neoplasms, requiring the surgical pathologist to be familiar with this entity. PMID:26261662

  15. 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

  16. Antibodies against distinct nuclear matrix proteins are characteristic for mixed connective tissue disease.

    PubMed Central

    Habets, W J; de Rooij, D J; Salden, M H; Verhagen, A P; van Eekelen, C A; van de Putte, L B; van Venrooij, W J

    1983-01-01

    Specific nuclear proteins, separated according to their molecular weight (mol. wt) by polyacrylamide gel electrophoresis (PAGE) and subsequently transferred to nitrocellulose sheets, are able to bind antibodies in sera from patients suffering from different types of connective tissue diseases. Antibodies against a characteristic set of nuclear protein antigens are found in sera from patients with mixed connective tissue disease (MCTD). Screening of 21 MCTD sera revealed a typical immunoblot pattern with major protein antigens of mol. wt 70,000 (20/21) (not identical with the Scl-70 antigen characteristic for scleroderma), mol. wt 31,000 (17/21), two proteins around mol. wt 23,000 (15/21) and two around mol. wt 19,000 (10/21). The 70,000, 23,000 and 19,000 antigens appeared to be rather insoluble nuclear proteins (i.e. components of the nuclear matrix). On behalf of their structural character they were present in nuclei from several types of cells but only in low amounts detectable in salt extracts of thymus acetone powder. The presence of antibodies directed against the mol. wt 70,000 antigen correlated strongly with the diagnosis of MCTD. This 70,000 antigen is not identical with the RNP antigen, a soluble ribonuclease sensitive ribonucleoprotein, since antibodies against nuclear RNP can be separated from anti-nuclear matrix antibodies by affinity chromatography using immobilized thymus salt extract. The distinct character of soluble nuclear RNP and structural nuclear matrix antigens is further supported by the fact that from 14 other anti-RNP sera obtained from patients with systemic lupus erythematosus (SLE), only three contained antibodies against the mol. wt 70,000 protein. Since the immunoblot pattern obtained with MCTD sera mostly was clearly distinguishable from the patterns obtained with sera from patients with related connective tissue diseases our results suggest that the immunoblotting technique might be useful as a diagnostic tool and support the

  17. 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

  18. [Anti-ENA antibody determination in various connective tissue diseases: comparison of 2 detection techniques].

    PubMed

    Vaccai, D; Cataldi, V; Morozzi, G; Bacarelli, M R; Ciali, A; Pucci, G; Marcolongo, R

    1993-01-01

    The authors compared two different techniques for the detection of anti-ENA antibodies (anti-Sm, anti-RNP, anti-SSA, anti-SSB) in several different connective tissue diseases, using double immunodiffusion (ID) and a new membrane-based enzyme immunoassay. The aim of the work was to research the assay sensibility and specificity of the results obtained with the two different methods. Notwithstanding the fact that the two techniques are equivalent in their performance, the recombinant DNA appears to have greater sensibility and less specificity compared to ID. The former requires less time of execution although it presents difficulty in interpreting low scale positive results. Although the number of sera examined was low, the authors assert that the recombinant DNA technique will require further development. PMID:8329190

  19. 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

  20. 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

  1. [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

  2. 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

  3. Exome analysis of connective tissue dysplasia: death and rebirth of clinical genetics?

    PubMed

    Wilson, Golder N

    2014-05-01

    Exome results are reported for two patients with connective tissue dysplasia, one refining a clinical diagnosis of Ehlers-Danlos to Marfan syndrome, the other suggesting arthrogryposis derived from maternofetal Stickler syndrome. Patient 1 had mutations in transthyretin (TTR), fibrillin (FBN1), and a calcium channel (CACNA1A) gene suggesting diagnoses of transthyretin amyloidosis, Marfan syndrome, and familial hemiplegic migraines, respectively. Patient 2 presented with arthrogryposis that was correlated with his mother's habitus and arthritis once COL2A1 mutations suggestive of Stickler syndrome were defined. Although DNA results often defy prediction by the best of clinicians, these patients illustrate needs for ongoing clinical scholarship (e.g., to delineate guidelines for management of mutations like that for hyperekplexia in Patient 2) and for interpretation of polygenic change that is optimized by clinical genetic/syndromology experience (e.g., suggesting acetazolamide therapy for Patient 1 and explaining arthrogryposis in Patient 2). PMID:24664531

  4. [Clinical features and physical fitness parameters in athletes with cardiac connective tissue dysplasia syndrome].

    PubMed

    Mikhaĭlova, A V; Smolenskiĭ, A V

    2004-01-01

    Seventy-seven athletes with different manifestations of the cardiac connective tissue dysplasia (CCTD) syndrome (mitral prolapse (MP), anomalously located chordae (ALC) of the left ventricle and/or their combination) and 23 athletes without signs of CCTD syndrome were examined. The purpose of the study was to determine the specific features of the phenotypic picture, ECG data, and physical fitness in athletes with the manifestations of CCTD syndrome. The characteristic features of anthropometric data (higher heights and decreased body mass index), a larger number of the phenotypic signs of CCTD, the specific features of ECG, and lower parameters of physical fitness and aerobic capacities in the groups of MP, ALC, and/or their combination were identified; the impact of MP and ALC on these parameters was evaluated. PMID:15468725

  5. 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. PMID:26617847

  6. 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

  7. Photothermal effects in connective tissues mediated by laser-activated gold nanorods.

    PubMed

    Ratto, Fulvio; Matteini, Paolo; Rossi, Francesca; Menabuoni, Luca; Tiwari, Neha; Kulkarni, Sulabha K; Pini, Roberto

    2009-06-01

    We report a study on the application of laser-activated nanoparticles in the direct welding of connective tissues, which may become a valuable technology in biomedicine. We use colloidal gold nanorods as new near-infrared chromophores to mediate functional photothermal effects in the eye lens capsules. Samples obtained ex vivo from porcine eyes are treated to simulate heterotransplants with 810-nm diode laser radiation in association with a stain of gold nanorods of aspect ratio approximately 4. This stain is applied at the interface between a patch of capsule from a donor eye and the capsule of a recipient eye. Then, by administration of laser pulses of 40 msec and approximately 100-140 J/cm(2), we achieved the local denaturation of the endogenous collagen filaments, which reveals that the treated area reached temperatures above 50 degrees C. The thermal damage is confined within 50-70 mum in a radial distance from the irradiated area. PMID:19223241

  8. 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

  9. [The role of connective tissue dysplasia in the forming of mitral valve prolapse].

    PubMed

    Filipenko, P S; Malookaia, Iu S

    2006-01-01

    Connective tissue (CT) is a multifunctional universal structure of great importance to the human organism. Constituting about 50% of the body mass, CT forms a frame (skeleton) and outer cover (skin), as well as the inner medium, through which all structural elements receive nutrients and extract metabolic products. The great number of links, constituting the CT system, each of which is controlled genetically and is liable to genetic lesions, creates conditions for heterogeneity of malformations and diseases involving CT. Non-differentiated CT dysplasia (NDCTD) is a genetically heterogenous group, presenting a basis for various chronic diseases. NDCTD may present the cause of dysplastic changes in the CT of different organs and systems. Thanks to modern diagnostic techniques, NDCTD is revealed frequently. NDCTD is underlied by molecular-, onto-, and pathogenetic mechanisms, leading to structural and functional changes in CT. This CT "weakness" is manifested by the peculiarities of the structure of various organs and systems. Mesenchimal heart dysplasias are the most widespread visceral markers of the given CT pathology. CT dysplasias of the heart are often combined with varied manifestations of system CT anomaly. Mitral valve prolapse (MVP) is the most wide-spread and well-studied minor heart anomalies. Primary MVP is a hereditary or congenital pathology and is not connected with a particular disease. It is a genetic pathology--CT dysplasia with autosomal dominant inheritance. Patients with MVP have an increased expression of Bw35 antigen of HLA system, which causes dysmetabolism of collagen in the mitral cusps. It has been revealed that tissue deficiency of magnesium is associated with antigen expression and correlates with clinical symptoms in MVP. Exogenic factors influencing MVP have been described. PMID:17294876

  10. 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

  11. Hypercatabolism of normal IgG; an unexplained immunoglobulin abnormality in the connective tissue diseases

    PubMed Central

    Wochner, R. Dean

    1970-01-01

    The metabolism of radioiodinated IgG was studied in a series of 42 patients with connective tissue diseases (16 systemic lupus erythematosus, nine rheumatoid arthritis, five polymyositis, five vasculitis, and seven miscellaneous diagnoses). Fractional catabolic rates were increased and survival half-lives were shortened in all diagnostic categories indicating hypercatabolism of IgG. This hypercatabolism was masked by increased IgG synthesis, resulting in elevated serum concentrations of IgG in patients with systemic lupus erythematosus and rheumatoid arthritis and in generally normal concentrations in the others. The metabolism of iodinated IgM was also studied in eight patients with systemic lupus erythematosus, in seven with rheumatoid arthritis, and in 12 controls. The fractional catabolic rates were normal in both groups of patients. Serum concentrations of both IgM and IgA were moderately elevated in all diagnostic categories. Serum albumin metabolism was entirely normal in the nine subjects studied who were not receiving corticosteroids; in three who were receiving them, moderate hypercatabolism was observed. The hypercatabolism of IgG could not be accounted for by factors previously known to alter IgG metabolism. It was not observed in 15 patients with other chronic, inflammatory diseases and was not explained by concomitant administration of adrenal corticosteroids to some patients. Identical results were obtained whether the IgG was obtained from a patient himself or from a normal donor, demonstrating that the hypercatabolism is a host defect and not an abnormality of the protein. Thus, patients with connective tissue disease of several different diagnostic categories have been shown to have an unexplained immunoglobulin abnormality: they catabolize normal IgG at an accelerated rate. PMID:5415673

  12. [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

  13. Alterations of Dermal Connective Tissue Collagen in Diabetes: Molecular Basis of Aged-Appearing Skin

    PubMed Central

    Argyropoulos, Angela J.; Robichaud, Patrick; Balimunkwe, Rebecca Mutesi; Fisher, Gary J.; Hammerberg, Craig; Yan, Yan

    2016-01-01

    Alterations of the collagen, the major structural protein in skin, contribute significantly to human skin connective tissue aging. As aged-appearing skin is more common in diabetes, here we investigated the molecular basis of aged-appearing skin in diabetes. Among all known human matrix metalloproteinases (MMPs), diabetic skin shows elevated levels of MMP-1 and MMP-2. Laser capture microdissection (LCM) coupled real-time PCR indicated that elevated MMPs in diabetic skin were primarily expressed in the dermis. Furthermore, diabetic skin shows increased lysyl oxidase (LOX) expression and higher cross-linked collagens. Atomic force microscopy (AFM) further indicated that collagen fibrils were fragmented/disorganized, and key mechanical properties of traction force and tensile strength were increased in diabetic skin, compared to intact/well-organized collagen fibrils in non-diabetic skin. In in vitro tissue culture system, multiple MMPs including MMP-1 and MM-2 were induced by high glucose (25 mM) exposure to isolated primary human skin dermal fibroblasts, the major cells responsible for collagen homeostasis in skin. The elevation of MMPs and LOX over the years is thought to result in the accumulation of fragmented and cross-linked collagen, and thus impairs dermal collagen structural integrity and mechanical properties in diabetes. Our data partially explain why old-looking skin is more common in diabetic patients. PMID:27104752

  14. Subsynovial Connective Tissue is Sensitive to Surgical Interventions in a Rabbit Model of Carpal Tunnel Syndrome

    PubMed Central

    Sun, Yu-Long; Moriya, Tamami; Zhao, Chunfeng; Kirk, Ramona L.; Chikenji, Takako; Passe, Sandra M.; An, Kai-Nan; Amadio, Peter C.

    2011-01-01

    The most common histological finding in carpal tunnel syndrome (CTS) is non-inflammatory fibrosis and thickening of the subsynovial connective tissue (SSCT) in the tunnel. While the cause of SSCT fibrosis and the relationship of SSCT fibrosis and CTS are unknown, one hypothesis is that SSCT injury causes fibrosis, and that the fibrosis then leads to CTS. We investigated the sensitivity of the SSCT to injuries. Two types of surgical intervention were performed in a rabbit model: a skin incision with tendon laceration and SSCT stretching sufficient to damage the SSCT, and skin incision alone,. Twelve weeks after surgery, the rabbit carpal tunnel tissues were studied with immunochemistry for TGF-β receptors 1, 2, and 3, collagen III, and collagen VI. All TGF-β receptors were expressed. The percentages of the TGF-β receptors’ expressions were less in the control SSCT fibroblasts than in the fibroblasts from rabbits with surgical interventions. The surgical interventions did not result in any alteration of collagen III expression. However, both surgical interventions resulted in a significant decrease in collagen VI expression compared to the control group. The two surgical interventions achieved similar expression of TGF-β receptors and collagens. Our results provide evidence that the SSCT is sensitive to surgical interventions, even when these are modest. Since SSCT fibrosis is a hallmark of carpal tunnel syndrome, these data also suggest that such fibrosis could result from relatively minor trauma. PMID:22009518

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

    PubMed

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

    2014-06-01

    Thermal acclimation can alter cardiac function and morphology in a number of fish species, but little is known about the regulation of these changes. The purpose of the present study was to determine how cold acclimation affects zebrafish (Danio rerio) cardiac morphology, collagen composition and connective tissue regulation. Heart volume, the thickness of the compact myocardium, collagen content and collagen fiber composition were compared between control (27°C) and cold-acclimated (20°C) zebrafish using serially sectioned hearts stained with Picrosirius Red. Collagen content and fiber composition of the pericardial membrane were also examined. Cold acclimation did not affect the volume of the contracted heart; however, there was a significant decrease in the thickness of the compact myocardium. There was also a decrease in the collagen content of the compact myocardium and in the amount of thick collagen fibers throughout the heart. Cold-acclimated zebrafish also increased expression of the gene transcript for matrix metalloproteinase 2, matrix metalloproteinase 9, tissue inhibitor of metalloproteinase 2 and collagen Type I α1. We propose that the reduction in the thickness of the compact myocardium as well as the change in collagen content may help to maintain the compliance of the ventricle as temperatures decrease. Together, these results clearly demonstrate that the zebrafish heart undergoes significant remodeling in response to cold acclimation. PMID:24577447

  16. Activin A-Smad Signaling Mediates Connective Tissue Growth Factor Synthesis in Liver Progenitor Cells

    PubMed Central

    Ding, Ze-Yang; Jin, Guan-Nan; Wang, Wei; Sun, Yi-Min; Chen, Wei-Xun; Chen, Lin; Liang, Hui-Fang; Datta, Pran K.; Zhang, Ming-Zhi; Zhang, Bixiang; Chen, Xiao-Ping

    2016-01-01

    Liver progenitor cells (LPCs) are activated in chronic liver damage and may contribute to liver fibrosis. Our previous investigation reported that LPCs produced connective tissue growth factor (CTGF/CCN2), an inducer of liver fibrosis, yet the regulatory mechanism of the production of CTGF/CCN2 in LPCs remains elusive. In this study, we report that Activin A is an inducer of CTGF/CCN2 in LPCs. Here we show that expression of both Activin A and CTGF/CCN2 were upregulated in the cirrhotic liver, and the expression of Activin A positively correlates with that of CTGF/CCN2 in liver tissues. We go on to show that Activin A induced de novo synthesis of CTGF/CCN2 in LPC cell lines LE/6 and WB-F344. Furthermore, Activin A contributed to autonomous production of CTGF/CCN2 in liver progenitor cells (LPCs) via activation of the Smad signaling pathway. Smad2, 3 and 4 were all required for this induction. Collectively, these results provide evidence for the fibrotic role of LPCs in the liver and suggest that the Activin A-Smad-CTGF/CCN2 signaling in LPCs may be a therapeutic target of liver fibrosis. PMID:27011166

  17. 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

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

    PubMed Central

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

    2012-01-01

    Background: Phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT) is a rare tumor typically occurring in soft tissues and bone, causing oncogenic (tumor-induced) osteomalacia (TIO) through secretion of the phosphaturic hormone, fibroblast growth factor-23 (FGF-23). Rare tumors identical to PMTMCT occur without known TIO. Intracranial localization of PMTMCT is extremely rare, with only two cases reported in the literature. We present a very unusual case of a patient with an intracranial PMTMCT that presented with neurologic changes without osteomalacia. Case Description: A 67-year-old woman presented with progressive incontinence, apathy, and abulia after having undergone a total knee replacement 1 month earlier. Imaging disclosed a large left frontal anterior fossa mass. She underwent uncomplicated surgical resection of this tumor. Surprisingly, histopathology suggested PMTMCT. Reverse transcription polymerase chain reaction (RT-PCR) assay demonstrating FGF-23 expression in the tumor confirmed the diagnosis. Serum FGF-23 levels postoperatively were normal and she had no clinical or laboratory evidence of osteomalacia or phosphaturia. Conclusion: This report should serve to alert clinicians to the possibility that PMTMCT can be included in the differential diagnosis of intracranial masses even in the absence of tumor-induced osteomalacia. PMID:23372968

  19. Control of connective tissue metabolism by lasers: recent developments and future prospects

    SciTech Connect

    Abergel, R.P.; Meeker, C.A.; Lam, T.S.; Dwyer, R.M.; Lesavoy, M.A.; Uitto, J.

    1984-12-01

    Various laser modalities are currently in extensive use in dermatology and plastic surgery, particularly for treatment of vascular and pigmented lesions. A relatively new area of laser utilization involves the possible biologic effects of the lasers. In this overview, recent studies are summarized which indicate that lasers at specific wavelengths and energy densities modulate the connective tissue metabolism by skin fibroblasts both in vitro and in vivo. Specifically, the neodymium-yttrium-aluminum-garnet (Nd: YAG) laser was shown to selectively suppress collagen production both in fibroblast cultures and in normal skin in vivo, thus suggesting that this laser modality may be useful for the treatment of fibrotic conditions such as keloids and hypertrophic scars. Furthermore, two low-energy lasers, helium-neon (He-Ne) and gallium-arsenide (Ga-As), were shown to stimulate collagen production in human skin fibroblast cultures, suggesting that these lasers could be used for enhancement of wound healing processes. These experimental approaches illustrate the future possibilities for applying lasers for the modulation of various biologic functions of cells in tissues and attest to the potential role of lasers in the treatment of cutaneous disorders.

  20. Connective-tissue growth factor modulates WNT signalling and interacts with the WNT receptor complex.

    PubMed

    Mercurio, Sara; Latinkic, Branko; Itasaki, Nobue; Krumlauf, Robb; Smith, J C

    2004-05-01

    Connective-tissue growth factor (CTGF) is a member of the CCN family of secreted proteins. CCN family members contain four characteristic domains and exhibit multiple activities: they associate with the extracellular matrix, they can mediate cell adhesion, cell migration and chemotaxis, and they can modulate the activities of peptide growth factors. Many of the effects of CTGF are thought to be mediated by binding to integrins, whereas others may be because of its recently identified ability to interact with BMP4 and TGF beta. We demonstrate, using Xenopus embryos, that CTGF also regulates signalling through the Wnt pathway, in accord with its ability to bind to the Wnt co-receptor LDL receptor-related protein 6 (LRP6). This interaction is likely to occur through the C-terminal (CT) domain of CTGF, which is distinct from the BMP- and TGF beta-interacting domain. Our results define new activities of CTGF and add to the variety of routes through which cells regulate growth factor activity in development, disease and tissue homeostasis. PMID:15105373

  1. 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

  2. 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

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

    PubMed

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

    2014-07-01

    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

  4. The wound/burn guidelines - 4: Guidelines for the management of skin ulcers associated with connective tissue disease/vasculitis.

    PubMed

    Fujimoto, Manabu; Asano, Yoshihide; Ishii, Takayuki; Ogawa, Fumihide; Kawakami, Tamihiro; Kodera, Masanari; Abe, Masatoshi; Isei, Taiki; Ito, Takaaki; Inoue, Yuji; Imafuku, Shinichi; Irisawa, Ryokichi; Ohtsuka, Masaki; Ohtsuka, Mikio; Kadono, Takafumi; Kawaguchi, Masakazu; Kukino, Ryuichi; Kono, Takeshi; Sakai, Keisuke; Takahara, Masakazu; Tanioka, Miki; Nakanishi, Takeshi; Nakamura, Yasuhiro; Hashimoto, Akira; Hasegawa, Minoru; Hayashi, Masahiro; Fujiwara, Hiroshi; Maekawa, Takeo; Matsuo, Koma; Madokoro, Naoki; Yamasaki, Osamu; Yoshino, Yuichiro; Le Pavoux, Andres; Tachibana, Takao; Ihn, Hironobu

    2016-07-01

    The Japanese Dermatological Association prepared guidelines focused on the treatment of skin ulcers associated with connective tissue disease/vasculitis practical in clinical settings of dermatological care. Skin ulcers associated with connective tissue diseases or vasculitis occur on the background of a wide variety of diseases including, typically, systemic sclerosis but also systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis (RA), various vasculitides and antiphospholipid antibody syndrome (APS). Therefore, in preparing the present guidelines, we considered diagnostic/therapeutic approaches appropriate for each of these disorders to be necessary and developed algorithms and clinical questions for systemic sclerosis, SLE, dermatomyositis, RA, vasculitis and APS. PMID:26972733

  5. 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.…

  6. 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.

  7. 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

  8. Examining the connectivity between different cellular processes in the Barrett tissue microenvironment.

    PubMed

    Phelan, J J; Feighery, R; Eldin, O S; Meachair, S Ó; Cannon, A; Byrne, R; MacCarthy, F; O'Toole, D; Reynolds, J V; O'Sullivan, J

    2016-02-28

    In Barrett associated tumorigenesis, oxidative phosphorylation and glycolysis are reprogrammed early in the disease sequence and act mutually to promote disease progression. However, the link between energy metabolism and its connection with other central cellular processes within the Barrett microenvironment is unknown. The aim of this study was to examine the relationship between metabolism (ATP5B/GAPDH), hypoxia (HIF1α), inflammation (IL1β/SERPINA3), p53 and obesity status using in-vivo and ex-vivo models of Barrett oesophagus. At the protein level, ATP5B (r = 0.71, P < 0.0001) and p53 (r = 0.455, P = 0.015) were found to be strongly associated with hypoxia. In addition, levels of ATP5B (r = 0.53, P = 0.0031) and GAPDH (r = -0.39, P = 0.0357) were positively associated with p53 expression. Moreover, we demonstrate that ATP5B (r = 0.8, P < 0.0001) and GAPDH (r = 0.43, P = 0.022) were positively associated with IL1β expression. Interestingly, obesity was negatively associated with oxidative phosphorylation (r = -0.6016, P = 0.0177) but positively associated with glycolysis (r = 0.743, P = 0.0015). Comparable correlations were exhibited in the ex-vivo explant tissue between metabolism, p53, hypoxia, inflammation and angiogenesis (P < 0.05). We have shown that metabolism is closely linked with many cellular processes in the Barrett tissue microenvironment. PMID:26688097

  9. Development of a hyperelastic material model of subsynovial connective tissue using finite element modeling.

    PubMed

    Matsuura, Yusuke; Thoreson, Andrew R; Zhao, Chunfeng; Amadio, Peter C; An, Kai-Nan

    2016-01-01

    Carpal tunnel syndrome (CTS) is one of the most common disorders of the hand. Assessment of carpal tunnel tissue mechanical behavior, especially that of the subsynovial connective tissue (SSCT), is important to better understand the mechanisms of CTS. The aim of this study was to develop a hyperelastic material model of human SSCT using mechanical test data and finite element modeling (FEM). Experimental shear test data of SSCT from 7 normal subjects and 7 CTS patients collected in a prior study was used to define material response. Hyperelastic coefficients (μ and α) from the first-order Ogden material property definition were iteratively solved using specimen-specific FEM models simulating the mechanical test conditions. A typical Ogden hyperelastic response for the normal and CTS SSCT was characterized by doing the same with data from all samples averaged together. The mean Ogden coefficients (μ/α) for the normal cadaver and CTS patient SSCT were 1.25×10(-5)MPa/4.51 and 1.99×10(-6)MPa/10.6, respectively when evaluating coefficients for individual specimens. The Ogden coefficients for the typical (averaged data) model for normal cadaver and CTS patient SSCT were 1.63×10(-5)MPa/3.93 and 5.00×10(-7)MPa/9.55, respectively. Assessment of SSCT mechanical response with a hyperelastic material model demonstrated significant differences between patient and normal cadaver. The refined assessment of these differences with this model may be important for future model development and in understanding clinical presentation of CTS. PMID:26482734

  10. 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

  11. 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

  12. U1-RNP and TLR receptors in the pathogenesis of mixed connective tissue diseasePart I. The U1-RNP complex and its biological significance in the pathogenesis of mixed connective tissue disease

    PubMed Central

    2015-01-01

    Mixed connective tissue disease (MCTD) is a rare autoimmune syndrome, signified by complex interactions between disease-related phenomena, including inflammation, proliferative vascular arteriopathy, thrombotic events and humoral autoimmune processes. It is still controversial whether MCTD is a distinct clinical entity among systemic connective tissue diseases, although several authors consider that it is distinct and underline characteristic, distinct clinical, serological and immunogenetic features. The putative target of autoimmunity in MCTD is U1-RNP, which is a complex of U1-RNA and small nuclear RNP. Both the U1-RNA component and the specific proteins, particularly U1-70K, engage immune cells and their receptors in a complex network of interactions that ultimately lead to autoimmunity, inflammation, and tissue injury. U1-RNA is capable of inducing manifestations consistent with TLR activation. Stimulation of innate immunity by native RNA molecules with a double-stranded secondary structure may help explain the high prevalence of autoimmunity to RNA binding proteins.

  13. Tissue types (image)

    MedlinePlus

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

  14. 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. PMID:24832082

  15. 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. PMID:26575166

  16. The response of the rabbit subsynovial connective tissue to a stress-relaxation test.

    PubMed

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

    2012-03-01

    The subsynovial connective tissue (SSCT) in the carpal tunnel may play a role in the etiology of carpal tunnel syndrome (CTS), yet the material properties of the SSCT remain unclear. Thus, we investigated the mechanical response of the SSCT in a rabbit model. Twenty-four rabbit cadaver paws were used for mechanical testing; two paws were used for scanning electron microscopy (SEM) imaging. After testing normal tendon excursion, the divided third digit flexor digitorum superficialis (FDS) tendon was pulled to displacements of 2, 3.5, 5, or 8 mm, maintained at that position until force decay, and then the process was repeated. Normal excursion of the FDS averaged 4.8 mm. The ratio of the second peak force to the first peak force in the 2 mm group was 0.98 (SD = 0.16), which was significantly higher than the other groups (3.5 mm: 0.74, 5 mm, 0.63, and 8 mm: 0.59; p < 0.05). SEM showed ruptured fibrils in the displaced specimen. The declining force ratio with displacements >2 mm suggests damage to the SSCT within the physiological tendon excursion. These data may be useful in understanding SSCT mechanics in CTS, which is associated with SSCT fibrosis. PMID:21898581

  17. Chronological ageing and photoageing of the fibroblasts and the dermal connective tissue.

    PubMed

    Ma, W; Wlaschek, M; Tantcheva-Poór, I; Schneider, L A; Naderi, L; Razi-Wolf, Z; Schüller, J; Scharffetter-Kochanek, K

    2001-10-01

    In recent years, the exposure of human skin to environmental and artificial UV irradiation has increased dramatically. This is due not only to increased solar UV irradiation as a consequence of stratospheric ozone depletion, but also to inappropriate social behaviour with the use of tanning salons still being very popular in the public view. Besides this, leisure activities and a lifestyle that often includes travel to equatorial regions add to the individual annual UV load. In addition to the common long-term detrimental effects such as immunosuppression and skin cancer, the photo-oxidative damage due to energy absorption of UV photons in an oxygenized environment leads to quantitative and qualitative alterations of cells and structural macromolecules of the dermal connective tissue responsible for tensile strength, resilience and stability of the skin. The clinical manifestations of UV/reactive oxygen species (ROS)-induced disturbances result in photoaged skin with wrinkle formation, laxity, leathery appearance as well as fragility, impaired wound healing capacities and higher vulnerability. Strategies to prevent or at least minimize ROS-induced photo-ageing and intrinsic ageing of the skin necessarily include protection against UV irradiation and antioxidant homeostasis. PMID:11696063

  18. Connective tissue and related disorders and preterm birth: clues to genes contributing to prematurity.

    PubMed

    Anum, E A; Hill, L D; Pandya, A; Strauss, J F

    2009-03-01

    To identify candidate genes contributing to preterm birth, we examined the existing literature on the association between known disorders of connective tissue synthesis and metabolism and related diseases and prematurity. Our hypothesis was that abnormal matrix metabolism contributes to prematurity by increasing risk of preterm premature rupture of membranes (PPROM) and cervical incompetence. Based on this review, we identified gene mutations inherited by the fetus that could predispose to preterm birth as a result of PPROM. The responsible genes include COL5A1, COL5A2, COL3A1, COL1A1, COL1A2, TNXB, PLOD1, ADAMTS2, CRTAP, LEPRE1 and ZMPSTE24. Marfan syndrome, caused by FBN1 mutations, and polymorphisms in the COL1A1 and TGFB1 genes have been associated with cervical incompetence. We speculate that an analysis of sequence variation at the loci noted above will reveal polymorphisms that may contribute to susceptibility to PPROM and cervical incompetence in the general population. PMID:19152976

  19. Successful Immunosuppressive Treatment of Mixed Connective Tissue Disease Complicated by Microscopic Polyangiitis.

    PubMed

    Sato, Shuzo; Yashiro, Makiko; Matsuoka, Naoki; Uematsu, Manabu; Asano, Tomoyuki; Kobayashi, Hiroko; Watanabe, Hiroshi; Ohira, Hiromasa

    2016-01-01

    Mixed connective tissue disease (MCTD) is characterized by a combination of clinical features of systemic lupus erythematosus, systemic sclerosis, and polymyositis with elevated antibodies to U1 small nuclear ribonucleoprotein (U1-RNP). MCTD is often accompanied by interstitial lung disease as pulmonary involvement. On the other hand, microscopic polyangiitis (MPA) is a systemic autoimmune disease characterized by the inflammation of small vessels (arterioles, capillaries, and venules) mainly affecting the lung and kidney. MPA is associated with elevated serum anti-neutrophil cytoplasmic antibody (ANCA). Complication of MPA in patients with MCTD is rare. So far, only nine case reports of MCTD complicated by MPA with serum myeloperoxidase-specific ANCA (MPO-ANCA) are available. Here, we describe a 64-year-old male suffering from MCTD with MPA. The patient developed interstitial pneumonia with alveolar hemorrhage accompanied by myositis, scleroderma, and elevated anti-U1-RNP antibody and MPO-ANCA levels with substantial systemic inflammation. Strong immunosuppressive therapy (corticosteroid, intravenous immunoglobulin, and cyclosporine A) ameliorated the myositis, interstitial lung disease, and inflammation, with the decrease of MPO-ANCA levels, despite that severe lung complications are often associated with poor outcomes. In conclusion, MCTD may be accompanied by MPA with alveolar hemorrhage. Severe lung complications may indicate a poor outcome, and therefore prompt immunosuppressive treatment should be performed in such patients. PMID:27238624

  20. 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

  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. Benefit of adjunctive tacrolimus in connective tissue disease-interstitial lung disease.

