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Sample records for adult human articular

  1. Nanosized fibers' effect on adult human articular chondrocytes behavior

    International Nuclear Information System (INIS)

    Stenhamre, Hanna; Thorvaldsson, Anna; Enochson, Lars; Walkenström, Pernilla; Lindahl, Anders; Brittberg, Mats; Gatenholm, Paul

    2013-01-01

    Tissue engineering with chondrogenic cell based therapies is an expanding field with the intention of treating cartilage defects. It has been suggested that scaffolds used in cartilage tissue engineering influence cellular behavior and thus the long-term clinical outcome. The objective of this study was to assess whether chondrocyte attachment, proliferation and post-expansion re-differentiation could be influenced by the size of the fibers presented to the cells in a scaffold. Polylactic acid (PLA) scaffolds with different fiber morphologies were produced, i.e. microfiber (MS) scaffolds as well as nanofiber-coated microfiber scaffold (NMS). Adult human articular chondrocytes were cultured in the scaffolds in vitro up to 28 days, and the resulting constructs were assessed histologically, immunohistochemically, and biochemically. Attachment of cells and serum proteins to the scaffolds was affected by the architecture. The results point toward nano-patterning onto the microfibers influencing proliferation of the chondrocytes, and the overall 3D environment having a greater influence on the re-differentiation. In the efforts of finding the optimal scaffold for cartilage tissue engineering, studies as the current contribute to the knowledge of how to affect and control chondrocytes behavior. - Highlights: ► Chondrocyte behavior in nanofiber-coated microfiber versus microfiber scaffolds ► High porosity (> 90%) and large pore sizes (a few hundred μm) of nanofibrous scaffolds ► Proliferation enhanced by presence of nanofibers ► Differentiation not significantly affected ► Cell attachment improved in presence of both nanofibers and serum

  2. Nanosized fibers' effect on adult human articular chondrocytes behavior

    Energy Technology Data Exchange (ETDEWEB)

    Stenhamre, Hanna [Biopolymer Technology, Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg (Sweden); Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg (Sweden); Thorvaldsson, Anna, E-mail: anna.thorvaldsson@swerea.se [Biopolymer Technology, Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg (Sweden); Swerea IVF, Mölndal (Sweden); Enochson, Lars [Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg (Sweden); Walkenström, Pernilla [Swerea IVF, Mölndal (Sweden); Lindahl, Anders [Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Gothenburg (Sweden); Brittberg, Mats [Cartilage Research Unit, University of Gothenburg, Department Orthopaedics, Kungsbacka Hospital, Kungsbacka (Sweden); Gatenholm, Paul [Biopolymer Technology, Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg (Sweden)

    2013-04-01

    Tissue engineering with chondrogenic cell based therapies is an expanding field with the intention of treating cartilage defects. It has been suggested that scaffolds used in cartilage tissue engineering influence cellular behavior and thus the long-term clinical outcome. The objective of this study was to assess whether chondrocyte attachment, proliferation and post-expansion re-differentiation could be influenced by the size of the fibers presented to the cells in a scaffold. Polylactic acid (PLA) scaffolds with different fiber morphologies were produced, i.e. microfiber (MS) scaffolds as well as nanofiber-coated microfiber scaffold (NMS). Adult human articular chondrocytes were cultured in the scaffolds in vitro up to 28 days, and the resulting constructs were assessed histologically, immunohistochemically, and biochemically. Attachment of cells and serum proteins to the scaffolds was affected by the architecture. The results point toward nano-patterning onto the microfibers influencing proliferation of the chondrocytes, and the overall 3D environment having a greater influence on the re-differentiation. In the efforts of finding the optimal scaffold for cartilage tissue engineering, studies as the current contribute to the knowledge of how to affect and control chondrocytes behavior. - Highlights: ► Chondrocyte behavior in nanofiber-coated microfiber versus microfiber scaffolds ► High porosity (> 90%) and large pore sizes (a few hundred μm) of nanofibrous scaffolds ► Proliferation enhanced by presence of nanofibers ► Differentiation not significantly affected ► Cell attachment improved in presence of both nanofibers and serum.

  3. Effect of homologous synovial membrane on adult human articular cartilage in organ culture, and failure to influence it with D-penicillamine.

    OpenAIRE

    Jacoby, R K

    1980-01-01

    Adult human articular cartilage has been maintained in organ culture for 8 days, and the culture medium, which was changed on alternate days, was pooled. Normal and rheumatoid cartilage was obtained from patients and 4 types of culture were prepared: (1) cartilage alone; (2) cartilage + D-penicillamine; (3) cartilage + homologous synovium; (4) cartilage, synovium, and D-penicillamine. The hexosamines and hexuronic acid were measured in the cartilage explants and in the medium. The quantity re...

  4. Prevalence and characteristics of articular manifestations in human ...

    African Journals Online (AJOL)

    Prevalence and characteristics of articular manifestations in human immune virus infection. ... Objectives: To determine the prevalence, types and characteristics of articular manifestations in the anti-retroviral treatment naive HIV infected patients. Design: Cross sectional descriptive study. Setting: Comprehensive care clinic ...

  5. Degenerated human articular cartilage at autopsy represents preclinical osteoarthritic cartilage: comparison with clinically defined osteoarthritic cartilage

    NARCIS (Netherlands)

    van Valburg, A. A.; Wenting, M. J.; Beekman, B.; te Koppele, J. M.; Lafeber, F. P.; Bijlsma, J. W.

    1997-01-01

    To investigate whether macroscopically fibrillated human articular knee cartilage observed at autopsy can be considered an early, preclinical phase of osteoarthritis (OA). Histological and biochemical characteristics of 3 types of articular knee cartilage were compared: macroscopically degenerated

  6. bFGF influences human articular chondrocyte differentiation

    DEFF Research Database (Denmark)

    Schmal, H; Zwingmann, J; Fehrenbach, M

    2007-01-01

    BACKGROUND: The possible functional role of basic fibroblast growth factor (bFGF) in regulating the mitotic and metabolic activity of primary human articular chondrocytes was investigated. METHODS: [EF1]Chondrocytes were enzymatically isolated from femoral head cartilage, and were cultured in vitro......FGF concentrations in supernatants of primary human articular chondrocytes peaked immediately after isolation and then declined. In a dose-dependent manner, bFGF enhanced cell amplification and viability. BFGF induced a decrease in the apoptotic cell population, while the number of proliferating cells remained...... by 53%, which was correlated with diminished mRNA production. Monolayer cultured chondrocytes secreted significant amounts of aggrecan that decreased over time. Secretion of this cartilage-specific marker was further reduced by the addition of bFGF. DISCUSSION: These findings highlight the potential...

  7. Identification and clonal characterisation of a progenitor cell sub-population in normal human articular cartilage.

    Directory of Open Access Journals (Sweden)

    Rebecca Williams

    Full Text Available BACKGROUND: Articular cartilage displays a poor repair capacity. The aim of cell-based therapies for cartilage defects is to repair damaged joint surfaces with a functional replacement tissue. Currently, chondrocytes removed from a healthy region of the cartilage are used but they are unable to retain their phenotype in expanded culture. The resulting repair tissue is fibrocartilaginous rather than hyaline, potentially compromising long-term repair. Mesenchymal stem cells, particularly bone marrow stromal cells (BMSC, are of interest for cartilage repair due to their inherent replicative potential. However, chondrocyte differentiated BMSCs display an endochondral phenotype, that is, can terminally differentiate and form a calcified matrix, leading to failure in long-term defect repair. Here, we investigate the isolation and characterisation of a human cartilage progenitor population that is resident within permanent adult articular cartilage. METHODS AND FINDINGS: Human articular cartilage samples were digested and clonal populations isolated using a differential adhesion assay to fibronectin. Clonal cell lines were expanded in growth media to high population doublings and karyotype analysis performed. We present data to show that this cell population demonstrates a restricted differential potential during chondrogenic induction in a 3D pellet culture system. Furthermore, evidence of high telomerase activity and maintenance of telomere length, characteristic of a mesenchymal stem cell population, were observed in this clonal cell population. Lastly, as proof of principle, we carried out a pilot repair study in a goat in vivo model demonstrating the ability of goat cartilage progenitors to form a cartilage-like repair tissue in a chondral defect. CONCLUSIONS: In conclusion, we propose that we have identified and characterised a novel cartilage progenitor population resident in human articular cartilage which will greatly benefit future cell

  8. ROCK inhibitor prevents the dedifferentiation of human articular chondrocytes

    International Nuclear Information System (INIS)

    Matsumoto, Emi; Furumatsu, Takayuki; Kanazawa, Tomoko; Tamura, Masanori; Ozaki, Toshifumi

    2012-01-01

    Highlights: ► ROCK inhibitor stimulates chondrogenic gene expression of articular chondrocytes. ► ROCK inhibitor prevents the dedifferentiation of monolayer-cultured chondrocytes. ► ROCK inhibitor enhances the redifferentiation of cultured chondrocytes. ► ROCK inhibitor is useful for preparation of un-dedifferentiated chondrocytes. ► ROCK inhibitor may be a useful reagent for chondrocyte-based regeneration therapy. -- Abstract: Chondrocytes lose their chondrocytic phenotypes in vitro. The Rho family GTPase ROCK, involved in organizing the actin cytoskeleton, modulates the differentiation status of chondrocytic cells. However, the optimum method to prepare a large number of un-dedifferentiated chondrocytes is still unclear. In this study, we investigated the effect of ROCK inhibitor (ROCKi) on the chondrogenic property of monolayer-cultured articular chondrocytes. Human articular chondrocytes were subcultured in the presence or absence of ROCKi (Y-27632). The expression of chondrocytic marker genes such as SOX9 and COL2A1 was assessed by quantitative real-time PCR analysis. Cellular morphology and viability were evaluated. Chondrogenic redifferentiation potential was examined by a pellet culture procedure. The expression level of SOX9 and COL2A1 was higher in ROCKi-treated chondrocytes than in untreated cells. Chondrocyte morphology varied from a spreading form to a round shape in a ROCKi-dependent manner. In addition, ROCKi treatment stimulated the proliferation of chondrocytes. The deposition of safranin O-stained proteoglycans and type II collagen was highly detected in chondrogenic pellets derived from ROCKi-pretreated chondrocytes. Our results suggest that ROCKi prevents the dedifferentiation of monolayer-cultured chondrocytes, and may be a useful reagent to maintain chondrocytic phenotypes in vitro for chondrocyte-based regeneration therapy.

  9. ROCK inhibitor prevents the dedifferentiation of human articular chondrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, Emi [Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikatacho, Kitaku, Okayama 700-8558 (Japan); Furumatsu, Takayuki, E-mail: matino@md.okayama-u.ac.jp [Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikatacho, Kitaku, Okayama 700-8558 (Japan); Kanazawa, Tomoko; Tamura, Masanori; Ozaki, Toshifumi [Department of Orthopaedic Surgery, Science of Functional Recovery and Reconstruction, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, 2-5-1 Shikatacho, Kitaku, Okayama 700-8558 (Japan)

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer ROCK inhibitor stimulates chondrogenic gene expression of articular chondrocytes. Black-Right-Pointing-Pointer ROCK inhibitor prevents the dedifferentiation of monolayer-cultured chondrocytes. Black-Right-Pointing-Pointer ROCK inhibitor enhances the redifferentiation of cultured chondrocytes. Black-Right-Pointing-Pointer ROCK inhibitor is useful for preparation of un-dedifferentiated chondrocytes. Black-Right-Pointing-Pointer ROCK inhibitor may be a useful reagent for chondrocyte-based regeneration therapy. -- Abstract: Chondrocytes lose their chondrocytic phenotypes in vitro. The Rho family GTPase ROCK, involved in organizing the actin cytoskeleton, modulates the differentiation status of chondrocytic cells. However, the optimum method to prepare a large number of un-dedifferentiated chondrocytes is still unclear. In this study, we investigated the effect of ROCK inhibitor (ROCKi) on the chondrogenic property of monolayer-cultured articular chondrocytes. Human articular chondrocytes were subcultured in the presence or absence of ROCKi (Y-27632). The expression of chondrocytic marker genes such as SOX9 and COL2A1 was assessed by quantitative real-time PCR analysis. Cellular morphology and viability were evaluated. Chondrogenic redifferentiation potential was examined by a pellet culture procedure. The expression level of SOX9 and COL2A1 was higher in ROCKi-treated chondrocytes than in untreated cells. Chondrocyte morphology varied from a spreading form to a round shape in a ROCKi-dependent manner. In addition, ROCKi treatment stimulated the proliferation of chondrocytes. The deposition of safranin O-stained proteoglycans and type II collagen was highly detected in chondrogenic pellets derived from ROCKi-pretreated chondrocytes. Our results suggest that ROCKi prevents the dedifferentiation of monolayer-cultured chondrocytes, and may be a useful reagent to maintain chondrocytic phenotypes in vitro for chondrocyte

  10. Low-intensity pulsed ultrasound affects human articular chondrocytes in vitro

    NARCIS (Netherlands)

    Korstjens, C.M.; van der Rijt, R.H.H.; Albers, G.H.; Semeins, C.M.; Klein-Nulend, J.

    2008-01-01

    We investigated whether low-intensity pulsed ultrasound (LIPUS) stimulates chondrocyte proliferation and matrix production in explants of human articular cartilage obtained from donors suffering from unicompartimental osteoarthritis of the knee, as well as in isolated human chondrocytes in vitro.

  11. Isolation and characterization of human articular chondrocytes from surgical waste after total knee arthroplasty (TKA

    Directory of Open Access Journals (Sweden)

    Jakob Naranda

    2017-03-01

    Full Text Available Background Cartilage tissue engineering is a fast-evolving field of biomedical engineering, in which the chondrocytes represent the most commonly used cell type. Since research in tissue engineering always consumes a lot of cells, simple and cheap isolation methods could form a powerful basis to boost such studies and enable their faster progress to the clinics. Isolated chondrocytes can be used for autologous chondrocyte implantation in cartilage repair, and are the base for valuable models to investigate cartilage phenotype preservation, as well as enable studies of molecular features, nature and scales of cellular responses to alterations in the cartilage tissue. Methods Isolation and consequent cultivation of primary human adult articular chondrocytes from the surgical waste obtained during total knee arthroplasty (TKA was performed. To evaluate the chondrogenic potential of the isolated cells, gene expression of collagen type 2 (COL2, collagen 1 (COL1 and aggrecan (ACAN was evaluated. Immunocytochemical staining of all mentioned proteins was performed to evaluate chondrocyte specific production. Results Cartilage specific gene expression of COL2 and ACAN has been shown that the proposed protocol leads to isolation of cells with a high chondrogenic potential, possibly even specific phenotype preservation up to the second passage. COL1 expression has confirmed the tendency of the isolated cells dedifferentiation into a fibroblast-like phenotype already in the second passage, which confirms previous findings that higher passages should be used with care in cartilage tissue engineering. To evaluate the effectiveness of our approach, immunocytochemical staining of the evaluated chondrocyte specific products was performed as well. Discussion In this study, we developed a protocol for isolation and consequent cultivation of primary human adult articular chondrocytes with the desired phenotype from the surgical waste obtained during TKA. TKA is a

  12. X-ray dark field imaging of human articular cartilage: Possible clinical application to orthopedic surgery

    International Nuclear Information System (INIS)

    Kunisada, Toshiyuki; Shimao, Daisuke; Sugiyama, Hiroshi; Takeda, Ken; Ozaki, Toshifumi; Ando, Masami

    2008-01-01

    Despite its convenience and non-invasiveness on daily clinical use, standard X-ray radiography cannot show articular cartilage. We developed a novel type of X-ray dark field imaging (DFI), which forms images only by a refracted beam with very low background illumination. We examined a disarticulated distal femur and a shoulder joint with surrounding soft tissue and skin, both excised from a human cadaver at the BL20B2 synchrotron beamline at SPring-8. The field was 90 mm wide and 90 mm high. Articular cartilage of the disarticulated distal femur was obvious on DFI, but not on standard X-ray images. Furthermore, DFI allowed visualization in situ of articular cartilage of the shoulder while covered with soft tissue and skin. The gross appearance of the articular cartilage on the dissected section of the proximal humerus was identical to the cartilage shown on the DFI image. These results suggested that DFI could provide a clinically accurate method of assessing articular cartilage. Hence, DFI would be a useful imaging tool for diagnosing joint disease such as osteoarthritis

  13. X-ray dark field imaging of human articular cartilage: Possible clinical application to orthopedic surgery

    Energy Technology Data Exchange (ETDEWEB)

    Kunisada, Toshiyuki [Department of Medical Materials for Musculoskeletal Reconstruction, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558 (Japan); Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558 (Japan)], E-mail: toshi-kunisada@umin.ac.jp; Shimao, Daisuke [Department of Radiological Sciences, Ibaraki Prefectural University of Health Sciences, Ibaraki 300-2394 (Japan); Sugiyama, Hiroshi [Photon Factory, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), Ibaraki 305-0801 (Japan); Takeda, Ken; Ozaki, Toshifumi [Department of Orthopaedic Surgery, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences, Okayama 700-8558 (Japan); Ando, Masami [Research Institute for Science and Technology, Tokyo University of Science, Chiba 278-8510 (Japan)

    2008-12-15

    Despite its convenience and non-invasiveness on daily clinical use, standard X-ray radiography cannot show articular cartilage. We developed a novel type of X-ray dark field imaging (DFI), which forms images only by a refracted beam with very low background illumination. We examined a disarticulated distal femur and a shoulder joint with surrounding soft tissue and skin, both excised from a human cadaver at the BL20B2 synchrotron beamline at SPring-8. The field was 90 mm wide and 90 mm high. Articular cartilage of the disarticulated distal femur was obvious on DFI, but not on standard X-ray images. Furthermore, DFI allowed visualization in situ of articular cartilage of the shoulder while covered with soft tissue and skin. The gross appearance of the articular cartilage on the dissected section of the proximal humerus was identical to the cartilage shown on the DFI image. These results suggested that DFI could provide a clinically accurate method of assessing articular cartilage. Hence, DFI would be a useful imaging tool for diagnosing joint disease such as osteoarthritis.

  14. Mechanical properties of the collagen network in human articular cartilage as measured by osmotic stress technique

    NARCIS (Netherlands)

    Basser, P.J.; Schneiderman, R.; Bank, R.A.; Wachtel, E.; Maroudas, A.

    1998-01-01

    We have used an isotropic osmotic stress technique to assess the swelling pressures of human articular cartilage over a wide range of hydrations in order to determine from these measurements, for the first time, the tensile stress in the collagen network, P(c), as a function of hydration. Osmotic

  15. Chondrogenic differentiation of human articular chondrocytes differs in biodegradable PGA/PLA scaffolds

    DEFF Research Database (Denmark)

    Zwingmann, Joern; Mehlhorn, Alexander T; Südkamp, Norbert

    2007-01-01

    Cartilage tissue engineering is applied clinically to cover and regenerate articular cartilage defects. Two bioresorbable nonwoven scaffolds, polyglycolic acid (PGA) and poly(lactic-co-glycolic acid) (PLGA) (90/10 copolymer of L-lactide and glycolide), were seeded with human chondrocytes after in...

  16. Intra-Articular Entrapment of the Medial Epicondyle following a Traumatic Fracture Dislocation of the Elbow in an Adult

    Science.gov (United States)

    Hassan, Youssef G.; Joukhadar, Nabih I.

    2018-01-01

    Medial epicondyle entrapment after an acute fracture dislocation of the elbow is a common finding in the pediatric population, but a rare finding in adults. We present a case of an adult patient diagnosed with a traumatic fracture dislocation of the elbow joint with intra-articular entrapment of the medial epicondyle. After initial evaluation, closed reduction was done. Stability testing after reduction showed an unstable joint; thus, open reduction and internal fixation was decided. PMID:29666736

  17. In situ measurements of human articular cartilage stiffness by means of a scanning force microscope

    International Nuclear Information System (INIS)

    Imer, Raphael; Akiyama, Terunobu; Rooij, Nico F de; Stolz, Martin; Aebi, Ueli; Kilger, Robert; Friederich, Niklaus F; Wirz, Dieter; Daniels, A U; Staufer, Urs

    2007-01-01

    Osteoarthritis is a painful and disabling progressive joint disease, characterized by degradation of articular cartilage. In order to study this disease at early stages, we have miniaturized and integrated a complete scanning force microscope into a standard arthroscopic device fitting through a standard orthopedic canula. This instrument will allow orthopedic surgeons to measure the mechanical properties of articular cartilage at the nanometer and micrometer scale in-vivo during a standard arthroscopy. An orthopedic surgeon assessed the handling of the instrument. First measurements of the elasticity-modulus of human cartilage were recorded in a cadaver knee non minimal invasive. Second, minimally invasive experiments were performed using arthroscopic instruments. Load-displacement curves were successfully recorded

  18. In situ measurements of human articular cartilage stiffness by means of a scanning force microscope

    Energy Technology Data Exchange (ETDEWEB)

    Imer, Raphael [Institute of Microtechnology, University of Neuchatel, Jaquet-Droz 1, 2007 Neuchatel (Switzerland); Akiyama, Terunobu [Institute of Microtechnology, University of Neuchatel, Jaquet-Droz 1, 2007 Neuchatel (Switzerland); Rooij, Nico F de [Institute of Microtechnology, University of Neuchatel, Jaquet-Droz 1, 2007 Neuchatel (Switzerland); Stolz, Martin [Maurice E. Mueller Institute, University of Basel, Klingelbergstr. 70, 4056 Basel (Switzerland); Aebi, Ueli [Maurice E. Mueller Institute, University of Basel, Klingelbergstr. 70, 4056 Basel (Switzerland); Kilger, Robert [Clinics for Orthopedic Surgery and Traumatology, Kantonsspital, 4101 Bruderholz (Switzerland); Friederich, Niklaus F [Clinics for Orthopedic Surgery and Traumatology, Kantonsspital, 4101 Bruderholz (Switzerland); Wirz, Dieter [Lab. for Orthopaedic Biomechanics, University of Basel, Klingelbergstr. 50-70, 4056 Basel (Switzerland); Daniels, A U [Lab. for Orthopaedic Biomechanics, University of Basel, Klingelbergstr. 50-70, 4056 Basel (Switzerland); Staufer, Urs [Institute of Microtechnology, University of Neuchatel, Jaquet-Droz 1, 2007 Neuchatel (Switzerland)

    2007-03-15

    Osteoarthritis is a painful and disabling progressive joint disease, characterized by degradation of articular cartilage. In order to study this disease at early stages, we have miniaturized and integrated a complete scanning force microscope into a standard arthroscopic device fitting through a standard orthopedic canula. This instrument will allow orthopedic surgeons to measure the mechanical properties of articular cartilage at the nanometer and micrometer scale in-vivo during a standard arthroscopy. An orthopedic surgeon assessed the handling of the instrument. First measurements of the elasticity-modulus of human cartilage were recorded in a cadaver knee non minimal invasive. Second, minimally invasive experiments were performed using arthroscopic instruments. Load-displacement curves were successfully recorded.

  19. The Regulatory Role of Signaling Crosstalk in Hypertrophy of MSCs and Human Articular Chondrocytes

    Directory of Open Access Journals (Sweden)

    Leilei Zhong

    2015-08-01

    Full Text Available Hypertrophic differentiation of chondrocytes is a main barrier in application of mesenchymal stem cells (MSCs for cartilage repair. In addition, hypertrophy occurs occasionally in osteoarthritis (OA. Here we provide a comprehensive review on recent literature describing signal pathways in the hypertrophy of MSCs-derived in vitro differentiated chondrocytes and chondrocytes, with an emphasis on the crosstalk between these pathways. Insight into the exact regulation of hypertrophy by the signaling network is necessary for the efficient application of MSCs for articular cartilage repair and for developing novel strategies for curing OA. We focus on articles describing the role of the main signaling pathways in regulating chondrocyte hypertrophy-like changes. Most studies report hypertrophic differentiation in chondrogenesis of MSCs, in both human OA and experimental OA. Chondrocyte hypertrophy is not under the strict control of a single pathway but appears to be regulated by an intricately regulated network of multiple signaling pathways, such as WNT, Bone morphogenetic protein (BMP/Transforming growth factor-β (TGFβ, Parathyroid hormone-related peptide (PTHrP, Indian hedgehog (IHH, Fibroblast growth factor (FGF, Insulin like growth factor (IGF and Hypoxia-inducible factor (HIF. This comprehensive review describes how this intricate signaling network influences tissue-engineering applications of MSCs in articular cartilage (AC repair, and improves understanding of the disease stages and cellular responses within an OA articular joint.

  20. Chondrocyte secreted CRTAC1: a glycosylated extracellular matrix molecule of human articular cartilage.

    Science.gov (United States)

    Steck, Eric; Bräun, Jessica; Pelttari, Karoliina; Kadel, Stephanie; Kalbacher, Hubert; Richter, Wiltrud

    2007-01-01

    Cartilage acidic protein 1 (CRTAC1), a novel human marker which allowed discrimination of human chondrocytes from osteoblasts and mesenchymal stem cells in culture was so far studied only on the RNA-level. We here describe its genomic organisation and detect a new brain expressed (CRTAC1-B) isoform resulting from alternate last exon usage which is highly conserved in vertebrates. In humans, we identify an exon sharing process with the neighbouring tail-to-tail orientated gene leading to CRTAC1-A. This isoform is produced by cultured human chondrocytes, localized in the extracellular matrix of articular cartilage and its secretion can be stimulated by BMP4. Of five putative O-glycosylation motifs in the last exon of CRTAC1-A, the most C-terminal one is modified according to exposure of serial C-terminal deletion mutants to the O-glycosylation inhibitor Benzyl-alpha-GalNAc. Both isoforms contain four FG-GAP repeat domains and an RGD integrin binding motif, suggesting cell-cell or cell-matrix interaction potential. In summary, CRTAC1 acquired an alternate last exon from the tail-to-tail oriented neighbouring gene in humans resulting in the glycosylated isoform CRTAC1-A which represents a new extracellular matrix molecule of articular cartilage.

  1. Boundary mode lubrication of articular cartilage by recombinant human lubricin.

    Science.gov (United States)

    Gleghorn, Jason P; Jones, Aled R C; Flannery, Carl R; Bonassar, Lawrence J

    2009-06-01

    Lubrication of cartilage involves a variety of physical and chemical factors, including lubricin, a synovial glycoprotein that has been shown to be a boundary lubricant. It is unclear how lubricin boundary lubricates a wide range of bearings from tissue to artificial surfaces, and if the mechanism is the same for both soluble and bound lubricin. In the current study, experiments were conducted to investigate the hypothesis that recombinant human lubricin (rh-lubricin) lubricates cartilage in a dose-dependent manner and that soluble and bound fractions of rh-lubricin both contribute to the lubrication process. An rh-lubricin dose response was observed with maximal lubrication achieved at concentrations of rh-lubricin greater than 50 microg/mL. A concentration-response variable-slope model was fit to the data, and indicated that rh-lubricin binding to cartilage was not first order. The pattern of decrease in equilibrium friction coefficient indicated that aggregation of rh-lubricin or steric arrangement may regulate boundary lubrication. rh-lubricin localized at the cartilage surface was found to lubricate a cartilage-glass interface in boundary mode, as did soluble rh-lubricin at high concentrations (150 microg/mL); however, the most effective lubrication occurred when both soluble and bound rh-lubricin were present at the interface. These findings point to two distinct mechanisms by which rh-lubricin lubricates, one mechanism involving lubricin bound to the tissue surface and the other involving lubricin in solution. Copyright 2008 Orthopaedic Research Society

  2. In vitro of quantitative MR imaging of early degenerative changes in human articular cartilage

    International Nuclear Information System (INIS)

    Kim, Ok Wha; Lee, Young Jun; Cha, Sung Suk; Hwa, Ryu Ji

    2004-01-01

    To assess the applicability of quantitative MR microscopy for the detection of glycosaminoglycan (GAG) depletion as an early sign of degeneration in the articular cartilage of humans treated by trypsin. Four cartilage-bone blocks were obtained from the patient who had suffered from osteoarthritis of the knee and underwent a total knee replacement arthroscopy. Each articular cartilage segment was resected as to a round disk shape (8 mm in diameter) with a remnant of subchondral bone 1 mm in thickness. Four different culture solutions were prepared, and these solutions were 0.2 mg/ml of trypsin solution (group 1), 1 mM of Gd (DTPA) 2-mixed trypsin solution (group 2), phosphate buffered saline (PBS) (group 3), and 1 mM of Gd (DTPA) 2-mixed PBS (group 4). The cartilages were cultured and then MR imagings were performed every hour for 5 hrs, and we continued the additional cultures of 24 hrs, 36 hrs and 48 hrs. Three imaging sequences were used: T1-weighted spin echo (TR/TE, 450/22), proton density turbo spin echo with fat suppression (TR/TE, 3000/25), and CPMG (Carr-Purcell-Meiboom-Gill) (TR/TE/TI, 760/21-168, 360). MR imaging data were analyzed with pixel-by-pixel comparisons in all groups. The GAG loss in the articular cartilage was increased proportionately to the culture duration. Mean changes of T1 relaxation time were 1.2% for group 1, -1.9% for group 3, -54.7% for group 2 and -64.2% for group 4 (p< 0.05). When comparing by linear profile on the T1-weighted images, SNR increased and T1 relaxation time decreased for group 2 and 4, as the culture duration increased (p< 0.05). On the correlation analysis, there is significant correlation between GAG loss and Gd (DTPA) 2-enhancement for group 2 (p=0.0431), but there was no significant difference for group 4 (p=0.0918). More enhancement with Gd (DTPA) 2-was noted for group 2 than for group 4. Group 2 showed a diffuse enhancement in all the layers of cartilage, but for group 4, prominent enhancement was noted only in

  3. Bovine lactoferricin is anti-inflammatory and anti-catabolic in human articular cartilage and synovium.

    Science.gov (United States)

    Yan, Dongyao; Chen, Di; Shen, Jie; Xiao, Guozhi; van Wijnen, Andre J; Im, Hee-Jeong

    2013-02-01

    Bovine lactoferricin (LfcinB) is a multi-functional peptide derived from proteolytic cleavage of bovine lactoferrin. LfcinB was found to antagonize the biological effects mediated by angiogenic growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) in endothelial cells. However, the effect of LfcinB on human articular cartilage remained unknown. Here, our findings demonstrate that LfcinB restored the proteoglycan loss promoted by catabolic factors (interleukin-1β) IL-1β and FGF-2 in vitro and ex vivo. Mechanistically, LfcinB attenuated the effects of IL-1β and FGF-2 on the expression of cartilage-degrading enzymes (MMP-1, MMP-3, and MMP-13), destructive cytokines (IL-1β and IL-6), and inflammatory mediators (iNOS and TLR2). LfcinB induced protective cytokine expression (IL-4 and IL-10), and downregulated aggrecanase basal expression. LfcinB specifically activated ERK MAPK and Akt signaling pathways, which may account for its anti-inflammatory activity. We also revealed that LfcinB exerted similar protective effects on human synovial fibroblasts challenged by IL-1β, with minimal cytotoxicity. Collectively, our results suggest that LfcinB possesses potent anti-catabolic and anti-inflammatory bioactivities in human articular tissues, and may be utilized for the prevention and/or treatment of OA in the future. Copyright © 2012 Wiley Periodicals, Inc.

  4. The distribution of YKL-40 in osteoarthritic and normal human articular cartilage

    DEFF Research Database (Denmark)

    Volck, B; Ostergaard, K; Johansen, J S

    1999-01-01

    YKL-40, also called human cartilage glycoprotein-39, is a major secretory protein of human chondrocytes in cell culture. YKL-40 mRNA is expressed by cartilage from patients with rheumatoid arthritis, but is not detectable in normal human cartilage. The aim was to investigate the distribution of YKL......-40 in osteoarthritic (n=9) and macroscopically normal (n=5) human articular cartilage, collected from 12 pre-selected areas of the femoral head, to discover a potential role for YKL-40 in cartilage remodelling in osteoarthritis. Immunohistochemical analysis showed that YKL-40 staining was found...... in chondrocytes of osteoarthritic cartilage mainly in the superficial and middle zone of the cartilage rather than the deep zone. There was a tendency for high number of YKL-40 positive chondrocytes in areas of the femoral head with a considerable biomechanical load. The number of chondrocytes with a positive...

  5. Tribological changes in the articular cartilage of a human femoral head with avascular necrosis.

    Science.gov (United States)

    Seo, Eun-Min; Shrestha, Suman K; Duong, Cong-Truyen; Sharma, Ashish Ranjan; Kim, Tae-Woo; Vijayachandra, Ayyappan; Thompson, Mark S; Cho, Myung Guk; Park, Sungchan; Kim, Kwanghoon; Park, Seonghun; Lee, Sang-Soo

    2015-06-29

    The present study evaluated the tribological properties of the articular cartilage surface of the human femoral head with postcollapse stage avascular necrosis (AVN) using atomic force microscopy. The cartilage surface in the postcollapse stage AVN of the femoral head was reported to resemble those of disuse conditions, which suggests that the damage could be reversible and offers the possibilities of success of head-sparing surgeries. By comparing the tribological properties of articular cartilage in AVN with that of osteoarthritis, the authors intended to understand the cartilage degeneration mechanism and reversibility of AVN. Human femoral heads with AVN were explanted from the hip replacement surgery of four patients (60-83 years old). Nine cylindrical cartilage samples (diameter, 5 mm and height, 0.5 mm) were sectioned from the weight-bearing areas of the femoral head with AVN, and the cartilage surface was classified according to the Outerbridge Classification System (AVN0, normal; AVN1, softening and swelling; and AVN2, partial thickness defect and fissuring). Tribological properties including surface roughness and frictional coefficients and histochemistry including Safranin O and lubricin staining were compared among the three groups. The mean surface roughness Rq values of AVN cartilage increased significantly with increasing Outerbridge stages: Rq = 137 ± 26 nm in AVN0, Rq = 274 ± 49 nm in AVN1, and Rq = 452 ± 77 nm in AVN2. Significant differences in Rq were observed among different Outerbridge stages in all cases (p AVN0, μ = 0.143 ± 0.025 in AVN1, and μ = 0.171 ± 0.039 in AVN2. Similarly to the statistical analysis of surface roughness, significant statistical differences were detected between different Outerbridge stages in all cases (p AVN. The underlying mechanism of these results can be related to proteoglycan loss within the articular cartilage that is also observed in osteoarthritis. With regard to the tribological properties, the

  6. μ-XRF and μ-XANES at calcification fronts of human articular cartilage

    International Nuclear Information System (INIS)

    Streli, C.; Zoeger, N.; Wobrauschek, P.; Jokubonis, C.; Pepponi, G.; Falkenberg, G.; Simon, P.; Roschger, P.; Tampieri, A.

    2006-01-01

    Full text: One of the main threats to human health from heavy metals is associated with exposure to lead (Pb), which is associated with chronic diseases in the nervous, hematopoietic, skeletal, renal and endocrine system. Although much progress has been made to limit Pb exposure in industrialized countries, primarily through the elimination of leaded gasoline, workplace exposures and leaded pipes, most adults have already accumulated a substantial body burden of Pb. Most of the affiliated Pb is deposited in human bones, where it is stored up to 20 years and accounts for 90.95 of the total lead body burden. Pb is able to displace Ca 2+ by cation exchange processes in the hydroxyapatite crystal (the main constituent of bone) and is liberated from it in cases of increased bone turnover such as osteoporosis, pregnancy, hyperthyroidism and hyperparathyroidism. Besides these phenomenological studies on the release of Pb from human calcified tissue analytical studies are essential to gain insight on storage sites and storage mechanisms on a microscopic scale. Therefore detailed synchrotron radiation induced micro x-ray fluorescence analyses (SR μ - XRF) have been carried out to study the distribution of Pb in bones from human joints (femoral heads and patellas). As a very recent result we found a highly specific accumulation of Pb in the tidemark, which is a metabolically active mineralization front (thickness about 5 - 10 μm) between calcified and non-calcified articular cartilage and plays an important role in developing osteoarthritis. From the results obtained for single tidemark bones one would expect an accumulation of Pb in both tidemarks of bones showing tidemark duplication. However, Pb shows a strong accumulation at the older of the two tidemarks, while it is not present at the younger one. A comparison of the Pb distribution with the one of other tidemark-seekers (e.g. Zn) exhibits a time difference in the accumulation of different metals at the calcification

  7. Human IGF-I propeptide A promotes articular chondrocyte biosynthesis and employs glycosylation-dependent heparin binding.

    Science.gov (United States)

    Shi, Shuiliang; Kelly, Brian J; Wang, Congrong; Klingler, Ken; Chan, Albert; Eckert, George J; Trippel, Stephen B

    2018-03-01

    Insulin-like growth factor I (IGF-I) is a key regulator of chondrogenesis, but its therapeutic application to articular cartilage damage is limited by rapid elimination from the repair site. The human IGF-I gene gives rise to three IGF-I propeptides (proIGF-IA, proIGF-IB and proIGF-IC) that are cleaved to create mature IGF-I. In this study, we elucidate the processing of IGF-I precursors by articular chondrocytes, and test the hypotheses that proIGF-I isoforms bind to heparin and regulate articular chondrocyte biosynthesis. Human IGF-I propeptides and mutants were overexpressed in bovine articular chondrocytes. IGF-I products were characterized by ELISA, western blot and FPLC using a heparin column. The biosynthetic activity of IGF-I products on articular chondrocytes was assayed for DNA and glycosaminoglycan that the cells produced. Secreted IGF-I propeptides stimulated articular chondrocyte biosynthetic activity to the same degree as mature IGF-I. Of the three IGF-I propeptides, only one, proIGF-IA, strongly bound to heparin. Interestingly, heparin binding of proIGF-IA depended on N-glycosylation at Asn92 in the EA peptide. To our knowledge, this is the first demonstration that N-glycosylation determines the binding of a heparin-binding protein to heparin. The biosynthetic and heparin binding abilities of proIGF-IA, coupled with its generation of IGF-I, suggest that proIGF-IA may have therapeutic value for articular cartilage repair. These data identify human pro-insulin-like growth factor IA as a bifunctional protein. Its combined ability to bind heparin and augment chondrocyte biosynthesis makes it a promising therapeutic agent for cartilage damage due to trauma and osteoarthritis. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. The relationship between ultra-short telomeres, aging of articular cartilage and the development of human hip osteoarthritis

    DEFF Research Database (Denmark)

    Harbo, M; Delaisse, J M; Kjaersgaard-Andersen, P

    2013-01-01

    Ultra-short telomeres caused by stress-induced telomere shortening are suggested to induce chondrocyte senescence in human osteoarthritic knees. Here we have further investigated the role of ultra-short telomeres in the development of osteoarthritis (OA) and in aging of articular cartilage in human...

  9. Mechanical Stimulation Protocols of Human Derived Cells in Articular Cartilage Tissue Engineering - A Systematic Review.

    Science.gov (United States)

    Khozoee, Baktash; Mafi, Pouya; Mafi, Reza; Khan, Wasim S

    2017-01-01

    Mechanical stimulation is a key factor in articular cartilage generation and maintenance. Bioreactor systems have been designed and built in order to deliver specific types of mechanical stimulation. The focus has been twofold, applying a type of preconditioning in order to stimulate cell differentiation, and to simulate in vivo conditions in order to gain further insight into how cells respond to different stimulatory patterns. Due to the complex forces at work within joints, it is difficult to simulate mechanical conditions using a bioreactor. The aim of this review is to gain a deeper understanding of the complexities of mechanical stimulation protocols by comparing those employed in bioreactors in the context of tissue engineering for articular cartilage, and to consider their effects on cultured cells. Allied and Complementary Medicine 1985 to 2016, Ovid MEDLINE[R] 1946 to 2016, and Embase 1974 to 2016 were searched using key terms. Results were subject to inclusion and exclusion criteria, key findings summarised into a table and subsequently discussed. Based on this review it is overwhelmingly clear that mechanical stimulation leads to increased chondrogenic properties in the context of bioreactor articular cartilage tissue engineering using human cells. However, given the variability and lack of controlled factors between research articles, results are difficult to compare, and a standardised method of evaluating stimulation protocols proved challenging. With improved standardisation in mechanical stimulation protocol reporting, bioreactor design and building processes, along with a better understanding of joint behaviours, we hope to perform a meta-analysis on stimulation protocols and methods. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  10. Analysis of human articular chondrocyte CD44 isoform expression and function in health and disease.

    Science.gov (United States)

    Salter, D M; Godolphin, J L; Gourlay, M S; Lawson, M F; Hughes, D E; Dunne, E

    1996-08-01

    Interactions between articular chondrocytes and components of the extracellular matrix are of potential importance in the normal function of cartilage and in the pathophysiology of arthritis. Little is known of the basis of these interactions, but cell adhesive molecules such as CD44 are likely to be involved. Immunohistology using six well-characterized anti-CD44 monoclonal antibodies demonstrated standard CD44 isoform (CD44H) expression by all chondrocytes in normal and osteoarthrotic (OA) cartilage but absence of the CD44E variant. Polymerase chain reaction (PCR) of reverse transcribed mRNA from monolayer cultures of normal and OA chondrocytes using primer sequences which span the region containing variably spliced exons produced a predominant band representing the standard form of CD44, which lacks the variable exons 6-15 (v1-v10). No product was seen at the expected size of the epithelial variant of CD44 (CD44v8-10). Use of exon-specific primers, however, showed expression of variant exons resulting in multiple minor isoforms. Standard CD44 was also shown to be the predominantly expressed isoform identified by immunoprecipitation, but human articular chondrocytes did not adhere to hyaluronan in vitro. Chondrocyte CD44 may function as an adhesion receptor for other matrix molecules such as fibronectin or collagen.

  11. Prenatal nicotine exposure induces poor articular cartilage quality in female adult offspring fed a high-fat diet and the intrauterine programming mechanisms.

    Science.gov (United States)

    Tie, Kai; Tan, Yang; Deng, Yu; Li, Jing; Ni, Qubo; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2016-04-01

    Prenatal nicotine exposure (PNE) induces skeletal growth retardation and dyslipidemia in offspring displaying intrauterine growth retardation (IUGR). Cholesterol accumulation resulting from cholesterol efflux dysfunction may reduce the quality of articular cartilage through fetal programming. This study evaluated the quality of articular cartilage of female adult offspring fed a high-fat diet and explored the mechanisms using a rat IUGR model established by the administration of 2.0mg/kg/d of subcutaneous nicotine from gestational days 11-20. The results demonstrated an increased OARSI (Osteoarthritis Research Society International) score and total cholesterol content, decreased serum corticosterone, and increased IGF1 and dyslipidemia with catch-up growth in PNE adult offspring. Cartilage matrix, IGF1 and cholesterol efflux pathway expression were reduced in PNE fetuses and adult offspring. Therefore, PNE induced poor articular cartilage quality in female adult offspring fed a high-fat diet via a dual programming mechanism. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Bonding of human meniscal and articular cartilage with photoactive 1,8-naphthalimide dyes

    Science.gov (United States)

    Judy, Millard M.; Nosir, Hany R.; Jackson, Robert W.; Matthews, James Lester; Lewis, David E.; Utecht, Ronald E.; Yuan, Dongwu

    1996-05-01

    This study focused on meniscal cartilage repair by using the laser-activated photoactive 1,8- naphthalimide dye N,N'-bis-{6-[2-(2-(2- aminoethoxy)ethoxy)ethoxyethyl]amino-1H-benz (de)isoquinolin-1,3(2H)-dion-2- yl}-1,11-diamino-3,6,9-trioxaundecane. Harvested cadaveric human menisci were debrided and carved into strips 1 mm thick, 10 mm long, and 3 mm wide. Each strip was divided into two flaps, the surface painted with photoactive dye, the painted surfaces overlapped, the sample wrapped in Saran film, and the composite sandwiched between two glass slides at a pressure of approximately 3 kg/cm2. The sample then was transilluminated by argon ion laser light of 457.9-nm wavelength at a power density of 200 mW/cm2 with exposure times up to 5 h (3902 J/cm2 energy density). Essentially, the same procedures were performed for human femoral articular cartilage samples. Control experiments were conducted with laser irradiation alone and with dye alone. All the specimens were stored in isotonic saline solution for 2 h after irradiation to ensure hydration. The bond shear-strength was then tested and samples prepared for optical and electron transmission microscopy. Shear strength values of up to 1.8 kg/cm2 for meniscal tissues and 1.2 kg/cm2 for articular cartilaginous tissues were obtained for exposures of 3902 J/cm2. Shear strength values of approximately 0.9 kg/cm2 and 0.4 kg/cm2, respectively, for meniscus and cartilage were obtained with 459 J/cm2 exposure. Dye- and light-only controls exhibited 0 kg/cm2 shear strength values. Microscopy revealed close contact at the bonded surface in the laser-activated, dye-treated-specimens. This study shows that the laser-activated photoactive dyes have the capability of athermally bonding the meniscal and articular cartilage surfaces.

  13. Fundamental study on articular disc with magnetic resonance imagings

    International Nuclear Information System (INIS)

    Chiba, Toyokazu

    1993-01-01

    In order to establish criteria of reading MRI of the temporomandibular joint, a morphological comparison between MRI and the section, and an observation of the articular disc associated with the opening were made. Five temporomandibular joints isolated from 3 human cadavers were subjected to MRI, and sections were prepared to examine criteria of reading MRI. In 20 male adults, 40 temporomandibular joints underwent MRI in three conditions of the intercuspal position, 10 and 20 mm opening positions, and the kinetics of the articular disc were examined. External feature of the head of mandible and that of the articular fossa, the articular tubercule and the postglenoid process were outlined in a row of blacks. The articular disc was outlined in a row of dark ashen areas of the anterior band, the intermediate region, and the posterior band. In the intercuspal position, the head of mandible was rarely covered with the articular disc, and being situated postero-inferiorly, at the most rear point of the posterior band of the articular disc. In the 10 mm-opening position, the head of mandible was practically covered with the articular disc. In the 20 mm-opening position, the intermediate region of the articular disc, and the head of mandible were situated in an approximate position. Quantitative movement of the articular disc was slower than that of the head of mandible. Comparison of various points of the articular disc revealed that movements of the anterior and posterior band varied almost proportionally to the opening distance, but with lesser movement of the intermediate region. (author)

  14. Recapitulation of physiological spatiotemporal signals promotes in vitro formation of phenotypically stable human articular cartilage

    Science.gov (United States)

    Wei, Yiyong; Zhou, Bin; Bernhard, Jonathan; Robinson, Samuel; Burapachaisri, Aonnicha; Guo, X. Edward

    2017-01-01

    Standard isotropic culture fails to recapitulate the spatiotemporal gradients present during native development. Cartilage grown from human mesenchymal stem cells (hMSCs) is poorly organized and unstable in vivo. We report that human cartilage with physiologic organization and in vivo stability can be grown in vitro from self-assembling hMSCs by implementing spatiotemporal regulation during induction. Self-assembling hMSCs formed cartilage discs in Transwell inserts following isotropic chondrogenic induction with transforming growth factor β to set up a dual-compartment culture. Following a switch in the basal compartment to a hypertrophic regimen with thyroxine, the cartilage discs underwent progressive deep-zone hypertrophy and mineralization. Concurrent chondrogenic induction in the apical compartment enabled the maintenance of functional and hyaline cartilage. Cartilage homeostasis, chondrocyte maturation, and terminal differentiation markers were all up-regulated versus isotropic control groups. We assessed the in vivo stability of the cartilage formed under different induction regimens. Cartilage formed under spatiotemporal regulation in vitro resisted endochondral ossification, retained the expression of cartilage markers, and remained organized following s.c. implantation in immunocompromised mice. In contrast, the isotropic control groups underwent endochondral ossification. Cartilage formed from hMSCs remained stable and organized in vivo. Spatiotemporal regulation during induction in vitro recapitulated some aspects of native cartilage development, and potentiated the maturation of self-assembling hMSCs into stable and organized cartilage resembling the native articular cartilage. PMID:28228529

  15. Effects of tofacitinib on nucleic acid metabolism in human articular chondrocytes.

    Science.gov (United States)

    Koizumi, Hideki; Arito, Mitsumi; Endo, Wataru; Kurokawa, Manae S; Okamoto, Kazuki; Omoteyama, Kazuki; Suematsu, Naoya; Beppu, Moroe; Kato, Tomohiro

    2015-07-01

    In our previous screening of chondrocyte protein profiles, the amount of adenosine monophosphate deaminase (AMPD) 2 was found to be decreased by tofacitinib. Extending the study, here we confirmed the decrease of AMPD2 by tofacitinib and further investigated effects of tofacitinib on purine nucleotide metabolism. Human articular chondrocytes and a chondrosarcoma cell line: OUMS-27 were stimulated with tofacitinib. Then the levels of AMPD2 and its related enzymes were investigated by Western blot. The levels of AMP and adenosine were assessed by mass spectrometry. We confirmed the significant decrease of AMPD2 by tofacitinib in chondrocytes (p = 0.025). The levels of adenosine kinase and 5'-nucleotidase were decreased in chondrocytes, although they did not meet statistical significance (p = 0.067 and p = 0.074, respectively). The results from OUMS-27 were similar to those from the chondrocytes. The cellular adenosine levels were significantly decreased by tofacitinib in OUMS-27 (p = 0.014). The cellular AMP levels were increased, although they did not meet statistical significance in OUMS-27 (p = 0.066). Our data indicate that tofacitinib increases the cellular levels of adenosine, which is known to have anti-inflammatory activity, through the downregulation of AMPD2. This would be a novel functional aspect of tofacitinib.

  16. Electromechanical Assessment of Human Knee Articular Cartilage with Compression-Induced Streaming Potentials.

    Science.gov (United States)

    Becher, Christoph; Ricklefs, Marcel; Willbold, Elmar; Hurschler, Christof; Abedian, Reza

    2016-01-01

    To assess the electromechanical properties of human knee articular cartilage with compression-induced streaming potentials for reliability among users and correlation with macroscopic and histological evaluation tools and sulfated glycosaminoglycan (sGAG) content. Streaming potentials are induced in cartilage in response to loading when mobile positive ions in the interstitial fluid temporarily move away from negatively charged proteoglycans. Streaming potential integrals (SPIs) were measured with an indentation probe on femoral condyles of 10 human knee specimens according to a standardized location scheme. Interobserver reliability was measured using an interclass correlation coefficient (ICC). The learning curves of 3 observers were evaluated by regression analysis. At each SPI measurement location the degradation level of the tissue was determined by means of the International Cartilage Repair Society (ICRS) score, Mankin score, and sGAG content. The computed ICC was 0.77 (0.70-0.83) indicating good to excellent linear agreement of SPI values among the 3 users. A significant positive linear correlation of the learning index values was observed for 2 of the 3 users. Statistically significant negative correlations between SPI and both ICRS and Mankin scores were observed (r = 0.502, P < 0.001, and r = 0.255, P = 0.02, respectively). No correlation was observed between SPI and sGAG content (r = 0.004, P = 0.973). SPI values may be used as a quantitative means of cartilage evaluation with sufficient reliability among users. Due to the significant learning curve, adequate training should be absolved before routine use of the technique.

  17. In Vivo Articular Cartilage Regeneration Using Human Dental Pulp Stem Cells Cultured in an Alginate Scaffold: A Preliminary Study

    Directory of Open Access Journals (Sweden)

    Manuel Mata

    2017-01-01

    Full Text Available Osteoarthritis is an inflammatory disease in which all joint-related elements, articular cartilage in particular, are affected. The poor regeneration capacity of this tissue together with the lack of pharmacological treatment has led to the development of regenerative medicine methodologies including microfracture and autologous chondrocyte implantation (ACI. The effectiveness of ACI has been shown in vitro and in vivo, but the use of other cell types, including bone marrow and adipose-derived mesenchymal stem cells, is necessary because of the poor proliferation rate of isolated articular chondrocytes. In this investigation, we assessed the chondrogenic ability of human dental pulp stem cells (hDPSCs to regenerate cartilage in vitro and in vivo. hDPSCs and primary isolated rabbit chondrocytes were cultured in chondrogenic culture medium and found to express collagen II and aggrecan. Both cell types were cultured in 3% alginate hydrogels and implanted in a rabbit model of cartilage damage. Three months after surgery, significant cartilage regeneration was observed, particularly in the animals implanted with hDPSCs. Although the results presented here are preliminary, they suggest that hDPSCs may be useful for regeneration of articular cartilage.

  18. In Vivo Articular Cartilage Regeneration Using Human Dental Pulp Stem Cells Cultured in an Alginate Scaffold: A Preliminary Study.

    Science.gov (United States)

    Mata, Manuel; Milian, Lara; Oliver, Maria; Zurriaga, Javier; Sancho-Tello, Maria; de Llano, Jose Javier Martin; Carda, Carmen

    2017-01-01

    Osteoarthritis is an inflammatory disease in which all joint-related elements, articular cartilage in particular, are affected. The poor regeneration capacity of this tissue together with the lack of pharmacological treatment has led to the development of regenerative medicine methodologies including microfracture and autologous chondrocyte implantation (ACI). The effectiveness of ACI has been shown in vitro and in vivo , but the use of other cell types, including bone marrow and adipose-derived mesenchymal stem cells, is necessary because of the poor proliferation rate of isolated articular chondrocytes. In this investigation, we assessed the chondrogenic ability of human dental pulp stem cells (hDPSCs) to regenerate cartilage in vitro and in vivo . hDPSCs and primary isolated rabbit chondrocytes were cultured in chondrogenic culture medium and found to express collagen II and aggrecan. Both cell types were cultured in 3% alginate hydrogels and implanted in a rabbit model of cartilage damage. Three months after surgery, significant cartilage regeneration was observed, particularly in the animals implanted with hDPSCs. Although the results presented here are preliminary, they suggest that hDPSCs may be useful for regeneration of articular cartilage.

  19. Platelet lysate activates quiescent cell proliferation and reprogramming in human articular cartilage: Involvement of hypoxia inducible factor 1.

    Science.gov (United States)

    Nguyen, Van Thi; Cancedda, Ranieri; Descalzi, Fiorella

    2018-03-01

    The idea of rescuing the body self-repair capability lost during evolution is progressively gaining ground in regenerative medicine. In particular, growth factors and bioactive molecules derived from activated platelets emerged as promising therapeutic agents acting as trigger for repair of tissue lesions and restoration of tissue functions. Aim of this study was to assess the potential of a platelet lysate (PL) for human articular cartilage repair considering its activity on progenitor cells and differentiated chondrocytes. PL induced the re-entry in the cell cycle of confluent, growth-arrested dedifferentiated/progenitor cartilage cells. In a cartilage permissive culture environment, differentiated cells also resumed proliferation after exposure to PL. These findings correlated with an up-regulation of the proliferation/survival pathways ERKs and Akt and with an induction of cyclin D1. In short- and long-term cultures of articular cartilage explants, we observed a release of proliferating chondroprogenitors able to differentiate and form an "in vitro" tissue with properties of healthy articular cartilage. Moreover, in cultured cartilage cells, PL induced a hypoxia-inducible factor (HIF-1) alpha increase, its nuclear relocation and the binding to HIF-1 responsive elements. These events were possibly related to the cell proliferation because the HIF-1 inhibitor acriflavine inhibited HIF-1 binding to HIF-1 responsive elements and cell proliferation. Our study demonstrates that PL induces quiescent cartilage cell activation and proliferation leading to new cartilage formation, identifies PL activated pathways playing a role in these processes, and provides a rationale to the application of PL for therapeutic treatment of damaged articular cartilage. Copyright © 2017 John Wiley & Sons, Ltd.

  20. Reconstruction of Hyaline Cartilage Deep Layer Properties in 3-Dimensional Cultures of Human Articular Chondrocytes.

    Science.gov (United States)

    Nanduri, Vibudha; Tattikota, Surendra Mohan; T, Avinash Raj; Sriramagiri, Vijaya Rama Rao; Kantipudi, Suma; Pande, Gopal

    2014-06-01

    Articular cartilage (AC) injuries and malformations are commonly noticed because of trauma or age-related degeneration. Many methods have been adopted for replacing or repairing the damaged tissue. Currently available AC repair methods, in several cases, fail to yield good-quality long-lasting results, perhaps because the reconstructed tissue lacks the cellular and matrix properties seen in hyaline cartilage (HC). To reconstruct HC tissue from 2-dimensional (2D) and 3-dimensional (3D) cultures of AC-derived human chondrocytes that would specifically exhibit the cellular and biochemical properties of the deep layer of HC. Descriptive laboratory study. Two-dimensional cultures of human AC-derived chondrocytes were established in classical medium (CM) and newly defined medium (NDM) and maintained for a period of 6 weeks. These cells were suspended in 2 mm-thick collagen I gels, placed in 24-well culture inserts, and further cultured up to 30 days. Properties of chondrocytes, grown in 2D cultures and the reconstructed 3D cartilage tissue, were studied by optical and scanning electron microscopic techniques, immunohistochemistry, and cartilage-specific gene expression profiling by reverse transcription polymerase chain reaction and were compared with those of the deep layer of native human AC. Two-dimensional chondrocyte cultures grown in NDM, in comparison with those grown in CM, showed more chondrocyte-specific gene activity and matrix properties. The NDM-grown chondrocytes in 3D cultures also showed better reproduction of deep layer properties of HC, as confirmed by microscopic and gene expression analysis. The method used in this study can yield cartilage tissue up to approximately 1.6 cm in diameter and 2 mm in thickness that satisfies the very low cell density and matrix composition properties present in the deep layer of normal HC. This study presents a novel and reproducible method for long-term culture of AC-derived chondrocytes and reconstruction of cartilage

  1. Snorc is a novel cartilage specific small membrane proteoglycan expressed in differentiating and articular chondrocytes

    DEFF Research Database (Denmark)

    Heinonen, J; Taipaleenmäki, H; Roering, P

    2011-01-01

    OBJECTIVE: Maintenance of chondrocyte phenotype is a major issue in prevention of degeneration and repair of articular cartilage. Although the critical pathways in chondrocyte maturation and homeostasis have been revealed, the in-depth understanding is deficient and novel modifying components...... subgroups. Cartilage specific expression was highest in proliferating and prehypertrophic zones during development, and in adult articular cartilage, expression was restricted to the uncalcified zone, including chondrocyte clusters in human osteoarthritic cartilage. Studies with experimental chondrogenesis...... chondrocytes and adult articular chondrocytes with possible functions associated with development and maintenance of chondrocyte phenotype....

  2. Age-related accumulation of Maillard reaction products in human articular cartilage collagen

    NARCIS (Netherlands)

    Verzijl, N.; Degroot, J.; Oldehinkel, E.; Bank, R. A.; Thorpe, S. R.; Baynes, J. W.; Bayliss, M. T.; Bijlsma, J. W.; Lafeber, F. P.; TeKoppele, J. M.

    2000-01-01

    Non-enzymic modification of tissue proteins by reducing sugars, the so-called Maillard reaction, is a prominent feature of aging. In articular cartilage, relatively high levels of the advanced glycation end product (AGE) pentosidine accumulate with age. Higher pentosidine levels have been associated

  3. Cellular automata model for human articular chondrocytes migration, proliferation and cell death: An in vitro validation.

    Science.gov (United States)

    Vaca-González, J J; Gutiérrez, M L; Guevara, J M; Garzón-Alvarado, D A

    2017-01-01

    Articular cartilage is characterized by low cell density of only one cell type, chondrocytes, and has limited self-healing properties. When articular cartilage is affected by traumatic injuries, a therapeutic strategy such as autologous chondrocyte implantation is usually proposed for its treatment. This approach requires in vitro chondrocyte expansion to yield high cell number for cell transplantation. To improve the efficiency of this procedure, it is necessary to assess cell dynamics such as migration, proliferation and cell death during culture. Computational models such as cellular automata can be used to simulate cell dynamics in order to enhance the result of cell culture procedures. This methodology has been implemented for several cell types; however, an experimental validation is required for each one. For this reason, in this research a cellular automata model, based on random-walk theory, was devised in order to predict articular chondrocyte behavior in monolayer culture during cell expansion. Results demonstrated that the cellular automata model corresponded to cell dynamics and computed-accurate quantitative results. Moreover, it was possible to observe that cell dynamics depend on weighted probabilities derived from experimental data and cell behavior varies according to the cell culture period. Thus, depending on whether cells were just seeded or proliferated exponentially, culture time probabilities differed in percentages in the CA model. Furthermore, in the experimental assessment a decreased chondrocyte proliferation was observed along with increased passage number. This approach is expected to having other uses as in enhancing articular cartilage therapies based on tissue engineering and regenerative medicine.

  4. Histological and biochemical evaluation of perichondrial transplants in human articular cartilage defects

    NARCIS (Netherlands)

    Bouwmeester, P; Kuijer, R; Terwindt-Rouwenhorst, E; van der Linden, Ton; Bulstra, K

    1999-01-01

    From 1986 to 1992, 88 patients with articular defects in the knee were treated with a perichondrial arthroplasty. In this study, we report on the results for 22 biopsies of grafted tissue with a mean follow-up of 21 months. Biopsies were obtained at routine arthroscopy after approximately 1 year or

  5. Accumulation of advanced glycation endproducts reduces chondrocyte-mediated extracellular matrix turnover in human articular cartilage

    NARCIS (Netherlands)

    Degroot, J.; Verzijl, N.; Jacobs, K. M.; Budde, M.; Bank, R. A.; Bijlsma, J. W.; TeKoppele, J. M.; Lafeber, F. P.

    2001-01-01

    The prevalence of osteoarthritis (OAs) increases with age and coincides with the accumulation of advanced glycation endproducts (AGEs) in articular cartilage, suggesting that accumulation of glycation products may be involved in the development of OA. This study was designed to examine the effects

  6. Bovine lactoferricin, an antimicrobial peptide, is anti-inflammatory and anti-catabolic in human articular cartilage and synovium

    Science.gov (United States)

    Yan, Dongyao; Chen, Di; Shen, Jie; Xiao, Guozhi; van Wijnen, Andre J; Im, Hee-Jeong

    2012-01-01

    Bovine lactoferricin (LfcinB) is a multi-functional peptide derived from proteolytic cleavage of bovine lactoferrin. LfcinB was found to antagonize the biological effects mediated by angiogenic growth factors such as vascular endothelial growth factor (VEGF) and fibroblast growth factor 2 (FGF-2) in endothelial cells. However, the effect of LfcinB on human articular cartilage remained unknown. Here, our findings demonstrate that LfcinB restored the proteoglycan loss promoted by catabolic factors (interleukin-1 β) IL-1β and FGF-2 in vitro and ex vivo. Mechanistically, LfcinB attenuated the effects of IL-1β and FGF-2 on the expression of cartilage-degrading enzymes (MMP-1, MMP-3, and MMP-13), destructive cytokines (IL-1β and IL-6), and inflammatory mediators (iNOS and TLR2). LfcinB induced protective cytokine expression (IL-4 and IL-10), and downregulated aggrecanase basal expression. LfcinB specifically activated ERK MAPK and Akt signaling pathways, which may account for its anti-inflammatory activity. We also revealed that LfcinB exerted similar protective effects on human synovial fibroblasts challenged by IL-1β, with minimal cytotoxicity. Collectively, our results suggest that LfcinB possesses potent anti-catabolic and anti-inflammatory bioactivities in human articular tissues, and may be utilized for the prevention and/or treatment of OA in the future. PMID:22740381

  7. Osteoarthritis: Control of human cartilage hypertrophic differentiation. Research highlight van: Gremlin1, frizzled-related protein, and Dkk-1 are key regulators of human articular cartilage homeostasis

    NARCIS (Netherlands)

    Buckland, J.; Leijten, Jeroen Christianus Hermanus; van Blitterswijk, Clemens; Karperien, Hermanus Bernardus Johannes

    2012-01-01

    Disruption of articular cartilage homeostasis is important in osteoarthritis (OA) pathogenesis, key to which is activation of articular chondrocyte hypertrophic differentiation. Healthy articular cartilage is resistant to hypertrophic differentiation, whereas growth-plate cartilage is destined to

  8. Can Double Osteotomy Be a Solution for Adult Hallux Valgus Deformity With an Increased Distal Metatarsal Articular Angle?

    Science.gov (United States)

    Park, Chul Hyun; Cho, Jae Ho; Moon, Jeong Jae; Lee, Woo Chun

    2016-01-01

    No previous study has reported the results of double metatarsal osteotomy for adult hallux valgus deformity with an increased distal metatarsal articular angle (DMAA). The purpose of the present study was to evaluate the results after double metatarsal osteotomy in adult patients with incongruent hallux valgus deformity. We retrospectively reviewed 16 cases of consecutive first metatarsal double metatarsal osteotomy without lateral soft tissue release in 14 patients with symptomatic hallux valgus associated with an increased DMAA (≥15° after proximal chevron osteotomy on intraoperative radiographs). Clinical results were assessed using the American Orthopaedic Foot and Ankle Society scale and the visual analog scale. The radiographic results were assessed over time, and changes in the DMAA and the relative length of the first metatarsal were assessed by measuring each value preoperatively and at the last follow-up visit. The American Orthopaedic Foot and Ankle Society and visual analog scale scores were significantly improved after surgery. The hallux valgus angle and intermetatarsal angle were stabilized >3 months after surgery. The sesamoid position did not increase significantly beyond the immediate postoperative period. The mean DMAA was corrected from 21.6° (range 15° to 29°) preoperatively to 11.1° (range -2° to 17°) at the last follow-up visit. The mean amount of shortening of the first metatarsal after surgery was 5.5 (range 4 to 7) mm. In conclusion, double metatarsal osteotomy without lateral soft tissue release in adult hallux valgus deformity results in high postoperative recurrence and complication rates. Copyright © 2016 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  9. Three-dimensional scaffold-free fusion culture: the way to enhance chondrogenesis of in vitro propagated human articular chondrocytes

    Directory of Open Access Journals (Sweden)

    M. Lehmann

    2013-11-01

    Full Text Available Cartilage regeneration based on isolated and culture-expanded chondrocytes has been studied in various in vitro models, but the quality varies with respect to the morphology and the physiology of the synthesized tissues. The aim of our study was to promote in vitro chondrogenesis of human articular chondrocytes using a novel three-dimensional (3-D cultivation system in combination with the chondrogenic differentiation factors transforming growth factor beta 2 (TGF-b2 and L-ascorbic acid. Articular chondrocytes isolated from six elderly patients were expanded in monolayer culture. A single-cell suspension of the dedifferentiated chondrocytes was then added to agar-coated dishes without using any scaffold material, in the presence, or absence of TGF-b2 and/or L-ascorbic acid. Three-dimensional cartilage-like constructs, called single spheroids, and microtissues consisting of several spheroids fused together, named as fusions, were formed. Generated tissues were mainly characterized using histological and immunohistochemical techniques. The morphology of the in vitro tissues shared some similarities to native hyaline cartilage in regard to differentiated S100-positive chondrocytes within a cartilaginous matrix, with strong collagen type II expression and increased synthesis of proteoglycans. Finally, our innovative scaffold-free fusion culture technique supported enhanced chondrogenesis of human articular chondrocytes in vitro. These 3-D hyaline cartilage-like microtissues will be useful for in vitro studies of cartilage differentiation and regeneration, enabling optimization of functional tissue engineering and possibly contributing to the development of new approaches to treat traumatic cartilage defects or osteoarthritis.

  10. Histochemistry for studying structure and function of the articular disc of the human temporomandibular joint

    Directory of Open Access Journals (Sweden)

    N. Kiga

    2012-02-01

    Full Text Available The articular disc of the temporomandibular joint (TMJ is composed of fibrocartilage, and the extracellular matrix of this disc is composed mainly of collagen, glycosaminoglycan and proteoglycans. Research on the changes that occur in the composition of the articular disc of the TMJ is necessary for understanding the basis of the pathological process of internal derangement (ID, and a number of reports have been published in recent years on the application of refined histochemical techniques to investigate the structure and function of the TMJ. The direction of future TMJ disc studies should be towards obtaining more evidence to support previous results, and should hopefully be of practical use in terms of prevention and cure of ID.

  11. Gremlin 1, Frizzled-related protein, and Dkk-1 are key regulators of human articular cartilage homeostasis

    NARCIS (Netherlands)

    Leijten, Jeroen Christianus Hermanus; Emons, J.; Sticht, C.; van Gool, S.; Decker, E.; Uitterlinden, A.; Rappold, G.; Hofman, A.; Rivadeneira, F.; Scherjon, S.; Wit, J.M.; van Meurs, J.; van Blitterswijk, Clemens; Karperien, Hermanus Bernardus Johannes

    2012-01-01

    Objective The development of osteoarthritis (OA) may be caused by activation of hypertrophic differentiation of articular chondrocytes. Healthy articular cartilage is highly resistant to hypertrophic differentiation, in contrast to other hyaline cartilage subtypes, such as growth plate cartilage.

  12. Bovine lactoferricin induces TIMP-3 via the ERK1/2-Sp1 axis in human articular chondrocytes.

    Science.gov (United States)

    Yan, Dongyao; Chen, Di; Hawse, John R; van Wijnen, Andre J; Im, Hee-Jeong

    2013-03-15

    Bovine lactoferricin (LfcinB) is a heparan sulfate-binding peptide with multiple bioactivities. In human articular cartilage, LfcinB antagonizes interleukin-1 β (IL-1β) and fibroblast growth factor 2 (FGF-2) in proteoglycan metabolism, catabolic protease expression, and induction of pro-inflammatory mediators. LfcinB specifically activates ERK1/2, p38 and Akt, but whether these signaling pathways control the expression of LfcinB target genes remained unknown. In this report, we characterized a novel aspect of LfcinB-mediated genetic response in human articular chondrocytes, tissue inhibitor of metalloproteinase 3 (TIMP-3) induction. Inhibition of individual signaling pathways revealed that ERK1/2 functions as the major pathway in TIMP-3 expression, whereas Akt plays a minor role. Further investigation identified Sp1 as a critical transcriptional activator in TIMP-3 regulation, and Sp1 activity is modulated by ERK1/2, not Akt. Comparative quantification indicates that significant downregulation of TIMP-3 occurs in OA chondrocytes, suggesting a beneficial role of LfcinB in OA pathogenesis. Our results collectively provide new insights into the mechanism of action of LfcinB, and support the candidacy of LfcinB as a chondroprotective agent. Copyright © 2013 Elsevier B.V. All rights reserved.