    PubMed

    Witt, Leah J; Demchuk, Carley; Curran, James J; Strek, Mary E

    2016-02-01

    We evaluated the safety and effectiveness of adjunctive tacrolimus therapy with conventional immunosuppression in patients with severe connective tissue disease-related interstitial lung disease (CTD-ILD). We included patients from our interstitial lung disease (ILD) registry with CTD-ILD, in whom tacrolimus was added to corticosteroids and an additional immunosuppressive agent. Demographic data, clinical features, lung function, radiographic images, and pathologic findings were reviewed. Effectiveness was assessed by comparing pulmonary function tests (PFTs) closest to tacrolimus initiation to PFTs approximately 6-12 months later. Corticosteroid dose at these time points was also evaluated. We report adverse events attributed to tacrolimus. Seventeen patients with CTD-ILD were included in adverse event analysis; twelve were included in efficacy analysis. Length of tacrolimus therapy ranged from 6 to 110 months (mean 38.8 months ± 31.4). The mean improvement in percent predicted total lung capacity was 7.5% ± 11.7 (p = 0.02). Forced vital capacity mean improvement was 7.4% ± 12.5 (p = 0.06). The average decrease in corticosteroid dose at follow-up was 20.3 mg ± 25.2 (p = 0.02) with complete discontinuation in six patients. No patients experienced a life-threatening adverse event attributed to tacrolimus. Tacrolimus can be effective and is well tolerated as an adjunctive therapy and allows tapering of corticosteroids. PMID:26762710

  3. [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

  4. Expression of p53, p21(CIP1/WAF1) and eIF4E in the adjacent tissues of oral squamous cell carcinoma: establishing the molecular boundary and a cancer progression model.

    PubMed

    Li, Yi; Li, Bo; Xu, Bo; Han, Bo; Xia, Hui; Chen, Qian-Ming; Li, Long-Jiang

    2015-09-01

    The present study evaluated the expression of key molecules and the status of DNA in both oral squamous cell carcinoma (OSCC) and adjacent tissues to establish a molecular surgical boundary and provide a cancer progression model. Biopsy samples from 50 OSCC patients were divided into T (cancer), P1 (0-0.5 cm), P2 (0.5-1 cm), P3 (1-1.5 cm) and P4 (1.5-2 cm) groups based on the distances from the visible boundary of the primary focus. Twenty samples of normal mucosa were used as controls. We used immunohistochemical staining and flow cytometry to evaluate p53, p21(CIP1/WAF1), eIF4E and Ki-67 expression and to determine DNA status, respectively. Sub-mucosal invasion was present in the P1 and P2 groups as determined by haematoxylin and eosin staining. Mutant p53 expression decreased gradually from cancerous to normal mucosae, whereas p21(CIP1/WAF1) expression displayed an opposite trend. eIF4E expression decreased from cancerous to normal mucosae. Ki-67 expression, the heteroploidy ratio, S-phase fraction and proliferative index decreased gradually with the distance from the tumour centre. Based on these results, we suggest that the resection boundary in OSCC surgery should be beyond 2 cm from the tumour. Additionally, the adjacent tissues of the primary focus could be used as a model for assessing cancer progression. PMID:25835715

  5. Epigenetic clustering of lung adenocarcinomas based on DNA methylation profiles in adjacent lung tissue: Its correlation with smoking history and chronic obstructive pulmonary disease.

    PubMed

    Sato, Takashi; Arai, Eri; Kohno, Takashi; Takahashi, Yoriko; Miyata, Sayaka; Tsuta, Koji; Watanabe, Shun-ichi; Soejima, Kenzo; Betsuyaku, Tomoko; Kanai, Yae

    2014-07-15

    The aim of this study was to clarify the significance of DNA methylation alterations during lung carcinogenesis. Infinium assay was performed using 139 paired samples of non-cancerous lung tissue (N) and tumorous tissue (T) from a learning cohort of patients with lung adenocarcinomas (LADCs). Fifty paired N and T samples from a validation cohort were also analyzed. DNA methylation alterations on 1,928 probes occurred in N samples relative to normal lung tissue from patients without primary lung tumors, and were inherited by, or strengthened in, T samples. Unsupervised hierarchical clustering using DNA methylation levels in N samples on all 26,447 probes subclustered patients into Cluster I (n = 32), Cluster II (n = 35) and Cluster III (n = 72). LADCs in Cluster I developed from the inflammatory background in chronic obstructive pulmonary disease (COPD) in heavy smokers and were locally invasive. Most patients in Cluster II were non-smokers and had a favorable outcome. LADCs in Cluster III developed in light smokers were most aggressive (frequently showing lymphatic and blood vessel invasion, lymph node metastasis and an advanced pathological stage), and had a poor outcome. DNA methylation levels of hallmark genes for each cluster, such as IRX2, HOXD8, SPARCL1, RGS5 and EI24, were again correlated with clinicopathological characteristics in the validation cohort. DNA methylation profiles reflecting carcinogenetic factors such as smoking and COPD appear to be established in non-cancerous lung tissue from patients with LADCs and may determine the aggressiveness of tumors developing in individual patients, and thus patient outcome. PMID:24921089

  6. Epigenetic clustering of lung adenocarcinomas based on DNA methylation profiles in adjacent lung tissue: Its correlation with smoking history and chronic obstructive pulmonary disease

    PubMed Central

    Sato, Takashi; Arai, Eri; Kohno, Takashi; Takahashi, Yoriko; Miyata, Sayaka; Tsuta, Koji; Watanabe, Shun-ichi; Soejima, Kenzo; Betsuyaku, Tomoko; Kanai, Yae

    2014-01-01

    The aim of this study was to clarify the significance of DNA methylation alterations during lung carcinogenesis. Infinium assay was performed using 139 paired samples of non-cancerous lung tissue (N) and tumorous tissue (T) from a learning cohort of patients with lung adenocarcinomas (LADCs). Fifty paired N and T samples from a validation cohort were also analyzed. DNA methylation alterations on 1,928 probes occurred in N samples relative to normal lung tissue from patients without primary lung tumors, and were inherited by, or strengthened in, T samples. Unsupervised hierarchical clustering using DNA methylation levels in N samples on all 26,447 probes subclustered patients into Cluster I (n = 32), Cluster II (n = 35) and Cluster III (n = 72). LADCs in Cluster I developed from the inflammatory background in chronic obstructive pulmonary disease (COPD) in heavy smokers and were locally invasive. Most patients in Cluster II were non-smokers and had a favorable outcome. LADCs in Cluster III developed in light smokers were most aggressive (frequently showing lymphatic and blood vessel invasion, lymph node metastasis and an advanced pathological stage), and had a poor outcome. DNA methylation levels of hallmark genes for each cluster, such as IRX2, HOXD8, SPARCL1, RGS5 and EI24, were again correlated with clinicopathological characteristics in the validation cohort. DNA methylation profiles reflecting carcinogenetic factors such as smoking and COPD appear to be established in non-cancerous lung tissue from patients with LADCs and may determine the aggressiveness of tumors developing in individual patients, and thus patient outcome. PMID:24921089

  7. Connective tissue responses to some heavy metals. III. Silver and dietary supplements of ascorbic acid. Histology and ultrastructure.

    PubMed Central

    Ellender, G.; Ham, K. N.

    1989-01-01

    Silver-loaded ion exchange resin beads implanted into loose connective tissue of the rat pinna produced a local reaction. Initially the lesion comprised local necrosis and tissue disruption with predominantly small round cell infiltration. The subsequent organization was delayed and disordered. Fibroblasts developed grossly dilated cisternae of the rough endoplasmic reticulum. The matrix contained poorly orientated collagen fibrils of varying size and ground substance appeared condensed and granular. Distorted collagen fibrils were identified within membrane-bound vacuoles in the cytoplasm of both fibroblasts and macrophages. Abnormalities of the silver lesion were indicative of disordered collagen biosynthesis. Silver interfered with the biosynthesis and assembly of matrix components of the connective tissue. The reaction to silver beads in rats maintained on a diet heavily supplemented with ascorbic acid approached that of the control (sodium-loaded bead) with respect to the time scale, tissue reaction and tissue organization. The collagen matrix which formed was more organized and of greater density than that in the rat maintained on a normal diet. However, the repair tissue retained some of the morphological features of the legacy of silver toxicity, in particular delayed repair and dense intracellular fibrils within fibroblasts and macrophages. The excess of ascorbic acid partially ameliorated the effect of silver, possibly by compensating catabolysis of ascorbic acid caused by the presence of the released silver. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 PMID:2923787

  8. Hypoxia induces expression of connective tissue growth factor in scleroderma skin fibroblasts

    PubMed Central

    Hong, K-H; Yoo, S-A; Kang, S-S; Choi, J-J; Kim, W-U; Cho, C-S

    2006-01-01

    Connective tissue growth factor (CTGF) plays a role in the fibrotic process of systemic sclerosis (SSc). Because hypoxia is associated with fibrosis in several profibrogenic conditions, we investigated whether CTGF expression in SSc fibroblasts is regulated by hypoxia. Dermal fibroblasts from patients with SSc and healthy controls were cultured in the presence of hypoxia or cobalt chloride (CoCl2), a chemical inducer of hypoxia-inducible factor (HIF)-1α. Expression of CTGF was evaluated by Northern and Western blot analyses. Dermal fibroblasts exposed to hypoxia (1% O2) or CoCl2 (1–100 µM) enhanced expression of CTGF mRNA. Skin fibroblasts transfected with HIF-1α showed the increased levels of CTGF protein and mRNA, as well as nuclear staining of HIF-1α, which was enhanced further by treatment of CoCl2. Simultaneous treatment of CoCl2 and transforming growth factor (TGF)-β additively increased CTGF mRNA in dermal fibroblasts. Interferon-γ inhibited the TGF-β-induced CTGF mRNA expression dose-dependently in dermal fibroblasts, but they failed to hamper the CoCl2-induced CTGF mRNA expression. In addition, CoCl2 treatment increased nuclear factor (NF)-κB binding activity for CTGF mRNA, while decreasing IκBα expression in dermal fibroblasts. Our data suggest that hypoxia, caused possibly by microvascular alterations, up-regulates CTGF expression through the activation of HIF-1α in dermal fibroblasts of SSc patients, and thereby contributes to the progression of skin fibrosis. PMID:17034590

  9. 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

  10. [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. PMID:26820723

  11. 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

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

    PubMed Central

    Strek, Mary E.

    2013-01-01

    Interstitial lung disease (ILD) is one of the most serious pulmonary complications associated with connective tissue diseases (CTDs), resulting in significant morbidity and mortality. Although the various CTDs associated with ILD often are considered together because of their shared autoimmune nature, there are substantial differences in the clinical presentations and management of ILD in each specific CTD. This heterogeneity and the cross-disciplinary nature of care have complicated the conduct of prospective multicenter treatment trials and hindered our understanding of the development of ILD in patients with CTD. In this update, we present new information regarding the diagnosis and treatment of patients with ILD secondary to systemic sclerosis, rheumatoid arthritis, dermatomyositis and polymyositis, and Sjögren syndrome. We review information on risk factors for the development of ILD in the setting of CTD. Diagnostic criteria for CTD are presented as well as elements of the clinical evaluation that increase suspicion for CTD-ILD. We review the use of medications in the treatment of CTD-ILD. Although a large, randomized study has examined the impact of immunosuppressive therapy for ILD secondary to systemic sclerosis, additional studies are needed to determine optimal treatment strategies for each distinct form of CTD-ILD. Finally, we review new information regarding the subgroup of patients with ILD who meet some, but not all, diagnostic criteria for a CTD. A careful and systematic approach to diagnosis in patients with ILD may reveal an unrecognized CTD or evidence of autoimmunity in those previously believed to have idiopathic ILD. PMID:23460159

  13. 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 .

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

    PubMed

    Subash, Meera; Patel, Gaurav; Welker, John; Nugent, Kenneth

    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

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

    PubMed

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

    2014-04-01

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

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

    PubMed Central

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

    2014-01-01

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

  17. Effects of interleukins on connective tissue type mast cells co-cultured with fibroblasts.

    PubMed Central

    Levi-Schaffer, F; Segal, V; Shalit, M

    1991-01-01

    We investigated the effects of interleukin-2 (IL-2), interleukin-3 (IL-3) and interleukin-4 (IL-4) on mouse and rat peritoneal mast cells (MC) co-cultured with 3T3 fibroblasts (MC/3T3). The continuous presence of these cytokines for 7-9 days in the culture media was neither toxic nor caused proliferation of MC, as determined by the stability of MC numbers in culture. Long-term incubation of mouse MC/3T3 with IL-2 (100 U/ml), IL-3 (50 U/ml), IL-4 (50 U/ml) or a mixture of IL-3 and IL-4 (25 U/ml) induced an increase in basal histamine release of 79.3 +/- 19.0%, 41.0 +/- 17.3%, 25.2 +/- 10.4% and 30.2 +/- 3.2%, respectively, over control cells incubated with medium alone. When rat MC/3T3 were incubated for 7 days with the various interleukins an enhancement in histamine release similar to that observed with mouse MC/3T3 was found. Preincubation (1 hr) of rat MC/3T3 with interleukins prior to immunological activation with anti-IgE antibodies enhanced histamine release. The highest effect was observed with IL-3 + IL-4 (60.4 +/- 10.8% increase) followed by IL-2 (51.5 +/- 4.5%), IL-4 (28.6 +/- 10.3%) and IL-3 (13.2 +/- 4.2%). This study demonstrates that when mouse and rat peritoneal MC are cultured with fibroblasts in the presence of interleukins they do not proliferate, suggesting that they preserve their connective tissue type MC phenotype. Moreover, interleukins display a pro-inflammatory effect on these cells by enhancing both basal and anti-IgE-mediated histamine release. PMID:2016117

  18. 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

  19. Molecular insights into connective tissue growth factor action in rat pancreatic stellate cells.

    PubMed

    Karger, Anna; Fitzner, Brit; Brock, Peter; Sparmann, Gisela; Emmrich, Jörg; Liebe, Stefan; Jaster, Robert

    2008-10-01

    Pancreatic fibrosis, a key feature of chronic pancreatitis and pancreatic cancer, is mediated by activated pancreatic stellate cells (PSC). Connective tissue growth factor (CTGF) has been suggested to play a major role in fibrogenesis by enhancing PSC activation after binding to alpha5beta1 integrin. Here, we have focussed on molecular determinants of CTGF action. Inhibition of CTGF expression in PSC by siRNA was associated with decreased proliferation, while application of exogenous CTGF stimulated both cell growth and collagen synthesis. Real-time PCR studies revealed that CTGF target genes in PSC not only include mediators of matrix remodelling but also the proinflammatory cytokines interleukin (IL)-1beta and IL-6. CTGF stimulated binding of NF-kappaB to the IL-6 promoter, and siRNA targeting the NF-kappaB subunit RelA interfered with CTGF-induced IL-6 expression, implicating the NF-kappaB pathway in the mediation of the CTGF effect. In further studies, we have analyzed regulation of CTGF expression in PSC. Transforming growth factor-beta1, activin A and tumor necrosis factor-alpha enhanced expression of the CTGF gene, while interferon-gamma displayed the opposite effect. The region from -74 to -125 of the CTGF promoter was revealed to be critical for its activity in PSC as well as for the inhibitory effect of interferon-gamma. Taken together, our results indicate a tight control of CTGF expression in PSC at the transcriptional level. CTGF promotes fibrogenesis both directly by enhancing PSC proliferation and matrix protein synthesis, and indirectly through the release of proinflammatory cytokines that may accelerate the process of chronic inflammation. PMID:18639630

  20. 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

  1. Influence of biologic therapy on growth in children with chronic inflammatory connective tissue diseases

    PubMed Central

    Zygmunt, Agnieszka; Biernacka-Zielińska, Małgorzata; Stańczyk, Jerzy; Smolewska, Elżbieta

    2015-01-01

    Objectives Connective tissue diseases (CTD) are a heterogeneous group of chronic inflammatory conditions. One of their complications in children is the inhibition of growth velocity. Due to direct inflammation within the musculoskeletal system as well as glucocorticoid therapy, this feature is the most essential and is mainly expressed in the course of juvenile spondyloarthropathies and juvenile idiopathic arthritis (JIA). Duration of the disease, but predominantly the activity of the inflammatory process, seems to have a significant impact on the abnormal growth profile in children. Effective biological therapy leads to improvement of the patient's clinical condition and also, through the extinction of disease activity and reduction of daily doses of glucocorticosteroids (GCS), it gradually accelerates and normalizes the growth rate in children with CTD. Our objective was to evaluate the impact of biological therapy on growth in children with chronic inflammatory CTD. Material and methods Data from 24 patients with CTD treated with tumor necrosis factor-α-blockers (etanercept, adalimumab, golimumab) and an interleukin-6 receptor blocker (tocilizumab) were reviewed at the time of disease onset, biological treatment initiation and at least 12 up to 24 months onwards. The rate of growth was correlated with the daily doses of GCS, and the type and duration of biological therapy. Results Patient median height, measured as the change in height standard deviation score, was 0.36 ±1.07 at disease onset and –0.13 ±1.02 at biologic therapy initiation. The growth velocity accelerated in 17 patients (70.1%) during the biological treatment. Mean height-SDS improvement between biological treatment initiation up to two years was 0.51 ±0.58. In 47% of patients daily doses of GCS were reduced to 0 mg/kg/day. Conclusions In the treatment of CTD, biological agents restore growth velocity not only by inflammation inhibition, but also through limiting GCS daily doses.

  2. 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.

  3. Gelatinase A (MMP-2) and cysteine proteinases are essential for the degradation of collagen in soft connective tissue.

    PubMed

    Creemers, L B; Jansen, I D; Docherty, A J; Reynolds, J J; Beertsen, W; Everts, V

    1998-04-01

    The degradation of soft connective tissue collagen is considered to depend on the activity of various proteolytic enzymes, particularly those belonging to the group of matrix metalloproteinases and cysteine proteinases. In the present study, we investigated the contribution of these enzymes to this process. Using a general inhibitor of MMPs (SC44463), collagen degradation was strongly inhibited, by about 40% after 24 h and up to 80% after 72 h of culturing. Blockage of cysteine proteinase activity (with leupeptin or E-64) reduced breakdown at these time intervals by 50% and 20%, respectively. Given the abundant presence of gelatinases--in particular gelatinase A (MMP-2)--in the tissue, the effect of an inhibitor selective for gelatinases (CT1166) was studied. Gelatinase inhibition resulted in a dose-dependent decrease of collagen breakdown up to 90% after 48 h. The ability of gelatinase A to degrade collagens was demonstrated by the induction of breakdown in devitalized explants by addition of activated gelatinase A, or by activation of endogenous enzyme with 4-aminophenylmercuric acetate. This latter effect was not found with plasmin, an activator of MMPs other than gelatinase A. Finally, the relevance of gelatinase A to the in vivo degradation of soft connective tissue collagen was implicated by the significant correlation found between its activity and the collagen turnover rates of four soft connective tissues (tooth pulp, periodontal ligament, molar gingiva and skin). We conclude that collagen degradation in soft connective tissue is mediated by MMPs and to a lesser extent by cysteine proteinases. Our data are the first to attach a key role to gelatinase A in this process. PMID:9628251

  4. Proteoglycan metabolism in the connective tissue of pregnant and non-pregnant human cervix. An in vitro study.

    PubMed

    Norman, M; Ekman, G; Ulmsten, U; Barchan, K; Malmström, A

    1991-04-15

    Profound changes occur in the cervix during pregnancy. In particular, the connective tissue is remodelled. To elucidate the mechanisms behind this process, the metabolism of cervical connective tissue was studied using tissue cultures. Cervical biopsies from non-pregnant and pregnant women were incubated with [35S]sulphate. The proteoglycans of the tissue specimens were purified by ion-exchange and gel chromatography and characterized by SDS/PAGE and by enzymic degradation. In the non-pregnant cervix, the incorporation of [35S]sulphate into the proteoglycans was linear for 48 h. During the first 6 h of incubation the accumulation of chiefly one small labelled proteoglycan (apparent Mr 110,000) substituted with dermatan sulphate was recorded. This is in accordance with the known proteoglycan composition of non-pregnant cervical tissue. In addition, small amounts of two larger radioactive dermatan/chondroitin sulphate proteoglycans (apparent Mr values 220,000 and greater than 500,000) were recorded. After longer periods of incubation the proportion of heparan sulphate proteoglycans increased considerably. The pregnant tissue showed a clearly different composition of labelled proteoglycans. An increased accumulation of the two larger dermatan/chondroitin sulphate proteoglycans was seen in addition to the dominant small dermatan sulphate proteoglycan of the non-pregnant cervix. The rate of accumulation of these two proteoglycans was about 3 times higher in the pregnant tissue, whereas that of the small dermatan sulphate proteoglycan was only increased 2-fold. The fact that the concentration of proteoglycans in the pregnant cervix is approximately one-half of that in the non-pregnant cervix indicates that the turnover of proteoglycans in pregnant cervical tissue is significantly increased. The major effect of this profound change of metabolism was a 50% decrease in proteoglycan content and a 2-fold increased proportion of a dermatan sulphate proteoglycan with an

  5. Proteoglycan metabolism in the connective tissue of pregnant and non-pregnant human cervix. An in vitro study.

    PubMed Central

    Norman, M; Ekman, G; Ulmsten, U; Barchan, K; Malmström, A

    1991-01-01

    Profound changes occur in the cervix during pregnancy. In particular, the connective tissue is remodelled. To elucidate the mechanisms behind this process, the metabolism of cervical connective tissue was studied using tissue cultures. Cervical biopsies from non-pregnant and pregnant women were incubated with [35S]sulphate. The proteoglycans of the tissue specimens were purified by ion-exchange and gel chromatography and characterized by SDS/PAGE and by enzymic degradation. In the non-pregnant cervix, the incorporation of [35S]sulphate into the proteoglycans was linear for 48 h. During the first 6 h of incubation the accumulation of chiefly one small labelled proteoglycan (apparent Mr 110,000) substituted with dermatan sulphate was recorded. This is in accordance with the known proteoglycan composition of non-pregnant cervical tissue. In addition, small amounts of two larger radioactive dermatan/chondroitin sulphate proteoglycans (apparent Mr values 220,000 and greater than 500,000) were recorded. After longer periods of incubation the proportion of heparan sulphate proteoglycans increased considerably. The pregnant tissue showed a clearly different composition of labelled proteoglycans. An increased accumulation of the two larger dermatan/chondroitin sulphate proteoglycans was seen in addition to the dominant small dermatan sulphate proteoglycan of the non-pregnant cervix. The rate of accumulation of these two proteoglycans was about 3 times higher in the pregnant tissue, whereas that of the small dermatan sulphate proteoglycan was only increased 2-fold. The fact that the concentration of proteoglycans in the pregnant cervix is approximately one-half of that in the non-pregnant cervix indicates that the turnover of proteoglycans in pregnant cervical tissue is significantly increased. The major effect of this profound change of metabolism was a 50% decrease in proteoglycan content and a 2-fold increased proportion of a dermatan sulphate proteoglycan with an

  6. Tissue Stretch Decreases Soluble TGF-β1 and Type-1 Procollagen in Mouse Subcutaneous Connective Tissue: Evidence From Ex Vivo and In Vivo Models

    PubMed Central

    Bouffard, Nicole A.; Cutroneo, Kenneth R.; Badger, Gary J.; White, Sheryl L.; Buttolph, Thomas R.; Ehrlich, H. Paul; Stevens-Tuttle, Debbie; Langevin, Helene M.

    2011-01-01

    Transforming growth factor beta 1 (TGF-β1) plays a key role in connective tissue remodeling, scarring, and fibrosis. The effects of mechanical forces on TGF-β1 and collagen deposition are not well understood. We tested the hypothesis that brief (10 min) static tissue stretch attenuates TGF-β1-mediated new collagen deposition in response to injury. We used two different models: (1) an ex vivo model in which excised mouse subcutaneous tissue (N = 44 animals) was kept in organ culture for 4 days and either stretched (20% strain for 10 min 1 day after excision) or not stretched; culture media was assayed by ELISA for TGF-β1; (2) an in vivo model in which mice (N = 22 animals) underwent unilateral subcutaneous microsurgical injury on the back, then were randomized to stretch (20–30% strain for 10 min twice a day for 7 days) or no stretch; subcutaneous tissues of the back were immunohistochemically stained for Type-1 procollagen. In the ex vivo model, TGF-β1 protein was lower in stretched versus non-stretched tissue (repeated measures ANOVA, P < 0.01). In the in vivo model, microinjury resulted in a significant increase in Type-1 procollagen in the absence of stretch (P < 0.001), but not in the presence of stretch (P = 0.21). Thus, brief tissue stretch attenuated the increase in both soluble TGF-β1 (ex vivo) and Type-1 procollagen (in vivo) following tissue injury. These results have potential relevance to the mechanisms of treatments applying brief mechanical stretch to tissues (e.g., physical therapy, respiratory therapy, mechanical ventilation, massage, yoga, acupuncture). PMID:17654495

  7. 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.

  8. 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.

  9. 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.

  10. [Chosen problems of mental functioning in patients with chronic systemic connective tissue diseases base on example of rheumatoid arthritis].

    PubMed

    Nasiłowska-Barud, Alicja; Żuk, Mariola

    2015-01-01

    Disorders in mental functioning are indicated as the cause of all connective tissue diseases and also as their consequences. That is why psychologist's help may be very important for patients with rheumatoid arthritis. Psychological observations of patients with chronic systemic connective tissue diseases show a number of negative emotional states such as fear, anxiety, insecurity, depressed mood, depression, impatience, anger and a sense of loss These patients constantly experience pain of varying intensity and location. In many of them progressive disease leads to the advancement of mental crisis. Methods of psychological therapy must be focused on strenghtening mental resilience and helping in surviving mental crisis. Psychological therapy should concentrate on raising self-esteem, training interpersonal skills and teaching relaxation techniques to cope better with pain and suffering. Psychological therapy should support the patient in struggling with the problems caused by the disease and developing ways of adapting to life with the disease. PMID:26753214

  11. 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

  12. 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. PMID:26377236

  13. 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

  14. Short- and Long-term Outcomes in Patients with Connective Tissue Diseases Undergoing Percutaneous Coronary Intervention

    PubMed Central

    Zhou, Li; Chen, Hui; Li, Wei-Ping; Gao, Hong-Li; Li, Dong-Bao; Zhao, Hui-Qiang; Yao, Dao-Kuo; Li, Hong-Wei

    2016-01-01

    Background: Coronary artery disease (CAD) is a leading cause of morbidity and mortality in patients with connective tissue diseases (CTDs). Risk factors and clinical characteristics in these patients are not equivalent to those in traditional CAD patients. The objective of this study was to report short- and long-term clinical outcomes in a consecutive series of patients with CTD who underwent percutaneous coronary intervention (PCI) with stent implantation. Methods: The study group comprised 106 consecutive patients with CTD who underwent PCI in Beijing Friendship Hospital between January 2009 and June 2012. Medical records were analyzed retrospectively including clinical basic material, coronary angiogram data, and the incidence of major adverse cardiac events (MACEs) during the short- and long-term (median 3 years) follow-up. Results: Ninety-two of the patients (86.8%) had one or more traditional CAD risk factors. Multivessel disease was present in more than 2/3 of patients (73.6%). The left anterior descending coronary artery was the most commonly affected vessel (65.1%). Five bare-metal stents and 202 drug-eluting stents were implanted. After a median follow-up period of 36 months, thirteen patients (12.3%) died from cardiac causes, the rate of stent thrombosis was 9.4%, and the rate of target vessel revascularization (TVR) was 14.2%. Multivariate analysis revealed that hypertension (hazard ratio [HR] = 3.07, 95% confidence interval [CI]: 1.30–7.24, P = 0.041), anterior myocardial infarction (HR = 2.77, 95% CI: 1.06–7.03, P = 0.04), longer duration of steroid treatment (HR = 3.60, 95% CI: 1.43–9.08, P = 0.032), and C-reactive protein level >10 mg/L (HR = 3.98, 95% CI: 1.19–12.56, P = 0.036) were independent predictors of MACEs. Conclusions: Patients with CTD and CAD may have severe coronary lesions. PCI in these patients tends to result in an increased rate of stent thrombosis and TVR during long-term follow-up, which may be influenced by traditional

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

    PubMed Central

    Yi, Zuohuizi; Huang, Dehui; Wei, Shihui

    2014-01-01

    Background Optic neuritis (ON) is often associated with other clinical or serological markers of connective tissue diseases (CTDs). To date, the effects of autoantibodies on ON are not clear. Purpose To assess the prevalence, clinical patterns, and short outcomes of autoantibodies and Sjögren’s syndrome (SS) involvement in Chinese ON patients and evaluate the relationship between ON, including their subtypes, and autoantibodies. Methods A total of 190 ON patients were divided into recurrent ON (RON), bilateral ON (BON), and isolated monocular ON (ION). Demographic, clinical, and serum autoantibodies data were compared between them with and without SS involvement. Serum was drawn for antinuclear antibody (ANA), extractable nuclear antigen antibodies (SSA/SSB), rheumatoid factor (RF), anticardiolipin antibodies (ACA), and anti-double-stranded DNA antibody (A-ds DNA), anticardiolipin antibody (ACLs), anti-β2-glycoprotein I (β2-GPI) and Aquaporin-4 antibodies (AQP4-Ab). Spectral-domain optical coherence tomography (SD-OCT) was used to evaluate the atrophy of the optic nerve. Results 68 patients (35.79%) had abnormal autoantibodies, 26(13.68%) patients met diagnostic criteria for CTDs, including 15(7.89%) patients meeting the criteria for SS. Antibodies including SSA/SSB 23 (30.26%) (p1 and p 2<0.001) and AQP4–Ab10 (13.16%) (p1 = 0.044, p2 = 0.01) were significantly different in patients in the RON group when compared with those in the BON (P1 = RON VS ION) and ION (p2 = RON VS ION) groups. SS was more common in RON patients (p1 = 0.04, p2 = 0.028). There was no significant difference between SSA/SSB positive and negative patients in disease characteristics or severity. Similar results were obtained when SS was diagnosed in SSA/SSB positive patients. Conclusion RON and BON were more likely associated with abnormal autoantibodies; furthermore, AQP4 antibody, SSA/SSB and SS were more common in the RON patients. AQP4 antibodydetermination is

  16. Predictors of mortality in connective tissue disease-associated pulmonary arterial hypertension: a cohort study

    PubMed Central

    2012-01-01

    Introduction Pulmonary arterial hypertension (PAH) is a major cause of mortality in connective tissue disease (CTD). We sought to quantify survival and determine factors predictive of mortality in a cohort of patients with CTD-associated PAH (CTD-PAH) in the current era of advanced PAH therapy. Methods Patients with right heart catheter proven CTD-PAH were recruited from six specialised PAH treatment centres across Australia and followed prospectively. Using survival methods including Cox proportional hazards regression, we modelled for all-cause mortality. Independent variables included demographic, clinical and hemodynamic data. Results Among 117 patients (104 (94.9%) with systemic sclerosis), during 2.6 ± 1.8 (mean ± SD) years of follow-up from PAH diagnosis, there were 32 (27.4%) deaths. One-, two- and three-year survivals were 94%, 89% and 73%, respectively. In multiple regression analysis, higher mean right atrial pressure (mRAP) at diagnosis (hazard ratio (HR) = 1.13, 95% CI: 1.04 to 1.24, P = 0.007), lower baseline six-minute walk distance (HR = 0.64, 95% CI: 0.43 to 0.97, P = 0.04), higher baseline World Health Organization functional class (HR = 3.42, 95% CI: 1.25 to 9.36, P = 0.04) and presence of a pericardial effusion (HR = 3.39, 95% CI: 1.07 to 10.68, P = 0.04) were predictive of mortality. Warfarin (HR = 0.20, 95% CI: 0.05 to 0.78, P = 0.02) and combination PAH therapy (HR = 0.20, 95% CI: 0.05 to 0.83, P = 0.03) were protective. Conclusions In this cohort of CTD-PAH patients, three-year survival was 73%. Independent therapeutic predictors of survival included warfarin and combination PAH therapy. Our findings suggest that anticoagulation and combination PAH therapy may improve survival in CTD-PAH. This observation merits further evaluation in randomised controlled trials. PMID:23039366

  17. 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

  18. 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. PMID:20085374

  19. 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

  20. 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

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

    PubMed Central

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

    2004-01-01

    Background Broad-band UVA, long-wave UVA1 and PUVA treatment have been described as an alternative/adjunct therapeutic option in a number of inflammatory and malignant skin diseases. Nevertheless, controlled studies investigating the efficacy of UVA irradiation in connective tissue diseases and related disorders are rare. Methods Searching the PubMed database the current article systematically reviews established and innovative therapeutic approaches of broad-band UVA irradiation, UVA1 phototherapy and PUVA photochemotherapy in a variety of different connective tissue disorders. Results Potential pathways include immunomodulation of inflammation, induction of collagenases and initiation of apoptosis. Even though holding the risk of carcinogenesis, photoaging or UV-induced exacerbation, UVA phototherapy seems to exhibit a tolerable risk/benefit ratio at least in systemic sclerosis, localized scleroderma, extragenital lichen sclerosus et atrophicus, sclerodermoid graft-versus-host disease, lupus erythematosus and a number of sclerotic rarities. Conclusions Based on the data retrieved from the literature, therapeutic UVA exposure seems to be effective in connective tissue diseases and related disorders. However, more controlled investigations are needed in order to establish a clear-cut catalogue of indications. PMID:15380024

  2. 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

  3. TE = 32 ms vs TE = 100 ms echo‐time 1H‐magnetic resonance spectroscopy in prostate cancer: Tumor metabolite depiction and absolute concentrations in tumors and adjacent tissues

    PubMed Central

    Basharat, Meer; Morgan, Veronica A.; Parker, Chris; Dearnaley, David; deSouza, Nandita M.

    2015-01-01

    Purpose To compare the depiction of metabolite signals in short and long echo time (TE) prostate cancer spectra at 3T, and to quantify their concentrations in tumors of different stage and grade, and tissues adjacent to tumor. Materials and Methods First, single‐voxel magnetic resonance imaging (MRI) spectra were acquired from voxels consisting entirely of tumor, as defined on T 2‐weighted and diffusion‐weighted (DW)‐MRI and from a biopsy‐positive octant, at TEs of 32 msec and 100 msec in 26 prostate cancer patients. Then, in a separate cohort of 26 patients, single‐voxel TE = 32 msec MR spectroscopy (MRS) was performed over a partial‐tumor region and a matching, contralateral normal‐appearing region, defined similarly. Metabolite depiction was compared between TEs using Cramér‐Rao lower bounds (CRLB), and absolute metabolite concentrations were calculated from TE = 32 msec spectra referenced to unsuppressed water spectra. Results Citrate and spermine resonances in tumor were better depicted (had significantly lower CRLB) at TE = 32 msec, while the choline resonance was better depicted at TE = 100 msec. Citrate and spermine concentrations were significantly lower in patients of more advanced stage, significantly lower in Gleason grade 3+4 than 3+3 tumors, and significantly lower than expected from the tumor fraction in partial‐tumor voxels (by 14 mM and 4 mM, respectively, P < 0.05). Conclusion Citrate and spermine resonances are better depicted at short TE than long TE in tumors. Reduction in these concentrations is related to increasing tumor stage and grade in vivo, while reductions in the normal‐appearing tissues immediately adjacent to tumor likely reflect tumor field effects. J. Magn. Reson. Imaging 2015;42:1086–1093. PMID:26258905

  4. Adjacent segment disease.

    PubMed

    Virk, Sohrab S; Niedermeier, Steven; Yu, Elizabeth; Khan, Safdar N

    2014-08-01

    EDUCATIONAL OBJECTIVES As a result of reading this article, physicians should be able to: 1. Understand the forces that predispose adjacent cervical segments to degeneration. 2. Understand the challenges of radiographic evaluation in the diagnosis of cervical and lumbar adjacent segment disease. 3. Describe the changes in biomechanical forces applied to adjacent segments of lumbar vertebrae with fusion. 4. Know the risk factors for adjacent segment disease in spinal fusion. Adjacent segment disease (ASD) is a broad term encompassing many complications of spinal fusion, including listhesis, instability, herniated nucleus pulposus, stenosis, hypertrophic facet arthritis, scoliosis, and vertebral compression fracture. The area of the cervical spine where most fusions occur (C3-C7) is adjacent to a highly mobile upper cervical region, and this contributes to the biomechanical stress put on the adjacent cervical segments postfusion. Studies have shown that after fusion surgery, there is increased load on adjacent segments. Definitive treatment of ASD is a topic of continuing research, but in general, treatment choices are dictated by patient age and degree of debilitation. Investigators have also studied the risk factors associated with spinal fusion that may predispose certain patients to ASD postfusion, and these data are invaluable for properly counseling patients considering spinal fusion surgery. Biomechanical studies have confirmed the added stress on adjacent segments in the cervical and lumbar spine. The diagnosis of cervical ASD is complicated given the imprecise correlation of radiographic and clinical findings. Although radiological and clinical diagnoses do not always correlate, radiographs and clinical examination dictate how a patient with prolonged pain is treated. Options for both cervical and lumbar spine ASD include fusion and/or decompression. Current studies are encouraging regarding the adoption of arthroplasty in spinal surgery, but more long

  5. 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

  6. 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

  7. Plasticity of integrin expression by nerve-derived connective tissue cells. Human Schwann cells, perineurial cells, and fibroblasts express markedly different patterns of beta 1 integrins during nerve development, neoplasia, and in vitro.

    PubMed Central

    Hsiao, L L; Peltonen, J; Jaakkola, S; Gralnick, H; Uitto, J

    1991-01-01

    Strikingly selective expression patterns of beta 1, alpha 2, alpha 3, and alpha 5 integrin subunits were revealed in endoneurium, perineurium, and epineurium of fetal and adult human peripheral nerve by immunostaining with specific antibodies. The alpha 2 subunit was expressed only on Schwann cells both in fetal and adult nerve, whereas the alpha 3 epitopes were expressed exclusively in the adult tissue and were primarily present on perineurial cells. The alpha 5 epitopes were expressed only on the innermost cell layer of perineurium of fetal and adult nerve. The tumor cells within schwannomas and cutaneous neurofibromas expressed both alpha 2 and alpha 3 subunits, indicating that Schwann cells have the potential to express also the alpha 3 subunit in vivo. Cell cultures established from human fetal nerve and neurofibromas revealed expression of the alpha 2 and alpha 5 epitopes on Schwann cells, perineurial cells, and fibroblasts, whereas only Schwann cells contained the alpha 3 epitopes which were occasionally concentrated on the adjacent Schwann cells at cell-cell contacts. Our findings emphasize that nerve connective tissue cells change their profiles for expression of extracellular matrix receptors under conditions which have different regulatory control signals exerted by, for example, axons, humoral factors, or the extracellular matrix of the peripheral nerve. This plasticity may play an important role during nerve development and in neoplastic processes affecting the connective tissue compartments of peripheral nerve. Images PMID:1999496

  8. 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

  9. Contribution of myofibrillar and connective tissue components to the Warner-Bratzler shear force of cooked beef.

    PubMed

    Girard, I; Bruce, H L; Basarab, J A; Larsen, I L; Aalhus, J L

    2012-12-01

    Myofibrillar (MF-SF) and connective tissue (CT-SF) peak shear forces were interpolated from Warner-Bratzler shear force (SF) deformation curves of cooked bovine M. gluteus medius (GM) and M. semitendinosus (ST) from 112 crossbred steers in a 2×2×2 factorial experiment examining the interactions between slaughter age, growth promotants and breed cross (British versus Continental). Mixed model analyses, Pearson correlations and stepwise multiple regression identified relationships between shear forces, meat quality measurements and production treatments. Connective tissue contribution to SF increased with slaughter age and implantation in the ST and with slaughter age only in the GM. Myofibrillar contribution to SF increased with slaughter age for the ST and with Continental genetics for the GM. Variation in ST SF and MF-SF was best described by muscle weight, which increased with animal age, while GM SF and MF-SF variation was best described by cooking loss, indicating that ST and GM SF were most affected by connective and myofibrillar proteins, respectively. PMID:22842042

  10. U1-RNP and Toll-like receptors in the pathogenesis of mixed connective tissue diseasePart II. Endosomal TLRs and their biological significance in the pathogenesis of mixed connective tissue disease

    PubMed Central

    2015-01-01

    Mixed connective tissue disease (MCTD) is a chronic autoimmune immunopathological disease of unknown etiology, which is characterized by the presence of various clinical symptoms and the presence of autoantibodies against U1-RNP particles. The U1-RNP component engages immune cells and their receptors in a complex network of interactions that ultimately lead to autoimmunity, inflammation, and tissue injury. The anti-U1-RNP autoantibodies form an immune complex with self-RNA, present in MCTD serum, which can act as endosomal Toll-like receptor (TLR) ligands. Inhibition of TLRs by nucleic acids is a promising area of research for the development of novel therapeutic strategies against pathogenic infection, tumorigenesis and autoimmunity. In this review we summarize current knowledge of endogenous TLRs and discuss their biological significance in the pathogenesis of MCTD. In part I we described the structure, biological function and significance of the U1-RNP complex in MCTD.

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

    PubMed Central

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

    2015-01-01

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

  12. [Effect of metabolic therapy on the course of heart failure in patients after myocarditis complicated with systemic connecting tissue diseases].

    PubMed

    Kuriata, A V; Karavanskaia, I L; Pavlichenko, N A

    2010-01-01

    In the course of observation over 40 patients after an old myocarditis against general systemic diseases of connective tissue who had been given a pharmacotherapy regarding main disease and a chronic heart failure, additionally Vazonat (campaign of "Olajnfarm", Latvia), preparation of the myocardial cytoprotection was prescribed in a therapeutic dose of 500 mg per day. Vazonat inclusion in basic therapy during 1 month was accompanied by improvement of a clinical condition of the patients, reduction of heart failure signs, and improvement of life quality. PMID:21488376

  13. Morphometric analysis of cellular and vascular changes in gingival connective tissue in long-term insulin-dependent diabetes.

    PubMed

    Seppälä, B; Sorsa, T; Ainamo, J

    1997-12-01

    This study examined cellular and vascular changes in gingival connective tissue samples by stereologic point-counting procedures and interactive digital analyzing systems in long-term insulin-dependent diabetes mellitus patients. Gingival connective tissue capillaries representing a clinically healthy sulcus with no evidence of periodontal disease at the site of biopsy were studied in 29 patients with diabetes. Based upon their long-term medical records, 19 were identified as having poorly controlled (PIDD) and 10 as controlled insulin-dependent diabetes mellitus (CIDD). Ten nondiabetic, age- and gender-matched individuals served as controls. Thirty-nine biopsies were processed for light microscopy, and the blood vessel area was analyzed using an interactive digital analyzing system; 9 gingival biopsies, 5 diabetic and 4 controls, were processed for morphometric electron microscopic analysis. For each individual, site-specific recordings were made for the plaque index, bleeding index, probing depth, loss of attachment, and radiographic loss of interproximal alveolar bone. No evident signs of periodontitis occurred at the biopsy sites. For each PIDD patient, respective volumetric and numeric densities of cellular components including fibroblasts, neutrophilic granulocytes, monocyte/macrophages, mast cells, lymphocytes, blast cells, and plasma cells were recorded in the inflamed connective tissue (ICT). Non-cellular components such as collagen fibers and blood vessels were also recorded. PIDD patients had elevated plasma cell levels relative to controls and they appeared also to have a decreased collagen fiber density. In addition, fibroblasts occupied less volume in the ICT of PIDD patients than in controls. PIDD patients had the largest mean area of cross-section of the blood vessels, but this difference was not statistically significant (P > or = 0.211; t-test). No specific characteristics of ICT or vascular changes were detectable in adult well-controlled long

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

    SciTech Connect

    Kubota, Jun; Tsunemura, Mami; Amano, Shigeko; Tokizawa, Shigemi; Oowada, Susumu; Shinkai, Hiroko; Maehara, Yasunobu; Endo, Keigo

    1997-05-15

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

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

    PubMed Central

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

    2014-01-01

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

  16. Unusual Glycosaminoglycans from a Deep Sea Hydrothermal Bacterium Improve Fibrillar Collagen Structuring and Fibroblast Activities in Engineered Connective Tissues

    PubMed Central

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

    2013-01-01

    Biopolymers produced by marine organisms can offer useful tools for regenerative medicine. Particularly, HE800 exopolysaccharide (HE800 EPS) secreted by a deep-sea hydrothermal bacterium displays an interesting glycosaminoglycan-like feature resembling hyaluronan. Previous studies demonstrated its effectiveness to enhance in vivo bone regeneration and to support osteoblastic cell metabolism in culture. Thus, in order to assess the usefulness of this high-molecular weight polymer in tissue engineering and tissue repair, in vitro reconstructed connective tissues containing HE800 EPS were performed. We showed that this polysaccharide promotes both collagen structuring and extracellular matrix settle by dermal fibroblasts. Furthermore, from the native HE800 EPS, a low-molecular weight sulfated derivative (HE800 DROS) displaying chemical analogy with heparan-sulfate, was designed. Thus, it was demonstrated that HE800 DROS mimics some properties of heparan-sulfate, such as promotion of fibroblast proliferation and inhibition of matrix metalloproteinase (MMP) secretion. Therefore, we suggest that the HE800EPS family can be considered as an innovative biotechnological source of glycosaminoglycan-like compounds useful to design biomaterials and drugs for tissue engineering and repair. PMID:23612369

  17. 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. PMID:25815693

  18. 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

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

    PubMed Central

    Castori, Marco

    2012-01-01

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

  20. Ehlers-danlos syndrome, hypermobility type: an underdiagnosed hereditary connective tissue disorder with mucocutaneous, articular, and systemic manifestations.

    PubMed

    Castori, Marco

    2012-01-01

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

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

    PubMed

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

    2013-05-01

    Mutations conferring loss of function at the FLNA (encoding filamin A) locus lead to X-linked periventricular nodular heterotopia (XL-PH), with seizures constituting the most common clinical manifestation of this disorder in female heterozygotes. Vascular dilatation (mainly the aorta), joint hypermobility and variable skin findings are also associated anomalies, with some reports suggesting that this might represents a separate syndrome allelic to XL-PH, termed as Ehlers-Danlos syndrome-periventricular heterotopia variant (EDS-PH). Here, we report a cohort of 11 males and females with both hypomorphic and null mutations in FLNA that manifest a wide spectrum of connective tissue and vascular anomalies. The spectrum of cutaneous defects was broader than previously described and is inconsistent with a specific type of EDS. We also extend the range of vascular anomalies associated with XL-PH to included peripheral arterial dilatation and atresia. Based on these observations, we suggest that there is little molecular or clinical justification for considering EDS-PH as a separate entity from XL-PH, but instead propose that there is a spectrum of vascular and connective tissues anomalies associated with this condition for which all individuals with loss-of-function mutations in FLNA should be evaluated. In addition, since some patients with XL-PH can present primarily with a joint hypermobility syndrome, we propose that screening for cardiovascular manifestations should be offered to those patients when there are associated seizures or an X-linked pattern of inheritance. PMID:23032111

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

    PubMed Central

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

    2011-01-01

    The directed migration of cells towards chemical stimuli incorporates simultaneous changes in both the concentration of a chemotactic agent and its concentration gradient, each of which may influence cell migratory response. In this study, we utilized a microfluidic system to examine the interactions between Epidermal Growth Factor (EGF) concentration and EGF gradient in stimulating the chemotaxis of connective-tissue derived fibroblast cells. Cells seeded within microfluidic devices were exposed to concentration gradients established by EGF concentrations that matched or exceeded those required for maximum chemotactic responses seen in transfilter migration assays. The migration of individual cells within the device was measured optically after steady-state gradients had been experimentally established. Results illustrate that motility was maximal at EGF concentration gradients between .01- and 0.1-ng/(mL.mm) for all concentrations used. In contrast, the numbers of motile cells continually increased with increasing gradient steepness for all concentrations examined. Microfluidics-based experiments exposed cells to minute changes in EGF concentration and gradient that were in line with the acute EGFR phosphorylation measured. Correlation of experimental data with established mathematical models illustrated that the fibroblasts studied exhibit an unreported chemosensitivity to minute changes in EGF concentration, similar to that reported for highly motile cells, such as macrophages. Our results demonstrate that shallow chemotactic gradients, while previously unexplored, are necessary to induce the rate of directed cellular migration and the number of motile cells in the connective tissue-derived cells examined. PMID:21536028

  3. The Fine Structure of Experimentally Induced Connective Tissue Complexes in the Human

    PubMed Central

    Stinson, W. W.; Richter, K. M.; Schilling, J. A.

    1974-01-01

    The growth, development and cellular activity of fibrocollagenous tissue complexes induced by the implantation of specially structured wire mesh cylinders in 22 human male volunteers were studied during the time course of fibroplasia utilizing light and electron microscopic techniques. The fibrocollagenous tissue complexes after 4 to 16 weeks of development demonstrated highly ordered lamellations made of zones consisting primarily of fibroblasts and zones consisting primarily of collagenous fibers. The development of the ordered lamellations is referable to specific fibrillogenic activities by the constituent fibroblasts. The initial role of the fibroblast in fibrillogenesis is indicative of an apocrine-like secretory process followed by a holocrine-like role which results in cytodestruction and concurrent formation of an avascular collagenic tissue referable to an organizing cicatrix in a healing wound. ImagesFigs. 1-3.Figs. 4-9.Fig. 10.Fig. 11.Fig. 12.Figs. 13, 14.Fig. 15.Fig. 16.Fig. 17.Fig. 18, 19.Figs. 20-22.Fig. 23.Fig. 24. PMID:4599224

  4. Increased connective tissue attachment to silicone implants by a water vapor plasma treatment.

    PubMed

    Jensen, C; Gurevich, L; Patriciu, A; Struijk, J J; Zachar, V; Pennisi, C P

    2012-12-01

    Polydimethylsiloxane (PDMS) is the most common type of silicone polymer for the fabrication of implantable medical devices. Because of its inherent hydrophobic nature, the PDMS surface does not readily promote cellular adhesion, which leads to diverse clinical issues. Previously, we reported a simple water vapor plasma treatment of PDMS surfaces that resulted in stable long-term wettability and excellent in vitro cell compatibility. In this work, we report investigation of the in vivo local responses to PDMS implants treated by water vapor plasma using a subcutaneous rat model. The local tissue responses were assessed after 2 and 4 weeks of implantation by means of macroscopic and histomorphometric analysis. After 2 weeks of implantation, the plasma-treated implants elicited the formation of fibrous tissue capsules that were significantly thinner, more adherent, and vascularized than the control counterparts. The improved cell adhesion was correlated with an increased amount of cells attached to the implant surface after retrieval. There was no difference in the inflammatory response between untreated and treated samples. This study provides a rational approach to optimize the long-term performance of silicone implants, which is likely to have a significant impact in clinical applications demanding enhanced tissue integration of the implants. PMID:22767530

  5. Integrin-extracellular matrix interactions in connective tissue remodeling and osteoblast differentiation

    NASA Technical Reports Server (NTRS)

    Globus, R. K.; Moursi, A.; Zimmerman, D.; Lull, J.; Damsky, C.

    1995-01-01

    The differentiaton of bone cells is a complex multistep process. Bone is somewhat unusual in that it is very actively and continually remodeled in the adult and that maintenance of its mass in the mature organism is exquisitely sensitive to mechanical as well as chemical signals. Bone is also unique because it consists of a very large amount of extracellular matrix (ECM) that is mineralized. The integrin family of ECM receptors has been shown to play an important role in tissue morphogenesis in several systems. Our studies on the regulation of matrix remodeling enzymes by integrins in rabbit synovial fibroblasts show that two b1 integrin fibronectin (FN) receptor complexes (alpha 5 beta 1 and alpha 4 beta 1) cooperate in detecting subtle changes in the composition of the ECM. As a result of signal transduction by these integrins, the levels of mRNA and protein for several members of the metalloproteinase family are regulated in these cells. We have also used antibody and RGD peptide perturbation studies to determine the significance of cell/ECM interactions to normal osteogenesis. We found that interactions between the cell binding domain of FN and integrins are required for both normal morphogenesis and gene expression in cultured osteoblasts that differentiate to form bone-like tissue in culture. These data lead us to propose that beta 1 integrins play an important role in osteoblast differentiation as well as in bone remodeling.

  6. 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. PMID:27100469

  7. 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

  8. Mycobacterium chelonae cutaneous infection in a patient with mixed connective tissue disease*

    PubMed Central

    Lage, Renan; Biccigo, Danilo Guerreiro Zeolo; Santos, Felipe Borba Calixto; Chimara, Erica; Pereira, Elisangela Samartin Pegas; da Costa, Adilson

    2015-01-01

    Around 50 mycobacteria species cause human disease. Immunosuppressive states predispose to non-tuberculous mycobaterium infection, such as Mycobacterium chelonae: AFB, non-tuberculous, fast growth of low virulence and uncommon as a human pathogen. It may compromise the skin and soft tissues, lungs, lymph nodes and there is also a disseminated presentation. The diagnosis involves AFB identification and culture on Agar and Lowenstein-Jensen medium base. A 41-year-old female with MCTD (LES predominance) is reported, presenting painless nodules in the right forearm. She denied local trauma. Immunosuppressed with prednisone and cyclophosphamide for 24 months. Lesion biopsy has demonstrated positive bacilloscopy (Ziehl-Neelsen stain) and M.chelonae in culture (Lowenstein-Jensen medium base), therefore clarithromycin treatment has been started (best therapy choice in the literature). PMID:25672306

  9. Use of Double Layer of Acellular Dermal Matrix and Modified Tunnel Technique to Treat Multiple Adjacent Gingival Recession Defects.

    PubMed

    Mahn, Douglas H

    2016-09-01

    The goal of connective tissue grafting is to cover exposed root surfaces with gingival tissues that are stable and have a natural appearance. The use of an acellular dermal matrix (ADM) has been shown to be a successful alternative to the palatal connective tissue graft. Use of a double layer of an ADM has been shown to have stable results for 1 year. Tunnel grafting techniques can yield root coverage with a natural appearing soft-tissue architecture. The purpose of this case report is to demonstrate the use of a modified tunnel technique and a double layer of ADM in the treatment of multiple adjacent gingival recession defects. Treated teeth were found to have root coverage and natural soft-tissue contours that were stable at 20 months. PMID:27606567

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

    PubMed Central

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

    2009-01-01

    Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome that results in renal phosphate wasting with hypophosphatemia. In most cases, the underlying cause of TIO is a small mesenchymal neoplasm that is often difficult to detect, resulting in delayed diagnosis. One such neoplasm is the phosphaturic mesenchymal tumor, mixed connective tissue variant (PMTMCT), an unusual entity with unique morphologic and biochemical features. The majority of these tumors are found at appendicular sites with only rare cases reported in the jaws. We describe a PMTMCT involving the mandible in a patient with a protracted history of osteomalacia. A review of the current literature is provided with emphasis on the clinical and histologic features, etiopathogenesis, and management of PMTMCT in the setting of TIO. PMID:19828339

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

    PubMed Central

    Quigley, Harry A.; Cone, Frances E.

    2013-01-01

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

  12. 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. PMID:25854827

  13. 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

  14. Effect of administration of oral contraceptives in vivo on collagen synthesis in tendon and muscle connective tissue in young women.

    PubMed

    Hansen, M; Miller, B F; Holm, L; Doessing, S; Petersen, S G; Skovgaard, D; Frystyk, J; Flyvbjerg, A; Koskinen, S; Pingel, J; Kjaer, M; Langberg, H

    2009-04-01

    Women are at greater risk than men for certain kinds of diseases and injuries, which may at least partly be caused by sex hormonal differences. We aimed to test the influence of estradiol in vivo on collagen synthesis in tendon, bone, and muscle. Two groups of young, healthy women similar in age, body composition, and exercise-training status were included. The two groups were either habitual users of oral contraceptives exposed to a high concentration of synthetic estradiol and progestogens (OC, n = 11), or non-OC-users tested in the follicular phase of the menstrual cycle characterized by low concentrations of estradiol and progesterone (control, n = 12). Subjects performed 1 h of one-legged kicking exercise. The next day collagen fractional synthesis rates (FSR) in tendon and muscle connective tissue were measured after a flooding dose of [(13)C]proline followed by biopsies from the patellar tendon and vastus lateralis in both legs. Simultaneously, microdialysis catheters were inserted in vastus lateralis and in front of the patellar tendon for measurement of insulin-like growth factor I (IGF-I) and its binding proteins. Serum NH(2)-terminal propeptide of type I collagen (PINP) and urine COOH-terminal telopeptides of type-I collagen (CTX-I) were measured as markers for bone synthesis and breakdown, respectively. Tendon FSR and PINP were lower in OC compared with control. An increase in muscle collagen FSR postexercise was only observed in control (P < 0.05). Furthermore, the results indicate a lower bioavailability of IGF-I in OC. In conclusion, synthetic female sex hormones administered as OC had an inhibiting effect on collagen synthesis in tendon, bone, and muscle connective tissue, which may be related to a lower bioavailability of IGF-I. PMID:18845777

  15. 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. PMID:16621940

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

    PubMed

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

    2014-11-01

    Adipose tissue serves as a host reservoir for the protozoan Trypanosoma cruzi, the causative organism in Chagas disease. Gap junctions interconnect cells of most tissues, serving to synchronize cell activities including secretion in glandular tissue, and we have previously demonstrated that gap junctions are altered in various tissues and cells infected with T. cruzi. Herein, we examined the gap junction protein connexin 43 (Cx43) expression in infected adipose tissues. Adipose tissue is the largest endocrine organ of the body and is also involved in other physiological functions. In mammals, it is primarily composed of white adipocytes. Although gap junctions are a prominent feature of brown adipocytes, they have not been explored extensively in white adipocytes, especially in the setting of infection. Thus, we examined functional coupling in both white and brown adipocytes in mice. Injection of electrical current or the dye Lucifer Yellow into adipocytes within fat tissue spread to adjacent cells, which was reduced by treatment with agents known to block gap junctions. Moreover, Cx43 was detected in both brown and white fat tissue. At thirty and ninety days post-infection, Cx43 was downregulated in brown adipocytes and upregulated in white adipocytes. Gap junction-mediated intercellular communication likely contributes to hormone secretion and other functions in white adipose tissue and to nonshivering thermogenesis in brown fat, and modulation of the coupling by T. cruzi infection is expected to impact these functions. PMID:25150689

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

    PubMed Central

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

    2015-01-01

    Adipose tissue serves as a host reservoir for the protozoan Trypanosoma cruzi, the causative organism in Chagas disease. Gap junctions interconnect cells of most tissues, serving to synchronize cell activities including secretion in glandular tissue, and we have previously demonstrated that gap junctions are altered in various tissues and cells infected with T. cruzi. Herein, we examined the gap junction protein connexin 43 (Cx43) expression in infected adipose tissues. Adipose tissue is the largest endocrine organ of the body and is also involved in other physiological functions. In mammals, it is primarily composed of white adipocytes. Although gap junctions are a prominent feature of brown adipocytes, they have not been explored extensively in white adipocytes, especially in the setting of infection. Thus, we examined functional coupling in both white and brown adipocytes in mice. Injection of electrical current or the dye Lucifer Yellow into adipocytes within fat tissue spread to adjacent cells, which was reduced by treatment with agents known to block gap junctions. Moreover, Cx43 was detected in both brown and white fat tissue. At thirty and ninety days post-infection, Cx43 was downregulated in brown adipocytes and upregulated in white adipocytes. Gap junction-mediated intercellular communication likely contributes to hormone secretion and other functions in white adipose tissue and to nonshivering thermogenesis in brown fat, and modulation of the coupling by T. cruzi infection is expected to impact these functions. PMID:25150689

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

    SciTech Connect

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

    1991-03-15

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

  19. Connecting brains to robots: an artificial body for studying the computational properties of neural tissues.

    PubMed

    Reger, B D; Fleming, K M; Sanguineti, V; Alford, S; Mussa-Ivaldi, F A

    2000-01-01

    We have created a hybrid neuro-robotic system that establishes two-way communication between the brain of a lamprey and a small mobile robot. The purpose of this system is to offer a new paradigm for investigating the behavioral, computational, and neurobiological mechanisms of sensory-motor learning in a unified context. The mobile robot acts as an artificial body that delivers sensory information to the neural tissue and receives command signals from it. The sensory information encodes the intensity of light generated by a fixed source. The closed-loop interaction between brain and robot generates autonomous behaviors whose features are strictly related to the structure and operation of the neural preparation. We provide a detailed description of the hybrid system, and we present experimental findings on its performance. In particular, we found (a) that the hybrid system generates stable behaviors, (b) that different preparations display different but systematic responses to the presentation of an optical stimulus, and (c) that alteration of the sensory input leads to short- and long-term adaptive changes in the robot responses. The comparison of the behaviors generated by the lamprey's brain stem with the behaviors generated by network models of the same neural system provides us with a new tool for investigating the computational properties of synaptic plasticity. PMID:11348584

  20. Changes in bone tissue under conditions of hypokinesia and in connection with age

    NASA Technical Reports Server (NTRS)

    Podrushnyak, E. P.; Suslov, E. I.