  13. Human articular cartilage: in vitro correlation of MRI and histologic findings

    International Nuclear Information System (INIS)

    Uhl, M.; Allmann, K.H.; Laubenberger, J.; Langer, M.; Ihling, C.; Tauer, U.; Adler, C.P.

    1998-01-01

    The aim of our study was to correlate MRI with histologic findings in normal and degenerative cartilage. Twenty-two human knees derived from patients undergoing amputation were examined with 1.0- and 1.5-T MR imaging units. Firstly, we optimized two fat-suppressed 3D gradient-echo sequences. In this pilot study two knees were examined with fast imaging with steady precession (FISP) sequences and fast low-angle shot (FLASH, SPGR) sequence by varying the flip angles (40, 60, 90 ) and combining each flip angle with different echo time (7, 10 or 11, 20 ms). We chose the sequences with the best visual contrast between the cartilage layers and the best measured contrast-to-noise ratio between cartilage and bone marrow. Therefore, we used a 3D FLASH fat-saturated sequence (TR/TE/flip angle = 50/11 ms/40 ) and a 3D FISP fat-saturated sequence (TR/TE/flip angle = 40/10 ms/40 ) for cartilage imaging in 22 human knees. The images were obtained at various angles of the patellar cartilage in relation to the main magnetic field (0, 55, 90 ). The MR appearances were classified into five categories: normal, intracartilaginous signal changes, diffuse thinning (cartilage thickness < 3 mm), superficial erosions, and cartilage ulcers. After imaging, the knees were examined macroscopically and photographed. In addition, we performed histologic studies using light microscopy with several different stainings, polarization, and dark field microscopy as well as electron microscopy. The structural characteristics with the cartilage lesions were correlated with the MR findings. We identified a hyperintense superficial zone in the MR image which did not correlate to the histologically identifiable superficial zone. The second lamina was hypointense on MRI and correlated to the bulk of the radial zone. The third (or deep) cartilage lamina in the MR image seemed to represent the combination of the lowest portion of the radial zone and the calcified cartilage. The width of the hypointense second

  14. Human articular cartilage: in vitro correlation of MRI and histologic findings

    Energy Technology Data Exchange (ETDEWEB)

    Uhl, M.; Allmann, K.H.; Laubenberger, J.; Langer, M. [Department of Diagnostic Radiology, University Hospital of Freiburg (Germany); Ihling, C.; Tauer, U.; Adler, C.P. [Department of Pathology, University Hospital of Freiburg (Germany)

    1998-09-01

    The aim of our study was to correlate MRI with histologic findings in normal and degenerative cartilage. Twenty-two human knees derived from patients undergoing amputation were examined with 1.0- and 1.5-T MR imaging units. Firstly, we optimized two fat-suppressed 3D gradient-echo sequences. In this pilot study two knees were examined with fast imaging with steady precession (FISP) sequences and fast low-angle shot (FLASH, SPGR) sequence by varying the flip angles (40, 60, 90 ) and combining each flip angle with different echo time (7, 10 or 11, 20 ms). We chose the sequences with the best visual contrast between the cartilage layers and the best measured contrast-to-noise ratio between cartilage and bone marrow. Therefore, we used a 3D FLASH fat-saturated sequence (TR/TE/flip angle = 50/11 ms/40 ) and a 3D FISP fat-saturated sequence (TR/TE/flip angle = 40/10 ms/40 ) for cartilage imaging in 22 human knees. The images were obtained at various angles of the patellar cartilage in relation to the main magnetic field (0, 55, 90 ). The MR appearances were classified into five categories: normal, intracartilaginous signal changes, diffuse thinning (cartilage thickness < 3 mm), superficial erosions, and cartilage ulcers. After imaging, the knees were examined macroscopically and photographed. In addition, we performed histologic studies using light microscopy with several different stainings, polarization, and dark field microscopy as well as electron microscopy. The structural characteristics with the cartilage lesions were correlated with the MR findings. We identified a hyperintense superficial zone in the MR image which did not correlate to the histologically identifiable superficial zone. The second lamina was hypointense on MRI and correlated to the bulk of the radial zone. The third (or deep) cartilage lamina in the MR image seemed to represent the combination of the lowest portion of the radial zone and the calcified cartilage. The width of the hypointense second

  15. Human articular chondrocytes secrete parathyroid hormone-related protein and inhibit hypertrophy of mesenchymal stem cells in coculture during chondrogenesis.

    Science.gov (United States)

    Fischer, J; Dickhut, A; Rickert, M; Richter, W

    2010-09-01

    The use of bone marrow-derived mesenchymal stem cells (MSCs) has shown promise in cell-based cartilage regeneration. A yet-unsolved problem, however, is the unwanted up-regulation of markers of hypertrophy, such as alkaline phosphatase (AP) and type X collagen, during in vitro chondrogenesis and the formation of unstable calcifying cartilage at heterotopic sites. In contrast, articular chondrocytes produce stable, nonmineralizing cartilage. The aim of this study was to address whether coculture of MSCs with human articular chondrocytes (HACs) can suppress the undesired hypertrophy in differentiating MSCs. MSCs were differentiated in chondrogenic medium that had or had not been conditioned by parallel culture with HAC pellets, or MSCs were mixed in the same pellet with the HACs (1:1 or 1:2 ratio) and cultured for 6 weeks. Following in vitro differentiation, the pellets were transplanted into SCID mice. The gene expression ratio of COL10A1 to COL2A1 and of Indian hedgehog (IHH) to COL2A1 was significantly reduced by differentiation in HAC-conditioned medium, and less type X collagen protein was deposited relative to type II collagen. AP activity was significantly lower (P chondrogenesis. The main inhibitory effects seen with HAC-conditioned medium were reproducible by PTHrP supplementation of unconditioned medium. HAC-derived soluble factors and direct coculture are potent means of improving chondrogenesis and suppressing the hypertrophic development of MSCs. PTHrP is an important candidate soluble factor involved in this effect.

  16. Intra-Articular Injection of Human Meniscus Stem/Progenitor Cells Promotes Meniscus Regeneration and Ameliorates Osteoarthritis Through Stromal Cell-Derived Factor-1/CXCR4-Mediated Homing

    Science.gov (United States)

    Shen, Weiliang; Chen, Jialin; Zhu, Ting; Chen, Longkun; Zhang, Wei; Fang, Zhi; Heng, Boon Chin; Yin, Zi; Chen, Xiao; Ji, Junfeng

    2014-01-01

    Meniscus injury is frequently encountered in clinical practice. Current surgical therapy involving partial or complete meniscectomy relieves pain in the short-term but often leads to osteoarthritis (OA) in the long-term. In this study, we report a new strategy of articular cartilage protection by intra-articular injection of novel human meniscus stem/progenitor cells (hMeSPCs). We found that hMeSPCs displayed both mesenchymal stem cell characteristics and high expression levels of collagen II. In the rat meniscus injury model, hMeSPC transplantation not only led to more neo-tissue formation and better-defined shape but also resulted in more rounded cells and matured extracellular matrix. Stromal cell-derived factor-1 (SDF-1) enhanced the migration of hMeSPCs, whereas AMD3100 abolished the chemotactic effects of SDF-1 on hMeSPCs, both in vitro and in vivo. In an experimental OA model, transplantation of hMeSPCs effectively protected articular cartilage, as evidenced by reduced expression of OA markers such as collagen I, collagen X, and hypoxia-inducible factor 2α but increased expression of collagen II. Our study demonstrated for the first time that intra-articular injection of hMeSPCs enhanced meniscus regeneration through the SDF-1/CXCR4 axis. Our study highlights a new strategy of intra-articular injection of hMeSPCs for meniscus regeneration. PMID:24448516

  17. Synovial Fluid Filtration by Articular Cartilage with a Worn-out Surface Zone in the Human Ankle Joint during Walking- II. Numerical Results for Steady Pure Sliding

    Czech Academy of Sciences Publication Activity Database

    Hlaváček, Miroslav

    2000-01-01

    Roč. 45, č. 4 (2000), s. 375-396 ISSN 0001-7043 R&D Projects: GA ČR GA103/00/0008 Keywords : biphasic articular cartilage * biphasic synovial fluid * boundary lubrication * human ankle joint Subject RIV: BK - Fluid Dynamics

  18. Synovial Fluid Filtration by Articular Cartilage with a Worn-out Surface Zone in the Human Ankle Joint during Walking- I.A Mathematical Mixture Model

    Czech Academy of Sciences Publication Activity Database

    Hlaváček, Miroslav

    2000-01-01

    Roč. 45, č. 3 (2000), s. 295-321 ISSN 0001-7043 R&D Projects: GA ČR GA103/00/0008 Keywords : asymptotic solution * biphasic articular cartilage * biphasic synovial fluid * human ankle joint Subject RIV: BK - Fluid Dynamics

  19. Effect of Human Adipose Tissue Mesenchymal Stem Cells on the Regeneration of Ovine Articular Cartilage.

    Science.gov (United States)

    Zorzi, Alessandro R; Amstalden, Eliane M I; Plepis, Ana Maria G; Martins, Virginia C A; Ferretti, Mario; Antonioli, Eliane; Duarte, Adriana S S; Luzo, Angela C M; Miranda, João B

    2015-11-09

    Cell therapy is a promising approach to improve cartilage healing. Adipose tissue is an abundant and readily accessible cell source. Previous studies have demonstrated good cartilage repair results with adipose tissue mesenchymal stem cells in small animal experiments. This study aimed to examine these cells in a large animal model. Thirty knees of adult sheep were randomly allocated to three treatment groups: CELLS (scaffold seeded with human adipose tissue mesenchymal stem cells), SCAFFOLD (scaffold without cells), or EMPTY (untreated lesions). A partial thickness defect was created in the medial femoral condyle. After six months, the knees were examined according to an adaptation of the International Cartilage Repair Society (ICRS 1) score, in addition to a new Partial Thickness Model scale and the ICRS macroscopic score. All of the animals completed the follow-up period. The CELLS group presented with the highest ICRS 1 score (8.3 ± 3.1), followed by the SCAFFOLD group (5.6 ± 2.2) and the EMPTY group (5.2 ± 2.4) (p = 0.033). Other scores were not significantly different. These results suggest that human adipose tissue mesenchymal stem cells promoted satisfactory cartilage repair in the ovine model.

  20. Postnatal development of articular cartilage

    NARCIS (Netherlands)

    Turnhout, van M.C.

    2010-01-01

    Articular cartilage (AC) is the thin layer of tissue that covers the ends of the bones in the synovial joints in mammals. Functional adult AC has depth-dependent mechanical properties that are not yet present at birth. These depth-dependent mechanical properties in adult life are the result of a

  1. Mechanical properties of human articular disk and its influence on TMJ loading studied with the finite element method.

    Science.gov (United States)

    Tanaka, E; Sasaki, A; Tahmina, K; Yamaguchi, K; Mori, Y; Tanne, K

    2001-03-01

    The present study was designed to investigate the elastic modulus of human temporomandibular joint (TMJ) disk under tension and its influences on TMJ loading. Seven human TMJ disks served as specimens. Continuous tensile stress was applied to each specimen, and the elastic moduli of human TMJ disks were calculated at 2% strain. Furthermore, using a three-dimensional finite element model of the mandible including the TMJ, changes in the TMJ stresses during clenching were evaluated in association of varying elastic moduli of the articular disk determined by the tensile tests. The elastic moduli at 2% strain varied from 27.1 to 65.2 MPa with a mean of 47.1 MPa. A significant correlation was found between the elastic moduli and age (P elastic moduli of the TMJ disk was varied from 25 to 65 MPa. In the TMJ disk, shear stresses in all the areas became larger with greater stiffness. In conclusion, it is shown that the elastic modulus of human TMJ disk is increased with age and that higher stiffness of the disk exerts substantial influences on mechanical loading for the TMJ structures.

  2. Development of a Novel Large Animal Model to Evaluate Human Dental Pulp Stem Cells for Articular Cartilage Treatment.

    Science.gov (United States)

    Fernandes, Tiago Lazzaretti; Shimomura, Kazunori; Asperti, Andre; Pinheiro, Carla Cristina Gomes; Caetano, Heloísa Vasconcellos Amaral; Oliveira, Claudia Regina G C M; Nakamura, Norimasa; Hernandez, Arnaldo José; Bueno, Daniela Franco

    2018-05-04

    Chondral lesion is a pathology with high prevalence, reaching as much as 63% of general population and 36% among athletes. The ability of human Dental Pulp Stem Cells (DPSCs) to differentiate into chondroblasts in vitro suggests that this stem cell type may be useful for tissue bioengineering. However, we have yet to identify a study of large animal models in which DPSCs were used to repair articular cartilage. Therefore, this study aimed to describe a novel treatment for cartilage lesion with DPSCs on a large animal model. Mesenchymal stem cells (MSC) were obtained from deciduous teeth and characterized by flow cytometry. DPSCs were cultured and added to a collagen type I/III biomaterial composite scaffold. Brazilian miniature pig (BR-1) was used. A 6-mm diameter, full-thickness chondral defect was created in each posterior medial condyle. The defects were covered with scaffold alone or scaffold + DPSCs on the contralateral side. Animals were euthanized 6 weeks post-surgery. Cartilage defects were analyzed macroscopically and histology according to modified O'Driscoll scoring system. Flow cytometry confirmed characterization of DPSCs as MSCs. Macroscopic and histological findings suggested that this time period was reasonable for evaluating cartilage repair. To our knowledge, this study provides the first description of an animal model using DPSCs to study the differentiation of hyaline articular cartilage in vivo. The animals tolerated the procedure well and did not show clinical or histological rejection of the DPSCs, reinforcing the feasibility of this descriptive miniature pig model for pre-clinical studies.

  3. Isotropic morphometry and multicomponent T1 ρ mapping of human knee articular cartilage in vivo at 3T.

    Science.gov (United States)

    Baboli, Rahman; Sharafi, Azadeh; Chang, Gregory; Regatte, Ravinder R

    2018-05-02

    The progressive loss of hyaline articular cartilage due to osteoarthritis (OA) changes the functional and biochemical properties of cartilage. Measuring the T 1 ρ along with the morphological assessment can potentially be used as noninvasive biomarkers in detecting early-stage OA. To correlate the biochemical and morphological data, submillimeter isotropic resolution for both studies is required. To implement a high spatial resolution 3D-isotropic-MRI sequence for simultaneous assessment of morphological and biexponential T 1 ρ relaxometry of human knee cartilage in vivo. Prospective. Ten healthy volunteers with no known inflammation, trauma, or pain in the knee. Standard FLASH sequence and customized Turbo-FLASH sequence to acquire 3D-isotropic-T 1 ρ-weighted images on a 3T MRI scanner. The mean volume and thickness along with mono- and biexponential T 1 ρ relaxations were assessed in the articular cartilage of 10 healthy volunteers. Nonparametric rank-sum tests. Bland-Altman analysis and coefficient of variation. The mean monoexponential T 1 ρ relaxation was 40.7 ± 4.8 msec, while the long and short components were 58.2 ± 3.9 msec and 6.5 ± 0.6 msec, respectively. The mean fractions of long and short T 1 ρ relaxation components were 63.7 ± 5.9% and 36.3 ± 5.9%, respectively. Statistically significant (P ≤ 0.03) differences were observed in the monoexponential and long components between some of the regions of interest (ROIs). No gender differences between biexponential components were observed (P > 0.05). Mean cartilage volume and thickness were 25.9 ± 6.4 cm 3 and 2.2 ± 0.7 mm, respectively. Cartilage volume (P = 0.01) and thickness (P = 0.03) were significantly higher in male than female participants across all ROIs. Bland-Altman analysis showed agreement between two morphological methods with limits of agreement between -1000 mm 3 and +1100 mm 3 for volume, and -0.78 mm and +0.46 mm for

  4. Articular surface approximation in equivalent spatial parallel mechanism models of the human knee joint: an experiment-based assessment.

    Science.gov (United States)

    Ottoboni, A; Parenti-Castelli, V; Sancisi, N; Belvedere, C; Leardini, A

    2010-01-01

    In-depth comprehension of human joint function requires complex mathematical models, which are particularly necessary in applications of prosthesis design and surgical planning. Kinematic models of the knee joint, based on one-degree-of-freedom equivalent mechanisms, have been proposed to replicate the passive relative motion between the femur and tibia, i.e., the joint motion in virtually unloaded conditions. In the mechanisms analysed in the present work, some fibres within the anterior and posterior cruciate and medial collateral ligaments were taken as isometric during passive motion, and articulating surfaces as rigid. The shapes of these surfaces were described with increasing anatomical accuracy, i.e. from planar to spherical and general geometry, which consequently led to models with increasing complexity. Quantitative comparison of the results obtained from three models, featuring an increasingly accurate approximation of the articulating surfaces, was performed by using experimental measurements of joint motion and anatomical structure geometries of four lower-limb specimens. Corresponding computer simulations of joint motion were obtained from the different models. The results revealed a good replication of the original experimental motion by all models, although the simulations also showed that a limit exists beyond which description of the knee passive motion does not benefit considerably from further approximation of the articular surfaces.

  5. The synovial microenvironment of osteoarthritic joints alters RNA-seq expression profiles of human primary articular chondrocytes

    Science.gov (United States)

    Lewallen, Eric A.; Bonin, Carolina A.; Li, Xin; Smith, Jay; Karperien, Marcel; Larson, A. Noelle; Lewallen, David G.; Cool, Simon M.; Westendorf, Jennifer J.; Krych, Aaron J.; Leontovich, Alexey A.; Im, Hee-Jeong; van Wijnen, Andre J.

    2018-01-01

    Osteoarthritis (OA) is a disabling degenerative joint disease that prompts pain with limited treatment options. To permit early diagnosis and treatment of OA, a high resolution mechanistic understanding of human chondrocytes in normal and diseased states is necessary. In this study, we assessed the biological effects of OA-related changes in the synovial microenvironment on chondrocytes embedded within anatomically intact cartilage from joints with different pathological grades by next generation RNA-sequencing (RNA-seq). We determined the transcriptome of primary articular chondrocytes derived from pristine knees and ankles, as well as from joints affected by OA. The GALAXY bioinformatics platform was used to facilitate biological interpretations. Comparisons of patient samples by k-means, hierarchical clustering and principal component analysis reveal that primary chondrocytes exhibit OA grade-related differences in gene expression, including genes involved in cell-adhesion, ECM production and immune response. We conclude that diseased synovial microenvironments in joints with different histopathological OA grades directly alter gene expression in chondrocytes. One ramification of this finding is that sampling anatomically intact cartilage from OA joints is not an ideal source of healthy chondrocytes, nor should they be used to generate a normal baseline for the molecular characterization of diseased joints. PMID:27378743

  6. Cell expansion of human articular chondrocytes on macroporous gelatine scaffolds-impact of microcarrier selection on cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Pettersson, Sofia; Kratz, Gunnar [Laboratory for Reconstructive Plastic Surgery, Department of Clinical and Experimental Medicine, Linkoeping University, SE-581 85 Linkoeping (Sweden); Wetteroe, Jonas [Rheumatology/AIR, Department of Clinical and Experimental Medicine, Linkoeping University, SE-581 85 Linkoeping (Sweden); Tengvall, Pentti, E-mail: sofia.pettersson@liu.se [Institute of Clinical Sciences, Department of Biomaterials, The Sahlgrenska Academy at University of Gothenburg, SE-405 30 Gothenburg (Sweden)

    2011-12-15

    This study investigates human chondrocyte expansion on four macroporous gelatine microcarriers (CultiSpher) differing with respect to two manufacturing processes-the amount of emulsifier used during initial preparation and the gelatine cross-linking medium. Monolayer-expanded articular chondrocytes from three donors were seeded onto the microcarriers and cultured in spinner flask systems for a total of 15 days. Samples were extracted every other day to monitor cell viability and establish cell counts, which were analysed using analysis of variance and piecewise linear regression. Chondrocyte densities increased according to a linear pattern for all microcarriers, indicating an ongoing, though limited, cell proliferation. A strong chondrocyte donor effect was seen during the initial expansion phase. The final cell yield differed significantly between the microcarriers and our results indicate that manufacturing differences affected chondrocyte densities at this point. Remaining cells stained positive for chondrogenic markers SOX-9 and S-100 but extracellular matrix formation was modest to undetectable. In conclusion, the four gelatine microcarriers supported chondrocyte adhesion and proliferation over a two week period. The best yield was observed for microcarriers produced with low emulsifier content and cross-linked in water and acetone. These results add to the identification of optimal biomaterial parameters for specific cellular processes and populations.

  7. Intra-articular lignocaine versus intravenous analgesia with or without sedation for manual reduction of acute anterior shoulder dislocation in adults.

    LENUS (Irish Health Repository)

    Wakai, Abel

    2012-01-31

    BACKGROUND: There is conflicting evidence regarding the use of intra-articular lignocaine injection for the closed manual reduction of acute anterior shoulder dislocations. A systematic review may help cohere the conflicting evidence. OBJECTIVES: To compare the clinical efficacy and safety of intra-articular lignocaine and intravenous analgesia (with or without sedation) for reduction of acute anterior shoulder dislocation. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 1), MEDLINE (1950 to March 2010), and EMBASE (1980 to March 2010). We searched Current Controlled Trials metaRegister of Clinical Trials (compiled by Current Science) (March 2010). We imposed no language restriction. SELECTION CRITERIA: Randomized controlled trials comparing intra-articular lignocaine (IAL) with intravenous analgesia with or without sedation (IVAS) in adults aged 18 years and over for reduction of acute anterior shoulder dislocation. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. Where possible, data were pooled and relative risks (RR) and mean differences (MD), each with 95% confidence intervals (CI), were computed using the Cochrane Review Manager statistical package (RevMan). MAIN RESULTS: Of 1041 publications obtained from the search strategy, we examined nine studies. Four studies were excluded, and five studies with 211 participants were eligible for inclusion. There was no difference in the immediate success rate of IAL when compared with IVAS in the closed manual reduction of acute anterior shoulder dislocation (RR 0.95; 95% CI 0.83 to 1.10). There were significantly fewer adverse effects associated with IAL compared with IVAS (RR 0.16; 95% CI 0.06 to 0.43). The mean time spent in the emergency department was significantly less with IAL compared with IVAS (MD 109.46 minutes; 95% CI 84.60 to 134.32). One trial reported significantly less time for

  8. The distribution of YKL-40 in osteoarthritic and normal human articular cartilage

    DEFF Research Database (Denmark)

    Volck, B; Ostergaard, K; Johansen, J S

    1999-01-01

    YKL-40, also called human cartilage glycoprotein-39, is a major secretory protein of human chondrocytes in cell culture. YKL-40 mRNA is expressed by cartilage from patients with rheumatoid arthritis, but is not detectable in normal human cartilage. The aim was to investigate the distribution of YKL...... in chondrocytes of osteoarthritic cartilage mainly in the superficial and middle zone of the cartilage rather than the deep zone. There was a tendency for high number of YKL-40 positive chondrocytes in areas of the femoral head with a considerable biomechanical load. The number of chondrocytes with a positive...

  9. Micromass co-culture of human articular chondrocytes and human bone marrow mesenchymal stem cells to investigate stable neocartilage tissue formation in vitro

    Directory of Open Access Journals (Sweden)

    S Giovannini

    2010-10-01

    Full Text Available Cell therapies for articular cartilage defects rely on expanded chondrocytes. Mesenchymal stem cells (MSC represent an alternative cell source should their hypertrophic differentiation pathway be prevented. Possible cellular instruction between human articular chondrocytes (HAC and human bone marrow MSC was investigated in micromass pellets. HAC and MSC were mixed in different percentages or incubated individually in pellets for 3 or 6 weeks with and without TGF-beta1 and dexamethasone (±T±D as chondrogenic factors. Collagen II, collagen X and S100 protein expression were assessed using immunohistochemistry. Proteoglycan synthesis was evaluated applying the Bern score and quantified using dimethylmethylene blue dye binding assay. Alkaline phosphatase activity (ALP was detected on cryosections and soluble ALP measured in pellet supernatants. HAC alone generated hyaline-like discs, while MSC formed spheroid pellets in ±T±D. Co-cultured pellets changed from disc to spheroid shape with decreasing number of HAC, and displayed random cell distribution. In -T-D, HAC expressed S100, produced GAG and collagen II, and formed lacunae, while MSC did not produce any cartilage-specific proteins. Based on GAG, collagen type II and S100 expression chondrogenic differentiation occurred in -T-D MSC co-cultures. However, quantitative experimental GAG and DNA values did not differ from predicted values, suggesting only HAC contribution to GAG production. MSC produced cartilage-specific matrix only in +T+D but underwent hypertrophy in all pellet cultures. In summary, influence of HAC on MSC was restricted to early signs of neochondrogenesis. However, MSC did not contribute to the proteoglycan deposition, and HAC could not prevent hypertrophy of MSC induced by chondrogenic stimuli.

  10. Articular cartilage explant culture; an appropriate in vitro system to compare osteoarthritic and normal human cartilage

    NARCIS (Netherlands)

    Lafeber, F. P.; Vander Kraan, P. M.; van Roy, J. L.; Huber-Bruning, O.; Bijlsma, J. W.

    1993-01-01

    Proteoglycan metabolism of normal and histologically mild to moderate osteoarthritic cartilage explants were studied. Explants were obtained from the human knee of donors aged over 40 years. Proteoglycan content, synthesis and release were very similar in normal cartilage obtained from donors with

  11. Chondrogenic Differentiation of Human Adipose-Derived Stem Cells: A New Path in Articular Cartilage Defect Management?

    Directory of Open Access Journals (Sweden)

    Jan-Philipp Stromps

    2014-01-01

    Full Text Available According to data published by the Centers for Disease Control and Prevention, over 6 million people undergo a variety of medical procedures for the repair of articular cartilage defects in the U.S. each year. Trauma, tumor, and age-related degeneration can cause major defects in articular cartilage, which has a poor intrinsic capacity for healing. Therefore, there is substantial interest in the development of novel cartilage tissue engineering strategies to restore articular cartilage defects to a normal or prediseased state. Special attention has been paid to the expansion of chondrocytes, which produce and maintain the cartilaginous matrix in healthy cartilage. This review summarizes the current efforts to generate chondrocytes from adipose-derived stem cells (ASCs and provides an outlook on promising future strategies.

  12. Revisiting spatial distribution and biochemical composition of calcium-containing crystals in human osteoarthritic articular cartilage.

    OpenAIRE

    Nguyen, C.; Bazin, D.; Daudon, M.; Chatron-Colliet, A.; Hannouche, D.; Bianchi, A.; Côme, D.; So, A.; Busso, N.; Lioté, F.; Ea, H.K.

    2013-01-01

    International audience; INTRODUCTION: Calcium-containing (CaC) crystals, including basic calcium phosphate (BCP) and calcium pyrophosphate dihydrate (CPP), are associated with destructive forms of osteoarthritis (OA). We assessed their distribution and biochemical and morphologic features in human knee OA cartilage. METHODS: We prospectively included 20 patients who underwent total knee replacement (TKR) for primary OA. CaC crystal characterization and identification involved Fourier-transfor...

  13. In vivo human adipose-derived mesenchymal stem cell tracking after intra-articular delivery in a rat osteoarthritis model

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    Meng Li

    2016-11-01

    Full Text Available Abstract Background Human adipose-derived mesenchymal stem cells (haMSCs have shown efficacy in treating osteoarthritis (OA both preclinically and clinically via intra-articular (IA injection. However, understanding the mode of action of the cell therapy has been limited by cell tracking capability and correlation between the pharmacokinetics of the injected cells and the intended pharmacodynamics effect. This study aims to explore methodology and to understand in vivo biodistribution of clinical-grade haMSCs labeled with fluorescent dye and injected into an immunocompetent OA rat model. Methods haMSCs labeled with fluorescent dye were investigated for their proliferation and differentiation capabilities. Labeled cells were used to establish detection threshold of a noninvasive biofluorescent imaging system before the cells (2.5 × 106 were injected into a conventional rat OA model induced by medial meniscectomy for 8 weeks. We attempted to reveal the existence of labeled cells in vivo by imaging and a molecular biomarker approach, and to correlate with the in vivo efficacy and physical presence over a follow-up period up to 10 weeks. Results In vitro proliferation and differentiation of haMSCs were not affected by the labeling of DiD dye. Detection thresholds of the labeled cells in vitro and in vivo were determined to be 104 and 105 cells, respectively. When 2.5 × 106 haMSCs were injected into the joints of a rat OA model, fluorescent signals (or >105 cells lasted for about 10 weeks in the surgical knee joint at the same time as efficacy was observed. Signals in nonsurgical rats only lasted for 4 weeks. The human MSCs were shown to engraft to the rat joint tissues and were proliferative. Human FOXP2 gene was only detected in the knee joint tissue, suggesting limited biodistribution locally to the joints. Conclusions The current study represents the first attempt to correlate cell therapy efficacy on OA with the physical presence

  14. Articular cartilage repair with recombinant human type II collagen/polylactide scaffold in a preliminary porcine study.

    Science.gov (United States)

    Muhonen, Virpi; Salonius, Eve; Haaparanta, Anne-Marie; Järvinen, Elina; Paatela, Teemu; Meller, Anna; Hannula, Markus; Björkman, Mimmi; Pyhältö, Tuomo; Ellä, Ville; Vasara, Anna; Töyräs, Juha; Kellomäki, Minna; Kiviranta, Ilkka

    2016-05-01

    The purpose of this study was to investigate the potential of a novel recombinant human type II collagen/polylactide scaffold (rhCo-PLA) in the repair of full-thickness cartilage lesions with autologous chondrocyte implantation technique (ACI). The forming repair tissue was compared to spontaneous healing (spontaneous) and repair with a commercial porcine type I/III collagen membrane (pCo). Domestic pigs (4-month-old, n = 20) were randomized into three study groups and a circular full-thickness chondral lesion with a diameter of 8 mm was created in the right medial femoral condyle. After 3 weeks, the chondral lesions were repaired with either rhCo-PLA or pCo together with autologous chondrocytes, or the lesion was only debrided and left untreated for spontaneous repair. The repair tissue was evaluated 4 months after the second operation. Hyaline cartilage formed most frequently in the rhCo-PLA treatment group. Biomechanically, there was a trend that both treatment groups resulted in better repair tissue than spontaneous healing. Adverse subchondral bone reactions developed less frequently in the spontaneous group (40%) and the rhCo-PLA treated group (50%) than in the pCo control group (100%). However, no statistically significant differences were found between the groups. The novel rhCo-PLA biomaterial showed promising results in this proof-of-concept study, but further studies will be needed in order to determine its effectiveness in articular cartilage repair. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:745-753, 2016. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  15. Redifferentiation of in vitro expanded adult articular chondrocytes by combining the hanging-drop cultivation method with hypoxic environment.

    Science.gov (United States)

    Martinez, Inigo; Elvenes, Jan; Olsen, Randi; Bertheussen, Kjell; Johansen, Oddmund

    2008-01-01

    The main purpose of this work has been to establish a new culturing technique to improve the chondrogenic commitment of isolated adult human chondrocytes, with the aim of being used during cell-based therapies or tissue engineering strategies. By using a rather novel technique to generate scaffold-free three-dimensional (3D) structures from in vitro expanded chondrocytes, we have explored the effects of different culture environments on cartilage formation. Three-dimensional chondrospheroids were developed by applying the hanging-drop technique. Cartilage tissue formation was attempted after combining critical factors such as serum-containing or serum-free media and atmospheric (20%) or low (2.5%) oxygen tensions. The quality of the formed microtissues was analyzed by histology, immunohistochemistry, electron microscopy, and real-time PCR, and directly compared with native adult cartilage. Our results revealed highly organized, 3D tissue-like structures developed by the hanging-drop method. All culture conditions allowed formation of 3D spheroids; however, cartilage generated under low oxygen tension had a bigger size, enhanced matrix deposition, and higher quality of cartilage formation. Real-time PCR demonstrated enhanced expression of cartilage-specific genes such us collagen type II and aggrecan in 3D cultures when compared to monolayers. Cartilage-specific matrix proteins and genes expressed in hanging-drop-developed spheroids were comparable to the expression obtained by applying the pellet culture system. In summary, our results indicate that a combination of 3D cultures of chondrocytes in hanging drops and a low oxygen environment represent an easy and convenient way to generate cartilage-like microstructures. We also show that a new specially tailored serum-free medium is suitable for in vitro cartilage tissue formation. This new methodology opens up the possibility of using autogenously produced solid 3D structures with redifferentiated chondrocytes as an

  16. The effect of insulin-like growth factor I on proteoglycan metabolism in immature and adult bovine articular cartilage

    International Nuclear Information System (INIS)

    Barone-Varelas, J.

    1989-01-01

    Explants of articular cartilage from calf (15 weeks old) and steer (18-24 months old) were cultured for up to 19 days in medium containing either insulin-like growth factor (IGF-I) or 20% fetal bovine serum (FBS). Explants cultured in medium alone were controls. 35 S-proteoglycans (PGs) synthesized on day 7 of culture during a 5-hour pulse with 35 S-sulfate were isolated, quantified and characterized. Lower concentrations of IGF-I were required for maximal stimulation of PG synthesis in calf than in steer (10 vs 20 ng/ml). In calf, IGF-I was as effective as 20% FABS in stimulating PG synthesis. In steer, PG synthesis in the presence of IGF-I reached its maximum at a rate that was half that obtained with 20% FBS. The stimulation by IGF-I or FBS was not accompanied at either age by alterations in the size and composition of the aggregating PGs nor by changes in the relative proportions of the CS-rich and CS-poor PG subpopulations. Importantly, the newly synthesized calf and steer PGs retained marked age-related differences in composition regardless of the culture conditions. The effects of exogenously added IGF-I and FBS on the rate of turnover of cartilage PGs was also studied. In calf, IGF-I and FBS did not significantly alter the rate of turnover of either the 35 S-PGs synthesized in vitro or of the unlabeled PGs representing mostly molecules synthesize and organized into the matrix in vivo. In steer, explants cultured in the absence of IGF-I or FBS exhibited very fast rates of turnover which resulted in severe depletion of matrix PG with time. Importantly, IGF-I and FBS were equally effective in reducing the turnover rate of 35 S-PGs and unlabeled PGs and in preventing PG depletion. These results demonstrate age-related differences in the effect of IGF-I on PG synthesis by articular chondrocytes

  17. Aging and oxidative stress reduce the response of human articular chondrocytes to insulin-like growth factor 1 and osteogenic protein 1.

    Science.gov (United States)

    Loeser, Richard F; Gandhi, Uma; Long, David L; Yin, Weihong; Chubinskaya, Susan

    2014-08-01

    To determine the effects of aging and oxidative stress on the response of human articular chondrocytes to insulin-like growth factor 1 (IGF-1) and osteogenic protein 1 (OP-1). Chondrocytes isolated from normal articular cartilage obtained from tissue donors were cultured in alginate beads or monolayer. Cells were stimulated with 50-100 ng/ml of IGF-1, OP-1, or both. Oxidative stress was induced using tert-butyl hydroperoxide. Sulfate incorporation was used to measure proteoglycan synthesis, and immunoblotting of cell lysates was performed to analyze cell signaling. Confocal microscopy was performed to measure nuclear translocation of Smad4. Chondrocytes isolated from the articular cartilage of tissue donors ranging in age from 24 years to 81 years demonstrated an age-related decline in proteoglycan synthesis stimulated by IGF-1 and IGF-1 plus OP-1. Induction of oxidative stress inhibited both IGF-1- and OP-1-stimulated proteoglycan synthesis. Signaling studies showed that oxidative stress inhibited IGF-1-stimulated Akt phosphorylation while increasing phosphorylation of ERK, and that these effects were greater in cells from older donors. Oxidative stress also increased p38 phosphorylation, which resulted in phosphorylation of Smad1 at the Ser(206) inhibitory site and reduced nuclear accumulation of Smad1. Oxidative stress also modestly reduced OP-1-stimulated nuclear translocation of Smad4. These results demonstrate an age-related reduction in the response of human chondrocytes to IGF-1 and OP-1, which are 2 important anabolic factors in cartilage, and suggest that oxidative stress may be a contributing factor by altering IGF-1 and OP-1 signaling. Copyright © 2014 by the American College of Rheumatology.

  18. An in vitro comparative study of T2 and T2* mappings of human articular cartilage at 3-Tesla MRI using histology as the standard of reference

    International Nuclear Information System (INIS)

    Kim, Taehee; Park, Sunghoon; Min, Byoung-Hyun; Yoon, Seung-Hyun; Kim, Hakil; Lee, Hyun Young; Kwack, Kyu-Sung

    2014-01-01

    The aim of this study was to evaluate the correlations between T2 value, T2* value, and histological grades of degenerated human articular cartilage. T2 mapping and T2* mapping of nine tibial osteochondral specimens were obtained using a 3-T MRI after total knee arthroplasty. A total of 94 ROIs were analyzed. Histological grades were assessed using the David-Vaudey scale. Spearman's rho correlation analysis and Pearson's correlation analysis were performed. The mean relaxation values in T2 map with different histological grades (0, 1, 2) of the cartilage were 51.9 ± 9.2 ms, 55.8 ± 12.8 ms, and 59.6 ± 10.2 ms, respectively. The mean relaxation values in T2* map with different histological grades (0, 1, 2) of the cartilage were 20.3 ± 10.3 ms, 21.1 ± 12.4 ms, and 15.4 ± 8.5 ms, respectively. Spearman's rho correlation analysis confirmed a positive correlation between T2 value and histological grade (ρ = 0.313, p < 0.05). Pearson's correlation analysis revealed a significant negative correlation between T2 and T2* (r = -0.322, p < 0.05). Although T2* values showed a decreasing trend with an increase in cartilage degeneration, this correlation was not statistically significant in this study (ρ = -0.192, p = 0.129). T2 mapping was correlated with histological degeneration, and it may be a good biomarker for osteoarthritis in human articular cartilage. However, the strength of the correlation was weak (ρ = 0.313). Although T2* values showed a decreasing trend with an increase in cartilage degeneration, the correlation was not statistically significant. Therefore, T2 mapping may be more appropriate for the initial diagnosis of articular cartilage degeneration in the knee joint. Further studies on T2* mapping are needed to confirm its reliability and mechanism in cartilage degeneration. (orig.)

  19. Developmentally inspired programming of adult human mesenchymal stromal cells toward stable chondrogenesis.

    Science.gov (United States)

    Occhetta, Paola; Pigeot, Sebastien; Rasponi, Marco; Dasen, Boris; Mehrkens, Arne; Ullrich, Thomas; Kramer, Ina; Guth-Gundel, Sabine; Barbero, Andrea; Martin, Ivan

    2018-05-01

    It is generally accepted that adult human bone marrow-derived mesenchymal stromal cells (hMSCs) are default committed toward osteogenesis. Even when induced to chondrogenesis, hMSCs typically form hypertrophic cartilage that undergoes endochondral ossification. Because embryonic mesenchyme is obviously competent to generate phenotypically stable cartilage, it is questioned whether there is a correspondence between mesenchymal progenitor compartments during development and in adulthood. Here we tested whether forcing specific early events of articular cartilage development can program hMSC fate toward stable chondrogenesis. Inspired by recent findings that spatial restriction of bone morphogenetic protein (BMP) signaling guides embryonic progenitors toward articular cartilage formation, we hypothesized that selective inhibition of BMP drives the phenotypic stability of hMSC-derived chondrocytes. Two BMP type I receptor-biased kinase inhibitors were screened in a microfluidic platform for their time- and dose-dependent effect on hMSC chondrogenesis. The different receptor selectivity profile of tested compounds allowed demonstration that transient blockade of both ALK2 and ALK3 receptors, while permissive to hMSC cartilage formation, is necessary and sufficient to maintain a stable chondrocyte phenotype. Remarkably, even upon compound removal, hMSCs were no longer competent to undergo hypertrophy in vitro and endochondral ossification in vivo, indicating the onset of a constitutive change. Our findings demonstrate that adult hMSCs effectively share properties of embryonic mesenchyme in the formation of transient but also of stable cartilage. This opens potential pharmacological strategies to articular cartilage regeneration and more broadly indicates the relevance of developmentally inspired protocols to control the fate of adult progenitor cell systems.

  20. STUDY OF THE MORPHOLOGIC AND MORPHOMETRIC PATTERNS OF TALAR ARTICULAR FACETS ON DRY ADULT CALCANEAL BONES IN SOUTH-EASTERN NIGERIAN POPULATION. Estudio de los patrones morfológicos y morfométricos de las facetas articulares talares en huesos calcaneos a

    Directory of Open Access Journals (Sweden)

    Ukoha Ukoha

    2017-08-01

    Full Text Available Background: Calcaneum is the largest and longest tarsal bone in the foot and forms the prominence of the heel. Objective: The aim of the study was to observe the variations in the morphology and morphometry of the talar articular facets on the superior surface of human calcanei in South-Eastern Nigeria. Materials and Methods: The study was carried out on 220 adult non-pathological dry calcanei of unknown sex from bone banks of various medical colleges in South-Eastern Nigeria. Each calcaneum was examined for various patterns of articulating facets. Results: Pattern 1 was 55.4% of the studied population, Pattern II 7.7%, Pattern III 12.7% and Pattern IV 24%. The oval shape was 52.86% and 64.39% in the anterior and middle talar articular facets respectively, oval and convex was 70% in the posterior facet and the elongated shape was 63.12% in the fused anterior and middle facet with elongated oval 27.87% in subtype 2 and elongated constricted 35.25% in subtype 1. The length of the calcanei was recorded at a mean±SD of 7.10±0.70cm (left side and 7.01±0.72cm (right side. The width was 2.77±0.38cm (left side and 2.77±0.37cm (right side. The distance between the anterior and middle facets was 0.50±0.15cm (left side and 0.48±0.15cm (right side; the posterior and middle facets at 0.59±0.20cm (left side and 0.56±0.17cm (right side and that between the anterior and posterior facets at 1.43±0.27cm (left side and 1.42±0.29cm (right side. Conclusion: A good knowledge of the calcaneal facet pattern and shape may be useful in forensic medicine. Antecedentes: El calcáneo es el hueso tarsiano más largo y más largo del pie y forma la prominencia del talón. El tercio medio de la superficie superior del calcáneo proporciona una faceta articular para el hueso del talud. Objetivo: El estudio busca observar las variaciones en la morfología y morfometría de las facetas articulares del talar en la superficie superior de huesos calcánicos secos de

  1. Imaging of articular cartilage

    Directory of Open Access Journals (Sweden)

    Bhawan K Paunipagar

    2014-01-01

    Full Text Available We tried to review the role of magnetic resonance imaging (MRI in understanding microscopic and morphologic structure of the articular cartilage. The optimal protocols and available spin-echo sequences in present day practice are reviewed in context of common pathologies of articular cartilage. The future trends of articular cartilage imaging have been discussed with their appropriateness. In diarthrodial joints of the body, articular cartilage is functionally very important. It is frequently exposed to trauma, degeneration, and repetitive wear and tear. MRI has played a vital role in evaluation of articular cartilage. With the availability of advanced repair surgeries for cartilage lesions, there has been an increased demand for improved cartilage imaging techniques. Recent advances in imaging strategies for native and postoperative articular cartilage open up an entirely new approach in management of cartilage-related pathologies.

  2. Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial.

    Science.gov (United States)

    Mumme, Marcus; Barbero, Andrea; Miot, Sylvie; Wixmerten, Anke; Feliciano, Sandra; Wolf, Francine; Asnaghi, Adelaide M; Baumhoer, Daniel; Bieri, Oliver; Kretzschmar, Martin; Pagenstert, Geert; Haug, Martin; Schaefer, Dirk J; Martin, Ivan; Jakob, Marcel

    2016-10-22

    Articular cartilage injuries have poor repair capacity, leading to progressive joint damage, and cannot be restored predictably by either conventional treatments or advanced therapies based on implantation of articular chondrocytes. Compared with articular chondrocytes, chondrocytes derived from the nasal septum have superior and more reproducible capacity to generate hyaline-like cartilage tissues, with the plasticity to adapt to a joint environment. We aimed to assess whether engineered autologous nasal chondrocyte-based cartilage grafts allow safe and functional restoration of knee cartilage defects. In a first-in-human trial, ten patients with symptomatic, post-traumatic, full-thickness cartilage lesions (2-6 cm 2 ) on the femoral condyle or trochlea were treated at University Hospital Basel in Switzerland. Chondrocytes isolated from a 6 mm nasal septum biopsy specimen were expanded and cultured onto collagen membranes to engineer cartilage grafts (30 × 40 × 2 mm). The engineered tissues were implanted into the femoral defects via mini-arthrotomy and assessed up to 24 months after surgery. Primary outcomes were feasibility and safety of the procedure. Secondary outcomes included self-assessed clinical scores and MRI-based estimation of morphological and compositional quality of the repair tissue. This study is registered with ClinicalTrials.gov, number NCT01605201. The study is ongoing, with an approved extension to 25 patients. For every patient, it was feasible to manufacture cartilaginous grafts with nasal chondrocytes embedded in an extracellular matrix rich in glycosaminoglycan and type II collagen. Engineered tissues were stable through handling with forceps and could be secured in the injured joints. No adverse reactions were recorded and self-assessed clinical scores for pain, knee function, and quality of life were improved significantly from before surgery to 24 months after surgery. Radiological assessments indicated variable degrees of

  3. The Variations in Calcaneal Articular Facets In North Indian Population and its Clinical Implication

    Directory of Open Access Journals (Sweden)

    Seema

    2012-01-01

    Full Text Available Aims and Objectives- To know the most common type of calcanei in North Indian population and itsclinical importance. There are three articular facets on superior surface of calcaneus- anterior, middle andposterior. Three types of calcanei are noted according to number and arrangement of the articular facets-type A, B and C. Methodology - The present studywas done on 300 dry adult human calcanei of unknownsex taken from Department of Anatomy Sri Guru Ram Das Institute of Medical Sciences and ResearchVallah (Amritsar. Results- In our study Type B was found as the most common type. Type A is the nextmost common. Interpretation- The talocalcaneal joint is important in arthritis and coalition, flat foot, valgus deformity, congenital anomalies and intra articular fractures.

  4. An in vitro comparative study of T2 and T2* mappings of human articular cartilage at 3-Tesla MRI using histology as the standard of reference

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Taehee; Park, Sunghoon [Ajou University School of Medicine, Department of Radiology, Suwon (Korea, Republic of); Ajou University Medical Center, Musculoskeletal Imaging Laboratory, Suwon (Korea, Republic of); Min, Byoung-Hyun [Ajou University School of Medicine, Department of Orthopaedic Surgery, Suwon (Korea, Republic of); Ajou University School of Medicine, Cartilage Regeneration Center, Suwon (Korea, Republic of); Yoon, Seung-Hyun [Ajou University School of Medicine, Cartilage Regeneration Center, Suwon (Korea, Republic of); Kim, Hakil [INHA University, School of Information and Communication Engineering, Incheon (Korea, Republic of); Lee, Hyun Young [Ajou University Medical Center, Regional Clinical Trial Center, Suwon (Korea, Republic of); Yonsei University College of Medicine, Department of Biostatistics, Seoul (Korea, Republic of); Kwack, Kyu-Sung [Ajou University School of Medicine, Department of Radiology, Suwon (Korea, Republic of); Ajou University Medical Center, Musculoskeletal Imaging Laboratory, Suwon (Korea, Republic of); Ajou University School of Medicine, Cartilage Regeneration Center, Suwon (Korea, Republic of)

    2014-07-15

    The aim of this study was to evaluate the correlations between T2 value, T2* value, and histological grades of degenerated human articular cartilage. T2 mapping and T2* mapping of nine tibial osteochondral specimens were obtained using a 3-T MRI after total knee arthroplasty. A total of 94 ROIs were analyzed. Histological grades were assessed using the David-Vaudey scale. Spearman's rho correlation analysis and Pearson's correlation analysis were performed. The mean relaxation values in T2 map with different histological grades (0, 1, 2) of the cartilage were 51.9 ± 9.2 ms, 55.8 ± 12.8 ms, and 59.6 ± 10.2 ms, respectively. The mean relaxation values in T2* map with different histological grades (0, 1, 2) of the cartilage were 20.3 ± 10.3 ms, 21.1 ± 12.4 ms, and 15.4 ± 8.5 ms, respectively. Spearman's rho correlation analysis confirmed a positive correlation between T2 value and histological grade (ρ = 0.313, p < 0.05). Pearson's correlation analysis revealed a significant negative correlation between T2 and T2* (r = -0.322, p < 0.05). Although T2* values showed a decreasing trend with an increase in cartilage degeneration, this correlation was not statistically significant in this study (ρ = -0.192, p = 0.129). T2 mapping was correlated with histological degeneration, and it may be a good biomarker for osteoarthritis in human articular cartilage. However, the strength of the correlation was weak (ρ = 0.313). Although T2* values showed a decreasing trend with an increase in cartilage degeneration, the correlation was not statistically significant. Therefore, T2 mapping may be more appropriate for the initial diagnosis of articular cartilage degeneration in the knee joint. Further studies on T2* mapping are needed to confirm its reliability and mechanism in cartilage degeneration. (orig.)

  5. Anatomical study of the articular branches innervated the hip and knee joint with reference to mechanism of referral pain in hip joint disease patients.

    Science.gov (United States)

    Sakamoto, Junya; Manabe, Yoshitaka; Oyamada, Joichi; Kataoka, Hideki; Nakano, Jiro; Saiki, Kazunobu; Okamoto, Keishi; Tsurumoto, Toshiyuki; Okita, Minoru

    2018-03-25

    Referred pain in the anterior knee joint is the most common symptom in hip disease patients. The development of referred pain is considered to be related to dichotomizing peripheral sensory fibers. However, no gross anatomical findings identify any dichotomizing fibers innervating both the hip and knee joints. We dissected the femoral and obturator nerves in human cadavers to investigate the distribution of the articular branches in the hip and knee joints. Fourteen embalmed left lower limbs from 14 Japanese adult cadavers (five from females, nine from males, average age 73.8 ± 14.1 years) were observed macroscopically. The articular branches of the femoral and obturator nerves were dissected at the anterior margin of the groin toward the thigh region. After dissections of the articular nerves of the hip joints, the femoral and obturator nerves were exposed from proximally to distally to identify the articular nerves of the knee joints. The branching pattern of the articular branches in the hip and knee joints was recorded. In six of 14 limbs (42.9%), the femoral nerve supplied articular branches to the anteromedial aspect of both the hip and knee joints. These articular branches were derived from the same bundle of femoral nerve. These gross anatomical findings suggested that dichotomizing peripheral sensory fibers innervate the hip and knee joints and these could relate to the referred pain confirmed in the anterior knee joints of patients with hip disease. Clin. Anat., 2018. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

  6. Topographic variation in redifferentiation capacity of chondrocytes in the adult human knee joint.

    Science.gov (United States)

    Stenhamre, H; Slynarski, K; Petrén, C; Tallheden, T; Lindahl, A

    2008-11-01

    The aim of this study was to investigate the topographic variation in matrix production and cell density in the adult human knee joint. Additionally, we have examined the redifferentiation potential of chondrocytes expanded in vitro from the different locations. Full thickness cartilage-bone biopsies were harvested from seven separate anatomical locations of healthy knee joints from deceased adult human donors. Chondrocytes were isolated, expanded in vitro and redifferentiated in a pellet mass culture. Biochemical analysis of total collagen, proteoglycans and cellular content as well as histology and immunohistochemistry were performed on biopsies and pellets. In the biochemical analysis of the biopsies, we found lower proteoglycan to collagen (GAG/HP) ratio in the non-weight bearing (NWB) areas compared to the weight bearing (WB) areas. The chondrocytes harvested from different locations in femur showed a significantly better attachment and proliferation ability as well as good post-expansion chondrogenic capacity in pellet mass culture compared with the cells harvested from tibia. These results demonstrate that there are differences in extra cellular content within the adult human knee in respect to GAG/HP ratio. Additionally, the data show that clear differences between chondrocytes harvested from femur and tibia from healthy human knee joints exist and that the differences are not completely abolished during the process of de- and redifferentiation. These findings emphasize the importance of the understanding of topographic variation in articular cartilage biology when approaching new cartilage repair strategies.

  7. Articular Cartilage of the Human Knee Joint: In Vivo Multicomponent T2 Analysis at 3.0 T

    Science.gov (United States)

    Choi, Kwang Won; Samsonov, Alexey; Spencer, Richard G.; Wilson, John J.; Block, Walter F.; Kijowski, Richard

    2015-01-01

    Purpose To compare multicomponent T2 parameters of the articular cartilage of the knee joint measured by using multicomponent driven equilibrium single-shot observation of T1 and T2 (mcDESPOT) in asymptomatic volunteers and patients with osteoarthritis. Materials and Methods This prospective study was performed with institutional review board approval and with written informed consent from all subjects. The mcDESPOT sequence was performed in the knee joint of 13 asymptomatic volunteers and 14 patients with osteoarthritis of the knee. Single-component T2 (T2Single), T2 of the fast-relaxing water component (T2F) and of the slow-relaxing water component (T2S), and the fraction of the fast-relaxing water component (FF) of cartilage were measured. Wilcoxon rank-sum tests and multivariate linear regression models were used to compare mcDESPOT parameters between volunteers and patients with osteoarthritis. Receiver operating characteristic analysis was used to assess diagnostic performance with mcDESPOT parameters for distinguishing morphologically normal cartilage from morphologically degenerative cartilage identified at magnetic resonance imaging in eight cartilage subsections of the knee joint. Results Higher cartilage T2Single (P cartilage FF (P cartilage T2F (P = .079) and T2S (P = .124) values were seen in patients with osteoarthritis compared with those in asymptomatic volunteers. Differences in T2Single and FF remained significant (P cartilage (P cartilage T2Single and significantly lower cartilage FF than did asymptomatic volunteers, and receiver operating characteristic analysis results suggested that FF may allow greater diagnostic performance than that with T2Single for distinguishing between normal and degenerative cartilage. © RSNA, 2015 Online supplemental material is available for this article. PMID:26024307

  8. Activin receptor subunits in normal and dysfunctional adult human testis

    DEFF Research Database (Denmark)

    Dias, V; Meachem, S; Rajpert-De Meyts, E

    2008-01-01

    The cellular sites of activin action and its regulation in the normal and dysfunctional adult human testis are unknown.......The cellular sites of activin action and its regulation in the normal and dysfunctional adult human testis are unknown....

  9. Human platelet lysate successfully promotes proliferation and subsequent chondrogenic differentiation of adipose-derived stem cells: a comparison with articular chondrocytes.

    Science.gov (United States)

    Hildner, F; Eder, M J; Hofer, K; Aberl, J; Redl, H; van Griensven, M; Gabriel, C; Peterbauer-Scherb, A

    2015-07-01

    Fetal calf serum (FCS) bears a potential risk for carrying diseases and eliciting immune reactions. Nevertheless, it still represents the gold standard as medium supplement in cell culture. In the present study, human platelet lysate (PL) was tested as an alternative to FCS for the expansion and subsequent chondrogenic differentiation of human adipose-derived stem cells (ASCs). ASCs were expanded with 10% FCS (group F) or 5% PL (group P). Subsequently, three-dimensional (3D) micromass pellets were created and cultured for 5 weeks in chondrogenic differentiation medium. Additionally, the de- and redifferentiation potential of human articular chondrocytes (HACs) was evaluated and compared to ASCs. Both HACs and ASCs cultured with PL showed strongly enhanced proliferation rates. Redifferentiation of HACs was possible for cells expanded up to 3.3 population doublings (PD). At this stage, PL-expanded HACs demonstrated better redifferentiation potential than FCS-expanded cells. ASCs could also be differentiated following extended passaging. Glycosaminoglycan (GAG) quantification and qRT-PCR of 10 cartilage related markers demonstrated a tendency for increased chondrogenic differentiation of PL-expanded ASCs compared to cells expanded with FCS. Histologically, collagen type II but also collagen type X was mainly present in group P. The present study demonstrates that PL strongly induces proliferation of ASCs, while the chondrogenic differentiation potential is retained. HACs also showed enhanced proliferation and even better redifferentiation when previously expanded with PL. This suggests that PL is superior to FCS as a supplement for the expansion of ASCs and HACs, particularly with regard to chondrogenic (re)differentiation. Copyright © 2013 John Wiley & Sons, Ltd.

  10. TGF-β1, GDF-5, and BMP-2 stimulation induces chondrogenesis in expanded human articular chondrocytes and marrow-derived stromal cells.

    Science.gov (United States)

    Murphy, Meghan K; Huey, Daniel J; Hu, Jerry C; Athanasiou, Kyriacos A

    2015-03-01

    Replacement of degenerated cartilage with cell-based cartilage products may offer a long-term solution to halt arthritis' degenerative progression. Chondrocytes are frequently used in cell-based FDA-approved cartilage products; yet human marrow-derived stromal cells (hMSCs) show significant translational potential, reducing donor site morbidity and maintaining their undifferentiated phenotype with expansion. This study sought to investigate the effects of transforming growth factor β1 (TGF-β1), growth/differentiation factor 5 (GDF-5), and bone morphogenetic protein 2 (BMP-2) during postexpansion chondrogenesis in human articular chondrocytes (hACs) and to compare chondrogenesis in passaged hACs with that of passaged hMSCs. Through serial expansion, chondrocytes dedifferentiated, decreasing expression of chondrogenic genes while increasing expression of fibroblastic genes. However, following expansion, 10 ng/mL TGF-β1, 100 ng/mL GDF-5, or 100 ng/mL BMP-2 supplementation during three-dimensional aggregate culture each upregulated one or more markers of chondrogenic gene expression in both hACs and hMSCs. Additionally, in both cell types, the combination of TGF-β1, GDF-5, and BMP-2 induced the greatest upregulation of chondrogenic genes, that is, Col2A1, Col2A1/Col1A1 ratio, SOX9, and ACAN, and synthesis of cartilage-specific matrix, that is, glycosaminoglycans (GAGs) and ratio of collagen II/I. Finally, TGF-β1, GDF-5, and BMP-2 stimulation yielded mechanically robust cartilage rich in collagen II and GAGs in both cell types, following 4 weeks maturation. This study illustrates notable success in using the self-assembling method to generate robust, scaffold-free neocartilage constructs using expanded hACs and hMSCs. © 2014 AlphaMed Press.

  11. Storing live embryonic and adult human cartilage grafts for transplantation using a joint simulating device.

    Science.gov (United States)

    Cohen, I; Robinson, D; Cohen, N; Nevo, Z

    2000-11-01

    Cartilage transplantation as a means to replace damaged articular surfaces is of interest. A major obstacle is the long-term preservation of cartilage grafts. The commonly used technique of freezing the grafts inevitably leads to cellular death. The current study compares the technique to an innovative approach using a pulsed-pressure perfusion system termed a joint simulating device (JSD), intended to simulate intra-articular mechanical forces. Human articular cartilage explants were harvested from both embryonic epiphyseal tissue and femoral heads of elderly women (over 70 years of age) undergoing a partial joint replacement (hemi-arthroplasty) and were divided in two groups: half of the samples were incubated in the JSD while the remaining half were grown in static culture within tissue culture plates. After 10 days all samples were evaluated for: (a) cell vitality as assessed by image analysis and XTT assay; (b) biosynthetic activity as expressed by radioactive sulfate incorporation into glycosaminoglycans (GAG's); and (c) proteoglycan content as assessed by alcian blue staining intensity. A 10-fold increase in sulfate incorporation in samples held in the JSD compared to the static culture group was observed in embryonic cartilage. In adult cartilage culture in the JSD elevated sulfate incorporation by threefold as compared to static culture. Central necrosis was observed in specimens grown in the static culture plates, while it did not occur in the samples held in the JSD. Cell vitality as assessed by XTT assay was significantly better in the JSD group as compared to static culture. The difference was more pronounced in the embryonic specimens as compared to adult cartilage. The specimens cultured within the JSD retained proteoglycans significantly better than those cultured in static culture. Maintenance of cartilage specimens in a JSD was highly effective in keeping the vitality of cartilage explants in vitro over a 10-day period. A possible future

  12. Expression of lumican related to CD34 and VEGF in the articular disc of the human temporomandibular joint.

    Directory of Open Access Journals (Sweden)

    N. Kiga

    2010-07-01

    Full Text Available Lumican belongs to the small leucine-rich repeat proteoglycan (SLRP gene family and has been reported to exist in the cornea, intervertebral disc and tendon. Lumican plays a significant role in the assembly and regulation of collagen fibres. The human temporomandibular joint (TMJ disc is made up of fibrocartilage with an extracellular matrix (ECM composed of collagen and proteoglycans. The existence and behaviour of lumican have not been studied in the human TMJ disc. Therefore, we used immunohistochemical methods to detect lumican, CD34 and vascular endothelial growth factor (VEGF and histochemical staining with toluidine blue in 13 human TMJ specimens (10 surgically removed and 3 obtained from autopsy. In both normal and deformed discs we observed staining with toluidine blue. We found that the area of metachromasia inside the deformed disc was uneven and expression of lumican was strong in the areas negative for metachromasia. Staining of VEGF and CD34 inside the deformed disc was seen. We confirmed the expression of lumican in the human TMJ disc and showed that a large number of fibroblastlike cells existed in the area of strong lumican expression. These new findings about the behaviour of lumican suggest that it may play a key role in the generation of a new collagen network by fibroblast-like cells.

  13. Contour interpolated radial basis functions with spline boundary correction for fast 3D reconstruction of the human articular cartilage from MR images

    International Nuclear Information System (INIS)

    Javaid, Zarrar; Unsworth, Charles P.; Boocock, Mark G.; McNair, Peter J.

    2016-01-01

    Purpose: The aim of this work is to demonstrate a new image processing technique that can provide a “near real-time” 3D reconstruction of the articular cartilage of the human knee from MR images which is user friendly. This would serve as a point-of-care 3D visualization tool which would benefit a consultant radiologist in the visualization of the human articular cartilage. Methods: The authors introduce a novel fusion of an adaptation of the contour method known as “contour interpolation (CI)” with radial basis functions (RBFs) which they describe as “CI-RBFs.” The authors also present a spline boundary correction which further enhances volume estimation of the method. A subject cohort consisting of 17 right nonpathological knees (ten female and seven male) is assessed to validate the quality of the proposed method. The authors demonstrate how the CI-RBF method dramatically reduces the number of data points required for fitting an implicit surface to the entire cartilage, thus, significantly improving the speed of reconstruction over the comparable RBF reconstruction method of Carr. The authors compare the CI-RBF method volume estimation to a typical commercial package (3D DOCTOR), Carr’s RBF method, and a benchmark manual method for the reconstruction of the femoral, tibial, and patellar cartilages. Results: The authors demonstrate how the CI-RBF method significantly reduces the number of data points (p-value < 0.0001) required for fitting an implicit surface to the cartilage, by 48%, 31%, and 44% for the patellar, tibial, and femoral cartilages, respectively. Thus, significantly improving the speed of reconstruction (p-value < 0.0001) by 39%, 40%, and 44% for the patellar, tibial, and femoral cartilages over the comparable RBF model of Carr providing a near real-time reconstruction of 6.49, 8.88, and 9.43 min for the patellar, tibial, and femoral cartilages, respectively. In addition, it is demonstrated how the CI-RBF method matches the volume

  14. Contour interpolated radial basis functions with spline boundary correction for fast 3D reconstruction of the human articular cartilage from MR images

    Energy Technology Data Exchange (ETDEWEB)

    Javaid, Zarrar; Unsworth, Charles P., E-mail: c.unsworth@auckland.ac.nz [Department of Engineering Science, The University of Auckland, Auckland 1010 (New Zealand); Boocock, Mark G.; McNair, Peter J. [Health and Rehabilitation Research Center, Auckland University of Technology, Auckland 1142 (New Zealand)

    2016-03-15

    Purpose: The aim of this work is to demonstrate a new image processing technique that can provide a “near real-time” 3D reconstruction of the articular cartilage of the human knee from MR images which is user friendly. This would serve as a point-of-care 3D visualization tool which would benefit a consultant radiologist in the visualization of the human articular cartilage. Methods: The authors introduce a novel fusion of an adaptation of the contour method known as “contour interpolation (CI)” with radial basis functions (RBFs) which they describe as “CI-RBFs.” The authors also present a spline boundary correction which further enhances volume estimation of the method. A subject cohort consisting of 17 right nonpathological knees (ten female and seven male) is assessed to validate the quality of the proposed method. The authors demonstrate how the CI-RBF method dramatically reduces the number of data points required for fitting an implicit surface to the entire cartilage, thus, significantly improving the speed of reconstruction over the comparable RBF reconstruction method of Carr. The authors compare the CI-RBF method volume estimation to a typical commercial package (3D DOCTOR), Carr’s RBF method, and a benchmark manual method for the reconstruction of the femoral, tibial, and patellar cartilages. Results: The authors demonstrate how the CI-RBF method significantly reduces the number of data points (p-value < 0.0001) required for fitting an implicit surface to the cartilage, by 48%, 31%, and 44% for the patellar, tibial, and femoral cartilages, respectively. Thus, significantly improving the speed of reconstruction (p-value < 0.0001) by 39%, 40%, and 44% for the patellar, tibial, and femoral cartilages over the comparable RBF model of Carr providing a near real-time reconstruction of 6.49, 8.88, and 9.43 min for the patellar, tibial, and femoral cartilages, respectively. In addition, it is demonstrated how the CI-RBF method matches the volume

  15. Human Articular Cartilage Progenitor Cells Are Responsive to Mechanical Stimulation and Adenoviral-Mediated Overexpression of Bone-Morphogenetic Protein 2.

    Directory of Open Access Journals (Sweden)

    Alexander J Neumann

    Full Text Available Articular cartilage progenitor cells (ACPCs represent a new and potentially powerful alternative cell source to commonly used cell sources for cartilage repair, such as chondrocytes and bone-marrow derived mesenchymal stem cells (MSCs. This is particularly due to the apparent resistance of ACPCs to hypertrophy. The current study opted to investigate whether human ACPCs (hACPCs are responsive towards mechanical stimulation and/or adenoviral-mediated overexpression of bone morphogenetic protein 2 (BMP-2. hACPCs were cultured in fibrin-polyurethane composite scaffolds. Cells were cultured in a defined chondro-permissive medium, lacking exogenous growth factors. Constructs were cultured, for 7 or 28 days, under free-swelling conditions or with the application of complex mechanical stimulation, using a custom built bioreactor that is able to generate joint-like movements. Outcome parameters were quantification of BMP-2 and transforming growth factor beta 1 (TGF-β1 concentration within the cell culture medium, biochemical and gene expression analyses, histology and immunohistochemistry. The application of mechanical stimulation alone resulted in the initiation of chondrogenesis, demonstrating the cells are mechanoresponsive. This was evidenced by increased GAG production, lack of expression of hypertrophic markers and a promising gene expression profile (significant up-regulation of cartilaginous marker genes, specifically collagen type II, accompanied by no increase in the hypertrophic marker collagen type X or the osteogenic marker alkaline phosphatase. To further investigate the resistance of ACPCs to hypertrophy, overexpression of a factor associated with hypertrophic differentiation, BMP-2, was investigated. A novel, three-dimensional, transduction protocol was used to transduce cells with an adenovirus coding for BMP-2. Over-expression of BMP-2, independent of load, led to an increase in markers associated with hypertropy. Taken together ACPCs

  16. NF-κB Mediates the Stimulation of Cytokine and Chemokine Expression by Human Articular Chondrocytes in Response to Fibronectin Fragments1

    Science.gov (United States)

    Pulai, Judit I.; Chen, Hong; Im, Hee-Jeong; Kumar, Sanjay; Hanning, Charles; Hegde, Priti S.; Loeser, Richard F.

    2010-01-01

    Fibronectin fragments (FN-f) that bind to the α5β1 integrin stimulate chondrocyte-mediated cartilage destruction and could play an important role in the progression of arthritis. The objective of this study was to identify potential cytokine mediators of cartilage inflammation and destruction induced by FN-f and to investigate the mechanism of their stimulation. Human articular chondrocytes, isolated from normal ankle cartilage obtained from tissue donors, were treated with a 110-kDa FN-f in serum-free culture, and expression of various cytokine genes was analyzed by cDNA microarray and by a cytokine protein array. Compared with untreated control cultures, stimulation by FN-f resulted in a >2-fold increase in IL-6, IL-8, MCP-1, and growth-related oncogene β (GRO-β). Constitutive and FN-f-inducible expression of GRO-α and GRO-γ were also noted by RT-PCR and confirmed by immunoblotting. Previous reports of IL-1β expression induced by FN-f were also confirmed, while TNF expression was found to be very low. Inhibitor studies revealed that FN-f-induced stimulation of chondrocyte chemokine expression was dependent on NF-κB activity, but independent of IL-1 autocrine signaling. The ability of FN-f to stimulate chondrocyte expression of multiple proinflammatory cytokines and chemokines suggests that damage to the cartilage matrix is capable of inducing a proinflammatory state responsible for further progressive matrix destruction, which also includes the chemoattraction of inflammatory cells. Targeting the signaling pathways activated by FN-f may be an effective means of inhibiting production of multiple mediators of cartilage destruction. PMID:15843581

  17. Clinical high-resolution mapping of the proteoglycan-bound water fraction in articular cartilage of the human knee joint.

    Science.gov (United States)

    Bouhrara, Mustapha; Reiter, David A; Sexton, Kyle W; Bergeron, Christopher M; Zukley, Linda M; Spencer, Richard G

    2017-11-01

    We applied our recently introduced Bayesian analytic method to achieve clinically-feasible in-vivo mapping of the proteoglycan water fraction (PgWF) of human knee cartilage with improved spatial resolution and stability as compared to existing methods. Multicomponent driven equilibrium single-pulse observation of T 1 and T 2 (mcDESPOT) datasets were acquired from the knees of two healthy young subjects and one older subject with previous knee injury. Each dataset was processed using Bayesian Monte Carlo (BMC) analysis incorporating a two-component tissue model. We assessed the performance and reproducibility of BMC and of the conventional analysis of stochastic region contraction (SRC) in the estimation of PgWF. Stability of the BMC analysis of PgWF was tested by comparing independent high-resolution (HR) datasets from each of the two young subjects. Unlike SRC, the BMC-derived maps from the two HR datasets were essentially identical. Furthermore, SRC maps showed substantial random variation in estimated PgWF, and mean values that differed from those obtained using BMC. In addition, PgWF maps derived from conventional low-resolution (LR) datasets exhibited partial volume and magnetic susceptibility effects. These artifacts were absent in HR PgWF images. Finally, our analysis showed regional variation in PgWF estimates, and substantially higher values in the younger subjects as compared to the older subject. BMC-mcDESPOT permits HR in-vivo mapping of PgWF in human knee cartilage in a clinically-feasible acquisition time. HR mapping reduces the impact of partial volume and magnetic susceptibility artifacts compared to LR mapping. Finally, BMC-mcDESPOT demonstrated excellent reproducibility in the determination of PgWF. Published by Elsevier Inc.