    1980-01-01

    X-ray micrography was used to study the optical density of the blackening of X-ray photographs made of five bones in 9 young people (ages 24 to 29) before and after strict bed rest for 16 to 37 days. Photometric studies of the X-ray film determined the relative concentration of bone structure before and after hypokinesia. In addition, the bone tissues of 25 cadavers of practically healthy individuals (aged 18 to 70) who died from injuries were investigated using X-ray structural analysis. Results show that the reaction to the state of hypokinesia is not uniform in different individuals and is quite often directly reversed. It was established that pronounced osteoporosis can be found in a relatively short time after conditions of hypokinesia in healthy young individuals. Results show that the stabilization of the crystalline structure of hydroxyapatite, especially its crystal formation, is finished by the age of 20 to 25. From 25 to 60, the crystal lattice remains in stable condition but X-ray analysis shows a reduction in the hydroxyapatite density.

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

    PubMed

    Waki, Tomonori; Kan, Joseph Y K

    2016-01-01

    Immediate implant placement and provisionalization in the esthetic zone have been documented with success. The benefit of immediate implant placement and provisionalization is the preservation of papillary mucosa. However, in cases with osseous defects presenting on the facial bony plate, immediate implant placement procedures have resulted in facial gingival recession. Subepithelial connective tissue grafts for immediate implant placement and provisionalization procedures have been reported with a good esthetic outcome. Biotype conversion around implants with subepithelial connective tissue grafts have been advocated, and the resulting tissues appear to be more resistant to recession. The dimensions of peri-implant mucosa in a thick biotype were significantly greater than in a thin biotype. Connective tissue graft with coronally positioned flap procedures on natural teeth has also been documented with success. This article describes a technique combining immediate implant placement, provisionalization, guided bone regeneration (GBR), connective tissue graft, and a coronally positioned flap in order to achieve more stable peri-implant tissue in facial osseous defect situations. PMID:27092345

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

    PubMed Central

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

    2008-01-01

    Background Zinc (Zn) is an essential trace element and it is abundant in connective tissues, however biological roles of Zn and its transporters in those tissues and cells remain unknown. Methodology/Principal Findings Here we report that mice deficient in Zn transporter Slc39a13/Zip13 show changes in bone, teeth and connective tissue reminiscent of the clinical spectrum of human Ehlers-Danlos syndrome (EDS). The Slc39a13 knockout (Slc39a13-KO) mice show defects in the maturation of osteoblasts, chondrocytes, odontoblasts, and fibroblasts. In the corresponding tissues and cells, impairment in bone morphogenic protein (BMP) and TGF-β signaling were observed. Homozygosity for a SLC39A13 loss of function mutation was detected in sibs affected by a unique variant of EDS that recapitulates the phenotype observed in Slc39a13-KO mice. Conclusions/Significance Hence, our results reveal a crucial role of SLC39A13/ZIP13 in connective tissue development at least in part due to its involvement in the BMP/TGF-β signaling pathways. The Slc39a13-KO mouse represents a novel animal model linking zinc metabolism, BMP/TGF-β signaling and connective tissue dysfunction. PMID:18985159

  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. Differences in irradiation susceptibility and turnover between mucosal and connective tissue-type mast cells of mice

    SciTech Connect

    Fukuzumi, T.; Waki, N.; Kanakura, Y.; Nagoshi, J.; Hirota, S.; Yoshikawa, K.; Kitamura, Y. )

    1990-08-01

    Although precursors of mast cells are derived from the bone marrow, phenotypes of mast cells are influenced by the tissues in which final differentiation occurs. Connective tissue-type mast cells (CTMC) and mucosal mast cells (MMC) are different in morphological, biochemical, immunological, and functional criteria. The purpose of the present study was to obtain information about the differentiation process of MMC. First, we compared changes in irradiation susceptibility in mice during the differentiation process of CTMC and MMC. The decrease in irradiation susceptibility was remarkable in the CTMC differentiation process, but it was moderate in that of MMC. Some morphologically identifiable CTMC in the peritoneal cavity had proliferative potential and were highly radioresistant, whereas such a radioresistant population of MMC was not detectable in the gastric mucosa. Second, we estimated the turnover of CTMC and MMC by determining the proportion of mast cells that were labeled with continuously administered bromodeoxyuridine. The turnover of MMC was significantly faster than that of CTMC. The absence of the radioresistant mast cell population in the gastric mucosa appeared to be related to the short life span of MMC.

  5. 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. PMID:22897576

  6. The Relationship between Frontotemporal Effective Connectivity during Picture Naming, Behavior, and Preserved Cortical Tissue in Chronic Aphasia.

    PubMed

    Meier, Erin L; Kapse, Kushal J; Kiran, Swathi

    2016-01-01

    While several studies of task-based effective connectivity of normal language processing exist, little is known about the functional reorganization of language networks in patients with stroke-induced chronic aphasia. During oral picture naming, activation in neurologically intact individuals is found in "classic" language regions involved with retrieval of lexical concepts [e.g., left middle temporal gyrus (LMTG)], word form encoding [e.g., left posterior superior temporal gyrus, (LpSTG)], and controlled retrieval of semantic and phonological information [e.g., left inferior frontal gyrus (LIFG)] as well as domain-general regions within the multiple demands network [e.g., left middle frontal gyrus (LMFG)]. After stroke, lesions to specific parts of the left hemisphere language network force reorganization of this system. While individuals with aphasia have been found to recruit similar regions for language tasks as healthy controls, the relationship between the dynamic functioning of the language network and individual differences in underlying neural structure and behavioral performance is still unknown. Therefore, in the present study, we used dynamic causal modeling (DCM) to investigate differences between individuals with aphasia and healthy controls in terms of task-induced regional interactions between three regions (i.e., LIFG, LMFG, and LMTG) vital for picture naming. The DCM model space was organized according to exogenous input to these regions and partitioned into separate families. At the model level, random effects family wise Bayesian Model Selection revealed that models with driving input to LIFG best fit the control data whereas models with driving input to LMFG best fit the patient data. At the parameter level, a significant between-group difference in the connection strength from LMTG to LIFG was seen. Within the patient group, several significant relationships between network connectivity parameters, spared cortical tissue, and behavior were

  7. The Relationship between Frontotemporal Effective Connectivity during Picture Naming, Behavior, and Preserved Cortical Tissue in Chronic Aphasia

    PubMed Central

    Meier, Erin L.; Kapse, Kushal J.; Kiran, Swathi

    2016-01-01

    While several studies of task-based effective connectivity of normal language processing exist, little is known about the functional reorganization of language networks in patients with stroke-induced chronic aphasia. During oral picture naming, activation in neurologically intact individuals is found in “classic” language regions involved with retrieval of lexical concepts [e.g., left middle temporal gyrus (LMTG)], word form encoding [e.g., left posterior superior temporal gyrus, (LpSTG)], and controlled retrieval of semantic and phonological information [e.g., left inferior frontal gyrus (LIFG)] as well as domain-general regions within the multiple demands network [e.g., left middle frontal gyrus (LMFG)]. After stroke, lesions to specific parts of the left hemisphere language network force reorganization of this system. While individuals with aphasia have been found to recruit similar regions for language tasks as healthy controls, the relationship between the dynamic functioning of the language network and individual differences in underlying neural structure and behavioral performance is still unknown. Therefore, in the present study, we used dynamic causal modeling (DCM) to investigate differences between individuals with aphasia and healthy controls in terms of task-induced regional interactions between three regions (i.e., LIFG, LMFG, and LMTG) vital for picture naming. The DCM model space was organized according to exogenous input to these regions and partitioned into separate families. At the model level, random effects family wise Bayesian Model Selection revealed that models with driving input to LIFG best fit the control data whereas models with driving input to LMFG best fit the patient data. At the parameter level, a significant between-group difference in the connection strength from LMTG to LIFG was seen. Within the patient group, several significant relationships between network connectivity parameters, spared cortical tissue, and behavior were

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

    PubMed Central

    Vestergaard, Peter; Støen, Ole-Gunnar; Swenson, Jon E.; Mosekilde, Leif; Heickendorff, Lene; Fröbert, Ole

    2011-01-01

    Background Extended physical inactivity causes disuse osteoporosis in humans. In contrast, brown bears (Ursus arctos) are highly immobilised for half of the year during hibernation without signs of bone loss and therefore may serve as a model for prevention of osteoporosis. Aim To study 25-hydroxy-vitamin D (25OHD) levels and bone turnover markers in brown bears during the hibernating state in winter and during the active state in summer. We measured vitamin D subtypes (D2 and D3), calcitropic hormones (parathyroid hormone [PTH], 1,25-dihydroxy-vitamin D [1,25(OH)2D]) and bone turnover parameters (osteocalcin, ICTP, CTX-I), PTH, serum calcium and PIIINP. Material and Methods We drew blood from seven immobilised wild brown bears during hibernation in February and in the same bears while active in June. Results Serum 25-hydroxy-cholecalciferol (25OHD3) was significantly higher in the summer than in the winter (22.8±4.6 vs. 8.8±2.1 nmol/l, two tailed p - 2p = 0.02), whereas 25-hydroxy-ergocalciferol (25OHD2) was higher in winter (54.2±8.3 vs. 18.7±1.7 nmol/l, 2p<0.01). Total serum calcium and PTH levels did not differ between winter and summer. Activated 1,25(OH)2D demonstrated a statistically insignificant trend towards higher summer levels. Osteocalcin levels were higher in summer than winter, whereas other markers of bone turnover (ICTP and CTX-I) were unchanged. Serum PIIINP, which is a marker of connective tissue and to some degree muscle turnover, was significantly higher during summer than during winter. Conclusions Dramatic changes were documented in the vitamin D3/D2 ratio and in markers of bone and connective tissue turnover in brown bears between hibernation and the active state. Because hibernating brown bears do not develop disuse osteoporosis, despite extensive physical inactivity we suggest that they may serve as a model for the prevention of this disease. PMID:21731765

  9. Heart rate recovery is an important predictor of outcomes in patients with connective tissue disease-associated pulmonary hypertension.

    PubMed

    Minai, Omar A; Nguyen, Quyen; Mummadi, Srinivas; Walker, Esteban; McCarthy, Kevin; Dweik, Raed A

    2015-09-01

    Reduced heart rate recovery (HRR) after exercise is associated with increased mortality in cardiac and pulmonary diseases. We sought to evaluate the association between HRR after the 6-minute walk test (6MWT) and outcomes in patients with connective tissue disease-associated pulmonary hypertension (CTD-PH). Data were obtained by review of the medical records. HRR was defined as the difference in heart rate at the end of the 6MWT and after 1 minute (HRR1), 2 minutes (HRR2), and 3 minutes (HRR3) of rest. All patients with pulmonary hypertension and a diagnosis of systemic sclerosis, systemic lupus erythematosus, or mixed connective tissue disease who underwent the 6MWT between August 1, 2009, and October 30, 2011, were included (n = 66). By Kaplan-Meier analysis, HRR1, HRR2, and HRR3 at different cutoff points were all good predictors, with HRR1 of <16 being the best predictor of time to clinical worsening (log-rank P < 0.0001), hospitalization (log-rank P = 0.0001), and survival (log-rank P < 0.003). By proportional hazards regression, patients with HRR1 of <16 were at increased risk of clinical worsening (hazard ratio [HR]: 6.4 [95% confidence interval (CI): 2.6-19.2]; P < 0.0001], hospitalization (HR: 6.6 [95% CI: 2.4-23]; P < 0.0001), and death (HR: 4.5 [95% CI: 1.6-15.7]; P = 0.003). Patients in the highest tercile (HRR1 of ≥19) were unlikely to have a clinical worsening event (HR: 0.1 [95% CI: 0.04-0.5]; P = 0.001], to be hospitalized (HR: 0.1 [95% CI: 0.02-0.5]; P = 0.001), or to die (HR: 0.3 [95% CI: 0.07-0.9]; P = 0.04]. In conclusion, in patients with CTD-PH, abnormal HRR1 (defined as HRR1 of <16) after the 6MWT is a strong predictor of clinical worsening, time to clinical worsening, survival, and hospitalization. PMID:26401258

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

    PubMed Central

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

    2010-01-01

    Connective tissue growth factor (CTGF) is a signaling molecule that primarily functions in extracellular matrix maintenance and repair. Increased Ctgf expression is associated with fibrosis in chronic organ injury. Studying the role of CTGF in fibrotic disease in vivo, however, has been hampered by perinatal lethality of the Ctgf null mice as well as the limited scope of previous mouse models of Ctgf overproduction. Here, we devised a new approach and engineered a single mutant mouse strain where the endogenous Ctgf-3′ untranslated region (3′UTR) was replaced with a cassette containing two 3′UTR sequences arranged in tandem. The modified Ctgf allele uses a 3′UTR from the mouse FBJ osteosarcoma oncogene (c-Fos) and produces an unstable mRNA, resulting in 60% of normal Ctgf expression (Lo allele). Upon Cre-expression, excision of the c-Fos-3′UTR creates a transcript utilizing the more stable bovine growth hormone (bGH) 3′UTR, resulting in increased Ctgf expression (Hi allele). Using the Ctgf Lo and Hi mutants, and crosses to a Ctgf knockout or Cre-expressing mice, we have generated a series of strains with a 30-fold range of Ctgf expression. Mice with the lowest Ctgf expression, 30% of normal, appear healthy, while a global nine-fold overexpression of Ctgf causes abnormalities, including developmental delay and craniofacial defects, and embryonic death at E10-12. Overexpression of Ctgf by tamoxifen-inducible Cre in the postnatal life, on the other hand, is compatible with life. The Ctgf Lo-Hi mutant mice should prove useful in further understanding the function of CTGF in fibrotic diseases. Additionally, this method can be used for the production of mouse lines with quantitative variations in other genes, particularly with genes that are broadly expressed, have distinct functions in different tissues, or where altered gene expression is not compatible with normal development. PMID:20877562

  11. Study of chemical properties and evaluation of collagen in mantle, epidermal connective tissue and tentacle of Indian Squid, Loligo duvauceli Orbigny.

    PubMed

    Raman, Maya; Mathew, Saleena

    2014-08-01

    The chemical composition and evaluation of Indian squid (Loligo duvauceli) mantle, epidermal connective tissue and tentacle is investigated in this current study. It is observed that squid mantle contains 22.2% total protein; 63.5% of the total protein is myofibrillar protein. The unique property of squid myofibrillar protein is its water solubility. Squid mantle contains 12.0% total collagen. Epidermal connective tissue has highest amounts of total collagen (17.8%). SDS-PAGE of total collagen identified high molecular weight α-, β- and γ- sub-chains. Amino acid profile analysis indicates that mantle and tentacle contain essential amino acids. Arginine forms a major portion of mantle collagen (272.5 g/100 g N). Isoleucine, glutamic acid and lysine are other amino acids that are found in significantly high amounts in the mantle. Sulphur containing cystine is deficit in mantle collagen. Papain digest of mantle and epidermal connective tissue is rich in uronic acid, while papain digest, collagenase digest and urea digest of epidermal connective tissue has significant amounts of sialic acid (25.2, 33.2 and 99.8 μmol /100 g, respectively). PAS staining of papain digest, collagenase digest and urea digest also identify the association of hexoses with low molecular weight collagen fragments. Histochemical sectioning also emphasized the localized distribution of collagen in epidermal and dermal region and very sparse fibres traverse the myotome bundles. PMID:25114341

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

    PubMed Central

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

    2015-01-01

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

  13. Comparison of two techniques of harvesting connective tissue and its effects on healing pattern at palate and recession coverage at recipient site

    PubMed Central

    Pandit, Nymphea; Khasa, Meenakshi; Gugnani, Shalini; Malik, Rajvir; Bali, Deepika

    2016-01-01

    Aim: To compare the healing pattern in palate following harvestation of connective tissue graft by two different techniques and to compare the recession coverage at the recipient sites. Materials and Methods: 30 recession sites with Miller's class I and II recession in 16 patients were recruited for this study. Sites were randomly divided into 2 treatment groups. Group I used Unigraft Knife to harvest the connective tissue whereas in group II patients Langer & Langer techniques was used to harvest the connective tissue graft from the palate. Healing was evaluated at the donor site using- wound size(WS), immediate bleeding (iB) and delayed bleeding (dB), complete wound epithelialization (CE), sensibility disorders (S) and post operative pain (PP) at baseline, 1st, 4th, and 12th week postoperatively. Recession coverage was assessed by measuring Clinical Attachment Level (CAL), vertical recession (VR), width of keratinized gingiva (KT). Results: On comparison between Group I and II, a statistically significant larger wound size was observed in Group I. CWE was higher in Group II. A non significant difference was observed when SD, and delayed bleeding were compared at all time intervals. A non-significant difference was observed in the clinical parameters at the recipient site. Conclusion: When evaluating the WS and CWE, the Langer and Langer technique was found to be better than the Unigraft knife technique for harvesting the connective tissue graft, whereas both the techniques were found to be effective in root coverage procedure outcomes. PMID:27041892

  14. 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

  15. Cucurbitacin I Attenuates Cardiomyocyte Hypertrophy via Inhibition of Connective Tissue Growth Factor (CCN2) and TGF- β/Smads Signalings

    PubMed Central

    Kang, Hara; Park, Kye Won; Park, Woo Jin; Yang, Seung Yul; Yang, Dong Kwon

    2015-01-01

    Cucurbitacin I is a naturally occurring triterpenoid derived from Cucurbitaceae family plants that exhibits a number of potentially useful pharmacological and biological activities. However, the therapeutic impact of cucurbitacin I on the heart has not heretofore been reported. To evaluate the functional role of cucurbitacin I in an in vitro model of cardiac hypertrophy, phenylephrine (PE)-stimulated cardiomyocytes were treated with a sub-cytotoxic concentration of the compound, and the effects on cell size and mRNA expression levels of ANF and β-MHC were investigated. Consequently, PE-induced cell enlargement and upregulation of ANF and β-MHC were significantly suppressed by pretreatment of the cardiomyocytes with cucurbitacin I. Notably, cucurbitacin I also impaired connective tissue growth factor (CTGF) and MAPK signaling, pro-hypertrophic factors, as well as TGF-β/Smad signaling, the important contributing factors to fibrosis. The protective impact of cucurbitacin I was significantly blunted in CTGF-silenced or TGF-β1-silenced hypertrophic cardiomyocytes, indicating that the compound exerts its beneficial actions through CTGF. Taken together, these findings signify that cucurbitacin I protects the heart against cardiac hypertrophy via inhibition of CTGF/MAPK, and TGF- β/Smad-facilitated events. Accordingly, the present study provides new insights into the defensive capacity of cucurbitacin I against cardiac hypertrophy, and further suggesting cucurbitacin I’s utility as a novel therapeutic agent for the management of heart diseases. PMID:26296085

  16. Reaction of Rat Subcutaneous Connective Tissue to Resin Composites Polymerized with Different Light Curing Units and Different Lightening Methods

    PubMed Central

    Feiz, Atiyeh; Arbabzadeh Zavareh, Farahnaz; Mohammad Razavi, Seyed; Badrian, Hamid; Dolatyar, Sepideh; Vajihi, Mansoureh

    2012-01-01

    The aim of the study was to determine and compare the reaction of rat subcutaneous connective tissue to resin composites polymerized with different lights curing and lightening methods. In this in vivo study, 20 mature Wister Albino rats were used. The composite discs, 4 mm in diameter and 2 mm thick, were cured by QTH or LED light curing units with 4 different lightning methods (full power QTH, full power LED, pulse LED, and ramp LED). Five resin composite discs were implanted in each rat, so that 4 of 5 discs for implantation of cured composite discs differently and central one as control without implantation. After sacrificing at 7, 14, 30, and 60 days the inflammatory grade, fibrosis, and necrosis were determined. Freedman and Cochran tests were used to analyze the data using SPSS software ver. 15. The results of the study showed significant differences in inflammation grade and fibrosis among control group and 4 experimental groups at day 14 (P < 0.05). In necrosis, there was no significant difference among 4 groups in different times (P > 0.05). In conclusion, neither the type of light curing units (LED or QTH) nor the lightening methods can affect the grade of inflammatory reaction. PMID:22761617

  17. 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

  18. Collagen gel contraction as a measure of fibroblast function in an animal model of subsynovial connective tissue fibrosis.

    PubMed

    Yang, Tai-Hua; Thoreson, Andrew R; Gingery, Anne; Larson, Dirk R; Passe, Sandra M; An, Kai-Nan; Zhao, Chunfeng; Amadio, Peter C

    2015-05-01

    Carpal tunnel syndrome (CTS) is a peripheral neuropathy characterized by non-inflammatory fibrosis of the subsynovial connective tissues (SSCT). A rabbit model of CTS was developed to test the hypothesis that SSCT fibrosis causes the neuropathy. We used a cell-seeded collagen-gel contraction model to characterize the fibrosis in this model in terms of cellular mechanics, specifically to compare the ability of SSCT cells from the rabbit model and normal rabbits to contract the gel, and to assess the effect of transforming growth factor-β1,which is upregulated in CTS, on these cells. SSCT fibrosis was induced in six retired breeder female rabbits which were sacrificed at 6 weeks (N = 3) and 12 weeks (n = 3). An additional two rabbits served as controls. SSCT was harvested according to a standard protocol. Gels seeded with SSCT cells from rabbits sacrificed at 6 weeks had significantly higher tensile strength (p < 0.001) and Young's modulus (p < 0.001) than gels seeded with cells from rabbits sacrificed at 12 weeks or control animals. TGF-β1 significantly increased the decay time constant (p < 0.001), tensile strength (p < 0.001), and Young's modulus (p < 0.001) regardless of the cell source. This model may be useful in screening therapeutic agents that may block SSCT fibrosis, identifying possible candidates for CTS treatment. PMID:25626430

  19. Characterization of fat-connective tissue size distribution in pre-sliced pork hams using multifractal analysis.

    PubMed

    Mendoza, Fernando; Valous, Nektarios A; Sun, Da-Wen; Allen, Paul

    2009-12-01

    Fat-connective tissue size distribution (FSD) in hams is a fundamental physical property for its quality assessment. FSD is related to the sensory properties such as texture, taste, quality of raw meat and visual appearance. In this paper we present a tool to carry out the multifractal analysis (MFA) of two-dimensional binary images of pre-sliced pork hams through the calculation of the f(α)-spectra, Rényi (D(q)) dimensions, and associated statistical regressions and parameters. The application is presented for the structural characterization of FSD in three qualities of pork hams (high yield, medium yield and premium quality hams) using image sections of 512×512pixels(2) with a spatial resolution of 0.102mm/pixel. MFA was carried out using the method of moments in the optimized box size range of 32-512pixels for all the ham images using powers of 2, and estimating the probability distribution for moments ranging from -10

  20. Autoantibodies to type II collagen: occurrence in rheumatoid arthritis, other arthritides, autoimmune connective tissue diseases, and chronic inflammatory syndromes.

    PubMed Central

    Choi, E K; Gatenby, P A; McGill, N W; Bateman, J F; Cole, W G; York, J R

    1988-01-01

    Serum IgG antibodies to native and denatured human type II collagen (Col II) were measured using an enzyme linked immunosorbent assay (ELISA). One hundred and thirty one patients with various forms of arthritis such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PSA). Reiter's Syndrome (RS), osteoarthritis (OA), and gout, 60 with autoimmune connective tissue disease, and 37 with the chronic inflammatory conditions--graft versus host disease and leprosy--were studied. With the exception of RS, PSA, OA, and gout, significant levels of Col II antibodies were detected in each disease group. Blocking studies with types I and II collagen on selected serum samples confirmed the specificity to native Col II, though some cross reactivity was apparent with denatured collagen. The patients with RA who were Col II antibody positive tended to fall into stage III of disease progression. There was, however, no correlation with rheumatoid factor, erythrocyte sedimentation rate, or disease duration and this, together with the finding that Col II antibodies are present in a wide array of diseases, makes their role in the pathogenesis of RA questionable. They may arise as a secondary disease perpetuating mechanism in some patients, or in turn may be an epiphenomenon secondary to generalised disturbed immunoregulation or B cell hyperreactivity, or both, that characterises these clinical conditions. PMID:3365030

  1. Induction of connective tissue growth factor (CTGF) in human endothelial cells by lysophosphatidic acid, sphingosine-1-phosphate, and platelets.

    PubMed

    Muehlich, Susanne; Schneider, Nadine; Hinkmann, Fabian; Garlichs, Christoph D; Goppelt-Struebe, Margarete

    2004-08-01

    Endothelial dysfunction is characterized by multiple interactions between endothelial cells and components of the blood. This study focussed on the induction of the pro-atherogenic connective tissue growth factor (CTGF) in endothelial cells by bioactive lipids and platelets. Lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) led to a time- and concentration-dependent increase in CTGF mRNA and protein expression in the human endothelial cell line EAHY 926 and in primary cultures of human umbilical vein endothelial cells (HUVEC). As both cell types expressed various receptors for LPA and S1P, signaling pathways were further characterized by pharmacological means: induction of CTGF was pertussis toxin-insensitive and inhibition of activation of p42/44 MAP kinases only partially reduced CTGF expression. On the contrary, interference with the RhoA signaling pathway by simvastatin, an inhibitor of geranylgeranyltransferases, or the Rho-kinase inhibitor Y27632 prevented induction of CTGF. Co-incubation of endothelial cells with freshly isolated human platelets significantly increased the expression of CTGF mRNA in endothelial cells, which was also sensitive to simvastatin. Up-regulation of CTGF in endothelial cells, induced by LPA, S1P, or platelets, may contribute to the initiation and progression of atherosclerosis. Interference of simvastatin with the synthesis of this pro-atherogenic factor further supports the anti-atherogenic role of statins. PMID:15262182

  2. The Prevalence of Atherosclerosis in Those with Inflammatory Connective Tissue Disease by Race, Age, and Traditional Risk Factors.

    PubMed

    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

  3. An autologous connective tissue tube with high healing ability as a small diameter vascular substitute with temporary antithrombogenicity.

    PubMed

    Satoh, S; Niu, S; Kanki, Y; Oka, T; Noishiki, Y; Kurumatani, H; Watanabe, K

    1989-01-01

    Although autologous connective tissue grafts (ACTG) are an ideal vascular substitute, they have not yet been used as small diameter vascular grafts because of thrombogenicity. We reported on ACTGs in which mesh tubes were fabricated from ultra-fine polyester fibers (UFPF) and used as a framework. Antithrombogenicity was established using an original heparinization method, with a 50% patency 1 month postimplantation. Early failure of these grafts was caused mainly by loss of antithrombogenicity before development of endothelialization on the inner surface. In this study, higher concentrations of heparin were used for in situ heparinization of the grafts before implantation in combination with antiplatelet therapy (cilostazol, OPC-13013 for the first month after substitution for canine carotid arteries. As a result, more complete healing of the grafts was attained, with a patency rate of 63% at 1 month, when small doses of antiplatelet agents were used. More intensive antiplatelet therapy resulted in impairment of graft healing, causing hematomas around the grafts. Thus, optimal doses of antiplatelet agents remain uncertain. PMID:2597440

  4. Cucurbitacin I Attenuates Cardiomyocyte Hypertrophy via Inhibition of Connective Tissue Growth Factor (CCN2) and TGF- β/Smads Signalings.

    PubMed

    Jeong, Moon Hee; Kim, Shang-Jin; Kang, Hara; Park, Kye Won; Park, Woo Jin; Yang, Seung Yul; Yang, Dong Kwon

    2015-01-01

    Cucurbitacin I is a naturally occurring triterpenoid derived from Cucurbitaceae family plants that exhibits a number of potentially useful pharmacological and biological activities. However, the therapeutic impact of cucurbitacin I on the heart has not heretofore been reported. To evaluate the functional role of cucurbitacin I in an in vitro model of cardiac hypertrophy, phenylephrine (PE)-stimulated cardiomyocytes were treated with a sub-cytotoxic concentration of the compound, and the effects on cell size and mRNA expression levels of ANF and β-MHC were investigated. Consequently, PE-induced cell enlargement and upregulation of ANF and β-MHC were significantly suppressed by pretreatment of the cardiomyocytes with cucurbitacin I. Notably, cucurbitacin I also impaired connective tissue growth factor (CTGF) and MAPK signaling, pro-hypertrophic factors, as well as TGF-β/Smad signaling, the important contributing factors to fibrosis. The protective impact of cucurbitacin I was significantly blunted in CTGF-silenced or TGF-β1-silenced hypertrophic cardiomyocytes, indicating that the compound exerts its beneficial actions through CTGF. Taken together, these findings signify that cucurbitacin I protects the heart against cardiac hypertrophy via inhibition of CTGF/MAPK, and TGF- β/Smad-facilitated events. Accordingly, the present study provides new insights into the defensive capacity of cucurbitacin I against cardiac hypertrophy, and further suggesting cucurbitacin I's utility as a novel therapeutic agent for the management of heart diseases. PMID:26296085

  5. Inhibition of collagen production in scleroderma fibroblast cultures by a connective tissue glycoprotein extracted from normal dermis

    SciTech Connect

    Maquart, F.X.; Bellon, G.; Cornillet-Stoupy, J.; Randoux, A.; Triller, R.; Kalis, B.; Borel, J.P.

    1985-08-01

    It was shown in a previous paper that a connective tissue glycoprotein (CTGP) extracted from normal rabbit dermis was able to inhibit total protein and collagen syntheses by normal dermis fibroblast cultures. In the present study, the effects of CTGP on scleroderma fibroblasts were investigated. (/sup 14/C)Proline incorporation into total proteins of the supernatant was not significantly different from that found in controls. By contrast, the amount of collagen, expressed as percentage of total secreted protein, was far higher in scleroderma cultures than in normal ones (14.4% +/- 6.0% vs 4.6% +/- 0.9%). Addition of CTGP to the medium induced a concentration-dependent inhibition of (/sup 14/C)proline incorporation into proteins from both control and scleroderma cells. In control cultures, no significant decrease of the percentage of collagen was observed, but over 60 micrograms/ml, both cytotoxic effects and inhibition of protein synthesis occurred. In scleroderma cultures, the inhibition was twice as effective on collagen as on noncollagen protein synthesis. The inhibition of collagen secretion was not related either to changes in collagen hydroxylation or to the intracellular catabolism of newly synthesized procollagen.

  6. Subepithelial connective tissue graft with and without the use of plasma rich in growth factors for treating root exposure

    PubMed Central

    Lafzi, Ardeshir; Shirmohammadi, Adileh; Behrozian, Ahmad; Kashefimehr, Atabak; Khashabi, Ehsan

    2012-01-01

    Purpose The aim of this study was to evaluate the clinical efficiency of the subepithelial connective tissue graft (SCTG) with and without plasma rich in growth factor (PRGF) in the treatment of gingival recessions. Methods Twenty bilateral buccal gingival Miller's Class I and II recessions were selected. Ten of the recessions were treated with SCTG and PRGF (test group). The rest ten of the recessions were treated with SCTG (control group). The clinical parameters including recession depth (RD), percentage of root coverage (RC), mucogingival junction (MGJ) position, clinical attachment level (CAL), and probing depth (PD) were measured at the baseline, and 1 and 3 months later. The data were analyzed using the Wilcoxon signed rank and Mann-Whitney U tests. Results After 3 months, both groups showed a significant improvement in all of the mentioned criteria except PD. Although the amount of improvement was better in the SCTG+PRGF group than the SCTG only group, this difference was not statistically significant. The mean RC was 70.85±12.57 in the test group and 75.83±24.68 in the control group. Conclusions Both SCTG+PRGF and SCTG only result in favorable clinical outcomes, but the added benefit of PRGF is not evident. PMID:23346462

  7. Application of a probabilistic microstructural model to determine reference length and toe-to-linear region transition in fibrous connective tissue.

    PubMed

    Hurschler, Christof; Provenzano, Paolo P; Vanderby, Ray

    2003-06-01

    This study shows how a probabilistic microstructural model for fibrous connective tissue behavior can be used to objectively describe soft tissue low-load behavior. More specifically, methods to determine tissue reference length and the transition from the strain-stiffening "toe-region" to the more linear region of the stress-strain curve of fibrous connective tissues are presented. According to a microstructural model for uniaxially loaded collagenous tissues, increasingly more fibers are recruited and bear load with increased tissue elongation. Fiber recruitment is represented statistically according to a Weibull probability density function (PDF). The Weibull PDF location parameter in this formulation corresponds to the stretch at which the first fibers begin to bear load and provides a convenient method of determining reference length. The toe-to-linear region transition is defined by utilizing the Weibull cumulative distribution function (CDF) which relates the fraction of loaded fibers to the tissue elongation. These techniques are illustrated using representative tendon and ligament data from the literature, and are shown to be applicable retrospectively to data from specimens that are not heavily preloaded. The reference length resulting from this technique provides an objective datum from which to calculate stretch, strain, and tangent modulus, while the Weibull CDF provides an objective parameter with which to characterize the limits of low-load behavior. PMID:12929247

  8. 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

  9. Tenascin-Y: a protein of novel domain structure is secreted by differentiated fibroblasts of muscle connective tissue.

    PubMed

    Hagios, C; Koch, M; Spring, J; Chiquet, M; Chiquet-Ehrismann, R

    1996-09-01

    Tenascin-Y was identified in chicken as a novel member of the tenascin (TN) family of ECM proteins. Like TN-C, TN-R, and TN-X, TN-Y is a multidomain protein consisting of heptad repeats, epidermal growth factor-like repeats, fibronectin type III-like (FNIII) domains and a domain homologous to fibrinogen. In contrast to all other known TNs, the series of FNIII domains is interrupted by a novel domain, rich in serines (S) and prolines (P) that occur as repeated S-P-X-motifs, where X stands for any amino acid. Interestingly, the TN-Y-type FNIII domains are 70-100% identical with respect to their DNA sequence. Different TN-Y variants are created by alternative splicing of FNIII domains. Although, based on sequence comparisons TN-Y is most similar to mammalian TN-X, these molecules are not species homologues. TN-Y is predominantly expressed in embryonic and adult chicken heart and skeletal muscle and, to a lower extent, also in several non-muscular tissues. Two major transcripts of approximately 6.5 and 9.5 kb are differentially expressed during heart and skeletal muscle development and are also present in the adult. Anti-TN-Y antibodies recognize a approximately 400-kD double band and a approximately 300-kD form of TN-Y on immunoblots of chicken heart extracts. In situ hybridization and immunofluorescence analysis of aortic smooth muscle, heart, and skeletal muscle revealed that TN-Y is mainly expressed and secreted by cells within muscle-associated connective tissue. Cultured primary muscle fibroblasts released a approximately 220-kD doublet and a approximately 170-kD single TN-Y variant only when cultured in 10% horse serum but not in medium containing 10% fetal calf serum. All TN-Y variants isolated bind to heparin under physiologically relevant conditions that may indicate an important function retained in all tenascins. PMID:8830777

  10. 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

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

    PubMed Central

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

    2010-01-01

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

  12. mTOR Complexes Repress Hypertrophic Agonist-Stimulated Expression of Connective Tissue Growth Factor in Adult Cardiac Muscle Cells.

    PubMed

    Sundararaj, Kamala; Pleasant, Dorea L; Moschella, Phillip C; Panneerselvam, Kavin; Balasubramanian, Sundaravadivel; Kuppuswamy, Dhandapani

    2016-02-01

    Connective tissue growth factor (CTGF) is a fibrogenic cytokine that promotes fibrosis in various organs. In the heart, both cardiomyocytes (CM) and cardiac fibroblasts have been reported as a source of CTGF expression, aiding cardiac fibrosis. Although the mammalian target of rapamycin (mTOR) forms 2 distinct complexes, mTORC1 and mTORC2, and plays a central role in integrating biochemical signals for protein synthesis and cellular homeostasis, we explored its role in CTGF expression in adult feline CM. CM were stimulated with 10 μM phenylephrine (PE), 200 nM angiotensin (Ang), or 100 nM insulin for 24 hours. PE and Ang, but not insulin, caused an increase in CTGF mRNA expression with the highest expression observed with PE. Inhibition of mTOR with torin1 but not rapamycin significantly enhanced PE-stimulated CTGF expression. Furthermore, silencing of raptor and rictor using shRNA adenoviral vectors to suppress mTORC1 and mTORC2, respectively, or blocking phosphatidylinositol 3-kinase (PI3K) signaling with LY294002 (LY) or Akt signaling by dominant-negative Akt expression caused a substantial increase in PE-stimulated CTGF expression as measured by both mRNA and secreted protein levels. However, studies with dominant-negative delta isoform of protein kinase C demonstrate that delta isoform of protein kinase C is required for both agonist-induced CTGF expression and mTORC2/Akt-mediated CTGF suppression. Finally, PE-stimulated CTGF expression was accompanied with a corresponding increase in Smad3 phosphorylation and pretreatment of cells with SIS3, a Smad3 specific inhibitor, partially blocked the PE-stimulated CTGF expression. Therefore, a PI3K/mTOR/Akt axis plays a suppressive role on agonist-stimulated CTGF expression where the loss of this mechanism could be a contributing factor for the onset of cardiac fibrosis in the hypertrophying myocardium. PMID:26371948

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

    SciTech Connect

    Mori, Yasuji; Hinchcliff, Monique; Wu, Minghua; Warner-Blankenship, Matthew; Lyons, Karen M.

    2008-03-10

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

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

    PubMed

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

    2016-05-01

    Overlap syndromes are known to occur with connective-tissue diseases (CTDs). Rarely, the overlap occurs at the same tissue site. We report the case of a patient with clinical and histopathologic findings consistent with the presence of discoid lupus erythematosus (DLE) and localized scleroderma within the same lesions. Based on our case and other reported cases in the literature, the following features are common in patients with an overlap of lupus erythematosus (LE) and localized scleroderma: predilection for young women, photodistributed lesions, DLE, linear morphology clinically, and positivity along the dermoepidermal junction on direct immunofluorescence. Most patients showed good response to antimalarials, topical steroids, or systemic steroids. PMID:27274545

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

    SciTech Connect

    Jones, P.A.; Werb, Z.

    1980-12-01

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

  16. Severe eczema and Hyper-IgE in Loeys-Dietz-syndrome - contribution to new findings of immune dysregulation in connective tissue disorders.

    PubMed

    Felgentreff, Kerstin; Siepe, Matthias; Kotthoff, Stefan; von Kodolitsch, Yskert; Schachtrup, Kristina; Notarangelo, Luigi D; Walter, Jolan E; Ehl, Stephan

    2014-01-01

    Loeys-Dietz syndrome (LDS) is a connective tissue disorder caused by monoallelic mutations in TGFBR1 and TGFBR2, which encode for subunits of the transforming growth factor beta (TGFβ) receptor. Affected patients are identified by vascular aneurysms with tortuosity and distinct morphological presentations similar to Marfan syndrome; however, an additional predisposition towards asthma and allergy has recently been found. We describe two patients with a novel missense mutation in TGFBR1 presenting with highly elevated levels of IgE and severe eczema similar to autosomal-dominant Hyper-IgE syndrome (HIES). Mild allergic manifestations with normal up to moderately increased IgE were observed in 3 out of 6 additional LDS patients. A comparison of this cohort with 4 HIES patients illustrates the significant overlap of both syndromes including eczema and elevated IgE as well as skeletal and connective tissue manifestations. PMID:24333532

  17. Differential diagnosis and diagnostic flow chart of joint hypermobility syndrome/ehlers-danlos syndrome hypermobility type compared to other heritable connective tissue disorders.

    PubMed

    Colombi, Marina; Dordoni, Chiara; Chiarelli, Nicola; Ritelli, Marco

    2015-03-01

    Joint hypermobility syndrome/Ehlers-Danlos syndrome hypermobility type (JHS/EDS-HT) is an evolving and protean disorder mostly recognized by generalized joint hypermobility and without a defined molecular basis. JHS/EDS-HT also presents with other connective tissue features affecting a variety of structures and organs, such as skin, eye, bone, and internal organs. However, most of these signs are present in variable combinations and severity in many other heritable connective tissue disorders. Accordingly, JHS/EDS-HT is an "exclusion" diagnosis which needs the absence of any consistent feature indicative of other partially overlapping connective tissue disorders. While both Villefranche and Brighton criteria include such an exclusion as a mandatory item, a systematic approach for reaching a stringent clinical diagnosis of JHS/EDS-HT is still lacking. The absence of a consensus on the diagnostic approach to JHS/EDS-HT concerning its clinical boundaries with similar conditions contribute to limit our actual understanding of the pathologic and molecular bases of this disorder. In this review, we revise the differential diagnosis of JHS/EDS-HT with those heritable connective tissue disorders which show a significant overlap with the former and mostly include EDS classic, vascular and kyphoscoliotic types, osteogenesis imperfecta, Marfan syndrome, Loeys-Dietz syndrome, arterial tortuosity syndrome, and lateral meningocele syndrome. A diagnostic flow chart is also offered with the attempt to support the less experienced clinician in stringently recognizing JHS/EDS-HT and stimulate the debate in the scientific community for both management and research purposes. PMID:25821090

  18. Regulation of connective tissue growth factor activity in cultured rat mesangial cells and its expression in experimental diabetic glomerulosclerosis.

    PubMed

    Riser, B L; Denichilo, M; Cortes, P; Baker, C; Grondin, J M; Yee, J; Narins, R G

    2000-01-01

    Connective tissue growth factor (CTGF) is a peptide secreted by cultured endothelial cells and fibroblasts when stimulated by transforming growth factor-beta (TGF-beta), and is overexpressed during fibrotic processes in coronary arteries and in skin. To determine whether CTGF is implicated in the pathogenesis of diabetic glomerulosclerosis, cultured rat mesangial cells (MC) as well as kidney cortex and microdissected glomeruli were examined from obese, diabetic db/db mice and their normal counterparts. Exposure of MC to recombinant human CTGF significantly increased fibronectin and collagen type I production. Furthermore, unstimulated MC expressed low levels of CTGF message and secreted minimal amounts of CTGF protein (36 to 38 kD) into the media. However, sodium heparin treatment resulted in a greater than fourfold increase in media-associated CTGF, suggesting that the majority of CTGF produced was cell- or matrix-bound. Exposure of MC to TGF-beta, increased glucose concentrations, or cyclic mechanical strain, all causal factors in diabetic glomerulosclerosis, markedly induced the expression of CTGF transcripts, while recombinant human CTGF was able to autoinduce its own expression. TGF-, and high glucose, but not mechanical strain, stimulated the concomitant secretion of CTGF protein, the former also inducing abundant quantities of a small molecular weight form of CTGF (18 kD) containing the heparin-binding domain. 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 reverse transcription-PCR demonstrated that although CTGF transcripts were low in the glomeruli of control mice, expression was increased 28-fold after approximately 3.5 mo of diabetes. This change occurred early in the course of diabetic nephropathy when mesangial expansion was mild, and interstitial disease and proteinuria were absent. A substantially reduced

  19. Assessment of the level of vaccine-induced anti-HBs antibodies in children with inflammatory systemic connective tissue diseases treated with immunosuppression

    PubMed Central

    Hernik, Elżbieta; Kwiatkowska, Małgorzata; Rutkowska-Sak, Lidia; Kołodziejczyk, Beata; Gazda, Agnieszka

    2015-01-01

    Objectives Protective vaccinations are the most effective method of prevention of type B virus hepatitis. The aim of the study was to determine whether in children receiving immunosuppressive therapy due to inflammatory systemic connective tissue diseases the protective concentration of the anti-HBs antibodies produced after vaccination against type B virus hepatitis in infancy is maintained. Material and methods The concentration of anti-HBs antibodies was assessed in the sera of 50 children with inflammatory connective tissue diseases – 37 girls (74%) and 13 boys (26%), aged 1.5–17.5 years – during the immunosuppressive treatment, which lasted at least 6 months. The control group consisted of 50 healthy children – 28 girls (56%) and 22 boys (44%) aged 2–17 years. All children were vaccinated in infancy with Engerix B vaccine according to the 0–1–6 months schedule. The antibody concentration of ≥ 10 mIU/ml in patients is regarded as protective. Results No protective antibody concentrations were found in 25 cases (50%) in the group of diseased children and only in 2 children in the control group (4%). Conclusions The concentration of vaccine-induced antibodies should be assessed in children with inflammatory systemic connective tissue diseases and, in case of the absence of a protective concentration, revaccination should be started. The use of glucocorticosteroids, synthetic and biological disease-modifying antirheumatic drugs is no contraindication to vaccination against hepatitis B. PMID:27407228

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

    SciTech Connect

    Boileau, C.; Coulon, M.; Alexandre, J.-A.; Junien, C. ); Jondeau, G.; Delorme, G.; Dubourg, O.; Bourdarias, J.-P. ); Babron, M.-C.; Bonaieti-Pellie, C. ); Sakai, L. ); Melki, J. )

    1993-07-01

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

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

    PubMed Central

    Heufelder, A E; Bahn, R S

    1993-01-01

    Activation of certain adhesion molecules within vascular endothelium and the surrounding extravascular space is a critical event in the recruitment and targeting of an inflammatory response or autoimmune attack to a particular tissue site. We have recently demonstrated that the adhesion of lymphocytes to cultured retroocular fibroblasts obtained from patients with Graves' ophthalmopathy (GO) is mediated predominantly by the interaction of lymphocyte function-associated antigen-1 (LFA-1), expressed on lymphocytes, with intercellular adhesion molecule-1 (ICAM-1), expressed by these cells following exposure to interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), IL-1 alpha or purified thyroid-stimulating immunoglobulins. We now report the expression and localization in situ of several adhesion molecules, ICAM-1, endothelial leucocyte adhesion molecule-1 (ELAM-1), vascular cell adhesion molecule-1 (VCAM-1), and LFA-3 in retroocular tissues derived from patients with severe GO (n = 4) and normal individuals (n = 3). Serial cryostat sections of tissue specimens were processed for immunoperoxidase staining using various MoAbs against ICAM-1, ELAM-1, VCAM-1 and LFA-3. In addition, consecutive sections were stained with MoAbs against LFA-1, CD45RO (UCHL-1)DR-human leucocyte antigen (HLA-DR), CD11b/CD18 (Mac-1), and CD11c/CD18 (p150,95). In GO-retroocular tissues, strong immunoreactivity for ICAM-1 and LFA-3 was detected in blood vessels (> 90%), in perimysial fibroblasts surrounding extraocular muscle fibres, and in connective tissue distinct from extraocular muscle. No ICAM-1 or LFA-3 immunoreactivity was present in extraocular muscle cells themselves. ICAM-1 and LFA-3 immunoreactivity in normal tissues was minimal or absent both in connective and muscle tissues. Vascular endothelium was strongly positive for ELAM-1 and VCAM-1 in GO-retroocular tissues, while VCAM-1 immunoreactivity was minimal (< 5% of blood vessels) and ELAM-1 immunoreactivity was

  2. Hammerhead Ribozyme-Mediated Knockdown of mRNA for Fibrotic Growth Factors: Transforming Growth Factor-Beta 1 and Connective Tissue Growth Factor

    PubMed Central

    Robinson, Paulette M.; Blalock, Timothy D.; Yuan, Rong; Lewin, Alfred S.; Schultz, Gregory S.

    2013-01-01

    Excessive scarring (fibrosis) is a major cause of pathologies in multiple tissues, including lung, liver, kidney, heart, cornea, and skin. The transforming growth factor- β (TGF- β) system has been shown to play a key role in regulating the formation of scar tissue throughout the body. Furthermore, connective tissue growth factor (CTGF) has been shown to mediate most of the fibrotic actions of TGF- β, including stimulation of synthesis of extracellular matrix and differentiation of fibroblasts into myofibroblasts. Currently, no approved drugs selectively and specifically regulate scar formation. Thus, there is a need for a drug that selectively targets the TGF- β cascade at the molecular level and has minimal off-target side effects. This chapter focuses on the design of hammerhead ribozymes, measurement of kinetic activity, and assessment of knockdown mRNAs of TGF- β and CTGF in cell cultures. PMID:22131029

  3. 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

  4. Effect of GaAIAs low-level laser therapy on the healing of human palate mucosa after connective tissue graft harvesting: randomized clinical trial.

    PubMed

    Dias, Stephanie Botti Fernanandes; Fonseca, Marcus Vinícius Alves; Dos Santos, Nídia Cristina Castro; Mathias, Ingrid Fernandes; Martinho, Frederico Canato; Junior, Milton Santamaria; Jardini, Maria Aparecida Neves; Santamaria, Mauro Pedrine

    2015-08-01

    Among the available techniques to treat gingival recession, connective tissue graft (CTG) presents more foreseeability and better results in the long term. However, this technique causes morbidity and discomfort in the palatine region due to graft removal at that site. The aim of this clinical trial was to evaluate the influence of low-level laser therapy (LLLT) on the healing of the donor palatine area after CTG. Thirty-two patients presenting buccal gingival recession were selected and randomly assigned to receive LLLT irradiation (test group) or LLLT sham (control group) in the palatine area after connective graft removal. A diode laser (AsGaAl, 660 nm) was applied to test the sites immediately after surgery and every other day for 7 days. The evaluated parameters were wound remaining area (WRA), scar and tissue colorimetry (TC), tissue thickness (TT), and postoperative discomfort (D). These parameters were evaluated at baseline and 7, 14, 45, 60, and 90 days after surgery. Two-way repeated measures ANOVA was used for analysis. The test group presented statistically significant smaller wounds at days 14 and 45. None of the patients presented a scar at the operated area, and colorimetry analysis revealed that there was no statistically significant difference between groups (p > 0.05). Patients reported mild to moderate discomfort, with low consumption of analgesic pills. We concluded that LLLT irradiation can accelerate wound healing on palatine mucosa after connective tissue removal for root coverage techniques (ClinicalTrial.org NCT02239042). PMID:25373688

  5. The beta 1 integrin, very late activation antigen-4 on human neutrophils can contribute to neutrophil migration through connective tissue fibroblast barriers.

    PubMed Central

    Gao, J X; Issekutz, A C

    1997-01-01

    Polymorphonuclear leucocyte (PMNL) accumulation in extravascular tissues and inflammatory exudates is dependent on their migration through blood vessel endothelium and then through connective tissue. Previously we utilized a barrier of human synovial and dermal fibroblasts (HSF or HDF) grown on microporous filters, as a model of PMNL migration through connective tissue. Those studies showed that beta 2 (CD18) and the beta 1 integrins, very late activation antigen-5 (VLA-5) and VLA-6, in part mediate this PMNL migration. Here we report that VLA-4, which can also be expressed at low levels on activated PMNL, is also involved in PMNL migration induced by C5a through fibroblast (HSF and HDF) barriers, because monoclonal antibody (mAb) to VLA-4 significantly inhibited (by 20-30%) PMNL migration. Blocking the function of CD18, VLA-5 or VLA-6 was not required for detection of the VLA-4-mediated migration. Combination treatment with mAb to VLA-4 and with mAb to VLA-5 or to VLA-6 further inhibited PMNL migration, irrespective of whether CD11/CD18 mechanisms were blocked with anti-CD18 mAb or not. Treatment of PMNL with a peptide based on the VLA-4-binding domain in the CS-1 fragment of fibronectin, but not a control peptide, inhibited PMNL migration to a comparable extent to treatment with mAb to VLA-4. A low level of VLA-4 was expressed on C5a-activated PMNL, detected by immunofluorescence flow cytometry. These results suggest that VLA-4 can be mobilized by human peripheral blood PMNL and can, in addition to VLA-5, VLA-6 and CD11/CD18 integrins, mediate PMNL migration through connective tissue. This is in marked contrast to PMNL transendothelial migration, where beta 1 integrins appear to play no significant role. PMID:9155654

  6. Human adipose CD34+ CD90+ stem cells and collagen scaffold constructs grafted in vivo fabricate loose connective and adipose tissues.

    PubMed

    Ferraro, Giuseppe A; De Francesco, Francesco; Nicoletti, Gianfranco; Paino, Francesca; Desiderio, Vincenzo; Tirino, Virginia; D'Andrea, Francesco

    2013-05-01

    Stem cell based therapies for the repair and regeneration of various tissues are of great interest for a high number of diseases. Adult stem cells, instead, are more available, abundant and harvested with minimally invasive procedures. In particular, mesenchymal stem cells (MSCs) are multi-potent progenitors, able to differentiate into bone, cartilage, and adipose tissues. Human adult adipose tissue seems to be the most abundant source of MSCs and, due to its easy accessibility; it is able to give a considerable amount of stem cells. In this study, we selected MSCs co-expressing CD34 and CD90 from adipose tissue. This stem cell population displayed higher proliferative capacity than CD34(-) CD90(-) cells and was able to differentiate in vitro into adipocytes (PPARγ(+) and adiponectin(+)) and endothelial cells (CD31(+) VEGF(+) Flk1(+)). In addition, in methylcellulose without VEGF, it formed a vascular network. The aim of this study was to investigate differentiation potential of human adipose CD34(+) /CD90(+) stem cells loaded onto commercial collagen sponges already used in clinical practice (Gingistat) both in vitro and in vivo. The results of this study clearly demonstrate that human adult adipose and loose connective tissues can be obtained in vivo, highlighting that CD34(+) /CD90 ASCs are extremely useful for regenerative medicine. PMID:23129214

  7. Adjacent Segment Pathology after Anterior Cervical Fusion

    PubMed Central

    Chung, Jae Yoon; Park, Jong-Beom; Seo, Hyoung-Yeon

    2016-01-01

    Anterior cervical fusion has become a standard of care for numerous pathologic conditions of the cervical spine. However, subsequent development of clinically significant disc disease at levels adjacent to fused discs is a serious long-term complication of this procedure. As more patients live longer after surgery, it is foreseeable that adjacent segment pathology (ASP) will develop in increasing numbers of patients. Also, ASP has been studied more intensively with the recent popularity of motion preservation technologies like total disc arthroplasty. The true nature and scope of ASP remains poorly understood. The etiology of ASP is most likely multifactorial. Various factors including altered biomechanical stresses, surgical disruption of soft tissue and the natural history of cervical disc disease contribute to the development of ASP. General factors associated with disc degeneration including gender, age, smoking and sports may play a role in the development of ASP. Postoperative sagittal alignment and type of surgery are also considered potential causes of ASP. Therefore, a spine surgeon must be particularly careful to avoid unnecessary disruption of the musculoligamentous structures, reduced risk of direct injury to the disc during dissection and maintain a safe margin between the plate edge and adjacent vertebrae during anterior cervical fusion. PMID:27340541

  8. Adjacent Segment Pathology after Anterior Cervical Fusion.

    PubMed

    Chung, Jae Yoon; Park, Jong-Beom; Seo, Hyoung-Yeon; Kim, Sung Kyu

    2016-06-01

    Anterior cervical fusion has become a standard of care for numerous pathologic conditions of the cervical spine. However, subsequent development of clinically significant disc disease at levels adjacent to fused discs is a serious long-term complication of this procedure. As more patients live longer after surgery, it is foreseeable that adjacent segment pathology (ASP) will develop in increasing numbers of patients. Also, ASP has been studied more intensively with the recent popularity of motion preservation technologies like total disc arthroplasty. The true nature and scope of ASP remains poorly understood. The etiology of ASP is most likely multifactorial. Various factors including altered biomechanical stresses, surgical disruption of soft tissue and the natural history of cervical disc disease contribute to the development of ASP. General factors associated with disc degeneration including gender, age, smoking and sports may play a role in the development of ASP. Postoperative sagittal alignment and type of surgery are also considered potential causes of ASP. Therefore, a spine surgeon must be particularly careful to avoid unnecessary disruption of the musculoligamentous structures, reduced risk of direct injury to the disc during dissection and maintain a safe margin between the plate edge and adjacent vertebrae during anterior cervical fusion. PMID:27340541

  9. 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.

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

    PubMed Central

    Elphick, Maurice R.

    2012-01-01

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

  11. Thrombotic thrombocytopenic purpura in the presence of connective tissue disease and HIV infection: A diagnostic and therapeutic challenge in a resource- constrained setting.

    PubMed

    Perumal, Rubeshan; Marais, Johannes Alexander; Brown, Susan

    2016-01-01

    Thrombotic thrombocytopenic purpura is a catastrophic disease and may occur in the presence of other confounding diseases. We present a case of TTP in a patient with connective tissue disease and HIV infection, in whom the diagnosis and management of TTP was challenging. It is important to understand the various underlying mechanisms that drive TTP in the presence of these comorbid diseases, so that an appropriate treatment strategy can be initiated. Our patient failed an initial trial of plasma infusion alone, but responded well to plasma exchange. PMID:27245723

  12. 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

  13. 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

  14. Nifedipine and phenytoin induce matrix synthesis, but not proliferation, in intact human gingival connective tissue ex vivo.