  18. Micro-Scale Distribution of CA4+ in Ex Vivo Human Articular Cartilage Detected with Contrast-Enhanced Micro-Computed Tomography Imaging

    Science.gov (United States)

    Karhula, Sakari S.; Finnilä, Mikko A.; Freedman, Jonathan D.; Kauppinen, Sami; Valkealahti, Maarit; Lehenkari, Petri; Pritzker, Kenneth P. H.; Nieminen, Heikki J.; Snyder, Brian D.; Grinstaff, Mark W.; Saarakkala, Simo

    2017-08-01

    Contrast-enhanced micro-computed tomography (CEµCT) with cationic and anionic contrast agents reveals glycosaminoglycan (GAG) content and distribution in articular cartilage (AC). The advantage of using cationic stains (e.g. CA4+) compared to anionic stains (e.g. Hexabrix®), is that it distributes proportionally with GAGs, while anionic stain distribution in AC is inversely proportional to the GAG content. To date, studies using cationic stains have been conducted with sufficient resolution to study its distributions on the macro-scale, but with insufficient resolution to study its distributions on the micro-scale. Therefore, it is not known whether the cationic contrast agents accumulate in extra/pericellular matrix and if they interact with chondrocytes. The insufficient resolution has also prevented to answer the question whether CA4+ accumulation in chondrons could lead to an erroneous quantification of GAG distribution with low-resolution µCT setups. In this study, we use high-resolution µCT to investigate whether CA4+ accumulates in chondrocytes, and further, to determine whether it affects the low-resolution ex vivo µCT studies of CA4+ stained human AC with varying degree of osteoarthritis. Human osteochondral samples were immersed in three different concentrations of CA4+ (3 mgI/ml, 6mgI/ml, and 24 mgI/ml) and imaged with high-resolution µCT at several timepoints. Different uptake diffusion profiles of CA4+ were observed between the segmented chondrons and the rest of the tissue. While the X-ray -detected CA4+ concentration in chondrons was greater than in the rest of the AC, its contribution to the uptake into the whole tissue was negligible and in line with macro-scale GAG content detected from histology. The efficient uptake of CA4+ into chondrons and surrounding territorial matrix can be explained by the micro-scale distribution of GAG content. CA4+ uptake in chondrons occurred regardless of the progression stage of osteoarthritis in the samples

  19. Micro-Scale Distribution of CA4+ in Ex vivo Human Articular Cartilage Detected with Contrast-Enhanced Micro-Computed Tomography Imaging

    Directory of Open Access Journals (Sweden)

    Sakari S. Karhula

    2017-08-01

    Full Text Available Contrast-enhanced micro-computed tomography (CEμCT with cationic and anionic contrast agents reveals glycosaminoglycan (GAG content and distribution in articular cartilage (AC. The advantage of using cationic stains (e.g., CA4+ compared to anionic stains (e.g., Hexabrix®, is that it distributes proportionally with GAGs, while anionic stain distribution in AC is inversely proportional to the GAG content. To date, studies using cationic stains have been conducted with sufficient resolution to study its distributions on the macro-scale, but with insufficient resolution to study its distributions on the micro-scale. Therefore, it is not known whether the cationic contrast agents accumulate in extra/pericellular matrix and if they interact with chondrocytes. The insufficient resolution has also prevented to answer the question whether CA4+ accumulation in chondrons could lead to an erroneous quantification of GAG distribution with low-resolution μCT setups. In this study, we use high-resolution μCT to investigate whether CA4+ accumulates in chondrocytes, and further, to determine whether it affects the low-resolution ex vivo μCT studies of CA4+ stained human AC with varying degree of osteoarthritis. Human osteochondral samples were immersed in three different concentrations of CA4+ (3 mgI/ml, 6 mgI/ml, and 24 mgI/ml and imaged with high-resolution μCT at several timepoints. Different uptake diffusion profiles of CA4+ were observed between the segmented chondrons and the rest of the tissue. While the X-ray -detected CA4+ concentration in chondrons was greater than in the rest of the AC, its contribution to the uptake into the whole tissue was negligible and in line with macro-scale GAG content detected from histology. The efficient uptake of CA4+ into chondrons and surrounding territorial matrix can be explained by the micro-scale distribution of GAG content. CA4+ uptake in chondrons occurred regardless of the progression stage of osteoarthritis

  20. Cell pattern in adult human corneal endothelium.

    Directory of Open Access Journals (Sweden)

    Carlos H Wörner

    Full Text Available A review of the current data on the cell density of normal adult human endothelial cells was carried out in order to establish some common parameters appearing in the different considered populations. From the analysis of cell growth patterns, it is inferred that the cell aging rate is similar for each of the different considered populations. Also, the morphology, the cell distribution and the tendency to hexagonallity are studied. The results are consistent with the hypothesis that this phenomenon is analogous with cell behavior in other structures such as dry foams and grains in polycrystalline materials. Therefore, its driving force may be controlled by the surface tension and the mobility of the boundaries.

  1. Intra-articular therapies for osteoarthritis.

    Science.gov (United States)

    Yu, Shirley P; Hunter, David J

    2016-10-01

    Conventional medical therapies for osteoarthritis are mainly palliative in nature, aiming to control pain and symptoms. Traditional intra-articular therapies are not recommended in guidelines as first line therapy, but are potential alternatives, when conventional therapies have failed. Current and future intra-articular drug therapies for osteoarthritis are highlighted, including corticosteroids, hyaluronate, and more controversial treatments marketed commercially, namely platelet rich plasma and mesenchymal cell therapy. Intraarticular disease modifying osteoarthritis drugs are the future of osteoarthritis treatments, aiming at structural modification and altering the disease progression. Interleukin-1β inhibitor, bone morphogenic protein-7, fibroblast growth factor 18, bradykinin B2 receptor antagonist, human serum albumin, and gene therapy are discussed in this review. The evolution of drug development in osteoarthritis is limited by the ability to demonstrate effect. High quality trials are required to justify the use of existing intra-articular therapies and to advocate for newer, promising therapies. Challenges in osteoarthritis therapy research are fundamentally related to the complexity of the pathological mechanisms of osteoarthritis. Novel drugs offer hope in a disease with limited medical therapy options. Whether these future intra-articular therapies will provide clinically meaningful benefits, remains unknown.

  2. Astrocitary niches in human adult medulla oblongata.

    Science.gov (United States)

    Rusu, Mugurel Constantin; Dermengiu, Dan; Loreto, Carla; Motoc, Andrei Gheorghe Marius; Pop, Elena

    2013-04-01

    Astrocytes are considered as neuromodulators of the CNS. Whereas experimental studies on astrocitary functions are gaining importance, the anatomy of the astrocitary niches in the human CNS has been overlooked. The study was performed on the brainstem of 10 adult cadavers. We aimed to determine astrocitary niches in the human medulla oblongata using immunohistochemical labeling with vimentin and also CD34 immunostaining to accurately diagnose associated microvessels. Niches rich in astrocytes were identified as follows: (a) the superficial layer of astrocytes, ventral and ventrolateral, in the rostral medulla oblongata; (b) the median raphe; (c) medullary nuclei: arcuate nucleus, area postrema, nucleus of the solitary tract; (d) the subependymal zone (SEZ, caudal medulla) and subventricular zone (SVZ, rostral medulla). Astrocytes were scarce in the ventrolateral medulla, and mostly present within the pyramidal tract and the olivary nucleus. Apart from the SEZ and SVZ, the brainstem niches of astrocytes mostly overlap those regions known to perform roles as central respiratory chemoreceptors. The astrocytes of the SEZ and SVZ, which are known as stem cell niches, are related to an increased microvascular density. Copyright © 2012 Elsevier GmbH. All rights reserved.

  3. Lithium Chloride Dependent Glycogen Synthase Kinase 3 Inactivation Links Oxidative DNA Damage, Hypertrophy and Senescence in Human Articular Chondrocytes and Reproduces Chondrocyte Phenotype of Obese Osteoarthritis Patients.

    Directory of Open Access Journals (Sweden)

    Serena Guidotti

    Full Text Available Recent evidence suggests that GSK3 activity is chondroprotective in osteoarthritis (OA, but at the same time, its inactivation has been proposed as an anti-inflammatory therapeutic option. Here we evaluated the extent of GSK3β inactivation in vivo in OA knee cartilage and the molecular events downstream GSK3β inactivation in vitro to assess their contribution to cell senescence and hypertrophy.In vivo level of phosphorylated GSK3β was analyzed in cartilage and oxidative damage was assessed by 8-oxo-deoxyguanosine staining. The in vitro effects of GSK3β inactivation (using either LiCl or SB216763 were evaluated on proliferating primary human chondrocytes by combined confocal microscopy analysis of Mitotracker staining and reactive oxygen species (ROS production (2',7'-dichlorofluorescin diacetate staining. Downstream effects on DNA damage and senescence were investigated by western blot (γH2AX, GADD45β and p21, flow cytometric analysis of cell cycle and light scattering properties, quantitative assessment of senescence associated β galactosidase activity, and PAS staining.In vivo chondrocytes from obese OA patients showed higher levels of phosphorylated GSK3β, oxidative damage and expression of GADD45β and p21, in comparison with chondrocytes of nonobese OA patients. LiCl mediated GSK3β inactivation in vitro resulted in increased mitochondrial ROS production, responsible for reduced cell proliferation, S phase transient arrest, and increase in cell senescence, size and granularity. Collectively, western blot data supported the occurrence of a DNA damage response leading to cellular senescence with increase in γH2AX, GADD45β and p21. Moreover, LiCl boosted 8-oxo-dG staining, expression of IKKα and MMP-10.In articular chondrocytes, GSK3β activity is required for the maintenance of proliferative potential and phenotype. Conversely, GSK3β inactivation, although preserving chondrocyte survival, results in functional impairment via

  4. Lithium Chloride Dependent Glycogen Synthase Kinase 3 Inactivation Links Oxidative DNA Damage, Hypertrophy and Senescence in Human Articular Chondrocytes and Reproduces Chondrocyte Phenotype of Obese Osteoarthritis Patients.

    Science.gov (United States)

    Guidotti, Serena; Minguzzi, Manuela; Platano, Daniela; Cattini, Luca; Trisolino, Giovanni; Mariani, Erminia; Borzì, Rosa Maria

    2015-01-01

    Recent evidence suggests that GSK3 activity is chondroprotective in osteoarthritis (OA), but at the same time, its inactivation has been proposed as an anti-inflammatory therapeutic option. Here we evaluated the extent of GSK3β inactivation in vivo in OA knee cartilage and the molecular events downstream GSK3β inactivation in vitro to assess their contribution to cell senescence and hypertrophy. In vivo level of phosphorylated GSK3β was analyzed in cartilage and oxidative damage was assessed by 8-oxo-deoxyguanosine staining. The in vitro effects of GSK3β inactivation (using either LiCl or SB216763) were evaluated on proliferating primary human chondrocytes by combined confocal microscopy analysis of Mitotracker staining and reactive oxygen species (ROS) production (2',7'-dichlorofluorescin diacetate staining). Downstream effects on DNA damage and senescence were investigated by western blot (γH2AX, GADD45β and p21), flow cytometric analysis of cell cycle and light scattering properties, quantitative assessment of senescence associated β galactosidase activity, and PAS staining. In vivo chondrocytes from obese OA patients showed higher levels of phosphorylated GSK3β, oxidative damage and expression of GADD45β and p21, in comparison with chondrocytes of nonobese OA patients. LiCl mediated GSK3β inactivation in vitro resulted in increased mitochondrial ROS production, responsible for reduced cell proliferation, S phase transient arrest, and increase in cell senescence, size and granularity. Collectively, western blot data supported the occurrence of a DNA damage response leading to cellular senescence with increase in γH2AX, GADD45β and p21. Moreover, LiCl boosted 8-oxo-dG staining, expression of IKKα and MMP-10. In articular chondrocytes, GSK3β activity is required for the maintenance of proliferative potential and phenotype. Conversely, GSK3β inactivation, although preserving chondrocyte survival, results in functional impairment via induction of

  5. Have you got any cholesterol? Adults' views of human nutrition

    Science.gov (United States)

    Schibeci, Renato; Wong, Khoon Yoong

    1994-12-01

    The general aim of our human nutrition project is to develop a health education model grounded in ‘everyday’ or ‘situated’ cognition (Hennessey, 1993). In 1993, we began pilot work to document adult understanding of human nutrition. We used a HyperCard stack as the basis for a series of interviews with 50 adults (25 university students, and 25 adults from offcampus). The interviews were transcribed and analysed using the NUDIST computer program. A summary of the views of these 50 adults on selected aspects of human nutrition is presented in this paper.

  6. Adult Education & Human Resource Development: Overlapping and Disparate Fields

    Science.gov (United States)

    Watkins, Karen E.; Marsick, Victoria J.

    2014-01-01

    Adult education and human resource development as fields of practice and study share some roots in common but have grown in different directions in their histories. Adult education's roots focused initially on citizenship for a democratic society, whereas human resource development's roots are in performance at work. While they have…

  7. Pendulum mass affects the measurement of articular friction coefficient.

    Science.gov (United States)

    Akelman, Matthew R; Teeple, Erin; Machan, Jason T; Crisco, Joseph J; Jay, Gregory D; Fleming, Braden C

    2013-02-01

    Friction measurements of articular cartilage are important to determine the relative tribologic contributions made by synovial fluid or cartilage, and to assess the efficacy of therapies for preventing the development of post-traumatic osteoarthritis. Stanton's equation is the most frequently used formula for estimating the whole joint friction coefficient (μ) of an articular pendulum, and assumes pendulum energy loss through a mass-independent mechanism. This study examines if articular pendulum energy loss is indeed mass independent, and compares Stanton's model to an alternative model, which incorporates viscous damping, for calculating μ. Ten loads (25-100% body weight) were applied in a random order to an articular pendulum using the knees of adult male Hartley guinea pigs (n=4) as the fulcrum. Motion of the decaying pendulum was recorded and μ was estimated using two models: Stanton's equation, and an exponential decay function incorporating a viscous damping coefficient. μ estimates decreased as mass increased for both models. Exponential decay model fit error values were 82% less than the Stanton model. These results indicate that μ decreases with increasing mass, and that an exponential decay model provides a better fit for articular pendulum data at all mass values. In conclusion, inter-study comparisons of articular pendulum μ values should not be made without recognizing the loads used, as μ values are mass dependent. Copyright © 2012 Elsevier Ltd. All rights reserved.

  8. The immediate effect of long-distance running on T2 and T2* relaxation times of articular cartilage of the knee in young healthy adults at 3.0 T MR imaging.

    Science.gov (United States)

    Behzadi, Cyrus; Welsch, Goetz H; Laqmani, Azien; Henes, Frank O; Kaul, Michael G; Schoen, Gerhard; Adam, Gerhard; Regier, Marc

    2016-08-01

    To quantitatively assess the immediate effect of long-distance running on T2 and T2* relaxation times of the articular cartilage of the knee at 3.0 T in young healthy adults. 30 healthy male adults (18-31 years) who perform sports at an amateur level underwent an initial MRI at 3.0 T with T2 weighted [16 echo times (TEs): 9.7-154.6 ms] and T2* weighted (24 TEs: 4.6-53.6 ms) relaxation measurements. Thereafter, all participants performed a 45-min run. After the run, all individuals were immediately re-examined. Data sets were post-processed using dedicated software (ImageJ; National Institute of Health, Bethesda, MD). 22 regions of interest were manually drawn in segmented areas of the femoral, tibial and patellar cartilage. For statistical evaluation, Pearson product-moment correlation coefficients and confidence intervals were computed. Mean initial values were 35.7 ms for T2 and 25.1 ms for T2*. After the run, a significant decrease in the mean T2 and T2* relaxation times was observed for all segments in all participants. A mean decrease of relaxation time was observed for T2 with 4.6 ms (±3.6 ms) and for T2* with 3.6 ms (±5.1 ms) after running. A significant decrease could be observed in all cartilage segments for both biomarkers. Both quantitative techniques, T2 and T2*, seem to be valuable parameters in the evaluation of immediate changes in the cartilage ultrastructure after running. This is the first direct comparison of immediate changes in T2 and T2* relaxation times after running in healthy adults.

  9. Towards Regeneration of Articular Cartilage

    Science.gov (United States)

    Iwamoto, Masahiro; Ohta, Yoichi; Larmour, Colleen; Enomoto-Iwamoto, Motomi

    2014-01-01

    Articular cartilage is classified into permanent hyaline cartilage and has significant differences in structure, extracelluar matrix components, gene expression profile, and mechanical property from transient hyaline cartilage found in growth plate. In the process of synovial joint development, articular cartilage is originated from the interzone, developing at the edge of the cartilaginous anlagen, it establishes zonal structure over time and supports smooth movement of the synovial joint through life. The cascade actions of key regulators such as Wnts, GDF5, Erg, and PTHLH coordinate sequential steps of articular cartilage formation. Articular chondrocytes are restrictedly controlled not to differentiate into a hypertrophic stage by autocrine and paracrine factors and extracerllular matrix microenvironment, but retain potential to undergo hypertrophy. The basal calcified zone of articular cartilage is connected with subchondral bone, but not invaded by blood vessels nor replaced by bone, which is highly contrasted with the growth plate. Articular cartilage has limited regenerative capacity, but likely possesses and potentially uses intrinsic stem cell source in the superficial layer, Ranvier’s groove, the intra-articular tissues such as synovium and fat pad, and marrow below the subchondral bone. Considering the biological views on articular cartilage, several important points are raised for regeneration of articular cartilage. We should evaluate the nature of regenerated cartilage as permanent hyaline cartilage and not just hyaline cartilage. We should study how a hypertrophic phenotype of transplanted cells can be lastingly suppressed in regenerating tissue. Further, we should develop the methods and reagents to activate recruitment of intrinsic stem/progenitor cells into the damaged site. PMID:24078496

  10. Postnatal development of collagen structure in ovine articular cartilage

    NARCIS (Netherlands)

    Turnhout, van M.C.; Schipper, H.; Engel, B.; Buist, W.; Kranenbarg, S.; Leeuwen, van J.L.

    2010-01-01

    Background Articular cartilage (AC) is the layer of tissue that covers the articulating ends of the bones in diarthrodial joints. Across species, adult AC shows an arcade-like structure with collagen predominantly perpendicular to the subchondral bone near the bone, and collagen predominantly

  11. Postnatal development of collagen structure in ovine articular cartilage

    NARCIS (Netherlands)

    Turnhout, van M.C.; Schipper, H.; Engel, B.; Buist, W.; Kranenbarg, S.; Leeuwen, van J.L.

    2010-01-01

    BACKGROUND:Articular cartilage (AC) is the layer of tissue that covers the articulating ends of the bones in diarthrodial joints. Across species, adult AC shows an arcade-like structure with collagen predominantly perpendicular to the subchondral bone near the bone, and collagen predominantly

  12. Contrast Agent-Enhanced Computed Tomography of Articular Cartilage: Association with Tissue Composition and Properties

    International Nuclear Information System (INIS)

    Silvast, T. S.; Jurvelin, J.S.; Aula, A.S.; Lammi, M.J.; Toeyraes, J.

    2009-01-01

    Background: Contrast agent-enhanced computed tomography may enable the noninvasive quantification of glycosaminoglycan (GAG) content of articular cartilage. It has been reported that penetration of the negatively charged contrast agent ioxaglate (Hexabrix) increases significantly after enzymatic degradation of GAGs. However, it is not known whether spontaneous degradation of articular cartilage can be quantitatively detected with this technique. Purpose: To investigate the diagnostic potential of contrast agent-enhanced cartilage tomography (CECT) in quantification of GAG concentration in normal and spontaneously degenerated articular cartilage by means of clinical peripheral quantitative computed tomography (pQCT). Material and Methods: In this in vitro study, normal and spontaneously degenerated adult bovine cartilage (n=32) was used. Bovine patellar cartilage samples were immersed in 21 mM contrast agent (Hexabrix) solution for 24 hours at room temperature. After immersion, the samples were scanned with a clinical pQCT instrument. From pQCT images, the contrast agent concentration in superficial as well as in full-thickness cartilage was calculated. Histological and functional integrity of the samples was quantified with histochemical and mechanical reference measurements extracted from our earlier study. Results: Full diffusion of contrast agent into the deep cartilage was found to take over 8 hours. As compared to normal cartilage, a significant increase (11%, P 0.5, P<0.01). Further, pQCT could be used to measure the thickness of patellar cartilage. Conclusion: The present results suggest that CECT can be used to diagnose proteoglycan depletion in spontaneously degenerated articular cartilage with a clinical pQCT scanner. Possibly, the in vivo use of clinical pQCT for CECT arthrography of human joints is feasible

  13. Mapping the nanostructures in human adult and baby tooth enamel

    International Nuclear Information System (INIS)

    Low, I.M.; Mahmood, U.; Duraman, N.

    2005-01-01

    This paper investigates and compares the variations in crystal structure, composition, and nanostructures within the human adult and deciduous teeth. The similarities and differences in the nanostructure of both types of teeth are highlighted and discussed. (author)

  14. Adult Functional Literacy Curriculum: Effective Strategy for Human ...

    African Journals Online (AJOL)

    Adult functional literacy curriculum no doubt, is a panacea to human resource development in Nigeria. Government and non-government organizations have roles to play in providing functional education to adults who drop out of school or have no opportunity of attending the formal school system for all round development.

  15. Editorial: Technology for higher education, adult learning and human performance

    OpenAIRE

    Minhong Wang; Chi-Cheng Chang; Feng Wu

    2013-01-01

    This special issue is dedicated to technology-enabled approaches for improving higher education, adult learning, and human performance. Improvement of learning and human development for sustainable development has been recognized as a key strategy for individuals, institutions, and organizations to strengthen their competitive advantages. It becomes crucial to help adult learners and knowledge workers to improve their self-directed and life-long learning capabilities. Meanwhile, advances in t...

  16. Postnatal development of collagen structure in ovine articular cartilage

    Directory of Open Access Journals (Sweden)

    Kranenbarg Sander

    2010-06-01

    Full Text Available Abstract Background Articular cartilage (AC is the layer of tissue that covers the articulating ends of the bones in diarthrodial joints. Across species, adult AC shows an arcade-like structure with collagen predominantly perpendicular to the subchondral bone near the bone, and collagen predominantly parallel to the articular surface near the articular surface. Recent studies into collagen fibre orientation in stillborn and juvenile animals showed that this structure is absent at birth. Since the collagen structure is an important factor for AC mechanics, the absence of the adult Benninghoff structure has implications for perinatal AC mechanobiology. The current objective is to quantify the dynamics of collagen network development in a model animal from birth to maturity. We further aim to show the presence or absence of zonal differentiation at birth, and to assess differences in collagen network development between different anatomical sites of a single joint surface. We use quantitative polarised light microscopy to investigate properties of the collagen network and we use the sheep (Ovis aries as our model animal. Results Predominant collagen orientation is parallel to the articular surface throughout the tissue depth for perinatal cartilage. This remodels to the Benninghoff structure before the sheep reach sexual maturity. Remodelling of predominant collagen orientation starts at a depth just below the future transitional zone. Tissue retardance shows a minimum near the articular surface at all ages, which indicates the presence of zonal differentiation at all ages. The absolute position of this minimum does change between birth and maturity. Between different anatomical sites, we find differences in the dynamics of collagen remodelling, but no differences in adult collagen structure. Conclusions The collagen network in articular cartilage remodels between birth and sexual maturity from a network with predominant orientation parallel to the

  17. ACTIVITY OF CANONICAL WNT SIGNAL SYSTEM IN HYALINE CARTILAGE ARTICULAR CHONDROCYTES IN PROCESS OF SYNOVIAL JOINT DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    A.O. Molotkov

    2009-03-01

    Full Text Available Canonical and non-canonical Wnt systems are essential regulators of chondrogenesis and bone development. However, the roles of these systems in synovial joint development are not well studied. To determine if canonical Wnt system is active in developing articular chondrocytes we used immunohistochemistry for в-galactosidase and doublecortin (cell-type specific marker for articular chondrocytes to double label sections through joint regions of E14.5, E18.5, P10 and adult mice. Here the following results are presented. Canonical Wnt signal system does not work in developing articular chondrocytes at early embryonic stages (E14.5; it is active in the articular chondrocytes at late embryonic stages (E16.5-E18.5 and during postnatal development (P7-P10, but is turned off again in the adult articular chondrocytes. These results suggest that canonical Wnt signaling is being regulated during articular chondrocytes differentiation and joint formation.

  18. Articular contact in a three-dimensional model of the knee

    NARCIS (Netherlands)

    Blankevoort, L.; Kuiper, J. H.; Huiskes, R.; Grootenboer, H. J.

    1991-01-01

    This study is aimed at the analysis of articular contact in a three-dimensional mathematical model of the human knee-joint. In particular the effect of articular contact on the passive motion characteristics is assessed in relation to experimentally obtained joint kinematics. Two basically different

  19. Endogenous versus Exogenous Growth Factor Regulation of Articular Chondrocytes

    Science.gov (United States)

    Shi, Shuiliang; Chan, Albert G.; Mercer, Scott; Eckert, George J.; Trippel, Stephen B.

    2014-01-01

    Anabolic growth factors that regulate the function of articular chondrocytes are candidates for articular cartilage repair. Such factors may be delivered by pharmacotherapy in the form of exogenous proteins, or by gene therapy as endogenous proteins. It is unknown whether delivery method influences growth factor effectiveness in regulating articular chondrocyte reparative functions. We treated adult bovine articular chondrocytes with exogenous recombinant insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1), or with the genes encoding these growth factors for endogenous production. Treatment effects were measured as change in chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression. We found that IGF-I stimulated chondrocyte biosynthesis similarly when delivered by either exogenous or endogenous means. In contrast, exogenous TGF-ß1 stimulated these reparative functions, while endogenous TGF-ß1 had little effect. Endogenous TGF-ß1 became more bioactive following activation of the transgene protein product. These data indicate that effective mechanisms of growth factor delivery for articular cartilage repair may differ for different growth factors. In the case of IGF-I, gene therapy or protein therapy appear to be viable options. In contrast, TGF-ß1 gene therapy may be constrained by a limited ability of chondrocytes to convert latent complexes to an active form. PMID:24105960

  20. Endogenous versus exogenous growth factor regulation of articular chondrocytes.

    Science.gov (United States)

    Shi, Shuiliang; Chan, Albert G; Mercer, Scott; Eckert, George J; Trippel, Stephen B

    2014-01-01

    Anabolic growth factors that regulate the function of articular chondrocytes are candidates for articular cartilage repair. Such factors may be delivered by pharmacotherapy in the form of exogenous proteins, or by gene therapy as endogenous proteins. It is unknown whether delivery method influences growth factor effectiveness in regulating articular chondrocyte reparative functions. We treated adult bovine articular chondrocytes with exogenous recombinant insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-β1), or with the genes encoding these growth factors for endogenous production. Treatment effects were measured as change in chondrocyte DNA content, glycosaminoglycan production, and aggrecan gene expression. We found that IGF-I stimulated chondrocyte biosynthesis similarly when delivered by either exogenous or endogenous means. In contrast, exogenous TGF-β1 stimulated these reparative functions, while endogenous TGF-β1 had little effect. Endogenous TGF-β1 became more bioactive following activation of the transgene protein product. These data indicate that effective mechanisms of growth factor delivery for articular cartilage repair may differ for different growth factors. In the case of IGF-I, gene therapy or protein therapy appear to be viable options. In contrast, TGF-β1 gene therapy may be constrained by a limited ability of chondrocytes to convert latent complexes to an active form. Published 2013 by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. This article is a U.S. Government work and is in the public domain in the USA.

  1. MR imaging of articular cartilage

    International Nuclear Information System (INIS)

    Schaefer, F.K.W.; Muhle, C.; Heller, M.; Brossmann, J.

    2001-01-01

    MR imaging has evolved to the best non-invasive method for the evaluation of articular cartilage. MR imaging helps to understand the structure and physiology of cartilage, and to diagnose cartilage lesions. Numerous studies have shown high accuracy and reliability concerning detection of cartilage lesions and early changes in both structure and biochemistry. High contrast-to-noise ratio and high spatial resolution are essential for analysis of articular cartilage. Fat-suppressed 3D-T 1 weighted gradient echo and T 2 -weighted fast spin echo sequences with or without fat suppression are recommended for clinical routine. In this article the anatomy and pathology of hyaline articular cartilage and the complex imaging characteristics of hyaline cartilage will be discussed. (orig.) [de

  2. Contribution of proteoglycan osmotic swelling pressure to the compressive properties of articular cartilage.

    Science.gov (United States)

    Han, EunHee; Chen, Silvia S; Klisch, Stephen M; Sah, Robert L

    2011-08-17

    The negatively charged proteoglycans (PG) provide compressive resistance to articular cartilage by means of their fixed charge density (FCD) and high osmotic pressure (π(PG)), and the collagen network (CN) provides the restraining forces to counterbalance π(PG). Our objectives in this work were to: 1), account for collagen intrafibrillar water when transforming biochemical measurements into a FCD-π(PG) relationship; 2), compute π(PG) and CN contributions to the compressive behavior of full-thickness cartilage during bovine growth (fetal, calf, and adult) and human adult aging (young and old); and 3), predict the effect of depth from the articular surface on π(PG) in human aging. Extrafibrillar FCD (FCD(EF)) and π(PG) increased with bovine growth due to an increase in CN concentration, whereas PG concentration was steady. This maturation-related increase was amplified by compression. With normal human aging, FCD(EF) and π(PG) decreased. The π(PG)-values were close to equilibrium stress (σ(EQ)) in all bovine and young human cartilage, but were only approximately half of σ(EQ) in old human cartilage. Depth-related variations in the strain, FCD(EF), π(PG), and CN stress profiles in human cartilage suggested a functional deterioration of the superficial layer with aging. These results suggest the utility of the FCD-π(PG) relationship for elucidating the contribution of matrix macromolecules to the biomechanical properties of cartilage. Copyright © 2011 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  3. Evaluation of the Thompson articular index

    NARCIS (Netherlands)

    van den Brink, H. R.; van der Heide, A.; Jacobs, J. W.; van der Veen, M. J.; Bijlsma, J. W.

    1993-01-01

    Three articular indices for measuring disease activity are compared. In a cross sectional study the Thompson articular index (a modified Lansbury index) correlated better with laboratory variables than the Ritchie articular index or a swollen joint score (Thompson 0.74-0.77; Ritchie 0.57-0.58;

  4. The weight of nations: an estimation of adult human biomass

    Directory of Open Access Journals (Sweden)

    Walpole Sarah

    2012-06-01

    Full Text Available Abstract Background The energy requirement of species at each trophic level in an ecological pyramid is a function of the number of organisms and their average mass. Regarding human populations, although considerable attention is given to estimating the number of people, much less is given to estimating average mass, despite evidence that average body mass is increasing. We estimate global human biomass, its distribution by region and the proportion of biomass due to overweight and obesity. Methods For each country we used data on body mass index (BMI and height distribution to estimate average adult body mass. We calculated total biomass as the product of population size and average body mass. We estimated the percentage of the population that is overweight (BMI > 25 and obese (BMI > 30 and the biomass due to overweight and obesity. Results In 2005, global adult human biomass was approximately 287 million tonnes, of which 15 million tonnes were due to overweight (BMI > 25, a mass equivalent to that of 242 million people of average body mass (5% of global human biomass. Biomass due to obesity was 3.5 million tonnes, the mass equivalent of 56 million people of average body mass (1.2% of human biomass. North America has 6% of the world population but 34% of biomass due to obesity. Asia has 61% of the world population but 13% of biomass due to obesity. One tonne of human biomass corresponds to approximately 12 adults in North America and 17 adults in Asia. If all countries had the BMI distribution of the USA, the increase in human biomass of 58 million tonnes would be equivalent in mass to an extra 935 million people of average body mass, and have energy requirements equivalent to that of 473 million adults. Conclusions Increasing population fatness could have the same implications for world food energy demands as an extra half a billion people living on the earth.

  5. Linking adult hippocampal neurogenesis with human physiology and disease.

    Science.gov (United States)

    Bowers, Megan; Jessberger, Sebastian

    2016-07-01

    We here review the existing evidence linking adult hippocampal neurogenesis and human brain function in physiology and disease. Furthermore, we aim to point out where evidence is missing, highlight current promising avenues of investigation, and suggest future tools and approaches to foster the link between life-long neurogenesis and human brain function. Developmental Dynamics 245:702-709, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. Development of artificial articular cartilage

    Indian Academy of Sciences (India)

    Mechanical strength of Poly(vinyl alcohol), PVA is improved up to 35 MPa. Manufacturing method is adopted considering colloidal stability of nano silica particle in PVA sol at specific pH = 1. An adhesive is also prepared from PVA/Si nanocomposite containing 40% TEOS for firm attachment of artificial articular cartilage on ...

  7. Qualitative analysis neurons in the adult human dentate nucleus

    Directory of Open Access Journals (Sweden)

    Marić Dušica

    2012-01-01

    Full Text Available Although many relevant findings regarding to the morphology and cytoarchitectural development of the dentate nucleus have been presented so far, very little qualitative information has been collected on neuronal morphology in the adult human dentate nucleus. The neurons were labelled by Golgi staining from thirty human cerebella, obtained from medico-legal forensic autopsies of adult human bodies and free of significant brain pathology. The human dentate neurons were qualitatively analyzed and these cells were classified into two main classes: the small and the large multipolar neurons. Considering the shape of the cell body, number of the primary dendrites, shape of the dendritic tree and their position within the dentate nucleus, three subclasses of the large multipolar neurons have been recognized. The classification of neurons from the human dentate nucleus has been qualitatively confirmed in fetuses and premature infants. This study represents the first qualitative analysis and classification of the large multipolar neurons in the dentate nucleus of the adult human.

  8. Histology of two rice bodies isolated from the stifle of an adult draught horse stallion.

    Science.gov (United States)

    Schneider, Nicole; Heimann, Marianne; Lejeune, Jean-Philippe; Verwilghen, Denis R V G; Deby-Dupont, Ginette P; Serteyn, Didier A

    2006-03-01

    In the human and equine species, different kinds of free floating intra-articular particles are related to certain disorders. Osteochondral fragments formed during osteochondrosis dissecans are the most common finding in the equine species, whereas in humans rice bodies due to rheumatoid arthritis are more frequent. Herein we report a third type of floating body inside the stifle of an adult draught horse stallion, in macroscopic appearance similar to articular rice bodies known in humans. As revealed by histologic examination, the two particles consist of polypoid degenerated structures derived from synovial villi. Their formation was probably induced by ischemia.

  9. Monocular Visual Deprivation Suppresses Excitability in Adult Human Visual Cortex

    DEFF Research Database (Denmark)

    Lou, Astrid Rosenstand; Madsen, Kristoffer Hougaard; Paulson, Olaf Bjarne

    2011-01-01

    The adult visual cortex maintains a substantial potential for plasticity in response to a change in visual input. For instance, transcranial magnetic stimulation (TMS) studies have shown that binocular deprivation (BD) increases the cortical excitability for inducing phosphenes with TMS. Here, we...... of visual deprivation has a substantial impact on experience-dependent plasticity of the human visual cortex.......The adult visual cortex maintains a substantial potential for plasticity in response to a change in visual input. For instance, transcranial magnetic stimulation (TMS) studies have shown that binocular deprivation (BD) increases the cortical excitability for inducing phosphenes with TMS. Here, we...... employed TMS to trace plastic changes in adult visual cortex before, during, and after 48 h of monocular deprivation (MD) of the right dominant eye. In healthy adult volunteers, MD-induced changes in visual cortex excitability were probed with paired-pulse TMS applied to the left and right occipital cortex...

  10. Creativity, Social Justice and Human Rights within Adult Education

    Science.gov (United States)

    Brown, Susannah

    2015-01-01

    In this paper, the author describes philosophical concepts of adult learning and their application as integrated with creative problem solving within the context of social justice and human rights. The context is framed by the work of the United Nations (1992) which emphasizes importance of women's roles and creativity in the process of forming a…

  11. Articular cartilage changes in chondromalacia patellae.

    Science.gov (United States)

    Bentley, G

    1985-11-01

    Full thickness samples of articular cartilage were removed from areas of chondromalacia on the medial and "odd" facets of the patellae of 21 adults and examined by histology, autoradiography and electron microscopy. Surface fibrillation, loss of superficial matrix staining and reduced 35SO4 labelling was seen, with little change in the deep zone. Ten cases showed "fibrous metaplasia" of the superficial cartilage with definite evidence of cell division and apparent smoothing of the surface. Scattered chondrocyte replication appeared to occur in the surrounding intact cartilage. The findings suggest that early lesions in chondromalacia patellae may heal either by cartilage or fibrous metaplasia and that this may account for the resolution of clinical symptoms.

  12. Age-Related Gene Expression Differences in Monocytes from Human Neonates, Young Adults, and Older Adults.

    Science.gov (United States)

    Lissner, Michelle M; Thomas, Brandon J; Wee, Kathleen; Tong, Ann-Jay; Kollmann, Tobias R; Smale, Stephen T

    2015-01-01

    A variety of age-related differences in the innate and adaptive immune systems have been proposed to contribute to the increased susceptibility to infection of human neonates and older adults. The emergence of RNA sequencing (RNA-seq) provides an opportunity to obtain an unbiased, comprehensive, and quantitative view of gene expression differences in defined cell types from different age groups. An examination of ex vivo human monocyte responses to lipopolysaccharide stimulation or Listeria monocytogenes infection by RNA-seq revealed extensive similarities between neonates, young adults, and older adults, with an unexpectedly small number of genes exhibiting statistically significant age-dependent differences. By examining the differentially induced genes in the context of transcription factor binding motifs and RNA-seq data sets from mutant mouse strains, a previously described deficiency in interferon response factor-3 activity could be implicated in most of the differences between newborns and young adults. Contrary to these observations, older adults exhibited elevated expression of inflammatory genes at baseline, yet the responses following stimulation correlated more closely with those observed in younger adults. Notably, major differences in the expression of constitutively expressed genes were not observed, suggesting that the age-related differences are driven by environmental influences rather than cell-autonomous differences in monocyte development.

  13. PRP and Articular Cartilage: A Clinical Update

    Science.gov (United States)

    Rossi, Roberto; Castoldi, Filippo; Michielon, Gianni

    2015-01-01

    The convincing background of the recent studies, investigating the different potentials of platelet-rich plasma, offers the clinician an appealing alternative for the treatment of cartilage lesions and osteoarthritis. Recent evidences in literature have shown that PRP may be helpful both as an adjuvant for surgical treatment of cartilage defects and as a therapeutic tool by intra-articular injection in patients affected by osteoarthritis. In this review, the authors introduce the trophic and anti-inflammatory properties of PRP and the different products of the available platelet concentrates. Then, in a complex scenario made of a great number of clinical variables, they resume the current literature on the PRP applications in cartilage surgery as well as the use of intra-articular PRP injections for the conservative treatment of cartilage degenerative lesions and osteoarthritis in humans, available as both case series and comparative studies. The result of this review confirms the fascinating biological role of PRP, although many aspects yet remain to be clarified and the use of PRP in a clinical setting has to be considered still exploratory. PMID:26075244

  14. PRP and Articular Cartilage: A Clinical Update

    Directory of Open Access Journals (Sweden)

    Antonio Marmotti

    2015-01-01

    Full Text Available The convincing background of the recent studies, investigating the different potentials of platelet-rich plasma, offers the clinician an appealing alternative for the treatment of cartilage lesions and osteoarthritis. Recent evidences in literature have shown that PRP may be helpful both as an adjuvant for surgical treatment of cartilage defects and as a therapeutic tool by intra-articular injection in patients affected by osteoarthritis. In this review, the authors introduce the trophic and anti-inflammatory properties of PRP and the different products of the available platelet concentrates. Then, in a complex scenario made of a great number of clinical variables, they resume the current literature on the PRP applications in cartilage surgery as well as the use of intra-articular PRP injections for the conservative treatment of cartilage degenerative lesions and osteoarthritis in humans, available as both case series and comparative studies. The result of this review confirms the fascinating biological role of PRP, although many aspects yet remain to be clarified and the use of PRP in a clinical setting has to be considered still exploratory.

  15. Distinct functional programming of human fetal and adult monocytes.

    Science.gov (United States)

    Krow-Lucal, Elisabeth R; Kim, Charles C; Burt, Trevor D; McCune, Joseph M

    2014-03-20

    Preterm birth affects 1 out of 9 infants in the United States and is the leading cause of long-term neurologic handicap and infant mortality, accounting for 35% of all infant deaths in 2008. Although cytokines including interferon-γ (IFN-γ), interleukin-10 (IL-10), IL-6, and IL-1 are produced in response to in utero infection and are strongly associated with preterm labor, little is known about how human fetal immune cells respond to these cytokines. We demonstrate that fetal and adult CD14(+)CD16(-) classical monocytes are distinct in terms of basal transcriptional profiles and in phosphorylation of signal transducers and activators of transcription (STATs) in response to cytokines. Fetal monocytes phosphorylate canonical and noncanonical STATs and respond more strongly to IFN-γ, IL-6, and IL-4 than adult monocytes. We demonstrate a higher ratio of SOCS3 to IL-6 receptor in adult monocytes than in fetal monocytes, potentially explaining differences in STAT phosphorylation. Additionally, IFN-γ signaling results in upregulation of antigen presentation and costimulatory machinery in adult, but not fetal, monocytes. These findings represent the first evidence that primary human fetal and adult monocytes are functionally distinct, potentially explaining how these cells respond differentially to cytokines implicated in development, in utero infections, and the pathogenesis of preterm labor.

  16. Does Acute Normobaric Hypoxia Induce Anapyrexia in Adult Humans?

    Science.gov (United States)

    Seo, Yongsuk; Gerhart, Hayden D; Vaughan, Jeremiah; Kim, Jung-Hyun; Glickman, Ellen L

    2017-06-01

    Seo, Yongsuk, Hayden D. Gerhart, Jeremiah Vaughan, Jung-Hyun Kim, and Ellen L. Glickman. Does acute normobaric hypoxia induce anapyrexia in adult humans? High Alt Med Biol. 18:185-190, 2017.-Exposure to hypoxia is known to induce a reduction in core body temperature as a protective mechanism, which has been shown in both animals and humans. The purpose of this study was to test if acute exposure to normobaric hypoxia (NH) induces anapyrexia in adult humans in association with decreased peripheral oxygen saturation (SpO 2 ). Ten healthy male subjects were seated in atmospheres of normobaric normoxia 21% (NN21), NH 17% (NH17), and 13% (NH13) O 2 for 60 minutes in a counterbalanced manner. Rectal temperature (Tre) was continuously monitored together with the quantification of metabolic heat production (MHP) and body heat storage (S). Baseline physiological measurements showed no differences between the three conditions. SpO 2 was significantly decreased in NH17 and NH13 compared with NN21 (p ≤ 0.001). Tre decreased following 60 minutes of resting in all conditions, but, independent of the conditions, showed no association between Tre and levels of hypoxic SpO 2 . There was also no significant difference in either MHP or S between conditions. The present results showed no evidence of hypoxia-induced anapyrexia in adult humans during 1 hour of resting after exposure to NH either at 13% or 17% O 2 .

  17. Covert spatial attention is functionally intact in amblyopic human adults

    OpenAIRE

    Roberts, Mariel; Cymerman, Rachel; Smith, R. Theodore; Kiorpes, Lynne; Carrasco, Marisa

    2016-01-01

    Certain abnormalities in behavioral performance and neural signaling have been attributed to a deficit of visual attention in amblyopia, a neurodevelopmental disorder characterized by a diverse array of visual deficits following abnormal binocular childhood experience. Critically, most have inferred attention's role in their task without explicitly manipulating and measuring its effects against a baseline condition. Here, we directly investigate whether human amblyopic adults benefit from cov...

  18. The mandibular angles of dry adult human mandibles from north ...

    African Journals Online (AJOL)

    The mandibular angles of dry adult human mandibles from north-eastern arid zone of Nigeria. EF Mbajiorgu, AU Ekanem. Abstract. (Central African Journal of Medicine: 2002 48 (1-2): 9-13). http://dx.doi.org/10.4314/cajm.v48i1.8417 · AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians ...

  19. The stimulation of mononuclear cells from patients with rheumatoid arthritis to degrade articular cartilage is not modulated by cartilage itself

    NARCIS (Netherlands)

    van Roon, J. A.; van Roy, J. L.; Lafeber, F. P.; Bijlsma, J. W.

    1996-01-01

    To study the modulation of mononuclear cell (MNC) activity in patients with rheumatoid arthritis (RA) by constituents released from human articular cartilage, which may be present in vivo during early events of the disease, when articular cartilage is not only mildly damaged. In an attempt to

  20. Can sleep deprivation studies explain why human adults sleep?

    Science.gov (United States)

    Brown, Lee K

    2012-11-01

    This review will concentrate on the consequences of sleep deprivation in adult humans. These findings form a paradigm that serves to demonstrate many of the critical functions of the sleep states. The drive to obtain food, water, and sleep constitutes important vegetative appetites throughout the animal kingdom. Unlike nutrition and hydration, the reasons for sleep have largely remained speculative. When adult humans are nonspecifically sleep-deprived, systemic effects may include defects in cognition, vigilance, emotional stability, risk-taking, and, possibly, moral reasoning. Appetite (for foodstuffs) increases and glucose intolerance may ensue. Procedural, declarative, and emotional memory are affected. Widespread alterations of immune function and inflammatory regulators can be observed, and functional MRI reveals profound changes in regional cerebral activity related to attention and memory. Selective deprivation of rapid eye movement (REM) sleep, on the contrary, appears to be more activating and to have lesser effects on immunity and inflammation. The findings support a critical need for sleep due to the widespread effects on the adult human that result from nonselective sleep deprivation. The effects of selective REM deprivation appear to be different and possibly less profound, and the functions of this sleep state remain enigmatic.

  1. Localization of Estrogen Receptors α and β in the Articular Surface of the Rat Femur

    International Nuclear Information System (INIS)

    Oshima, Yasushi; Matsuda, Ken-ichi; Yoshida, Atsuhiko; Watanabe, Nobuyoshi; Kawata, Mitsuhiro; Kubo, Toshikazu

    2007-01-01

    It has been suggested that the degradation of the articular cartilage and osteoarthritis (OA) are associated with gender and the estrogen hormone. Although many investigators have reported the presence of the estrogen receptors (ERs) α and β in the articular cartilage, the localization of these receptors and the difference in their in vivo expression have not yet been clearly demonstrated. We performed immunofluorescence staining of ERα and ERβ to elucidate the localization of the ERs and to note the effects of gender and the aging process on these receptors. The results revealed that ERα and ERβ were expressed in the articular cartilage and subchondral bone layers of adult rats of both sexes. We also observed the high expression of these receptors in immature rats. In contrast, their expression levels decreased in an ovariectomised model, as a simulation of postmenopause, and in aged female rats. Therefore, this study suggests the direct effects of estrogen and ER expression on articular surface metabolism

  2. Intra-articular chondroma of the knee

    Energy Technology Data Exchange (ETDEWEB)

    Talwalkar, S.C.; Kambhampati, S.B.S.; Lang Stevenson, A.I. [Oldchurch Hospital, Romford, Essex (United Kingdom); Whitehouse, R. [Manchester University, Department of Radiology, Manchester (United Kingdom); Freemont, A. [University of Manchester, Department of Osteoarticular Pathology, Manchester (United Kingdom)

    2005-06-01

    Chondromas are tumours that develop in relation to the periosteum and, although they are common around the knee, most reports deal with soft tissue chondromas in para-articular locations or intracortical tumours in extra-articular regions. We report a rare case of an intra-articular chondroma in a 16-year-old boy of Asian origin developing in the region of the medial femoral condyle of the femur and extending into the femoral sulcus and the patellofemoral joint. (orig.)

  3. Intra-articular chondroma of the knee

    International Nuclear Information System (INIS)

    Talwalkar, S.C.; Kambhampati, S.B.S.; Lang Stevenson, A.I.; Whitehouse, R.; Freemont, A.

    2005-01-01

    Chondromas are tumours that develop in relation to the periosteum and, although they are common around the knee, most reports deal with soft tissue chondromas in para-articular locations or intracortical tumours in extra-articular regions. We report a rare case of an intra-articular chondroma in a 16-year-old boy of Asian origin developing in the region of the medial femoral condyle of the femur and extending into the femoral sulcus and the patellofemoral joint. (orig.)

  4. Oogenesis in cultures derived from adult human ovaries

    Directory of Open Access Journals (Sweden)

    Caudle Michael R

    2005-05-01

    Full Text Available Abstract Ten years ago, we reported that in adult human females the ovarian surface epithelium (OSE is a source of germ cells. Recently, we also demonstrated that new primary follicles are formed by assembly of oocytes with nests of primitive granulosa cells in the ovarian cortex. The components of the new primary follicles, primitive granulosa and germ cells, differentiated sequentially from the OSE, which arises from cytokeratin positive mesenchymal progenitor cells residing in the ovarian tunica albuginea. In the present study, we investigated the possibility that the oocytes and granulosa cells may differentiate in cultures derived from adult human ovaries. Cells were scrapped from the surface of ovaries and cultured for 5 to 6 days, in the presence or absence of estrogenic stimuli [phenol red (PhR]. The OSE cells cultured in the medium without PhR differentiated into small (15 micron cells of granulosa phenotype, and epithelial, neural, and mesenchymal type cells. In contrast, OSE cells cultured in the presence of PhR differentiated directly into large (180 micron cells of the oocyte phenotype. Such cells exhibited germinal vesicle breakdown, expulsion of the polar body, and surface expression of zona pellucida proteins, i.e. characteristics of secondary oocytes. These in vitro studies confirm our in vivo observations that in adult human ovaries, the OSE is a bipotent source of oocytes and granulosa cells. Development of numerous mature oocytes from adult ovarian stem cells in vitro offers new strategies for the egg preservation, IVF utilization, and treatment of female infertility. In addition, other clinical applications aiming to utilize stem cells, and basic stem cell research as well, may employ totipotent embryonic stem cells developing from fertilized oocytes.

  5. In vitro proliferation of adult human beta-cells.

    Directory of Open Access Journals (Sweden)

    Sabine Rutti

    Full Text Available A decrease in functional beta-cell mass is a key feature of type 2 diabetes. Glucagon-like peptide 1 (GLP-1 analogues induce proliferation of rodent beta-cells. However, the proliferative capacity of human beta-cells and its modulation by GLP-1 analogues remain to be fully investigated. We therefore sought to quantify adult human beta-cell proliferation in vitro and whether this is affected by the GLP-1 analogue liraglutide.Human islets from 7 adult cadaveric organ donors were dispersed into single cells. Beta-cells were purified by FACS. Non-sorted cells and the beta-cell enriched ("beta-cells" population were plated on extracellular matrix from rat (804G and human bladder carcinoma cells (HTB9 or bovine corneal endothelial ECM (BCEC. Cells were maintained in culture+/-liraglutide for 4 days in the presence of BrdU.Rare human beta-cell proliferation could be observed either in the purified beta-cell population (0.051±0.020%; 22 beta-cells proliferating out of 84'283 beta-cells counted or in the non-sorted cell population (0.055±0.011%; 104 proliferating beta-cells out of 232'826 beta-cells counted, independently of the matrix or the culture conditions. Liraglutide increased human beta-cell proliferation on BCEC in the non-sorted cell population (0.082±0.034% proliferating beta-cells vs. 0.017±0.008% in control, p<0.05.These results indicate that adult human beta-cell proliferation can occur in vitro but remains an extremely rare event with these donors and particular culture conditions. Liraglutide increases beta-cell proliferation only in the non-sorted cell population and only on BCEC. However, it cannot be excluded that human beta-cells may proliferate to a greater extent in situ in response to natural stimuli.

  6. The nutrition intervention improved adult human capital and economic productivity.

    Science.gov (United States)

    Martorell, Reynaldo; Melgar, Paul; Maluccio, John A; Stein, Aryeh D; Rivera, Juan A

    2010-02-01

    This article reviews key findings about the long-term impact of a nutrition intervention carried out by the Institute of Nutrition of Central America and Panama from 1969 to 1977. Results from follow-up studies in 1988-89 and 2002-04 show substantial impact on adult human capital and economic productivity. The 1988-89 study showed that adult body size and work capacity increased for those provided improved nutrition through age 3 y, whereas the 2002-04 follow-up showed that schooling was increased for women and reading comprehension and intelligence increased in both men and women. Participants were 26-42 y of age at the time of the 2002-04 follow-up, facilitating the assessment of economic productivity. Wages of men increased by 46% in those provided with improved nutrition through age 2 y. Findings for cardiovascular disease risk factors were heterogeneous; however, they suggest that improved nutrition in early life is unlikely to increase cardiovascular disease risk later in life and may indeed lower risk. In conclusion, the substantial improvement in adult human capital and economic productivity resulting from the nutrition intervention provides a powerful argument for promoting improvements in nutrition in pregnant women and young children.

  7. Squeeze-film Lubrication of the Human Ankle Joint with Synovial Fluid Filtrated by Articular Cartilage with the Superficial Zone Worn out

    Czech Academy of Sciences Publication Activity Database

    Hlaváček, Miroslav

    2000-01-01

    Roč. 33, č. 11 (2000), s. 1415-1422 ISSN 0021-9290 R&D Projects: GA ČR GA103/00/0008 Keywords : human ankle joint * squeeze-film lubrication * synovial fluid filtration * worn-out cartilage superficial zone Subject RIV: BK - Fluid Dynamics Impact factor: 1.474, year: 2000

  8. Neurons in the white matter of the adult human neocortex

    Directory of Open Access Journals (Sweden)

    M Luisa Suarez-Sola

    2009-06-01

    Full Text Available The white matter (WM of the adult human neocortex contains the so-called “interstitial neurons”. They are most numerous in the superficial WM underlying the cortical gyri, and decrease in density toward the deep WM. They are morphologically heterogeneous. A subgroup of interstitial neurons display pyramidal-cell like morphologies, characterized by a polarized dendritic tree with a dominant apical dendrite, and covered with a variable number of dendritic spines. In addition, a large contingent of interstitial neurons can be classified as interneurons based on their neurochemical profile as well as on morphological criteria. WM- interneurons have multipolar or bipolar shapes and express GABA and a variety of other neuronal markers, such as calbindin and calretinin, the extracellular matrix protein reelin, or neuropeptide Y, somatostatin, and nitric oxide synthase. The heterogeneity of interstitial neurons may be relevant for the pathogenesis of Alzheimer disease and schizophrenia. Interstitial neurons are most prominent in human brain, and only rudimentary in the brain of non-primate mammals. These evolutionary differences have precluded adequate experimental work on this cell population, which is usually considered as a relict of the subplate, a transient compartment proper of development and without a known function in the adult brain. The primate-specific prominence of the subplate in late fetal stages points to an important role in the establishment of interstitial neurons. Neurons in the adult WM may be actively involved in coordinating inter-areal connectivity and regulation of blood flow. Further studies in primates will be needed to elucidate the developmental history, adult components and activities of this large neuronal system.

  9. Manifestações articulares nas viroses exantemáticas Joint complaints in exanthematic diseases

    Directory of Open Access Journals (Sweden)

    Solange Artimos de Oliveira

    1999-04-01

    Full Text Available A freqüência de manifestações articulares foi avaliada em 251 pacientes com diagnóstico clínico e laboratorial (detecção de IgM por ensaio imunoenzimático de virose exantemática. As artropatias (artralgia e/ou artrite foram mais observadas nos casos de dengue (49% e de rubéola (38,2% do que naqueles com parvovirose humana (30% e sarampo (28,1%. Com exceção do sarampo, as artropatias predominaram nos adultos (315 anos de idade, sendo tal diferença estatisticamente significativa. A ocorrência maior de artropatias em adultos foi mais evidente nos pacientes com parvovirose (75%, rubéola (65% e dengue (57,7% do que naqueles com sarampo (31%. As queixas articulares também predominaram nos pacientes do sexo feminino para todas as viroses avaliadas. Os resultados encontrados demonstram o freqüente acometimento articular nas doenças estudadas, e indicam a necessidade de comprovação laboratorial para o diagnóstico diferencial entre elas.The frequency of arthropathy was evaluated in 251 patients with clinical and serological diagnosis (specific IgM detection by enzyme immunoassay of exanthematic disease. Arthropathy (arthralgia and/or arthritis was more frequent in dengue fever (49% and rubella (38.2% cases than in human parvovirus (30% and measles (28.1% cases. Except for measles cases, joint complaints prevailed in adults (315 years of age and this difference was significant. The higher frequency of arthropathy in adults was more evident in human parvovirus (75%, rubella (65% and dengue fever (57.7% cases than in measles cases (31%. Arthropathy was also more frequent in females for all rash diseases studied. The results of this study showed the high occurrence of joint complaints in the diseases described here and the importance of laboratory confirmation for their differential diagnosis.

  10. Periodontitis and oral human papillomavirus infection among Hispanic adults

    Directory of Open Access Journals (Sweden)

    Ana Patricia Ortiz

    2018-06-01

    Full Text Available Introduction: Research on the association between periodontitis and oral human papilloma virus (HPV infection is inconsistent. The cross-sectional association of severe periodontitis with oral HPV infection was investigated in a sample of Hispanic adults. Methods: Data from the 2014–2016 San Juan Overweight Adults Longitudinal Study (n = 740 was analyzed. Periodontitis assessment and self-collection of oral HPV samples followed the National Health and Nutrition Examination Survey methodology. Periodontitis was defined using the Centers of Disease Control and Prevention/American Academy of Periodontology definition. HPV typing was performed using polymerase chain reaction. Multivariate logistic regression models were used to calculate odds ratios (ORs and 95% confidence intervals (CIs. Results: 5.7% of participants had oral HPV infection and 20.3% had severe periodontitis. Adults with severe periodontitis had higher odds of oral HPV infection than those with none/mild disease (OR=2.9, 95% CI: 1.0–8.4, p < 0.05 in multivariable analysis. Adults with clinical attachment loss≥ 7 mm and pocket depth PD≥ 6 mm had 2- to 3-fold higher odds of HPV infection. Conclusions: Severe periodontitis was positively associated to oral HPV infection. Longitudinal evaluation of periodontal inflammation's role in acquisition and persistence of oral HPV infection is needed, as periodontitis screening could identify individuals at increased risk of HPV-related oral malignancies. Keywords: Periodontitis, Oral HPV, Hispanics, Adults, Oral health, Puerto Rico

  11. Effect of donor age on DNA repair by articular chondrocytes

    International Nuclear Information System (INIS)

    Lipman, J.M.

    1986-01-01

    The hypothesis that aging of articular chondrocytes at a cellular level results from loss of DNA repair capability was studied by two different measures: unscheduled DNA synthesis (UDS) and O 6 -methylguanine acceptor protein (MGAP) activity. UDS following damage by 254 nm ultraviolet irradiation (20J/m 2 ) was examined in intact articular cartilage from rabbits of different ages. Semiconservative DNA synthesis was suppressed with hydroxurea and repair followed by the incorporation of [ 3 H]-thymidine ([ 3 H]-dThd). After repair the cartilage was digested in proteinase K (0.5mg/ml) with dodecyl sodium sulfate (0.2%) and DNA determined with Hoechst 33258 dye. UDS (dpm [ 3 H]-dThd/μg DNA) was greater in articular cartilage from 3- than 39-month-old rabbits. MGAP was studied in cell extracts of cultured human and rabbit chondrocytes by transfer of [ 3 H] O 6 -methyl groups from exogenous DNA to protein. It was significantly less in rabbit than in human cells on a per protein or DNA basis. There was no decline in this activity in human chondrocytes from newborn to 60 years of age; and rabbits from 3- to 36-months-old. The data indicate that in the two different repair mechanisms, age differences are found with resting but not dividing chondrocytes

  12. Topographical Variation of Human Femoral Articular Cartilage Thickness, T1rho and T2 Relaxation Times Is Related to Local Loading during Walking.

    Science.gov (United States)

    Van Rossom, Sam; Wesseling, Mariska; Van Assche, Dieter; Jonkers, Ilse

    2018-01-01

    Objective Early detection of degenerative changes in the cartilage matrix composition is essential for evaluating early interventions that slow down osteoarthritis (OA) initiation. T1rho and T2 relaxation times were found to be effective for detecting early changes in proteoglycan and collagen content. To use these magnetic resonance imaging (MRI) methods, it is important to document the topographical variation in cartilage thickness, T1rho and T2 relaxation times in a healthy population. As OA is partially mechanically driven, the relation between these MRI-based parameters and localized mechanical loading during walking was investigated. Design MR images were acquired in 14 healthy adults and cartilage thickness and T1rho and T2 relaxation times were determined. Experimental gait data was collected and processed using musculoskeletal modeling to identify weight-bearing zones and estimate the contact force impulse during gait. Variation of the cartilage properties (i.e., thickness, T1rho, and T2) over the femoral cartilage was analyzed and compared between the weight-bearing and non-weight-bearing zone of the medial and lateral condyle as well as the trochlea. Results Medial condyle cartilage thickness was correlated to the contact force impulse ( r = 0.78). Lower T1rho, indicating increased proteoglycan content, was found in the medial weight-bearing zone. T2 was higher in all weight-bearing zones compared with the non-weight-bearing zones, indicating lower relative collagen content. Conclusions The current results suggest that medial condyle cartilage is adapted as a long-term protective response to localized loading during a frequently performed task and that the weight-bearing zone of the medial condyle has superior weight bearing capacities compared with the non-weight-bearing zones.

  13. Transcriptional profiling differences for articular cartilage and repair tissue in equine joint surface lesions

    Directory of Open Access Journals (Sweden)

    Stromberg Arnold J

    2009-09-01

    Full Text Available Abstract Background Full-thickness articular cartilage lesions that reach to the subchondral bone yet are restricted to the chondral compartment usually fill with a fibrocartilage-like repair tissue which is structurally and biomechanically compromised relative to normal articular cartilage. The objective of this study was to evaluate transcriptional differences between chondrocytes of normal articular cartilage and repair tissue cells four months post-microfracture. Methods Bilateral one-cm2 full-thickness defects were made in the articular surface of both distal femurs of four adult horses followed by subchondral microfracture. Four months postoperatively, repair tissue from the lesion site and grossly normal articular cartilage from within the same femorotibial joint were collected. Total RNA was isolated from the tissue samples, linearly amplified, and applied to a 9,413-probe set equine-specific cDNA microarray. Eight paired comparisons matched by limb and horse were made with a dye-swap experimental design with validation by histological analyses and quantitative real-time polymerase chain reaction (RT-qPCR. Results Statistical analyses revealed 3,327 (35.3% differentially expressed probe sets. Expression of biomarkers typically associated with normal articular cartilage and fibrocartilage repair tissue corroborate earlier studies. Other changes in gene expression previously unassociated with cartilage repair were also revealed and validated by RT-qPCR. Conclusion The magnitude of divergence in transcriptional profiles between normal chondrocytes and the cells that populate repair tissue reveal substantial functional differences between these two cell populations. At the four-month postoperative time point, the relative deficiency within repair tissue of gene transcripts which typically define articular cartilage indicate that while cells occupying the lesion might be of mesenchymal origin, they have not recapitulated differentiation to

  14. Functional anatomy of the equine temporomandibular joint: Collagen fiber texture of the articular surfaces.

    Science.gov (United States)

    Adams, K; Schulz-Kornas, E; Arzi, B; Failing, K; Vogelsberg, J; Staszyk, C

    2016-11-01

    In the last decade, the equine masticatory apparatus has received much attention. Numerous studies have emphasized the importance of the temporomandibular joint (TMJ) in the functional process of mastication. However, ultrastructural and histological data providing a basis for biomechanical and histopathological considerations are not available. The aim of the present study was to analyze the architecture of the collagen fiber apparatus in the articular surfaces of the equine TMJ to reveal typical morphological features indicating biomechanical adaptions. Therefore, the collagen fiber alignment was visualized using the split-line technique in 16 adult warmblood horses without any history of TMJ disorders. Within the central two-thirds of the articular surfaces of the articular tubercle, the articular disc and the mandibular head, split-lines ran in a correspondent rostrocaudal direction. In the lateral and medial aspects of these articular surfaces, the split-line pattern varied, displaying curved arrangements in the articular disc and punctual split-lines in the bony components. Mediolateral orientated split-lines were found in the rostral and caudal border of the articular disc and in the mandibular fossa. The complex movements during the equine chewing cycle are likely assigned to different areas of the TMJ. The split-line pattern of the equine TMJ is indicative of a relative movement of the joint components in a preferential rostrocaudal direction which is consigned to the central aspects of the TMJ. The lateral and medial aspects of the articular surfaces provide split-line patterns that indicate movements particularly around a dorsoventral axis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Early reversal cells in adult human bone remodeling

    DEFF Research Database (Denmark)

    Abdelgawad, Mohamed Essameldin; Delaissé, Jean-Marie; Hinge, Maja

    2016-01-01

    The mechanism coupling bone resorption and formation is a burning question that remains incompletely answered through the current investigations on osteoclasts and osteoblasts. An attractive hypothesis is that the reversal cells are likely mediators of this coupling. Their nature is a big matter...... of debate. The present study performed on human cancellous bone is the first one combining in situ hybridization and immunohistochemistry to demonstrate their osteoblastic nature. It shows that the Runx2 and CD56 immunoreactive reversal cells appear to take up TRAcP released by neighboring osteoclasts....... Earlier preclinical studies indicate that reversal cells degrade the organic matrix left behind by the osteoclasts and that this degradation is crucial for the initiation of the subsequent bone formation. To our knowledge, this study is the first addressing these catabolic activities in adult human bone...

  16. Segmenting articular cartilage automatically using a voxel classification approach

    DEFF Research Database (Denmark)

    Folkesson, Jenny; Dam, Erik B; Olsen, Ole F

    2007-01-01

    We present a fully automatic method for articular cartilage segmentation from magnetic resonance imaging (MRI) which we use as the foundation of a quantitative cartilage assessment. We evaluate our method by comparisons to manual segmentations by a radiologist and by examining the interscan...... reproducibility of the volume and area estimates. Training and evaluation of the method is performed on a data set consisting of 139 scans of knees with a status ranging from healthy to severely osteoarthritic. This is, to our knowledge, the only fully automatic cartilage segmentation method that has good...... agreement with manual segmentations, an interscan reproducibility as good as that of a human expert, and enables the separation between healthy and osteoarthritic populations. While high-field scanners offer high-quality imaging from which the articular cartilage have been evaluated extensively using manual...

  17. Hyaluronic acid versus saline intra-articular injections for amelioration of chronic knee osteoarthritis: A canine model.

    Science.gov (United States)

    Pashuck, Troy D; Kuroki, Keiichi; Cook, Cristi R; Stoker, Aaron M; Cook, James L

    2016-10-01

    The objective of this study was to assess the safety and efficacy of intra-articular injections of hyaluronic acid (HA) versus saline for symptomatic treatment of osteoarthritis (OA). Twenty-five adult purpose-bred dogs underwent meniscal release of one knee. Clinical, arthroscopic, and radiographic signs of OA were confirmed in all dogs prior to treatment. Dogs were randomized into five groups: HA-1 (n = 5), HA-3 (n = 5), HA-5 (n = 5), Saline-1 (n = 5), and Saline-3 (n = 5). Each dog received intra-articular injections of the respective substance into the affected knee at the pre-determined time points. Dogs were assessed for heat, swelling, and erythema after each injection and for lameness, pain, effusion, range of motion, kinetics, radiographic OA scoring, and arthroscopic scoring prior to treatment and for 6 months after injection. Dogs were then humanely euthanatized and the knees assessed grossly and histologically. Only mild heat, swelling, and/or erythema were noted in some dogs following injection and resolved within 1 week. Dogs treated with HA-1, HA-3, and HA-5 were significantly (p injection protocols were safe, superior to saline for short-term amelioration of symptoms associated with chronic OA, and can be translated to human OA treatment. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1772-1779, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  18. Smart and Controllable rAAV Gene Delivery Carriers in Progenitor Cells for Human Musculoskeletal Regenerative Medicine with a Focus on the Articular Cartilage.

    Science.gov (United States)

    Rey-Rico, Ana; Cucchiarini, Magali

    2017-01-01

    Cell therapy using mesenchymal stem cells (MSCs) is a powerful tool for the treatment of various diseases and injuries. Still, important limitations including the large amounts of cells required for application in vivo and the age-related decline in lifespan, proliferation, and potency may hinder the use of MSCs in patients. In this regard, gene therapy may offer strong approaches to optimize the use of MSCs for regenerative medicine. Diverse nonviral and viral gene vehicles have been manipulated to genetically modify MSCs, among which the highly effective and relatively safe recombinant adeno-associated viral (rAAV) vectors that emerged as the preferred gene delivery system to treat human disorders. Yet, clinical adaptation of such gene vehicles may be limited by several hurdles, including the possibility of dissemination to nontarget sites and the presence of immune and toxic responses in the host organism that may impair their therapeutic actions. The use of smart biomaterials acting as interfaces to enhance the temporal and spatial presentation of therapeutic agents in the target place and/or acting as scaffolding for MSC growth is an innovative, valuable approach to overcome these shortcomings that else restrain the efficacy of such potent cell populations. Here, we provide an overview on the most recent tissue engineering approaches based on the use of biomaterials acting as vehicles for rAAV vectors to target MSCs directly in the recipient (in vivo strategy) or as supportive matrices for rAAV-modified MSCs for indirect cell reimplantation (ex vivo strategy) as means to activate the reparative processes in tissues of the musculoskeletal system. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  19. Synergistic chondroprotective effects of curcumin and resveratrol in human articular chondrocytes: inhibition of IL-1beta-induced NF-kappaB-mediated inflammation and apoptosis.