    PubMed

    Kim, Shawna S; Michelsons, Sarah; Creber, Kendal; Rieder, Michael J; Hamilton, Douglas W

    2015-12-01

    Drug-induced gingival enlargement (DIGE) is a fibrotic condition that can be caused by the antihypertensive drug nifedipine and the anti-seizure drug phenytoin, but the molecular etiology of this type of fibrosis is not well understood and the role of confounding factors such as inflammation remains to be fully investigated. The aim of this study was to develop an ex vivo gingival explant system to allow investigation of the effects of nifedipine and phenytoin alone on human gingival tissue. Comparisons were made to the histology of human DIGE tissue retrieved from individuals with DIGE. Increased collagen, fibronectin, and proliferating fibroblasts were evident, but myofibroblasts were not detected in DIGE samples caused by nifedipine and phenytoin. In healthy gingiva cultured in nifedipine or phenytoin-containing media, the number of cells positive for p-SMAD2/3 increased, concomitant with increased CCN2 and periostin immunoreactivity compared to untreated explants. Collagen content assessed through hydroxyproline assays was significantly higher in tissues cultured with either drug compared to control tissues, which was confirmed histologically. Matrix fibronectin levels were also qualitatively greater in tissues treated with either drug. No significant differences in proliferating cells were observed between any of the conditions. Our study demonstrates that nifedipine and phenytoin activate canonical transforming growth factor-beta signaling, CCN2 and periostin expression, as well as increase collagen density, but do not influence cell proliferation or induce myofibroblast differentiation. We conclude that in the absence of confounding variables, nifedipine and phenytoin alter matrix homeostasis in gingival tissue explants ex vivo, and drug administration is a significant factor influencing ECM accumulation in gingival enlargement. PMID:26296421

  15. Use of Cis-[18F]Fluoro-Proline for Assessment of Exercise-Related Collagen Synthesis in Musculoskeletal Connective Tissue

    PubMed Central

    Skovgaard, Dorthe; Kjaer, Andreas; Heinemeier, Katja Maria; Brandt-Larsen, Malene; Madsen, Jacob; Kjaer, Michael

    2011-01-01

    Protein turnover in collagen rich tissue is influenced by exercise, but can only with difficulty be studied in vivo due to use of invasive procedure. The present study was done to investigate the possibility of applying the PET-tracer, cis-[18F]fluoro-proline (cis-Fpro), for non-invasive assessment of collagen synthesis in rat musculoskeletal tissues at rest and following short-term (3 days) treadmill running. Musculoskeletal collagen synthesis was studied in rats at rest and 24 h post-exercise. At each session, rats were PET scanned at two time points following injection of cis-FPro: (60 and 240 min p.i). SUV were calculated for Achilles tendon, calf muscle and tibial bone. The PET-derived results were compared to mRNA expression of collagen type I and III. Tibial bone had the highest SUV that increased significantly (p<0.001) from the early (60 min) to the late (240 min) PET scan, while SUV in tendon and muscle decreased (p<0.001). Exercise had no influence on SUV, which was contradicted by an increased gene expression of collagen type I and III in muscle and tendon. The clearly, visible uptake of cis-Fpro in the collagen-rich musculoskeletal tissues is promising for multi-tissue studies in vivo. The tissue-specific differences with the highest basal uptake in bone are in accordance with earlier studies relying on tissue incorporation of isotopic-labelled proline. A possible explanation of the failure to demonstrate enhanced collagen synthesis following exercise, despite augmented collagen type I and III transcription, is that SUV calculations are not sensitive enough to detect minor changes in collagen synthesis. Further studies including kinetic compartment modeling must be performed to establish whether cis-Fpro can be used for non-invasive in-vivo assessment of exercise-induced changes in musculoskeletal collagen synthesis. PMID:21347251

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

    PubMed

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

    2016-06-01

    Fibrosis occurs in skeletal muscle under various pathophysiological conditions such as Duchenne muscular dystrophy (DMD), a devastating disease characterized by fiber degeneration that results in progressive loss of muscle mass, weakness and increased extracellular matrix (ECM) accumulation. Fibrosis is also observed after skeletal muscle denervation and repeated cycles of damage followed by regeneration. The ECM is synthesized largely by fibroblasts in the muscle connective tissue under normal conditions. Myofibroblasts, cells that express α-smooth muscle actin (α-SMA), play a role in many tissues affected by fibrosis. In skeletal muscle, fibro/adipogenic progenitors (FAPs) that express cell-surface platelet-derived growth factor receptor-α (PDGFR-α) and the transcription factor Tcf4 seem to be responsible for connective tissue synthesis and are good candidates for the origin of myofibroblasts. We show that cells positive for Tcf4 and PDGFR-α are expressed in skeletal muscle under normal conditions and are increased in various skeletal muscles of mdx mice, a murine model for DMD, wild type muscle after sciatic denervation and muscle subjected to chronic damage. These cells co-label with the myofibroblast marker α-SMA in dystrophic muscle but not in normal tissue. The Tcf4-positive cells lie near macrophages mainly concentrated in dystrophic necrotic-regenerating foci. The close proximity of Tcf4-positive cells to inflammatory cells and their previously described role in muscle regeneration might reflect an active interaction between these cell types and growth factors, possibly resulting in a muscular regenerative or fibrotic condition. PMID:26742767

  17. Biocompatible Silk Noil-Based Three-Dimensional Carded-Needled Nonwoven Scaffolds Guide the Engineering of Novel Skin Connective Tissue.

    PubMed

    Chiarini, Anna; Freddi, Giuliano; Liu, Daisong; Armato, Ubaldo; Dal Prà, Ilaria

    2016-08-01

    Retracting hypertrophic scars resulting from healed burn wounds heavily impact on the patients' life quality. Biomaterial scaffolds guiding burned-out skin regeneration could suppress or lessen scar retraction. Here we report a novel silk noil-based three-dimensional (3D) nonwoven scaffold produced by carding and needling with no formic acid exposure, which might improve burn healing. Once wetted, it displays human skin-like physical features and a high biocompatibility. Human keratinocyte-like cervical carcinoma C4-I cells seeded onto the carded-needled nonwovens in vitro quickly adhered to them, grew, and actively metabolized glutamine releasing lactate. As on plastic, they released no proinflammatory IL-1β, although secreting tumor necrosis factor-alpha, an inducer of the autocrine mitogen amphiregulin in such cells. Once grafted into interscapular subcutaneous tissue of mice, carded-needled nonwovens guided the afresh assembly of a connective tissue enveloping the fibroin microfibers and filling the interposed voids within 3 months. Fibroblasts and a few poly- or mononucleated macrophages populated the engineered tissue. Besides, its extracellular matrix contained thin sparse collagen fibrils and a newly formed vascular network whose endothelin-1-expressing endothelial cells grew first on the fibroin microfibrils and later expanded into the intervening matrix. Remarkably, no infiltrates of inflammatory leukocytes and no packed collagen fibers bundles among fibroin microfibers, no fibrous capsules at the grafts periphery, and hence no foreign body response was obtained at the end of 3 months of observation. Therefore, we posit that silk noil-based 3D carded-needled nonwoven scaffolds are tools for translational medicine studies as they could guide connective tissue regeneration at deep burn wounds averting scar retraction with good functional results. PMID:27411949

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

    PubMed Central

    García-Sancho, Miguel

    2011-01-01

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

  19. 3T3 fibroblasts induce cloned interleukin 3-dependent mouse mast cells to resemble connective tissue mast cells in granular constituency

    SciTech Connect

    Dayton, E.T.; Pharr, P.; Ogawa, M.; Serafin, W.E.; Austen, K.F.; Levi-Schaffer, F.; Stevens, R.L.

    1988-01-01

    As assessed by ultrastructure, histochemical staining, and T-cell dependency, in vitro-differentiated interleukin 3-dependent mouse mast cells are comparable to the mast cells that reside in the gastrointestinal mucosa but not in the skin or the serosal cavity of the mouse. The authors now demonstrate that when cloned interleukin 3-dependent mast cells are cocultured with mouse skin-derived 3T3 fibroblasts in the presence of WEHI-3 conditioned medium for 28 days, the mast cells acquire the ability to stain with safranin, increase their histamine content approx. 50-fold and their carboxypeptidase. A content approx. 100-fold, and augment approx. their biosynthesis of proteoglycans bearing /sup 35/S-labeled haparin relative to /sup 35/S-labeled chondroitin sulfate glycosaminoglycans. Thus, fibroblasts induce interleukin 3-dependent mouse mast cells to change phenotype from mucosal-like to connective tissue-like, indicating that the biochemical and functional characteristics of this mast cell type are strongly influenced by the connective tissue microenvironment.

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

    PubMed Central

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

    2014-01-01

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

  1. New insights into the structure, assembly and biological roles of 10-12 nm connective tissue microfibrils from fibrillin-1 studies.

    PubMed

    Jensen, Sacha A; Handford, Penny A

    2016-04-01

    The 10-12 nm diameter microfibrils of the extracellular matrix (ECM) impart both structural and regulatory properties to load-bearing connective tissues. The main protein component is the calcium-dependent glycoprotein fibrillin, which assembles into microfibrils at the cell surface in a highly regulated process involving specific proteolysis, multimerization and glycosaminoglycan interactions. In higher metazoans, microfibrils act as a framework for elastin deposition and modification, resulting in the formation of elastic fibres, but they can also occur in elastin-free tissues where they perform structural roles. Fibrillin microfibrils are further engaged in a number of cell matrix interactions such as with integrins, bone morphogenetic proteins (BMPs) and the large latent complex of transforming growth factor-β (TGFβ). Fibrillin-1 (FBN1) mutations are associated with a range of heritable connective disorders, including Marfan syndrome (MFS) and the acromelic dysplasias, suggesting that the roles of 10-12 nm diameter microfibrils are pleiotropic. In recent years the use of molecular, cellular and whole-organism studies has revealed that the microfibril is not just a structural component of the ECM, but through its network of cell and matrix interactions it can exert profound regulatory effects on cell function. In this review we assess what is known about the molecular properties of fibrillin that enable it to assemble into the 10-12 nm diameter microfibril and perform such diverse roles. PMID:27026396

  2. CD4 T-cell hyporesponsiveness induced by schistosome larvae is not dependent upon eosinophils but may involve connective tissue mast cells.

    PubMed

    Prendergast, C T; Sanin, D E; Mountford, A P

    2016-02-01

    In areas endemic for schistosomiasis, people can often be in contact with contaminated water resulting in repeated exposures to infective Schistosoma mansoni cercariae. Using a murine model, repeated infections result in IL-10-dependent CD4(+) T-cell hyporesponsiveness in the skin-draining lymph nodes (sdLN), which could be caused by an abundance of eosinophils and connective tissue mast cells at the skin infection site. Here, we show that whilst the absence of eosinophils did not have a significant effect on cytokine production, MHC-II(+) cells were more numerous in the dermal cell exudate population. Nevertheless, the absence of dermal eosinophils did not lead to an increase in the responsiveness of CD4(+) T cells in the sdLN, revealing that eosinophils in repeatedly exposed skin did not impact on the development of CD4(+) T-cell hyporesponsiveness. On the other hand, the absence of connective tissue mast cells led to a reduction in dermal IL-10 and to an increase in the number of MHC-II(+) cells infiltrating the skin. There was also a small but significant alleviation of hyporesponsiveness in the sdLN, suggesting that mast cells may have a role in regulating immune responses after repeated exposures of the skin to S. mansoni cercariae. PMID:26679416

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed

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

    2014-04-01

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

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

    PubMed

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

    2009-12-01

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

  6. The rehabilitation of facial involvement in systemic sclerosis: efficacy of the combination of connective tissue massage, Kabat's technique and kinesitherapy: a randomized controlled trial.

    PubMed

    Maddali-Bongi, S; Landi, G; Galluccio, F; Del Rosso, A; Miniati, I; Conforti, M L; Casale, R; Matucci-Cerinic, M

    2011-07-01

    In Systemic Sclerosis (SSc), face involvement causes functional loss as well as aesthetic changes and loss of the self-image. The aim of the work is to evaluate the efficacy of a rehabilitation program based on the combination of Kabat's technique, connective massage and kinesitherapy specifically conceived for the face of SSc patients. Forty SSc patients were enrolled: 20 patients (interventional group) were treated for 9 weeks (twice a week, 1 h per session) with a combined connective tissue massage, Kabat's technique, kinesitherapy and home exercise program, and 20 patients (control group) were assigned only home exercise program. All patients were assessed at baseline (T0), at the end of the treatment (T1) and after 9 weeks of follow-up (T2). They were evaluated with SF-36, HAQ, modified Rodnan skin score, mouth opening in centimeters and Mouth Handicap in Systemic Sclerosis (MHISS) scale. At T1, both groups improved in mouth opening (P < 0.05), but the improvement was maintained at T2 only in interventional group. In interventional group, facial skin score ameliorated at T1 and maintained at T2 (P < 0.05 vs. T0), while no change was observed in controls. In both groups, SF-36 and HAQ were not affected by the treatment. MHISS scale improved significantly in interventional group at T1 (P < 0.001), while no change was found in controls. The combination of connective tissue massage, Kabat's technique, kinesitherapy and home-based exercises is more effective than a home exercise program alone in the rehabilitative treatment of SSc facial involvement. PMID:20238221

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

    PubMed Central

    2014-01-01

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

  8. Comparative evaluation of a bioabsorbable collagen membrane and connective tissue graft in the treatment of localized gingival recession: A clinical study

    PubMed Central

    Babu, Harsha Mysore; Gujjari, Sheela Kumar; Prasad, Deepak; Sehgal, Praveen Kumar; Srinivasan, Aishwarya

    2011-01-01

    Background: Gingival recession (GR) can result in root sensitivity, esthetic concern to the patient, and predilection to root caries. The purpose of this randomized clinical study was to evaluate (1) the effect of guided tissue regeneration (GTR) procedure using a bioabsorbable collagen membrane, in comparison to autogenous subepithelial connective tissue graft (SCTG) for root coverage in localized gingival recession defects; and (2) the change in width of keratinized gingiva following these two procedures. Materials and Methods: A total of 10 cases, showing at least two localized Miller's Class I or Class II gingival recession, participated in this study. In a split mouth design, the pairs of defects were randomly assigned for treatment with either SCTG (SCTG Group) or GTR-based collagen membrane (GTRC Group). Both the grafts were covered with coronally advanced flap. Recession depth (RD), recession width (RW), width of keratinized gingiva (KG), probing depth (PD), relative attachment level (RAL), plaque index (PI), and gingival index (GI) were recorded at baseline, 3 and 6 months postoperatively. Results: Six months following root coverage procedures, the mean root coverage was found to be 84.84% ± 16.81% and 84.0% ± 15.19% in SCTG Group and GTRC Group, respectively. The mean keratinized gingival width increase was 1.50 ± 0.70 mm and 2.30 ± 0.67 mm in the SCTG and GTRC group, respectively, which was not statistically significant. Conclusion: It may be concluded that resorbable collagen membrane can be a reliable alternative to autogenous connective tissue graft in the treatment of gingival recession. PMID:22368359

  9. Differential localization of type I and type III procollagen messenger ribonucleic acids in inflamed periodontal and periapical connective tissues by in situ hybridization.

    PubMed

    Larjava, H; Sandberg, M; Happonen, R P; Vuorio, E

    1990-01-01

    Inflammatory lesions of periodontal and periapical connective tissue were studied by in situ hybridization to detect cells responsible for type I and type III collagen production. Formalin-fixed and paraffin-embedded tissue specimens from patients with oral lesions of various stages of inflammation were hybridized with cDNA probes specific for human pro alpha 1(I) and pro alpha 1(III) collagen mRNAs, and with bacteriophage lambda DNA as a control probe. This technique permitted us to localize fibroblasts active in type I collagen synthesis in the vicinity of inflammatory infiltrates in all the samples studied. Cells containing high levels of type III collagen mRNA were seen in early abscess formation and they were particularly abundant in pyogenic granuloma and irritation fibroma. Type I collagen mRNA was prominent in gingival fibrosis. In the infrabony lesions with active inflammatory infiltrations the production of collagen was confined mostly to the periphery of the lesions. These findings give indirect evidence that cytokines liberated during the early stages of the inflammatory process stimulate expression of the type III collagen gene by fibroblasts. In chronic lesions a gradual switch from type III to type I collagen gene expression occurs. The change in collagen types appears to underlie the observed isolation of the inflammation by a collagenous capsule. In all the samples studied fibroblasts exhibited marked variation in their levels of procollagen mRNAs, supporting previous views about their heterogeneity in connective tissues. The approach presented here offers new possibilities to study cellular interactions and metabolic activities in inflammatory lesions. PMID:2296161

  10. Connective tissue polarity. Optical second-harmonic microscopy, crossed-beam summation, and small-angle scattering in rat-tail tendon.

    PubMed Central

    Freund, I; Deutsch, M; Sprecher, A

    1986-01-01

    Connective tissue polarity has remained an intractable enigma for over two decades. We present new data on optical second harmonic generation in native, wet, rat-tail tendon. Scanning second-harmonic microscopy has revealed, for the first time, the existence of a discrete network of fine, polar, filamentous or columnar, structures, and, also, the presence of strongly polar surface, or near-surface patches. The thickness of these features was probed via crossed-beam optical frequency summation and the polar material is estimated to occupy a few percent of the tendon volume. The three-dimensional spatial distribution of filaments was studied with the aid of small-angle second-harmonic scattering, and the filaments were found to permeate the tendon cross-section in an apparently random fashion. These latter measurements also revealed that essentially all polar filaments had the same directionality. Concomitant studies of the polar collagen fibrils that comprise the bulk of tendon were in full accord with prior electron microscope results that had demonstrated that the directionality of these fibrils varies up/down in a purely random fashion, and thus cannot yield a net macroscopic polarity. Quantitative analysis of the second-harmonic data yields the conclusion that the observed polar structures cannot be simply local regions containing some accidental net excess of similarly oriented fibrils. The analytical expressions used in the analysis of the data obtained for this complex tissue were supported by extensive, realistic computer simulations. The discovery that the polarity of rat-tail tendon, and possibly other forms of connective tissue, resides in discrete structures, some of which are located near the tendon surface, should permit the ready isolation of polar-rich material for further study by a variety of techniques. Images FIGURE 2 PMID:3779007

  11. Characterization of dermal structural assembly in normal and pathological connective tissues by intrinsic signal multiphoton optical microscopy

    NASA Astrophysics Data System (ADS)

    Lyubovitsky, Julia G.; Xu, Xiaoman; Sun, Chung-ho; Andersen, Bogi; Krasieva, Tatiana B.; Tromberg, Bruce J.

    2008-02-01

    Employing a reflectance multi-photon microscopy (MPM) technique, we developed novel method to quantitatively study the three-dimensional assembly of structural proteins within bulk of dermal ECMs. Using a structurally simplified model of skin with enzymatically dissected epidermis, we find that low resolution MPM clearly discriminates between normal and pathological dermis. High-resolution images revealed that the backscattered MPM signals are affected by the assembly of collagen fibrils and fibers within this system. Exposure of tissues to high concentrations of potentially denaturing chemicals also resulted in the reduction of SHG signals from structural proteins which coincided with the appearance of aggregated fluorescent structures.

  12. Structural investigation of loose connective tissue by using a series of dextran fractions as non-interacting macromolecular probes.

    PubMed

    Meyer, F A; Koblentz, M; Silberberg, A

    1977-02-01

    The ability of the uncharged open-coil dextran molecules to penetrate tissue space, without coil-shape change, was utilized to probe (by partitioning experiments) the structural arrangement of the collagen-fibre network and the proteoglycan system. Hyaluronidase digests most of the proteoglycans away and enables the respective contributions to the exclusion volume to be evaluated by using a series of different-molecular-weight dextrans. It appears that the major part of the exclusion volume is due to the collagen-fibril as a rod and the dextran coil as an impenetrable sphere. The additional exclusion due to the proteoglycans could be accounted for by a set of points (regions of high proteoglycan-segment density) over which the dextran coild cannot pass. These points are an average of 50 nm apart and are indicative of local extensive entanglement of high-molecular-weight proteoglycans with each other. Reasons are given why these entanglements could not act as cross-links in long-term elastic loading of the tissue. PMID:849263

  13. Structural investigation of loose connective tissue by using a series of dextran fractions as non-interacting macromolecular probes.

    PubMed Central

    Meyer, F A; Koblentz, M; Silberberg, A

    1977-01-01

    The ability of the uncharged open-coil dextran molecules to penetrate tissue space, without coil-shape change, was utilized to probe (by partitioning experiments) the structural arrangement of the collagen-fibre network and the proteoglycan system. Hyaluronidase digests most of the proteoglycans away and enables the respective contributions to the exclusion volume to be evaluated by using a series of different-molecular-weight dextrans. It appears that the major part of the exclusion volume is due to the collagen-fibril as a rod and the dextran coil as an impenetrable sphere. The additional exclusion due to the proteoglycans could be accounted for by a set of points (regions of high proteoglycan-segment density) over which the dextran coild cannot pass. These points are an average of 50 nm apart and are indicative of local extensive entanglement of high-molecular-weight proteoglycans with each other. Reasons are given why these entanglements could not act as cross-links in long-term elastic loading of the tissue. PMID:849263

  14. Glucocorticoid effect on repair processes in vascular connective tissue. Morphological examination and biochemical studies on collagen RNA and DNA in rabbit aorta.

    PubMed

    Manthorpe, R; Garbarsch, C; Lorenzen, I

    1975-10-01

    Male rabbits were injured by a single mechanical dilatation of the aorta and then injected with prednisone 2 mg/kg saline for 14 days or starved. Morphological studies and biochemical measurements of the collagen metabolism, the content of alpha-amino nitrogen, RNA, DNA, water and fat, and the aorta to serum ratio of 125I-albumin were performed on the intima-media layer of the descending thoracic aorta. Prednisone inhibited the intimal thickening. In the media the infiltration by mononuclear cells, the proliferation and regeneration of the smooth muscle cells and the calcification were reduced. Prednisone caused a decrease in 0.45 M NaCl soluble collagen as well as in the dialysable and non-dialysable 14C-hydroxyproline fractions. The total amount of collagen, elastin and alpha-amino nitrogen was unchanged, whereas the 14C-proline incorporation in the non-dialysable protein fraction was inhibited to a greater extent than the 14C-hydroxyproline synthesis. The findings indicate that prednisone inhibits the biosynthesis of collagen, which is inhibited to a greater extent than the general protein synthesis. Prednisone increased the dialysable to non-dialysable 14C-hydroxyproline ratio consistent with a relative increase in the catabolism of newly synthesized collagen. The aortic content of RNA and DNA was reduced consistent with the inhibition of protein synthesis and cell proliferation. Finally prednisone decreased the aortic content of water when related to the wet weight and increased the aortic content of fat. The aorta to serum ratio of 125I-albumin was not influenced by prednisone. It is concluded that administration of glucocorticoid for 14 days exerts an inhibitory action on the histological reaction to injury as well as on the biosynthesis of collagen of the repair processes in vascular connective tissue. A comparison with the effects of prednisone on undamaged rabbit aorta (Manthorpe et al. 1974) demonstrates that the metabolism of collagen of vascular

  15. Association of serum KL-6 levels with interstitial lung disease in patients with connective tissue disease: a cross-sectional study.

    PubMed

    Oguz, Ekin Oktay; Kucuksahin, Orhan; Turgay, Murat; Yildizgoren, Mustafa Turgut; Ates, Askin; Demir, Nalan; Kumbasar, Ozlem Ozdemir; Kinikli, Gulay; Duzgun, Nursen

    2016-03-01

    It was aimed to evaluate KL-6 glycoprotein levels to determine if it may be a diagnostic marker for the connective tissue diseases (CTDs) predicting CTD-related interstitial lung diseases (ILDs) (CTD-ILD) development and to examine if there was a difference between patients and healthy controls. The study included 113 patients with CTD (45 CTD without lung involvement, 68 CTD-ILD) and 45 healthy control subjects. KL-6 glycoprotein levels were analyzed with ELISA in patients and the control group. The relationship between KL-6 glycoprotein levels and CTD-ILD was assessed. In the comparison of all the groups in the study, significantly higher levels of KL-6 were determined in the CTD-ILD group than in either the CTD without pulmonary involvement group or the healthy control group (p < 0.008 and p < 0.001, respectively). There was no statistically significant difference between the KL-6 levels in the healthy control group and the CTD without pulmonary involvement group (p = 0.289). The KL-6 levels did not differ significantly according to the connective tissue diseases in the diagnostic groups (systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, mixed connective tissue disease, scleroderma, polymyositis/ dermatomyositis). In the healthy control group, there was a statistically significant difference between KL-6 levels in smokers and non-smokers. Smokers had significantly higher serum KL-6 levels compared with non-smokers (p < 0.05). There was no statistically significant difference between smoking status (pack-year) and serum KL-6 levels. There was no statistically significant correlation between serum KL-6 levels and time since diagnosis of CTD and CTD-ILD. The level of KL-6 as a predictive factor could be used to identify the clinical development of ILD before it is detected on imaging modality. Further prospective clinical studies are needed to define whether levels of KL-6 might have prognostic value or might predict

  16. On the Adjacent Eccentric Distance Sum Index of Graphs

    PubMed Central

    Qu, Hui; Cao, Shujuan

    2015-01-01

    For a given graph G, ε(v) and deg(v) denote the eccentricity and the degree of the vertex v in G, respectively. The adjacent eccentric distance sum index of a graph G is defined as ξsv(G)=∑v∈V(G)ε(v)D(v)deg(v), where D(v)=∑u∈V(G)d(u,v) is the sum of all distances from the vertex v. In this paper we derive some bounds for the adjacent eccentric distance sum index in terms of some graph parameters, such as independence number, covering number, vertex connectivity, chromatic number, diameter and some other graph topological indices. PMID:26091095

  17. Comparative clinical evaluation of laterally positioned pedicle graft and subepithelial connective tissue graft in the treatment of Miller's Class I and II gingival recession: A 6 months study

    PubMed Central

    Dulani, Kirti Satish; Bhavsar, Neeta Vijay; Trivedi, Sakshee Rahul; Trivedi, Rahul Anil

    2015-01-01

    Aim: The purpose of the study was to compare clinical outcomes of laterally positioned pedicle graft (LPPG) and subepithelial connective tissue graft (SCTG) for treatment of Miller's Class I and II gingival recession defects, at the end of 6 months. Materials and Methods: Sixty Miller's Class I or II gingival recession defects (≥3 mm) (n = 30 each) on the labial aspect of anterior teeth were treated by either of the above techniques. Clinical parameters including recession depth (RD), width of keratinized gingiva (WKG), percentage of root coverage (%RC), and complete RC were recorded at baseline and 6 months postoperatively. Data were recorded and statistical analysis was done for both intergroup and intragroup. Statistical Analysis Used: Paired t-test intragroup and Student's t-test intergroup. Results: In LPPG, RD decreased from 4.9 ± 0.99 mm to 1.1 ± 0.3 mm and WKG increased from 0.7 ± 0.87 to 4.5 ± 0.86 mm at 6 months, while in SCTG, RD decreased from 4.67 ± 1.12 mm to 0.46 ± 0.68 mm and WKG increased from 1.1 ± 0.99 to 5.33 ± 0.72 mm at 6 months postoperatively. The values of the soft tissue coverage remained stable for 6 months. Conclusions: Highly significant and effective soft tissue coverage was obtained by both techniques. LPPG resulted in effective soft tissue coverage for isolated deep narrow defects while SCTG in isolated and multiple, deep narrow and wide defects. PMID:26941517

  18. Epithelial-connective tissue interactions induced by thyroid hormone receptor are essential for adult stem cell development in the Xenopus laevis intestine

    PubMed Central

    Hasebe, Takashi; Buchholz, Daniel R.; Shi, Yun-Bo; Ishizuya-Oka, Atsuko

    2012-01-01

    In the amphibian intestine during metamorphosis, stem cells appear and generate the adult absorptive epithelium, analogous to the mammalian one, under the control of thyroid hormone (TH). We have previously shown that the adult stem cells originate from differentiated larval epithelial cells in the Xenopus laevis intestine. To clarify whether TH signaling in the epithelium alone is sufficient for inducing the stem cells, we have now performed tissue recombinant culture experiments, using transgenic X. laevis tadpoles that express a dominant positive TH receptor (dpTR) under a control of heat shock promoter. Wild-type (Wt) or dpTR transgenic (Tg) larval epithelium (Ep) was isolated from the tadpole intestine, recombined with homologous or heterologous non-epithelial tissues (non-Ep), and then cultivated in the absence of TH with daily heat shocks to induce transgenic dpTR expression. Adult epithelial progenitor cells expressing sonic hedgehog became detectable on day 5 in both the recombinant intestine of Tg Ep and Tg non-Ep (Tg/Tg) and that of Tg Ep and Wt non-Ep (Tg/Wt). However, in Tg/Wt intestine, they did not express other stem cell markers such as Musashi-1 and never generated the adult epithelium expressing a marker for absorptive epithelial cells. Our results indicate that, while it is unclear why some larval epithelial cells dedifferentiate into adult progenitor/stem cells, TR-mediated gene expression in the surrounding tissues other than the epithelium is required for them to develop into adult stem cells, suggesting the importance of TH-inducible epithelial-connective tissue interactions in establishment of the stem cell niche in the amphibian intestine. PMID:21280164

  19. MicroRNA-143-3p inhibits hyperplastic scar formation by targeting connective tissue growth factor CTGF/CCN2 via the Akt/mTOR pathway.