    Science.gov (United States)

    Csaki, Constanze; Mobasheri, Ali; Shakibaei, Mehdi

    2009-01-01

    Currently available treatments for osteoarthritis (OA) are restricted to nonsteroidal anti-inflammatory drugs, which exhibit numerous side effects and are only temporarily effective. Thus novel, safe and more efficacious anti-inflammatory agents are needed for OA. Naturally occurring polyphenolic compounds, such as curcumin and resveratrol, are potent agents for modulating inflammation. Both compounds mediate their effects by targeting the NF-kappaB signalling pathway. We have recently demonstrated that in chondrocytes resveratrol modulates the NF-kappaB pathway by inhibiting the proteasome, while curcumin modulates the activation of NF-kappaB by inhibiting upstream kinases (Akt). However, the combinational effects of these compounds in chondrocytes has not been studied and/or compared with their individual effects. The aim of this study was to investigate the potential synergistic effects of curcumin and resveratrol on IL-1beta-stimulated human chondrocytes in vitro using immunoblotting and electron microscopy. Treatment with curcumin and resveratrol suppressed NF-kappaB-regulated gene products involved in inflammation (cyclooxygenase-2, matrix metalloproteinase (MMP)-3, MMP-9, vascular endothelial growth factor), inhibited apoptosis (Bcl-2, Bcl-xL, and TNF-alpha receptor-associated factor 1) and prevented activation of caspase-3. IL-1beta-induced NF-kappaB activation was suppressed directly by cocktails of curcumin and resveratrol through inhibition of Ikappakappa and proteasome activation, inhibition of IkappaBalpha phosphorylation and degradation, and inhibition of nuclear translocation of NF-kappaB. The modulatory effects of curcumin and resveratrol on IL-1beta-induced expression of cartilage specific matrix and proinflammatory enzymes were mediated in part by the cartilage-specific transcription factor Sox-9. We propose that combining these natural compounds may be a useful strategy in OA therapy as compared with separate treatment with each individual

  20. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults

    DEFF Research Database (Denmark)

    Larsen, Nadja; Vogensen, Finn Kvist; van der Berg, Franciscus Winfried J

    2010-01-01

    . Methods and Findings The study included 36 male adults with a broad range of age and body-mass indices (BMIs), among which 18 subjects were diagnosed with diabetes type 2. The fecal bacterial composition was investigated by real-time quantitative PCR (qPCR) and in a subgroup of subjects (N = 20) by tag...... = 0.04). Conclusions The results of this study indicate that type 2 diabetes in humans is associated with compositional changes in intestinal microbiota. The level of glucose tolerance should be considered when linking microbiota with metabolic diseases such as obesity and developing strategies......Background Recent evidence suggests that there is a link between metabolic diseases and bacterial populations in the gut. The aim of this study was to assess the differences between the composition of the intestinal microbiota in humans with type 2 diabetes and non-diabetic persons as control...

  1. Current status of imaging of articular cartilage

    International Nuclear Information System (INIS)

    Hodler, J.; Resnick, D.

    1996-01-01

    Various imaging methods have been applied to assessment of articular cartilage. These include standard radiography, arthrography, CT, CT arthrography, ultrasonography, and MR imaging. Radiography remains the initial musculoskeletal imaging method. However, it is insensitive to early stages of cartilage abnormalities. MR imaging has great potential in the assessment of articular cartilage, although high-quality scans are required because imaging signs of cartilage abnormalities may be subtle. The potential and limitations of various sequences and techniques are discussed, including MR arthrography. The role of the other imaging methods in assessment of articular cartilage appears to be limited. (orig.). With 8 figs., 6 tabs

  2. Postnatal development of depth-dependent collagen density in ovine articular cartilage

    NARCIS (Netherlands)

    Turnhout, van M.C.; Schipper, H.; Lagen, van B.; Zuilhof, H.; Kranenbarg, S.; Leeuwen, van J.L.

    2010-01-01

    Articular cartilage (AC) is the layer of tissue that covers the articulating ends of the bones in diarthrodial joints. Adult AC is characterised by a depth-dependent composition and structure of the extracellular matrix that results in depth-dependent mechanical properties, important for the

  3. Postnatal development of depth-dependent collagen density in ovine articular cartilage

    NARCIS (Netherlands)

    Turnhout, van M.C.; Schipper, H.; Lagen, van B.; Zuilhof, H.; Kranenbarg, S.; Leeuwen, van J.L.

    2010-01-01

    Background Articular cartilage (AC) is the layer of tissue that covers the articulating ends of the bones in diarthrodial joints. Adult AC is characterised by a depth-dependent composition and structure of the extracellular matrix that results in depth-dependent mechanical properties, important for

  4. Supporting Biomaterials for Articular Cartilage Repair

    Science.gov (United States)

    Duarte Campos, Daniela Filipa; Drescher, Wolf; Rath, Björn; Tingart, Markus

    2012-01-01

    Orthopedic surgeons and researchers worldwide are continuously faced with the challenge of regenerating articular cartilage defects. However, until now, it has not been possible to completely mimic the biological and biochemical properties of articular cartilage using current research and development approaches. In this review, biomaterials previously used for articular cartilage repair research are addressed. Furthermore, a brief discussion of the state of the art of current cell printing procedures mimicking native cartilage is offered in light of their use as future alternatives for cartilage tissue engineering. Inkjet cell printing, controlled deposition cell printing tools, and laser cell printing are cutting-edge techniques in this context. The development of mimetic hydrogels with specific biological properties relevant to articular cartilage native tissue will support the development of improved, functional, and novel engineered tissue for clinical application. PMID:26069634

  5. Articular manifestations in patients with Lyme disease.

    Science.gov (United States)

    Vázquez-López, María Esther; Díez-Morrondo, Carolina; Sánchez-Andrade, Amalia; Pego-Reigosa, Robustiano; Díaz, Pablo; Castro-Gago, Manuel

    To determine the percentage of Lyme patients with articular manifestations in NW Spain and to know their evolution and response to treatment. A retrospective study (2006-2013) was performed using medical histories of confirmed cases of Lyme disease showing articular manifestations. Clinical and laboratory characteristics, together with the treatment and evolution of the patients, were analysed. Seventeen out of 108 LD confirmed patients (15.7%) showed articular manifestations. Regarding those 17 patients, 64.7%, 29.4% and 5.9% presented arthritis, arthralgia and bursitis, respectively. The knee was the most affected joint. Articular manifestations were often associated to neurological, dermatological and cardiac pathologies. Otherwise, most patients were in Stage III. The 11.8% of the cases progressed to a recurrent chronic arthritis despite the administration of an appropriate treatment. Lyme disease patients showing articular manifestations should be included in the diagnosis of articular affections in areas of high risk of hard tick bite, in order to establish a suitable and early treatment and to avoid sequels. Copyright © 2015 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  6. The Effect of Body Mass on Outdoor Adult Human Decomposition.

    Science.gov (United States)

    Roberts, Lindsey G; Spencer, Jessica R; Dabbs, Gretchen R

    2017-09-01

    Forensic taphonomy explores factors impacting human decomposition. This study investigated the effect of body mass on the rate and pattern of adult human decomposition. Nine males and three females aged 49-95 years ranging in mass from 73 to 159 kg who were donated to the Complex for Forensic Anthropology Research between December 2012 and September 2015 were included in this study. Kelvin accumulated degree days (KADD) were used to assess the thermal energy required for subjects to reach several total body score (TBS) thresholds: early decomposition (TBS ≥6.0), TBS ≥12.5, advanced decomposition (TBS ≥19.0), TBS ≥23.0, and skeletonization (TBS ≥27.0). Results indicate no significant correlation between body mass and KADD at any TBS threshold. Body mass accounted for up to 24.0% of variation in decomposition rate depending on stage, and minor differences in decomposition pattern were observed. Body mass likely has a minimal impact on postmortem interval estimation. © 2017 American Academy of Forensic Sciences.

  7. Histomorphometry and cortical robusticity of the adult human femur.

    Science.gov (United States)

    Miszkiewicz, Justyna Jolanta; Mahoney, Patrick

    2018-01-13

    Recent quantitative analyses of human bone microanatomy, as well as theoretical models that propose bone microstructure and gross anatomical associations, have started to reveal insights into biological links that may facilitate remodeling processes. However, relationships between bone size and the underlying cortical bone histology remain largely unexplored. The goal of this study is to determine the extent to which static indicators of bone remodeling and vascularity, measured using histomorphometric techniques, relate to femoral midshaft cortical width and robusticity. Using previously published and new quantitative data from 450 adult human male (n = 233) and female (n = 217) femora, we determine if these aspects of femoral size relate to bone microanatomy. Scaling relationships are explored and interpreted within the context of tissue form and function. Analyses revealed that the area and diameter of Haversian canals and secondary osteons, and densities of secondary osteons and osteocyte lacunae from the sub-periosteal region of the posterior midshaft femur cortex were significantly, but not consistently, associated with femoral size. Cortical width and bone robusticity were correlated with osteocyte lacunae density and scaled with positive allometry. Diameter and area of osteons and Haversian canals decreased as the width of cortex and bone robusticity increased, revealing a negative allometric relationship. These results indicate that microscopic products of cortical bone remodeling and vascularity are linked to femur size. Allometric relationships between more robust human femora with thicker cortical bone and histological products of bone remodeling correspond with principles of bone functional adaptation. Future studies may benefit from exploring scaling relationships between bone histomorphometric data and measurements of bone macrostructure.

  8. Optical and Biometric Characteristics of Anisomyopia in Human Adults

    Science.gov (United States)

    Tian, Yibin; Tarrant, Janice; Wildsoet, Christine F.

    2011-01-01

    Purpose To investigate the role of higher order optical aberrations and thus retinal image degradation in the development of myopia, through the characterization of anisomyopia in human adults in terms of their optical and biometric characteristics. Methods The following data were collected from both eyes of fifteen young adult anisometropic myopes and sixteen isometropic myopes: subjective and objective refractive errors, corneal power and shape, monochromatic optical aberrations, anterior chamber depth, lens thickness, vitreous chamber depth, and best corrected visual acuity. Monochromatic aberrations were analyzed in terms of their higher order components, and further analyzed in terms of 31 optical quality metrics. Interocular differences for the two groups (anisomyopes vs. isomyopes) were compared and the relationship between measured ocular parameters and refractive errors also analyzed across all eyes. Results As expected, anisomyopes and isomyopes differed significantly in terms of interocular differences in vitreous chamber depth, axial length and refractive error. However, interocular differences in other optical properties showed no significant intergroup differences. Overall, higher myopia was associated with deeper anterior and vitreous chambers, higher astigmatism, more prolate corneas, and more positive spherical aberration. Other measured optical and biometric parameters were not significantly correlated with spherical refractive error, although some optical quality metrics and corneal astigmatism were significantly correlated with refractive astigmatism. Conclusions An optical cause for anisomyopia related to increased higher order aberrations is not supported by our data. Corneal shape changes and increased astigmatism in more myopic eyes may be a by-product of the increased anterior chamber growth in these eyes; likewise, the increased positive spherical aberration in more myopic eyes may be a product of myopic eye growth. PMID:21797915

  9. Articular chondrocyte metabolism and osteoarthritis

    Energy Technology Data Exchange (ETDEWEB)

    Leipold, H.R.

    1989-01-01

    The three main objectives of this study were: (1) to determine if depletion of proteoglycans from the cartilage matrix that occurs during osteoarthritis causes a measurable increase of cartilage proteoglycan components in the synovial fluid and sera, (2) to observe what effect intracellular cAMP has on the expression of matrix components by chondrocytes, and (3) to determine if freshly isolated chondrocytes contain detectable levels of mRNA for fibronectin. Canine serum keratan sulfate and hyaluronate were measured to determine if there was an elevation of these serum glycosaminoglycans in a canine model of osteoarthritis. A single intra-articular injection of chymopapain into a shoulder joint increased serum keratan sulfate 10 fold and hyaluronate less than 2 fold in 24 hours. Keratan sulfate concentrations in synovial fluids of dogs about one year old were unrelated to the presence of spontaneous cartilage degeneration in the joints. High keratan sulfate in synovial fluids correlated with higher keratan sulfate in serum. The mean keratan sulfate concentration in sera of older dogs with osteoarthritis was 37% higher than disease-free controls, but the difference between the groups was not statistically significant. Treatment of chondrocytes with 0.5 millimolar (mM) dibutyryl cAMP (DBcAMP) caused the cells to adopt a more rounded morphology. There was no difference between the amount of proteins synthesized by cultures treated with DBcAMP and controls. The amount of fibronectin (FN) in the media of DBcAMP treated cultures detected by an ELISA was specifically reduced, and the amount of {sup 35}S-FN purified by gelatin affinity chromatography decreased. Moreover, the percentage of FN containing the extra domain. A sequence was reduced. Concomitant with the decrease in FN there was an increase in the concentration of keratan sulfate.

  10. Body Weight Independently Affects Articular Cartilage Catabolism

    Directory of Open Access Journals (Sweden)

    W. Matt Denning, Jason G. Winward, Michael Becker Pardo, J. Ty Hopkins, Matthew K. Seeley

    2015-06-01

    Full Text Available Although obesity is associated with osteoarthritis, it is unclear whether body weight (BW independently affects articular cartilage catabolism (i.e., independent from physiological factors that also accompany obesity. The primary purpose of this study was to evaluate the independent effect of BW on articular cartilage catabolism associated with walking. A secondary purpose was to determine how decreased BW influenced cardiovascular response due to walking. Twelve able-bodied subjects walked for 30 minutes on a lower-body positive pressure treadmill during three sessions: control (unadjusted BW, +40%BW, and -40%BW. Serum cartilage oligomeric matrix protein (COMP was measured immediately before (baseline and after, and 15 and 30 minutes after the walk. Heart rate (HR and rate of perceived exertion (RPE were measured every three minutes during the walk. Relative to baseline, average serum COMP concentration was 13% and 5% greater immediately after and 15 minutes after the walk. Immediately after the walk, serum COMP concentration was 14% greater for the +40%BW session than for the -40%BW session. HR and RPE were greater for the +40%BW session than for the other two sessions, but did not differ between the control and -40%BW sessions. BW independently influences acute articular cartilage catabolism and cardiovascular response due to walking: as BW increases, so does acute articular cartilage catabolism and cardiovascular response. These results indicate that lower-body positive pressure walking may benefit certain individuals by reducing acute articular cartilage catabolism, due to walking, while maintaining cardiovascular response.

  11. Imaging of the cervical articular pillar

    Energy Technology Data Exchange (ETDEWEB)

    Yeomans, E. [Orange Base Hospital, Orange, NSW (Australia)

    1998-12-01

    The cervical articular pillar, due to the complex anatomical structure of the cervical spine, is not well demonstrated in routine plain radiographic views. Dedicated views have been devised to demonstrate the pillar, yet their performance has abated considerably since the inception of Computed Tomography (CT) in the 1970`s. It is the consideration that CT does not image the articular pillar with a 10 per cent accuracy that poses the question: Is there still a need for plain radiography of the cervical articular pillar? This paper studies the anatomy, plain radiography, and incidence of injury to the cervical articular pillar. It discusses (with reference to current and historic literature) the efficacy of current imaging protocols in depicting this injury. It deals with plain radiography, CT, complex tomography, and Magnetic Resonance Imaging (MRI) of the cervical spine to conclude there may still be a position in current imaging protocols for plain radiography of the cervical articular pillar. Copyright (1998) Australian Institute of Radiography 43 refs., 5 figs.

  12. Diverse roles of integrin receptors in articular cartilage.

    Science.gov (United States)

    Shakibaei, M; Csaki, C; Mobasheri, A

    2008-01-01

    Integrins are heterodimeric integral membrane proteins made up of alpha and beta subunits. At least eighteen alpha and eight beta subunit genes have been described in mammals. Integrin family members are plasma membrane receptors involved in cell adhesion and active as intra- and extracellular signalling molecules in a variety of processes including embryogenesis, hemostasis, tissue repair, immune response and metastatic spread of tumour cells. Integrin beta 1 (beta1-integrin), the protein encoded by the ITGB1 gene (also known as CD29 and VLAB), is a multi-functional protein involved in cell-matrix adhesion, cell signalling, cellular defense, cell adhesion, protein binding, protein heterodimerisation and receptor-mediated activity. It is highly expressed in the human body (17.4 times higher than the average gene in the last updated revision of the human genome). The extracellular matrix (ECM) of articular cartilage is a unique environment. Interactions between chondrocytes and the ECM regulate many biological processes important to homeostasis and repair of articular cartilage, including cell attachment, growth, differentiation and survival. The beta1-integrin family of cell surface receptors appears to play a major role in mediating cell-matrix interactions that are important in regulating these fundamental processes. Chondrocyte mechanoreceptors have been proposed to incorporate beta1-integrins and mechanosensitive ion channels which link with key ECM, cytoskeletal and signalling proteins to maintain the chondrocyte phenotype, prevent chondrocyte apoptosis and regulate chondrocyte-specific gene expression. This review focuses on the expression and function of beta1-integrins in articular chondrocytes, its role in the unique biology of these cells and its distribution in cartilage.

  13. Spread of Injectate Around Hip Articular Sensory Branches of the Femoral Nerve in Cadavers

    DEFF Research Database (Denmark)

    Nielsen, Niels Dalsgaard; Greher, Manfred; Moriggl, Bernhard

    2018-01-01

    of the femoral nerve. Methods: Fifteen cadaver sides were injected with 5 mL dye in the iliopsoas plane guided by ultrasound. Dissection was performed to verify the spread of injectate around the hip articular branches of the femoral nerve. Results: In 10 dissections (67% [95% confidence interval: 38.......2-32%]) adhesions partially obstructed the spread of dye. Conclusion: An injection of 5 mL in the iliopsoas plane spreads around all hip articular branches of the femoral nerve in 10 of 15 cadaver sides. If these findings translate to living humans, injection of local anaesthetic into the iliopsoas plane could...

  14. Rabbit articular cartilage defects treated by allogenic chondrocyte transplantation

    OpenAIRE

    Boopalan, P. R. J. V. C.; Sathishkumar, Solomon; Kumar, Senthil; Chittaranjan, Samuel

    2006-01-01

    Articular cartilage defects have a poor capacity for repair. Most of the current treatment options result in the formation of fibro-cartilage, which is functionally inferior to normal hyaline articular cartilage. We studied the effectiveness of allogenic chondrocyte transplantation for focal articular cartilage defects in rabbits. Chondrocytes were cultured in vitro from cartilage harvested from the knee joints of a New Zealand White rabbit. A 3 mm defect was created in the articular cartilag...

  15. Understanding Older Adult's Perceptions of Factors that Support Trust in Human and Robot Care Providers.

    Science.gov (United States)

    Stuck, Rachel E; Rogers, Wendy A

    2017-06-01

    As the population of older adults increase so will the need for care providers, both human and robot. Trust is a key aspect to establish and maintain a successful older adult-care provider relationship. However, due to trust volatility it is essential to understand it within specific contexts. This proposed mixed methods study will explore what dimensions of trust emerge as important within the human-human and human-robot dyads in older adults and care providers. First, this study will help identify key qualities that support trust in a care provider relationship. By understanding what older adults perceive as needing to trust humans and robots for various care tasks, we can begin to provide recommendations based on user expectations for design to support trust.

  16. Transcriptional profiling of adult neural stem-like cells from the human brain.

    Directory of Open Access Journals (Sweden)

    Cecilie Jonsgar Sandberg

    Full Text Available There is a great potential for the development of new cell replacement strategies based on adult human neural stem-like cells. However, little is known about the hierarchy of cells and the unique molecular properties of stem- and progenitor cells of the nervous system. Stem cells from the adult human brain can be propagated and expanded in vitro as free floating neurospheres that are capable of self-renewal and differentiation into all three cell types of the central nervous system. Here we report the first global gene expression study of adult human neural stem-like cells originating from five human subventricular zone biopsies (mean age 42, range 33-60. Compared to adult human brain tissue, we identified 1,189 genes that were significantly up- and down-regulated in adult human neural stem-like cells (1% false discovery rate. We found that adult human neural stem-like cells express stem cell markers and have reduced levels of markers that are typical of the mature cells in the nervous system. We report that the genes being highly expressed in adult human neural stem-like cells are associated with developmental processes and the extracellular region of the cell. The calcium signaling pathway and neuroactive ligand-receptor interactions are enriched among the most differentially regulated genes between adult human neural stem-like cells and adult human brain tissue. We confirmed the expression of 10 of the most up-regulated genes in adult human neural stem-like cells in an additional sample set that included adult human neural stem-like cells (n = 6, foetal human neural stem cells (n = 1 and human brain tissues (n = 12. The NGFR, SLITRK6 and KCNS3 receptors were further investigated by immunofluorescence and shown to be heterogeneously expressed in spheres. These receptors could potentially serve as new markers for the identification and characterisation of neural stem- and progenitor cells or as targets for manipulation of cellular

  17. Pure waterjet drilling of articular bone: an in vitro feasibility study.

    NARCIS (Netherlands)

    den Dunnen, Steven; Kraaij, Gert; Biskup, Christian; Kerkhoffs, Gino M. M. J.; Tuijthof, Gabriëlle J. M.

    2013-01-01

    The clinical application of waterjet technology for machining tough human tissues, such as articular bone, has advantages, as it produces clean sharp cuts without tissue heating. Additionally, water supply is possible via flexible tubing, which enables minimally invasive surgical access. This pilot

  18. Comparison of MRI-based estimates of articular cartilage contact area in the tibiofemoral joint.

    Science.gov (United States)

    Henderson, Christopher E; Higginson, Jill S; Barrance, Peter J

    2011-01-01

    Knee osteoarthritis (OA) detrimentally impacts the lives of millions of older Americans through pain and decreased functional ability. Unfortunately, the pathomechanics and associated deviations from joint homeostasis that OA patients experience are not well understood. Alterations in mechanical stress in the knee joint may play an essential role in OA; however, existing literature in this area is limited. The purpose of this study was to evaluate the ability of an existing magnetic resonance imaging (MRI)-based modeling method to estimate articular cartilage contact area in vivo. Imaging data of both knees were collected on a single subject with no history of knee pathology at three knee flexion angles. Intra-observer reliability and sensitivity studies were also performed to determine the role of operator-influenced elements of the data processing on the results. The method's articular cartilage contact area estimates were compared with existing contact area estimates in the literature. The method demonstrated an intra-observer reliability of 0.95 when assessed using Pearson's correlation coefficient and was found to be most sensitive to changes in the cartilage tracings on the peripheries of the compartment. The articular cartilage contact area estimates at full extension were similar to those reported in the literature. The relationships between tibiofemoral articular cartilage contact area and knee flexion were also qualitatively and quantitatively similar to those previously reported. The MRI-based knee modeling method was found to have high intra-observer reliability, sensitivity to peripheral articular cartilage tracings, and agreeability with previous investigations when using data from a single healthy adult. Future studies will implement this modeling method to investigate the role that mechanical stress may play in progression of knee OA through estimation of articular cartilage contact area.

  19. Radiation synovectomy stimulates glycosaminoglycan synthesis by normal articular cartilage

    International Nuclear Information System (INIS)

    Myers, S.L.; Slowman, S.D.; Brandt, K.D.

    1989-01-01

    Radiation synovectomy has been considered a therapeutic alternative to surgical synovectomy. Whether intraarticular irradiation affects the composition or biochemistry, and therefore the biomechanical properties, of normal articular cartilage has not been established. In the present study, yttrium 90 silicate was injected into one knee of nine normal adult dogs, and three other dogs received nonradioactive yttrium silicate. When the animals were killed 4 to 13 weeks after the injection, synovium from the irradiated knees showed areas of necrosis and fibrosis. Up to 29% less hyaluronate was synthesized in vitro by the synovial intima from irradiated knees than by the intima from the contralateral knees (mean difference 18%). Morphologic abnormalities were not observed in articular cartilage from either the irradiated or control knees, nor did the water content or concentrations of uronic acid or DNA in cartilage from the irradiated knees differ from that in cartilage from the contralateral knees. However, net 35 SO 4 -labeled glycosaminoglycan synthesis in organ cultures of cartilage from irradiated knees was increased (mean difference 21%, p = 0.03) in comparison with that in cultures of contralateral knee cartilage

  20. Radiation synovectomy stimulates glycosaminoglycan synthesis by normal articular cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Myers, S.L.; Slowman, S.D.; Brandt, K.D.

    1989-07-01

    Radiation synovectomy has been considered a therapeutic alternative to surgical synovectomy. Whether intraarticular irradiation affects the composition or biochemistry, and therefore the biomechanical properties, of normal articular cartilage has not been established. In the present study, yttrium 90 silicate was injected into one knee of nine normal adult dogs, and three other dogs received nonradioactive yttrium silicate. When the animals were killed 4 to 13 weeks after the injection, synovium from the irradiated knees showed areas of necrosis and fibrosis. Up to 29% less hyaluronate was synthesized in vitro by the synovial intima from irradiated knees than by the intima from the contralateral knees (mean difference 18%). Morphologic abnormalities were not observed in articular cartilage from either the irradiated or control knees, nor did the water content or concentrations of uronic acid or DNA in cartilage from the irradiated knees differ from that in cartilage from the contralateral knees. However, net /sup 35/SO/sub 4/-labeled glycosaminoglycan synthesis in organ cultures of cartilage from irradiated knees was increased (mean difference 21%, p = 0.03) in comparison with that in cultures of contralateral knee cartilage.

  1. Germline stem cells and neo-oogenesis in the adult human ovary.

    Science.gov (United States)

    Liu, Yifei; Wu, Chao; Lyu, Qifeng; Yang, Dongzi; Albertini, David F; Keefe, David L; Liu, Lin

    2007-06-01

    It remains unclear whether neo-oogenesis occurs in postnatal ovaries of mammals, based on studies in mice. We thought to test whether adult human ovaries contain germline stem cells (GSCs) and undergo neo-oogenesis. Rather than using genetic manipulation which is unethical in humans, we took the approach of analyzing the expression of meiotic marker genes and genes for germ cell proliferation, which are required for neo-oogenesis, in adult human ovaries covering an age range from 28 to 53 years old, compared to testis and fetal ovaries served as positive controls. We show that active meiosis, neo-oogenesis and GSCs are unlikely to exist in normal, adult, human ovaries. No early meiotic-specific or oogenesis-associated mRNAs for SPO11, PRDM9, SCP1, TERT and NOBOX were detectable in adult human ovaries using RT-PCR, compared to fetal ovary and adult testis controls. These findings are further corroborated by the absence of early meiocytes and proliferating germ cells in adult human ovarian cortex probed with markers for meiosis (SCP3), oogonium (OCT3/4, c-KIT), and cell cycle progression (Ki-67, PCNA), in contrast to fetal ovary controls. If postnatal oogenesis is confirmed in mice, then this species would represent an exception to the rule that neo-oogenesis does not occur in adults.

  2. Advanced Strategies for Articular Cartilage Defect Repair

    Directory of Open Access Journals (Sweden)

    Fergal J. O'Brien

    2013-02-01

    Full Text Available Articular cartilage is a unique tissue owing to its ability to withstand repetitive compressive stress throughout an individual’s lifetime. However, its major limitation is the inability to heal even the most minor injuries. There still remains an inherent lack of strategies that stimulate hyaline-like articular cartilage growth with appropriate functional properties. Recent scientific advances in tissue engineering have made significant steps towards development of constructs for articular cartilage repair. In particular, research has shown the potential of biomaterial physico-chemical properties significantly influencing the proliferation, differentiation and matrix deposition by progenitor cells. Accordingly, this highlights the potential of using such properties to direct the lineage towards which such cells follow. Moreover, the use of soluble growth factors to enhance the bioactivity and regenerative capacity of biomaterials has recently been adopted by researchers in the field of tissue engineering. In addition, gene therapy is a growing area that has found noteworthy use in tissue engineering partly due to the potential to overcome some drawbacks associated with current growth factor delivery systems. In this context, such advanced strategies in biomaterial science, cell-based and growth factor-based therapies that have been employed in the restoration and repair of damaged articular cartilage will be the focus of this review article.

  3. A Cell Model to Evaluate Chemical Effects on Adult Human Cardiac Progenitor Cell Differentiation and Function

    Science.gov (United States)

    Adult cardiac stem cells (CSC) and progenitor cells (CPC) represent a population of cells in the heart critical for its regeneration and function over a lifetime. The impact of chemicals on adult human CSC/CPC differentiation and function is unknown. Research was conducted to dev...

  4. The potential pitfalls of studying adult sex ratios at aggregate levels in humans

    NARCIS (Netherlands)

    Pollet, Thomas V.; Stoevenbelt, Andrea H.; Kuppens, Toon

    2017-01-01

    Human adult sex ratios have been studied extensively across the biological and social sciences. While several studies have examined adult sex ratio effects in a multilevel perspective, many studies have focused on effects at an aggregated level only. In this paper, we review some key issues relating

  5. [Technique and value of direct MR arthrography applying articular distraction].

    Science.gov (United States)

    Becce, Fabio; Wettstein, Michael; Guntern, Daniel; Mouhsine, Elyazid; Palhais, Nuno; Theumann, Nicolas

    2010-02-24

    Direct MR arthrography has a better diagnostic accuracy than MR imaging alone. However, contrast material is not always homogeneously distributed in the articular space. Lesions of cartilage surfaces or intra-articular soft tissues can thus be misdiagnosed. Concomitant application of axial traction during MR arthrography leads to articular distraction. This enables better distribution of contrast material in the joint and better delineation of intra-articular structures. Therefore, this technique improves detection of cartilage lesions. Moreover, the axial stress applied on articular structures may reveal lesions invisible on MR images without traction. Based on our clinical experience, we believe that this relatively unknown technique is promising and should be further developed.

  6. Intra-articular osteoid osteoma as a differential diagnosis of diffuse mono-articular joint pain.

    Science.gov (United States)

    Rolvien, Tim; Zustin, Jozef; Mussawy, Haider; Schmidt, Tobias; Pogoda, Pia; Ueblacker, Peter

    2016-11-04

    The aim of this retrospective study was to investigate the frequency of intra-articular osteoid osteoma (iaOO) in a large study cohort and to demonstrate its clinical relevance as an important differential diagnosis of non-specific mono-articular joint pain. We searched the registry for bone tumours of the University Medical Centre Hamburg-Eppendorf for osteoid osteomas in the last 42 years. Herein, we present three selected iaOO which were detected in the three major weight-bearing joints. Computed tomography (CT) or magnetic resonance imaging (MRI) scans were performed for initial diagnosis. Out of a total of 367 osteoid osteomas, 19 (5.2 %) tumours were localized intra-articularly. In all three presented tumours, a history of severe mono-articular pain was reported; however, the mean time to correct diagnosis was delayed to 20.7 months. Clearly, the nidus seen in CT and MRI images in combination with inconsistent salicylate-responsive nocturnal pain led to the diagnosis of iaOO. Rarely, osteoid osteoma can occur in an intra-articular location. In cases of diffuse mono-articular pain, iaOO should be considered both in large and smaller joints to avoid delays in diagnosis and therapy of this benign bone tumour.

  7. Morphometric anatomical and CT study of the human adult sacroiliac region.

    Science.gov (United States)

    Postacchini, Roberto; Trasimeni, Guido; Ripani, Francesca; Sessa, Pasquale; Perotti, Stefano; Postacchini, Franco

    2017-01-01

    To identify and describe the morphometry and CT features of the articular and extra-articular portions of the sacroiliac region. The resulting knowledge might help to avoid complications in sacroiliac joint (SIJ) fusion. We analyzed 102 dry hemi-sacra, 80 ilia, and 10 intact pelves and assessed the pelvic computerized tomography (CT) scans of 90 patients, who underwent the examination for conditions not involving the pelvis. We assessed both the posterior aspect of sacrum with regard to the depressions located externally to the lateral sacral crest at the level of the proximal three sacral vertebrae and the posteroinferior aspect of ilium. Coronal and axial CT scans of the SIJ of patients were obtained and the joint space was measured. On each side, the sacrum exhibits three bone depressions, not described in anatomic textbooks or studies, facing the medial aspect of the posteroinferior ilium, not yet described in detail. Both structures are extra-articular portions situated posteriorly to the SIJ. Coronal CT scans of patients showing the first three sacral foramens and the interval between sacrum and ilium as a continuous space display only the S1 and S3 portions of SIJ, the intermediate portion being extra-articular. The S2 portion is visible on the most anterior coronal scan. Axial scans show articular and extra-articular portions and features improperly described as anatomic variations. Extra-articular portions of the sacroiliac region, not yet described exhaustively, have often been confused with SIJ. Coronal CT scans through the middle part of sacrum, the most used to evaluate degenerative and inflammatory conditions of SIJ, show articular and extra-articular portions of the region.

  8. The potential pitfalls of studying adult sex ratios at aggregate levels in humans.

    Science.gov (United States)

    Pollet, Thomas V; Stoevenbelt, Andrea H; Kuppens, Toon

    2017-09-19

    Human adult sex ratios have been studied extensively across the biological and social sciences. While several studies have examined adult sex ratio effects in a multilevel perspective, many studies have focused on effects at an aggregated level only. In this paper, we review some key issues relating to such analyses. We address not only nation-level analyses, but also aggregation at lower levels, to investigate whether these issues extend to lower levels of aggregation. We illustrate these issues with novel databases covering a broad range of variables. Specifically, we discuss distributional issues with aggregated measures of adult sex ratio, significance testing, and statistical non-independence when using aggregate data. Firstly, we show that there are severe distributional issues with national adult sex ratio, such as extreme cases. Secondly, we demonstrate that many 'meaningless' variables are significantly correlated with adult sex ratio (e.g. the max. elevation level correlates with sex ratio at US state level). Finally, we re-examine associations between adult sex ratios and teenage fertility and find no robust evidence for an association at the aggregate level. Our review highlights the potential issues of using aggregate data on adult sex ratios to test hypotheses from an evolutionary perspective in humans.This article is part of the themed issue 'Adult sex ratios and reproductive decisions: a critical re-examination of sex differences in human and animal societies'. © 2017 The Author(s).

  9. THE FUNCTIONAL EFFECTIVENESS OF A CELL-ENGINEERED CONSTRUCT FOR THE REGENERATION OF ARTICULAR CARTILAGE

    Directory of Open Access Journals (Sweden)

    V. I. Sevastianov

    2015-01-01

    Full Text Available The aim of this study is an analysis of the functional effectiveness of a biomedical cell product consisting of a biopolymer microheterogeneous collagen-containing hydrogel (BMCH, human adipose-derived mesenchymal stromal cells (hADMSCs, and chondrogenic induction medium in the regeneration of articular cartilage. Materials and methods. The test model of the adjuvant arthritis was used (female Soviet Chinchilla rabbits with the further development into osteoarthrosis (OA combined with the clinical, biochemical, radiological, and histochemical trials. Results. On Day 92 of the OA model it has been found that the intra-articular introduction of a BMCH with hADMSCs into the left knee joint (n = 3 30 days after the OA modeling, as opposed to the right joint (negative control, n = 3, stimulates the regenerative processes of the cartilaginous tissue structure characterized by the formation of chondrocyte «columns», the emergence of isogenic groups in the intracellular matrix and the regeneration of its structure. Upon the intra-articular introduction of a BMCH (n = 3 such effects are markedly less pronounced. Conclusions. A significant regenerative potential of a cell-engineered construct of human articular tissue (CEC ATh has been proven. It is possible to presume that biostimulating properties of CEC ATh are due to the activating effect of a biomedical cell product on the stem cell migration processes from the surrounding tissue into the injured area with their subsequent differentiation. 

  10. Human Capital Development: Reforms for Adult and Community Education

    Science.gov (United States)

    Choy, Sarojni; Haukka, Sandra

    2007-01-01

    The adult and community education (ACE) sector is consistently responsive to changing community needs and government priorities. It is this particular function that has drawn ACE into the lifelong learning debate as one model for sustaining communities. The responsiveness of ACE means that the sector and its programs continue to make valuable…

  11. Molecular identification of Giardia lamblia isolates from adult human ...

    African Journals Online (AJOL)

    ARL

    2013-02-27

    Feb 27, 2013 ... Giardia lamblia is a flagellated protozoa that infects the intestinal tract of a wide range of mammalian hosts, including both wild and domestic animals as well as humans. Two genotypes A and B are commonly reported among humans. The purpose of this study was to investigate the genotypes of G.

  12. Adult Education and Human Capital: Leadership from the Fortune 500.

    Science.gov (United States)

    Palmer, Teresa M.

    1992-01-01

    A survey of 333 Fortune 500 firms received 81 replies indicating that (1) two-thirds formally recognized the value of human resources; (2) most had changed corporate policy regarding human capital; and (3) most training was provided in the ares of new employee orientation, current job needs, customer relations, personal development, and…

  13. Alternative Sources of Adult Stem Cells: Human Amniotic Membrane

    Science.gov (United States)

    Wolbank, Susanne; van Griensven, Martijn; Grillari-Voglauer, Regina; Peterbauer-Scherb, Anja

    Human amniotic membrane is a highly promising cell source for tissue engineering. The cells thereof, human amniotic epithelial cells (hAEC) and human amniotic mesenchymal stromal cells (hAMSC), may be immunoprivileged, they represent an early developmental status, and their application is ethically uncontroversial. Cell banking strategies may use freshly isolated cells or involve in vitro expansion to increase cell numbers. Therefore, we have thoroughly characterized the effect of in vitro cultivation on both phenotype and differentiation potential of hAEC. Moreover, we present different strategies to improve expansion including replacement of animal-derived supplements by human platelet products or the introduction of the catalytic subunit of human telomerase to extend the in vitro lifespan of amniotic cells. Characterization of the resulting cultures includes phenotype, growth characteristics, and differentiation potential, as well as immunogenic and immunomodulatory properties.

  14. A century of trends in adult human height

    DEFF Research Database (Denmark)

    Damsgaard, Camilla Trab; Michaelsen, Kim F.; Molbo, Drude

    2016-01-01

    in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5-22.7) and 16.5 cm (13.3-19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over...... the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8-144.8). The height differential between the tallest...... and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries....

  15. Intra-articular morphine in horses

    DEFF Research Database (Denmark)

    Lindegaard, Casper

    separated by a three week washout period. Before each treatment, radiocarpal synovitis was induced by IA injection of lipopolysaccharide (LPS). For each of the two 168-hours study periods, local and systemic measures of pain and inflammation as well as blood and synovial fluid (SF) samples...... for pharmacological analysis were obtained repeatedly. Pain was evaluated by degree of lameness as well as using a visual analogue scale of pain intensity (VAS) and a composite measure pain scale (CMPS), developed for this purpose. Intra-articular injection of LPS elicited a marked synovitis resulting in lameness...... and pain. Intra-articularly administered morphine showed a significant analgesic effect as measured by reduced lameness scores, less administered rescue analgesia and lower pain scores. A significant anti-inflammatory effect was demonstrated by reduced joint swelling, reduced SF serum amyloid A (SAA...

  16. The minor collagens in articular cartilage

    DEFF Research Database (Denmark)

    Luo, Yunyun; Sinkeviciute, Dovile; He, Yi

    2017-01-01

    Articular cartilage is a connective tissue consisting of a specialized extracellular matrix (ECM) that dominates the bulk of its wet and dry weight. Type II collagen and aggrecan are the main ECM proteins in cartilage. However, little attention has been paid to less abundant molecular components......, especially minor collagens, including type IV, VI, IX, X, XI, XII, XIII, and XIV, etc. Although accounting for only a small fraction of the mature matrix, these minor collagens not only play essential structural roles in the mechanical properties, organization, and shape of articular cartilage, but also...... fulfil specific biological functions. Genetic studies of these minor collagens have revealed that they are associated with multiple connective tissue diseases, especially degenerative joint disease. The progressive destruction of cartilage involves the degradation of matrix constituents including...

  17. Fetal hyperglycemia changes human preadipocyte function in adult life

    DEFF Research Database (Denmark)

    Hansen, Ninna Schiøler; Strasko, Klaudia Stanislawa; Hjort, Line

    2017-01-01

    Context: Offspring of women with gestational diabetes (O-GDM) or type 1 diabetes mellitus (O-T1DM) have been exposed to hyperglycemia in utero and have an increased risk of developing metabolic disease in adulthood. Design: In total, we recruited 206 adult offspring comprising the two fetal...... acid supply. Conclusions: Taken together, these findings show that intrinsic epigenetic and functional changes exist in preadipocyte cultures from individuals exposed to fetal hyperglycemia who are at increased risk of developing metabolic disease....

  18. Oxygen, nitric oxide and articular cartilage

    Directory of Open Access Journals (Sweden)

    B Fermor

    2007-04-01

    Full Text Available Molecular oxygen is required for the production of nitric oxide (NO, a pro-inflammatory mediator that is associated with osteoarthritis and rheumatoid arthritis. To date there has been little consideration of the role of oxygen tension in the regulation of nitric oxide production associated with arthritis. Oxygen tension may be particularly relevant to articular cartilage since it is avascular and therefore exists at a reduced oxygen tension. The superficial zone exists at approximately 6% O2, while the deep zone exists at less than 1% O2. Furthermore, oxygen tension can alter matrix synthesis, and the material properties of articular cartilage in vitro.The increase in nitric oxide associated with arthritis can be caused by pro-inflammatory cytokines and mechanical stress. Oxygen tension significantly alters endogenous NO production in articular cartilage, as well as the stimulation of NO in response to both mechanical loading and pro-inflammatory cytokines. Mechanical loading and pro-inflammatory cytokines also increase the production of prostaglandin E2 (PGE2. There is a complex interaction between NO and PGE2, and oxygen tension can alter this interaction. These findings suggest that the relatively low levels of oxygen within the joint may have significant influences on the metabolic activity, and inflammatory response of cartilage as compared to ambient levels. A better understanding of the role of oxygen in the production of inflammatory mediators in response to mechanical loading, or pro-inflammatory cytokines, may aid in the development of strategies for therapeutic intervention in arthritis.

  19. Pharmacokinetics of triamcinolone acetonide following intramuscular and intra-articular administration to exercised Thoroughbred horses.

    Science.gov (United States)

    Knych, H K; Vidal, M A; Casbeer, H C; McKemie, D S

    2013-11-01

    The use of triamcinolone acetonide (TA) in performance horses necessitates establishing appropriate withdrawal times prior to performance. To describe the plasma pharmacokinetics of TA and time-related urine and synovial fluid concentrations following i.m. and intra-articular administration to exercised Thoroughbred horses. Block design. Twelve racing fit adult Thoroughbred horses received a single i.m. administration of TA (0.1 mg/kg bwt). After an appropriate washout period, the same horses then received a single intra-articular TA administration (9 mg) into the right antebrachiocarpal joint. Blood, urine and synovial fluid samples were collected prior to, and at various times, up to 60 days post drug administration and analysed using liquid chromatography-mass spectrometry. Plasma data were analysed using noncompartmental analysis. Maximum measured plasma TA concentrations were 0.996 ± 0.391 at 13.2 h and 1.27 ± 0.278 ng/ml at 6.5 h for i.m. and intra-articular administration, respectively. The plasma terminal elimination half-life was 11.4 ± 6.53 and 0.78 ± 1.00 days for i.m. and intra-articular administration, respectively. Following i.m. administration, TA was below the limit of detection (LOD) by Days 52 and 60 in plasma and urine, respectively. Following intra-articular administration TA was undetectable by Day 7 in plasma and Day 8 in urine. Triamcinolone acetonide was also undetectable in any of the joints sampled following i.m. administration and remained above the limit of quantitation (LOQ) for 21 days following intra-articular administration. This study extends previous studies describing the pharmacokinetics of TA following i.m. and intra-articular administration to the horse and suggests that plasma and urine concentrations are not a good indicator of synovial fluid concentrations. Furthermore, results of this study supports an extended withdrawal time for TA given i.m. © 2013 EVJ Ltd.

  20. Development of a Spring-Loaded Impact Device to Deliver Injurious Mechanical Impacts to the Articular Cartilage Surface

    Science.gov (United States)

    Alexander, Peter G.; Song, Yingjie; Taboas, Juan M.; Chen, Faye H.; Melvin, Gary M.; Manner, Paul A.

    2013-01-01

    Objective: Traumatic impacts on the articular joint surface in vitro are known to lead to degeneration of the cartilage. The main objective of this study was to develop a spring-loaded impact device that can be used to deliver traumatic impacts of consistent magnitude and rate and to find whether impacts cause catabolic activities in articular cartilage consistent with other previously reported impact models and correlated with the development of osteoarthritic lesions. In developing the spring-loaded impactor, the operating hypothesis is that a single supraphysiologic impact to articular cartilage in vitro can affect cartilage integrity, cell viability, sulfated glycosaminoglycan and inflammatory mediator release in a dose-dependent manner. Design: Impacts of increasing force are delivered to adult bovine articular cartilage explants in confined compression. Impact parameters are correlated with tissue damage, cell viability, matrix and inflammatory mediator release, and gene expression 24 hours postimpact. Results: Nitric oxide release is first detected after 7.7 MPa impacts, whereas cell death, glycosaminoglycan release, and prostaglandin E2 release are first detected at 17 MPa. Catabolic markers increase linearly to maximal levels after ≥36 MPa impacts. Conclusions: A single supraphysiologic impact negatively affects cartilage integrity, cell viability, and GAG release in a dose-dependent manner. Our findings showed that 7 to 17 MPa impacts can induce cell death and catabolism without compromising the articular surface, whereas a 17 MPa impact is sufficient to induce increases in most common catabolic markers of osteoarthritic degeneration. PMID:26069650

  1. Hesperetin induces melanin production in adult human epidermal melanocytes.

    Science.gov (United States)

    Usach, Iris; Taléns-Visconti, Raquel; Magraner-Pardo, Lorena; Peris, José-Esteban

    2015-06-01

    One of the major sources of flavonoids for humans are citrus fruits, hesperidin being the predominant flavonoid. Hesperetin (HSP), the aglycon of hesperidin, has been reported to provide health benefits such as antioxidant, anti-inflammatory and anticarcinogenic effects. However, the effect of HSP on skin pigmentation is not clear. Some authors have found that HSP induces melanogenesis in murine B16-F10 melanoma cells, which, if extrapolated to in vivo conditions, might protect skin against photodamage. Since the effect of HSP on normal melanocytes could be different to that observed on melanoma cells, the described effect of HSP on murine melanoma cells has been compared to the effect obtained using normal human melanocytes. HSP concentrations of 25 and 50 µM induced melanin synthesis and tyrosinase activity in human melanocytes in a concentration-dependent manner. Compared to control melanocytes, 25 µM HSP increased melanin production and tyrosinase activity 1.4-fold (p melanin production in human melanocyte cultures could be reproduced on human skin. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Role of platelet-rich plasma in articular cartilage injury and disease.

    Science.gov (United States)

    Mascarenhas, Randy; Saltzman, Bryan M; Fortier, Lisa A; Cole, Brian J

    2015-02-01

    Clinical and laboratory research aimed at biological approaches to cartilage repair are currently in high demand due to the poor regenerative capacity of articular cartilage in the setting of a diseased articular environment. Platelet-rich plasma (PRP) takes advantage of supraphysiological concentrations of platelets and their growth factors harbored in α-granules, which together attempt to return the diseased articular cartilage to a preinjury state. The local use of PRP directly at the site of cartilage injury is thought to stimulate a natural healing cascade and accelerate the formation of cartilage repair tissue. This article provides an overview of the basic science behind the use of PRP in the treatment of cartilage injury and disease. Both initial and current examples of the use of intra-articular PRP in clinical human studies are provided. These include the use of PRP either alone or as an augmentation device with various other procedures, including arthroscopic microfracture and cell-free resorbable polyglycolic acid-hyaluronan implantation. Finally, the authors describe some of the potential future roles of PRP in clinical settings based on recent literature. These include Achilles tendon rupture, chronic tendinosis, chronic rotator cuff tendinopathy or tearing, muscle injury, and meniscal repair. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  3. Molecular Mechanism of Adult Neurogenesis and its Association with Human Brain Diseases

    Directory of Open Access Journals (Sweden)

    He Liu

    2016-01-01

    Full Text Available Recent advances in neuroscience challenge the old dogma that neurogenesis occurs only during embryonic development. Mounting evidence suggests that functional neurogenesis occurs throughout adulthood. This review article discusses molecular factors that affect adult neurogenesis, including morphogens, growth factors, neurotransmitters, transcription factors, and epigenetic factors. Furthermore, we summarize and compare current evidence of associations between adult neurogenesis and human brain diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and brain tumors.

  4. Customized Fabrication of Osteochondral Tissue for Articular Joint Surface Repair

    Science.gov (United States)

    2016-09-01

    AWARD NUMBER: W81XWH-14-1-0217 TITLE: Customized Fabrication of Osteochondral Tissue for Articular Joint Surface Repair PRINCIPAL INVESTIGATOR...4. TITLE AND SUBTITLE Customized Fabrication of Osteochondral Tissue for Articular Joint Surface Repair 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH...applicability of these novel osteochondral tissues for articular cartilage repair in rabbit model, using medical imaging-guided PSL. Such an approach may

  5. Development and application of the Chinese adult female computational phantom Rad-HUMAN

    International Nuclear Information System (INIS)

    Wu, Yican; Cheng, Mengyun; Wang, Wen; Fan, Yanchang; Zhao, Kai; He, Tao; Pei, Xi; Shang, Leiming; Chen, Chaobin; Long, Pengcheng; Cao, Ruifen; Wang, Guozhong; Zhou, Shaoheng; Yu, Shengpeng; Hu, Liqin; Zeng, Q.

    2013-01-01

    Rad-HUMAN is a whole-body numerical phantom of a Chinese adult woman which contains 46 organs and tissues and was created by MCAM6 software using the color photographs of the Chinese Visible Human dataset. This dataset was obtained from a 22-year old Chinese female cadaver judged to represent normal human anatomy as much as possible. The density and elemental composition recommended in the ICRP Publication 89 and in the ICRU report 44 were assigned to the organ and tissue in Rad-HUMAN for radiation protection purpose. The last step was to implement the anatomical data into a Monte Carlo code. Rad-HUMAN contains more than 28.8 billion tiny volume units, which produces an accurately whole-body numerical phantom of a Chinese adult female

  6. Postnatal development of depth-dependent collagen density in ovine articular cartilage

    Directory of Open Access Journals (Sweden)

    Kranenbarg Sander

    2010-10-01

    Full Text Available Abstract Background Articular cartilage (AC is the layer of tissue that covers the articulating ends of the bones in diarthrodial joints. Adult AC is characterised by a depth-dependent composition and structure of the extracellular matrix that results in depth-dependent mechanical properties, important for the functions of adult AC. Collagen is the most abundant solid component and it affects the mechanical behaviour of AC. The current objective is to quantify the postnatal development of depth-dependent collagen density in sheep (Ovis aries AC between birth and maturity. We use Fourier transform infra-red micro-spectroscopy to investigate collagen density in 48 sheep divided over ten sample points between birth (stillborn and maturity (72 weeks. In each animal, we investigate six anatomical sites (caudal, distal and rostral locations at the medial and lateral side of the joint in the distal metacarpus of a fore leg and a hind leg. Results Collagen density increases from birth to maturity up to our last sample point (72 weeks. Collagen density increases at the articular surface from 0.23 g/ml ± 0.06 g/ml (mean ± s.d., n = 48 at 0 weeks to 0.51 g/ml ± 0.10 g/ml (n = 46 at 72 weeks. Maximum collagen density in the deeper cartilage increases from 0.39 g/ml ± 0.08 g/ml (n = 48 at 0 weeks to 0.91 g/ml ± 0.13 g/ml (n = 46 at 72 weeks. Most collagen density profiles at 0 weeks (85% show a valley, indicating a minimum, in collagen density near the articular surface. At 72 weeks, only 17% of the collagen density profiles show a valley in collagen density near the articular surface. The fraction of profiles with this valley stabilises at 36 weeks. Conclusions Collagen density in articular cartilage increases in postnatal life with depth-dependent variation, and does not stabilize up to 72 weeks, the last sample point in our study. We find strong evidence for a valley in collagen densities near the articular surface that is present in the youngest

  7. Resident aerobic microbiota of the adult human nasal cavity

    DEFF Research Database (Denmark)

    Rasmussen, TT; Kirkeby Nielsen, LP; Poulsen, Knud

    2000-01-01

    Recent evidence strongly suggests that the microbiota of the nasal cavity plays a crucial role in determining the reaction patterns of the mucosal and systemic immune system. However, little is known about the normal microbiota of the nasal cavity. The purpose of this study was to determine...... the microbiota in different parts of the nasal cavity and to develop and evaluate methods for this purpose. Samples were collected from 10 healthy adults by nasal washes and by swabbing of the mucosa through a sterile introduction device. Both methods gave results that were quantitatively and qualitatively...... reproducible, and revealed significant differences in the density of the nasal microbiota between individuals. The study revealed absence of gram-negative bacteria that are regular members of the commensal microbiota of the pharynx. Likewise, viridans type streptococci were sparsely represented. The nasal...

  8. Magnetic resonance imaging of articular cartilage: ex vivo study on normal cartilage correlated with magnetic resonance microscopy

    International Nuclear Information System (INIS)

    Cova, M.; Frezza, F.; Pozzi-Mucelli, R.S.; Dalla-Palma, L.; Toffanin, R.; Pozzi-Mucelli, M.; Mlynarik, V.; Vittur, F.

    1998-01-01

    The aims of this study were (a) to compare the MR appearance of normal articular cartilage in ex vivo MR imaging (MRI) and MR microscopy (MRM) images of disarticulated human femoral heads, (b) to evaluate by MRM the topographic variations in articular cartilage of disarticulated human femoral heads, and subsequently, (c) to compare MRM images with histology. Ten disarticulated femoral heads were examined. Magnetic resonance images were obtained using spin-echo (SE) and gradient-echo (GE) sequences. Microimages were acquired on cartilage-bone cylindrical plugs excised from four regions (superior, inferior, anterior, posterior) of one femoral head, using a modified SE sequence. Both MRI and MRM images were obtained before and after a 90 rotation of the specimen, around the axis perpendicular to the examined cartilage surface. Finally, MRM images were correlated with histology. A trilaminar appearance of articular cartilage was observed with MRI and with a greater detail with MRM. A good correlation between MRI and MRM features was demonstrated. Both MRI and MRM showed a loss of the trilaminar cartilage appearance after specimen rotation, with greater evidence on MRM images. Cartilage excised from the four regions of the femoral head showed a different thickness, being thickest in the samples excised from the superior site. The MRM technique confirms the trilaminar MRI appearance of human articular cartilage, showing good correlation with histology. The loss of the trilaminar appearance of articular cartilage induced by specimen rotation suggests that this feature is partially related to the collagen-fiber orientation within the different layers. The MRM technique also shows topographic variations in thickness of human articular cartilage. (orig.)

  9. Expansion of Adult Human Pancreatic Tissue Yields Organoids Harboring Progenitor Cells with Endocrine Differentiation Potential

    Directory of Open Access Journals (Sweden)

    Cindy J.M. Loomans

    2018-03-01

    Full Text Available Summary: Generating an unlimited source of human insulin-producing cells is a prerequisite to advance β cell replacement therapy for diabetes. Here, we describe a 3D culture system that supports the expansion of adult human pancreatic tissue and the generation of a cell subpopulation with progenitor characteristics. These cells display high aldehyde dehydrogenase activity (ALDHhi, express pancreatic progenitors markers (PDX1, PTF1A, CPA1, and MYC, and can form new organoids in contrast to ALDHlo cells. Interestingly, gene expression profiling revealed that ALDHhi cells are closer to human fetal pancreatic tissue compared with adult pancreatic tissue. Endocrine lineage markers were detected upon in vitro differentiation. Engrafted organoids differentiated toward insulin-positive (INS+ cells, and circulating human C-peptide was detected upon glucose challenge 1 month after transplantation. Engrafted ALDHhi cells formed INS+ cells. We conclude that adult human pancreatic tissue has potential for expansion into 3D structures harboring progenitor cells with endocrine differentiation potential. : In the context of β cell replacement therapy for diabetes, de Koning and colleagues describe a 3D culture platform that supports ex vivo expansion of human pancreatic tissue as organoids. These organoids harbor a subpopulation of ALDHhi cells that display proliferative capacity and can differentiate to an endocrine fate. Keywords: pancreas, organoid, human, ALDH, endocrine differentiation, beta cells, insulin, progenitor, fetal, diabetes

  10. A bi-articular model for scapular-humeral rhythm reconstruction through data from wearable sensors.

    Science.gov (United States)

    Lorussi, Federico; Carbonaro, Nicola; De Rossi, Danilo; Tognetti, Alessandro

    2016-04-23

    Patient-specific performance assessment of arm movements in daily life activities is fundamental for neurological rehabilitation therapy. In most applications, the shoulder movement is simplified through a socket-ball joint, neglecting the movement of the scapular-thoracic complex. This may lead to significant errors. We propose an innovative bi-articular model of the human shoulder for estimating the position of the hand in relation to the sternum. The model takes into account both the scapular-toracic and gleno-humeral movements and their ratio governed by the scapular-humeral rhythm, fusing the information of inertial and textile-based strain sensors. To feed the reconstruction algorithm based on the bi-articular model, an ad-hoc sensing shirt was developed. The shirt was equipped with two inertial measurement units (IMUs) and an integrated textile strain sensor. We built the bi-articular model starting from the data obtained in two planar movements (arm abduction and flexion in the sagittal plane) and analysing the error between the reference data - measured through an optical reference system - and the socket-ball approximation of the shoulder. The 3D model was developed by extending the behaviour of the kinematic chain revealed in the planar trajectories through a parameter identification that takes into account the body structure of the subject. The bi-articular model was evaluated in five subjects in comparison with the optical reference system. The errors were computed in terms of distance between the reference position of the trochlea (end-effector) and the correspondent model estimation. The introduced method remarkably improved the estimation of the position of the trochlea (and consequently the estimation of the hand position during reaching activities) reducing position errors from 11.5 cm to 1.8 cm. Thanks to the developed bi-articular model, we demonstrated a reliable estimation of the upper arm kinematics with a minimal sensing system suitable for

  11. Contact and perspective taking improve humanness standards and perceptions of humanness of older adults and people with dementia: a cross-sectional survey study.

    Science.gov (United States)

    Miron, Anca M; McFadden, Susan H; Hermus, Nathan J; Buelow, Jennifer; Nazario, Amanda S; Seelman, Katarena

    2017-10-01

    No empirical work has systematically explored perceptions of humanness of people with dementia and of older adults and the variables that could improve these perceptions. We thus investigated the role of contact and perspective taking in improving perceptions of humanness of these social groups. To do so, we developed a new concept, humanness standards, defined as the amount of evidence of ability impairment needed to conclude that elderly people and those with dementia have lost personhood. We used a cross-sectional survey design (n = 619) to assess participants' humanness standards and perceptions of uniquely human characteristics and human nature characteristics of two social groups (people with dementia and older adults). Half the participants (n = 311) completed a survey about people with dementia and half (n = 308) assessed older adults. People with dementia were perceived as possessing humanness characteristics to a lesser extent than were older adults. For both groups, contact predicted enhanced perceptions of humanness characteristics. Participants' degree of contact with individuals with dementia also predicted humanness standards, but only under low perspective-taking conditions. As predicted, for older adults, participants set the highest humanness impairment thresholds in the high contact/high perspective-taking condition. We conclude that while social programs that bring persons with dementia and other individuals in contact could change humanness standards and perceptions of humanness characteristics of people with dementia, in the case of elderly adults, the contact must be supplemented by variables that facilitate taking the perspective of the person.

  12. Viral articular deformations in a goat

    International Nuclear Information System (INIS)

    Périe, P.; Maillard, R.; Polack, B.; Millemann, Y.

    2006-01-01

    A goat belonging to an animal aid association was presented for bilateral deformation of the tarsus and carpus and signs of high-grade pain. ELISA serology was positive for Caprine Arthritis-Encephalitis Virus. Radiography revealed marked osseous remodelling of the tarsus. The blood fibrinogen concentration was very elevated. On infected commercial farms, it is recommended that both seropositive animals and their offspring are culled when the level of infected is low, or to separate the kids from the mothers at an early age. In this case, palliative treatment was prescribed based on non-steroidal anti-inflammatory drugs, antibiotics and articular puncture-lavages [it

  13. Coordinate and synergistic effects of extensive treadmill exercise and ovariectomy on articular cartilage degeneration

    OpenAIRE

    Miyatake, Kazumasa; Muneta, Takeshi; Ojima, Miyoko; Yamada, Jun; Matsukura, Yu; Abula, Kahaer; Sekiya, Ichiro; Tsuji, Kunikazu

    2016-01-01

    Background Although osteoarthritis (OA) is a multifactorial disease, little has been reported regarding the cooperative interaction among these factors on cartilage metabolism. Here we examined the synergistic effect of ovariectomy (OVX) and excessive mechanical stress (forced running) on articular cartilage homeostasis in a mouse model resembling a human postmenopausal condition. Methods Mice were randomly divided into four groups, I: Sham, II: OVX, III: Sham and forced running (60?km in 6?w...

  14. Deficiency of Thrombospondin-4 in Mice Does Not Affect Skeletal Growth or Bone Mass Acquisition, but Causes a Transient Reduction of Articular Cartilage Thickness.

    Directory of Open Access Journals (Sweden)

    Anke Jeschke

    Full Text Available Although articular cartilage degeneration represents a major public health problem, the underlying molecular mechanisms are still poorly characterized. We have previously utilized genome-wide expression analysis to identify specific markers of porcine articular cartilage, one of them being Thrombospondin-4 (Thbs4. In the present study we analyzed Thbs4 expression in mice, thereby confirming its predominant expression in articular cartilage, but also identifying expression in other tissues, including bone. To study the role of Thbs4 in skeletal development and integrity we took advantage of a Thbs4-deficient mouse model that was analyzed by undecalcified bone histology. We found that Thbs4-deficient mice do not display phenotypic differences towards wildtype littermates in terms of skeletal growth or bone mass acquisition. Since Thbs4 has previously been found over-expressed in bones of Phex-deficient Hyp mice, we additionally generated Thbs4-deficient Hyp mice, but failed to detect phenotypic differences towards Hyp littermates. With respect to articular cartilage we found that Thbs4-deficient mice display transient thinning of articular cartilage, suggesting a protective role of Thbs4 for joint integrity. Gene expression analysis using porcine primary cells revealed that Thbs4 is not expressed by synovial fibroblasts and that it represents the only member of the Thbs gene family with specific expression in articular, but not in growth plate chondrocytes. In an attempt to identify specific molecular effects of Thbs4 we treated porcine articular chondrocytes with human THBS4 in the absence or presence of conditioned medium from porcine synovial fibroblasts. Here we did not observe a significant influence of THBS4 on proliferation, metabolic activity, apoptosis or gene expression, suggesting that it does not act as a signaling molecule. Taken together, our data demonstrate that Thbs4 is highly expressed in articular chondrocytes, where its

  15. Bridging the Gap between Human Resource Development and Adult Education: Part Two, the Critical Turn

    Science.gov (United States)

    Hatcher, Tim; Bowles, Tuere

    2014-01-01

    Human resource development (HRD) as a scholarly endeavor and as a practice is often criticized in the adult education (AE) literature and by AE scholars as manipulative and oppressive and, through training and other interventions, controlling workers for strictly economic ends (Baptiste, 2001; Cunningham, 2004; Schied, 2001; Welton, 1995). The…

  16. Perspectives on Adult Education, Human Resource Development, and the Emergence of Workforce Development

    Science.gov (United States)

    Jacobs, Ronald L.

    2014-01-01

    This article presents a perspective on the relationship between adult education and human resource development of the past two decades and the subsequent emergence of workforce development. The lesson taken from the article should be more than simply a recounting of events related to these fields of study. Instead, the more general lesson may be…

  17. Bridging the Gap between Human Resource Development and Adult Education: Part One, Assumptions, Definitions, and Critiques

    Science.gov (United States)

    Hatcher, Tim; Bowles, Tuere

    2013-01-01

    Human resource development (HRD) as a scholarly endeavor and as a practice is often criticized in the adult education (AE) literature and by AE scholars as manipulative and oppressive and, through training and other interventions, controlling workers for strictly economic ends (Baptiste, 2001; Cunningham, 2004; Schied, 2001; Welton, 1995).…

  18. Embryonic stem cell-like cells derived from adult human testis

    NARCIS (Netherlands)

    Mizrak, S. C.; Chikhovskaya, J. V.; Sadri-Ardekani, H.; van Daalen, S.; Korver, C. M.; Hovingh, S. E.; Roepers-Gajadien, H. L.; Raya, A.; Fluiter, K.; de Reijke, Th M.; de la Rosette, J. J. M. C. H.; Knegt, A. C.; Belmonte, J. C.; van der Veen, F.; de rooij, D. G.; Repping, S.; van Pelt, A. M. M.

    2010-01-01

    Given the significant drawbacks of using human embryonic stem (hES) cells for regenerative medicine, the search for alternative sources of multipotent cells is ongoing. Studies in mice have shown that multipotent ES-like cells can be derived from neonatal and adult testis. Here we report the

  19. Equality and Human Capital: Conflicting Concepts within State-Funded Adult Education in Ireland

    Science.gov (United States)

    Hurley, Kevin

    2015-01-01

    This article offers a critique of the concept of equality as it informs the White Paper on Adult Education: Learning for Life (2000). It also outlines the extent to which human capital theory can be seen to have effectively colonised lifelong learning from the outset of its adoption by the European Union with highly constraining implications for…

  20. CD4+ T-Lymphocytes cell counts in adults with human ...

    African Journals Online (AJOL)

    Objectives: To evaluate the CD4+ cell counts in adults with human immunodeficiency virus (HIV) infections presenting at the medical department of the Federal Medical Centre, Ido-Ekiti, Nigeria. Methods: This study was carried out at the medical department of the Federal Medical Centre (FMC), Ido-Ekiti, Nigeria, in the ...

  1. ABSORPTION-SPECTRA OF HUMAN FETAL AND ADULT OXYHEMOGLOBIN, DE-OXYHEMOGLOBIN, CARBOXYHEMOGLOBIN, AND METHEMOGLOBIN

    NARCIS (Netherlands)

    ZIJLSTRA, WG; MEEUWSENVANDERROEST, WP

    We determined the millimolar absorptivities of the four clinically relevant derivatives of fetal and adult human hemoglobin in the visible and near-infrared spectral range (450-1000 nm). As expected, spectral absorption curves of similar shape were found, but the small differences between fetal and

  2. Intra Articular Therapeutic Delivery for Post Traumatic Osteoarthritis

    Science.gov (United States)

    2016-10-01

    size distribution therapeutic timepoints EPIC-µCT Articular cartilage Subchondral bone Osteophytes Proteoglycans 3. OVERALL PROJECT SUMMARY: In...joint degeneration induced by MMT. Previously documented in Year 1 annual report: Changes in articular cartilage and subchondral bone morphology...and resulted in increased cartilage thickness at 3 weeks. The majority of alterations to subchondral bone (density, thickness) were detected at 3

  3. Radiosynovectomy of Painful Synovitis of Knee Joints Due to Rheumatoid Arthritis by Intra-Articular Administration of (177)Lu-Labeled Hydroxyapatite Particulates: First Human Study and Initial Indian Experience.

    Science.gov (United States)

    Shinto, Ajit S; Kamaleshwaran, K K; Chakraborty, Sudipta; Vyshakh, K; Thirumalaisamy, S G; Karthik, S; Nagaprabhu, V N; Vimalnath, K V; Das, Tapas; Banerjee, Sharmila

    2015-01-01

    The aim of this study is to assess the effectiveness of Radiosynovectomy (RSV) using (177)Lu-labeled hydroxyapatite ((177)Lu-HA) in the treatment of painful synovitis and recurrent joint effusion of knee joints in rheumatoid arthritis (RA). Ten patients, diagnosed with RA and suffering from chronic painful resistant synovitis of the knee joints were referred for RSV. The joints were treated with 333 ± 46 MBq of (177)Lu-HA particles administered intra-articularly. Monitoring of activity distribution was performed by static imaging of knee joint and whole-body gamma imaging. The patients were evaluated clinically before RSV and at 6 months after the treatment by considering the pain improvement from baseline values in terms of a 100-point visual analog scale (VAS), the improvement of knee flexibility and the pain remission during the night. RSV response was classified as poor (VAS body scan. Static scans of the joint at 1 month revealed complete retention of (177)Lu-HA in the joints. All patients showed decreased joint swelling and pains, resulting in increased joint motion after 6 months. The percentage of VAS improvement from baseline values was 79.5 ± 20.0% 6 months after RS and found to be significantly related to patients' age (P = 0.01) and duration of the disease (P = 0.03). Knees with Steinbrocker's Grades 0 and I responded better than those with more advanced changes (Steinbrocker's Grades III and IV) in terms of VAS improvement (75% vs. 45.8%) (P level was not different before and after RSV. RSV side-effects assessed for the whole follow-up period were minor and not significant. RSV with (177)Lu-HA was safe and effective in patients with knee joint chronic painful synovitis of rheumatoid origin. It exhibited significant therapeutic effect after 6 months follow-up period with no significant side-effects. The preliminary investigations reveal that (177)Lu-labeled HA particles hold considerable promise as a cost-effective agent for RSV. More elaborate and

  4. Self-Control and Impulsiveness in Nondieting Adult Human Females: Effects of Visual Food Cues and Food Deprivation

    Science.gov (United States)

    Forzano, Lori-Ann B.; Chelonis, John J.; Casey, Caitlin; Forward, Marion; Stachowiak, Jacqueline A.; Wood, Jennifer

    2010-01-01

    Self-control can be defined as the choice of a larger, more delayed reinforcer over a smaller, less delayed reinforcer, and impulsiveness as the opposite. Previous research suggests that exposure to visual food cues affects adult humans' self-control. Previous research also suggests that food deprivation decreases adult humans' self-control. The…

  5. Neuroscience of Human Social Interactions and Adult Attachment Style

    Directory of Open Access Journals (Sweden)

    Pascal eVrticka

    2012-07-01

    Full Text Available Since its first description four decades ago, attachment theory has become one of the principal developmental psychological frameworks for describing the role of individual differences in the establishment and maintenance of social bonds between people. Yet, still little is known about the neurobiological underpinnings of attachment orientations and their well-established impact on a range of social and affective behaviors. In the present review, we summarize data from recent studies using cognitive and imaging approaches to characterize attachment styles and their effect on emotion and social cognition. We propose a functional neuroanatomical framework to integrate the key brain mechanisms involved in the perception and regulation of social emotional information, and their modulation by individual differences in terms of secure versus insecure (more specifically avoidant, anxious, or resolved vs. unresolved attachment traits. This framework describes how each individual’s attachment style (built through interactions between personal relationship history and predispositions may influence the encoding of approach versus aversion tendencies (safety versus threat in social encounters, implicating the activation of a network of subcortical (amygdala, hippocampus, striatum and cortical (insula, cingulate limbic areas. These basic and automatic affective mentalization mechanisms are in turn modulated by more elaborate and voluntary cognitive mentalization processes, subserving theory of mind, cognitive control, and emotion regulation capacities, implicating a distinct network (in medial prefrontal cortex, superior temporal sulcus, and temporo-parietal junction, among others. Such research does not only help better understand the neural underpinnings of human social behavior, but also provides important insights on psychopathological conditions where attachment dysregulations is likely to play an important (causal role.

  6. Intra-articular injection of hyaluronic acid for treatment of osteoarthritis knee: comparative study to intra-articular corticosteroids

    Directory of Open Access Journals (Sweden)

    Soad A Elsawy

    2017-01-01

    Conclusion Both HA and corticosteroid groups showed improvement in pain and knee function, but the intra-articular HA was superior to corticosteroid on long-term follow-up. This supports the potential rate of intra-articular HA as an effective long-term therapeutic option for patients with OA of the knee.

  7. Induction of GLUT-1 protein in adult human skeletal muscle fibers

    DEFF Research Database (Denmark)

    Gaster, M; Franch, J; Staehr, P

    2000-01-01

    Prompted by our recent observations that GLUT-1 is expressed in fetal muscles, but not in adult muscle fibers, we decided to investigate whether GLUT-1 expression could be reactivated. We studied different stimuli concerning their ability to induce GLUT-1 expression in mature human skeletal muscle...... fibers. Metabolic stress (obesity, non-insulin-dependent diabetes mellitus), contractile activity (training), and conditions of de- and reinnervation (amyotrophic lateral sclerosis) could not induce GLUT-1 expression in human muscle fibers. However, regenerating muscle fibers in polymyositis expressed...... GLUT-1. In contrast to GLUT-1, GLUT-4 was expressed in all investigated muscle fibers. Although the significance of GLUT-1 in adult human muscle fibers appears limited, GLUT-1 may be of importance for the glucose supplies in immature and regenerating muscle....

  8. Noninvasive assessment of articular cartilage surface damage using reflected polarized light microscopy

    Science.gov (United States)

    Huynh, Ruby N.; Nehmetallah, George; Raub, Christopher B.

    2017-06-01

    Articular surface damage occurs to cartilage during normal aging, osteoarthritis, and in trauma. A noninvasive assessment of cartilage microstructural alterations is useful for studies involving cartilage explants. This study evaluates polarized reflectance microscopy as a tool to assess surface damage to cartilage explants caused by mechanical scraping and enzymatic degradation. Adult bovine articular cartilage explants were scraped, incubated in collagenase, or underwent scrape and collagenase treatments. In an additional experiment, cartilage explants were subject to scrapes at graduated levels of severity. Polarized reflectance parameters were compared with India ink surface staining, features of histological sections, changes in explant wet weight and thickness, and chondrocyte viability. The polarized reflectance signal was sensitive to surface scrape damage and revealed individual scrape features consistent with India ink marks. Following surface treatments, the reflectance contrast parameter was elevated and correlated with image area fraction of India ink. After extensive scraping, polarized reflectance contrast and chondrocyte viability were lower than that from untreated explants. As part of this work, a mathematical model was developed and confirmed the trend in the reflectance signal due to changes in surface scattering and subsurface birefringence. These results demonstrate the effectiveness of polarized reflectance microscopy to sensitively assess surface microstructural alterations in articular cartilage explants.

  9. Mental rotation and the human body: Children's inflexible use of embodiment mirrors that of adults.

    Science.gov (United States)

    Krüger, Markus; Ebersbach, Mirjam

    2017-12-25

    Adults' mental rotation performance with body-like stimuli is enhanced if these stimuli are anatomically compatible with a human body, but decreased by anatomically incompatible stimuli. In this study, we investigated these effects for kindergartners and first-graders: When asked to mentally rotate cube configurations attached with human body parts in an anatomically compatible way, allowing for the projection of a human body, children performed better than with pure cube combinations. By contrast, when body parts were attached in an anatomically incompatible way, disallowing the projection of a human body, children performed worse than with pure combinations. This experiment is of specific interest against the background of two different theoretical approaches concerning imagery and the motor system in development: One approach assumes an increasing integration of motor processes and imagery over time that enables older children and adults to requisition motor resources for imagery processes, while the other postulates that imagery stems from early sensorimotor processes in the first place, and is disentangled from it over time. The finding that children of the two age groups tested show exactly the same effects as adults when mentally rotating anatomically compatible and incompatible stimuli is interpreted in favour of the latter approach. Statement of contribution What is already known on this subject? In mental rotation, adults perform better when rotating anatomically possible stimuli as compared to rotating standard cube combinations. Performance is worse when rotating anatomically impossible stimuli. What does this study add? The present study shows that children's mental transformations mirror those of adults in these respects. In case of the anatomically impossible stimuli, this highlights an inflexible use of embodiment in both age groups. This is in line with the Piagetian assumption of imagery being based on sensorimotor processes. © 2017 The British

  10. Human Centred Design Considerations for Connected Health Devices for the Older Adult

    Directory of Open Access Journals (Sweden)

    Richard P. Harte

    2014-06-01

    Full Text Available Connected health devices are generally designed for unsupervised use, by non-healthcare professionals, facilitating independent control of the individuals own healthcare. Older adults are major users of such devices and are a population significantly increasing in size. This group presents challenges due to the wide spectrum of capabilities and attitudes towards technology. The fit between capabilities of the user and demands of the device can be optimised in a process called Human Centred Design. Here we review examples of some connected health devices chosen by random selection, assess older adult known capabilities and attitudes and finally make analytical recommendations for design approaches and design specifications.

  11. Radiosynovectomy of Painful Synovitis of Knee Joints Due to Rheumatoid Arthritis by Intra-Articular Administration of 177Lu-Labeled Hydroxyapatite Particulates: First Human Study and Initial Indian Experience

    International Nuclear Information System (INIS)

    Shinto, Ajit S.; Kamaleshwaran, K. K.; Chakraborty, Sudipta; Vyshakh, K.; Thirumalaisamy, S. G.; Karthik, S.; Nagaprabhu, V. N.; Vimalnath, K. V.; Das, Tapas; Banerjee, Sharmila

    2015-01-01

    The aim of this study is to assess the effectiveness of Radiosynovectomy (RSV) using 177 Lu-labeled hydroxyapatite ( 177 Lu-HA) in the treatment of painful synovitis and recurrent joint effusion of knee joints in rheumatoid arthritis (RA). Ten patients, diagnosed with RA and suffering from chronic painful resistant synovitis of the knee joints were referred for RSV. The joints were treated with 333 ± 46 MBq of 177 Lu-HA particles administered intra-articularly. Monitoring of activity distribution was performed by static imaging of knee joint and whole-body gamma imaging. The patients were evaluated clinically before RSV and at 6 months after the treatment by considering the pain improvement from baseline values in terms of a 100-point visual analog scale (VAS), the improvement of knee flexibility and the pain remission during the night. RSV response was classified as poor (VAS < 25), fair (VAS ≥ 25-50), good (VAS ≥ 50-75) and excellent (VAS ≥ 75), with excellent and good results considered to be success, while fair and poor as failure and also by range of motion. Three phase bone scan (BS) was repeated after 6 months and changes in the second phase of BS3 were assessed visually, using a four-degree scale and in the third phase, semiquantitatively with J/B ratio to see the response. Biochemical analysis of C-reactive protein (CRP) and fibrinogen was repeated after 48 h, 4 and 24 weeks. In all 10 patients, no leakage of administered activity to nontarget organs was visible in the whole-body scan. Static scans of the joint at 1 month revealed complete retention of 177 Lu-HA in the joints. All patients showed decreased joint swelling and pains, resulting in increased joint motion after 6 months. The percentage of VAS improvement from baseline values was 79.5 ± 20.0% 6 months after RS and found to be significantly related to patients' age (P = 0.01) and duration of the disease (P = 0.03). Knees with Steinbrocker's Grades 0 and I responded better than

  12. On the problem of knee joint articular space in the X-ray film

    International Nuclear Information System (INIS)

    Saure, D.; Emminger, A.; Freyschmidt, J.

    1980-01-01

    Measurements of the width of the intraarticular space were performed in X-ray films of 64 human knee joints (32 patients), taken laterally, and in standing position after 24 hours of rest in bed or after exposure to load for one hour. In more than half of the knee joints, the width of the intraarticular space increased after load. However, the distance between the articular surfaces rarely changed in the same patient in the same sense in the right and left knee joint, respectively medially and laterally. Hence, this method of indirect measurement of the cartilaginous layer is unsuitable, and the question raised in literature regarding the cartilaginous changes under load can be explained as being due to influx of fluid or as an expression of the viso-elastic properties of the articular cartilage. (orig.) 891 MG/orig. 892 MB [de

  13. Imaging diagnosis of the articular cartilage disorders

    International Nuclear Information System (INIS)

    Liu Sirun; Zhu Tianyuan; Huang Li; Leng Xiaoming

    2003-01-01

    Objective: To evaluate the diagnosis and differential diagnosis among the chronic osteoarthritis, rheumatoid arthritis and other chronic cartilage lesions on the plain films and MR images. Methods: Eighty-nine cases, including 115 joints, underwent plain film and MRI examination, and enhanced MRI scan was performed on 32 of them, including 44 joints. MRI scan sequences consisted of T 1 WI, T 2 WI + PDWI, STIR, and 3D FS SPGR. There were 90 knee joints in this group and each of the articular cartilage was divided into four parts: patella, femoral medial condyle, femoral lateral condyle, and tibia facet on MR images. The cartilage disorders were classified according to the outerbridge method. In addition, 61 cases including 75 joints were observed as a control group on the plain films and MR images. Results: 115 cartilage lesions were found on MR images, in which thinness of the cartilage (58 cases, 50.4%), bone changes under the cartilage (22 cases, 19.7%), medullar edema (22 cases, 19.7%), and synovial hyperplasia (52 cases, 45.2%) were seen. The patella cartilage was the most likely affected part (81/90, 90%). So the patellar cartilage lesions were divided as group 1 (grade I-II) and group 2 (grade III-IV) on MR images, which were compared with the plain film signs. The narrowing of the joint space and saccules under the articular surface were statistically significant with each other, and χ 2 values were 9.349 and 9.885, respectively (P=0.002). Conclusion: No constant signs could be seen on the plain films with grade I-II cartilage disorders. While the narrowing joint space and saccules under the joint surface could be seen on them with grade III-IV cartilage disorders, which were mainly correlated with the cartilage disorders and bone changes under the articular cartilages. A combination of the plain films and MR images is the best imaging method for examining the joints and joint cartilages. Enhanced MRI scan is very helpful on the diagnosis and differential

  14. The Longitudinal Study of Aging in Human Young Adults: Knowledge Gaps and Research Agenda.

    Science.gov (United States)

    Moffitt, Terrie E; Belsky, Daniel W; Danese, Andrea; Poulton, Richie; Caspi, Avshalom

    2017-02-01

    To prevent onset of age-related diseases and physical and cognitive decline, interventions to slow human aging and extend health span must eventually be applied to people while they are still young and healthy. Yet most human aging research examines older adults, many with chronic disease, and little is known about aging in healthy young humans. This article explains how this knowledge gap is a barrier to extending health span and puts forward the case that geroscience should invest in researching the pace of aging in young adults. As one illustrative example, we describe an initial effort to study the pace of aging in a young-adult birth cohort by using repeated waves of biomarkers collected across the third and fourth decades to quantify the pace of coordinated physiological deterioration across multiple organ systems (eg, pulmonary, periodontal, cardiovascular, renal, hepatic, metabolic, and immune function). Findings provided proof of principle that it is possible to quantify individual variation in the pace of aging in young adults still free of age-related diseases. This article articulates research needs to improve longitudinal measurement of the pace of aging in young people, to pinpoint factors that slow or speed the pace of aging, to compare pace of aging against genomic clocks, to explain slow-aging young adults, and to apply pace of aging in preventive clinical trials of antiaging therapies. This article puts forward a research agenda to fill the knowledge gap concerning lifelong causes of aging. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Comparison of Kaposi Sarcoma risk in human immunodeficiency virus-positive adults across 5 continents

    DEFF Research Database (Denmark)

    Rohner, Eliane; Bütikofer, Lukas; Schmidlin, Kurt

    2017-01-01

    Background: We compared Kaposi sarcoma (KS) risk in adults who started antiretroviral therapy (ART) across the Asia-Pacific, South Africa, Europe, Latin, and North America. Methods: We included cohort data of human immunodeficiency virus (HIV)-positive adults who started ART after 1995 within...... KS risk was 6 times higher in men who have sex with men (aHR, 5.95; 95% CI, 5.09-6.96) than in women. Comparing patients with current CD4 cell counts ≥700 cells/μL with those whose counts were ...% in other regions. Conclusions. Despite important ART-related declines in KS incidence, men and women in South Africa and men who have sex with men remain at increased KS risk, likely due to high human herpesvirus 8 coinfection rates. Early ART initiation and maintenance of high CD4 cell counts...

  16. Regulated gene expression in cultured type II cells of adult human lung

    OpenAIRE

    Ballard, Philip L.; Lee, Jae W.; Fang, Xiaohui; Chapin, Cheryl; Allen, Lennell; Segal, Mark R.; Fischer, Horst; Illek, Beate; Gonzales, Linda W.; Kolla, Venkatadri; Matthay, Michael A.

    2010-01-01

    Alveolar type II cells have multiple functions, including surfactant production and fluid clearance, which are critical for lung function. Differentiation of type II cells occurs in cultured fetal lung epithelial cells treated with dexamethasone plus cAMP and isobutylmethylxanthine (DCI) and involves increased expression of 388 genes. In this study, type II cells of human adult lung were isolated at ∼95% purity, and gene expression was determined (Affymetrix) before and after culturing 5 days...

  17. Attitudes of Korean adults towards human dignity: a Q methodology approach.

    Science.gov (United States)

    Jo, Kae Hwa; An, Gyeong-Ju; Doorenbos, Ardith Z

    2012-06-01

    The aim of this study was to identify the perceived attitudes of Korean adults towards human dignity in order to determine the relationship of human dignity to its social and cultural background. The Q methodology research technique was used to explore perceived attitude typology on the basis of the respondents' ranking order for different statements. A convenience sampling method was used to select 40 Korean adults who were interested in human dignity to create statements. From the questionnaires, in-depth interviews, and a literature review, a total of 158 statements was obtained. The final 34 Q samples were selected from a review by two nursing professors and a Q methodology expert. Moreover, 38 respondents participated as P samples by sorting 34 Q statements on a nine-point normal distribution scale. The data were analyzed by using the QUANL software package. The following four types of attitudes about human dignity were identified in Korea: a happiness-oriented-self-pursuit type, relationship-oriented-self-recognition type, reflection-oriented-self-unification type, and discrimination-oriented-self-maintenance type. The results indicate that approaches to developing human dignity education need to take this typology into account and the characteristics of the participants who fall into each category. These results provide general guidelines to understand Korean values for professional practice in various healthcare settings. © 2011 The Authors. Japan Journal of Nursing Science © 2011 Japan Academy of Nursing Science.

  18. Intra-articular corticosteroid for knee osteoarthritis.

    Science.gov (United States)

    Jüni, Peter; Hari, Roman; Rutjes, Anne W S; Fischer, Roland; Silletta, Maria G; Reichenbach, Stephan; da Costa, Bruno R

    2015-10-22

    Knee osteoarthritis is a leading cause of chronic pain, disability, and decreased quality of life. Despite the long-standing use of intra-articular corticosteroids, there is an ongoing debate about their benefits and safety. This is an update of a Cochrane review first published in 2005. To determine the benefits and harms of intra-articular corticosteroids compared with sham or no intervention in people with knee osteoarthritis in terms of pain, physical function, quality of life, and safety. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE (from inception to 3 February 2015), checked trial registers, conference proceedings, reference lists, and contacted authors. We included randomised or quasi-randomised controlled trials that compared intra-articular corticosteroids with sham injection or no treatment in people with knee osteoarthritis. We applied no language restrictions. We calculated standardised mean differences (SMDs) and 95% confidence intervals (CI) for pain, function, quality of life, joint space narrowing, and risk ratios (RRs) for safety outcomes. We combined trials using an inverse-variance random-effects meta-analysis. We identified 27 trials (13 new studies) with 1767 participants in this update. We graded the quality of the evidence as 'low' for all outcomes because treatment effect estimates were inconsistent with great variation across trials, pooled estimates were imprecise and did not rule out relevant or irrelevant clinical effects, and because most trials had a high or unclear risk of bias. Intra-articular corticosteroids appeared to be more beneficial in pain reduction than control interventions (SMD -0.40, 95% CI -0.58 to -0.22), which corresponds to a difference in pain scores of 1.0 cm on a 10-cm visual analogue scale between corticosteroids and sham injection and translates into a number needed to treat for an additional beneficial outcome (NNTB) of 8 (95% CI 6 to 13). An I(2) statistic of 68

  19. Oral Human Papillomavirus Detection in Older Adults Who Have Human Immunodeficiency Virus Infection

    Science.gov (United States)

    Fatahzadeh, Mahnaz; Schlecht, Nicolas F.; Chen, Zigui; Bottalico, Danielle; McKinney, Sharod; Ostoloza, Janae; Dunne, Anne; Burk, Robert D.

    2014-01-01

    Objective To evaluate reproducibility of oral rinse self-collection for HPV detection and investigate associations between oral HPV, oral lesions, immune and sociodemographic factors, we performed a cross-sectional study of older adults with HIV infection. Study Design We collected oral rinse samples from 52 subjects at two different times of day followed by an oral examination and interview. We identified HPV using PCR platforms optimized for detection of mucosal and cutaneous types. Results Eighty seven percent of individuals had oral HPV, of which 23% had oncogenic alpha, 40% had non-oncogenic alpha, and 46% had beta or gamma HPV. Paired oral specimens were concordant in all parameters tested. Significant associations observed for oral HPV with increased HIV viral load, hepatitis-C seropositivity, history of sexually transmitted diseases and lifetime number of sexual partners. Conclusions Oral cavity may be a reservoir of subclinical HPV in older adults who have HIV infection. Understanding natural history, transmission and potential implications of oral HPV warrants further investigations. PMID:23375488

  20. Populations of subplate and interstitial neurons in fetal and adult human telencephalon.

    Science.gov (United States)

    Judaš, Miloš; Sedmak, Goran; Pletikos, Mihovil; Jovanov-Milošević, Nataša

    2010-10-01

    In the adult human telencephalon, subcortical (gyral) white matter contains a special population of interstitial neurons considered to be surviving descendants of fetal subplate neurons [Kostovic & Rakic (1980) Cytology and the time of origin of interstitial neurons in the white matter in infant and adult human and monkey telencephalon. J Neurocytol9, 219]. We designate this population of cells as superficial (gyral) interstitial neurons and describe their morphology and distribution in the postnatal and adult human cerebrum. Human fetal subplate neurons cannot be regarded as interstitial, because the subplate zone is an essential part of the fetal cortex, the major site of synaptogenesis and the 'waiting' compartment for growing cortical afferents, and contains both projection neurons and interneurons with distinct input-output connectivity. However, although the subplate zone is a transient fetal structure, many subplate neurons survive postnatally as superficial (gyral) interstitial neurons. The fetal white matter is represented by the intermediate zone and well-defined deep periventricular tracts of growing axons, such as the corpus callosum, anterior commissure, internal and external capsule, and the fountainhead of the corona radiata. These tracts gradually occupy the territory of transient fetal subventricular and ventricular zones.The human fetal white matter also contains distinct populations of deep fetal interstitial neurons, which, by virtue of their location, morphology, molecular phenotypes and advanced level of dendritic maturation, remain distinct from subplate neurons and neurons in adjacent structures (e.g. basal ganglia, basal forebrain). We describe the morphological, histochemical (nicotinamide-adenine dinucleotide phosphate-diaphorase) and immunocytochemical (neuron-specific nuclear protein, microtubule-associated protein-2, calbindin, calretinin, neuropeptide Y) features of both deep fetal interstitial neurons and deep (periventricular

  1. Fractures of the articular processes of the cervical spine

    Energy Technology Data Exchange (ETDEWEB)

    Woodring, J.H.; Goldstein, S.J.

    1982-08-01

    Fractures of the articular processes occurred in 16 (20.8%) of 77 patients with cervical spine fractures as demonstrated by multidirectional tomography. Plain films demonstrated the fractures in only two patients. Acute cervical radiculopathy occurred in five of the patients with articular process fractures (superior process, two cases; inferior process, three cases). Persistent neck pain occurred in one other patient without radiculopathy. Three patients suffered spinal cord damage at the time of injury, which was not the result of the articular process fracture itself. In the other seven cases, no definite sequelae occurred. However, disruption of the facet joint may predispose to early degenerative joint disease and chronic pain; unilateral or bilateral facet dislocation was present in five patients. In patients with cervical trauma who develop cervical radiculopathy, tomography should be performed to evaluate the articular processes.

  2. Follistatin Alleviates Synovitis and Articular Cartilage Degeneration Induced by Carrageenan

    Directory of Open Access Journals (Sweden)

    Jun Yamada

    2014-01-01

    Full Text Available Activins are proinflammatory cytokines which belong to the TGFβ superfamily. Follistatin is an extracellular decoy receptor for activins. Since both activins and follistatin are expressed in articular cartilage, we hypothesized that activin-follistatin signaling participates in the process of joint inflammation and cartilage degeneration. To test this hypothesis, we examined the effects of follistatin in a carrageenan-induced mouse arthritis model. Synovitis induced by intra-articular injection of carrageenan was significantly alleviated by preinjection with follistatin. Macrophage infiltration into the synovial membrane was significantly reduced in the presence of follistatin. In addition, follistatin inhibited proteoglycan erosion induced by carrageenan in articular cartilage. These data indicate that activin-follistatin signaling is involved in joint inflammation and cartilage homeostasis. Our data suggest that follistatin can be a new therapeutic target for inflammation-induced articular cartilage degeneration.

  3. Fractures of the articular processes of the cervical spine

    International Nuclear Information System (INIS)

    Woodring, J.H.; Goldstein, S.J.

    1982-01-01

    Fractures of the articular processes occurred in 16 (20.8%) of 77 patients with cervical spine fractures as demonstrated by multidirectional tomography. Plain films demonstrated the fractures in only two patients. Acute cervical radiculopathy occurred in five of the patients with articular process fractures (superior process, two cases; inferior process, three cases). Persistent neck pain occurred in one other patient without radiculopathy. Three patients suffered spinal cord damage at the time of injury, which was not the result of the articular process fracture itself. In the other seven cases, no definite sequelae occurred. However, disruption of the facet joint may predispose to early degenerative joint disease and chronic pain; unilateral or bilateral facet dislocation was present in five patients. In patients with cervical trauma who develop cervical radiculopathy, tomography should be performed to evaluate the articular processes

  4. Coordinate and synergistic effects of extensive treadmill exercise and ovariectomy on articular cartilage degeneration.

    Science.gov (United States)

    Miyatake, Kazumasa; Muneta, Takeshi; Ojima, Miyoko; Yamada, Jun; Matsukura, Yu; Abula, Kahaer; Sekiya, Ichiro; Tsuji, Kunikazu

    2016-05-31

    Although osteoarthritis (OA) is a multifactorial disease, little has been reported regarding the cooperative interaction among these factors on cartilage metabolism. Here we examined the synergistic effect of ovariectomy (OVX) and excessive mechanical stress (forced running) on articular cartilage homeostasis in a mouse model resembling a human postmenopausal condition. Mice were randomly divided into four groups, I: Sham, II: OVX, III: Sham and forced running (60 km in 6 weeks), and IV: OVX and forced running. Histological and immunohistochemical analyses were performed to evaluate the degeneration of articular cartilage and synovitis in the knee joint. Morphological changes of subchondral bone were analyzed by micro-CT. Micro-CT analyses showed significant loss of metaphyseal trabecular bone volume/tissue volume (BV/TV) after OVX as described previously. Forced running increased the trabecular BV/TV in all mice. In the epiphyseal region, no visible alteration in bone morphology or osteophyte formation was observed in any of the four groups. Histological analysis revealed that OVX or forced running respectively had subtle effects on cartilage degeneration. However, the combination of OVX and forced running synergistically enhanced synovitis and articular cartilage degeneration. Although morphological changes in chondrocytes were observed during OA initiation, no signs of bone marrow edema were observed in any of the four experimental groups. We report the coordinate and synergistic effects of extensive treadmill exercise and ovariectomy on articular cartilage degeneration. Since no surgical procedure was performed on the knee joint directly in this model, this model is useful in addressing the molecular pathogenesis of naturally occurring OA.

  5. Regulated gene expression in cultured type II cells of adult human lung.

    Science.gov (United States)

    Ballard, Philip L; Lee, Jae W; Fang, Xiaohui; Chapin, Cheryl; Allen, Lennell; Segal, Mark R; Fischer, Horst; Illek, Beate; Gonzales, Linda W; Kolla, Venkatadri; Matthay, Michael A

    2010-07-01

    Alveolar type II cells have multiple functions, including surfactant production and fluid clearance, which are critical for lung function. Differentiation of type II cells occurs in cultured fetal lung epithelial cells treated with dexamethasone plus cAMP and isobutylmethylxanthine (DCI) and involves increased expression of 388 genes. In this study, type II cells of human adult lung were isolated at approximately 95% purity, and gene expression was determined (Affymetrix) before and after culturing 5 days on collagen-coated dishes with or without DCI for the final 3 days. In freshly isolated cells, highly expressed genes included SFTPA/B/C, SCGB1A, IL8, CXCL2, and SFN in addition to ubiquitously expressed genes. Transcript abundance was correlated between fetal and adult cells (r = 0.88), with a subset of 187 genes primarily related to inflammation and immunity that were expressed >10-fold higher in adult cells. During control culture, expression increased for 8.1% of expressed genes and decreased for approximately 4% including 118 immune response and 10 surfactant-related genes. DCI treatment promoted lamellar body production and increased expression of approximately 3% of probed genes by > or =1.5-fold; 40% of these were also induced in fetal cells. Highly induced genes (> or =10-fold) included PGC, ZBTB16, DUOX1, PLUNC, CIT, and CRTAC1. Twenty-five induced genes, including six genes related to surfactant (SFTPA/B/C, PGC, CEBPD, and ADFP), also had decreased expression during control culture and thus are candidates for hormonal regulation in vivo. Our results further define the adult human type II cell molecular phenotype and demonstrate that a subset of genes remains hormone responsive in cultured adult cells.

  6. Cadaveric Study of the Articular Branches of the Shoulder Joint.

    Science.gov (United States)

    Eckmann, Maxim S; Bickelhaupt, Brittany; Fehl, Jacob; Benfield, Jonathan A; Curley, Jonathan; Rahimi, Ohmid; Nagpal, Ameet S

    This cadaveric study investigated the anatomic relationships of the articular branches of the suprascapular (SN), axillary (AN), and lateral pectoral nerves (LPN), which are potential targets for shoulder analgesia. Sixteen embalmed cadavers and 1 unembalmed cadaver, including 33 shoulders total, were dissected. Following dissections, fluoroscopic images were taken to propose an anatomical landmark to be used in shoulder articular branch blockade. Thirty-three shoulders from 17 total cadavers were studied. In a series of 16 shoulders, 16 (100%) of 16 had an intact SN branch innervating the posterior head of the humerus and shoulder capsule. Suprascapular sensory branches coursed laterally from the spinoglenoid notch then toward the glenohumeral joint capsule posteriorly. Axillary nerve articular branches innervated the posterolateral head of the humerus and shoulder capsule in the same 16 (100%) of 16 shoulders. The AN gave branches ascending circumferentially from the quadrangular space to the posterolateral humerus, deep to the deltoid, and inserting at the inferior portion of the posterior joint capsule. In 4 previously dissected and 17 distinct shoulders, intact LPNs could be identified in 14 (67%) of 21 specimens. Of these, 12 (86%) of 14 had articular branches innervating the anterior shoulder joint, and 14 (100%) of 14 LPN articular branches were adjacent to acromial branches of the thoracoacromial blood vessels over the superior aspect of the coracoid process. Articular branches from the SN, AN, and LPN were identified. Articular branches of the SN and AN insert into the capsule overlying the glenohumeral joint posteriorly. Articular branches of the LPN exist and innervate a portion of the anterior shoulder joint.

  7. Intra-Articular Therapeutic Delivery for Post Traumatic Osteoarthritis

    Science.gov (United States)

    2015-10-01

    cartilage Subchondral bone Osteophytes Proteoglycans 3. OVERALL PROJECT SUMMARY: In the first annual funding period (Sept 2014 – Sept 2015...Depiction of medial tibial articular cartilage and subchondral bone quantification regions (medial 1/3 and medial marginal osteophyte ). Figure 7...Conclusions A B C D E 12 Articular cartilage composition, subchondral bone, and osteophyte data showed a beneficial effect of single dHACM injection

  8. Imaging diagnosis of the juxta-articular bone cyst

    International Nuclear Information System (INIS)

    Zhang Zekun; Ren Jinjun; Wang Dongmei; Zhang Wei; Ding Jianping; Ding Yang

    2008-01-01

    Objective: To investigate the imaging features of the juxta-articular bone cyst(intra- osseous ganglia). Methods: The imaging findings of 54 cases histopathologically confirmed were studied retrospectively. X-ray, CT, and MRI were performed in 46 eases, 30 cases, and 14 cases, respectively. Results: Of the 54 cases, 27 arised from the ankle (including multiple lesions), 16 from the knee joint, 7 from the hip joint, 1 from the proximate end of the humerus, ulna, trapezium bone, the first phalange in each, and 1 from the talus and the distal end of the tibia. There were 43 cases (44 lesions) in the ankle and knee joints, with 29 (65.9%) lesions located in the medial articular surface. Fifty-four cases had thinning sclerotic rim, showing a unilocular round osteolytic appearance in 44 cases and a multiloculated-cystic appearance with septa in 10 cases. Discontinuous articular surface were seen in 15 cases, reticular surface collapse in 1, gas density in 3 and fluid-fluid plane in 1. (1) On x-ray films, 46 cases (47 lesions) with well-defined sclerotic rim revealed round, arch or irregular lyric areas at the adjacent articular surface. The fissures were found at the adjacent articular surface in 6 lesions. No joint spaces were abnormal. (2)On CT, 30 cases with sclerotic rim showed round in 19 lesions, arch in 3, and irregular in 8. The fissures were seen at the adjacent articular surface in 14 lesions. The density showed homogeneous in 27 lesions, and gas existed in 3. (3) Fourteen cases (15 lesions)showed hypointense to isointense signal on MR T 1 WI and hyperintense signal on T 2 WI. Fluid-fluid plane was found in 1 case. The fissures were observed at the adjacent articular surface in 8 lesions. 7 cases showed swelling soft tissue. Conclusion: The characteristic locations combined with the typical imaging features may suggest the diagnosis of jaxta-articular bone cyst. (authors)

  9. MRI evaluation of acute articular cartilage injury of knee

    International Nuclear Information System (INIS)

    Zhang Jun; Wu Zhenhua; Fan Guoguang; Pan Shinong; Guo Qiyong

    2003-01-01

    Objective: To study the MRI manifestation of acute articular cartilage injury of knee for evaluating the extension and degree of the injury and guiding treatment. Methods: MRI of 34 patients with acute articular cartilage injury of knee within one day to fifteen days confirmed by arthroscopy and arthrotomy was reviewed and analyzed, with emphasis on articular cartilage and subchondral lesion. And every manifestation on MRI and that of arthroscopy and operation was compared. Results: The articular cartilage injury was diagnosed on MRI in 29 of 34 cases. Cartilage signal changes were found only in 4. The changes of cartilage shape were variable. Thinning of focal cartilage was showed in 3, osteochondral impaction in 3, creases of cartilage in 3, disrupted cartilage with fissuring in 13, cracks cartilage in 2, and cracks cartilage with displaced fragment in 1. Bone bruise and occult fracture were found only on MRI. Conclusion: The assessment of MRI and arthroscopy in acute articular cartilage injury are consistent. Combined with arthroscopy, MRI can succeed in assessing the extension and degree of acute articular injury and allowing treatment planning

  10. Estimated Human and Economic Burden of Four Major Adult Vaccine-Preventable Diseases in the United States, 2013

    OpenAIRE

    McLaughlin, John M.; McGinnis, Justin J.; Tan, Litjen; Mercatante, Annette; Fortuna, Joseph

    2015-01-01

    Low uptake of routinely recommended adult immunizations is a public health concern. Using data from the peer-reviewed literature, government disease-surveillance programs, and the US Census, we developed a customizable model to estimate human and economic burden caused by four major adult vaccine-preventable diseases (VPD) in 2013 in the United States, and for each US state individually. To estimate the number of cases for each adult VPD for a given population, we multiplied age-specific inci...

  11. A Transcriptomic and Epigenomic Comparison of Fetal and Adult Human Cardiac Fibroblasts Reveals Novel Key Transcription Factors in Adult Cardiac Fibroblasts

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    Malin K.B. Jonsson, PhD

    2016-12-01

    Full Text Available Cardiovascular disease remains the number one global cause of death and presents as multiple phenotypes in which the interplay between cardiomyocytes and cardiac fibroblasts (CFs has become increasingly highlighted. Fetal and adult CFs influence neighboring cardiomyocytes in different ways. Thus far, a detailed comparison between the two is lacking. Using a genome-wide approach, we identified and validated 2 crucial players for maintaining the adult primary human CF phenotype. Knockdown of these factors induced significant phenotypical changes, including senescence and reduced collagen gene expression. These may now represent novel therapeutic targets against deleterious functions of CFs in adult cardiovascular disease.

  12. Evaluating human papillomavirus vaccination programs in Canada: should provincial healthcare pay for voluntary adult vaccination?

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    Smith? Robert J

    2008-04-01

    Full Text Available Abstract Background Recently, provincial health programs in Canada and elsewhere have begun rolling out vaccination against human papillomavirus for girls aged 9–13. While vaccination is voluntary, the cost of vaccination is waived, to encourage parents to have their daughters vaccinated. Adult women who are eligible for the vaccine may still receive it, but at a cost of approximately CAN$400. Given the high efficacy and immunogenicity of the vaccine, the possibility of eradicating targeted types of the virus may be feasible, assuming the vaccination programs are undertaken strategically. Methods We develop a mathematical model to describe the epidemiology of vaccination against human papillomavirus, accounting for a widespread childhood vaccination program that may be supplemented by voluntary adult vaccination. A stability analysis is performed to determine the stability of the disease-free equilibrium. The critical vaccine efficacy and immunogenicity thresholds are derived, and the minimum level of adult vaccination required for eradication of targeted types is determined. Results We demonstrate that eradication of targeted types is indeed feasible, although the burden of coverage for a childhood-only vaccination program may be high. However, if a small, but non-negligible, proportion of eligible adults can be vaccinated, then the possibility of eradication of targeted types becomes much more favourable. We provide a threshold for eradication in general communities and illustrate the results with numerical simulations. We also investigate the effects of suboptimal efficacy and immunogenicity and show that there is a critical efficacy below which eradication of targeted types is not possible. If eradication is possible, then there is a critical immunogenicity such that even 100% childhood vaccination will not eradicate the targeted types of the virus and must be supplemented with voluntary adult vaccination. However, the level of adult

  13. Identification of distinct layers within the stratified squamous epithelium of the adult human true vocal fold.

    Science.gov (United States)

    Dowdall, Jayme R; Sadow, Peter M; Hartnick, Christopher; Vinarsky, Vladimir; Mou, Hongmei; Zhao, Rui; Song, Phillip C; Franco, Ramon A; Rajagopal, Jayaraj

    2015-09-01

    A precise molecular schema for classifying the different cell types of the normal human vocal fold epithelium is lacking. We hypothesize that the true vocal fold epithelium has a cellular architecture and organization similar to that of other stratified squamous epithelia including the skin, cornea, oral mucosa, and esophagus. In analogy to disorders of the skin and gastrointestinal tract, a molecular definition of the normal cell types within the human vocal fold epithelium and a description of their geometric relationships should serve as a foundation for characterizing cellular changes associated with metaplasia, dysplasia, and cancer. Qualitative study with adult human larynges. Histologic sections of normal human laryngeal tissue were analyzed for morphology (hematoxylin and eosin) and immunohistochemical protein expression profile, including cytokeratins (CK13 and CK14), cornified envelope proteins (involucrin), basal cells (NGFR/p75), and proliferation markers (Ki67). We demonstrated that three distinct cell strata with unique marker profiles are present within the stratified squamous epithelium of the true vocal fold. We used these definitions to establish that cell proliferation is restricted to certain cell types and layers within the epithelium. These distinct cell types are reproducible across five normal adult larynges. We have established that three layers of cells are present within the normal adult stratified squamous epithelium of the true vocal fold. Furthermore, replicating cell populations are largely restricted to the parabasal strata within the epithelium. This delineation of distinct cell populations will facilitate future studies of vocal fold regeneration and cancer. N/A. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.

  14. Immunohistochemical Study of Expression of Sohlh1 and Sohlh2 in Normal Adult Human Tissues.

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    Xiaoli Zhang

    Full Text Available The expression pattern of Sohlh1 (spermatogenesis and oogenesis specific basic helix-loop-helix 1 and Sohlh2 in mice has been reported in previous studies. Sohlh1 and Sohlh2 are specifically expressed in spermatogonia, prespermatogonia in male mice and oocytes of primordial and primary follicles in female mice. In this report, we studied the expression pattern of Sohlh1 and Sohlh2 in human adult tissues. Immunohistochemical staining of Sohlh1 and Sohlh2 was performed in 5 samples of normal ovaries and testes, respectively. The results revealed that Sohlh genes are not only expressed in oocytes and spermatogonia, but also in granular cells, theca cells, Sertoli cells and Leydig cells, and in smooth muscles of blood vessel walls. To further investigate the expression of Sohlh genes in other adult human tissues, we collected representative normal adult tissues developed from three embryonic germ layers. Compared with the expression in mice, Sohlhs exhibited a much more extensive expression pattern in human tissues. Sohlhs were detected in testis, ovary and epithelia developed from embryonic endoderm, ectoderm and tissues developed from embryonic mesoderm. Sohlh signals were found in spermatogonia, Sertoli cells and also Leydig cells in testis, while in ovary, the expression was mainly in oocytes of primordial and primary follicles, granular cells and theca cells of secondary follicles. Compared with Sohlh2, the expression of Sohlh1 was stronger and more extensive. Our study explored the expression of Sohlh genes in human tissues and might provide insights for functional studies of Sohlh genes.

  15. Intra-articular enzyme replacement therapy with rhIDUA is safe, well-tolerated, and reduces articular GAG storage in the canine model of mucopolysaccharidosis type I.

    Science.gov (United States)

    Wang, Raymond Y; Aminian, Afshin; McEntee, Michael F; Kan, Shih-Hsin; Simonaro, Calogera M; Lamanna, William C; Lawrence, Roger; Ellinwood, N Matthew; Guerra, Catalina; Le, Steven Q; Dickson, Patricia I; Esko, Jeffrey D

    2014-08-01

    Treatment with intravenous enzyme replacement therapy and hematopoietic stem cell transplantation for mucopolysaccharidosis (MPS) type I does not address joint disease, resulting in persistent orthopedic complications and impaired quality of life. A proof-of-concept study was conducted to determine the safety, tolerability, and efficacy of intra-articular recombinant human iduronidase (IA-rhIDUA) enzyme replacement therapy in the canine MPS I model. Four MPS I dogs underwent monthly rhIDUA injections (0.58 mg/joint) into the right elbow and knee for 6 months. Contralateral elbows and knees concurrently received normal saline. No intravenous rhIDUA therapy was administered. Monthly blood counts, chemistries, anti-rhIDUA antibody titers, and synovial fluid cell counts were measured. Lysosomal storage of synoviocytes and chondrocytes, synovial macrophages and plasma cells were scored at baseline and 1 month following the final injection. All injections were well-tolerated without adverse reactions. One animal required prednisone for spinal cord compression. There were no clinically significant abnormalities in blood counts or chemistries. Circulating anti-rhIDUA antibody titers gradually increased in all dogs except the prednisone-treated dog; plasma cells, which were absent in all baseline synovial specimens, were predominantly found in synovium of rhIDUA-treated joints at study-end. Lysosomal storage in synoviocytes and chondrocytes following 6 months of IA-rhIDUA demonstrated significant reduction compared to tissues at baseline, and saline-treated tissues at study-end. Mean joint synovial GAG levels in IA-rhIDUA joints were 8.62 ± 5.86 μg/mg dry weight and 21.6 ± 10.4 μg/mg dry weight in control joints (60% reduction). Cartilage heparan sulfate was also reduced in the IA-rhIDUA joints (113 ± 39.5 ng/g wet weight) compared to saline-treated joints (142 ± 56.4 ng/g wet weight). Synovial macrophage infiltration, which was present in all joints at baseline, was

  16. Acceptance and Attitudes Toward a Human-like Socially Assistive Robot by Older Adults.

    Science.gov (United States)

    Louie, Wing-Yue Geoffrey; McColl, Derek; Nejat, Goldie

    2014-01-01

    Recent studies have shown that cognitive and social interventions are crucial to the overall health of older adults including their psychological, cognitive, and physical well-being. However, due to the rapidly growing elderly population of the world, the resources and people to provide these interventions is lacking. Our work focuses on the use of social robotic technologies to provide person-centered cognitive interventions. In this article, we investigate the acceptance and attitudes of older adults toward the human-like expressive socially assistive robot Brian 2.1 in order to determine if the robot's human-like assistive and social characteristics would promote the use of the robot as a cognitive and social interaction tool to aid with activities of daily living. The results of a robot acceptance questionnaire administered during a robot demonstration session with a group of 46 elderly adults showed that the majority of the individuals had positive attitudes toward the socially assistive robot and its intended applications.

  17. Isolation and characterization of multipotent progenitor cells from the Bowman's capsule of adult human kidneys.

    Science.gov (United States)

    Sagrinati, Costanza; Netti, Giuseppe Stefano; Mazzinghi, Benedetta; Lazzeri, Elena; Liotta, Francesco; Frosali, Francesca; Ronconi, Elisa; Meini, Claudia; Gacci, Mauro; Squecco, Roberta; Carini, Marco; Gesualdo, Loreto; Francini, Fabio; Maggi, Enrico; Annunziato, Francesco; Lasagni, Laura; Serio, Mario; Romagnani, Sergio; Romagnani, Paola

    2006-09-01

    Regenerative medicine represents a critical clinical goal for patients with ESRD, but the identification of renal adult multipotent progenitor cells has remained elusive. It is demonstrated that in human adult kidneys, a subset of parietal epithelial cells (PEC) in the Bowman's capsule exhibit coexpression of the stem cell markers CD24 and CD133 and of the stem cell-specific transcription factors Oct-4 and BmI-1, in the absence of lineage-specific markers. This CD24+CD133+ PEC population, which could be purified from cultured capsulated glomeruli, revealed self-renewal potential and a high cloning efficiency. Under appropriate culture conditions, individual clones of CD24+CD133+ PEC could be induced to generate mature, functional, tubular cells with phenotypic features of proximal and/or distal tubules, osteogenic cells, adipocytes, and cells that exhibited phenotypic and functional features of neuronal cells. The injection of CD24+CD133+ PEC but not of CD24-CD133- renal cells into SCID mice that had acute renal failure resulted in the regeneration of tubular structures of different portions of the nephron. More important, treatment of acute renal failure with CD24+CD133+ PEC significantly ameliorated the morphologic and functional kidney damage. This study demonstrates the existence and provides the characterization of a population of resident multipotent progenitor cells in adult human glomeruli, potentially opening new avenues for the development of regenerative medicine in patients who have renal diseases.

  18. Arthoscopy La artroscopia y las lesiones articulares

    Directory of Open Access Journals (Sweden)

    Raúl J. Naranjo

    1991-01-01

    Full Text Available

    A general view is presented on arthroscopy; its history, indications and limitations are described and analyzed; its advantages in comparison with open surgery are emphasized.

    La artroscopia es un procedimiento que permite, mediante un instrumento óptico, evaluar el Interior de las cavidades articulares. Comenzó a desarrollarse como un procedimiento diagnóstico y pronto sus grandes ventajas frente a las exploraciones abiertas aceleraron el desarrollo de las técnicas y del instrumental. La minimización del trauma a los tejidos y la menor morbilidad posoperatoria permiten que la deambulación y la recuperación funcional sean precoces lo cual, sumado a un mejor resultado estético, ha colocado a la artroscopia como procedimiento de elección para el diagnóstico y el tratamiento de múltiples estados patológicos intraarticulares.

  19. Articular cartilage: from formation to tissue engineering.

    Science.gov (United States)

    Camarero-Espinosa, Sandra; Rothen-Rutishauser, Barbara; Foster, E Johan; Weder, Christoph

    2016-05-26

    Hyaline cartilage is the nonlinear, inhomogeneous, anisotropic, poro-viscoelastic connective tissue that serves as friction-reducing and load-bearing cushion in synovial joints and is vital for mammalian skeletal movements. Due to its avascular nature, low cell density, low proliferative activity and the tendency of chondrocytes to de-differentiate, cartilage cannot regenerate after injury, wear and tear, or degeneration through common diseases such as osteoarthritis. Therefore severe damage usually requires surgical intervention. Current clinical strategies to generate new tissue include debridement, microfracture, autologous chondrocyte transplantation, and mosaicplasty. While articular cartilage was predicted to be one of the first tissues to be successfully engineered, it proved to be challenging to reproduce the complex architecture and biomechanical properties of the native tissue. Despite significant research efforts, only a limited number of studies have evolved up to the clinical trial stage. This review article summarizes the current state of cartilage tissue engineering in the context of relevant biological aspects, such as the formation and growth of hyaline cartilage, its composition, structure and biomechanical properties. Special attention is given to materials development, scaffold designs, fabrication methods, and template-cell interactions, which are of great importance to the structure and functionality of the engineered tissue.

  20. Deficient retinoid-driven angiogenesis may contribute to failure of adult human lung regeneration in emphysema.

    Science.gov (United States)

    Ng-Blichfeldt, John-Poul; Alçada, Joana; Montero, M Angeles; Dean, Charlotte H; Griesenbach, Uta; Griffiths, Mark J; Hind, Matthew

    2017-06-01

    Molecular pathways that regulate alveolar development and adult repair represent potential therapeutic targets for emphysema. Signalling via retinoic acid (RA), derived from vitamin A, is required for mammalian alveologenesis, and exogenous RA can induce alveolar regeneration in rodents. Little is known about RA signalling in the human lung and its potential role in lung disease. To examine regulation of human alveolar epithelial and endothelial repair by RA, and characterise RA signalling in human emphysema. The role of RA signalling in alveolar epithelial repair was investigated with a scratch assay using an alveolar cell line (A549) and primary human alveolar type 2 (AT2) cells from resected lung, and the role in angiogenesis using a tube formation assay with human lung microvascular endothelial cells (HLMVEC). Localisation of RA synthetic (RALDH-1) and degrading (cytochrome P450 subfamily 26 A1 (CYP26A1)) enzymes in human lung was determined by immunofluorescence. Regulation of RA pathway components was investigated in emphysematous and control human lung tissue by quantitative real-time PCR and Western analysis. RA stimulated HLMVEC angiogenesis in vitro; this was partially reproduced with a RAR-α agonist. RA induced mRNA expression of vascular endothelial growth factor A (VEGFA) and VEGFR2. RA did not modulate AT2 repair. CYP26A1 protein was identified in human lung microvasculature, whereas RALDH-1 partially co-localised with vimentin-positive fibroblasts. CYP26A1 mRNA and protein were increased in emphysema. RA regulates lung microvascular angiogenesis; the endothelium produces CYP26A1 which is increased in emphysema, possibly leading to reduced RA availability. These data highlight a role for RA in maintenance of the human pulmonary microvascular endothelium. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  1. Reassembly of adult human testicular cells: can testis cord-like structures be created in vitro?

    Science.gov (United States)

    Mincheva, M; Sandhowe-Klaverkamp, R; Wistuba, J; Redmann, K; Stukenborg, J-B; Kliesch, S; Schlatt, S

    2018-02-01

    Can enzymatically dispersed testicular cells from adult men reassemble into seminiferous cord-like structures in vitro? Adult human testicular somatic cells reassembled into testicular cord-like structures via dynamic interactions of Sertoli and peritubular cells. In vitro approaches using dispersed single cell suspensions of human testes to generate seminiferous tubule structures and to initiate their functionality have as yet shown only limited success. Testes from 15 adult gender dysphoria patients (mean ± standard deviation age 35 ± 9.3 years) showing spermatogonial arrest became available for this study after sex-reassignment surgery. In vitro primary testicular somatic cell cultures were generated to explore the self-organizing ability of testicular somatic cells to form testis cords over a 2-week period. Morphological phenotype, protein marker expression and temporal dynamics of cell reassembly were analyzed. Cell suspensions obtained by two-step enzymatic digestion were plated onto glass coverslips in 24-well plates. To obtain adherent somatic cells, the supernatant was discarded on Day 2. The culture of the attached cell population was continued. Reassembly into cord-like structures was analyzed daily by microscopic observations. Endpoints were qualitative changes in morphology. Cell types were characterized by phase-contrast microscopy and immunohistochemistry. Dynamics of cord formation were recorded by time-lapse microscopy. Primary adult human testicular cells underwent sequential morphological changes including compaction and reaggregation resulting in round or elongated cord-like structures. Time-lapse video recordings within the first 4 days of culture revealed highly dynamic processes of migration and coalescence of reaggregated cells. The cellular movements were mediated by peritubular cells. Immunohistochemical analysis showed that both SRY-related high mobility box 9-positive Sertoli and α-smooth muscle actin-positive peritubular myoid cells

  2. Limits on efficient human mindreading: convergence across Chinese adults and Semai children.

    Science.gov (United States)

    Wang, Bo; Hadi, Nur Shafiqah Abdul; Low, Jason

    2015-11-01

    We tested Apperly and Butterfill's (2009, Psychological Review, 116, 753) theory that humans have two mindreading systems whereby the efficient-system guiding anticipatory glances displays signature limits that do not apply to the flexible system guiding verbal predictions. Experiments 1 and 2 tested urban Mainland-Chinese adults (n = 64) and Experiment 3 tested Semai children living in the rainforests of Peninsular Malaysia (3- to 4-year-olds, n = 60). Participants - across different ages, groups and methods - anticipated others' false-beliefs about object-location but not object-identity. Convergence in signature limits signalled that the early-developing efficient system involved minimal theory-of-mind. Chinese adults and older Semai children showed flexibility in their direct predictions. The flexible mindreading system in ascribing others' beliefs as such was task-sensitive and implicated maturational and cultural contributions. © 2015 The British Psychological Society.

  3. Physical Exercise Habits Correlate with Gray Matter Volume of the Hippocampus in Healthy Adult Humans

    Science.gov (United States)

    Killgore, William D. S.; Olson, Elizabeth A.; Weber, Mareen

    2013-12-01

    Physical activity facilitates neurogenesis of dentate cells in the rodent hippocampus, a brain region critical for memory formation and spatial representation. Recent findings in humans also suggest that aerobic exercise can lead to increased hippocampal volume and enhanced cognitive functioning in children and elderly adults. However, the association between physical activity and hippocampal volume during the period from early adulthood through middle age has not been effectively explored. Here, we correlated the number of minutes of self-reported exercise per week with gray matter volume of the hippocampus using voxel-based morphometry (VBM) in 61 healthy adults ranging from 18 to 45 years of age. After controlling for age, gender, and total brain volume, total minutes of weekly exercise correlated significantly with volume of the right hippocampus. Findings highlight the relationship between regular physical exercise and brain structure during early to middle adulthood.

  4. Plasticity of adult human pancreatic duct cells by neurogenin3-mediated reprogramming.

    Directory of Open Access Journals (Sweden)

    Nathalie Swales

    Full Text Available AIMS/HYPOTHESIS: Duct cells isolated from adult human pancreas can be reprogrammed to express islet beta cell genes by adenoviral transduction of the developmental transcription factor neurogenin3 (Ngn3. In this study we aimed to fully characterize the extent of this reprogramming and intended to improve it. METHODS: The extent of the Ngn3-mediated duct-to-endocrine cell reprogramming was measured employing genome wide mRNA profiling. By modulation of the Delta-Notch signaling or addition of pancreatic endocrine transcription factors Myt1, MafA and Pdx1 we intended to improve the reprogramming. RESULTS: Ngn3 stimulates duct cells to express a focused set of genes that are characteristic for islet endocrine cells and/or neural tissues. This neuro-endocrine shift however, is incomplete with less than 10% of full duct-to-endocrine reprogramming achieved. Transduction of exogenous Ngn3 activates endogenous Ngn3 suggesting auto-activation of this gene. Furthermore, pancreatic endocrine reprogramming of human duct cells can be moderately enhanced by inhibition of Delta-Notch signaling as well as by co-expressing the transcription factor Myt1, but not MafA and Pdx1. CONCLUSIONS/INTERPRETATION: The results provide further insight into the plasticity of adult human duct cells and suggest measurable routes to enhance Ngn3-mediated in vitro reprogramming protocols for regenerative beta cell therapy in diabetes.

  5. Gonadotropin-releasing hormone immunoreactivity in the adult and fetal human olfactory system.

    Science.gov (United States)

    Kim, K H; Patel, L; Tobet, S A; King, J C; Rubin, B S; Stopa, E G

    1999-05-01

    Studies in fetal brain tissue of rodents, nonhuman primates and birds have demonstrated that cells containing gonadotropin-releasing hormone (GnRH) migrate from the olfactory placode across the nasal septum into the forebrain. The purpose of this study was to examine GnRH neurons in components of the adult and fetal human olfactory system. In the adult human brain (n=4), immunoreactive GnRH was evident within diffusely scattered cell bodies and processes in the olfactory bulb, olfactory nerve, olfactory cortex, and nervus terminalis located on the anterior surface of the gyrus rectus. GnRH-immunoreactive structures showed a similar distribution in 20-week human fetal brains (n=2), indicating that the migration of GnRH neurons is complete at this time. In 10-11-week fetal brains (n=2), more cells were noted in the nasal cavity than in the brain. Our data are consistent with observations made in other species, confirming olfactory derivation and migration of GnRH neurons into the brain from the olfactory placode. Copyright 1999 Elsevier Science B.V.

  6. The language of geometry: Fast comprehension of geometrical primitives and rules in human adults and preschoolers

    Science.gov (United States)

    Amalric, Marie; Wang, Liping; Figueira, Santiago; Sigman, Mariano; Dehaene, Stanislas

    2017-01-01

    During language processing, humans form complex embedded representations from sequential inputs. Here, we ask whether a “geometrical language” with recursive embedding also underlies the human ability to encode sequences of spatial locations. We introduce a novel paradigm in which subjects are exposed to a sequence of spatial locations on an octagon, and are asked to predict future locations. The sequences vary in complexity according to a well-defined language comprising elementary primitives and recursive rules. A detailed analysis of error patterns indicates that primitives of symmetry and rotation are spontaneously detected and used by adults, preschoolers, and adult members of an indigene group in the Amazon, the Munduruku, who have a restricted numerical and geometrical lexicon and limited access to schooling. Furthermore, subjects readily combine these geometrical primitives into hierarchically organized expressions. By evaluating a large set of such combinations, we obtained a first view of the language needed to account for the representation of visuospatial sequences in humans, and conclude that they encode visuospatial sequences by minimizing the complexity of the structured expressions that capture them. PMID:28125595

  7. Preliminary histopathological study of intra-articular injection of a novel highly cross-linked hyaluronic acid in a rabbit model of knee osteoarthritis.

    Science.gov (United States)

    Iannitti, Tommaso; Elhensheri, Mohamed; Bingöl, Ali O; Palmieri, Beniamino

    2013-04-01

    Osteoarthritis is a degenerative joint disease mostly occurring in the knee and commonly seen in middle-aged and elderly adults. Intra-articular injection of hyaluronic acid has been widely used for treatment of knee osteoarthritis. The aim of this study was to evaluate the efficacy of intra-articular injection of a novel highly cross-linked hyaluronic acid, alone or in combination with ropivacaine hydrochloride and triamcinolone acetonide, on knee articular cartilage in a rabbit model of collagenase-induced knee osteoarthritis. After induction of experimental osteoarthritis by intra-articular injection of collagenase, adult New Zealand white rabbits (n = 12) were divided into 3 groups. Group 1 (control group) received 0.3 ml phosphate buffered saline into the right knee joint. Group 2 received 0.3 ml cross-linked hyaluronic acid (33 mg/ml) into the right knee joint. Group 3 received a mixture of 0.15 ml cross-linked hyaluronic acid (33 mg/ml), 0.05 ml ropivacaine hydrochloride 1 % and 0.1 ml triamcinolone acetonide (10 mg/ml) into the right knee joint. Intra-articular injections were given 4 weeks after first collagenase injection and were administered once a week for 3 weeks. Gross pathology and histological evaluation of rabbits' knee joints were performed after 16 weeks following initial collagenase injection. Histological analysis of sections of right knee joints at lesion sites showed a significant decrease in Mankin's score in groups treated with hyaluronic acid alone or in combination with ropivacaine hydrochloride and triamcinolone acetonide versus control group (p hyaluronic acid, alone or in combination with ropivacaine hydrochloride and triamcinolone acetonide, produces a significant improvement in knee articular cartilage degeneration in a rabbit model of collagenase-induced osteoarthritis.

  8. Is the repair of articular cartilage lesion by costal chondrocyte transplantation donor age-dependent? An experimental study in rabbits.

    Directory of Open Access Journals (Sweden)

    Janusz Popko

    2006-09-01

    Full Text Available The repair of chondral injuries is a very important problem and a subject of many experimental and clinical studies. Different techniques to induce articular cartilage repair are under investigation. In the present study, we have investigated whether the repair of articular cartilage folowing costal chondrocyte transplantation is donor age-dependent. Transplantation of costal chondrocytes from 4- and 24-week old donors, with artificially induced femoral cartilage lesion, was performed on fourteen 20-week-old New Zealand White male rabbits. In the control group, the lesion was left without chondrocyte transplantation. The evaluation of the cartilage repair was performed after 12 weeks of transplantation. We analyzed the macroscopic and histological appearance of the newly formed tissue. Immunohistochemistry was also performed using monoclonal antibodies against rabbit collagen type II. The newly formed tissue had a hyaline-like appearance in most of the lesions after chondrocyte transplantation. Positive immunohistochemical reaction for collagen II was also observed in both groups with transplanted chondrocytes. Cartilage from adult donors required longer isolation time and induced slightly poorer repair. However, hyaline-like cartilage was observed in most specimens from this group, in contrast to the control group, where fibrous connective tissue filled the lesions. Rabbit costal chondrocytes seem to be a potentially useful material for inducing articular cartilage repair and, even more important, they can also be derived from adult, sexually mature animals.

  9. Expression pattern of thymosin beta 4 in the adult human liver

    Directory of Open Access Journals (Sweden)

    S. Nemolato

    2011-09-01

    Full Text Available Thymosin beta-4 (Tβ4 is a member of beta-thymosins, a family of small peptides involved in polymerization of G-actin, and in many critical biological processes including apoptosis, cell migration, angiogenesis, and fibrosis. Previous studies in the newborn liver did not reveal any significant reactivity for Tβ4 during the intrauterine life. The aim of the present study was to investigate by immunohistochemistry Tβ4 expression in the adult normal liver. Thirty-five human liver samples, including 11 needle liver biopsies and 24 liver specimens obtained at autopsy, in which no pathological change was detected at the histological examination, were immunostained utilizing an anti-Tβ4 commercial antibody. Tβ4 was detected in the hepatocytes of all adult normal livers examined. A zonation of Tβ4 expression was evident in the vast majority of cases. Immunostaining was preferentially detected in zone 3, while a minor degree of reactivity was detected in periportal hepatocytes (zone 1. At higher power, Tβ4-reactive granules appeared mainly localized at the biliary pole of hepatocytes. In cases with a strong immunostaining, even perinuclear areas and the sinusoidal pole of hepatocytes appeared interested by immunoreactivity for Tβ4. The current work first evidences a strong diffuse expression of Tβ4 in the adult human liver, and adds hepatocytes to the list of human cells able to synthesize large amounts of Tβ4 in adulthood. Moreover, Tβ4 should be added to the liver proteins characterized by a zonate expression pattern, in a descending gradient from the terminal vein to the periportal areas of the liver acinus. Identifying the intimate role played by this peptide intracellularly and extracellularly, in physiology and in different liver diseases, is a major challenge for future research focusing on Tβ4.

  10. Cortical surface area and cortical thickness in the precuneus of adult humans.

    Science.gov (United States)

    Bruner, E; Román, F J; de la Cuétara, J M; Martin-Loeches, M; Colom, R

    2015-02-12

    The precuneus has received considerable attention in the last decade, because of its cognitive functions, its role as a central node of the brain networks, and its involvement in neurodegenerative processes. Paleoneurological studies suggested that form changes in the deep parietal areas represent a major character associated with the origin of the modern human brain morphology. A recent neuroanatomical survey based on shape analysis suggests that the proportions of the precuneus are also a determinant source of overall brain geometrical differences among adult individuals, influencing the brain spatial organization. Here, we evaluate the variation of cortical thickness and cortical surface area of the precuneus in a sample of adult humans, and their relation with geometry and cognition. Precuneal thickness and surface area are not correlated. There is a marked individual variation. The right precuneus is thinner and larger than the left one, but there are relevant fluctuating asymmetries, with only a modest correlation between the hemispheres. Males have a thicker cortex but differences in cortical area are not significant between sexes. The surface area of the precuneus shows a positive allometry with the brain surface area, although the correlation is modest. The dilation/contraction of the precuneus, described as a major factor of variability within adult humans, is associated with absolute increase/decrease of its surface, but not with variation in thickness. Precuneal thickness, precuneal surface area and precuneal morphology are not correlated with psychological factors such as intelligence, working memory, attention control, and processing speed, stressing further possible roles of this area in supporting default mode functions. Beyond gross morphology, the processes underlying the large phenotypic variation of the precuneus must be further investigated through specific cellular analyses, aimed at considering differences in cellular size, density

  11. Evidence for a stem cell hierarchy in the adult human breast

    DEFF Research Database (Denmark)

    Villadsen, René; Fridriksdottir, Agla J; Rønnov-Jessen, Lone

    2007-01-01

    Cellular pathways that contribute to adult human mammary gland architecture and lineages have not been previously described. In this study, we identify a candidate stem cell niche in ducts and zones containing progenitor cells in lobules. Putative stem cells residing in ducts were essentially...... in laminin-rich extracellular matrix gels. Staining for the lineage markers keratins K14 and K19 further revealed multipotent cells in the stem cell zone and three lineage-restricted cell types outside this zone. Multiparameter cell sorting and functional characterization with reference to anatomical sites...

  12. Empirical evaluation of the inter-relationship of articular elements involved in the pathoanatomy of knee osteoarthritis using magnetic resonance imaging.

    Science.gov (United States)

    Meredith, Dennis S; Losina, Elena; Neumann, Gesa; Yoshioka, Hiroshi; Lang, Philipp K; Katz, Jeffrey N

    2009-10-29

    In this cross-sectional study, we conducted a comprehensive assessment of all articular elements that could be measured using knee MRI. We assessed the association of pathological change in multiple articular structures involved in the pathoanatomy of osteoarthritis. Knee MRI scans from patients over 45 years old were assessed using a semi-quantitative knee MRI assessment form. The form included six distinct elements: cartilage, bone marrow lesions, osteophytes, subchondral sclerosis, joint effusion and synovitis. Each type of pathology was graded using an ordinal scale with a value of zero indicating no pathology and higher values indicating increasingly severe levels of pathology. The principal dependent variable for comparison was the mean cartilage disease score (CDS), which captured the aggregate extent of involvement of articular cartilage. The distribution of CDS was compared to the individual and cumulative distributions of each articular element using the Chi-squared test. The correlations between pathological change in the various articular structures were assessed in a Spearman correlation table. Data from 140 patients were available for review. The cohort had a median age of 61 years (range 45-89) and was 61% female. The cohort included a wide spectrum of OA severity. Our analysis showed a statistically significant trend towards pathological change involving more articular elements as CDS worsened (p-value for trend osteophytes (p-value for trend subchondral sclerosis (p = 0.009), but not joint effusion or synovitis. There was a moderate correlation between cartilage damage, osteophytes and BMLs as well as a moderate correlation between joint effusion and synovitis. However, cartilage damage and osteophytes were only weakly associated with synovitis or joint effusion. Our results support an inter-relationship of multiple articular elements in the pathoanatomy of knee OA. Prospective studies of OA pathogenesis in humans are needed to correlate these

  13. Validation of endogenous normalizing genes for expression analyses in adult human testis and germ cell neoplasms

    DEFF Research Database (Denmark)

    Svingen, T; Jørgensen, Anne; Rajpert-De Meyts, E

    2014-01-01

    to define suitable normalizing genes for specific cells and tissues. Here, we report on the performance of a panel of nine commonly employed normalizing genes in adult human testis and testicular pathologies. Our analyses revealed significant variability in transcript abundance for commonly used normalizers......, highlighting the importance of selecting appropriate normalizing genes as comparative measurements can yield variable results when different normalizing genes are employed. Based on our results, we recommend using RPS20, RPS29 or SRSF4 when analysing relative gene expression levels in human testis...... and associated testicular pathologies. OCT4 and SALL4 can be used with caution as second-tier normalizers when determining changes in gene expression in germ cells and germ cell tumour components, but the relative transcript abundance appears variable between different germ cell tumour types. We further...

  14. 40 CFR 26.1704 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted before April 7, 2006. 26.1704 Section 26.1704 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS...

  15. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted after April 7, 2006. 26.1705 Section 26.1705 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GENERAL PROTECTION OF HUMAN SUBJECTS...

  16. Bi-articular Knee-Ankle-Foot Exoskeleton Produces Higher Metabolic Cost Reduction than Weight-Matched Mono-articular Exoskeleton

    Science.gov (United States)

    Malcolm, Philippe; Galle, Samuel; Derave, Wim; De Clercq, Dirk

    2018-01-01

    The bi-articular m. gastrocnemius and the mono-articular m. soleus have different and complementary functions during walking. Several groups are starting to use these biological functions as inspiration to design prostheses with bi-articular actuation components to replace the function of the m. gastrocnemius. Simulation studies indicate that a bi-articular configuration and spring that mimic the m. gastrocnemius could be beneficial for orthoses or exoskeletons. Our aim was to test the effect of a bi-articular and spring configuration that mimics the m. gastrocnemius and compare this to a no-spring and mono-articular configuration. We tested nine participants during walking with knee-ankle-foot exoskeletons with dorsally mounted pneumatic muscle actuators. In the bi-articular plus spring condition the pneumatic muscles were attached to the thigh segment with an elastic cord. In the bi-articular no-spring condition the pneumatic muscles were also attached to the thigh segment but with a non-elastic cord. In the mono-articular condition the pneumatic muscles were attached to the shank segment. We found the highest reduction in metabolic cost of 13% compared to walking with the exoskeleton powered-off in the bi-articular plus spring condition. Possible explanations for this could be that the exoskeleton delivered the highest total positive work in this condition at the ankle and the knee and provided more assistance during the isometric phase of the biological plantarflexors. As expected we found that the bi-articular conditions reduced m. gastrocnemius EMG more than the mono-articular condition but this difference was not significant. We did not find that the mono-articular condition reduces the m. soleus EMG more than the bi-articular conditions. Knowledge of specific effects of different exoskeleton configurations on metabolic cost and muscle activation could be useful for providing customized assistance for specific gait impairments. PMID:29551959

  17. Bi-articular Knee-Ankle-Foot Exoskeleton Produces Higher Metabolic Cost Reduction than Weight-Matched Mono-articular Exoskeleton

    Directory of Open Access Journals (Sweden)

    Philippe Malcolm

    2018-03-01

    Full Text Available The bi-articular m. gastrocnemius and the mono-articular m. soleus have different and complementary functions during walking. Several groups are starting to use these biological functions as inspiration to design prostheses with bi-articular actuation components to replace the function of the m. gastrocnemius. Simulation studies indicate that a bi-articular configuration and spring that mimic the m. gastrocnemius could be beneficial for orthoses or exoskeletons. Our aim was to test the effect of a bi-articular and spring configuration that mimics the m. gastrocnemius and compare this to a no-spring and mono-articular configuration. We tested nine participants during walking with knee-ankle-foot exoskeletons with dorsally mounted pneumatic muscle actuators. In the bi-articular plus spring condition the pneumatic muscles were attached to the thigh segment with an elastic cord. In the bi-articular no-spring condition the pneumatic muscles were also attached to the thigh segment but with a non-elastic cord. In the mono-articular condition the pneumatic muscles were attached to the shank segment. We found the highest reduction in metabolic cost of 13% compared to walking with the exoskeleton powered-off in the bi-articular plus spring condition. Possible explanations for this could be that the exoskeleton delivered the highest total positive work in this condition at the ankle and the knee and provided more assistance during the isometric phase of the biological plantarflexors. As expected we found that the bi-articular conditions reduced m. gastrocnemius EMG more than the mono-articular condition but this difference was not significant. We did not find that the mono-articular condition reduces the m. soleus EMG more than the bi-articular conditions. Knowledge of specific effects of different exoskeleton configurations on metabolic cost and muscle activation could be useful for providing customized assistance for specific gait impairments.

  18. Bi-articular Knee-Ankle-Foot Exoskeleton Produces Higher Metabolic Cost Reduction than Weight-Matched Mono-articular Exoskeleton.