    PubMed

    Mu, Shengzhi; Kang, Bei; Zeng, Weihui; Sun, Yaowen; Yang, Fan

    2016-05-01

    Post-traumatic hypertrophic scar (HS) is a fibrotic disease with excessive extracellular matrix (ECM) production, which is a response to tissue injury by fibroblasts. Although emerging evidence has indicated that miRNA contributes to hypertrophic scarring, the role of miRNA in HS formation remains unclear. In this study, we found that miR-143-3p was markedly downregulated in HS tissues and fibroblasts (HSFs) using qRT-PCR. The expression of connective tissue growth factor (CTGF/CCN2) was upregulated both in HS tissues and HSFs, which is proposed to play a key role in ECM deposition in HS. The protein expression of collagen I (Col I), collagen III (Col III), and α-smooth muscle actin (α-SMA) was obviously inhibited after treatment with miR-143-3p in HSFs. The CCK-8 assay showed that miR-143-3p transfection reduced the proliferation ability of HSFs, and flow cytometry showed that either early or late apoptosis of HSFs was upregulated by miR-143-3p. In addition, the activity of caspase 3 and caspase 9 was increased after miR-143-3p transfection. On the contrary, the miR-143-3p inhibitor was demonstrated to increase cell proliferation and inhibit apoptosis of HSFs. Moreover, miR-143-3p targeted the 3'-UTR of CTGF and caused a significant decrease of CTGF. Western blot demonstrated that Akt/mTOR phosphorylation and the expression of CTGF, Col I, Col III, and α-SMA were inhibited by miR-143-3p, but increased by CTGF overexpression. In conclusion, we found that miR-143-3p inhibits hypertrophic scarring by regulating the proliferation and apoptosis of human HSFs, inhibiting ECM production-associated protein expression by targeting CTGF, and restraining the Akt/mTOR pathway. PMID:27075467

  20. Clinical and biochemical profiles suggest fibromuscular dysplasia is a systemic disease with altered TGF-β expression and connective tissue features

    PubMed Central

    Ganesh, Santhi K.; Xu, Zhi; Schoenhoff, Florian; Griswold, Benjamin F.; Yang, Jiandong; Tong, Lan; Yang, Min-Lee; Hunker, Kristina; Sloper, Leslie; Kuo, Shinie; Raza, Rafi; Milewicz, Dianna M.; Francomano, Clair A.; Dietz, Harry C.; Van Eyk, Jennifer; McDonnell, Nazli B.

    2014-01-01

    Fibromuscular dysplasia (FMD) is a rare, nonatherosclerotic arterial disease for which the molecular basis is unknown. We comprehensively studied 47 subjects with FMD, including physical examination, spine magnetic resonance imaging, bone densitometry, and brain magnetic resonance angiography. Inflammatory biomarkers in plasma and transforming growth factor β (TGF-β) cytokines in patient-derived dermal fibroblasts were measured by ELISA. Arterial pathology other than medial fibrodysplasia with multifocal stenosis included cerebral aneurysm, found in 12.8% of subjects. Extra-arterial pathology included low bone density (P<0.001); early onset degenerative spine disease (95.7%); increased incidence of Chiari I malformation (6.4%) and dural ectasia (42.6%); and physical examination findings of a mild connective tissue dysplasia (95.7%). Screening for mutations causing known genetically mediated arteriopathies was unrevealing. We found elevated plasma TGF-β1 (P=0.009), TGF-β2 (P=0.004) and additional inflammatory markers, and increased TGF-β1 (P=0.0009) and TGF-β2 (P=0.0001) secretion in dermal fibroblast cell lines from subjects with FMD compared to age- and gender-matched controls. Detailed phenotyping of patients with FMD allowed us to demonstrate that FMD is a systemic disease with alterations in common with the spectrum of genetic syndromes that involve altered TGF-β signaling and offers TGF-β as a marker of FMD.—Ganesh, S. K., Morissette, R., Xu, Z., Schoenhoff, F., Griswold, B. F., Yang, J., Tong, L., Yang, M.-L., Hunker, K., Sloper, L., Kuo, S., Raza, R., Milewicz, D. M., Francomano, C. A., Dietz, H. C., Van Eyk, J., McDonnell, N. B. Clinical and biochemical profiles suggest fibromuscular dysplasia is a systemic disease with altered TGF-β expression and connective tissue features. PMID:24732132

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

    PubMed

    Nicolas, G; Gaill, F; Zylberberg, L

    1997-01-01

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

  2. The problem with medical research on tissue and organ samples taken in connection with forensic autopsies in France.

    PubMed

    Rougé-Maillart, C; Dupont, V; Jousset, N

    2016-02-01

    Currently, in France, it is legally impossible to conduct scientific research on tissue and organ samples taken from forensic autopsies. In fact, the law schedules the destruction of such samples at the end of the judicial investigation, and the common law rules governing cadaver research cannot be applied to the forensic context. However, nothing seems in itself to stand in the way of such research since, despite their specific nature, these samples from forensic autopsies could be subject, following legislative amendments, to common law relating to medical research on samples taken from deceased persons. But an essential legislative amendment, firstly to allow the Biomedicine Agency to become authorized to issue a research permit and secondly, to change the research conditions in terms of the non-opposition of the deceased to said research. Such an amendment would be a true breakthrough because it would allow teams to continue to move forward calmly in research, and allow this research to be placed within a legal framework, which would promote international exchanges. PMID:26694871

  3. 5. Former P&LE tracks (now CSXT) adjacent to trestle towards ...

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

    5. Former P&LE tracks (now CSXT) adjacent to trestle towards west. - Monongahela Connecting Railroad Company, Y Trestle, South side of Monongahela River between Thirty-fourth & Twenty-ninth Streets, Pittsburgh, Allegheny County, PA

  4. A virus-like particle-based connective tissue growth factor vaccine suppresses carbon tetrachloride-induced hepatic fibrosis in mice.

    PubMed

    Li, Shuang; Lv, Yi-Fei; Su, Hou-Qiang; Zhang, Qian-Nan; Wang, Li-Rong; Hao, Zhi-Ming

    2016-01-01

    Connective tissue growth factor (CTGF) has been recognized as a central mediator and promising therapeutic target in hepatic fibrosis. In this study, we generated a novel virus-like particle (VLP) CTGF vaccine by inserting the 138-159 amino acid (aa) fragment of CTGF into the central c/e1 epitope of C-terminus truncated hepatitis B virus core antigen (HBc, aa 1-149) using a prokaryotic expression system. Immunization of BALB/c mice with the VLP vaccine efficiently elicited the production of anti-CTGF neutralizing antibodies. Vaccination with this CTGF vaccine significantly protected BALB/c mice from carbon tetrachloride (CCl4)-induced hepatic fibrosis, as indicated by decreased hepatic hydroxyproline content and lower fibrotic score. CCl4 intoxication-induced hepatic stellate cell activation was inhibited by the vaccination, as indicated by decreased α-smooth muscle actin expression and Smad2 phosphorylation. Vaccination against CTGF also attenuated the over-expression of some profibrogenic factors, such as CTGF, transforming growth factor-β1, platelet-derived growth factor-B and tissue inhibitor of metalloproteinase-1 in the fibrotic mouse livers, decreased hepatocyte apoptosis and accelerated hepatocyte proliferation in the fibrotic mouse livers. Our results clearly indicate that vaccination against CTGF inhibits fibrogenesis, alleviates hepatocyte apoptosis and facilitate hepatic regeneration. We suggest that the vaccine should be developed into an effective therapeutic measure for hepatic fibrosis. PMID:27562139

  5. Connective tissue growth factor mediates growth differentiation factor 8-induced increase of lysyl oxidase activity in human granulosa-lutein cells.

    PubMed

    Chang, Hsun-Ming; Fang, Ying; Liu, Pang-Pin; Cheng, Jung-Chien; Yang, Xiaokui; Leung, Peter C K

    2016-10-15

    Lysyl oxidase (LOX) is an essential enzyme for the stabilization of the extracellular matrix (ECM) and the subsequent follicle and oocyte maturation. Currently, there is limited information pertaining to the regulation of LOX activity in human ovarian tissue. Growth differentiation factor 8 (GDF8) is a unique member of the transforming growth factor-β superfamily that is expressed in human granulosa cells and has important roles in regulating a variety of ovarian functions. The aim of the present study was to investigate the effects of GDF8 on the regulation of LOX expression and activity in human granulosa cells and to examine the underlying molecular determinants. An established immortalized human granulosa cell line (SVOG) and primary granulosa-lutein cells were used as study models. Using dual inhibition approaches (TGF-β type I inhibitor SB505124 and small interfering RNAs) and ChIP analyses, we have demonstrated that GDF8 up-regulated the expression of connective tissue growth factor (CTGF) through the activin receptor-like kinase 5-mediated SMAD2/3-SMAD4 signaling pathways. In addition, the increase in CTGF expression contributed to the GDF8-induced increase in LOX expression and activity. Our findings suggest that GDF8 and CTGF may play critical roles in the regulation of ECM formation in human granulosa cells. PMID:27392496

  6. A virus-like particle-based connective tissue growth factor vaccine suppresses carbon tetrachloride-induced hepatic fibrosis in mice

    PubMed Central

    Li, Shuang; Lv, Yi-Fei; Su, Hou-Qiang; Zhang, Qian-Nan; Wang, Li-Rong; Hao, Zhi-Ming

    2016-01-01

    Connective tissue growth factor (CTGF) has been recognized as a central mediator and promising therapeutic target in hepatic fibrosis. In this study, we generated a novel virus-like particle (VLP) CTGF vaccine by inserting the 138–159 amino acid (aa) fragment of CTGF into the central c/e1 epitope of C-terminus truncated hepatitis B virus core antigen (HBc, aa 1–149) using a prokaryotic expression system. Immunization of BALB/c mice with the VLP vaccine efficiently elicited the production of anti-CTGF neutralizing antibodies. Vaccination with this CTGF vaccine significantly protected BALB/c mice from carbon tetrachloride (CCl4)-induced hepatic fibrosis, as indicated by decreased hepatic hydroxyproline content and lower fibrotic score. CCl4 intoxication-induced hepatic stellate cell activation was inhibited by the vaccination, as indicated by decreased α-smooth muscle actin expression and Smad2 phosphorylation. Vaccination against CTGF also attenuated the over-expression of some profibrogenic factors, such as CTGF, transforming growth factor-β1, platelet-derived growth factor-B and tissue inhibitor of metalloproteinase-1 in the fibrotic mouse livers, decreased hepatocyte apoptosis and accelerated hepatocyte proliferation in the fibrotic mouse livers. Our results clearly indicate that vaccination against CTGF inhibits fibrogenesis, alleviates hepatocyte apoptosis and facilitate hepatic regeneration. We suggest that the vaccine should be developed into an effective therapeutic measure for hepatic fibrosis. PMID:27562139

  7. Changes in the growth and metabolism of cells cultured from normal, sclerotic and rheumatoid connective tissue brought about by D-penicillamine and by sodium salicylate.

    PubMed

    Priestley, G C

    1980-06-01

    D-penicillamine and sodium salicylate were equally effective in suppressing the proliferation of fibroblasts from normal and scleroderma skin and rheumatoid synovial cells. The effects were concentration-dependent, beginning at around 100 microgram/ml, and proliferation was almost halted at 1600 microgram/ml. Individual cell strains of each type showed differences in drug susceptibility but there was no consistent difference between cells from normal and abnormal tissues. Acid mucopolysaccharide secretion was more clearly inhibited in scleroderma fibroblasts than in synovial cells, and penicillamine produced greater inhibition than salicylate, beginning at 10 microgram/ml and reaching almost 50% at 500 microgram/ml. Confluent cultures of scleroderma fibroblasts showed 23% less incorporation of 3H-proline into collagenase-sensitive protein in the presence of 1600 microgram/ml penicillamine, without significant effect on other protein synthesis; sodium salicylate had no effect. These data suggest that D-penicillamine may affect connective tissue metabolism in other ways than by interfering with collagen synthesis or cross-linking. PMID:6445922

  8. Neo-Epitopes—Fragments of Cartilage and Connective Tissue Degradation in Early Rheumatoid Arthritis and Unclassified Arthritis

    PubMed Central

    Karsdal, Morten Asser; Gerlag, Daniëlle M.; Tak, Paul Peter; Bay-Jensen, Anne Christine

    2016-01-01

    Objective Tissue destruction in rheumatoid arthritis (RA) is predominantly mediated by matrix metalloproteinases (MMPs), thereby generating protein fragments. Previous studies have revealed that these fragments include MMP-mediated collagen type I, II, and III degradation, citrullinated and MMP-degraded vimentin and MMP degraded C-reactive protein. We evaluated if biomarkers measuring serum levels of specific sequences of the mentioned fragments would provide further information of diagnostic and/or prognostic processes in early arthritis. Methods Ninety-two early arthritis patients (arthritis duration<1 year, DMARD naïve) were enrolled. Patients either fulfilled the ACR/EULAR2010 criteria for RA (n = 60) or had unclassified arthritis (UA) (n = 32). Patients fulfilling the RA criteria after 2 years follow-up were classified into non-erosive (n = 25), or erosive disease (n = 13). Concentrations of the biomarkers: C1M, C2M, C3M, VICM and CRPM were measured in baseline serum. Results C1M, C3M and CRPM were able to discriminate between the UA and RA baseline diagnosis in 92 patients with an AUROC of 0.64 (95%CI 0.517 to 0.762), 0.73 (95%CI 0.622 to 0.838) and 0.68 (95%CI 0.570 to 0.795). C2M showed a potential for discrimination between non-erosive and erosive disease in 38 patients with an AUROC of 0.75 (95%CI 0.597 to 0.910). All of the applied biomarkers correlated with one or more of the disease activity parameters: DAS28, ESR, CRP, SJC66, TJC68 and/or HAQ. Conclusion This is the first study evaluating the applied biomarkers at this early stage of arthritis. C1M, C3M, CRPM might be the best diagnostic marker, whereas high levels of C2M indicated progression of disease at follow-up in early RA patients. PMID:27019199

  9. 46 CFR 148.445 - Adjacent spaces.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

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

  10. 46 CFR 148.445 - Adjacent spaces.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

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

  11. 46 CFR 148.445 - Adjacent spaces.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

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

  12. 46 CFR 148.445 - Adjacent spaces.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

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

  13. Treatment Options for Adult Soft Tissue Sarcoma

    MedlinePlus

    ... superficial (in subcutaneous tissue with no spread into connective tissue or muscle below) or deep (in the muscle ... superficial (in subcutaneous tissue with no spread into connective tissue or muscle below) or deep (in the muscle ...

  14. Treatment Option Overview (Adult Soft Tissue Sarcoma)

    MedlinePlus

    ... superficial (in subcutaneous tissue with no spread into connective tissue or muscle below) or deep (in the muscle ... superficial (in subcutaneous tissue with no spread into connective tissue or muscle below) or deep (in the muscle ...

  15. Stages of Adult Soft Tissue Sarcoma

    MedlinePlus

    ... superficial (in subcutaneous tissue with no spread into connective tissue or muscle below) or deep (in the muscle ... superficial (in subcutaneous tissue with no spread into connective tissue or muscle below) or deep (in the muscle ...

  16. Assessment of Methods for Rapid Intraoperative Concentration and Selection of Marrow-Derived Connective Tissue Progenitors for Bone Regeneration Using the Canine Femoral Multidefect Model.

    PubMed

    Luangphakdy, Viviane; Boehm, Cynthia; Pan, Hui; Herrick, James; Zaveri, Phil; Muschler, George F

    2016-01-01

    Treatment of large bone defects remains an unsolved clinical challenge, despite a wide array of existing bone graft materials and strategies. Local deficiency in osteogenic connective tissue progenitors (CTP-Os) due to tissue loss is one of the central biological barriers to bone regeneration. Density separation (DS) and selective retention (SR) represent two promising methods that can be used intraoperatively to rapidly concentrate cells and potentially select CTP-Os. This project was designed to compare DS and SR using the canine femoral multidefect (CFMD) model. Mineralized cancellous allograft (MCA) was used as a standardized scaffold for cell transplantation. Two experiments were performed using a cohort of six animals in each comparison. In Cohort I, unprocessed bone marrow aspirate (BMA) clot was compared to DS processing. MCA combined with raw BMA or DS processed cells produced a robust and advanced stage of bone regeneration throughout the defect in 4 weeks with reconstitution of hematopoietic marrow. However, the retention of DS processed cells and CTP-Os in the MCA matrix was low compared to BMA clot. In Cohort II, MCA with DS-T cells (addition of calcium chloride thrombin to induce clotting and enhance cell and CTP-O retention) was compared to MCA with SR cells. A mean of 276 ± 86 million nucleated cells and 29,030 ± 10,510 CTP-Os were implanted per defect in the DS-T group. A mean of 76 ± 42 million nucleated cells and 30,266 ± 15,850 CTP-Os were implanted in the SR group. Bone formation was robust and not different between treatments. Histologically, both groups demonstrated regeneration of hematopoietic marrow tissue. However, SR sites contained more hematopoietic vascular tissues, less fibrosis, and less residual allograft, particularly in the intramedullary cavity, suggesting a more advanced stage of remodeling (p = 0.04). These data demonstrate excellent overall performance of DS and SR processing methods. Both methods achieve a bone

  17. Molecular disorganization of axons adjacent to human lacunar infarcts

    PubMed Central

    Lee, Monica D.; Tung, Spencer; Vinters, Harry V.; Carmichael, S. Thomas

    2015-01-01

    Cerebral microvascular disease predominantly affects brain white matter and deep grey matter, resulting in ischaemic damage that ranges from lacunar infarcts to white matter hyperintensities seen on magnetic resonance imaging. These lesions are common and result in both clinical stroke syndromes and accumulate over time, resulting in cognitive deficits and dementia. Magnetic resonance imaging studies suggest that these lesions progress over time, accumulate adjacent to prior lesions and have a penumbral region susceptible to further injury. The pathological correlates of this adjacent injury in surviving myelinated axons have not been previously defined. In this study, we sought to determine the molecular organization of axons in tissue adjacent to lacunar infarcts and in the regions surrounding microinfarcts, by determining critical elements in axonal function: the morphology and length of node of Ranvier segments and adjacent paranodal segments. We examined post-mortem brain tissue from six patients with lacunar infarcts and tissue from two patients with autosomal dominant retinal vasculopathy and cerebral leukoencephalopathy (previously known as hereditary endotheliopathy with retinopathy, nephropathy and stroke) who accumulate progressive white matter ischaemic lesions in the form of lacunar and microinfarcts. In axons adjacent to lacunar infarcts yet extending up to 150% of the infarct diameter away, both nodal and paranodal length increase by ∼20% and 80%, respectively, reflecting a loss of normal cell-cell adhesion and signalling between axons and oligodendrocytes. Using premorbid magnetic resonance images, brain regions from patients with retinal vasculopathy and cerebral leukoencephalopathy that harboured periventricular white matter hyperintensities were selected and the molecular organization of axons was determined within these regions. As in regions adjacent to lacunar infarcts, nodal and paranodal length in white matter of these patients is

  18. Biological findings from the PheWAS catalog: focus on connective tissue-related disorders (pelvic floor dysfunction, abdominal hernia, varicose veins and hemorrhoids).

    PubMed

    Salnikova, Lyubov E; Khadzhieva, Maryam B; Kolobkov, Dmitry S

    2016-07-01

    Pelvic floor dysfunction, specifically genital prolapse (GP) and stress urinary inconsistency (SUI) presumably co-occur with other connective tissue disorders such as hernia, hemorrhoids, and varicose veins. Observations on non-random coexistence of these disorders have never been summarized in a meta-analysis. The performed meta-analysis demonstrated that varicose veins and hernia are associated with GP. Disease connections on the molecular level may be partially based on shared genetic susceptibility. A unique opportunity to estimate shared genetic susceptibility to disorders is provided by a PheWAS (phenome-wide association study) designed to utilize GWAS data concurrently to many phenotypes. We searched the PheWAS Catalog, which includes the results of the PheWAS study with P value < 0.05, for genes associated with GP, SUI, abdominal hernia, varicose veins and hemorrhoids. We found pronounced signals for the associations of the SLC2A9 gene with SUI (P = 6.0e-05) and the MYH9 gene with varicose veins of lower extremity (P = 0.0001) and hemorrhoids (P = 0.0007). The comparison of the PheWAS Catalog and the NHGRI Catalog data revealed enrichment of genes associated with bone mineral density in GP and with activated partial thromboplastin time in varicose veins of lower extremity. In cross-phenotype associations, genes responsible for peripheral nerve functions seem to predominate. This study not only established novel biologically plausible associations that may warrant further studies but also exemplified an effective use of the PheWAS Catalog data. PMID:27126235

  19. 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

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

    2016-08-01

    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

  20. 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

  1. Root coverage using subepithelial connective tissue graft with platelet-rich plasma in the treatment of gingival recession: A clinical study

    PubMed Central

    Srinivas, B. V. V.; Rupa, N.; Halini Kumari, K. V.; Prasad, S. S. V.; Varalakshmi, U.; Sudhakar, K.

    2015-01-01

    Introduction: The presence of gingival recession associated with an insufficient amount of keratinized tissue may indicate gingival augmentation procedure. It is a multifaceted problem for which several treatment options are available. The most predictable technique used for gingival augmentation is the subepithelial connective tissue graft (SCTG). Platelet-rich plasma (PRP) is an enhanced source of growth factors and helps in accelerated periodontal repair and regeneration. Aims: The aim of this study was to evaluate the efficacy of SCTG along with PRP in the treatment of Miller's class I and II gingival recessions. Materials and Methods: Eleven subjects with Miller's class I and II gingival recessions were treated using SCTG with PRP. Clinical variables, including plaque index, gingival index, recession depth (RD), Recession width (RW), width of the keratinized gingiva, probing pocket depth (PD) and clinical attachment level (CAL) were recorded. Patients were recalled at baseline, 3 months, 6 months and 1-year after surgery and clinical recordings were taken. Root coverage percentage (%) was measured at the end of 1-year. Results: The clinical parameters were analyzed during the follow-up period by repeated measures ANOVA test. Twelve months follow-up results showed significant improvements in all the clinical parameters. Reduction of recession resulted in a significant decrease in CAL, PD, RW and RD at the end of 12 months. A statistically significant gain in width of keratinized gingiva and a mean root coverage of 84.72 ± 19.10 was obtained at the end of 12 months. Conclusion: From the results of this study, it may be concluded that SCTG with PRP is an effective and predictable method to treat miller's class I and II gingival recession. PMID:26538912

  2. Enamel matrix proteins (Emdogain) in combination with coronally advanced flap or subepithelial connective tissue graft in the treatment of shallow gingival recessions.

    PubMed

    Berlucchi, Ignazio; Francetti, Luca; Del Fabbro, Massimo; Testori, Tiziano; Weinstein, Roberto L

    2002-12-01

    This article describes two different surgical techniques of root coverage using Emdogain and shows preliminary results on 26 shallow recessions in 14 patients. For the treatment of 13 recessions, Emdogain was used in combination with a coronally advanced flap (CAF+EMD group). In the other 13 recessions, Emdogain and the flap were used in combination with a subepithelial connective tissue graft (CAF+CTG+EMD group). For the CAF+EMD group, the root coverage at 6 months was 93.97%, with an attachment gain of 3.2 mm; for the CAF+CTG+EMD group, the root coverage was 93.59%, with an attachment gain of 3.4 mm (no statistically significant difference between groups). When complete root coverage was not achieved, the residual recession was 1 mm in four cases and 2 mm in one case. Keratinized gingiva was increased for both groups, but more for the CAF+CTG+EMD group (1.38 mm versus 0.69 mm; statistically significant difference). Clinical attachment level decreased significantly in both groups, from 4.46 to 1.23 mm in the CAF+EMD group, and from 4.62 to 1.23 mm in the CAF+CTG+EMD group. Preliminary results show that Emdogain, in combination with CAF or CAF+CTG for the treatment of Miller Class I or II gingival recessions, displays good clinical results, with percentage of root coverage comparable or superior to other techniques. Further experimental studies on the dynamics of wound healing are needed to prove that EMD is really responsible for improving the percentage of regenerated versus repaired tissues with respect to other techniques. PMID:12516830

  3. HBX Protein-Induced Downregulation of microRNA-18a is Responsible for Upregulation of Connective Tissue Growth Factor in HBV Infection-Associated Hepatocarcinoma

    PubMed Central

    Liu, Xiaomin; Zhang, Yingjian; Wang, Ping; Wang, Hongyun; Su, Huanhuan; Zhou, Xin; Zhang, Lamei

    2016-01-01

    Background This study was designed to improve our understanding of the role of miR-18a and its target (connective tissue growth factor (CTGF), which are mediators in HBX-induced hepatocellular carcinoma (HCC). Material/Methods We first investigated the expression of several candidate microRNAs (miRNAs) reported to have been aberrantly expressed between HepG2 and HepG2.2.15, which is characterized by stable HBV infection, while the CTGF is identified as a target of miR-18a. Furthermore, the expression of CTGF evaluated in HepG2 was transfected with HBX, while the HepG2.2.15 was transfected with miR-18a and CTGF siRNA. We examined the cell cycle at the same time. Results We found that the expression of miR-18a was abnormally reduced in the HBV-positive HCC tissue samples compared with HBV-negative HCC samples. Through the use of a luciferase reporter system, we also identified CTGF 3′UTR (1046–1052 bp) as the exact binding site for miR-18a. We also observed a clear increase in CTGF mRNA and protein expression levels in HBV-positive HCC human tissue samples in comparison with the HBV-negative controls, indicating a possible negatively associated relationship between miR-18a and CTGF. Furthermore, we investigated the effect of HBX overexpression on miR-18a and CTGF, as well as the viability and cell cycle status of HepG2 cells. In addition, we found that HBX introduction downregulated miR-18a, upregulated CTGF, elevated the viability, and promoted cell cycle progression. We transfected HepG2.2.15 with miR-18a mimics and CTGF siRNA, finding that upregulated miR-18a and downregulated CTGF suppress the viability and cause cell cycle arrest. Conclusions Our study shows the role of the CTGF gene as a target of miR-18a, and identifies the function of HBV/HBX/miR-18a/CTGF as a key signaling pathway mediating HBV infection-induced HCC. PMID:27421245

  4. Comparison of prostaglandin F2alpha, bimatoprost (prostamide), and butaprost (EP2 agonist) on Cyr61 and connective tissue growth factor gene expression.

    PubMed

    Liang, Yanbin; Li, Chen; Guzman, Victor M; Evinger, Albert J; Protzman, Charles E; Krauss, Achim H-P; Woodward, David F

    2003-07-18

    Connective tissue growth factor (CTGF) and Cyr61 (cysteine-rich angiogenic protein 61) are members of the CCN gene family that encode multifunctional, extracellular matrix-associated signaling proteins. Because the mechanism of action of certain anti-glaucoma drugs involves extracellular matrix remodeling of ocular ciliary muscle, with a resultant increase in drainage of aqueous humor from the eye, we compared the effects of three pharmacologically distinct ocular hypotensive agents on Cyr61 and CTGF gene expression. Thus, prostaglandin F2alpha (PGF2alpha) (FP receptor agonist), Butaprost (EP2 receptor agonist), and Bimatoprost (a prostamide) were compared. Using Affymetrix gene chip technology, we first identified that PGF2alpha dramatically up-regulated Cyr61 and CTGF mRNA expression in HEK 293/EBNA cells (hFP-HEK 293/EBNA). Northern blot further confirmed the Cyr61 and CTGF up-regulation is in a dose- and time-dependent manner. PGF2alpha-induced up-regulation of Cyr61 appeared to exclusively involve the Rho pathway, and up-regulation of CTGF was via multiple intracellular pathways. Because prostamide receptors are, to date, defined only at the pharmacological level, Bimatoprost effects on Cyr61 and CTGF were studied in the isolated feline iris sphincter preparation, a tissue highly responsive to prostamides. Both PGF2alpha and Bimatoprost up-regulated Cyr61 mRNA expression in the cat iris tissue. Only PGF2alpha up-regulated CTGF mRNA expression in the cat iris. Therefore, PGF2alpha and Bimatoprost appear to interact with different receptors populations in the cat iris, according to their markedly different effects on CTGF. Activation of prostaglandin EP2 receptors (Gs-coupled) also up-regulated Cyr61 but not CTGF mRNA expression in the isolated cat iris. Similar data were observed in human primary ciliary smooth muscle cells. Thus, despite quite different signal transduction pathways, FP receptor stimulation up-regulates CTGF and Cyr61. The prostamide analog

  5. In-Vivo Nonlinear Optical Microscopy (NLOM) of Epithelial-Connective Tissue Interface (ECTI) Reveals Quantitative Measures of Neoplasia in Hamster Oral Mucosa

    PubMed Central

    Pal, Rahul; Yang, Jinping; Ortiz, Daniel; Qiu, Suimin; Resto, Vicente; McCammon, Susan; Vargas, Gracie

    2015-01-01

    The epithelial-connective tissue interface (ECTI) plays an integral role in epithelial neoplasia, including oral squamous cell carcinoma (OSCC). This interface undergoes significant alterations due to hyperproliferating epithelium that supports the transformation of normal epithelium to precancers and cancer. We present a method based on nonlinear optical microscopy to directly assess the ECTI and quantify dysplastic alterations using a hamster model for oral carcinogenesis. Neoplastic and non-neoplastic normal mucosa were imaged in-vivo by both multiphoton autofluorescence microscopy (MPAM) and second harmonic generation microscopy (SHGM) to obtain cross-sectional reconstructions of the oral epithelium and lamina propria. Imaged sites were biopsied and processed for histopathological grading and measurement of ECTI parameters. An ECTI shape parameter was calculated based on deviation from the linear geometry (ΔLinearity) seen in normal mucosa was measured using MPAM-SHGM and histology. The ECTI was readily visible in MPAM-SHGM and quantitative shape analysis showed ECTI deformation in dysplasia but not in normal mucosa. ΔLinearity was significantly (p < 0.01) higher in dysplasia (0.41±0.24) than normal (0.11±0.04) as measured in MPAM-SHGM and results were confirmed in histology which showed similar trends in ΔLinearity. Increase in ΔLinearity was also statistically significant for different grades of dysplasia. In-vivo ΔLinearity measurement alone from microscopy discriminated dysplasia from normal tissue with 87.9% sensitivity and 97.6% specificity, while calculations from histology provided 96.4% sensitivity and 85.7% specificity. Among other quantifiable architectural changes, a progressive statistically significant increase in epithelial thickness was seen with increasing grade of dysplasia. MPAM-SHGM provides new noninvasive ways for direct characterization of ECTI which may be used in preclinical studies to investigate the role of this interface in

  6. Urinary monocyte chemoattractant protein-1 (MCP-1) and connective tissue growth factor (CCN2) as prognostic markers for progression of diabetic nephropathy.