    Science.gov (United States)

    Malcolm, Philippe; Galle, Samuel; Derave, Wim; De Clercq, Dirk

    2018-01-01

    The bi-articular m. gastrocnemius and the mono-articular m. soleus have different and complementary functions during walking. Several groups are starting to use these biological functions as inspiration to design prostheses with bi-articular actuation components to replace the function of the m. gastrocnemius. Simulation studies indicate that a bi-articular configuration and spring that mimic the m. gastrocnemius could be beneficial for orthoses or exoskeletons. Our aim was to test the effect of a bi-articular and spring configuration that mimics the m. gastrocnemius and compare this to a no-spring and mono-articular configuration. We tested nine participants during walking with knee-ankle-foot exoskeletons with dorsally mounted pneumatic muscle actuators. In the bi-articular plus spring condition the pneumatic muscles were attached to the thigh segment with an elastic cord. In the bi-articular no-spring condition the pneumatic muscles were also attached to the thigh segment but with a non-elastic cord. In the mono-articular condition the pneumatic muscles were attached to the shank segment. We found the highest reduction in metabolic cost of 13% compared to walking with the exoskeleton powered-off in the bi-articular plus spring condition . Possible explanations for this could be that the exoskeleton delivered the highest total positive work in this condition at the ankle and the knee and provided more assistance during the isometric phase of the biological plantarflexors. As expected we found that the bi-articular conditions reduced m. gastrocnemius EMG more than the mono-articular condition but this difference was not significant. We did not find that the mono-articular condition reduces the m. soleus EMG more than the bi-articular conditions . Knowledge of specific effects of different exoskeleton configurations on metabolic cost and muscle activation could be useful for providing customized assistance for specific gait impairments.

  19. Effect of Transplanting Various Concentrations of a Composite of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells and Hyaluronic Acid Hydrogel on Articular Cartilage Repair in a Rabbit Model.

    Directory of Open Access Journals (Sweden)

    Yong-Beom Park

    Full Text Available Mesenchymal stem cells (MSCs are known to have therapeutic potential for cartilage repair. However, the optimal concentration of MSCs for cartilage repair remains unclear. Therefore, we aimed to explore the feasibility of cartilage repair by human umbilical cord blood-derived MSCs (hUCB-MSCs and to determine the optimal concentrations of the MSCs in a rabbit model.Osteochondral defects were created in the trochlear groove of femur in 55 rabbits. Four experimental groups (11 rabbits/group were treated by transplanting the composite of hUCB-MSCs and HA with various MSCs concentrations (0.1, 0.5, 1.0, and 1.5 x 107 cells/ml. One control group was left untreated. At 4, 8, and 16 weeks post-transplantation, the degree of cartilage repair was evaluated grossly and histologically.Overall, transplanting hUCB-MSCs and HA hydrogel resulted in cartilage repair tissue with better quality than the control without transplantation (P = 0.015 in 0.1, P = 0.004 in 0.5, P = 0.004 in 1.0, P = 0.132 in 1.5 x 107 cells/ml. Interestingly, high cell concentration of hUCB-MSCs (1.5×107 cells/ml was inferior to low cell concentrations (0.1, 0.5, and 1.0 x 107 cells/ml in cartilage repair (P = 0.394,P = 0.041, P = 0.699, respectively. The 0.5 x 107 cells/ml group showed the highest cartilage repair score at 4, 8 and 16 weeks post transplantation, and followed by 0.1x107 cells/ml group or 1.0 x 107 cell/ml group.The results of this study suggest that transplantation of the composite of hUCB-MSCs and HA is beneficial for cartilage repair. In addition, this study shows that optimal MSC concentration needs to be determined for better cartilage repair.

  20. 24R,25-Dihydroxyvitamin D3 Protects against Articular Cartilage Damage following Anterior Cruciate Ligament Transection in Male Rats.

    Directory of Open Access Journals (Sweden)

    Barbara D Boyan

    Full Text Available Osteoarthritis (OA in humans is associated with low circulating 25-hydroxyvitamin D3 [25(OHD3]. In vitamin D replete rats, radiolabeled 24R,25-dihydroxyvitamin D3 [24R,25(OH2D3] accumulates in articular cartilage following injection of [3H]-25(OHD3. Previously, we showed that 24R,25(OH2D3 blocks chondrocyte apoptosis via phospholipase D and p53, suggesting a role for 24R,25(OH2D3 in maintaining cartilage health. We examined the ability of 24R,25(OH2D3 to prevent degenerative changes in articular cartilage in an OA-like environment and the potential mechanisms involved. In vitro, rat articular chondrocytes were treated with IL-1β with and without 24R,25(OH2D3 or 1α,25(OH2D3. 24R,25(OH2D3 but not 1α,25(OH2D3 blocked the effects of IL-1β in a dose-dependent manner, and its effect was partially mediated through the TGF-β1 signaling pathway. In vivo, unilateral anterior cruciate ligament transections were performed in immunocompetent rats followed by intra-articular injections of 24R,25(OH2D3 or vehicle (t = 0, 7, 14, 21 days. Tissues were harvested on day 28. Joints treated with vehicle had changes typical of OA whereas joints treated with 24R,25(OH2D3 had less articular cartilage damage and levels of inflammatory mediators. These results indicate that 24R,25(OH2D3 protects against OA, and suggest that it may be a therapeutic approach for preventing trauma-induced osteoarthritis.

  1. Isolation and characterization of adult human liver progenitors from ischemic liver tissue derived from therapeutic hepatectomies.

    Science.gov (United States)

    Stachelscheid, Harald; Urbaniak, Thomas; Ring, Alexander; Spengler, Berlind; Gerlach, Jörg C; Zeilinger, Katrin

    2009-07-01

    Recent evidence suggests that progenitor cells in adult tissues and embryonic stem cells share a high resistance to hypoxia and ischemic stress. To study the ischemic resistance of adult liver progenitors, we characterized remaining viable cells in human liver tissue after cold ischemic treatment for 24-168 h, applied to the tissue before cell isolation. In vitro cultures of isolated cells showed a rapid decline of the number of different cell types with increasing ischemia length. After all ischemic periods, liver progenitor-like cells could be observed. The comparably small cells exhibited a low cytoplasm-to-nucleus ratio, formed densely packed colonies, and showed a hepatobiliary marker profile. The cells expressed epithelial cell adhesion molecule, epithelial-specific (CK8/18) and biliary-specific (CK7/19) cytokeratins, albumin, alpha-1-antitrypsin, cytochrome-P450 enzymes, as well as weak levels of hepatocyte nuclear factor-4 and gamma-glutamyl transferase, but not alpha-fetoprotein or Thy-1. In vitro survival and expansion was facilitated by coculture with mouse embryonic fibroblasts. Hepatic progenitor-like cells exhibit a high resistance to ischemic stress and can be isolated from human liver tissue after up to 7 days of ischemia. Ischemic liver tissue from various sources, thought to be unsuitable for cell isolation, may be considered as a prospective source of hepatic progenitor cells.

  2. Skeletal 212Pb retention following 224Ra injection: extrapolation of animal data to adult humans

    International Nuclear Information System (INIS)

    Schlenker, R.A.

    1988-01-01

    Two methods of interspecies extrapolation, one based on a correlation of skeletal 212 Pb/ 224 Ra with body weight, the other based on the mechanistic relationship between skeletal 212 Pb/ 224 Ra and reciprocal bone surface-to-volume ratio, lead to the conclusion that the retention of 212 Pb in the adult human skeleton is approximately complete a few days after injection. The correlation-based method gives most probable values for 212 Pb/ 224 Ra of 1.0 and 1.1 at 2 d and 7 d after injection, compared with values of 1.05 and 1.27 expected at these same times if the retention of 212 Pb were complete from the time of injection and if no 212 Pb were in the injection solution. The range of values corresponding to one geometric standard error on either side of the most probable value is 0.87 to 1.21 at 2 d post-injection. With the method based on the reciprocal bone surface-to-volume ratio, the best estimate of 212 Pb/ 224 Ra at 2 d after injection is 0.88, equal to the value observed in young adult beagles. An alternative interpretation of the results of this latter method leads to the conclusion that retention is complete, with 212 Pb/ 224 Ra equal to 1.0 for a 212 Pb-free injection solution and 1.1 for a solution containing 212 Pb in secular equilibrium with 224 Ra. This work, which uses 224 Ra daughter product retention data from mice, rats and dogs following 224Ra injection, provides a scientific foundation for retention assumptions made in the calculation of mean skeletal dose for adult humans. There now appear to be few uncertainties in these latter dose values, stemming from inaccurate retention assumptions; but substantial uncertainties remain in the mean skeletal dose values for juveniles and in the endosteal tissue doses regardless of age

  3. In Vitro Generation of Functional Liver Organoid-Like Structures Using Adult Human Cells.

    Science.gov (United States)

    Ramachandran, Sarada Devi; Schirmer, Katharina; Münst, Bernhard; Heinz, Stefan; Ghafoory, Shahrouz; Wölfl, Stefan; Simon-Keller, Katja; Marx, Alexander; Øie, Cristina Ionica; Ebert, Matthias P; Walles, Heike; Braspenning, Joris; Breitkopf-Heinlein, Katja

    2015-01-01

    In this study we used differentiated adult human upcyte® cells for the in vitro generation of liver organoids. Upcyte® cells are genetically engineered cell strains derived from primary human cells by lenti-viral transduction of genes or gene combinations inducing transient proliferation capacity (upcyte® process). Proliferating upcyte® cells undergo a finite number of cell divisions, i.e., 20 to 40 population doublings, but upon withdrawal of proliferation stimulating factors, they regain most of the cell specific characteristics of primary cells. When a defined mixture of differentiated human upcyte® cells (hepatocytes, liver sinusoidal endothelial cells (LSECs) and mesenchymal stem cells (MSCs)) was cultured in vitro on a thick layer of Matrigel™, they self-organized to form liver organoid-like structures within 24 hours. When further cultured for 10 days in a bioreactor, these liver organoids show typical functional characteristics of liver parenchyma including activity of cytochromes P450, CYP3A4, CYP2B6 and CYP2C9 as well as mRNA expression of several marker genes and other enzymes. In summary, we hereby describe that 3D functional hepatic structures composed of primary human cell strains can be generated in vitro. They can be cultured for a prolonged period of time and are potentially useful ex vivo models to study liver functions.

  4. Non-Viral Generation of Neural Precursor-like Cells from Adult Human Fibroblasts

    Directory of Open Access Journals (Sweden)

    Maucksch C

    2012-01-01

    Full Text Available Recent studies have reported direct reprogramming of human fibroblasts to mature neurons by the introduction of defined neural genes. This technology has potential use in the areas of neurological disease modeling and drug development. However, use of induced neurons for large-scale drug screening and cell-based replacement strategies is limited due to their inability to expand once reprogrammed. We propose it would be more desirable to induce expandable neural precursor cells directly from human fibroblasts. To date several pluripotent and neural transcription factors have been shown to be capable of converting mouse fibroblasts to neural stem/precursor-like cells when delivered by viral vectors. Here we extend these findings and demonstrate that transient ectopic insertion of the transcription factors SOX2 and PAX6 to adult human fibroblasts through use of non-viral plasmid transfection or protein transduction allows the generation of induced neural precursor (iNP colonies expressing a range of neural stem and pro-neural genes. Upon differentiation, iNP cells give rise to neurons exhibiting typical neuronal morphologies and expressing multiple neuronal markers including tyrosine hydroxylase and GAD65/67. Importantly, iNP-derived neurons demonstrate electrophysiological properties of functionally mature neurons with the capacity to generate action potentials. In addition, iNP cells are capable of differentiating into glial fibrillary acidic protein (GFAP-expressing astrocytes. This study represents a novel virus-free approach for direct reprogramming of human fibroblasts to a neural precursor fate.

  5. Adult, embryonic and fetal hemoglobin are expressed in human glioblastoma cells.

    Science.gov (United States)

    Emara, Marwan; Turner, A Robert; Allalunis-Turner, Joan

    2014-02-01

    Hemoglobin is a hemoprotein, produced mainly in erythrocytes circulating in the blood. However, non-erythroid hemoglobins have been previously reported in other cell types including human and rodent neurons of embryonic and adult brain, but not astrocytes and oligodendrocytes. Human glioblastoma multiforme (GBM) is the most aggressive tumor among gliomas. However, despite extensive basic and clinical research studies on GBM cells, little is known about glial defence mechanisms that allow these cells to survive and resist various types of treatment. We have shown previously that the newest members of vertebrate globin family, neuroglobin (Ngb) and cytoglobin (Cygb), are expressed in human GBM cells. In this study, we sought to determine whether hemoglobin is also expressed in GBM cells. Conventional RT-PCR, DNA sequencing, western blot analysis, mass spectrometry and fluorescence microscopy were used to investigate globin expression in GBM cell lines (M006x, M059J, M059K, M010b, U87R and U87T) that have unique characteristics in terms of tumor invasion and response to radiotherapy and hypoxia. The data showed that α, β, γ, δ, ζ and ε globins are expressed in all tested GBM cell lines. To our knowledge, we are the first to report expression of fetal, embryonic and adult hemoglobin in GBM cells under normal physiological conditions that may suggest an undefined function of those expressed hemoglobins. Together with our previous reports on globins (Ngb and Cygb) expression in GBM cells, the expression of different hemoglobins may constitute a part of series of active defence mechanisms supporting these cells to resist various types of treatments including chemotherapy and radiotherapy.

  6. Intra-Articular Osteotomy for Distal Humerus Malunion

    Directory of Open Access Journals (Sweden)

    René K. Marti

    2009-01-01

    Full Text Available Intra-articular osteotomy is considered in the rare case of malunion after a fracture of the distal humerus to restore humeral alignment and gain a functional arc of elbow motion. Traumatic and iatrogenic disruption of the limited blood flow to the distal end of the humerus resulting in avascular necrosis of capitellum or trochlea is a major pitfall of the this technically challenging procedure. Two cases are presented which illustrate the potential problems of intra-articular osteotomy for malunion of the distal humerus.

  7. Small-Diameter Awls Improve Articular Cartilage Repair After Microfracture Treatment in a Translational Animal Model.

    Science.gov (United States)

    Orth, Patrick; Duffner, Julia; Zurakowski, David; Cucchiarini, Magali; Madry, Henning

    2016-01-01

    Microfracture is the most commonly applied arthroscopic marrow stimulation procedure. Articular cartilage repair is improved when the subchondral bone is perforated by small-diameter microfracture awls compared with larger awls. Controlled laboratory study. Standardized rectangular (4 × 8 mm) full-thickness chondral defects (N = 24) were created in the medial femoral condyle of 16 adult sheep and debrided down to the subchondral bone plate. Three treatment groups (n = 8 defects each) were tested: 6 microfracture perforations using small-diameter awls (1.0 mm; group 1), large-diameter awls (1.2 mm; group 2), or without perforations (debridement control; group 3). Osteochondral repair was assessed at 6 months in vivo using established macroscopic, histological, immunohistochemical, biochemical, and micro-computed tomography analyses. Compared with control defects, histological cartilage repair was always improved after both microfracture techniques (P Subchondral bone cysts and intralesional osteophytes were frequently observed after either microfracture treatment. Macroscopic grading, DNA, proteoglycan, and type I and type II collagen contents as well as degenerative changes within the adjacent cartilage remained unaffected by the awl diameter. Small-diameter microfracture awls improve articular cartilage repair in the translational sheep model more effectively than do larger awls. These data support the use of small microfracture instruments for the surgical treatment of cartilage defects and warrant prolonged clinical investigations. © 2015 The Author(s).

  8. Impact of exercise on articular cartilage: Systematic reviews and meta-analyses of randomised controlled trials

    DEFF Research Database (Denmark)

    Bricca, Alessio

    2018-01-01

    This thesis summarizes the evidence on the impact of exercise on articular cartilage. No evidence was found to support beneficial effects of exercise on articular cartilage, although in people at risk of, or with, knee osteoarthritis, exercise is not harmful for articular cartilage structure and ...

  9. Behaviour of solitary adult Scandinavian brown bears (Ursus arctos when approached by humans on foot.

    Directory of Open Access Journals (Sweden)

    Gro Kvelprud Moen

    Full Text Available Successful management has brought the Scandinavian brown bear (Ursus arctos L. back from the brink of extinction, but as the population grows and expands the probability of bear-human encounters increases. More people express concerns about spending time in the forest, because of the possibility of encountering bears, and acceptance for the bear is decreasing. In this context, reliable information about the bear's normal behaviour during bear-human encounters is important. Here we describe the behaviour of brown bears when encountering humans on foot. During 2006-2009, we approached 30 adult (21 females, 9 males GPS-collared bears 169 times during midday, using 1-minute positioning before, during and after the approach. Observer movements were registered with a handheld GPS. The approaches started 869±348 m from the bears, with the wind towards the bear when passing it at approximately 50 m. The bears were detected in 15% of the approaches, and none of the bears displayed any aggressive behaviour. Most bears (80% left the initial site during the approach, going away from the observers, whereas some remained at the initial site after being approached (20%. Young bears left more often than older bears, possibly due to differences in experience, but the difference between ages decreased during the berry season compared to the pre-berry season. The flight initiation distance was longer for active bears (115±94 m than passive bears (69±47 m, and was further affected by horizontal vegetation cover and the bear's age. Our findings show that bears try to avoid confrontations with humans on foot, and support the conclusions of earlier studies that the Scandinavian brown bear is normally not aggressive during encounters with humans.

  10. In-Depth Analysis of Human Neonatal and Adult IgM Antibody Repertoires

    Directory of Open Access Journals (Sweden)

    Binbin Hong

    2018-02-01

    Full Text Available Although high-throughput sequencing and associated bioinformatics technologies have enabled the in-depth, sequence-based characterization of human immune repertoires, only a few studies on a relatively small number of sequences explored the characteristics of antibody repertoires in neonates, with contradictory conclusions. To gain a more comprehensive understanding of the human IgM antibody repertoire, we performed Illumina sequencing and IMGT/HighV-QUEST analysis of IgM heavy chain repertoire of the B lymphocytes from the cord blood (CB of neonates, as well as the repertoire from peripheral blood of healthy human adults (HH. The comparative study revealed unexpectedly high levels of similarity between the neonatal and adult repertoires. In both repertoires, the VDJ gene usage showed no significant difference, and the most frequently used VDJ gene was IGHV4-59, IGHD3-10, and IGHJ3. The average amino acid (aa length of CDR1 (CB: 8.5, HH: 8.4 and CDR2 (CB: 7.6, HH: 7.5, as well as the aa composition and the average hydrophobicity of the CDR3 demonstrated no significant difference between the two repertories. However, the average aa length of CDR3 was longer in the HH repertoire than the CB repertoire (CB: 14.5, HH: 15.5. Besides, the frequencies of aa mutations in CDR1 (CB: 19.33%, HH: 25.84% and CDR2 (CB: 9.26%, HH: 17.82% were higher in the HH repertoire compared to the CB repertoire. Interestingly, the most prominent difference between the two repertoires was the occurrence of N2 addition (CB: 64.87%, HH: 85.69%, a process that occurs during V-D-J recombination for introducing random nucleotide additions between D- and J-gene segments. The antibody repertoire of healthy adults was more diverse than that of neonates largely due to the higher occurrence of N2 addition. These findings may lead to a better understanding of antibody development and evolution pathways and may have potential practical value for facilitating the generation of more

  11. Specific metabolomics adaptations define a differential regional vulnerability in the adult human cerebral cortex

    Directory of Open Access Journals (Sweden)

    Rosanna Cabré

    2016-12-01

    Full Text Available Brain neurons offer diverse responses to stresses and detrimental factors during development and aging, and as a result of both neurodegenerative and neuropsychiatric disorders. This multiplicity of responses can be ascribed to the great diversity among neuronal populations. Here we have determined the metabolomic profile of three healthy adult human brain regions—entorhinal cortex, hippocampus, and frontal cortex—using mass spectrometry-based technologies. Our results show the existence of a lessened energy demand, mitochondrial stress, and lower one-carbon metabolism (particularly restricted to the methionine cycle specifically in frontal cortex. These findings, along with the better antioxidant capacity and lower mTOR signaling also seen in frontal cortex, suggest that this brain region is especially resistant to stress compared to the entorhinal cortex and hippocampus, which are more vulnerable regions. Globally, our results show the presence of specific metabolomics adaptations in three mature, healthy human brain regions, confirming the existence of cross-regional differences in cell vulnerability in the human cerebral cortex.

  12. From the Cover: Cell-replacement therapy for diabetes: Generating functional insulin-producing tissue from adult human liver cells

    Science.gov (United States)

    Sapir, Tamar; Shternhall, Keren; Meivar-Levy, Irit; Blumenfeld, Tamar; Cohen, Hamutal; Skutelsky, Ehud; Eventov-Friedman, Smadar; Barshack, Iris; Goldberg, Iris; Pri-Chen, Sarah; Ben-Dor, Lya; Polak-Charcon, Sylvie; Karasik, Avraham; Shimon, Ilan; Mor, Eytan; Ferber, Sarah

    2005-05-01

    Shortage in tissue availability from cadaver donors and the need for life-long immunosuppression severely restrict the large-scale application of cell-replacement therapy for diabetic patients. This study suggests the potential use of adult human liver as alternate tissue for autologous beta-cell-replacement therapy. By using pancreatic and duodenal homeobox gene 1 (PDX-1) and soluble factors, we induced a comprehensive developmental shift of adult human liver cells into functional insulin-producing cells. PDX-1-treated human liver cells express insulin, store it in defined granules, and secrete the hormone in a glucose-regulated manner. When transplanted under the renal capsule of diabetic, immunodeficient mice, the cells ameliorated hyperglycemia for prolonged periods of time. Inducing developmental redirection of adult liver offers the potential of a cell-replacement therapy for diabetics by allowing the patient to be the donor of his own insulin-producing tissue. pancreas | transdifferentiation

  13. Finite element analysis of intramedullary nailing and double locking plate for treating extra-articular proximal tibial fractures.

    Science.gov (United States)

    Chen, Fancheng; Huang, Xiaowei; Ya, Yingsun; Ma, Fenfen; Qian, Zhi; Shi, Jifei; Guo, Shuolei; Yu, Baoqing

    2018-01-16

    Proximal tibia fractures are one of the most familiar fractures. Surgical approaches are usually needed for anatomical reduction. However, no single treatment method has been widely established as the standard care. Our present study aims to compare the stress and stability of intramedullary nails (IMN) fixation and double locking plate (DLP) fixation in the treatment of extra-articular proximal tibial fractures. A three-dimensional (3D) finite element model of the extra-articular proximal tibial fracture, whose 2-cm bone gap began 7 cm from the tibial plateau articular surface, was created fixed by different fixation implants. The axial compressive load on an adult knee during single-limb stance was imitated by an axial force of 2500 N with a distribution of 60% to the medial compartment, while the distal end was fixed effectively. The equivalent von Mises stress and displacement of the model was used as the output measures for analysis. The maximal equivalent von Mises stress value of the system in the IMN model was 293.23 MPa, which was higher comparing against that in the DLP fixation model (147.04 MPa). And the mean stress of the model in the IMN model (9.25 MPa) was higher than that of the DLP fixation system in terms of equivalent von Mises stress (EVMS) (P tibial fractures of young patients.

  14. Patterns of triangular fibrocartilage complex (TFCC) injury associated with severely dorsally displaced extra-articular distal radius fractures.

    Science.gov (United States)

    Scheer, Johan H; Adolfsson, Lars E

    2012-06-01

    The aim of the study was to examine triangular fibrocartilage (TFCC) injury patterns associated with unstable, extra-articular dorsally displaced distal radius fractures. Twenty adult patients with an Arbeitsgemeinschaft für Osteosynthesefragen (AO), type A2 or A3, distal radius fracture with an initial dorsal angulation greater than 20° were included. Nine had a tip fracture (distal to the base) of the ulnar styloid and 11 had no such fracture. They were all openly explored from an ulnopalmar approach and TFCC injuries were documented. Eleven patients also underwent arthroscopy and intra-articular pathology was recorded. All patients had TFCC lesions of varying severity, having an extensor carpi ulnaris subsheath avulsion in common. Eighteen out of 20 also displayed deep foveal radioulnar ligament lesions, with decreasingly dorsal fibres remaining. The extent of this foveal injury could not be appreciated by radiocarpal arthroscopy. Severe displacement of an extra-articular radius fracture suggests an ulnar-sided ligament injury to the TFCC. The observed lesions concur with findings in a previous cadaver study. The lesions follow a distinct pattern affecting both radioulnar as well as ulnocarpal stabilisers. Copyright © 2012 Elsevier Ltd. All rights reserved.

  15. Pharmacokinetics of betamethasone in plasma, urine, and synovial fluid following intra-articular administration to exercised thoroughbred horses.

    Science.gov (United States)

    Knych, Heather K; Stanley, Scott D; Harrison, Linda M; Mckemie, Daniel S

    2017-09-01

    The use of corticosteroids, such as betamethasone, in performance horses is tightly regulated. The objective of the current study was to describe the plasma pharmacokinetics of betamethasone as well as time-related urine and synovial fluid concentrations following intra-articular administration to horses. Twelve racing-fit adult Thoroughbred horses received a single intra-articular administration (9 mg) of a betamethasone sodium phosphate and betamethasone acetate injectable suspension into the right antebrachiocarpal joint. Blood, urine, and synovial fluid samples were collected prior to and at various times up to 21 days post drug administration. All samples were analyzed using tandem liquid chromatography-mass spectrometry. Plasma data were analyzed using compartmental pharmacokinetic modeling. Maximum measured plasma betamethasone concentrations were 3.97 ± 0.23 ng/mL at 1.45 ± 0.20 h. The plasma elimination half-life was 7.48 ± 0.39 h. Betamethasone concentrations were below the limit of detection in all horses by 96 h and 7 days in plasma and urine, respectively. Betamethasone fell below the limit of detection in the right antebrachiocarpal joint between 14 and 21 days. Results of this study provide information that can be used to regulate the use of intra-articular betamethasone in the horse. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  16. Prevalence and correlates of beta human papillomavirus detection in fingernail samples from mid-adult women

    Directory of Open Access Journals (Sweden)

    Rachel L. Winer

    2018-06-01

    Full Text Available Cutaneous human papillomaviruses (HPVs have not been evaluated in fingernails from healthy individuals. To determine prevalence and correlates of β-HPVs in fingernails from healthy mid-adult women, we tested archived samples collected from 2011 to 2012 using a multiplex PCR combined with Luminex technology for 46 β-HPV genotypes. One hundred thirteen (61.1% of 185 fingernail samples were positive for β-HPV, and the median number of types detected in positive samples was 2 (interquartile range: 1–4. The most common genotypes detected were HPV-23 (β−2 (13.5%, HPV-38 (β−2 (13.0%, HPV-5 (β−1 (9.2%, HPV-107 (β−2 (8.7%, and HPV-120 (β−2 (8.7%. In multivariate analysis, β-HPV detection was associated with age (prevalence ratio [PR] for women 40–51 years versus 30–39 years = 1.30, 95% CI: 1.05–1.62 and race (PR for non-white versus white race = 0.65, 95% CI: 0.45–0.94. The prevalence of β-HPV in fingernail samples from healthy mid-adult women was similar to the prevalence of β-HPV reported at other cutaneous sites in prior studies. We did not identify any significant health or sexual behavior predictors of β-HPV detection in fingernails. Our results support the hypothesis that fingers may serve as a source of transmission or autoinoculation of cutaneous HPVs to other anatomic sites. Keywords: Fingernails, Women, Beta-HPV, Prevalence, Mid-adult, Risk factor

  17. Human parvovirus PARV4 DNA in tissues from adult individuals: a comparison with human parvovirus B19 (B19V

    Directory of Open Access Journals (Sweden)

    Rotellini Matteo

    2010-10-01

    Full Text Available Abstract Background PARV4 is a new member of the Parvoviridae family not closely related to any of the known human parvoviruses. Viremia seems to be a hallmark of PARV4 infection and viral DNA persistence has been demonstrated in a few tissues. Till now, PARV4 has not been associated with any disease and its prevalence in human population has not been clearly established. This study was aimed to assess the tissue distribution and the ability to persist of PARV4 in comparison to parvovirus B19 (B19V. Results PARV4 and B19V DNA detection was carried out in various tissues of individuals without suspect of acute viral infection, by a real time PCR and a nested PCR, targeting the ORF2 and the ORF1 respectively. Low amount of PARV4 DNA was found frequently (>40% in heart and liver of adults individuals, less frequently in lungs and kidneys (23,5 and 18% respectively and was rare in bone marrow, skin and synovium samples (5,5%, 4% and 5%, respectively. By comparison, B19V DNA sequences were present in the same tissues with a higher frequency (significantly higher in myocardium, skin and bone marrow except than in liver where the frequency was the same of PARV4 DNA and in plasma samples where B19V frequency was significantly lower than that of PARV4 Conclusions The particular tropism of PARV4 for liver and heart, here emerged, suggests to focus further studies on these tissues as possible target for viral replication and on the possible role of PARV4 infection in liver and heart diseases. Neither bone marrow nor kidney seem to be a common target of viral replication.

  18. Novel use of levodopa in human immunodeficiency virus encephalopathy-mediated parkinsonism in an adult

    Directory of Open Access Journals (Sweden)

    M F Devine

    2018-01-01

    Full Text Available We report a case of a 36-year-old man with a medical history of human immunodeficiency virus (HIV infection who presented with hypomimia, hypophonia, bradykinesia, rigidity, and freezing of gait. His clinical presentation and magnetic resonance imaging were consistent with HIV encephalopathy with involvement of the bilateral basal ganglia and diffuse leukoencephalopathy. We initiated a trial of carbidopa-levodopa. The dose was escalated to 1050 mg levodopa daily. Amantadine was also started. The patient was closely monitored for behavioral, neurological, or systemic side effects. He tolerated therapy well without adverse effects. The patient's neurological status significantly improved with levodopa, including hypomimia, hypophonia, bradykinesia, and fluidity of gait. This case demonstrates that carbidopa-levodopa can be safely utilized to manage parkinsonism in an adult patient with HIV encephalopathy.

  19. The evidence for increased L1 activity in the site of human adult brain neurogenesis.

    Directory of Open Access Journals (Sweden)

    Alexey A Kurnosov

    Full Text Available Retroelement activity is a common source of polymorphisms in human genome. The mechanism whereby retroelements contribute to the intraindividual genetic heterogeneity by inserting into the DNA of somatic cells is gaining increasing attention. Brain tissues are suspected to accumulate genetic heterogeneity as a result of the retroelements somatic activity. This study aims to expand our understanding of the role retroelements play in generating somatic mosaicism of neural tissues. Whole-genome Alu and L1 profiling of genomic DNA extracted from the cerebellum, frontal cortex, subventricular zone, dentate gyrus, and the myocardium revealed hundreds of somatic insertions in each of the analyzed tissues. Interestingly, the highest concentration of such insertions was detected in the dentate gyrus-the hotspot of adult neurogenesis. Insertions of retroelements and their activity could produce genetically diverse neuronal subsets, which can be involved in hippocampal-dependent learning and memory.

  20. Second generation codon optimized minicircle (CoMiC) for nonviral reprogramming of human adult fibroblasts.

    Science.gov (United States)

    Diecke, Sebastian; Lisowski, Leszek; Kooreman, Nigel G; Wu, Joseph C

    2014-01-01

    The ability to induce pluripotency in somatic cells is one of the most important scientific achievements in the fields of stem cell research and regenerative medicine. This technique allows researchers to obtain pluripotent stem cells without the controversial use of embryos, providing a novel and powerful tool for disease modeling and drug screening approaches. However, using viruses for the delivery of reprogramming genes and transcription factors may result in integration into the host genome and cause random mutations within the target cell, thus limiting the use of these cells for downstream applications. To overcome this limitation, various non-integrating techniques, including Sendai virus, mRNA, minicircle, and plasmid-based methods, have recently been developed. Utilizing a newly developed codon optimized 4-in-1 minicircle (CoMiC), we were able to reprogram human adult fibroblasts using chemically defined media and without the need for feeder cells.

  1. Dog Walking, the Human-Animal Bond and Older Adults' Physical Health.

    Science.gov (United States)

    Curl, Angela L; Bibbo, Jessica; Johnson, Rebecca A

    2017-10-01

    This study explored the associations between dog ownership and pet bonding with walking behavior and health outcomes in older adults. We used data from the 12th wave (2012) of the Health and Retirement Study which included an experimental human-animal interaction module. Ordinary least squares regression and binary logistic regression models controlling for demographic variables were used to answer the research questions. Dog walking was associated with lower body mass index, fewer activities of daily living limitations, fewer doctor visits, and more frequent moderate and vigorous exercise. People with higher degrees of pet bonding were more likely to walk their dog and to spend more time walking their dog each time, but they reported walking a shorter distance with their dog than those with weaker pet bonds. Dog ownership was not associated with better physical health or health behaviors. This study provides evidence for the association between dog walking and physical health using a large, nationally representative sample. The relationship with one's dog may be a positive influence on physical activity for older adults. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Proteolytic activity in the adult and larval stages of the human roundworm parasite Angiostrongylus costaricensis

    Directory of Open Access Journals (Sweden)

    Karina Mastropasqua Rebello

    2012-09-01

    Full Text Available Angiostrongylus costaricensis is a nematode that causes abdominal angiostrongyliasis, a widespread human parasitism in Latin America. This study aimed to characterize the protease profiles of different developmental stages of this helminth. First-stage larvae (L1 were obtained from the faeces of infected Sigmodon hispidus rodents and third-stage larvae (L3 were collected from mollusks Biomphalaria glabrata previously infected with L1. Adult worms were recovered from rodent mesenteric arteries. Protein extraction was performed after repeated freeze-thaw cycles followed by maceration of the nematodes in 40 mM Tris base. Proteolysis of gelatin was observed by zymography and found only in the larval stages. In L3, the gelatinolytic activity was effectively inhibited by orthophenanthroline, indicating the involvement of metalloproteases. The mechanistic class of the gelatinases from L1 could not be precisely determined using traditional class-specific inhibitors. Adult worm extracts were able to hydrolyze haemoglobin in solution, although no activity was observed by zymography. This haemoglobinolytic activity was ascribed to aspartic proteases following its effective inhibition by pepstatin, which also inhibited the haemoglobinolytic activity of L1 and L3 extracts. The characterization of protease expression throughout the A. costaricensis life cycle may reveal key factors influencing the process of parasitic infection and thus foster our understanding of the disease pathogenesis.

  3. Human T cell leukemia virus reactivation with progression of adult T-cell leukemia-lymphoma.

    Directory of Open Access Journals (Sweden)

    Lee Ratner

    Full Text Available Human T-cell leukemia virus-associated adult T-cell leukemia-lymphoma (ATLL has a very poor prognosis, despite trials of a variety of different treatment regimens. Virus expression has been reported to be limited or absent when ATLL is diagnosed, and this has suggested that secondary genetic or epigenetic changes are important in disease pathogenesis.We prospectively investigated combination chemotherapy followed by antiretroviral therapy for this disorder. Nineteen patients were prospectively enrolled between 2002 and 2006 at five medical centers in a phase II clinical trial of infusional chemotherapy with etoposide, doxorubicin, and vincristine, daily prednisone, and bolus cyclophosphamide (EPOCH given for two to six cycles until maximal clinical response, and followed by antiviral therapy with daily zidovudine, lamivudine, and alpha interferon-2a for up to one year. Seven patients were on study for less than one month due to progressive disease or chemotherapy toxicity. Eleven patients achieved an objective response with median duration of response of thirteen months, and two complete remissions. During chemotherapy induction, viral RNA expression increased (median 190-fold, and virus replication occurred, coincident with development of disease progression.EPOCH chemotherapy followed by antiretroviral therapy is an active therapeutic regimen for adult T-cell leukemia-lymphoma, but viral reactivation during induction chemotherapy may contribute to treatment failure. Alternative therapies are sorely needed in this disease that simultaneously prevent virus expression, and are cytocidal for malignant cells.

  4. [Detection and Analysis of Human Parainfluenza Virus Infection in Hospitalized Adults with Acute Respiratory Tract Infections].

    Science.gov (United States)

    Li, Xing-Qiao; Liu, Xue-Wei; Zhou, Tao; Pei, Xiao-Fang

    2017-11-01

    To investigate the prevalence and gene characteristics of different groups of human parainfluenza virus (HPIV) infection in hospitalized adults with acute respiratory tract infections (ARI). RT-PCR was used to detect HPIV hemagglutinin (HA) DNA,which was extracted from sputum samples of 1 039 adult patients with ARI from March,2014 to June,2016. The HA gene amplified from randomly selected positive samples were sequenced to analyze the homology and variation. 10.6% (110/1 039) of these samples were positive for HPIV,including 8 cases of HPIV-1,22 cases of HPIV-2,46 cases of HPIV-3 and 34 cases of HPIV-4. Detectable rate varied among different groups of HPIV according to seasons of the year and ages of patients. No significant differences were found between the positive samples and the reference sequences. Compared with different reference strains of different regions,the genetic distance of nucleotide is the smallest between the strains tested in this study and the reference strains of other provinces and cities in China. In Chengdu region,HPIV virus is highly detected in ARI,all subtypes were detected with HPIV-3 being the main subtype.

  5. Differential oxidative stress induced by dengue virus in monocytes from human neonates, adult and elderly individuals.

    Directory of Open Access Journals (Sweden)

    Nereida Valero

    Full Text Available Changes in immune response during lifespan of man are well known. These changes involve decreased neonatal and elderly immune response. In addition, it has been shown a relationship between immune and oxidative mechanisms, suggesting that altered immune response could be associated to altered oxidative response. Increased expression of nitric oxide (NO has been documented in dengue and in monocyte cultures infected with different types of dengue virus. However, there is no information about the age-dependent NO oxidative response in humans infected by dengue virus. In this study, monocyte cultures from neonatal, elderly and adult individuals (n = 10 each group were infected with different dengue virus types (DENV- 1 to 4 and oxidative/antioxidative responses and apoptosis were measured at days 1 and 3 of culture. Increased production of NO, lipid peroxidation and enzymatic and nonenzymatic anti-oxidative responses in dengue infected monocyte cultures were observed. However, neonatal and elderly monocytes had lower values of studied parameters when compared to those in adult-derived cultures. Apoptosis was present in infected monocytes with higher values at day 3 of culture. This reduced oxidant/antioxidant response of neonatal and elderly monocytes could be relevant in the pathogenesis of dengue disease.

  6. Nogo-A is a reliable oligodendroglial marker in adult human and mouse CNS and in demyelinated lesions

    DEFF Research Database (Denmark)

    Kuhlmann, Tanja; Remington, Leah; Maruschak, Brigitte

    2007-01-01

    to be strongly expressed in mature oligodendrocytes in vivo. In the present investigation we analyzed the expression patterns of Nogo-A in adult mouse and human CNS as well as in demyelinating animal models and multiple sclerosis lesions. Nogo-A expression was compared with that of other frequently used...... oligodendroglial markers such as CC1, CNP, and in situ hybridization for proteolipid protein mRNA. Nogo-A strongly and reliably labeled oligodendrocytes in the adult CNS as well as in demyelinating lesions and thus represents a valuable tool for the identification of oligodendrocytes in human and mouse CNS tissue...

  7. CCL2 binding is CCR2 independent in primary adult human astrocytes.

    Science.gov (United States)

    Fouillet, A; Mawson, J; Suliman, O; Sharrack, B; Romero, I A; Woodroofe, M N

    2012-02-09

    Chemokines are low relative molecular mass proteins, which have chemoattractant actions on many cell types. The chemokine, CCL2, has been shown to play a major role in the recruitment of monocytes in central nervous system (CNS) lesions in multiple sclerosis (MS). Since resident astrocytes constitute a major source of chemokine synthesis including CCL2, we were interested to assess the regulation of CCL2 by astrocytes. We showed that CCL2 bound to the cell surface of astrocytes and binding was not modulated by inflammatory conditions. However, CCR2 protein was not detected nor was activation of the classical CCR2 downstream signaling pathways. Recent studies have shown that non-signaling decoy chemokine receptors bind and modulate the expression of chemokines at site of inflammation. Here, we show that the D6 chemokine decoy receptor is constitutively expressed by primary human adult astrocytes at both mRNA and protein level. In addition, CCL3, which binds to D6, but not CCL19, which does not bind to D6, displaced CCL2 binding to astrocytes; indicating that CCL2 may bind to this cell type via the D6 receptor. Our results suggest that CCL2 binding to primary adult human astrocytes is CCR2-independent and is likely to be mediated via the D6 decoy chemokine receptor. Therefore we propose that astrocytes are implicated in both the establishment of chemokine gradients for the migration of leukocytes into and within the CNS and in the regulation of CCL2 levels at inflammatory sites in the CNS. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. A balanced view of the cerebrospinal fluid composition and functions: Focus on adult humans.

    Science.gov (United States)

    Spector, Reynold; Robert Snodgrass, S; Johanson, Conrad E

    2015-11-01

    In this review, a companion piece to our recent examination of choroid plexus (CP), the organ that secretes the cerebrospinal fluid (CSF), we focus on recent information in the context of reliable older data concerning the composition and functions of adult human CSF. To accomplish this, we define CSF, examine the methodology employed in studying the CSF focusing on ideal or near ideal experiments and discuss the pros and cons of several widely used analogical descriptions of the CSF including: the CSF as the "third circulation," the CSF as a "nourishing liquor," the similarities of the CSF/choroid plexus to the glomerular filtrate/kidney and finally the CSF circulation as part of the "glymphatic system." We also consider the close interrelationship between the CSF and extracellular space of brain through gap junctions and the paucity of data suggesting that the cerebral capillaries secrete a CSF-like fluid. Recently human CSF has been shown to be in dynamic flux with heart-beat, posture and especially respiration. Functionally, the CSF provides buoyancy, nourishment (e.g., vitamins) and endogenous waste product removal for the brain by bulk flow into the venous (arachnoid villi and nerve roots) and lymphatic (nasal) systems, and by carrier-mediated reabsorptive transport systems in CP. The CSF also presents many exogenous compounds to CP for metabolism or removal, indirectly cleansing the extracellular space of brain (e.g., of xenobiotics like penicillin). The CSF also carries hormones (e.g., leptin) from blood via CP or synthesized in CP (e.g., IGF-2) to the brain. In summary the CP/CSF, the third circulation, performs many functions comparable to the kidney including nourishing the brain and contributing to a stable internal milieu for the brain. These tasks are essential to normal adult brain functioning. Copyright © 2015. Published by Elsevier Inc.

  9. Laser biostimulation of articular cartilage: in vitro evaluation

    Science.gov (United States)

    Jia, Yali; Guo, Zhouyi; Yang, Xiaohong; Zeng, Chang-Chun

    2004-07-01

    In the orthopaedic field, the repair of ariticular cartilage is still a difficult problem, because of the physiological characters of cartilaginous tissues and chondrocytes. To find an effective method of stimulating their regeneration, this in vitro study focuses on the biostimulation of rabbit articular chondrocytes by low-power He-Ne laser. The articular chondrocytes isolated from the cartilage of the medial condyle of the femur of the rabbit were incubated in HamF12 medium. The second passage culture were spread on 24 petri dishes and were irradiated with laser at power density of 2 - 12 mW/cm2 for 6.5 minutes, corresponding to the energy density of 1-6 J/cm2. Laser treatment was performed three times at a 24-hour interval. After lasering, incubation was continued for 24 hours. Non-irradiated cells were kept under the same conditions as the irradiated ones. The cell proliferation activity was evaluated with a XTT colorimetric method. Irradiation of 4 - 6 J/cm2 revealed a considerably higher cell proliferation activity comparing to control cultures. Thereinto, the energy density of 4 and 5 J/cm2 remarkably increased cell growth (P<0.01). The present study showed that a particular laser irradiation stimulates articular chondrocytes proliferation. These findings might be clinically relevant, indicating that low-power laser irradiation treatment is likely to achieve the repair of articular cartilage in clinic.

  10. Reduction of intra-articular adhesion by topical application of ...

    African Journals Online (AJOL)

    Effect of daidzein on intra articular adhesion was estimated by visual score through macroscopic examination, histopathology study, hydroxyproline content, fibroblast and collage density. Results: Data obtained in the study suggest that topical application of daidzein (5 and 10 mg/ml) loose the collagen and significantly ...

  11. Clinical and Laboratory Predictors of Articular Disorders Among HIV ...

    African Journals Online (AJOL)

    laboratory features of HIV‑infected patients and articular disorders. Aims: To ... The recruitment of subjects for the study took place ..... [4-8,10]. The reported range is wide and reflects prevalence from ... this study may be close to the true value because the subjects .... hence higher ESR values, indicating widespread systemic.

  12. Peroneal tendon displacement accompanying intra-articular calcaneal fractures.

    Science.gov (United States)

    Toussaint, Rull James; Lin, Darius; Ehrlichman, Lauren K; Ellington, J Kent; Strasser, Nicholas; Kwon, John Y

    2014-02-19

    Peroneal tendon displacement (subluxation or dislocation) accompanying an intra-articular calcaneal fracture is often undetected and under-treated. The goals of this study were to determine (1) the prevalence of peroneal tendon displacement accompanying intra-articular calcaneal fractures, (2) the association of tendon displacement with fracture classifications, (3) the association of tendon displacement with heel width, and (4) the rate of missed diagnosis of the tendon displacement on radiographs and computed tomography (CT) scans and the resulting treatment rate. A retrospective radiographic review of all calcaneal fractures presenting at three institutions from June 30, 2006, to June 30, 2011, was performed. CT imaging of 421 intra-articular calcaneal fractures involving the posterior facet was available for review. The prevalence of peroneal tendon displacement was noted and its associations with fracture classification and heel width were evaluated. Peroneal tendon displacement was identified in 118 (28.0%) of the 421 calcaneal fracture cases. The presence of tendon displacement was significantly associated with joint-depression fractures compared with tongue-type fractures (p displacement had been identified in the radiology reports. Although sixty-five (55.1%) of the fractures with tendon displacement had been treated with internal fixation, the tendon displacement was treated surgically in only seven (10.8%) of these cases. Analysis of CT images showed a 28% prevalence of peroneal tendon displacement accompanying intra-articular calcaneal fractures. Surgeons and radiologists are encouraged to consider this association.

  13. Early micromovement of the Articular Surface Replacement (ASR) femoral component

    DEFF Research Database (Denmark)

    Penny, J O; Ding, M; Varmarken, J E

    2012-01-01

    Radiostereometric analysis (RSA) can detect early micromovement in unstable implant designs which are likely subsequently to have a high failure rate. In 2010, the Articular Surface Replacement (ASR) was withdrawn because of a high failure rate. In 19 ASR femoral components, the mean micromovement...

  14. Experimental articular cartilage repair in the Göttingen minipig

    DEFF Research Database (Denmark)

    Christensen, Bjørn Borsøe; Foldager, Casper Bindzus; Olesen, Morten Lykke

    2015-01-01

    BACKGROUND: A gold standard treatment for articular cartilage injuries is yet to be found, and a cost-effective and predictable large animal model is needed to bridge the gap between in vitro studies and clinical studies. Ideally, the animal model should allow for testing of clinically relevant...

  15. Intra-articular lipoma causing snapping in the patellofemoral joint

    International Nuclear Information System (INIS)

    Yilmaz, E.; Karakurt, L.; Yildirim, H.; Ozercan, R.

    2007-01-01

    Intra-articular lipoma is an exceedingly rare diagnosis. We identified a lipoma that was seated in the retropatellar are and caused snapping of the patella during flexion of the knee joint. The tumor was easily and totally excised under arthroscopic guidance after the thin pedicle was cut. (author)

  16. Clinical outcome scoring of intra-articular calcaneal fractures

    NARCIS (Netherlands)

    Schepers, Tim; Heetveld, Martin J.; Mulder, Paul G. H.; Patka, Peter

    2008-01-01

    Outcome reporting of intra-articular calcaneal fractures is inconsistent. This study aimed to identify the most cited outcome scores in the literature and to analyze their reliability and validity. A systematic literature search identified 34 different outcome scores. The most cited outcome score

  17. Clinical Outcome Scoring of Intra-articular Calcaneal Fractures

    NARCIS (Netherlands)

    T. Schepers (Tim); M.J. Heetveld (Martin); P.G.H. Mulder (Paul); P. Patka (Peter)

    2008-01-01

    textabstractOutcome reporting of intra-articular calcaneal fractures is inconsistent. This study aimed to identify the most cited outcome scores in the literature and to analyze their reliability and validity. A systematic literature search identified 34 different outcome scores. The most cited

  18. Clinical and Laboratory Predictors of Articular Disorders Among HIV ...

    African Journals Online (AJOL)

    radiologist for features of avascular necrosis (AVN) and sacroiliitis, respectively. Synovial fluid was obtained, for analysis and microscopy, culture/sensitivity testing and acid fast bacilli detection in those with demonstrable joint effusion. The clinically evident articular features, laboratory, and radiographic findings were used ...

  19. Automatic quantification of local and global articular cartilage surface curvature

    DEFF Research Database (Denmark)

    Folkesson, Jenny; Dam, Erik B; Olsen, Ole F

    2008-01-01

    The objective of this study was to quantitatively assess the surface curvature of the articular cartilage from low-field magnetic resonance imaging (MRI) data, and to investigate its role in populations with varying radiographic signs of osteoarthritis (OA), cross-sectionally and longitudinally...

  20. Intra-articular osteotomy for distal humerus malunion

    NARCIS (Netherlands)

    Marti, René K.; Doornberg, Job

    2009-01-01

    Intra-articular osteotomy is considered in the rare case of malunion after a fracture of the distal humerus to restore humeral alignment and gain a functional arc of elbow motion. Traumatic and iatrogenic disruption of the limited blood flow to the distal end of the humerus resulting in avascular

  1. Norovirus-specific memory T cell responses in adult human donors

    Directory of Open Access Journals (Sweden)

    Maria Malm

    2016-10-01

    Full Text Available Norovirus (NoV is a leading cause of acute gastroenteritis in people of all ages worldwide. NoV specific serum antibodies which block the binding of NoV virus-like particles (VLPs to the cell receptors have been thoroughly investigated. In contrast, only a few publications are available on the NoV capsid VP1 protein-specific T cell responses in humans naturally infected with the virus. Freshly isolated peripheral blood mononuclear cells of eight healthy adult human donors previously exposed to NoV were stimulated with purified VLPs derived from NoV GII.4-1999, GII.4-2012 (Sydney, and GI.3, and IFN-g production was measured by an ELISPOT assay. In addition, 76 overlapping synthetic peptides spanning the entire 539 amino acid sequence of GII.4 VP1 were pooled into two-dimensional matrices and used to identify putative T cell epitopes. Seven of the eight subjects produced IFN-g in response to the peptides and five subjects produced IFN-g in response to the VLPs of the same origin. In general, stronger T cell responses were induced with the peptides in each donor compared to the VLPs. A CD8+ T cell epitope in the shell domain of the VP1 (134SPSQVTMFPHIIVDVRQL151 was identified in two subjects, both having human leukocyte antigen (HLA-A*02:01 allele. To our knowledge, this is the first report using synthetic peptides to study NoV-specific T cell responses in human subjects and identify T cell epitopes.

  2. Extra-Articular Manifestations of Seronegative and Seropositive Rheumatoid Arthritis

    Directory of Open Access Journals (Sweden)

    Vjollca Sahatçiu-Meka

    2010-02-01

    Full Text Available Although considered a “joint disease,” rheumatoid arthritis is associated with the involvement of extra-articular manifestations. The aim of the study is the investigation and comparison of frequency and type of extra-articular manifestations in a well defined community based cohort of patients with seropositive and seronegative rheumatoid arthritis. Using the ACR (1987 criteria for rheumatoid arthritis, patients have been classified into the 2nd and 3rd functional class (ARA. The studied group consisted of 125 seronegative patients with titters lower than 1:64 as defined by Rose-Waaler test, whereas the control group consisted of 125 seropositive patients with titters of 1:64 or higher. All patients were between 25-60 years of age (Xb=49,96, with disease duration between 1-27 years (Xb=6,41. In order to present the findings of the study, the structure, prevalence, arithmetic mean (Xb, standard deviation (SB, variation quotient (QV% and variation interval (Rmax-Rmin have been used. Probability level has been expressed by p<0,01 and p<0,05. Correlation between the number of extra-articular manifestations and duration of the disease has been calculated by means of Pearson linear correlation. Higher presence of diffuse lung fibrosis, central and peripheral nervous system damages have been confirmed in the seropositive group, and osteoporosis in the seronegative; however, no statistical difference has been found. In extra-articular manifestations, “rheumatoid core” in the seropositive subset (χ2=4,80, p<0,05 presented significant statistical difference. Rheumatoid nodules were more frequent in seropositive subset (12%:16%, in both sexes; however, they were not of significant statistical difference. Neuropathy and lung diseases were also frequently present in seropositive group, but no statistical difference has been found regarding the statistical difference. Longer duration of the disease resulted in an increase of the number of extra-articular

  3. Extra-articular manifestations of seronegative and seropositive rheumatoid arthritis.

    Science.gov (United States)

    Sahatciu-Meka, Vjollca; Rexhepi, Sylejman; Manxhuka-Kerliu, Suzana; Rexhepi, Mjellma

    2010-02-01

    Although considered a "joint disease," rheumatoid arthritis is associated with the involvement of extra-articular manifestations. The aim of the study is the investigation and comparison of frequency and type of extra-articular manifestations in a well defined community based cohort of patients with seropositive and seronegative rheumatoid arthritis. Using the ACR (1987) criteria for rheumatoid arthritis, patients have been classified into the 2nd and 3rd functional class (ARA). The studied group consisted of 125 seronegative patients with titters lower than 1:64 as defined by Rose-Waaler test, whereas the control group consisted of 125 seropositive patients with titters of 1:64 or higher. All patients were between 25-60 years of age (Xb=49,96), with disease duration between 1-27 years (Xb=6,41). In order to present the findings of the study, the structure, prevalence, arithmetic mean (Xb), standard deviation (SB), variation quotient (QV%) and variation interval (Rmax-Rmin) have been used. Probability level has been expressed by p<0,01 and p<0,05. Correlation between the number of extra-articular manifestations and duration of the disease has been calculated by means of Pearson linear correlation. Higher presence of diffuse lung fibrosis, central and peripheral nervous system damages have been confirmed in the seropositive group, and osteoporosis in the seronegative; however, no statistical difference has been found. In extra-articular manifestations, "rheumatoid core" in the seropositive subset (chi2=4,80, p<0,05) presented significant statistical difference. Rheumatoid nodules were more frequent in seropositive subset (12%:16%), in both sexes; however, they were not of significant statistical difference. Neuropathy and lung diseases were also frequently present in seropositive group, but no statistical difference has been found regarding the statistical difference. Longer duration of the disease resulted in an increase of the number of extra-articular

  4. Synovial folds in equine articular process joints

    DEFF Research Database (Denmark)

    Thomsen, Line Nymann; Berg, Lise Charlotte; Markussen, Bo

    2013-01-01

    Cervical synovial folds have been suggested as a potential cause of neck pain in humans. Little is known about the extent and characteristics of cervical synovial folds in horses.......Cervical synovial folds have been suggested as a potential cause of neck pain in humans. Little is known about the extent and characteristics of cervical synovial folds in horses....

  5. Examination of Oral Microbiota Diversity in Adults and Older Adults as an Approach to Prevent Spread of Risk Factors for Human Infections.

    Science.gov (United States)

    Zawadzki, Paweł J; Perkowski, Konrad; Padzik, Marcin; Mierzwińska-Nastalska, Elżbieta; Szaflik, Jacek P; Conn, David Bruce; Chomicz, Lidia

    2017-01-01

    The oral cavity environment may be colonized by polymicrobial communities with complex, poorly known interrelations. The aim of this study was to determine oral microbiota diversity in order to prevent the spread of infectious microorganisms that are risk factors for human health complications in patients requiring treatment due to various disabilities. The study examined Polish adults aged between 40 and 70 years; parasitological, microbiological, and mycological data collected before treatment were analyzed. The diversity of oral microbiota, including relatively high prevalences of some opportunistic, potentially pathogenic strains of bacteria, protozoans, and fungi detected in the patients analyzed, may result in increasing risk of disseminated infections from the oral cavity to neighboring structures and other organs. Increasing ageing of human populations is noted in recent decades in many countries, including Poland. The growing number of older adults with different oral health disabilities, who are more prone to development of oral and systemic pathology, is an increasing medical problem. Results of this retrospective study showed the urgent need to pay more attention to the pretreatment examination of components of the oral microbiome, especially to the strains, which are etiological agents of human opportunistic infections and are particularly dangerous for older adults.

  6. Examination of Oral Microbiota Diversity in Adults and Older Adults as an Approach to Prevent Spread of Risk Factors for Human Infections

    Directory of Open Access Journals (Sweden)

    Paweł J. Zawadzki

    2017-01-01

    Full Text Available The oral cavity environment may be colonized by polymicrobial communities with complex, poorly known interrelations. The aim of this study was to determine oral microbiota diversity in order to prevent the spread of infectious microorganisms that are risk factors for human health complications in patients requiring treatment due to various disabilities. The study examined Polish adults aged between 40 and 70 years; parasitological, microbiological, and mycological data collected before treatment were analyzed. The diversity of oral microbiota, including relatively high prevalences of some opportunistic, potentially pathogenic strains of bacteria, protozoans, and fungi detected in the patients analyzed, may result in increasing risk of disseminated infections from the oral cavity to neighboring structures and other organs. Increasing ageing of human populations is noted in recent decades in many countries, including Poland. The growing number of older adults with different oral health disabilities, who are more prone to development of oral and systemic pathology, is an increasing medical problem. Results of this retrospective study showed the urgent need to pay more attention to the pretreatment examination of components of the oral microbiome, especially to the strains, which are etiological agents of human opportunistic infections and are particularly dangerous for older adults.

  7. Development and characteristics of pannus-like soft tissue in osteoarthritic articular surface in rat osteoarthritis model.

    Science.gov (United States)

    Duc, P A; Yudoh, K; Masuko, K; Kato, T; Nishioka, K; Nakamura, H

    2008-01-01

    Pannus is invasive granulation tissue found on the articular cartilage having rheumatoid arthritis (RA). However, pannus-like tissue has also been found in osteoarthritis (OA). Our previous study showed that pannus-like tissue in OA (OA pannus) was frequently found in human OA samples. The purpose of the study is to investigate the development and the characteristics of OA pannus in a rat OA model. Ligaments of the knee joint were transected in Wister rats to induce OA. The knee joints were removed at weeks 1, 2, 4 and 6, and subjected to histological study. Samples were stained with hematoxylin and eosin (HE), Safranin-O and immuno-stained for vimentin, CD34, type II collagen and MMP-3. The whole knee joint of OA rats was implanted in SCID mice and kept for a further 3 weeks. Then the histological findings were evaluated in HE sections. OA pannus appeared at week 2 and extend over the articular surface. OA pannus cells were positive for vimentin and/or CD34. At week 6, a part of articular surface was restored with matrix. OA pannus cells expressed MMP-3 as well as type II collagen. Histological study of rat OA knees implanted in SCID mice showed that OA pannus cells filled the joint space and invaded articular cartilage. The presence of OA pannus was found in a rat OA model and its features were similar to those in human OA. OA pannus had both catabolic and reparative features, and the latter feature were speculated to be dominant in the later phase of the disease under a certain environmental condition.

  8. Matrix development in self-assembly of articular cartilage.

    Directory of Open Access Journals (Sweden)

    Gidon Ofek

    2008-07-01

    Full Text Available Articular cartilage is a highly functional tissue which covers the ends of long bones and serves to ensure proper joint movement. A tissue engineering approach that recapitulates the developmental characteristics of articular cartilage can be used to examine the maturation and degeneration of cartilage and produce fully functional neotissue replacements for diseased tissue.This study examined the development of articular cartilage neotissue within a self-assembling process in two phases. In the first phase, articular cartilage constructs were examined at 1, 4, 7, 10, 14, 28, 42, and 56 days immunohistochemically, histologically, and through biochemical analysis for total collagen and glycosaminoglycan (GAG content. Based on statistical changes in GAG and collagen levels, four time points from the first phase (7, 14, 28, and 56 days were chosen to carry into the second phase, where the constructs were studied in terms of their mechanical characteristics, relative amounts of collagen types II and VI, and specific GAG types (chondroitin 4-sulfate, chondroitin 6-sulfate, dermatan sulfate, and hyaluronan. Collagen type VI was present in initial abundance and then localized to a pericellular distribution at 4 wks. N-cadherin activity also spiked at early stages of neotissue development, suggesting that self-assembly is mediated through a minimization of free energy. The percentage of collagen type II to total collagen significantly increased over time, while the proportion of collagen type VI to total collagen decreased between 1 and 2 wks. The chondroitin 6- to 4- sulfate ratio decreased steadily during construct maturation. In addition, the compressive properties reached a plateau and tensile characteristics peaked at 4 wks.The indices of cartilage formation examined in this study suggest that tissue maturation in self-assembled articular cartilage mirrors known developmental processes for native tissue. In terms of tissue engineering, it is

  9. Effect of Enrofloxacin on Histochemistry, Immunohistochemistry and Molecular Changes in Lamb Articular Cartilage.

    Science.gov (United States)

    Khazaeel, Kaveh; Mazaheri, Yazdan; Hashemi Tabar, Mahmood; Najafzadeh, Hossein; Morovvati, Hassan; Ghadrdan, Alireza

    2015-01-01

    Enrofloxacin is a synthetic chemotherapeutic agent from the class of the fluoroquinolones that is widely used to treat bacterial infections. It is metabolized to ciprofloxacin in the body as active metabolite. Fluoroquinolones change in the articular cartilage, especially with high doses and more than two weeks use. So, due to relatively excessive use of enrofloxacin in mammals and similarity of lambs to human subjects with respect to skeletal activity cycles, this study was done to investigate the effects of enrofloxacin on some cellular and molecular changes in growing lamb articular cartilage to evaluate some possible mechanisms involved these changes. Twelve, 2-month-old male lambs divided into three groups: control group received only normal saline; therapeutic group received 5mg/kg enrofloxacin subcutaneously, daily, for 15 days and toxic group received 35 mg/kg enrofloxacin in the same manner as therapeutic group. Twenty four hours after the last dose, the animals were sacrificed, and their stifle joints were dissected. Sampling from distal femoral and proximal tibial extremities was done quickly for further histological and molecular studies. Collagen-п content was studied with avidin-biotin immunohistochemistry method in different groups. Expression of Sox9 and caspase-3 was evaluated by Real-time PCR. Immunohistochemical changes were included decreases of matrix proteoglycans, carbohydrates, and Collagen-п in the toxic group. Some of these changes were observed in the therapeutic group with less intensity in comparison to the toxic group. Enrofloxacin were significantly decreased (P≤0.05). Sox9 expression in therapeutic and toxic groups compared to control group. But caspase -3 expressions in the toxic group significantly increased (P≤0.0001) with a comparison to other groups, while, between control and therapeutic groups, there were no significant differences. So, it can be concluded that enrofloxacin increases apoptosis in chondrocytes and

  10. Silk fibroin-chondroitin sulfate scaffold with immuno-inhibition property for articular cartilage repair.

    Science.gov (United States)

    Zhou, Feifei; Zhang, Xianzhu; Cai, Dandan; Li, Jun; Mu, Qin; Zhang, Wei; Zhu, Shouan; Jiang, Yangzi; Shen, Weiliang; Zhang, Shufang; Ouyang, Hong Wei

    2017-11-01

    The demand of favorable scaffolds has increased for the emerging cartilage tissue engineering. Chondroitin sulfate (CS) and silk fibroin have been investigated and reported with safety and excellent biocompatibility as tissue engineering scaffolds. However, the rapid degradation rate of pure CS scaffolds presents a challenge to effectively recreate neo-tissue similar to natural articular cartilage. Meanwhile the silk fibroin is well used as a structural constituent material because its remarkable mechanical properties, long-lasting in vivo stability and hypoimmunity. The application of composite silk fibroin and CS scaffolds for joint cartilage repair has not been well studied. Here we report that the combination of silk fibroin and CS could synergistically promote articular cartilage defect repair. The silk fibroin (silk) and silk fibroin/CS (silk-CS) scaffolds were fabricated with salt-leaching, freeze-drying and crosslinking methodologies. The biocompatibility of the scaffolds was investigated in vitro by cell adhesion, proliferation and migration with human articular chondrocytes. We found that silk-CS scaffold maintained better chondrocyte phenotype than silk scaffold; moreover, the silk-CS scaffolds reduced chondrocyte inflammatory response that was induced by interleukin (IL)-1β, which is in consistent with the well-documented anti-inflammatory activities of CS. The in vivo cartilage repair was evaluated with a rabbit osteochondral defect model. Silk-CS scaffold induced more neo-tissue formation and better structural restoration than silk scaffold after 6 and 12weeks of implantation in ICRS histological evaluations. In conclusion, we have developed a silk fibroin/ chondroitin sulfate scaffold for cartilage tissue engineering that exhibits immuno-inhibition property and can improve the self-repair capacity of cartilage. Severe cartilage defect such as osteoarthritis (OA) is difficult to self-repair because of its avascular, aneural and alymphatic nature

  11. MORPHOMETRY OF THE ARTICULAR FACETS ON THE SUPERIOR, MEDIAL AND LATERAL SURFACES OF THE BODY OF TALUS AND ITS CLINICAL RELEVANCE

    Directory of Open Access Journals (Sweden)

    Goda Jatin B, Patel Shailesh M, Parmar Ajay M, Agarwal GC

    2015-07-01

    Full Text Available Background: In the formation of Ankle joint, tibio-fibular mortice receives superior, medial and lateral articular surfaces of body of Talus. Because of very limited availability of the data on the Morphometry of the articular facets on the Body of the dry human tali, this study was undertaken. Aims: To prepare the database on the articular facets on the superior, medial and lateral surfaces of body of talus, to find if there is statistically significant difference between both the sides of measurements and to compare the results with the previous studies. Methods and Material: 40 Dry Human Tali (20 Right and 20 Left were measured with Digital vernier caliper for the following Measurements: On the Trochlear surface: Medial length, Central length, Lateral length, Anterior width, Central width, Posterior width. On the lateral triangular articular facet: Central height, Central width. On the coma shaped medial articular facet: Central height, Central width. Results: Mean values of Medial, Central and Lateral lengths were 31.02, 30.39 and 29.63mm on Right side and 31.79, 30.65 and 29.45mm on Left side. Mean Anterior, Central and Posterior widths were 28.87, 28.16 and 21.59mm on right side and 29.08, 27.54 and 21.78mm on left side. On the medial articular surface, mean central height was 11.93mm on the right side and 11.29mm on the left side, Mean central width was 27.94mm on the right side and 28.29mm on the left side. On the lateral articular surface, mean central height was 22.14mm on the right side and 22.63mm on the left side. Mean central width was 18.93mm on the right side and 18.99mm on the left side. There is no significant difference between right and left sides of measurements. Conclusion: The trochlear articular surface is wider in front, measurements of opposite talus bone can be used as a control during talus bone replacement surgery, it may help surgeons to plan pre-operatively the complex talar fracture surgeries, to design accurate

  12. Defining the role of common variation in the genomic and biological architecture of adult human height.

    Science.gov (United States)

    Wood, Andrew R; Esko, Tonu; Yang, Jian; Vedantam, Sailaja; Pers, Tune H; Gustafsson, Stefan; Chu, Audrey Y; Estrada, Karol; Luan, Jian'an; Kutalik, Zoltán; Amin, Najaf; Buchkovich, Martin L; Croteau-Chonka, Damien C; Day, Felix R; Duan, Yanan; Fall, Tove; Fehrmann, Rudolf; Ferreira, Teresa; Jackson, Anne U; Karjalainen, Juha; Lo, Ken Sin; Locke, Adam E; Mägi, Reedik; Mihailov, Evelin; Porcu, Eleonora; Randall, Joshua C; Scherag, André; Vinkhuyzen, Anna A E; Westra, Harm-Jan; Winkler, Thomas W; Workalemahu, Tsegaselassie; Zhao, Jing Hua; Absher, Devin; Albrecht, Eva; Anderson, Denise; Baron, Jeffrey; Beekman, Marian; Demirkan, Ayse; Ehret, Georg B; Feenstra, Bjarke; Feitosa, Mary F; Fischer, Krista; Fraser, Ross M; Goel, Anuj; Gong, Jian; Justice, Anne E; Kanoni, Stavroula; Kleber, Marcus E; Kristiansson, Kati; Lim, Unhee; Lotay, Vaneet; Lui, Julian C; Mangino, Massimo; Mateo Leach, Irene; Medina-Gomez, Carolina; Nalls, Michael A; Nyholt, Dale R; Palmer, Cameron D; Pasko, Dorota; Pechlivanis, Sonali; Prokopenko, Inga; Ried, Janina S; Ripke, Stephan; Shungin, Dmitry; Stancáková, Alena; Strawbridge, Rona J; Sung, Yun Ju; Tanaka, Toshiko; Teumer, Alexander; Trompet, Stella; van der Laan, Sander W; van Setten, Jessica; Van Vliet-Ostaptchouk, Jana V; Wang, Zhaoming; Yengo, Loïc; Zhang, Weihua; Afzal, Uzma; Arnlöv, Johan; Arscott, Gillian M; Bandinelli, Stefania; Barrett, Amy; Bellis, Claire; Bennett, Amanda J; Berne, Christian; Blüher, Matthias; Bolton, Jennifer L; Böttcher, Yvonne; Boyd, Heather A; Bruinenberg, Marcel; Buckley, Brendan M; Buyske, Steven; Caspersen, Ida H; Chines, Peter S; Clarke, Robert; Claudi-Boehm, Simone; Cooper, Matthew; Daw, E Warwick; De Jong, Pim A; Deelen, Joris; Delgado, Graciela; Denny, Josh C; Dhonukshe-Rutten, Rosalie; Dimitriou, Maria; Doney, Alex S F; Dörr, Marcus; Eklund, Niina; Eury, Elodie; Folkersen, Lasse; Garcia, Melissa E; Geller, Frank; Giedraitis, Vilmantas; Go, Alan S; Grallert, Harald; Grammer, Tanja B; Gräßler, Jürgen; Grönberg, Henrik; de Groot, Lisette C P G M; Groves, Christopher J; Haessler, Jeffrey; Hall, Per; Haller, Toomas; Hallmans, Goran; Hannemann, Anke; Hartman, Catharina A; Hassinen, Maija; Hayward, Caroline; Heard-Costa, Nancy L; Helmer, Quinta; Hemani, Gibran; Henders, Anjali K; Hillege, Hans L; Hlatky, Mark A; Hoffmann, Wolfgang; Hoffmann, Per; Holmen, Oddgeir; Houwing-Duistermaat, Jeanine J; Illig, Thomas; Isaacs, Aaron; James, Alan L; Jeff, Janina; Johansen, Berit; Johansson, Åsa; Jolley, Jennifer; Juliusdottir, Thorhildur; Junttila, Juhani; Kho, Abel N; Kinnunen, Leena; Klopp, Norman; Kocher, Thomas; Kratzer, Wolfgang; Lichtner, Peter; Lind, Lars; Lindström, Jaana; Lobbens, Stéphane; Lorentzon, Mattias; Lu, Yingchang; Lyssenko, Valeriya; Magnusson, Patrik K E; Mahajan, Anubha; Maillard, Marc; McArdle, Wendy L; McKenzie, Colin A; McLachlan, Stela; McLaren, Paul J; Menni, Cristina; Merger, Sigrun; Milani, Lili; Moayyeri, Alireza; Monda, Keri L; Morken, Mario A; Müller, Gabriele; Müller-Nurasyid, Martina; Musk, Arthur W; Narisu, Narisu; Nauck, Matthias; Nolte, Ilja M; Nöthen, Markus M; Oozageer, Laticia; Pilz, Stefan; Rayner, Nigel W; Renstrom, Frida; Robertson, Neil R; Rose, Lynda M; Roussel, Ronan; Sanna, Serena; Scharnagl, Hubert; Scholtens, Salome; Schumacher, Fredrick R; Schunkert, Heribert; Scott, Robert A; Sehmi, Joban; Seufferlein, Thomas; Shi, Jianxin; Silventoinen, Karri; Smit, Johannes H; Smith, Albert Vernon; Smolonska, Joanna; Stanton, Alice V; Stirrups, Kathleen; Stott, David J; Stringham, Heather M; Sundström, Johan; Swertz, Morris A; Syvänen, Ann-Christine; Tayo, Bamidele O; Thorleifsson, Gudmar; Tyrer, Jonathan P; van Dijk, Suzanne; van Schoor, Natasja M; van der Velde, Nathalie; van Heemst, Diana; van Oort, Floor V A; Vermeulen, Sita H; Verweij, Niek; Vonk, Judith M; Waite, Lindsay L; Waldenberger, Melanie; Wennauer, Roman; Wilkens, Lynne R; Willenborg, Christina; Wilsgaard, Tom; Wojczynski, Mary K; Wong, Andrew; Wright, Alan F; Zhang, Qunyuan; Arveiler, Dominique; Bakker, Stephan J L; Beilby, John; Bergman, Richard N; Bergmann, Sven; Biffar, Reiner; Blangero, John; Boomsma, Dorret I; Bornstein, Stefan R; Bovet, Pascal; Brambilla, Paolo; Brown, Morris J; Campbell, Harry; Caulfield, Mark J; Chakravarti, Aravinda; Collins, Rory; Collins, Francis S; Crawford, Dana C; Cupples, L Adrienne; Danesh, John; de Faire, Ulf; den Ruijter, Hester M; Erbel, Raimund; Erdmann, Jeanette; Eriksson, Johan G; Farrall, Martin; Ferrannini, Ele; Ferrières, Jean; Ford, Ian; Forouhi, Nita G; Forrester, Terrence; Gansevoort, Ron T; Gejman, Pablo V; Gieger, Christian; Golay, Alain; Gottesman, Omri; Gudnason, Vilmundur; Gyllensten, Ulf; Haas, David W; Hall, Alistair S; Harris, Tamara B; Hattersley, Andrew T; Heath, Andrew C; Hengstenberg, Christian; Hicks, Andrew A; Hindorff, Lucia A; Hingorani, Aroon D; Hofman, Albert; Hovingh, G Kees; Humphries, Steve E; Hunt, Steven C; Hypponen, Elina; Jacobs, Kevin B; Jarvelin, Marjo-Riitta; Jousilahti, Pekka; Jula, Antti M; Kaprio, Jaakko; Kastelein, John J P; Kayser, Manfred; Kee, Frank; Keinanen-Kiukaanniemi, Sirkka M; Kiemeney, Lambertus A; Kooner, Jaspal S; Kooperberg, Charles; Koskinen, Seppo; Kovacs, Peter; Kraja, Aldi T; Kumari, Meena; Kuusisto, Johanna; Lakka, Timo A; Langenberg, Claudia; Le Marchand, Loic; Lehtimäki, Terho; Lupoli, Sara; Madden, Pamela A F; Männistö, Satu; Manunta, Paolo; Marette, André; Matise, Tara C; McKnight, Barbara; Meitinger, Thomas; Moll, Frans L; Montgomery, Grant W; Morris, Andrew D; Morris, Andrew P; Murray, Jeffrey C; Nelis, Mari; Ohlsson, Claes; Oldehinkel, Albertine J; Ong, Ken K; Ouwehand, Willem H; Pasterkamp, Gerard; Peters, Annette; Pramstaller, Peter P; Price, Jackie F; Qi, Lu; Raitakari, Olli T; Rankinen, Tuomo; Rao, D C; Rice, Treva K; Ritchie, Marylyn; Rudan, Igor; Salomaa, Veikko; Samani, Nilesh J; Saramies, Jouko; Sarzynski, Mark A; Schwarz, Peter E H; Sebert, Sylvain; Sever, Peter; Shuldiner, Alan R; Sinisalo, Juha; Steinthorsdottir, Valgerdur; Stolk, Ronald P; Tardif, Jean-Claude; Tönjes, Anke; Tremblay, Angelo; Tremoli, Elena; Virtamo, Jarmo; Vohl, Marie-Claude; Amouyel, Philippe; Asselbergs, Folkert W; Assimes, Themistocles L; Bochud, Murielle; Boehm, Bernhard O; Boerwinkle, Eric; Bottinger, Erwin P; Bouchard, Claude; Cauchi, Stéphane; Chambers, John C; Chanock, Stephen J; Cooper, Richard S; de Bakker, Paul I W; Dedoussis, George; Ferrucci, Luigi; Franks, Paul W; Froguel, Philippe; Groop, Leif C; Haiman, Christopher A; Hamsten, Anders; Hayes, M Geoffrey; Hui, Jennie; Hunter, David J; Hveem, Kristian; Jukema, J Wouter; Kaplan, Robert C; Kivimaki, Mika; Kuh, Diana; Laakso, Markku; Liu, Yongmei; Martin, Nicholas G; März, Winfried; Melbye, Mads; Moebus, Susanne; Munroe, Patricia B; Njølstad, Inger; Oostra, Ben A; Palmer, Colin N A; Pedersen, Nancy L; Perola, Markus; Pérusse, Louis; Peters, Ulrike; Powell, Joseph E; Power, Chris; Quertermous, Thomas; Rauramaa, Rainer; Reinmaa, Eva; Ridker, Paul M; Rivadeneira, Fernando; Rotter, Jerome I; Saaristo, Timo E; Saleheen, Danish; Schlessinger, David; Slagboom, P Eline; Snieder, Harold; Spector, Tim D; Strauch, Konstantin; Stumvoll, Michael; Tuomilehto, Jaakko; Uusitupa, Matti; van der Harst, Pim; Völzke, Henry; Walker, Mark; Wareham, Nicholas J; Watkins, Hugh; Wichmann, H-Erich; Wilson, James F; Zanen, Pieter; Deloukas, Panos; Heid, Iris M; Lindgren, Cecilia M; Mohlke, Karen L; Speliotes, Elizabeth K; Thorsteinsdottir, Unnur; Barroso, Inês; Fox, Caroline S; North, Kari E; Strachan, David P; Beckmann, Jacques S; Berndt, Sonja I; Boehnke, Michael; Borecki, Ingrid B; McCarthy, Mark I; Metspalu, Andres; Stefansson, Kari; Uitterlinden, André G; van Duijn, Cornelia M; Franke, Lude; Willer, Cristen J; Price, Alkes L; Lettre, Guillaume; Loos, Ruth J F; Weedon, Michael N; Ingelsson, Erik; O'Connell, Jeffrey R; Abecasis, Goncalo R; Chasman, Daniel I; Goddard, Michael E; Visscher, Peter M; Hirschhorn, Joel N; Frayling, Timothy M

    2014-11-01

    Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

  13. Defining the role of common variation in the genomic and biological architecture of adult human height

    Science.gov (United States)

    Chu, Audrey Y; Estrada, Karol; Luan, Jian’an; Kutalik, Zoltán; Amin, Najaf; Buchkovich, Martin L; Croteau-Chonka, Damien C; Day, Felix R; Duan, Yanan; Fall, Tove; Fehrmann, Rudolf; Ferreira, Teresa; Jackson, Anne U; Karjalainen, Juha; Lo, Ken Sin; Locke, Adam E; Mägi, Reedik; Mihailov, Evelin; Porcu, Eleonora; Randall, Joshua C; Scherag, André; Vinkhuyzen, Anna AE; Westra, Harm-Jan; Winkler, Thomas W; Workalemahu, Tsegaselassie; Zhao, Jing Hua; Absher, Devin; Albrecht, Eva; Anderson, Denise; Baron, Jeffrey; Beekman, Marian; Demirkan, Ayse; Ehret, Georg B; Feenstra, Bjarke; Feitosa, Mary F; Fischer, Krista; Fraser, Ross M; Goel, Anuj; Gong, Jian; Justice, Anne E; Kanoni, Stavroula; Kleber, Marcus E; Kristiansson, Kati; Lim, Unhee; Lotay, Vaneet; Lui, Julian C; Mangino, Massimo; Leach, Irene Mateo; Medina-Gomez, Carolina; Nalls, Michael A; Nyholt, Dale R; Palmer, Cameron D; Pasko, Dorota; Pechlivanis, Sonali; Prokopenko, Inga; Ried, Janina S; Ripke, Stephan; Shungin, Dmitry; Stancáková, Alena; Strawbridge, Rona J; Sung, Yun Ju; Tanaka, Toshiko; Teumer, Alexander; Trompet, Stella; van der Laan, Sander W; van Setten, Jessica; Van Vliet-Ostaptchouk, Jana V; Wang, Zhaoming; Yengo, Loïc; Zhang, Weihua; Afzal, Uzma; Ärnlöv, Johan; Arscott, Gillian M; Bandinelli, Stefania; Barrett, Amy; Bellis, Claire; Bennett, Amanda J; Berne, Christian; Blüher, Matthias; Bolton, Jennifer L; Böttcher, Yvonne; Boyd, Heather A; Bruinenberg, Marcel; Buckley, Brendan M; Buyske, Steven; Caspersen, Ida H; Chines, Peter S; Clarke, Robert; Claudi-Boehm, Simone; Cooper, Matthew; Daw, E Warwick; De Jong, Pim A; Deelen, Joris; Delgado, Graciela; Denny, Josh C; Dhonukshe-Rutten, Rosalie; Dimitriou, Maria; Doney, Alex SF; Dörr, Marcus; Eklund, Niina; Eury, Elodie; Folkersen, Lasse; Garcia, Melissa E; Geller, Frank; Giedraitis, Vilmantas; Go, Alan S; Grallert, Harald; Grammer, Tanja B; Gräßler, Jürgen; Grönberg, Henrik; de Groot, Lisette C.P.G.M.; Groves, Christopher J; Haessler, Jeffrey; Hall, Per; Haller, Toomas; Hallmans, Goran; Hannemann, Anke; Hartman, Catharina A; Hassinen, Maija; Hayward, Caroline; Heard-Costa, Nancy L; Helmer, Quinta; Hemani, Gibran; Henders, Anjali K; Hillege, Hans L; Hlatky, Mark A; Hoffmann, Wolfgang; Hoffmann, Per; Holmen, Oddgeir; Houwing-Duistermaat, Jeanine J; Illig, Thomas; Isaacs, Aaron; James, Alan L; Jeff, Janina; Johansen, Berit; Johansson, Åsa; Jolley, Jennifer; Juliusdottir, Thorhildur; Junttila, Juhani; Kho, Abel N; Kinnunen, Leena; Klopp, Norman; Kocher, Thomas; Kratzer, Wolfgang; Lichtner, Peter; Lind, Lars; Lindström, Jaana; Lobbens, Stéphane; Lorentzon, Mattias; Lu, Yingchang; Lyssenko, Valeriya; Magnusson, Patrik KE; Mahajan, Anubha; Maillard, Marc; McArdle, Wendy L; McKenzie, Colin A; McLachlan, Stela; McLaren, Paul J; Menni, Cristina; Merger, Sigrun; Milani, Lili; Moayyeri, Alireza; Monda, Keri L; Morken, Mario A; Müller, Gabriele; Müller-Nurasyid, Martina; Musk, Arthur W; Narisu, Narisu; Nauck, Matthias; Nolte, Ilja M; Nöthen, Markus M; Oozageer, Laticia; Pilz, Stefan; Rayner, Nigel W; Renstrom, Frida; Robertson, Neil R; Rose, Lynda M; Roussel, Ronan; Sanna, Serena; Scharnagl, Hubert; Scholtens, Salome; Schumacher, Fredrick R; Schunkert, Heribert; Scott, Robert A; Sehmi, Joban; Seufferlein, Thomas; Shi, Jianxin; Silventoinen, Karri; Smit, Johannes H; Smith, Albert Vernon; Smolonska, Joanna; Stanton, Alice V; Stirrups, Kathleen; Stott, David J; Stringham, Heather M; Sundström, Johan; Swertz, Morris A; Syvänen, Ann-Christine; Tayo, Bamidele O; Thorleifsson, Gudmar; Tyrer, Jonathan P; van Dijk, Suzanne; van Schoor, Natasja M; van der Velde, Nathalie; van Heemst, Diana; van Oort, Floor VA; Vermeulen, Sita H; Verweij, Niek; Vonk, Judith M; Waite, Lindsay L; Waldenberger, Melanie; Wennauer, Roman; Wilkens, Lynne R; Willenborg, Christina; Wilsgaard, Tom; Wojczynski, Mary K; Wong, Andrew; Wright, Alan F; Zhang, Qunyuan; Arveiler, Dominique; Bakker, Stephan JL; Beilby, John; Bergman, Richard N; Bergmann, Sven; Biffar, Reiner; Blangero, John; Boomsma, Dorret I; Bornstein, Stefan R; Bovet, Pascal; Brambilla, Paolo; Brown, Morris J; Campbell, Harry; Caulfield, Mark J; Chakravarti, Aravinda; Collins, Rory; Collins, Francis S; Crawford, Dana C; Cupples, L Adrienne; Danesh, John; de Faire, Ulf; den Ruijter, Hester M; Erbel, Raimund; Erdmann, Jeanette; Eriksson, Johan G; Farrall, Martin; Ferrannini, Ele; Ferrières, Jean; Ford, Ian; Forouhi, Nita G; Forrester, Terrence; Gansevoort, Ron T; Gejman, Pablo V; Gieger, Christian; Golay, Alain; Gottesman, Omri; Gudnason, Vilmundur; Gyllensten, Ulf; Haas, David W; Hall, Alistair S; Harris, Tamara B; Hattersley, Andrew T; Heath, Andrew C; Hengstenberg, Christian; Hicks, Andrew A; Hindorff, Lucia A; Hingorani, Aroon D; Hofman, Albert; Hovingh, G Kees; Humphries, Steve E; Hunt, Steven C; Hypponen, Elina; Jacobs, Kevin B; Jarvelin, Marjo-Riitta; Jousilahti, Pekka; Jula, Antti M; Kaprio, Jaakko; Kastelein, John JP; Kayser, Manfred; Kee, Frank; Keinanen-Kiukaanniemi, Sirkka M; Kiemeney, Lambertus A; Kooner, Jaspal S; Kooperberg, Charles; Koskinen, Seppo; Kovacs, Peter; Kraja, Aldi T; Kumari, Meena; Kuusisto, Johanna; Lakka, Timo A; Langenberg, Claudia; Le Marchand, Loic; Lehtimäki, Terho; Lupoli, Sara; Madden, Pamela AF; Männistö, Satu; Manunta, Paolo; Marette, André; Matise, Tara C; McKnight, Barbara; Meitinger, Thomas; Moll, Frans L; Montgomery, Grant W; Morris, Andrew D; Morris, Andrew P; Murray, Jeffrey C; Nelis, Mari; Ohlsson, Claes; Oldehinkel, Albertine J; Ong, Ken K; Ouwehand, Willem H; Pasterkamp, Gerard; Peters, Annette; Pramstaller, Peter P; Price, Jackie F; Qi, Lu; Raitakari, Olli T; Rankinen, Tuomo; Rao, DC; Rice, Treva K; Ritchie, Marylyn; Rudan, Igor; Salomaa, Veikko; Samani, Nilesh J; Saramies, Jouko; Sarzynski, Mark A; Schwarz, Peter EH; Sebert, Sylvain; Sever, Peter; Shuldiner, Alan R; Sinisalo, Juha; Steinthorsdottir, Valgerdur; Stolk, Ronald P; Tardif, Jean-Claude; Tönjes, Anke; Tremblay, Angelo; Tremoli, Elena; Virtamo, Jarmo; Vohl, Marie-Claude; Amouyel, Philippe; Asselbergs, Folkert W; Assimes, Themistocles L; Bochud, Murielle; Boehm, Bernhard O; Boerwinkle, Eric; Bottinger, Erwin P; Bouchard, Claude; Cauchi, Stéphane; Chambers, John C; Chanock, Stephen J; Cooper, Richard S; de Bakker, Paul IW; Dedoussis, George; Ferrucci, Luigi; Franks, Paul W; Froguel, Philippe; Groop, Leif C; Haiman, Christopher A; Hamsten, Anders; Hayes, M Geoffrey; Hui, Jennie; Hunter, David J.; Hveem, Kristian; Jukema, J Wouter; Kaplan, Robert C; Kivimaki, Mika; Kuh, Diana; Laakso, Markku; Liu, Yongmei; Martin, Nicholas G; März, Winfried; Melbye, Mads; Moebus, Susanne; Munroe, Patricia B; Njølstad, Inger; Oostra, Ben A; Palmer, Colin NA; Pedersen, Nancy L; Perola, Markus; Pérusse, Louis; Peters, Ulrike; Powell, Joseph E; Power, Chris; Quertermous, Thomas; Rauramaa, Rainer; Reinmaa, Eva; Ridker, Paul M; Rivadeneira, Fernando; Rotter, Jerome I; Saaristo, Timo E; Saleheen, Danish; Schlessinger, David; Slagboom, P Eline; Snieder, Harold; Spector, Tim D; Strauch, Konstantin; Stumvoll, Michael; Tuomilehto, Jaakko; Uusitupa, Matti; van der Harst, Pim; Völzke, Henry; Walker, Mark; Wareham, Nicholas J; Watkins, Hugh; Wichmann, H-Erich; Wilson, James F; Zanen, Pieter; Deloukas, Panos; Heid, Iris M; Lindgren, Cecilia M; Mohlke, Karen L; Speliotes, Elizabeth K; Thorsteinsdottir, Unnur; Barroso, Inês; Fox, Caroline S; North, Kari E; Strachan, David P; Beckmann, Jacques S.; Berndt, Sonja I; Boehnke, Michael; Borecki, Ingrid B; McCarthy, Mark I; Metspalu, Andres; Stefansson, Kari; Uitterlinden, André G; van Duijn, Cornelia M; Franke, Lude; Willer, Cristen J; Price, Alkes L.; Lettre, Guillaume; Loos, Ruth JF; Weedon, Michael N; Ingelsson, Erik; O’Connell, Jeffrey R; Abecasis, Goncalo R; Chasman, Daniel I; Goddard, Michael E

    2014-01-01

    Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explain one-fifth of heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ~2,000, ~3,700 and ~9,500 SNPs explained ~21%, ~24% and ~29% of phenotypic variance. Furthermore, all common variants together captured the majority (60%) of heritability. The 697 variants clustered in 423 loci enriched for genes, pathways, and tissue-types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/beta-catenin, and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants. PMID:25282103

  14. ECM microenvironment unlocks brown adipogenic potential of adult human bone marrow-derived MSCs.

    Science.gov (United States)

    Lee, Michelle H; Goralczyk, Anna G; Kriszt, Rókus; Ang, Xiu Min; Badowski, Cedric; Li, Ying; Summers, Scott A; Toh, Sue-Anne; Yassin, M Shabeer; Shabbir, Asim; Sheppard, Allan; Raghunath, Michael

    2016-02-17

    Key to realizing the diagnostic and therapeutic potential of human brown/brite adipocytes is the identification of a renewable, easily accessible and safe tissue source of progenitor cells, and an efficacious in vitro differentiation protocol. We show that macromolecular crowding (MMC) facilitates brown adipocyte differentiation in adult human bone marrow mesenchymal stem cells (bmMSCs), as evidenced by substantially upregulating uncoupling protein 1 (UCP1) and uncoupled respiration. Moreover, MMC also induced 'browning' in bmMSC-derived white adipocytes. Mechanistically, MMC creates a 3D extracellular matrix architecture enshrouding maturing adipocytes in a collagen IV cocoon that is engaged by paxillin-positive focal adhesions also at the apical side of cells, without contact to the stiff support structure. This leads to an enhanced matrix-cell signaling, reflected by increased phosphorylation of ATF2, a key transcription factor in UCP1 regulation. Thus, tuning the dimensionality of the microenvironment in vitro can unlock a strong brown potential dormant in bone marrow.

  15. Effect of exercise on fluoride metabolism in adult humans: a pilot study.

    Science.gov (United States)

    V Zohoori, Fatemeh; Innerd, Alison; Azevedo, Liane B; Whitford, Gary M; Maguire, Anne

    2015-11-19

    An understanding of all aspects of fluoride metabolism is critical to identify its biological effects and avoid fluoride toxicity in humans. Fluoride metabolism and subsequently its body retention may be affected by physiological responses to acute exercise. This pilot study investigated the effect of exercise on plasma fluoride concentration, urinary fluoride excretion and fluoride renal clearance following no exercise and three exercise intensity conditions in nine healthy adults after taking a 1-mg Fluoride tablet. After no, light, moderate and vigorous exercise, respectively, the mean (SD) baseline-adjusted i) plasma fluoride concentration was 9.6(6.3), 11.4(6.3), 15.6(7.7) and 14.9(10.0) ng/ml; ii) rate of urinary fluoride excretion over 0-8 h was 46(15), 44(22), 34(17) and 36(17) μg/h; and iii) rate of fluoride renal clearance was 26.5(9.0), 27.2(30.4), 13.1(20.4) and 18.3(34.9) ml/min. The observed trend of a rise in plasma fluoride concentration and decline in rate of fluoride renal clearance with increasing exercise intensity needs to be investigated in a larger trial. This study, which provides the first data on the effect of exercise with different intensities on fluoride metabolism in humans, informs sample size planning for any subsequent definitive trial, by providing a robust estimate of the variability of the effect.

  16. Delayed intramuscular human neurotrophin-3 improves recovery in adult and elderly rats after stroke.

    Science.gov (United States)

    Duricki, Denise A; Hutson, Thomas H; Kathe, Claudia; Soleman, Sara; Gonzalez-Carter, Daniel; Petruska, Jeffrey C; Shine, H David; Chen, Qin; Wood, Tobias C; Bernanos, Michel; Cash, Diana; Williams, Steven C R; Gage, Fred H; Moon, Lawrence D F

    2016-01-01

    There is an urgent need for a therapy that reverses disability after stroke when initiated in a time frame suitable for the majority of new victims. We show here that intramuscular delivery of neurotrophin-3 (NT3, encoded by NTF3) can induce sensorimotor recovery when treatment is initiated 24 h after stroke. Specifically, in two randomized, blinded preclinical trials, we show improved sensory and locomotor function in adult (6 months) and elderly (18 months) rats treated 24 h following cortical ischaemic stroke with human NT3 delivered using a clinically approved serotype of adeno-associated viral vector (AAV1). Importantly, AAV1-hNT3 was given in a clinically-feasible timeframe using a straightforward, targeted route (injections into disabled forelimb muscles). Magnetic resonance imaging and histology showed that recovery was not due to neuroprotection, as expected given the delayed treatment. Rather, treatment caused corticospinal axons from the less affected hemisphere to sprout in the spinal cord. This treatment is the first gene therapy that reverses disability after stroke when administered intramuscularly in an elderly body. Importantly, phase I and II clinical trials by others show that repeated, peripherally administered high doses of recombinant NT3 are safe and well tolerated in humans with other conditions. This paves the way for NT3 as a therapy for stroke. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. The predictive nature of transcript expression levels on protein expression in adult human brain.

    Science.gov (United States)

    Bauernfeind, Amy L; Babbitt, Courtney C

    2017-04-24

    Next generation sequencing methods are the gold standard for evaluating expression of the transcriptome. When determining the biological implications of such studies, the assumption is often made that transcript expression levels correspond to protein levels in a meaningful way. However, the strength of the overall correlation between transcript and protein expression is inconsistent, particularly in brain samples. Following high-throughput transcriptomic (RNA-Seq) and proteomic (liquid chromatography coupled with tandem mass spectrometry) analyses of adult human brain samples, we compared the correlation in the expression of transcripts and proteins that support various biological processes, molecular functions, and that are located in different areas of the cell. Although most categories of transcripts have extremely weak predictive value for the expression of their associated proteins (R 2 values of < 10%), transcripts coding for protein kinases and membrane-associated proteins, including those that are part of receptors or ion transporters, are among those that are most predictive of downstream protein expression levels. The predictive value of transcript expression for corresponding proteins is variable in human brain samples, reflecting the complex regulation of protein expression. However, we found that transcriptomic analyses are appropriate for assessing the expression levels of certain classes of proteins, including those that modify proteins, such as kinases and phosphatases, regulate metabolic and synaptic activity, or are associated with a cellular membrane. These findings can be used to guide the interpretation of gene expression results from primate brain samples.

  18. Impact of experimental human pneumococcal carriage on nasopharyngeal bacterial densities in healthy adults.

    Science.gov (United States)

    Shak, Joshua R; Cremers, Amelieke J H; Gritzfeld, Jenna F; de Jonge, Marien I; Hermans, Peter W M; Vidal, Jorge E; Klugman, Keith P; Gordon, Stephen B

    2014-01-01

    Colonization of the nasopharynx by Streptococcus pneumoniae is a necessary precursor to pneumococcal diseases that result in morbidity and mortality worldwide. The nasopharynx is also host to other bacterial species, including the common pathogens Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis. To better understand how these bacteria change in relation to pneumococcal colonization, we used species-specific quantitative PCR to examine bacterial densities in 52 subjects 7 days before, and 2, 7, and 14 days after controlled inoculation of healthy human adults with S. pneumoniae serotype 6B. Overall, 33 (63%) of subjects carried S. pneumoniae post-inoculation. The baseline presence and density of S. aureus, H. influenzae, and M. catarrhalis were not statistically associated with likelihood of successful pneumococcal colonization at this study's sample size, although a lower rate of pneumococcal colonization in the presence of S. aureus (7/14) was seen compared to that in the presence of H. influenzae (12/16). Among subjects colonized with pneumococci, the number also carrying either H. influenzae or S. aureus fell during the study and at 14 days post-inoculation, the proportion carrying S. aureus was significantly lower among those who were colonized with S. pneumoniae (p = 0.008) compared to non-colonized subjects. These data on bacterial associations are the first to be reported surrounding experimental human pneumococcal colonization and show that co-colonizing effects are likely subtle rather than absolute.

  19. Impact of experimental human pneumococcal carriage on nasopharyngeal bacterial densities in healthy adults.

    Directory of Open Access Journals (Sweden)

    Joshua R Shak

    Full Text Available Colonization of the nasopharynx by Streptococcus pneumoniae is a necessary precursor to pneumococcal diseases that result in morbidity and mortality worldwide. The nasopharynx is also host to other bacterial species, including the common pathogens Staphylococcus aureus, Haemophilus influenzae, and Moraxella catarrhalis. To better understand how these bacteria change in relation to pneumococcal colonization, we used species-specific quantitative PCR to examine bacterial densities in 52 subjects 7 days before, and 2, 7, and 14 days after controlled inoculation of healthy human adults with S. pneumoniae serotype 6B. Overall, 33 (63% of subjects carried S. pneumoniae post-inoculation. The baseline presence and density of S. aureus, H. influenzae, and M. catarrhalis were not statistically associated with likelihood of successful pneumococcal colonization at this study's sample size, although a lower rate of pneumococcal colonization in the presence of S. aureus (7/14 was seen compared to that in the presence of H. influenzae (12/16. Among subjects colonized with pneumococci, the number also carrying either H. influenzae or S. aureus fell during the study and at 14 days post-inoculation, the proportion carrying S. aureus was significantly lower among those who were colonized with S. pneumoniae (p = 0.008 compared to non-colonized subjects. These data on bacterial associations are the first to be reported surrounding experimental human pneumococcal colonization and show that co-colonizing effects are likely subtle rather than absolute.

  20. High adult mortality among Hiwi hunter-gatherers: implications for human evolution.

    Science.gov (United States)

    Hill, Kim; Hurtado, A M; Walker, R S

    2007-04-01

    Extant apes experience early sexual maturity and short life spans relative to modern humans. Both of these traits and others are linked by life-history theory to mortality rates experienced at different ages by our hominin ancestors. However, currently there is a great deal of debate concerning hominin mortality profiles at different periods of evolutionary history. Observed rates and causes of mortality in modern hunter-gatherers may provide information about Upper Paleolithic mortality that can be compared to indirect evidence from the fossil record, yet little is published about causes and rates of mortality in foraging societies around the world. To our knowledge, interview-based life tables for recent hunter-gatherers are published for only four societies (Ache, Agta, Hadza, and Ju/'hoansi). Here, we present mortality data for a fifth group, the Hiwi hunter-gatherers of Venezuela. The results show comparatively high death rates among the Hiwi and highlight differences in mortality rates among hunter-gatherer societies. The high levels of conspecific violence and adult mortality in the Hiwi may better represent Paleolithic human demographics than do the lower, disease-based death rates reported in the most frequently cited forager studies.

  1. Lack of tissue renewal in human adult Achilles tendon is revealed by nuclear bomb 14C

    Science.gov (United States)

    Heinemeier, Katja Maria; Schjerling, Peter; Heinemeier, Jan; Magnusson, Stig Peter; Kjaer, Michael

    2013-01-01

    Tendons are often injured and heal poorly. Whether this is caused by a slow tissue turnover is unknown, since existing data provide diverging estimates of tendon protein half-life that range from 2 mo to 200 yr. With the purpose of determining life-long turnover of human tendon tissue, we used the 14C bomb-pulse method. This method takes advantage of the dramatic increase in atmospheric levels of 14C, produced by nuclear bomb tests in 1955–1963, which is reflected in all living organisms. Levels of 14C were measured in 28 forensic samples of Achilles tendon core and 4 skeletal muscle samples (donor birth years 1945–1983) with accelerator mass spectrometry (AMS) and compared to known atmospheric levels to estimate tissue turnover. We found that Achilles tendon tissue retained levels of 14C corresponding to atmospheric levels several decades before tissue sampling, demonstrating a very limited tissue turnover. The tendon concentrations of 14C approximately reflected the atmospheric levels present during the first 17 yr of life, indicating that the tendon core is formed during height growth and is essentially not renewed thereafter. In contrast, 14C levels in muscle indicated continuous turnover. Our observation provides a fundamental premise for understanding tendon function and pathology, and likely explains the poor regenerative capacity of tendon tissue.—Heinemeier, K. M., Schjerling, P., Heinemeier, J., Magnusson, S. P., Kjaer, M. Lack of tissue renewal in human adult Achilles tendon is revealed by nuclear bomb 14C. PMID:23401563

  2. Effect of retinoic acid on proteoglycan turnover in bovine articular cartilage cultures

    International Nuclear Information System (INIS)

    Campbell, M.A.; Handley, C.J.

    1987-01-01

    This paper describes proteoglycan catabolism by adult bovine articular cartilage treated with retinoic acid as a means of stimulating the loss of this macromolecule from the extracellular matrix of cartilage. Addition of retinoic acid (10(-12)-10(-6) M) to adult bovine articular cartilage which had been labeled with [ 35 S]sulfate for 6 h after 5 days in culture, resulted in a dose-dependent increase in the rate of loss of 35 S-labeled proteoglycans from the matrix of the tissue. Concomitant with this loss was a decrease in the proteoglycan content of the tissue. Incubation of cultures treated with 1 microM retinoic acid, at 4 degrees C, or with 0.5 mM cycloheximide, resulted in a significant decrease in the rate of retinoic acid-induced loss of proteoglycans and demonstrated cellular involvement in this process. Analysis of the 35 S-labeled proteoglycans remaining in the matrix showed that the percentage of radioactivity associated with the small proteoglycan species extracted from the matrix of articular cartilage explants labeled with [ 35 S]sulfate after 5 days in culture was 15% and this increased to 22% in tissue maintained in medium alone. In tissue treated with 1 microM retinoic acid for 6 days, the percentage of radioactivity associated with the small proteoglycan was 58%. Approximately 93% of the 35 S-labeled proteoglycans released into the medium of control and retinoic acid-treated cultures was recovered in high density fractions after CsCl gradient centrifugation and eluted on Sepharose CL-2B as a broad peak with a Kav of 0.30-0.37. Less than 17% of these proteoglycans was capable of aggregating with hyaluronate. These results indicate that in both control and retinoic acid-treated cultures the larger proteoglycan species is lost to the medium at a greater rate than the small proteoglycan species. The effect of retinoic acid on proteoglycan turnover was shown to be reversible

  3. THE PELVIS, ARTICULAR INTERFACE BETWEEN VERTEBRAL COLUMN AND LOWER LIMBS. ANALYSIS BY THE SOFTWARE DE-VISU

    OpenAIRE

    Tardieu , Christine; Hecquet , Jérome; Barrau , Anne; Loridon , Philippe; Boulay , Christophe; Legaye , Jean; Carlier , Robert; Marty , Catherine; Duval-Beaupière , Geneviève

    2006-01-01

    We analyzed 51 adult pelvis (25 women, 26 men) by the software DE-VISU conceived by one of us, J. Hecquet. It allows the description of the pelvis as the keystone of the articular system linking vertebral column, pelvis and lower limbs. The variations of the sagittal pelvic parameter, “angle of incidence” (mean 54°), are mainly responsible of individual variation in sagittal spine curves. The extreme values of incidence (32°-76°) correspond to pathological situations. This angle was discovere...

  4. Validation of endogenous normalizing genes for expression analyses in adult human testis and germ cell neoplasms.

    Science.gov (United States)

    Svingen, T; Jørgensen, A; Rajpert-De Meyts, E

    2014-08-01

    The measurement of gene expression levels in cells and tissues typically depends on a suitable point of reference for inferring biological relevance. For quantitative (or real-time) RT-PCR assays, the method of choice is often to normalize gene expression data to an endogenous gene that is stably expressed across the samples analysed: a so-called normalizing or housekeeping gene. Although this is a valid strategy, the identification of stable normalizing genes has proved challenging and a gene showing stable expression across all cells or tissues is unlikely to exist. Therefore, it is necessary to define suitable normalizing genes for specific cells and tissues. Here, we report on the performance of a panel of nine commonly employed normalizing genes in adult human testis and testicular pathologies. Our analyses revealed significant variability in transcript abundance for commonly used normalizers, highlighting the importance of selecting appropriate normalizing genes as comparative measurements can yield variable results when different normalizing genes are employed. Based on our results, we recommend using RPS20, RPS29 or SRSF4 when analysing relative gene expression levels in human testis and associated testicular pathologies. OCT4 and SALL4 can be used with caution as second-tier normalizers when determining changes in gene expression in germ cells and germ cell tumour components, but the relative transcript abundance appears variable between different germ cell tumour types. We further recommend that such studies should be accompanied by additional assessment of histology and cellularity of each sample. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. BAY11 enhances OCT4 synthetic mRNA expression in adult human skin cells.

    Science.gov (United States)

    Awe, Jason P; Crespo, Agustin Vega; Li, You; Kiledjian, Megerditch; Byrne, James A

    2013-02-06

    The OCT4 transcription factor is involved in many cellular processes, including development, reprogramming, maintaining pluripotency and differentiation. Synthetic OCT4 mRNA was recently used (in conjunction with other reprogramming factors) to generate human induced pluripotent stem cells. Here, we discovered that BAY 11-7082 (BAY11), at least partially through an NF-κB-inhibition based mechanism, could significantly increase the expression of OCT4 following transfection of synthetic mRNA (synRNA) into adult human skin cells. We tested various chemical and molecular small molecules on their ability to suppress the innate immune response seen upon synthetic mRNA transfection. Three molecules - B18R, BX795, and BAY11 - were used in immunocytochemical and proliferation-based assays. We also utilized global transcriptional meta-analysis coupled with quantitative PCR to identify relative gene expression downstream of OCT4. We found that human skin cells cultured in the presence of BAY11 resulted in reproducible increased expression of OCT4 that did not inhibit normal cell proliferation. The increased levels of OCT4 resulted in significantly increased expression of genes downstream of OCT4, including the previously identified SPP1, DUSP4 and GADD45G, suggesting the expressed OCT4 was functional. We also discovered a novel OCT4 putative downstream target gene SLC16A9 which demonstrated significantly increased expression following elevation of OCT4 levels. For the first time we have shown that small molecule-based stabilization of synthetic mRNA expression can be achieved with use of BAY11. This small molecule-based inhibition of innate immune responses and subsequent robust expression of transfected synthetic mRNAs may have multiple applications for future cell-based research and therapeutics.

  6. Intermittent Hypoxia Causes Inflammation and Injury to Human Adult Cardiac Myocytes.

    Science.gov (United States)

    Wu, Jing; Stefaniak, Joanna; Hafner, Christina; Schramel, Johannes Peter; Kaun, Christoph; Wojta, Johann; Ullrich, Roman; Tretter, Verena Eva; Markstaller, Klaus; Klein, Klaus Ulrich

    2016-02-01

    Intermittent hypoxia may occur in a number of clinical scenarios, including interruption of myocardial blood flow or breathing disorders such as obstructive sleep apnea. Although intermittent hypoxia has been linked to cardiovascular and cerebrovascular disease, the effect of intermittent hypoxia on the human heart is not fully understood. Therefore, in the present study, we compared the cellular responses of cultured human adult cardiac myocytes (HACMs) exposed to intermittent hypoxia and different conditions of continuous hypoxia and normoxia. HACMs were exposed to intermittent hypoxia (0%-21% O2), constant mild hypoxia (10% O2), constant severe hypoxia (0% O2), or constant normoxia (21% O2), using a novel cell culture bioreactor with gas-permeable membranes. Cell proliferation, lactate dehydrogenase release, vascular endothelial growth factor release, and cytokine (interleukin [IL] and macrophage migration inhibitory factor) release were assessed at baseline and after 8, 24, and 72 hours of exposure. A signal transduction pathway finder array was performed to determine the changes in gene expression. In comparison with constant normoxia and constant mild hypoxia, intermittent hypoxia induced earlier and greater inflammatory response and extent of cell injury as evidenced by lower cell numbers and higher lactate dehydrogenase, vascular endothelial growth factor, and proinflammatory cytokine (IL-1β, IL-6, IL-8, and macrophage migration inhibitory factor) release. Constant severe hypoxia showed more detrimental effects on HACMs at later time points. Pathway analysis demonstrated that intermittent hypoxia primarily altered gene expression in oxidative stress, Wnt, Notch, and hypoxia pathways. Intermittent and constant severe hypoxia, but not constant mild hypoxia or normoxia, induced inflammation and cell injury in HACMs. Cell injury occurred earliest and was greatest after intermittent hypoxia exposure. Our in vitro findings suggest that intermittent hypoxia

  7. Expression of FGFR3 during human testis development and in germ cell-derived tumours of young adults

    DEFF Research Database (Denmark)

    Ewen, Katherine A; Olesen, Inge A; Winge, Sofia B

    2013-01-01

    development and to ascertain whether FGFR3 signalling is linked to germ cell proliferation and the pathogenesis of testicular germ cell tumours (TGCTs) of young adult men. Using RT-PCR, immunohistochemistry and Western blotting, we examined 58 specimens of human testes throughout development for FGFR3...... expression, and then compared expression of FGFR3 with proliferation markers (PCNA or Ki67). We also analysed for FGFR3 expression 30 TGCTs and 28 testes containing the tumour precursor cell, carcinoma in situ (CIS). Fetal and adult testes expressed exclusively the FGFR3IIIc isoform. FGFR3 protein expression...... was restricted to the cytoplasm/plasma membrane of spermatogonia and was most prevalent at mid-gestation, infancy and from puberty onwards. Phosphorylated (p)FGFR was detected in pre-spermatogonia at mid-gestation and in spermatogonia during puberty and in the adult testis. Throughout normal human testis...

  8. TP53 mutation and human papilloma virus status of oral squamous cell carcinomas in young adult patients

    NARCIS (Netherlands)

    Braakhuis, B.J.M.; Rietbergen, M.M.; Buijze, M.; Snijders, P.J.F.; Bloemena, E.; Brakenhoff, R.H.; Leemans, C.R.

    2014-01-01

    Objective Little is known about the molecular carcinogenesis of oral squamous cell carcinoma (OSCC) in young adult patients. The aim of this study was to investigate the detailed TP53 mutation and human papilloma virus (HPV) status of OSCC in patients, younger than 45 years. Methods TP53 mutations

  9. Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males

    Science.gov (United States)

    Mokrysz, C; Freeman, T P; Korkki, S; Griffiths, K; Curran, H V

    2016-01-01

    Preclinical research demonstrates that cannabinoids have differing effects in adolescent and adult animals. Whether these findings translate to humans has not yet been investigated. Here we believe we conducted the first study to compare the acute effects of cannabis in human adolescent (n=20; 16–17 years old) and adult (n=20; 24–28 years old) male cannabis users, in a placebo-controlled, double-blind cross-over design. After inhaling vaporized active or placebo cannabis, participants completed tasks assessing spatial working memory, episodic memory and response inhibition, alongside measures of blood pressure and heart rate, psychotomimetic symptoms and subjective drug effects (for example, ‘stoned', ‘want to have cannabis'). Results showed that on active cannabis, adolescents felt less stoned and reported fewer psychotomimetic symptoms than adults. Further, adults but not adolescents were more anxious and less alert during the active cannabis session (both pre- and post-drug administration). Following cannabis, cognitive impairment (reaction time on spatial working memory and prose recall following a delay) was greater in adults than adolescents. By contrast, cannabis impaired response inhibition accuracy in adolescents but not in adults. Moreover, following drug administration, the adolescents did not show satiety; instead they wanted more cannabis regardless of whether they had taken active or placebo cannabis, while the opposite was seen for adults. These contrasting profiles of adolescent resilience (blunted subjective, memory, physiological and psychotomimetic effects) and vulnerability (lack of satiety, impaired inhibitory processes) show some degree of translation from preclinical findings, and may contribute to escalated cannabis use by human adolescents. PMID:27898071

  10. Evaluation of degenerative changes in articular cartilage of osteoarthritis by Raman spectroscopy

    Science.gov (United States)

    Oshima, Yusuke; Ishimaru, Yasumitsu; Kiyomatsu, Hiroshi; Hino, Kazunori; Miura, Hiromasa

    2018-02-01

    Osteoarthritis (OA) is a very common joint disease in the aging population. Main symptom of OA is accompanied by degenerative changes of articular cartilage. Cartilage contains mostly type II collagen and proteoglycans, so it is difficult to access the quality and morphology of cartilage tissue in situ by conventional diagnostic tools (X-ray, MRI and echography) directly or indirectly. Raman spectroscopy is a label-free technique which enables to analyze molecular composition in degenerative cartilage. In this proposal, we aim to develop Raman spectroscopic system for the quality assessment of articular cartilage during arthroscopic surgery. Toward this goal, we are focusing on the proteoglycan content and collagen fiber alignment in cartilage matrix which may be associated with degenerative changes in OA, and we designed an original Raman device for remote sensing during arthroscopic surgery. In this project, we define the grading system for cartilage defect based on Raman spectroscopy, and we complete the evaluation of the Raman probing system which makes it possible to detect early stage of degenerative cartilage as a novel tool for OA diagnosis using human subject.

  11. A Computational/Experimental Platform for Investigating Three-Dimensional Puzzle Solving of Comminuted Articular Fractures

    Science.gov (United States)

    Thomas, Thaddeus P.; Anderson, Donald D.; Willis, Andrew R.; Liu, Pengcheng; Frank, Matthew C.; Marsh, J. Lawrence; Brown, Thomas D.

    2011-01-01

    Reconstructing highly comminuted articular fractures poses a difficult surgical challenge, akin to solving a complicated three-dimensional (3D) puzzle. Pre-operative planning using CT is critically important, given the desirability of less invasive surgical approaches. The goal of this work is to advance 3D puzzle solving methods toward use as a pre-operative tool for reconstructing these complex fractures. Methodology for generating typical fragmentation/dispersal patterns was developed. Five identical replicas of human distal tibia anatomy, were machined from blocks of high-density polyetherurethane foam (bone fragmentation surrogate), and were fractured using an instrumented drop tower. Pre- and post-fracture geometries were obtained using laser scans and CT. A semi-automatic virtual reconstruction computer program aligned fragment native (non-fracture) surfaces to a pre-fracture template. The tibias were precisely reconstructed with alignment accuracies ranging from 0.03-0.4mm. This novel technology has potential to significantly enhance surgical techniques for reconstructing comminuted intra-articular fractures, as illustrated for a representative clinical case. PMID:20924863

  12. Transcription factor ERG and joint and articular cartilage formation during mouse limb and spine skeletogenesis.

    Science.gov (United States)

    Iwamoto, Masahiro; Tamamura, Yoshihiro; Koyama, Eiki; Komori, Toshihisa; Takeshita, Nobuo; Williams, Julie A; Nakamura, Takashi; Enomoto-Iwamoto, Motomi; Pacifici, Maurizio

    2007-05-01

    Articular cartilage and synovial joints are critical for skeletal function, but the mechanisms regulating their development are largely unknown. In previous studies we found that the ets transcription factor ERG and its alternatively-spliced variant C-1-1 have roles in joint formation in chick. Here, we extended our studies to mouse. We found that ERG is also expressed in developing mouse limb joints. To test regulation of ERG expression, beads coated with the joint master regulator protein GDF-5 were implanted close to incipient joints in mouse limb explants; this led to rapid and strong ectopic ERG expression. We cloned and characterized several mammalian ERG variants and expressed a human C-1-1 counterpart (hERG3Delta81) throughout the cartilaginous skeleton of transgenic mice, using Col2a1 gene promoter/enhancer sequences. The skeletal phenotype was severe and neonatal lethal, and the transgenic mice were smaller than wild type littermates and their skeletons were largely cartilaginous. Limb long bone anlagen were entirely composed of chondrocytes actively expressing collagen IX and aggrecan as well as articular markers such as tenascin-C. Typical growth plates were absent and there was very low expression of maturation and hypertrophy markers, including Indian hedgehog, collagen X and MMP-13. The results suggest that ERG is part of molecular mechanisms leading chondrocytes into a permanent developmental path and become joint forming cells, and may do so by acting downstream of GDF-5.

  13. Development of body weight support gait training system using antagonistic bi-articular muscle model.

    Science.gov (United States)

    Shibata, Yoshiyuki; Imai, Shingo; Nobutomo, Tatsuya; Miyoshi, Tasuku; Yamamoto, Shin-Ichiroh

    2010-01-01

    The purpose of this study is to develop a body weight support gait training system for stroke and spinal cord injury. This system consists of a powered orthosis, treadmill and equipment of body weight support. Attachment of the powered orthosis is able to fit subject who has difference of body size. This powered orthosis is driven by pneumatic McKibben actuator. Actuators are arranged as pair of antagonistic bi-articular muscle model and two pairs of antagonistic mono-articular muscle model like human musculoskeletal system. Part of the equipment of body weight support suspend subject by wire harness, and body weight of subject is supported continuously by counter weight. The powered orthosis is attached equipment of body weight support by parallel linkage, and movement of the powered orthosis is limited at sagittal plane. Weight of the powered orthosis is compensated by parallel linkage with gas-spring. In this study, we developed system that has orthosis powered by pneumatic McKibben actuators and equipment of body weight support. We report detail of our developed body weight support gait training system.

  14. Building a prototype using Human-Centered design to engage older adults in healthcare decision-making.

    Science.gov (United States)

    Kumar, Ajit; Maskara, Sanjeev; Chiang, I-Jen

    2014-01-01

    The prevalence of chronic diseases and disabilities are higher in older adults, which is one of the key factors of rising health care costs. Health care stakeholders wish older adults to take more control of their health to delay the onset of age-related disabilities and chronic diseases. Engaging older adults in their health care decision making would cut down health care costs and prepare a health care system to be more sustainable. We used the Human-Centered Design approach to propose a prototype that more effectively engages older adults in their health care decision-making. Four participants from four different countries - Taiwan, USA, Austria, and Germany; and two facilitators from the USA participated in this study. The participants interviewed a total of four subjects in their respective countries. This study used the Human-Centered Design approach, which embraced three main phases - observation, identification, and ideation. Each phase involved brainstorming, voting, and consensus among participants. This study derived 14 insights, 20 categories, 4 themes, a conceptual framework, some potential solutions, and a prototype. This study showed that older adults could be engaged in their health care decision-making by offering them health care products and services that were user-friendly and technology enabled. A 'gradual change management plan' could assist older adults to adopt technologies more effectively. The health care products and services should be centered on the needs of older adults. Moreover, the possibilities of older adults maintaining control over their own health may rely on proper timing, a personal approach, right products, and services.

  15. Effects of C5/C6 Intervertebral Space Distraction Height on Pressure on the Adjacent Intervertebral Disks and Articular Processes and Cervical Vertebrae Range of Motion.

    Science.gov (United States)

    Lu, Tingsheng; Luo, Chunshan; Ouyang, Beiping; Chen, Qiling; Deng, Zhongliang

    2018-04-25

    BACKGROUND This study aimed to investigate the association between range of motion of the cervical vertebrae and various C5/C6 intervertebral space distraction heights. MATERIAL AND METHODS The cervical vertebrae from 6 fresh adult human cadavers were used to prepare the models. Changes in C4/C5 and C6/C7 intervertebral disk pressures, articular process pressure, and range of motion of the cervical vertebrae before and after the distraction of the C5/C6 intervertebral space at benchmark heights of 100%, 120%, 140%, and 160% were tested under different exercise loads. RESULTS The pressure on the adjacent intervertebral disks was highest with the standing upright position before distraction, varied with different positions of the specimens and distraction heights after distraction, and was closest to that before distraction at a distraction height of 120% (Particular processes was highest with left and right rotations before distraction, varied with different positions of the specimens and distraction heights after distraction, and was lowest under the same exercise load with different positions at a distraction height of 120% (Pdistraction and at a distraction height of 120% after distraction, respectively (Particular processes and range of motion of the cervical vertebrae and is therefore an appropriate intervertebral space distraction height.

  16. A new frailty syndrome: central obesity and frailty in older adults with the human immunodeficiency virus.

    Science.gov (United States)

    Shah, Krupa; Hilton, Tiffany N; Myers, Lauren; Pinto, Jonathan F; Luque, Amneris E; Hall, William J

    2012-03-01

    To evaluate the relationships between body composition and physical frailty in community-dwelling older adults with the human immunodeficiency virus (HIV) (HOA). Cross-sectional. Academic hospital-based infectious disease clinic in Rochester, New York. Forty community-dwelling HOA aged 50 and older undergoing antiretroviral therapy who were able to ambulate without assistive devices with a mean age of 58, a mean BMI of 29.0 kg/m(2), mean CD4 count of 569 cells/mL, and a mean duration since HIV diagnosis of 17 years; 28% were female and 57% Caucasian. Subjective and objective measures of functional status were evaluated using the Physical Performance Test (PPT), the graded treadmill test, knee strength, gait speed, balance, and the Functional Status Questionnaire (FSQ). Body composition was evaluated using dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI). Sixty percent (25/40) of the participants met standard criteria for physical frailty. Frail (FR) and nonfrail (NF) participants were comparable in age, sex, CD4 count, and viral load. FR HOA had greater impairments in PPT, peak oxygen uptake, FSQ, walking speed, balance, and muscle quality than NF HOA. FR HOA had a greater body mass index (BMI), fat mass, and truncal fat with lipodystrophy. Moreover, PPT score was inversely related to trunk fat (correlation coefficient (r) = -0.34; P = .04) and ratio of intermuscular fat to total fat (r = -0.60; P = .02) after adjusting for covariates. HOA represent an emerging cohort of older adults who frequently experience frailty at a much younger age than the general older population. Central obesity and fat redistribution are important predictors of frailty in community-dwelling HOA. These findings suggest that physical frailty in HOA may be amenable to lifestyle interventions, especially exercise and diet therapy. © 2012, Copyright the Authors Journal compilation © 2012, The American Geriatrics Society.

  17. Per rectal endoscopic myotomy for the treatment of adult Hirschsprung's disease: First human case (with video).

    Science.gov (United States)

    Bapaye, Amol; Wagholikar, Gajanan; Jog, Sameer; Kothurkar, Aditi; Purandare, Shefali; Dubale, Nachiket; Pujari, Rajendra; Mahadik, Mahesh; Vyas, Viral; Bapaye, Jay

    2016-09-01

    Hirschsprung's disease (HD) is a congenital disorder characterized by the absence of intrinsic ganglion cells in submucosal and myenteric plexuses of the hindgut; and presents with constipation, intestinal obstruction and/or megacolon. HD commonly involves the rectosigmoid region (short segment HD), although shorter and longer variants of the disease are described. Standard treatment involves pull-through surgery for short segment HD or posterior anorectal myotomy in selected ultrashort segment candidates. Third space endoscopy has evolved during the past few years. Per oral endoscopic myotomy and per oral pyloromyotomy are described for treatment of achalasia cardia and refractory gastroparesis, respectively. Using the same philosophy of muscle/sphincter disruption for spastic bowel segments, per rectal endoscopic myotomy could be considered as a treatment option for short segment HD. A 24-year-old male patient presented with refractory constipation since childhood, and habituated to high-dose laxative combinations. Diagnosis was confirmed as adult short segment HD by barium enema, colonoscopic deep suction mucosal biopsies and anorectal manometry. Histopathology confirmed aganglionosis in the distal 15 cm. By implementing principles of third space endoscopy, per rectal endoscopic myotomy 20 cm in length was successfully carried out. At 24-week follow up, the patient reported significant relief of constipation and associated symptoms. Sigmoidoscopy, anorectal manometry and barium enema confirm improved rectal distensibility and reduced rectal pressures. The present case report describes the first human experience of per rectal endoscopic myotomy for successful treatment of adult short segment HD. © 2016 Japan Gastroenterological Endoscopy Society.

  18. Early developmental gene enhancers affect subcortical volumes in the adult human brain.

    Science.gov (United States)

    Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

    2016-05-01

    Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Epidemiology of Human Papillomavirus Detected in the Oral Cavity and Fingernails of Mid-Adult Women.

    Science.gov (United States)

    Fu, Tsung-chieh Jane; Hughes, James P; Feng, Qinghua; Hulbert, Ayaka; Hawes, Stephen E; Xi, Long Fu; Schwartz, Stephen M; Stern, Joshua E; Koutsky, Laura A; Winer, Rachel L

    2015-12-01

    Oral and fingernail human papillomavirus (HPV) detection may be associated with HPV-related carcinoma risk at these nongenital sites and foster transmission to the genitals. We describe the epidemiology of oral and fingernail HPV among mid-adult women. Between 2011 and 2012, 409 women aged 30 to 50 years were followed up for 6 months. Women completed health and behavior surveys and provided self-collected oral, fingernail, and vaginal specimens at enrollment and exit for type-specific HPV DNA testing. Concordance of type-specific HPV detection across anatomical sites was described with κ statistics. Using generalized estimating equations or exact logistic regression, we measured the univariate associations of various risk factors with type-specific oral and fingernail HPV detection. Prevalence of detecting HPV in the oral cavity (2.4%) and fingernails (3.8%) was low compared with the vagina (33.1%). Concordance across anatomical sites was poor (κ history (OR, 11.1; 95% CI, 2.8-infinity), lifetime number of male vaginal sex partners at least 10 (OR vs. 0-3 partners, 5.0; 95% CI, 1.2-infinity), and lifetime number of open-mouth kissing partners at least 16 (OR vs. 0-15 partners, infinity; 95% CI, 2.6-infinity, by exact logistic regression) were each associated with oral HPV detection. Although our findings support HPV DNA deposition or autoinoculation between anatomical sites in mid-adult women, the rarity of HPV in the oral cavity and fingernails suggests that oral/fingernail HPV does not account for a significant fraction of HPV in genital sites.

  20. Assessment of human papilloma virus infection in adult laryngeal papilloma using a screening test.

    Science.gov (United States)

    Makiyama, Kiyoshi; Hirai, Ryoji; Matsuzaki, Hiroumi; Ikeda, Minoru

    2013-03-01

    Human papilloma virus (HPV) infection is involved in both juvenile and adult laryngeal papilloma. We wished to determine which types of adult laryngeal papilloma were clinically related to HPV infection. We hypothesized that multiple-site and recurrent papillomas would have a strong relationship to HPV and conducted the present study to test this hypothesis. Thirteen male patients with adult laryngeal papilloma who underwent resection of papilloma between August 2006 and September 2009 were studied. We examined the relationships between whether the tumor was solitary or multiple, presence or absence of recurrence after surgery, and HPV infection. High-risk HPV types (HPV-DNA types 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, and 68) and low-risk HPV types (6, 11, 42, 43, and 44) were tested by a liquid-phase hybridization method. In addition, HPV typing was performed for patients positive for low-risk HPV types. Twenty patients with laryngeal carcinoma or laryngeal leukoplakia were enrolled as the control group. In the laryngeal papilloma group, all patients tested were negative for high-risk HPV and 69.2% were positive for low-risk HPV. Typing performed for seven of the patients who tested positive for low-risk HPV showed that one patient was positive for HPV-11, whereas the remaining six patients were positive for HPV-6. All patients with recurrent laryngeal papillomatosis (RLP) were positive for low-risk HPV. All patients who were positive for low-risk HPV had RLP. Tumor samples from repeat operations were positive for low-risk HPV in all patients tested. HPV was not detected in the control group. The relationship between RLP and low-risk HPV was strong, with all cases that were positive for low-risk HPV showing recurrence. Tumor tissue resected at the time of repeat surgery was positive for low-risk HPV in all cases tested. Copyright © 2013 The Voice Foundation. Published by Mosby, Inc. All rights reserved.

  1. Perivascular Mesenchymal Stem Cells in Sheep: Characterization and Autologous Transplantation in a Model of Articular Cartilage Repair.

    Science.gov (United States)

    Hindle, Paul; Baily, James; Khan, Nusrat; Biant, Leela C; Simpson, A Hamish R; Péault, Bruno

    2016-11-01

    Previous research has indicated that purified perivascular stem cells (PSCs) have increased chondrogenic potential compared to conventional mesenchymal stem cells (MSCs) derived in culture. This study aimed to develop an autologous large animal model for PSC transplantation and to specifically determine if implanted cells are retained in articular cartilage defects. Immunohistochemistry and fluorescence-activated cell sorting were used to ascertain the reactivity of anti-human and anti-ovine antibodies, which were combined and used to identify and isolate pericytes (CD34 - CD45 - CD146 + ) and adventitial cells (CD34 + CD45 - CD146 - ). The purified cells demonstrated osteogenic, adipogenic, and chondrogenic potential in culture. Autologous ovine PSCs (oPSCs) were isolated, cultured, and efficiently transfected using a green fluorescence protein (GFP) encoding lentivirus. The cells were implanted into articular cartilage defects on the medial femoral condyle using hydrogel and collagen membranes. Four weeks following implantation, the condyle was explanted and confocal laser scanning microscopy demonstrated the presence of oPSCs in the defect repaired with the hydrogel. These data suggest the testability in a large animal of native MSC autologous grafting, thus avoiding possible biases associated with xenotransplantation. Such a setting will be used in priority for indications in orthopedics, at first to model articular cartilage repair.

  2. Molecular changes in articular cartilage and subchondral bone in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis.

    Science.gov (United States)

    Pickarski, Maureen; Hayami, Tadashi; Zhuo, Ya; Duong, Le T

    2011-08-24

    Osteoarthritis (OA) is a debilitating, progressive joint disease. Similar to the disease progression in humans, sequential events of early cartilage degradation, subchondral osteopenia followed by sclerosis, and late osteophyte formation were demonstrated in the anterior cruciate ligament transection (ACLT) or ACLT with partial medial meniscectomy (ACLT + MMx) rat OA models. We describe a reliable and consistent method to examine the time dependent changes in the gene expression profiles in articular cartilage and subchondral bone. Local regulation of matrix degradation markers was demonstrated by a significant increase in mRNA levels of aggrecanase-1 and MMP-13 as early as the first week post-surgery, and expression remained elevated throughout the 10 week study. Immunohistochemistry confirmed MMP-13 expression in differentiated chondrocytes and synovial fibroblasts at week-2 and cells within osteophytes at week-10 in the surgically-modified-joints. Concomitant increases in chondrocyte differentiation markers, Col IIA and Sox 9, and vascular invasion markers, VEGF and CD31, peaked around week-2 to -4, and returned to Sham levels at later time points in both models. Indeed, VEGF-positive cells were found in the deep articular chondrocytes adjacent to subchondral bone. Osteoclastic bone resorption markers, cathepsin K and TRAP, were also elevated at week-2. Confirming bone resorption is an early local event in OA progression, cathepsin K positive osteoclasts were found invading the articular cartilage from the subchondral region at week 2. This was followed by late disease events, including subchondral sclerosis and osteophyte formation, as demonstrated by the upregulation of the osteoanabolic markers runx2 and osterix, toward week-4 to 6 post-surgery. In summary, this study demonstrated the temporal and cohesive gene expression changes in articular cartilage and subchondral bone using known markers of OA progression. The findings here support genome-wide profiling

  3. Molecular changes in articular cartilage and subchondral bone in the rat anterior cruciate ligament transection and meniscectomized models of osteoarthritis

    Directory of Open Access Journals (Sweden)

    Zhuo Ya

    2011-08-01

    Full Text Available Abstract Background Osteoarthritis (OA is a debilitating, progressive joint disease. Methods Similar to the disease progression in humans, sequential events of early cartilage degradation, subchondral osteopenia followed by sclerosis, and late osteophyte formation were demonstrated in the anterior cruciate ligament transection (ACLT or ACLT with partial medial meniscectomy (ACLT + MMx rat OA models. We describe a reliable and consistent method to examine the time dependent changes in the gene expression profiles in articular cartilage and subchondral bone. Results Local regulation of matrix degradation markers was demonstrated by a significant increase in mRNA levels of aggrecanase-1 and MMP-13 as early as the first week post-surgery, and expression remained elevated throughout the 10 week study. Immunohistochemistry confirmed MMP-13 expression in differentiated chondrocytes and synovial fibroblasts at week-2 and cells within osteophytes at week-10 in the surgically-modified-joints. Concomitant increases in chondrocyte differentiation markers, Col IIA and Sox 9, and vascular invasion markers, VEGF and CD31, peaked around week-2 to -4, and returned to Sham levels at later time points in both models. Indeed, VEGF-positive cells were found in the deep articular chondrocytes adjacent to subchondral bone. Osteoclastic bone resorption markers, cathepsin K and TRAP, were also elevated at week-2. Confirming bone resorption is an early local event in OA progression, cathepsin K positive osteoclasts were found invading the articular cartilage from the subchondral region at week 2. This was followed by late disease events, including subchondral sclerosis and osteophyte formation, as demonstrated by the upregulation of the osteoanabolic markers runx2 and osterix, toward week-4 to 6 post-surgery. Conclusions In summary, this study demonstrated the temporal and cohesive gene expression changes in articular cartilage and subchondral bone using known markers of

  4. Empowering Adult Learners. NIF Literacy Program Helps ABE Accomplish Human Development Mission.

    Science.gov (United States)

    Hurley, Mary E.

    1991-01-01

    The National Issues Forum's Literacy Program uses study circles and group discussion to promote empowerment and enhance adult literacy through civic education. The program has helped the Westonka (Minnesota) Adult Basic Education project accomplish its mission and has expanded the staff's view of adult learning. (SK)

  5. Human Dental Pulp Cells Differentiate toward Neuronal Cells and Promote Neuroregeneration in Adult Organotypic Hippocampal Slices In Vitro.

    Science.gov (United States)

    Xiao, Li; Ide, Ryoji; Saiki, Chikako; Kumazawa, Yasuo; Okamura, Hisashi

    2017-08-11

    The adult mammalian central nerve system has fundamental difficulties regarding effective neuroregeneration. The aim of this study is to investigate whether human dental pulp cells (DPCs) can promote neuroregeneration by (i) being differentiated toward neuronal cells and/or (ii) stimulating local neurogenesis in the adult hippocampus. Using immunostaining, we demonstrated that adult human dental pulp contains multipotent DPCs, including STRO-1, CD146 and P75-positive stem cells. DPC-formed spheroids were able to differentiate into neuronal, vascular, osteogenic and cartilaginous lineages under osteogenic induction. However, under neuronal inductive conditions, cells in the DPC-formed spheroids differentiated toward neuronal rather than other lineages. Electrophysiological study showed that these cells consistently exhibit the capacity to produce action potentials, suggesting that they have a functional feature in neuronal cells. We further co-cultivated DPCs with adult mouse hippocampal slices on matrigel in vitro. Immunostaining and presto blue assay showed that DPCs were able to stimulate the growth of neuronal cells (especially neurons) in both the CA1 zone and the edges of the hippocampal slices. Brain-derived neurotrophic factor (BDNF), was expressed in co-cultivated DPCs. In conclusion, our data demonstrated that DPCs are well-suited to differentiate into the neuronal lineage. They are able to stimulate neurogenesis in the adult mouse hippocampus through neurotrophic support in vitro.

  6. The effect of human engagement depicted in contextual photographs on the visual attention patterns of adults with traumatic brain injury.

    Science.gov (United States)

    Thiessen, Amber; Brown, Jessica; Beukelman, David; Hux, Karen

    2017-09-01

    Photographs are a frequently employed tool for the rehabilitation of adults with traumatic brain injury (TBI). Speech-language pathologists (SLPs) working with these individuals must select photos that are easily identifiable and meaningful to their clients. In this investigation, we examined the visual attention response to camera- (i.e., depicted human figure looking toward camera) and task-engaged (i.e., depicted human figure looking at and touching an object) contextual photographs for a group of adults with TBI and a group of adults without neurological conditions. Eye-tracking technology served to accurately and objectively measure visual fixations. Although differences were hypothesized given the cognitive deficits associated with TBI, study results revealed little difference in the visual fixation patterns of adults with and without TBI. Specifically, both groups of participants tended to fixate rapidly on the depicted human figure and fixate more on objects in which a human figure was task-engaged than when a human figure was camera-engaged. These results indicate that strategic placement of human figures in a contextual photograph may modify the way in which individuals with TBI visually attend to and interpret photographs. In addition, task-engagement appears to have a guiding effect on visual attention that may be of benefit to SLPs hoping to select more effective contextual photographs for their clients with TBI. Finally, the limited differences in visual attention patterns between individuals with TBI and their age and gender matched peers without neurological impairments indicates that these two groups find similar photograph regions to be worthy of visual fixation. Readers will gain knowledge regarding the photograph selection process for individuals with TBI. In addition, readers will be able to identify camera- and task-engaged photographs and to explain why task-engagement may be a beneficial component of contextual photographs. Copyright © 2017

  7. Early-life experiences and the development of adult diseases with a focus on mental illness: The Human Birth Theory.

    Science.gov (United States)

    Maccari, Stefania; Polese, Daniela; Reynaert, Marie-Line; Amici, Tiziana; Morley-Fletcher, Sara; Fagioli, Francesca

    2017-02-07

    In mammals, early adverse experiences, including mother-pup interactions, shape the response of an individual to chronic stress or to stress-related diseases during adult life. This has led to the elaboration of the theory of the developmental origins of health and disease, in particular adult diseases such as cardiovascular and metabolic disorders. In addition, in humans, as stated by Massimo Fagioli's Human Birth Theory, birth is healthy and equal for all individuals, so that mental illness develop exclusively in the postnatal period because of the quality of the relationship in the first year of life. Thus, this review focuses on the importance of programming during the early developmental period on the manifestation of adult diseases in both animal models and humans. Considering the obvious differences between animals and humans we cannot systematically move from animal models to humans. Consequently, in the first part of this review, we will discuss how animal models can be used to dissect the influence of adverse events occurring during the prenatal and postnatal periods on the developmental trajectories of the offspring, and in the second part, we will discuss the role of postnatal critical periods on the development of mental diseases in humans. Epigenetic mechanisms that cause reversible modifications in gene expression, driving the development of a pathological phenotype in response to a negative early postnatal environment, may lie at the core of this programming, thereby providing potential new therapeutic targets. The concept of the Human Birth Theory leads to a comprehension of the mental illness as a pathology of the human relationship immediately after birth and during the first year of life. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

  8. An association between human hippocampal volume and topographical memory in healthy young adults.

    Directory of Open Access Journals (Sweden)

    Tom eHartley

    2012-12-01

    Full Text Available The association between human hippocampal structure and topographical memory was investigated in healthy adults (N=30. Structural MR images were acquired, and voxel-based morphometry (VBM was used to estimate local gray matter volume throughout the brain. A complementary automated mesh-based segmentation approach was used to independently isolate and measure specified structures including the hippocampus. Topographical memory was assessed using a version of the Four Mountains Task, a short test designed to target hippocampal spatial function. Each item requires subjects to briefly study a landscape scene before recognizing the depicted place from a novel viewpoint and under altered non-spatial conditions when presented amongst similar alternative scenes. Positive correlations between topographical memory performance and hippocampal volume were observed in both VBM and segmentation-based analyses. Score on the topographical memory task was also correlated with the volume of some subcortical structures, extra-hippocampal gray matter and total brain volume, with the most robust and extensive covariation seen in circumscribed neocortical regions in the insula and anterior temporal lobes. Taken together with earlier findings, the results suggest that global variations in brain morphology affect the volume of the hippocampus and its specific contribution to topographical memory. We speculate that behavioral variation might arise directly through the impact of resource constraints on spatial representations in the hippocampal formation and its inputs, and perhaps indirectly through an increased reliance on non-allocentric strategies.