    PubMed

    Tam, Frederick W K; Riser, Bruce L; Meeran, Karim; Rambow, JoAnn; Pusey, Charles D; Frankel, Andrew H

    2009-07-01

    Profibrotic growth factors and inflammatory chemokines have been implicated in the pathogenesis of diabetic nephropathy (DN). However, measurement of urinary monocyte chemoattractant protein-1 (MCP-1) and connective tissue growth factor (CCN2) as prognostic markers has not previously been reported, and neither have two such molecules in urine been examined in a single study of DN. In this prospective observational study, 43 adult diabetic patients were studied, 40 were followed up for 6years. Urinary MCP-1/creatinine ratios were found to be significantly higher in patients with macroalbuminuria (3.3- and 2.1-fold higher (p<0.01) than normoalbuminuric and microalbuminuric patients, respectively). CCN2 exhibited a pattern different from that of urinary MCP-1. Urinary CCN2/creatinine ratios were greatly elevated in both microalbuminuric and macroalbuminuric patients (125- and 74-fold higher than normoalbuminuric patients, respectively, p<0.01 and p<0.05, respectively). Further, urinary CCN2, but not MCP-1, correlated with progression of microalbuminuria (R=0.49, p<0.05). In contrast, MCP-1, but not CCN2, correlated with the rate of eGFR decline for all patients (R=0.61, p<0.0001), reflective of its predictive value in patients with macroalbuminuria, but not for patients with microalbuminuria or normoalbuminuria. In conclusion, increased urinary CCN2 is associated with the early progression of DN, whereas MCP-1 is associated with later stage disease. PMID:19409809

  7. Connective tissue growth factor (CTGF) is regulated by Wnt and bone morphogenetic proteins signaling in osteoblast differentiation of mesenchymal stem cells.

    PubMed

    Luo, Qing; Kang, Quan; Si, Weike; Jiang, Wei; Park, Jong Kyung; Peng, Ying; Li, Xinmin; Luu, Hue H; Luo, Jeffrey; Montag, Anthony G; Haydon, Rex C; He, Tong-Chuan

    2004-12-31

    Osteoblast lineage-specific differentiation of mesenchymal stem cells is a well regulated but poorly understood process. Both bone morphogenetic proteins (BMPs) and Wnt signaling are implicated in regulating osteoblast differentiation and bone formation. Here we analyzed the expression profiles of mesenchymal stem cells stimulated with Wnt3A and osteogenic BMPs, and we identified connective tissue growth factor (CTGF) as a potential target of Wnt and BMP signaling. We confirmed the microarray results, and we demonstrated that CTGF was up-regulated at the early stage of BMP-9 and Wnt3A stimulations and that Wnt3A-regulated CTGF expression was beta-catenin-dependent. RNA interference-mediated knockdown of CTGF expression significantly diminished BMP-9-induced, but not Wnt3A-induced, osteogenic differentiation, suggesting that Wnt3A may also regulate osteoblast differentiation in a CTGF-independent fashion. However, constitutive expression of CTGF was shown to inhibit both BMP-9- and Wnt3A-induced osteogenic differentiation. Exogenous expression of CTGF was shown to promote cell migration and recruitment of mesenchymal stem cells. Our findings demonstrate that CTGF is up-regulated by Wnt3A and BMP-9 at the early stage of osteogenic differentiation, which may regulate the proliferation and recruitment of osteoprogenitor cells; however, CTGF is down-regulated as the differentiation potential of committed pre-osteoblasts increases, strongly suggesting that tight regulation of CTGF expression may be essential for normal osteoblast differentiation of mesenchymal stem cells. PMID:15496414

  8. Stroma-Derived Connective Tissue Growth Factor Maintains Cell Cycle Progression and Repopulation Activity of Hematopoietic Stem Cells In Vitro

    PubMed Central

    Istvánffy, Rouzanna; Vilne, Baiba; Schreck, Christina; Ruf, Franziska; Pagel, Charlotta; Grziwok, Sandra; Henkel, Lynette; Prazeres da Costa, Olivia; Berndt, Johannes; Stümpflen, Volker; Götze, Katharina S.; Schiemann, Matthias; Peschel, Christian; Mewes, Hans-Werner; Oostendorp, Robert A.J.

    2015-01-01

    Summary Hematopoietic stem cells (HSCs) are preserved in co-cultures with UG26-1B6 stromal cells or their conditioned medium. We performed a genome-wide study of gene expression changes of UG26-1B6 stromal cells in contact with Lineage− SCA-1+ KIT+ (LSK) cells. This analysis identified connective tissue growth factor (CTGF) to be upregulated in response to LSK cells. We found that co-culture of HSCs on CTGF knockdown stroma (shCtgf) shows impaired engraftment and long-term quality. Further experiments demonstrated that CD34− CD48− CD150+ LSK (CD34− SLAM) cell numbers from shCtgf co-cultures increase in G0 and senescence and show delayed time to first cell division. To understand this observation, a CTGF signaling network model was assembled, which was experimentally validated. In co-culture experiments of CD34− SLAM cells with shCtgf stromal cells, we found that SMAD2/3-dependent signaling was activated, with increasing p27Kip1 expression and downregulating cyclin D1. Our data support the view that LSK cells modulate gene expression in the niche to maintain repopulating HSC activity. PMID:26527384

  9. Advanced Glycation End-Products Induce Connective Tissue Growth Factor-Mediated Renal Fibrosis Predominantly through Transforming Growth Factor β-Independent Pathway

    PubMed Central

    Zhou, Guihua; Li, Cai; Cai, Lu

    2004-01-01

    Advanced glycation end-products (AGEs) play a critical role in diabetic nephropathy by stimulating extracellular matrix (ECM) synthesis. Connective tissue growth factor (CTGF) is a potent inducer of ECM synthesis and increases in the diabetic kidneys. To determine the critical role of CTGF in AGE-induced ECM accumulation leading to diabetic nephropathy, rats were given AGEs by intravenous injection for 6 weeks. AGE treatment induced a significant renal ECM accumulation, as shown by increases in periodic acid-Schiff-positive materials, fibronectin, and type IV collagen (Col IV) accumulation in glomeruli, and a mild renal dysfunction, as shown by increases in urinary volume and protein content. AGE treatment also caused significant increases in renal CTGF and transforming growth factor (TGF)-β1 mRNA and protein expression. Direct exposure of rat mesangial cells to AGEs in vitro significantly induced increases in fibronectin and Col IV production, which could be completely prevented by pretreatment with anti-CTGF antibody. AGE treatment also significantly increased both TGF-β1 and CTGF mRNA expression; however, inhibition of TGF-β1 mRNA expression by shRNA or neutralization of TGF-β1 protein by anti-TGF-β1 antibody did not significantly prevent AGE-increased expression of CTGF mRNA and protein. These results suggest that AGE-induced CTGF expression, predominantly through a TGF-β1-independent pathway, plays a critical role in renal ECM accumulation leading to diabetic nephropathy. PMID:15579446

  10. A 12 Months Clinical and Radiographic Study to Assess the Efficacy of Open Flap Debridement and Subepithelial Connective Tissue Graft in Management of Supracrestal Defects

    PubMed Central

    Chhina, Shivjot

    2015-01-01

    Background: An improvement in clinical parameters along with regeneration is the desired outcome of periodontal therapy. The aim of this study was to analyze and contrast the efficaciousness of combined open flap debridement (OFD) and subepithelial connective tissue graft (SECTG) to OFD in the management of periodontal supracrestal defects. Materials and Methods: Totally, 20 paired sites exhibiting supracrestal defects were subjected to surgical treatment adopting the split mouth design. The defects were divided randomly for treatment with OFD and SECTG (test) or OFD alone (control). The clinical effectiveness of the two arms of treatment was evaluated at 6 months and 12 months post-operatively by assessing clinical and radiographic parameters. The measurements carried out included probing pocket depth (PPD), relative attachment level (RAL), gingival marginal level, radiographic bone level (BL). Results: The mean reduction in PPD at 0-12 months was 3.20 ± 0.82 mm and RAL gain of 3.10 ± 1.51 mm was observed, the OFD and SECTG (test) group; corresponding observations for OFD (control) were 2.10 ± 0.63 mm and 1.90 ± 0.57 mm. However, BL changes did not follow the pattern of clinical improvement on the radiographic assessment of either treatment group. Post-operative evaluation was made. Improvement in different clinical parameters was statistically significant (P < 0.01). Conclusion: Treatment of supracrestal defects with a combination of OFD and SECTG led to significantly better clinical results compared to OFD alone. PMID:26464551

  11. Connective tissue growth factor is critical for proper β-cell function and pregnancy-induced β-cell hyperplasia in adult mice.

    PubMed

    Pasek, Raymond C; Dunn, Jennifer C; Elsakr, Joseph M; Aramandla, Mounika; Matta, Anveetha R; Gannon, Maureen

    2016-09-01

    During pregnancy, maternal β-cells undergo compensatory changes, including increased β-cell mass and enhanced glucose-stimulated insulin secretion. Failure of these adaptations to occur results in gestational diabetes mellitus. The secreted protein connective tissue growth factor (CTGF) is critical for normal β-cell development and promotes regeneration after partial β-cell ablation. During embryogenesis, CTGF is expressed in pancreatic ducts, vasculature, and β-cells. In adult pancreas, CTGF is expressed only in the vasculature. Here we show that pregnant mice with global Ctgf haploinsufficiency (Ctgf(LacZ/+)) have an impairment in maternal β-cell proliferation; no difference was observed in virgin Ctgf(LacZ/+) females. Using a conditional CTGF allele, we found that mice with a specific inactivation of CTGF in endocrine cells (Ctgf(ΔEndo)) develop gestational diabetes during pregnancy, but this is due to a reduction in glucose-stimulated insulin secretion rather than impaired maternal β-cell proliferation. Moreover, virgin Ctgf(ΔEndo) females also display impaired GSIS with glucose intolerance, indicating that underlying β-cell dysfunction precedes the development of gestational diabetes in this animal model. This is the first time a role for CTGF in β-cell function has been reported. PMID:27460898

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

    PubMed Central

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

    2013-01-01

    In order to identify disease biomarkers for the clinical and therapeutic management of autoimmune diseases such as systemic sclerosis (SSc) and undifferentiated connective tissue disease (UCTD), we have explored the setting of peripheral T regulatory (T reg) cells and assessed an expanded profile of autoantibodies in patients with SSc, including either limited (lcSSc) or diffuse (dcSSc) disease, and in patients presenting with clinical signs and symptoms of UCTD. A large panel of serum antibodies directed towards nuclear, nucleolar, and cytoplasmic antigens, including well-recognized molecules as well as less frequently tested antigens, was assessed in order to determine whether different antibody profiles might be associated with distinct clinical settings. Beside the well-recognized association between lcSSc and anti-centromeric or dcSSC and anti-topoisomerase-I antibodies, we found a significative association between dcSSc and anti-SRP or anti-PL-7/12 antibodies. In addition, two distinct groups emerged on the basis of anti-RNP or anti-PM-Scl 75/100 antibody production among UCTD patients. The levels of T reg cells were significantly lower in patients with SSc as compared to patients with UCTD or to healthy controls; in patients with lcSSc, T reg cells were inversely correlated to disease duration, suggesting that their levels may represent a marker of disease progression. PMID:23818915

  13. A Rare Case of Mixed Connective Tissue Disease (MCTD) with Intricate Features of Lupus, Polymyositis and Rheumatoid Arthritis Presenting with Severe Myositis.

    PubMed

    S, Lokesh; Tony, Kadavanu; Raghupathy; V, Suresh; Malepati, Balakrishna

    2015-03-01

    Mixed connective tissue disease (MCTD) includes clinical and laboratorial manifestations of systemic lupus erythematosus, scleroderma and polymyositis along with high titres of anti-U1RNP antibodies. In the initial phases of the disease, muscle enzyme levels increase but the disease remains generally subclinical. Presentation with myositis is uncommon. Our objective is to report a rare case of a patient who presented with a severe onset of myositis characterized by dysphagia, an increase in myopathy and joint involvement suggestive of RA. The patient was initiated on pulse corticosteroid therapy along with methotrexate in view of her elevated Creatine Kinase levels and biopsy findings that were suggestive of severe myositis. The patient showed clinical and laboratory improvement with this regimen. Though severe myositis and arthritis can occur in overlap syndrome, MCTD evolved as a separate disease entity due to presence of high titres of Anti U1-RNP antibodies. The authors emphasize that this is an extremely rare presentation of MCTD with only two previous cases seen in literature, one of a 13 year old child and the other being an adult female both of whom had evidence of myositis on presentation. PMID:25954655

  14. Comparative Morphology of the Papillae Linguales and their Connective Tissue Cores in the Tongue of the Greater Japanese Shrew-mole, Urotrichus talpoides

    PubMed Central

    Yoshimura, K; Shindo, J; Kageyama, I

    2013-01-01

    The external morphology of the papillae linguales (papillae filiformes, papillae fungiformes and papillae vallatae) and their connective tissue cores (CTCs) of the greater Japanese shrew-mole (Urotrichus talpoides) were analysed by optical and scanning electron microscopy. Papillae filiformes were distributed over the dorsal surface of the apex linguae, and on the rostral and caudal regions of the corpus linguae but were less numerous in the mid-region. They were absent from the radix linguae. A pair of oval papillae vallatae was situated at the border between the corpus linguae and the radix linguae. Papillae foliatae were absent. The epithelial surface of each papilla filiformis consisted of a circular concavity, a ring-like wall and either a single thumb-like process or 2–3 slender pointed processes, depending on their location. The morphology of the CTCs of the papillae filiformes also varied regionally. The papillae linguales of the Japanese shrew-mole were morphologically similar to those of other Talpidae and Soricidae, including the common shrew, particularly with respect to the papillae filiformes in the mid- and caudal regions of the corpus linguae. PMID:22571539

  15. Exosomes mediate intercellular transfer of pro-fibrogenic connective tissue growth factor (CCN2) between hepatic stellate cells, the principal fibrotic cells in the liver

    PubMed Central

    Charrier, Alyssa; Chen, Ruju; Chen, Li; Kemper, Sherri; Hattori, Takako; Takigawa, Masaharu; Brigstock, David R.

    2014-01-01

    Background Fibrogenic pathways in the liver are principally regulated by hepatic stellate cells (HSC) which produce and respond to fibrotic mediators such as connective tissue growth factor (CCN2). The aim of this study was to determine whether CCN2 is shuttled between HSC in membraneous nanovesicles, or “exosomes”. Methods Exosomes were incubated with HSC after isolation from conditioned medium of control or CCN2-GFP-transfected primary mouse HSC or human LX-2 HSC. Some exosomes were flourescently stained with PKH26. HSC co-culture experiments were performed in the presence of GW4869 exosome inhibitor. CCN2 or CCN2-GFP were evaluated by qRT-PCR or Western blot. Results HSC-derived exosomes contained CCN2 or CCN2 mRNA, each of which increased in concentration during HSC activation or after transfection of HSC with CCN2-GFP. Exosomes, stained with either PKH26 or purified from CCN2-GFP-transfected cells, were taken up by activated or quiescent HSC resulting in CCN2-GFP delivery, as shown by their direct addition to recipient cells or by the GW4869-dependency of donor HSC. Conclusions CCN2 is packaged into secreted nano-sized exosomes which mediate its intercellular transfer between HSC. Exosomal CCN2 may amplify or fine-tune fibrogenic signaling and may, in conjunction with other exosome constituents, have utility as a noninvasive biomarker to assess hepatic fibrosis. PMID:24882759

  16. FG-3019 anti-connective tissue growth factor monoclonal antibody: results of an open-label clinical trial in idiopathic pulmonary fibrosis.

    PubMed

    Raghu, Ganesh; Scholand, Mary Beth; de Andrade, João; Lancaster, Lisa; Mageto, Yolanda; Goldin, Jonathan; Brown, Kevin K; Flaherty, Kevin R; Wencel, Mark; Wanger, Jack; Neff, Thomas; Valone, Frank; Stauffer, John; Porter, Seth

    2016-05-01

    FG-3019 is a fully human monoclonal antibody that interferes with the action of connective tissue growth factor, a central mediator in the pathogenesis of fibrosis.This open-label phase 2 trial evaluated the safety and efficacy of two doses of FG-3019 administered by intravenous infusion every 3 weeks for 45 weeks in patients with idiopathic pulmonary fibrosis (IPF). Subjects had a diagnosis of IPF within the prior 5 years defined by either usual interstitial pneumonia (UIP) pattern on a recent high-resolution computed tomography (HRCT) scan, or a possible UIP pattern on HRCT scan and a recent surgical lung biopsy showing UIP pattern. Pulmonary function tests were performed every 12 weeks, and changes in the extent of pulmonary fibrosis were measured by quantitative HRCT scans performed at baseline and every 24 weeks.FG-3019 was safe and well-tolerated in IPF patients participating in the study. Changes in fibrosis were correlated with changes in pulmonary function.Further investigation of FG-3019 in IPF with a placebo-controlled clinical trial is warranted and is underway. PMID:26965296

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

    PubMed

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

    2015-03-10

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

  18. Comparative evaluation of management of gingival recession using subepithelial connective tissue graft and collagen membrane by periodontal microsurgical technique: A clinical study of 40 cases

    PubMed Central

    Thankkappan, Prasanth; Roy, Subrata; Mandlik, Vivek Bapurao

    2016-01-01

    Background: New technologies, instruments, and surgical techniques are necessary to help the clinician ensure the best result and satisfy the patient's expectations, and surgical microscope has been thoroughly demonstrated as a useful tool. A clinical study was carried out to compare 2 different types of root coverage procedures using periodontal microsurgical procedure. Materials and Methods: Forty patients were selected and divided into Group A and Group B. Group A subjects were treated with subepithelial connective tissue graft (CTG) whereas Group B subjects were treated using a resorbable collagen membrane. The procedures were performed with the help of an operating microscope using 250 mm objective lens and ×6 magnification. Results: A comparison between baseline, 1, 3, and 12 months have been done between groups among all parameters. It has been noticed that the root coverage was better in Group A subjects at all time. At 12 months, Group A showed 81.42% coverage where in Group B it was 70.08%. Similarly, increase in the width of keratinized gingiva and attached gingiva were more in Group A. Conclusions: The present study showed that use of microsurgical instrument helped to deliver precise incision, better visual acuity, and improved illumination which facilitate to gain a better final outcome. Root coverage was better in the patients using CTG. PMID:27143833

  19. Reconciling Healthcare Professional and Patient Perspectives in the Development of Disease Activity and Response Criteria in Connective Tissue Disease Related Interstitial Lung Diseases

    PubMed Central

    Saketkoo, LA; Mittoo, S; Frankel, S; LeSage, D; Sarver, C; Phillips, K; Strand, V; Matteson, EL

    2015-01-01

    Interstitial lung diseases (ILD), including connective tissue disease (CTD) related and idiopathic pulmonary fibrosis (IPF), carry a high morbidity and mortality. Great efforts are underway to develop and investigate meaningful treatments in the context of clinical trials. However, these efforts have been challenged by the lack of validated outcome measures and inconsistent use of measures in the context of clinical trials. This lack of consensus has fragmented effective use of investigative in CTD-ILD and IPF with a history of resultant difficulties in agency approval of treatment interventions. Patient perspective in determination of domains and outcome measures in CTD-ILD and IPF, prior to this effort, has never occurred. These efforts demonstrate unequivocally the value and impact of patient involvement on core set development. Regarding CTD-ILD, this is the first OMERACT working group to directly address a manifestation/co-morbidity of a rheumatic disease (ILD) as well as a disease not considered rheumatic (IPF). The OMERACT 11 proceedings of the CTD-ILD Working Group describe the forward and lateral process to include both the medical and patient perspectives in the urgently needed identification of a core set of preliminary domains and outcome measures in CTD-ILD and IPF. PMID:24488412

  20. Preliminary Report of Endovascular Treatment for Critical Limb Ischemia Patients with Connective Tissue Disease: Cases Series and Review of the Literature.

    PubMed

    Obara, Hideaki; Matsubara, Kentaro; Fujimura, Naoki; Sekimoto, Yasuhito; Kitagawa, Yuko

    2015-06-01

    Only few studies have addressed the surgical revascularization in patients with both connective tissue disease (CTD) and critical limb ischemia (CLI), and the evidence for the endovascular treatment (EVT) is lacking in such patients. The main purpose of this study is to assess our outcome of EVT in patients with CTD and ischemic leg ulcers and review the current situation of the revascularization in such patients. Medical records of 10 consecutive patients with coexistent CTD and CLI-related leg ulcers (in 11 limbs) treated endovascularly at our institution between 2009 and 2013 were reviewed retrospectively. The patients had rheumatoid arthritis (n = 5), systemic lupus erythematosus (n = 1), progressive systemic scleroderma (n = 3), or polyarteritis nodosa (n = 1). EVT was technically successful in all the cases. No procedure-related morbidity or mortality occurred. During the mean follow-up period of 26 months, there were no major amputations, and sustained clinical improvement (ulcer healing and reduction in Rutherford category) was observed in eight limbs. The overall 1-year rates of amputation-free survival and freedom from reintervention were 89 and 81%, respectively. In our series of patients with CTD and ischemic leg ulcers, EVT had acceptable outcomes and may be recommended as a safe and reasonably effective initial treatment option for such patients. PMID:26060386

  1. Characterisation of novel fungal and bacterial protease preparations and evaluation of their ability to hydrolyse meat myofibrillar and connective tissue proteins.

    PubMed

    Ryder, Kate; Ha, Minh; Bekhit, Alaa El-Din; Carne, Alan

    2015-04-01

    The catalytic capability of four commercially available food-grade fungal and bacterial protease preparations (AFP, FPII, F60K and HT) was evaluated over a range of pH, temperature and substrate conditions using esterase and caseinolytic activity assays and time course hydrolysis over 120 and 60 min of myofibrillar and connective tissue proteins, respectively. The protease preparations displayed similar casein hydrolysis kinetics and were active in hydrolysing BODIPY-FL casein to varying extents at postmortem aging meat pH (5.0-6.0). All of the four proteases exhibited selective hydrolytic activity towards meat myofibrillar proteins including myosin and actin. Significant hydrolysis of two meat tenderisation protein markers troponin T and desmin by the four proteases was detected by western blot. The results obtained indicate that the new fungal protease preparations AFP and FPII, bacterial protease preparation HT and the new source of fungal protease preparation F60K have potential for use in meat tenderising applications. PMID:25442543

  2. Heritable Disorders of Connective Tissue

    MedlinePlus

    ... Harry C. Dietz, M.D., Johns Hopkins University School of Medicine, Baltimore, MD; Carolyn Levering and Eileen ... Marfan Foundation ; Francisco Ramirez, M.D., Mount Sinai School of Medicine of the City University of New ...

  3. An engineered dimeric protein pore that spans adjacent lipid bilayers

    PubMed Central

    Mantri, Shiksha; Sapra, K. Tanuj; Cheley, Stephen; Sharp, Thomas H.; Bayley, Hagan

    2013-01-01

    The bottom-up construction of artificial tissues is an underexplored area of synthetic biology. An important challenge is communication between constituent compartments of the engineered tissue and between the engineered tissue and additional compartments, including extracellular fluids, further engineered tissue and living cells. Here we present a dimeric transmembrane pore that can span two adjacent lipid bilayers and thereby allow aqueous compartments to communicate. Two heptameric staphylococcal α-hemolysin (αHL) pores were covalently linked in an aligned cap-to-cap orientation. The structure of the dimer, (α7)2, was confirmed by biochemical analysis, transmission electron microscopy (TEM) and single-channel electrical recording. We show that one of two β barrels of (α7)2 can insert into the lipid bilayer of a small unilamellar vesicle, while the other spans a planar lipid bilayer. (α7)2 pores spanning two bilayers were also observed by TEM. PMID:23591892

  4. CXCL12 induces connective tissue growth factor expression in human lung fibroblasts through the Rac1/ERK, JNK, and AP-1 pathways.

    PubMed

    Lin, Chien-Huang; Shih, Chung-Huang; Tseng, Chih-Chieh; Yu, Chung-Chi; Tsai, Yuan-Jhih; Bien, Mauo-Ying; Chen, Bing-Chang

    2014-01-01

    CXCL12 (stromal cell-derived factor-1, SDF-1) is a potent chemokine for homing of CXCR4+ fibrocytes to injury sites of lung tissue, which contributes to pulmonary fibrosis. Overexpression of connective tissue growth factor (CTGF) plays a critical role in pulmonary fibrosis. In this study, we investigated the roles of Rac1, extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and activator protein-1 (AP-1) in CXCL12-induced CTGF expression in human lung fibroblasts. CXCL12 caused concentration- and time-dependent increases in CTGF expression and CTGF-luciferase activity. CXCL12-induced CTGF expression was inhibited by a CXCR4 antagonist (AMD3100), small interfering RNA of CXCR4 (CXCR4 siRNA), a dominant negative mutant of Rac1 (RacN17), a mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor (PD98059), a JNK inhibitor (SP600125), a p21-activated kinase inhibitor (PAK18), c-Jun siRNA, and an AP-1 inhibitor (curcumin). Treatment of cells with CXCL12 caused activations of Rac1, Rho, ERK, and c-Jun. The CXCL12-induced increase in ERK phosphorylation was inhibited by RacN17. Treatment of cells with PD98059 and SP600125 both inhibited CXCL12-induced c-Jun phosphorylation. CXCL12 caused the recruitment of c-Jun and c-Fos binding to the CTGF promoter. Furthermore, CXCL12 induced an increase in α-smooth muscle actin (α-SMA) expression, a myofibroblastic phenotype, and actin stress fiber formation. CXCL12-induced actin stress fiber formation and α-SMA expression were respectively inhibited by AMD3100 and CTGF siRNA. Taken together, our results suggest that CXCL12, acting through CXCR4, activates the Rac/ERK and JNK signaling pathways, which in turn initiates c-Jun phosphorylation, and recruits c-Jun and c-Fos to the CTGF promoter and ultimately induces CTGF expression in human lung fibroblasts. Moreover, overexpression of CTGF mediates CXCL12-induced α-SMA expression. PMID:25121739

  5. Local amino acid sequence patterns dominate the heterogeneous phenotype for the collagen connective tissue disease Osteogenesis Imperfecta resulting from Gly mutations.

    PubMed

    Xiao, Jianxi; Yang, Zhangfu; Sun, Xiuxia; Addabbo, Rayna; Baum, Jean

    2015-10-01

    Osteogenesis Imperfecta (OI), a hereditary connective tissue disease in collagen that arises from a single Gly → X mutation in the collagen chain, varies widely in phenotype from perinatal lethal to mild. It is unclear why there is such a large variation in the severity of the disease considering the repeating (Gly-X-Y)n sequence and the uniform rod-like structure of collagen. We systematically evaluate the effect of local (Gly-X-Y)n sequence around the mutation site on OI phenotype using integrated bio-statistical approaches, including odds ratio analysis and decision tree modeling. We show that different Gly → X mutations have different local sequence patterns that are correlated with lethal and nonlethal phenotypes providing a mechanism for understanding the sensitivity of local context in defining lethal and non-lethal OI. A number of important trends about which factors are related to OI phenotypes are revealed by the bio-statistical analyses; most striking is the complementary relationship between the placement of Pro residues and small residues and their correlation to OI phenotype. When Pro is present or small flexible residues are absent nearby a mutation site, the OI case tends to be lethal; when Pro is present or small flexible residues are absent further away from the mutation site, the OI case tends to be nonlethal. The analysis also reveals the dominant role of local sequence around mutation sites in the Major Ligand Binding Regions that are primarily responsible for collagen binding to its receptors and shows that non-lethal mutations are highly predicted by local sequence considerations alone whereas lethal mutations are not as easily predicted and may be a result of more complex interactions. Understanding the sequence determinants of OI mutations will enhance genetic counseling and help establish which steps in the collagen hierarchy to target for drug therapy. PMID:25980613

  6. The RIN2 syndrome: a new autosomal recessive connective tissue disorder caused by deficiency of Ras and Rab interactor 2 (RIN2).

    PubMed

    Syx, Delfien; Malfait, Fransiska; Van Laer, Lut; Hellemans, Jan; Hermanns-Lê, Trinh; Willaert, Andy; Benmansour, Abdelmajid; De Paepe, Anne; Verloes, Alain

    2010-07-01

    Defects leading to impaired intracellular trafficking have recently been shown to play an important role in the pathogenesis of genodermatoses, such as the Ehlers-Danlos and the cutis laxa syndromes. A new genodermatosis, termed macrocephaly, alopecia, cutis laxa and scoliosis (MACS) syndrome has been described, resulting from a homozygous 1-bp deletion in RIN2. RIN2 encodes the Ras and Rab interactor 2, involved in the regulation of Rab5-mediated early endocytosis. We performed a clinical, ultrastructural and molecular study in a consanguineous Algerian family with three siblings affected by a distinctive autosomal recessive genodermatosis, reported in 2005 by Verloes et al. The most striking clinical features include progressive facial coarsening, gingival hypertrophy, severe scoliosis, sparse hair and skin and joint hyperlaxity. Ultrastructural studies of the skin revealed important abnormalities in the collagen fibril morphology, and fibroblasts exhibited a dilated endoplasmic reticulum and an abnormal Golgi apparatus with rarefied and dilated cisternae. Molecular analysis of RIN2 revealed a novel homozygous 2-bp deletion in all affected individuals. The c.1914_1915delGC mutation introduces a frameshift and creates a premature termination codon, leading to nonsense-mediated mRNA decay. These findings confirm that RIN2 defects are associated with a distinct genodermatosis and underscore the involvement of RIN2 and its associated pathways in the pathogenesis of connective tissue disorders. The current family displays considerable phenotypic overlap with MACS syndrome. However, our family shows a dermatological and ultrastructural phenotype belonging to the Ehlers-Danlos rather than the cutis laxa spectrum. Therefore, the MACS acronym is not entirely appropriate for the current family. PMID:20424861

  7. Extracellular acidification induces connective tissue growth factor production through proton-sensing receptor OGR1 in human airway smooth muscle cells

    SciTech Connect

    Matsuzaki, Shinichi; Ishizuka, Tamotsu; Yamada, Hidenori; Kamide, Yosuke; Hisada, Takeshi; Ichimonji, Isao; Aoki,