  9. Growth of the human lens in the Indian adult population: Preliminary observations

    Directory of Open Access Journals (Sweden)

    Ashik Mohamed

    2012-01-01

    Full Text Available Context: The eye lens grows throughout life by the addition of new cells inside the surrounding capsule. How this growth affects the properties of the lens is essential for understanding disorders such as cataract and presbyopia. Aims: To examine growth of the human lens in the Indian population and compare this with the growth in Western populations by measuring in vitro dimensions together with wet and dry weights. Settings and Design: The study was conducted at the research wing of a tertiary eye care center in South India and the study design was prospective. Materials and Methods: Lenses were removed from eye bank eyes and their dimensions measured with a digital caliper. They were then carefully blotted dry and weighed before being placed in 5% buffered formalin. After 1 week fixation, the lenses were dried at 80 °C until constant weight was achieved. The constant weight was noted as the dry weight of the lens. Statistical Analysis Used: Lens parameters were analyzed as a function of age using linear and logarithmic regression methods. Results: Data were obtained for 251 lenses, aged 16-93 years, within a median postmortem time of 22 h. Both wet and dry weights increased linearly at 1.24 and 0.44 mg/year, respectively, throughout adult life. The dimensions also increased continuously throughout this time. Conclusions: Over the age range examined, lens growth in the Indian population is very similar to that in Western populations.

  10. Redetection of human papillomavirus type 16 infections of the cervix in mid-adult life

    Directory of Open Access Journals (Sweden)

    Aaron Ermel

    2018-06-01

    Full Text Available Purpose: To assess whether HPV 16 originally detected in adolescent women can be redetected in adulthood. Methods: A convenience sample of 27 adult women with known HPV 16 detection during adolescence was assessed for HPV 16 redetection. A comparison of the long control region (LCR DNA sequences was performed on some of the original and redetected HPV 16 isolates. Results: Median age at reenrollment was 27.5 years (interquartile range of 26.7–29.6. Reenrollment occurred six years on average after the original HPV 16 detection. Eleven of 27 women had HPV 16 redetected. Some of these HPV 16 infections had apparently cleared during adolescence. LCR sequencing was successful in paired isolates from 6 women; in 5 of 6 cases the redetected HPV 16 isolates were identical to those detected during adolescence, Conclusions: HPV 16 may be episodically detected in young women, even over long time periods. HPV 16 redetection with identical LCR sequences suggests low-level persistent infection rather than true clearance, although newly acquired infection with an identical HPV 16 isolate cannot be excluded. However, this study suggests that a new HPV 16-positive test in a clinical setting may not indicate a new infection. Keywords: Human papillomavirus (HPV, Redetection, Latency, Long control region, Sequencing

  11. Chondroitin sulfate reduces the friction coefficient of articular cartilage.

    Science.gov (United States)

    Basalo, Ines M; Chahine, Nadeen O; Kaplun, Michael; Chen, Faye H; Hung, Clark T; Ateshian, Gerard A

    2007-01-01

    The objective of this study was to investigate the effect of chondroitin sulfate (CS)-C on the frictional response of bovine articular cartilage. The main hypothesis is that CS decreases the friction coefficient of articular cartilage. Corollary hypotheses are that viscosity and osmotic pressure are not the mechanisms that mediate the reduction in the friction coefficient by CS. In Experiment 1, bovine articular cartilage samples (n=29) were tested in either phosphate buffered saline (PBS) or in PBS containing 100mg/ml of CS following 48h incubation in PBS or in PBS+100mg/ml CS (control specimens were not subjected to any incubation). In Experiment 2, samples (n=23) were tested in four different solutions: PBS, PBS+100mg/ml CS, and PBS+polyethylene glycol (PEG) (133 or 170mg/ml). In Experiment 3, samples (n=18) were tested in three solutions of CS (0, 10 and 100mg/ml). Frictional tests (cartilage-on-glass) were performed under constant stress (0.5MPa) for 3600s and the time-dependent friction coefficient was measured. Samples incubated or tested in a 100mg/ml CS solution exhibited a significantly lower equilibrium friction coefficient than the respective PBS control. PEG solutions delayed the rise in the friction coefficient relative to the PBS control, but did not reduce the equilibrium value. Testing in PBS+10mg/ml of CS did not cause any significant decrease in the friction coefficient. In conclusion, CS at a concentration of 100mg/ml significantly reduces the friction coefficient of bovine articular cartilage and this mechanism is neither mediated by viscosity nor osmolarity. These results suggest that direct injection of CS into the joint may provide beneficial tribological effects.

  12. Repair and tissue engineering techniques for articular cartilage

    OpenAIRE

    Makris, Eleftherios A.; Gomoll, Andreas H.; Malizos, Konstantinos N.; Hu, Jerry C.; Athanasiou, Kyriacos A.

    2014-01-01

    © 2015 Macmillan Publishers Limited. All rights reserved. Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable s...

  13. Sonographic evaluation of femoral articular cartilage in the knee

    International Nuclear Information System (INIS)

    Hong, Sung Hwan; Kong Keun Young; Chung, Hye Won; Choi, Young Ho; Song, Yeong Wook; Kang, Heung Sik

    2000-01-01

    To investigate the usefulness of sonography for the evaluation of osteoarthritic articular cartilage. Ten asymptomatic volunteers and 20 patients with osteoarthritis of the knee underwent sonographic evaluation. For this, the knee was maintained of full flexion in order to expose the deep portion of femoral condylar cartilage. Both transverse and longitudinal scans were obtained in standardized planes. Sonographic images of the articular cartilages were analyzed in terms of surface sharpness, echogenicity and thickness, along with associated bone changes. Normal cartilages showed a clearly-defined surface, homogeneously low echogenicity and regular thickness. Among 20 patients, the findings for medial and lateral condyles, respectively, were as follows: poorly defined cartilage surface, 16 (80%) and ten (50%); increased echogenicity of cartilage, 17 (85%) and 16 (80%); cartilage thinning, 16 (80%) and 14 (70%) (two medial condyles demonstrated obvious cartilage thickening); the presence of thick subchondral hyperechoic bands, five (25%) and four (20%); the presence of osteophytes, 13 (65%) and 12 (60%). Sonography is a convenient and accurate modality for the evaluation of femoral articular cartilage. In particular, it can be useful for detecting early degenerative cartilaginous change and for studying such change during clinical follow-up. (author)

  14. Solute transport across the articular surface of injured cartilage.

    Science.gov (United States)

    Chin, Hooi Chuan; Moeini, Mohammad; Quinn, Thomas M

    2013-07-15

    Solute transport through extracellular matrix (ECM) is important to physiology and contrast agent-based clinical imaging of articular cartilage. Mechanical injury is likely to have important effects on solute transport since it involves alteration of ECM structure. Therefore it is of interest to characterize effects of mechanical injury on solute transport in cartilage. Using cartilage explants injured by an established mechanical compression protocol, effective partition coefficients and diffusivities of solutes for transport across the articular surface were measured. A range of fluorescent solutes (fluorescein isothiocyanate, 4 and 40kDa dextrans, insulin, and chondroitin sulfate) and an X-ray contrast agent (sodium iodide) were used. Mechanical injury was associated with a significant increase in effective diffusivity versus uninjured explants for all solutes studied. On the other hand, mechanical injury had no effects on effective partition coefficients for most solutes tested, except for 40kDa dextran and chondroitin sulfate where small but significant changes in effective partition coefficient were observed in injured explants. Findings highlight enhanced diffusive transport across the articular surface of injured cartilage, which may have important implications for injury and repair situations. Results also support development of non-equilibrium methods for identification of focal cartilage lesions by contrast agent-based clinical imaging. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Repair and tissue engineering techniques for articular cartilage.

    Science.gov (United States)

    Makris, Eleftherios A; Gomoll, Andreas H; Malizos, Konstantinos N; Hu, Jerry C; Athanasiou, Kyriacos A

    2015-01-01

    Chondral and osteochondral lesions due to injury or other pathology commonly result in the development of osteoarthritis, eventually leading to progressive total joint destruction. Although current progress suggests that biologic agents can delay the advancement of deterioration, such drugs are incapable of promoting tissue restoration. The limited ability of articular cartilage to regenerate renders joint arthroplasty an unavoidable surgical intervention. This Review describes current, widely used clinical repair techniques for resurfacing articular cartilage defects; short-term and long-term clinical outcomes of these techniques are discussed. Also reviewed is a developmental pipeline of acellular and cellular regenerative products and techniques that could revolutionize joint care over the next decade by promoting the development of functional articular cartilage. Acellular products typically consist of collagen or hyaluronic-acid-based materials, whereas cellular techniques use either primary cells or stem cells, with or without scaffolds. Central to these efforts is the prominent role that tissue engineering has in translating biological technology into clinical products; therefore, concomitant regulatory processes are also discussed.

  16. A vision on the future of articular cartilage repair

    Directory of Open Access Journals (Sweden)

    M Cucchiarini

    2014-05-01

    Full Text Available An AO Foundation (Davos, Switzerland sponsored workshop "Cell Therapy in Cartilage Repair" from the Symposium "Where Science meets Clinics" (September 5-7, 2013, Davos gathered leaders from medicine, science, industry, and regulatory organisations to debate the vision of cell therapy in articular cartilage repair and the measures that could be taken to narrow the gap between vision and current practice. Cell-based therapy is already in clinical use to enhance the repair of cartilage lesions, with procedures such as microfracture and articular chondrocyte implantation. However, even though long term follow up is good from a clinical perspective and some of the most rigorous randomised controlled trials in the regenerative medicine/orthopaedics field show beneficial effect, none of these options have proved successful in restoring the original articular cartilage structure and functionality in patients so far. With the remarkable recent advances in experimental research in cell biology (new sources for chondrocytes, stem cells, molecular biology (growth factors, genes, biomaterials, biomechanics, and translational science, a combined effort between scientists and clinicians with broad expertise may allow development of an improved cell therapy for cartilage repair. This position paper describes the current state of the art in the field to help define a procedure adapted to the clinical situation for upcoming translation in the patient.

  17. MRI diagnosis of reverse and separation of meniscus articular capsule

    International Nuclear Information System (INIS)

    Tang Xiaofeng; Zhou Chengtao; Mu Renqi; Zhang Guanghui; Xu Yongzhong

    2005-01-01

    Objective: To explore the MR imaging of reverse and separation of meniscal articular capsule. Methods: MR imaging of reverse and separation of meniscus articular capsule confirmed by surgery and arthroscope were analyzed retrospectively in 8 cases. Results: The 'Butterfly knot sign' disappeared and was replaced with fluid signal on the sagittal slice of meniscal body in 8 cases. Part of back angle remained in 3 cases. 'Double anterior cruciate ligament sign' was showed on one side of middle sagittal slice in 7 cases. 'Reverse meniscus sign' was revealed in intercondylar fossa on the coronary view in 8 cases. Abnormal high signal was showed in the injured meniscus in 6 cases. Abnormal high signal was detected in the opposite meniscus in 5 cases. Conclusion: The MR findings of reverse and separation of meniscus articular capsule include disappearance of 'butterfly knot sign', appearance of 'reverse meniscus sign' and 'double anterior cruciate ligament sign'. The diagnosis would be established if the former 2 signs were present or all the 3 signs were present simultaneously. (authors)

  18. Visualization of the extra-articular portion of the long head of the biceps tendon during intra-articular shoulder arthroscopy.

    Science.gov (United States)

    Festa, Anthony; Allert, Jesse; Issa, Kimona; Tasto, James P; Myer, Jonathan J

    2014-11-01

    To quantify the amount of the extra-articular long head of the biceps tendon (LHBT) seen during intra-articular shoulder arthroscopy by pulling the tendon into the joint with a probe through an anterior portal while viewing through a standard posterior portal. Intra-articular shoulder arthroscopy was performed on 10 forequarter cadaveric specimens. The extra-articular portion of the LHBT was evaluated by pulling the tendon into the joint with an arthroscopic probe inserted through an anterior portal. The tendon was marked at the pulley insertion on the humerus with a vascular clip before and after the tendon was pulled into the joint. An open deltopectoral approach was performed, and the amount of extra-articular tendon visualized was calculated as an absolute amount and in relation to nearby anatomic structures. An additional 1.9 cm (range, 1.4 to 2.6 cm) of extra-articular LHBT was viewed by pulling the tendon into the joint with an arthroscopic probe through an anterior portal during shoulder arthroscopy. This represented 30.8% of the extra-articular portion of the tendon, 47.7% of tendon in the bicipital groove, and 76.3% of the tendon that lies under the area from the pulley insertion to the distal edge of the transverse humeral ligament. During intra-articular shoulder arthroscopy, the extra-articular portion of the LHBT is incompletely visualized by pulling the tendon into the joint with a probe placed through an anterior portal while viewing through a standard posterior portal. An additional extra-articular portion of the LHBT may be viewed by pulling the tendon into the joint with an arthroscopic probe during shoulder arthroscopy. Copyright © 2014 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

  19. Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

    Energy Technology Data Exchange (ETDEWEB)

    Manceur, Aziza P. [Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario (Canada); Donnelly Centre, University of Toronto, Toronto, Ontario (Canada); Tseng, Michael [Laboratory of Cellular and Molecular Pathophysiology, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario (Canada); Department of Psychiatry, University of Toronto, Toronto, ON (Canada); Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Holowacz, Tamara [Donnelly Centre, University of Toronto, Toronto, Ontario (Canada); Witterick, Ian [Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Department of Otolaryngology, Head and Neck Surgery, University of Toronto, ON (Canada); Weksberg, Rosanna [Institute of Medical Science, University of Toronto, Toronto, ON (Canada); The Hospital for Sick Children, Research Institute, Program in Genetics and Genomic Biology, Toronto, Ontario Canada (Canada); McCurdy, Richard D. [The Hospital for Sick Children, Research Institute, Program in Genetics and Genomic Biology, Toronto, Ontario Canada (Canada); Warsh, Jerry J. [Laboratory of Cellular and Molecular Pathophysiology, Centre for Addiction and Mental Health (CAMH), University of Toronto, Toronto, Ontario (Canada); Department of Psychiatry, University of Toronto, Toronto, ON (Canada); Institute of Medical Science, University of Toronto, Toronto, ON (Canada); Audet, Julie, E-mail: julie.audet@utoronto.ca [Institute of Biomaterials and Biomedical Engineering (IBBME), University of Toronto, Toronto, Ontario (Canada); Donnelly Centre, University of Toronto, Toronto, Ontario (Canada)

    2011-09-10

    The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B) inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.

  20. Inhibition of glycogen synthase kinase-3 enhances the differentiation and reduces the proliferation of adult human olfactory epithelium neural precursors

    International Nuclear Information System (INIS)

    Manceur, Aziza P.; Tseng, Michael; Holowacz, Tamara; Witterick, Ian; Weksberg, Rosanna; McCurdy, Richard D.; Warsh, Jerry J.; Audet, Julie

    2011-01-01

    The olfactory epithelium (OE) contains neural precursor cells which can be easily harvested from a minimally invasive nasal biopsy, making them a valuable cell source to study human neural cell lineages in health and disease. Glycogen synthase kinase-3 (GSK-3) has been implicated in the etiology and treatment of neuropsychiatric disorders and also in the regulation of murine neural precursor cell fate in vitro and in vivo. In this study, we examined the impact of decreased GSK-3 activity on the fate of adult human OE neural precursors in vitro. GSK-3 inhibition was achieved using ATP-competitive (6-bromoindirubin-3'-oxime and CHIR99021) or substrate-competitive (TAT-eIF2B) inhibitors to eliminate potential confounding effects on cell fate due to off-target kinase inhibition. GSK-3 inhibitors decreased the number of neural precursor cells in OE cell cultures through a reduction in proliferation. Decreased proliferation was not associated with a reduction in cell survival but was accompanied by a reduction in nestin expression and a substantial increase in the expression of the neuronal differentiation markers MAP1B and neurofilament (NF-M) after 10 days in culture. Taken together, these results suggest that GSK-3 inhibition promotes the early stages of neuronal differentiation in cultures of adult human neural precursors and provide insights into the mechanisms by which alterations in GSK-3 signaling affect adult human neurogenesis, a cellular process strongly suspected to play a role in the etiology of neuropsychiatric disorders.

  1. Primary cutaneous marginal zone lymphoma associated with juxta-articular fibrotic nodules in a teenager.

    Science.gov (United States)

    Ghatalia, Pooja; Porter, Joanne; Wroblewski, Danielle; Carlson, John Andrew

    2013-05-01

    Primary cutaneous marginal zone lymphoma (PCMZL) has rarely been reported in teenagers and is occasionally associated with Borrelia burgdorferi infection. Juxta-articular fibrotic nodules represent a unique, localized fibrosing response to spirochete infections, namely Borreliosis. Herein, we report a 15-year-old healthy boy who presented with a 4-year history of progressive acquisition of asymptomatic, erythematous nodules, ≤ 3 cm, beginning with his right forearm (3), then right arm (1) and lastly his right inner thigh (1). Biopsy showed PCMZL in three of five samples, and inflamed, fibrotic nodules, near the elbow in two. The bottom heavy lymphomatous nodules consisted of mostly small CD20+ CD43+ lymphocytes, some with plasmacytoid features. Mature plasma cells were lambda light chain restricted by in situ hybridization. The juxta-articular fibrotic nodules were located in the deep dermis and subcutis, had peripheral plasma cell-rich infiltrates, and showed nodular sclerosis (morphea profunda-like) in one, and lamellar and angiocentric sclerosis in the other reminiscent of quiescent lesions of chronic localized fibrosing leukocytoclastic vasculitis. Immunohistochemistry for B. burgdorferi revealed rare positive organisms; however, polymerase chain reaction (PCR) and serology were negative for B. burgdorferi as were serologic and/or PCR assays for Bartonella henselae, Ba. quintana, Ehrlichia chaffeensis, Treponema pallidum, Helicobacter pylori and Babesia microti. No evidence of extracutaneous disease was found by the review of systems and imaging studies. A 4-week trial of doxycycline therapy failed, whereas intralesional (IL) corticosteroid therapy induced rapid regression of his nodules. After two local recurrences, also treated with IL corticosteroids, he is well, without cutaneous disease, 20 months later. A literature review of 19 pediatric cases PCMZL reveals a similar natural history as adult PCMZL. Despite negative serology and PCR for B. burgdorferi

  2. Antagonistic Mono- and Bi-Articular Lower-Limb Muscle Activities’ Model Characterization at Different Speeds

    Directory of Open Access Journals (Sweden)

    Dzahir M.A.M

    2017-01-01

    Full Text Available Nowadays, medical rehabilitation system has become a requirement due to increment in national rehabilitation centres and medical hospitals. An assistive rehabilitation orthosis becomes essential and was used for rehabilitation therapy, condition monitoring, and physical strengthening. This study focused on the lower limb assistive rehabilitation orthosis development using pneumatic artificial muscle. To successfully control this orthosis system which consists of antagonistic mono- and biarticular muscle actuators, it is necessary to construct a reliable control algorithm. The suitable control scheme and strategy to manoeuvre this orthosis system similar to human musculoskeletal system have yet to be fully developed and established. Based on the review study, it is said that the co-contraction controls of anterior-posterior pneumatic muscles was able to improve the joint stiffness and stability of the orthosis as well as good manoeuvrability. Therefore, a characterization model of an antagonistic mono- and bi-articular muscles activities of human's lowerlimb during walking motion will be necessary. A healthy young male subject was used as test subject to obtain the sEMG muscle activities for antagonistic mono- and bi-articular muscles (i.e., Vastus Medialis-VM, Vastus Lateralis-VL, Rectus Femoris-RF, and Bicep Femoris-BF. The tests were carried out at different speeds of 2km/h, 3km/h, and 4km/h for one minute walking motion on a treadmill. Then, the patterns of the sEMG muscle activities were modelled and characterised using fifth order polynomial equation. Based on the results, it is shown that the anterior and posterior muscles were exhibited a muscle synergy in-between multiple anterior or posterior muscles and muscle co-contraction between anteriorposterior muscles in order to control the movements at the joints during walking motion. As conclusion, it is proven that the sEMG muscle activities of the antagonistic mono- and bi-articular

  3. Articular soft tissue anatomy of the archosaur hip joint: Structural homology and functional implications.

    Science.gov (United States)

    Tsai, Henry P; Holliday, Casey M

    2015-06-01

    Archosaurs evolved a wide diversity of locomotor postures, body sizes, and hip joint morphologies. The two extant archosaurs clades (birds and crocodylians) possess highly divergent hip joint morphologies, and the homologies and functions of their articular soft tissues, such as ligaments, cartilage, and tendons, are poorly understood. Reconstructing joint anatomy and function of extinct vertebrates is critical to understanding their posture, locomotor behavior, ecology, and evolution. However, the lack of soft tissues in fossil taxa makes accurate inferences of joint function difficult. Here, we describe the soft tissue anatomies and their osteological correlates in the hip joint of archosaurs and their sauropsid outgroups, and infer structural homology across the extant taxa. A comparative sample of 35 species of birds, crocodylians, lepidosaurs, and turtles ranging from hatchling to skeletally mature adult were studied using dissection, imaging, and histology. Birds and crocodylians possess topologically and histologically consistent articular soft tissues in their hip joints. Epiphyseal cartilages, fibrocartilages, and ligaments leave consistent osteological correlates. The archosaur acetabulum possesses distinct labrum and antitrochanter structures on the supraacetabulum. The ligamentum capitis femoris consists of distinct pubic- and ischial attachments, and is homologous with the ventral capsular ligament of lepidosaurs. The proximal femur has a hyaline cartilage core attached to the metaphysis via a fibrocartilaginous sleeve. This study provides new insight into soft tissue structures and their osteological correlates (e.g., the antitrochanter, the fovea capitis, and the metaphyseal collar) in the archosaur hip joint. The topological arrangement of fibro- and hyaline cartilage may provide mechanical support for the chondroepiphysis. The osteological correlates identified here will inform systematic and functional analyses of archosaur hindlimb evolution and

  4. MR imaging of canine osteoarthritis shows sustained hypertrophic repair of articular cartilage

    International Nuclear Information System (INIS)

    Braunstein, E.M.; Albrecht, M.; Brandt, K.D.

    1989-01-01

    This paper reports MR imaging used to evaluate cartilage abnormalities in three dogs in which the anterior cruciate ligament (ACL) of one hind limb had been transected to produce osteoarthritis. In this model changes mirror those in human osteoarthritis, but they are not progressive after a few months. The authors performed serial plain radiography and MR imaging of the osteoarthritic knee and control knee 3 years after ACL transection. Coronal T1- weighted images and sagittal multiecho and field echo summed images were obtained. Radiographs showed osteophytes, geodes, and subchondral sclerosis of the operated knees, with no progression between 2 and 3 years. Contralateral knees were normal. On MR images in each case there was indistinctness and thickening of articular cartilage in the abnormal knee compared with the contralateral knee

  5. FASH and MASH: female and male adult human phantoms based on polygon mesh surfaces: I. Development of the anatomy

    Science.gov (United States)

    Cassola, V. F.; de Melo Lima, V. J.; Kramer, R.; Khoury, H. J.

    2010-01-01

    Among computational models, voxel phantoms based on computer tomographic (CT), nuclear magnetic resonance (NMR) or colour photographic images of patients, volunteers or cadavers have become popular in recent years. Although being true to nature representations of scanned individuals, voxel phantoms have limitations, especially when walled organs have to be segmented or when volumes of organs or body tissues, like adipose, have to be changed. Additionally, the scanning of patients or volunteers is usually made in supine position, which causes a shift of internal organs towards the ribcage, a compression of the lungs and a reduction of the sagittal diameter especially in the abdominal region compared to the regular anatomy of a person in the upright position, which in turn can influence organ and tissue absorbed or equivalent dose estimates. This study applies tools developed recently in the areas of computer graphics and animated films to the creation and modelling of 3D human organs, tissues, skeletons and bodies based on polygon mesh surfaces. Female and male adult human phantoms, called FASH (Female Adult meSH) and MASH (Male Adult meSH), have been designed using software, such as MakeHuman, Blender, Binvox and ImageJ, based on anatomical atlases, observing at the same time organ masses recommended by the International Commission on Radiological Protection for the male and female reference adult in report no 89. 113 organs, bones and tissues have been modelled in the FASH and the MASH phantoms representing locations for adults in standing posture. Most organ and tissue masses of the voxelized versions agree with corresponding data from ICRP89 within a margin of 2.6%. Comparison with the mesh-based male RPI_AM and female RPI_AF phantoms shows differences with respect to the material used, to the software and concepts applied, and to the anatomies created.

  6. FASH and MASH: female and male adult human phantoms based on polygon mesh surfaces: I. Development of the anatomy

    International Nuclear Information System (INIS)

    Cassola, V F; Kramer, R; Khoury, H J; De Melo Lima, V J

    2010-01-01

    Among computational models, voxel phantoms based on computer tomographic (CT), nuclear magnetic resonance (NMR) or colour photographic images of patients, volunteers or cadavers have become popular in recent years. Although being true to nature representations of scanned individuals, voxel phantoms have limitations, especially when walled organs have to be segmented or when volumes of organs or body tissues, like adipose, have to be changed. Additionally, the scanning of patients or volunteers is usually made in supine position, which causes a shift of internal organs towards the ribcage, a compression of the lungs and a reduction of the sagittal diameter especially in the abdominal region compared to the regular anatomy of a person in the upright position, which in turn can influence organ and tissue absorbed or equivalent dose estimates. This study applies tools developed recently in the areas of computer graphics and animated films to the creation and modelling of 3D human organs, tissues, skeletons and bodies based on polygon mesh surfaces. Female and male adult human phantoms, called FASH (Female Adult meSH) and MASH (Male Adult meSH), have been designed using software, such as MakeHuman, Blender, Binvox and ImageJ, based on anatomical atlases, observing at the same time organ masses recommended by the International Commission on Radiological Protection for the male and female reference adult in report no 89. 113 organs, bones and tissues have been modelled in the FASH and the MASH phantoms representing locations for adults in standing posture. Most organ and tissue masses of the voxelized versions agree with corresponding data from ICRP89 within a margin of 2.6%. Comparison with the mesh-based male RPI A M and female RPI A F phantoms shows differences with respect to the material used, to the software and concepts applied, and to the anatomies created.

  7. Characterization of Insulin-Immunoreactive Cells and Endocrine Cells Within the Duct System of the Adult Human Pancreas.

    Science.gov (United States)

    Li, Rong; Zhang, Xiaoxi; Yu, Lan; Zou, Xia; Zhao, Hailu

    2016-01-01

    The adult pancreatic duct system accommodates endocrine cells that have the potential to produce insulin. Here we report the characterization and distribution of insulin-immunoreactive cells and endocrine cells within the ductal units of adult human pancreas. Sequential pancreas sections from 12 nondiabetic adults were stained with biomarkers of ductal epithelial cells (cytokeratin 19), acinar cells (amylase), endocrine cells (chromogranin A; neuron-specific enolase), islet hormones (insulin, glucagon, somatostatin, pancreatic polypeptide), cell proliferation (Ki-67), and neogenesis (CD29). The number of islet hormone-immunoreactive cells increased from large ducts to the terminal branches. The insulin-producing cells outnumbered endocrine cells reactive for glucagon, somatostatin, or pancreatic polypeptide. The proportions of insulin-immunoreactive count compared with local islets (100% as a baseline) were 1.5% for the main ducts, 7.2% for interlobular ducts, 24.8% for intralobular ducts, 67.9% for intercalated ducts, and 348.9% for centroacinar cells. Both Ki-67- and CD29-labeled cells were predominantly localized in the terminal branches around the islets. The terminal branches also showed cells coexpressing islet hormones and cytokeratin 19. The adult human pancreatic ducts showed islet hormone-producing cells. The insulin-reactive cells predominantly localized in terminal branches where they may retain potential capability for β-cell neogenesis.

  8. Short-acting insulin analogues versus regular human insulin for adults with type 1 diabetes mellitus.

    Science.gov (United States)

    Fullerton, Birgit; Siebenhofer, Andrea; Jeitler, Klaus; Horvath, Karl; Semlitsch, Thomas; Berghold, Andrea; Plank, Johannes; Pieber, Thomas R; Gerlach, Ferdinand M

    2016-06-30

    Short-acting insulin analogue use for people with diabetes is still controversial, as reflected in many scientific debates. To assess the effects of short-acting insulin analogues versus regular human insulin in adults with type 1 diabetes. We carried out the electronic searches through Ovid simultaneously searching the following databases: Ovid MEDLINE(R), Ovid MEDLINE(R) In-Process & Other Non-Indexed Citations, Ovid MEDLINE(R) Daily and Ovid OLDMEDLINE(R) (1946 to 14 April 2015), EMBASE (1988 to 2015, week 15), the Cochrane Central Register of Controlled Trials (CENTRAL; March 2015), ClinicalTrials.gov and the European (EU) Clinical Trials register (both March 2015). We included all randomised controlled trials with an intervention duration of at least 24 weeks that compared short-acting insulin analogues with regular human insulins in the treatment of adults with type 1 diabetes who were not pregnant. Two review authors independently extracted data and assessed trials for risk of bias, and resolved differences by consensus. We graded overall study quality using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) instrument. We used random-effects models for the main analyses and presented the results as odds ratios (OR) with 95% confidence intervals (CI) for dichotomous outcomes. We identified nine trials that fulfilled the inclusion criteria including 2693 participants. The duration of interventions ranged from 24 to 52 weeks with a mean of about 37 weeks. The participants showed some diversity, mainly with regard to diabetes duration and inclusion/exclusion criteria. The majority of the trials were carried out in the 1990s and participants were recruited from Europe, North America, Africa and Asia. None of the trials was carried out in a blinded manner so that the risk of performance bias, especially for subjective outcomes such as hypoglycaemia, was present in all of the trials. Furthermore, several trials showed inconsistencies in

  9. Foetal and adult human CYP3A isoforms in the bioactivation of organophosphorothionate insecticides.

    Science.gov (United States)

    Buratti, Franca M; Leoni, Claudia; Testai, Emanuela

    2006-12-15

    In humans organophosphorothionate pesticides (OPT) prenatal exposure has been demonstrated. Since OPT-induced neurodevelopmental effects may be due to in situ bioactivation by foetal enzymes, the catalytic activity of the foetal CYP3A7 toward chlorpyrifos (CPF), parathion (PAR), malathion (MAL) and fenthion (FEN) has been assessed by using recombinant enzymes. A comparison with the adult isoforms CYP3A4 and CYP3A5 has been also carried out. CYP3A7 was able to produce significant levels of oxon or sulfoxide from the four OPTs in the range of tested concentrations (0.05-200 microM). When the efficiencies of CYP3A isoforms were compared, the ranking, expressed as CLi values, were: CPF=3A4>3A5>3A7; PAR=3A4>3A7>3A5; MAL=3A4>3A7>3A5; FEN (sulfoxide formation)=3A4>3A5>3A7. The CYP3A5 efficiency appeared to be more dependent on the single insecticide than its related isozyme CYP3A4. Our results indicate that the levels of toxic metabolite formed in situ by CYP3A7 from CPF, MAL and PAR but not from FEN have the chance to inhibit acetylcholinesterase, following prenatal exposure to OPTs. However, due to the smaller weight of foetal liver, the contribution to total OPT biotransformation is relatively low. On the other hand, our results clearly indicate that at low CPF concentrations, the formation of the non-toxic metabolites is highly favoured in the foetus.

  10. Applied anatomic study of testicular veins in adult cadavers and in human fetuses

    Directory of Open Access Journals (Sweden)

    Luciano A. Favorito

    2007-04-01

    Full Text Available OBJECTIVES: Analyze the anatomic variations of the testicular veins in human cadavers and fetuses. MATERIALS AND METHODS: One hundred male adult cadavers and 24 fetuses were studied. Four anatomic aspects were considered: 1 Number of testicular veins, 2 The local of vein termination, 3 Type and number of collaterals present and 4 Testicular vein termination angle. RESULTS: Cadavers - Right side - One testicular vein occurred in 85% and 2 veins in 5% of the cases. There were communicating veins with the colon in 21% of the cases. Left side - One testicular vein occurred in 82%, two veins in 15%, three veins in 2% and four veins in 1% of the cases. There were communicating veins with the colon in 31% of the cases. Fetuses - Right side -One testicular vein occurred in all cases. This vein drained to the vena cava in 83.3% of the cases, to the junction of the vena cava with the renal vein in 12.5% and to the renal vein in 4.2%. There were communicating veins with the colon in 25% of the cases. Left side - One testicular vein occurred in 66.6% of the cases, and 2 veins in occurred 33.3%. Communicating veins with the colon were found in 41.6% of the cases. CONCLUSION: The testicular vein presents numeric variations and also variations in its local of termination. In approximately 30% of the cases, there are collaterals that communicate the testicular vein with retroperitoneal veins. These anatomic findings can help understanding the origin of varicocele and its recurrence after surgical interventions.

  11. The pharmacokinetic profile of crocetin in healthy adult human volunteers after a single oral administration.

    Science.gov (United States)

    Umigai, N; Murakami, K; Ulit, M V; Antonio, L S; Shirotori, M; Morikawa, H; Nakano, T

    2011-05-15

    Crocetin, a unique carotenoid with a short carbon chain length, is an active compound of saffron and Gardenia jasminoides Ellis used as traditional herbal medicine. The present study was undertaken to investigate the pharmacokinetic profiles of crocetin in healthy adult subjects. The study was conducted as an open-label, single dose escalation with 10 Filipino volunteers (5 men and 5 women). The subjects received a single dose of crocetin at three doses (7.5, 15 and 22.5 mg) in one week interval. Blood samples were collected from the brachial vein before and at 1, 2, 4, 6, 8, 10 and 24 h after administration. Plasma concentrations of crocetin were determined by high-performance liquid chromatography (HPLC). Crocetin was rapidly absorbed and detected within an hour of administration with a mean time to reach maximum concentration (T(max)) of crocetin ranging from 4.0 to 4.8 h. The mean values of C(max) and AUC(0-24h) ranged from 100.9 to 279.7 ng/ml and 556.5 to 1720.8 ng. h/ml respectively. C(max) and AUC values increased with dose proportional manner. Crocetin was eliminated from human plasma with a mean elimination half life (T(½) of 6.1 to 7.5 h. In summary, there were no serious adverse events up to 22.5 mg dose of crocetin while crocetin was found to be absorbed more quickly than the other carotenoids such as β-carotene, lutein and lycopene. Copyright © 2010 Elsevier GmbH. All rights reserved.

  12. Sulcal pattern, extension, and morphology of the precuneus in adult humans.

    Science.gov (United States)

    Pereira-Pedro, Ana Sofia; Bruner, Emiliano

    2016-11-01

    The precuneus represents a relevant cortical component of the parietal lobes. It is involved in visuospatial integration, imagery and simulation, self-awareness, and it is a main node of the Default Mode Network. Its morphology is extremely variable among adult humans, and it has been hypothesized to have undergone major morphological changes in the evolution of Homo sapiens. Recent studies have evidenced a marked variation also associated with its sulcal patterns. The present survey contributes to add further information on this topic, investigating the extension of its main folds, their geometrical influence on the lateral parietal areas, and the relationships with the sulcal schemes. The subparietal sulcus, on average, extends 14mm in its anterior and middle regions and 11mm in its posterior area. The precuneal area extends 36mm above this sulcus. The subparietal sulcus is generally wider on the right hemisphere. Males have larger values than females, but differences are not significant. Sulcal pattern is not correlated with the size of the subparietal sulcus extension. There is a lack of consistent correspondence between hemispheres in the sulcal patterns, pointing further towards a notable individual variability and random asymmetries. The vertical extension of the precuneus influences the height and proportions of the upper parietal profile, but the lateral parietal outline is not sensitive to precuneal variation. There is no correlation between external cortical shape and the size of the subparietal sulcus. Morphological analyses of the precuneus must be integrated with studies on histological factors involved in its variability and, ultimately, with analyses on possible relationships with functional factors. Copyright © 2016 Elsevier GmbH. All rights reserved.

  13. Plasmid-based generation of induced neural stem cells from adult human fibroblasts

    Directory of Open Access Journals (Sweden)

    Philipp Capetian

    2016-10-01

    Full Text Available Direct reprogramming from somatic to neural cell types has become an alternative to induced pluripotent stem cells. Most protocols employ viral expression systems, posing the risk of random genomic integration. Recent developments led to plasmid-based protocols, lowering this risk. However, these protocols either relied on continuous presence of a variety of small molecules or were only able to reprogram murine cells. We therefore established a reprogramming protocol based on vectors containing the Epstein-Barr virus (EBV-derived oriP/EBNA1 as well as the defined expression factors Oct3/4, Sox2, Klf4, L-myc, Lin28, and a small hairpin directed against p53. We employed a defined neural medium in combination with the neurotrophins bFGF, EGF and FGF4 for cultivation without the addition of small molecules. After reprogramming, cells demonstrated a temporary increase in the expression of endogenous Oct3/4. We obtained induced neural stem cells (iNSC 30 days after transfection. In contrast to previous results, plasmid vectors as well as a residual expression of reprogramming factors remained detectable in all cell lines. Cells showed a robust differentiation into neuronal (72% and glial cells (9% astrocytes, 6% oligodendrocytes. Despite the temporary increase of pluripotency-associated Oct3/4 expression during reprogramming, we did not detect pluripotent stem cells or non-neural cells in culture (except occasional residual fibroblasts. Neurons showed electrical activity and functional glutamatergic synapses. Our results demonstrate that reprogramming adult human fibroblasts to iNSC by plasmid vectors and basic neural medium without small molecules is possible and feasible. However, a full set of pluripotency-associated transcription factors may indeed result in the acquisition of a transient (at least partial pluripotent intermediate during reprogramming. In contrast to previous reports, the EBV-based plasmid system remained present and active inside

  14. Low/Negative Expression of PDGFR-α Identifies the Candidate Primary Mesenchymal Stromal Cells in Adult Human Bone Marrow

    Directory of Open Access Journals (Sweden)

    Hongzhe Li

    2014-12-01

    Full Text Available Human bone marrow (BM contains a rare population of nonhematopoietic mesenchymal stromal cells (MSCs, which are of central importance for the hematopoietic microenvironment. However, the precise phenotypic definition of these cells in adult BM has not yet been reported. In this study, we show that low/negative expression of CD140a (PDGFR-α on lin−/CD45−/CD271+ BM cells identified a cell population with very high MSC activity, measured as fibroblastic colony-forming unit frequency and typical in vitro and in vivo stroma formation and differentiation capacities. Furthermore, these cells exhibited high levels of genes associated with mesenchymal lineages and HSC supportive function. Moreover, lin−/CD45−/CD271+/CD140alow/− cells effectively mediated the ex vivo expansion of transplantable CD34+ hematopoietic stem cells. Taken together, these data indicate that CD140a is a key negative selection marker for adult human BM-MSCs, which enables to prospectively isolate a close to pure population of candidate human adult stroma stem/progenitor cells with potent hematopoiesis-supporting capacity.

  15. Adult Continuing Education and Human Resource Development: Present Competitors, Potential Partners

    Science.gov (United States)

    Smith, Douglas H.

    2013-01-01

    "Author's Note": In May 1989, this article was published in "Livelong Learning," the monthly practitioner journal of the American Association for Adult and Continuing Education (Vol. 12, No. 7, pp. 13-17). Now viewed as a period reference article, it presents the relationship of adult and continuing education (ACE) and…

  16. Estimated Human and Economic Burden of Four Major Adult Vaccine-Preventable Diseases in the United States, 2013.

    Science.gov (United States)

    McLaughlin, John M; McGinnis, Justin J; Tan, Litjen; Mercatante, Annette; Fortuna, Joseph

    2015-08-01

    Low uptake of routinely recommended adult immunizations is a public health concern. Using data from the peer-reviewed literature, government disease-surveillance programs, and the US Census, we developed a customizable model to estimate human and economic burden caused by four major adult vaccine-preventable diseases (VPD) in 2013 in the United States, and for each US state individually. To estimate the number of cases for each adult VPD for a given population, we multiplied age-specific incidence rates obtained from the literature by age-specific 2013 Census population data. We then multiplied the estimated number of cases for a given population by age-specific, estimated medical and indirect (non-medical) costs per case. Adult VPDs examined were: (1) influenza, (2) pneumococcal disease (both invasive disease and pneumonia), (3) herpes zoster (shingles), and (4) pertussis (whooping cough). Sensitivity analyses simulated the impact of various epidemiological scenarios on the total estimated economic burden. Estimated US annual cost for the four adult VPDs was $26.5 billion (B) among adults aged 50 years and older, $15.3B (58 %) of which was attributable to those 65 and older. Among adults 50 and older, influenza, pneumococcal disease, herpes zoster, and pertussis made up $16.0B (60 %), $5.1B (19 %), $5.0B (19 %), and $0.4B (2 %) of the cost, respectively. Among those 65 and older, they made up $8.3B (54 %), $3.8B (25 %), $3.0B (20 %), and 0.2B (1 %) of the cost, respectively. Most (80-85 %) pneumococcal costs stemmed from nonbacteremic pneumococcal pneumonia (NPP). Cost attributable to adult VPD in the United States is substantial. Broadening adult immunization efforts beyond influenza only may help reduce the economic burden of adult VPD, and a pneumococcal vaccination effort, primarily focused on reducing NPP, may constitute a logical starting place. Sensitivity analyses revealed that a pandemic influenza season or change in size of the US elderly population

  17. Comparison of hyaluronic acid and PRP intra-articular injection with combined intra-articular and intraosseous PRP injections to treat patients with knee osteoarthritis.

    Science.gov (United States)

    Su, Ke; Bai, Yuming; Wang, Jun; Zhang, Haisen; Liu, Hao; Ma, Shiyun

    2018-05-01

    The aim of this study was to evaluate the benefit provided by intraosseous infiltration combined with intra-articular injection of platelet-rich plasma to treat mild and moderate stages of knee joint degeneration (Kellgren-Lawrence score II-III) compared with other treatments, specifically intra-articular injection of PRP and of HA. Eighty-six patients with grade II to grade III knee OA according to the Kellgren-Lawrence classification were randomly assigned to intra-articular combined with intraosseous injection of PRP (group A), intra-articular PRP (group B), or intra-articular HA (group C). Patients in group A received intra-articular combined with intraosseous injection of PRP (administered twice, 2 weeks apart). Patients in group B received intra-articular injection of PRP every 14 days. Patients in group C received a series of five intra-articular injections of HA every 7 days. All patients were evaluated using the Visual Analogue Scale (VAS) and Western Ontario and McMaster Universities (WOMAC) score before the treatment and at 1, 3, 6, 12, and 18 months after treatment. There were significant improvements at the end of the 1st month. Notably, group A patients had significantly superior VAS and WOMAC scores than were observed in groups B and C. The VAS scores were similar in groups B and group C after the 6th month. Regarding the WOMAC scores, groups B and C differed at the 1st, 3rd, 6th, and 12th months; however, no significant difference was observed at the 18th month. The combination of intraosseous with intra-articular injections of PRP resulted in a significantly superior clinical outcome, with sustained lower VAS and WOMAC scores and improvement in quality of life within 18 months.

  18. Intraarticular and intravenous administration of 99MTc-HMPAO-labeled human mesenchymal stem cells (99MTC-AH-MSCS): In vivo imaging and biodistribution

    International Nuclear Information System (INIS)

    Meseguer-Olmo, Luis; Montellano, Antonio Jesús; Martínez, Teresa; Martínez, Carlos M.; Revilla-Nuin, Beatriz; Roldán, Marta; Mora, Cristina Fuente; López-Lucas, Maria Dolores; Fuente, Teodomiro

    2017-01-01

    Introduction: Therapeutic application of intravenous administered (IV) human bone marrow-derived mesenchymal stem cells (ahMSCs) appears to have as main drawback the massive retention of cells in the lung parenchyma, questioning the suitability of this via of administration. Intraarticular administration (IAR) could be considered as an alternative route for therapy in degenerative and traumatic joint lesions. Our work is outlined as a comparative study of biodistribution of 99m Tc-ahMSCs after IV and IAR administration, via scintigraphic study in an animal model. Methods: Isolated primary culture of adult human mesenchymal stem cells was labeled with 99m Tc-HMPAO for scintigraphic study of in vivo distribution after intravenous and intra-articular (knee) administration in rabbits. Results: IV administration of radiolabeled ahMSCs showed the bulk of radioactivity in the lung parenchyma while IAR images showed activity mainly in the injected cavity and complete absence of uptake in pulmonary bed. Conclusions: Our study shows that IAR administration overcomes the limitations of IV injection, in particular, those related to cells destruction in the lung parenchyma. After IAR administration, cells remain within the joint cavity, as expected given its size and adhesion properties. Advances in knowledge: Intra-articular administration of adult human mesenchymal stem cells could be a suitable route for therapeutic effect in joint lesions. Implications for patient care: Local administration of adult human mesenchymal stem cells could improve their therapeutic effects, minimizing side effects in patients.

  19. Disposition of isoflupredone acetate in plasma, urine and synovial fluid following intra-articular administration to exercised Thoroughbred horses.

    Science.gov (United States)

    Knych, Heather K; Harrison, Linda M; White, Alexandria; McKemie, Daniel S

    2016-01-01

    The use of isoflupredone acetate in performance horses and the scarcity of published pharmacokinetic data necessitate further study. The objective of the current study was to describe the plasma pharmacokinetics of isoflupredone acetate as well as time-related urine and synovial fluid concentrations following intra-articular administration to horses. Twelve racing-fit adult Thoroughbred horses received a single intra-articular administration (8 mg) of isoflupredone acetate into the right antebrachiocarpal joint. Blood, urine and synovial fluid samples were collected prior to and at various times up to 28 days post drug administration. All samples were analyzed using liquid chromatography-Mass Spectrometry. Plasma data were analyzed using a population pharmacokinetic compartmental model. Maximum measured plasma isoflupredone concentrations were 1.76 ± 0.526 ng/mL at 4.0 ± 1.31 h and 1.63 ± 0.243 ng/mL at 4.75 ± 0.5 h, respectively, for horses that had synovial fluid collected and for those that did not. The plasma beta half-life was 24.2 h. Isoflupredone concentrations were below the limit of detection in all horses by 48 h and 7 days in plasma and urine, respectively. Isoflupredone was detected in the right antebrachiocarpal and middle carpal joints for 8.38 ± 5.21 and 2.38 ± 0.52 days, respectively. Results of this study provide information that can be used to regulate the use of intra-articular isoflupredone in the horse. Copyright © 2015 John Wiley & Sons, Ltd.

  20. Disposition of methylprednisolone acetate in plasma, urine, and synovial fluid following intra-articular administration to exercised thoroughbred horses.

    Science.gov (United States)

    Knych, H K; Harrison, L M; Casbeer, H C; McKemie, D S

    2014-04-01

    Methylprednisolone acetate (MPA) is commonly administered to performance horses, and therefore, establishing appropriate withdrawal times prior to performance is critical. The objectives of this study were to describe the plasma pharmacokinetics of MPA and time-related urine and synovial fluid concentrations following intra-articular administration to sixteen racing fit adult Thoroughbred horses. Horses received a single intra-articular administration of MPA (100 mg). Blood, urine, and synovial fluid samples were collected prior to and at various times up to 77 days postdrug administration and analyzed using tandem liquid chromatography-mass spectrometry (LC-MS/MS). Maximum measured plasma MPA concentrations were 6.06 ± 1.57 at 0.271 days (6.5 h; range: 5.0-7.92 h) and 6.27 ± 1.29 ng/mL at 0.276 days (6.6 h; range: 4.03-12.0 h) for horses that had synovial fluid collected (group 1) and those that did not (group 2), respectively. The plasma terminal half-life was 1.33 ± 0.80 and 0.843 ± 0.414 days for groups 1 and 2, respectively. MPA was undetectable by day 6.25 ± 2.12 (group 1) and 4.81 ± 2.56 (group 2) in plasma and day 17 (group 1) and 14 (group 2) in urine. MPA concentrations in synovial fluid remained above the limit of detection (LOD) for up to 77 days following intra-articular administration, suggesting that plasma and urine concentrations are not a good indicator of synovial fluid concentrations. © 2013 John Wiley & Sons Ltd.

  1. Sensitive Tumorigenic Potential Evaluation of Adult Human Multipotent Neural Cells Immortalized by hTERT Gene Transduction.

    Directory of Open Access Journals (Sweden)

    Kee Hang Lee

    Full Text Available Stem cells and therapeutic genes are emerging as a new therapeutic approach to treat various neurodegenerative diseases with few effective treatment options. However, potential formation of tumors by stem cells has hampered their clinical application. Moreover, adequate preclinical platforms to precisely test tumorigenic potential of stem cells are controversial. In this study, we compared the sensitivity of various animal models for in vivo stem cell tumorigenicity testing to identify the most sensitive platform. Then, tumorigenic potential of adult human multipotent neural cells (ahMNCs immortalized by the human telomerase reverse transcriptase (hTERT gene was examined as a stem cell model with therapeutic genes. When human glioblastoma (GBM cells were injected into adult (4-6-week-old Balb/c-nu, adult NOD/SCID, adult NOG, or neonate (1-2-week-old NOG mice, the neonate NOG mice showed significantly faster tumorigenesis than that of the other groups regardless of intracranial or subcutaneous injection route. Two kinds of ahMNCs (682TL and 779TL were primary cultured from surgical samples of patients with temporal lobe epilepsy. Although the ahMNCs were immortalized by lentiviral hTERT gene delivery (hTERT-682TL and hTERT-779TL, they did not form any detectable masses, even in the most sensitive neonate NOG mouse platform. Moreover, the hTERT-ahMNCs had no gross chromosomal abnormalities on a karyotype analysis. Taken together, our data suggest that neonate NOG mice could be a sensitive animal platform to test tumorigenic potential of stem cell therapeutics and that ahMNCs could be a genetically stable stem cell source with little tumorigenic activity to develop regenerative treatments for neurodegenerative diseases.

  2. Dynamic of distribution of human bone marrow-derived mesenchymal stem cells after transplantation into adult unconditioned mice.

    Science.gov (United States)

    Allers, Carolina; Sierralta, Walter D; Neubauer, Sonia; Rivera, Francisco; Minguell, José J; Conget, Paulette A

    2004-08-27

    The use of mesenchymal stem cells (MSC) for cell therapy relies on their capacity to engraft and survive long-term in the appropriate target tissue(s). Animal models have demonstrated that the syngeneic or xenogeneic transplantation of MSC results in donor engraftment into the bone marrow and other tissues of conditioned recipients. However, there are no reliable data showing the fate of human MSC infused into conditioned or unconditioned adult recipients. In the present study, the authors investigated, by using imaging, polymerase chain reaction (PCR), and in situ hybridization, the biodistribution of human bone marrow-derived MSC after intravenous infusion into unconditioned adult nude mice. As assessed by imaging (gamma camera), PCR, and in situ hybridization analysis, the authors' results demonstrate the presence of human MSC in bone marrow, spleen, and mesenchymal tissues of recipient mice. These results suggest that human MSC transplantation into unconditioned recipients represents an option for providing cellular therapy and avoids the complications associated with drugs or radiation conditioning.

  3. Quantitative magnetic resonance imaging of articular cartilage in osteoarthritis

    Directory of Open Access Journals (Sweden)

    G Blumenkrantz

    2007-05-01

    Full Text Available Magnetic resonance imaging of articular cartilage has recently been recognized as a tool for the characterization of cartilage morphology, biochemistry and function. In this paper advancements in cartilage imaging, computation of cartilage volume and thickness, and measurement of relaxation times (T2 and T1Ρ are presented. In addition, the delayed uptake of Gadolinium DTPA as a marker of proteoglycan depletion is also reviewed. The cross-sectional and longitudinal studies using these imaging techniques show promise for cartilage assessment and for the study of osteoarthritis.

  4. Impact of antibiotic use in adult dairy cows on antimicrobial resistance of veterinary and human pathogens: a comprehensive review.

    Science.gov (United States)

    Oliver, Stephen P; Murinda, Shelton E; Jayarao, Bhushan M

    2011-03-01

    Antibiotics have saved millions of human lives, and their use has contributed significantly to improving human and animal health and well-being. Use of antibiotics in food-producing animals has resulted in healthier, more productive animals; lower disease incidence and reduced morbidity and mortality in humans and animals; and production of abundant quantities of nutritious, high-quality, and low-cost food for human consumption. In spite of these benefits, there is considerable concern from public health, food safety, and regulatory perspectives about the use of antimicrobials in food-producing animals. Over the last two decades, development of antimicrobial resistance resulting from agricultural use of antibiotics that could impact treatment of diseases affecting the human population that require antibiotic intervention has become a significant global public health concern. In the present review, we focus on antibiotic use in lactating and nonlactating cows in U.S. dairy herds, and address four key questions: (1) Are science-based data available to demonstrate antimicrobial resistance in veterinary pathogens that cause disease in dairy cows associated with use of antibiotics in adult dairy cows? (2) Are science-based data available to demonstrate that antimicrobial resistance in veterinary pathogens that cause disease in adult dairy cows impacts pathogens that cause disease in humans? (3) Does antimicrobial resistance impact the outcome of therapy? (4) Are antibiotics used prudently in the dairy industry? On the basis of this review, we conclude that scientific evidence does not support widespread, emerging resistance among pathogens isolated from dairy cows to antibacterial drugs even though many of these antibiotics have been used in the dairy industry for treatment and prevention of disease for several decades. However, it is clear that use of antibiotics in adult dairy cows and other food-producing animals does contribute to increased antimicrobial resistance

  5. Adult and Non-Formal Education: An Imperative for Human Capacity ...

    African Journals Online (AJOL)

    DR Nneka

    capacity development could be defined as the development of a workforce .... and the community and between theory and practice in Adult Education, ... ANFE provides education for women in order to empower them, enable them gain.

  6. Neurons from the adult human dentate nucleus: neural networks in the neuron classification.

    Science.gov (United States)

    Grbatinić, Ivan; Marić, Dušica L; Milošević, Nebojša T

    2015-04-07

    Topological (central vs. border neuron type) and morphological classification of adult human dentate nucleus neurons according to their quantified histomorphological properties using neural networks on real and virtual neuron samples. In the real sample 53.1% and 14.1% of central and border neurons, respectively, are classified correctly with total of 32.8% of misclassified neurons. The most important result present 62.2% of misclassified neurons in border neurons group which is even greater than number of correctly classified neurons (37.8%) in that group, showing obvious failure of network to classify neurons correctly based on computational parameters used in our study. On the virtual sample 97.3% of misclassified neurons in border neurons group which is much greater than number of correctly classified neurons (2.7%) in that group, again confirms obvious failure of network to classify neurons correctly. Statistical analysis shows that there is no statistically significant difference in between central and border neurons for each measured parameter (p>0.05). Total of 96.74% neurons are morphologically classified correctly by neural networks and each one belongs to one of the four histomorphological types: (a) neurons with small soma and short dendrites, (b) neurons with small soma and long dendrites, (c) neuron with large soma and short dendrites, (d) neurons with large soma and long dendrites. Statistical analysis supports these results (pneurons can be classified in four neuron types according to their quantitative histomorphological properties. These neuron types consist of two neuron sets, small and large ones with respect to their perykarions with subtypes differing in dendrite length i.e. neurons with short vs. long dendrites. Besides confirmation of neuron classification on small and large ones, already shown in literature, we found two new subtypes i.e. neurons with small soma and long dendrites and with large soma and short dendrites. These neurons are

  7. Of mice, men and elephants: the relation between articular cartilage thickness and body mass.

    Directory of Open Access Journals (Sweden)

    Jos Malda

    Full Text Available Mammalian articular cartilage serves diverse functions, including shock absorption, force transmission and enabling low-friction joint motion. These challenging requirements are met by the tissue's thickness combined with its highly specific extracellular matrix, consisting of a glycosaminoglycan-interspersed collagen fiber network that provides a unique combination of resilience and high compressive and shear resistance. It is unknown how this critical tissue deals with the challenges posed by increases in body mass. For this study, osteochondral cores were harvested post-mortem from the central sites of both medial and lateral femoral condyles of 58 different mammalian species ranging from 25 g (mouse to 4000 kg (African elephant. Joint size and cartilage thickness were measured and biochemical composition (glycosaminoclycan, collagen and DNA content and collagen cross-links densities were analyzed. Here, we show that cartilage thickness at the femoral condyle in the mammalian species investigated varies between 90 µm and 3000 µm and bears a negative allometric relationship to body mass, unlike the isometric scaling of the skeleton. Cellular density (as determined by DNA content decreases with increasing body mass, but gross biochemical composition is remarkably constant. This however need not affect life-long performance of the tissue in heavier mammals, due to relatively constant static compressive stresses, the zonal organization of the tissue and additional compensation by joint congruence, posture and activity pattern of larger mammals. These findings provide insight in the scaling of articular cartilage thickness with body weight, as well as in cartilage biochemical composition and cellularity across mammalian species. They underscore the need for the use of appropriate in vivo models in translational research aiming at human applications.

  8. Of Mice, Men and Elephants: The Relation between Articular Cartilage Thickness and Body Mass

    Science.gov (United States)

    Malda, Jos; de Grauw, Janny C.; Benders, Kim E. M.; Kik, Marja J. L.; van de Lest, Chris H. A.; Creemers, Laura B.; Dhert, Wouter J. A.; van Weeren, P. René

    2013-01-01

    Mammalian articular cartilage serves diverse functions, including shock absorption, force transmission and enabling low-friction joint motion. These challenging requirements are met by the tissue’s thickness combined with its highly specific extracellular matrix, consisting of a glycosaminoglycan-interspersed collagen fiber network that provides a unique combination of resilience and high compressive and shear resistance. It is unknown how this critical tissue deals with the challenges posed by increases in body mass. For this study, osteochondral cores were harvested post-mortem from the central sites of both medial and lateral femoral condyles of 58 different mammalian species ranging from 25 g (mouse) to 4000 kg (African elephant). Joint size and cartilage thickness were measured and biochemical composition (glycosaminoclycan, collagen and DNA content) and collagen cross-links densities were analyzed. Here, we show that cartilage thickness at the femoral condyle in the mammalian species investigated varies between 90 µm and 3000 µm and bears a negative allometric relationship to body mass, unlike the isometric scaling of the skeleton. Cellular density (as determined by DNA content) decreases with increasing body mass, but gross biochemical composition is remarkably constant. This however need not affect life-long performance of the tissue in heavier mammals, due to relatively constant static compressive stresses, the zonal organization of the tissue and additional compensation by joint congruence, posture and activity pattern of larger mammals. These findings provide insight in the scaling of articular cartilage thickness with body weight, as well as in cartilage biochemical composition and cellularity across mammalian species. They underscore the need for the use of appropriate in vivo models in translational research aiming at human applications. PMID:23437402

  9. Expression of FGFR3 during human testis development and in germ cell-derived tumours of young adults.

    Science.gov (United States)

    Ewen, Katherine A; Olesen, Inge A; Winge, Sofia B; Nielsen, Ana R; Nielsen, John E; Graem, Niels; Juul, Anders; Rajpert-De Meyts, Ewa

    2013-01-01

    Observations in patients with an activating mutation of fibroblast growth factor receptor 3 (FGFR3) suggest a role for FGFR3 signalling in promoting proliferation or survival of germ cells. In this study, we aimed to identify the FGFR3 subtype and the ontogeny of expression during human testis development and to ascertain whether FGFR3 signalling is linked to germ cell proliferation and the pathogenesis of testicular germ cell tumours (TGCTs) of young adult men. Using RT-PCR, immunohistochemistry and Western blotting, we examined 58 specimens of human testes throughout development for FGFR3 expression, and then compared expression of FGFR3 with proliferation markers (PCNA or Ki67). We also analysed for FGFR3 expression 30 TGCTs and 28 testes containing the tumour precursor cell, carcinoma in situ (CIS). Fetal and adult testes expressed exclusively the FGFR3IIIc isoform. FGFR3 protein expression was restricted to the cytoplasm/plasma membrane of spermatogonia and was most prevalent at mid-gestation, infancy and from puberty onwards. Phosphorylated (p)FGFR was detected in pre-spermatogonia at mid-gestation and in spermatogonia during puberty and in the adult testis. Throughout normal human testis development, expression of FGFR3 did not directly correlate with proliferation markers. In preinvasive CIS cells and in TGCTs, including classical seminoma and embryonal carcinoma, FGFR3IIIc was detected only in a small number of cells, with a heterogeneous expression pattern. FGFR3 is an excellent marker for human pre-/spermatogonia throughout development. Signalling through this receptor is likely associated with spermatogonial survival rather than proliferation. FGFR3 is not expressed in gonocytes and may not be essential to the aetiology of TGCTs stemming from CIS.

  10. Widespread epigenomic, transcriptomic and proteomic differences between hip osteophytic and articular chondrocytes in osteoarthritis.

    Science.gov (United States)

    Steinberg, Julia; Brooks, Roger A; Southam, Lorraine; Bhatnagar, Sahir; Roumeliotis, Theodoros I; Hatzikotoulas, Konstantinos; Zengini, Eleni; Wilkinson, J Mark; Choudhary, Jyoti S; McCaskie, Andrew W; Zeggini, Eleftheria

    2018-05-08

    To identify molecular differences between chondrocytes from osteophytic and articular cartilage tissue from OA patients. We investigated genes and pathways by combining genome-wide DNA methylation, RNA sequencing and quantitative proteomics in isolated primary chondrocytes from the cartilaginous layer of osteophytes and matched areas of low- and high-grade articular cartilage across nine patients with OA undergoing hip replacement surgery. Chondrocytes from osteophytic cartilage showed widespread differences to low-grade articular cartilage chondrocytes. These differences were similar to, but more pronounced than, differences between chondrocytes from osteophytic and high-grade articular cartilage, and more pronounced than differences between high- and low-grade articular cartilage. We identified 56 genes with significant differences between osteophytic chondrocytes and low-grade articular cartilage chondrocytes on all three omics levels. Several of these genes have known roles in OA, including ALDH1A2 and cartilage oligomeric matrix protein, which have functional genetic variants associated with OA from genome-wide association studies. An integrative gene ontology enrichment analysis showed that differences between osteophytic and low-grade articular cartilage chondrocytes are associated with extracellular matrix organization, skeletal system development, platelet aggregation and regulation of ERK1 and ERK2 cascade. We present a first comprehensive view of the molecular landscape of chondrocytes from osteophytic cartilage as compared with articular cartilage chondrocytes from the same joints in OA. We found robust changes at genes relevant to chondrocyte function, providing insight into biological processes involved in osteophyte development and thus OA progression.

  11. On the genesis of articular cartilage. Embryonic joint development and gene expression - implications for tissue engineering

    NARCIS (Netherlands)

    Jenner, F

    2013-01-01

    Articular chondrocytes descend from a distinct cohort of progenitor cells located in the embryonic joint anlagen, termed interzones. Their unique lineage might explain some of the problems encountered using chondrocytes of different lineages for articular cartilage tissue engineering. While it is

  12. Indications for intra-articular steroid in osteoarthritis of the ankle and ...

    African Journals Online (AJOL)

    The results of treatment with intra-articular steroid in an unselected group of patients with osteo-arthritis of the ankle and metatarsophalangeal joint of the big toe are described. From the results of this trial it is possible to lay down indications for the use of intra-articular steroid in these conditions. In the ankle joint it is ...

  13. Healthy young adults implement distinctive avoidance strategies while walking and circumventing virtual human vs. non-human obstacles in a virtual environment.

    Science.gov (United States)

    Souza Silva, Wagner; Aravind, Gayatri; Sangani, Samir; Lamontagne, Anouk

    2018-03-01

    This study examines how three types of obstacles (cylinder, virtual human and virtual human with footstep sounds) affect circumvention strategies of healthy young adults. Sixteen participants aged 25.2 ± 2.5 years (mean ± 1SD) were tested while walking overground and viewing a virtual room through a helmet mounted display. As participants walked towards a stationary target in the far space, they avoided an obstacle (cylinder or virtual human) approaching either from the right (+40°), left (-40°) or head-on (0°). Obstacle avoidance strategies were characterized using the position and orientation of the head. Repeated mixed model analysis showed smaller minimal distances (p = 0.007) while avoiding virtual humans as compared to cylinders. Footstep sounds added to virtual humans did not modify (p = 0.2) minimal distances compared to when no sound was provided. Onset times of avoidance strategies were similar across conditions (p = 0.06). Results indicate that the nature of the obstacle (human-like vs. non-human object) matters and can modify avoidance strategies. Smaller obstacle clearances in response to virtual humans may reflect the use of a less conservative avoidance strategy, due to a resemblance of obstacles to pedestrians and a recall of strategies used in daily locomotion. The lack of influence of footstep sounds supports the fact that obstacle avoidance primarily relies on visual cues and the principle of 'inverse effectiveness' whereby multisensory neurons' response to multimodal stimuli becomes weaker when the unimodal sensory stimulus (vision) is strong. Present findings should be taken into consideration to optimize the ecological validity of VR-based obstacle avoidance paradigms used in research and rehabilitation. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Chondrocyte heterogeneity: immunohistologically defined variation of integrin expression at different sites in human fetal knees.

    Science.gov (United States)

    Salter, D M; Godolphin, J L; Gourlay, M S

    1995-04-01

    During development and at maturity different forms of cartilage vary in morphology and macromolecular content. This reflects heterogeneity of chondrocyte activity, in part involving differential interactions with the adjacent extracellular matrix via specialized cell surface receptors such as integrins. We undertook an immunohistological study on a series of human fetal knee joints to assess variation in the expression of integrins by chondrocytes and potential matrix ligands in articular, epiphyseal, growth plate, and meniscal cartilage. The results show that articular chondrocytes (beta 1+, beta 5 alpha V+, alpha 1+, alpha 2+/-, alpha 5+, weakly alpha 6+, alpha V+) differed from epiphyseal (beta 1+, beta 5 alpha V+, alpha 1+/-, alpha 2+/-, alpha 5+, alpha 6+, alpha V+) growth plate (beta 1+, beta 5 alpha V+, alpha 1-, alpha 2-, alpha 5+, alpha 6+, alpha V+), and meniscal cells (beta 1+, beta 5 alpha V+, alpha 1+, strongly alpha 2+, alpha 5+, alpha 6+, alpha V+ in expression of integrin subunits. There was no expression of beta 3, beta 4, beta 6, or alpha 3 by chondrocytes. These results differ from previous reports on the expression of integrins by adult articular cartilage, where alpha 2 and alpha 6 are not seen. Variation in distribution of matrix ligands was also seen. Fibronectin, laminin and Type VI collagen were expressed in all cartilages but there was restricted expression of tenascin, ED-A and ED-B fibronectin isoforms (articular cartilage and meniscus), and vitronectin (absent from growth plate cartilage). Regulated expression of integrins by chondrocytes, associated with changes in the pericellular matrix composition, is of potential importance in control of cartilage differentiation and function in health and disease.

  15. The bio in the ink: cartilage regeneration with bioprintable hydrogels and articular cartilage-derived progenitor cells.

    Science.gov (United States)

    Levato, Riccardo; Webb, William R; Otto, Iris A; Mensinga, Anneloes; Zhang, Yadan; van Rijen, Mattie; van Weeren, René; Khan, Ilyas M; Malda, Jos

    2017-10-01

    Cell-laden hydrogels are the primary building blocks for bioprinting, and, also termed bioinks, are the foundations for creating structures that can potentially recapitulate the architecture of articular cartilage. To be functional, hydrogel constructs need to unlock the regenerative capacity of encapsulated cells. The recent identification of multipotent articular cartilage-resident chondroprogenitor cells (ACPCs), which share important traits with adult stem cells, represents a new opportunity for cartilage regeneration. However, little is known about the suitability of ACPCs for tissue engineering, especially in combination with biomaterials. This study aimed to investigate the potential of ACPCs in hydrogels for cartilage regeneration and biofabrication, and to evaluate their ability for zone-specific matrix production. Gelatin methacryloyl (gelMA)-based hydrogels were used to culture ACPCs, bone marrow mesenchymal stromal cells (MSCs) and chondrocytes, and as bioinks for printing. Our data shows ACPCs outperformed chondrocytes in terms of neo-cartilage production and unlike MSCs, ACPCs had the lowest gene expression levels of hypertrophy marker collagen type X, and the highest expression of PRG4, a key factor in joint lubrication. Co-cultures of the cell types in multi-compartment hydrogels allowed generating constructs with a layered distribution of collagens and glycosaminoglycans. By combining ACPC- and MSC-laden bioinks, a bioprinted model of articular cartilage was generated, consisting of defined superficial and deep regions, each with distinct cellular and extracellular matrix composition. Taken together, these results provide important information for the use of ACPC-laden hydrogels in regenerative medicine, and pave the way to the biofabrication of 3D constructs with multiple cell types for cartilage regeneration or in vitro tissue models. Despite its limited ability to repair, articular cartilage harbors an endogenous population of progenitor cells

  16. Arthroscopic ankle arthrodesis with intra-articular distraction.

    Science.gov (United States)

    Kim, Hyong Nyun; Jeon, June Young; Noh, Kyu Cheol; Kim, Hong Kyun; Dong, Quanyu; Park, Yong Wook

    2014-01-01

    Arthroscopic ankle arthrodesis has shown high rates of union comparable to those with open arthrodesis but with substantially less postoperative morbidity, shorter operative times, less blood loss, and shorter hospital stays. To easily perform arthroscopic resection of the articular cartilage, sufficient distraction of the joint is necessary to insert the arthroscope and instruments. However, sometimes, standard noninvasive ankle distraction will not be sufficient in post-traumatic ankle arthritis, with the development of arthrofibrosis and joint contracture after severe ankle trauma. In the present report, we describe a technique to distract the ankle joint by inserting a 4.6-mm stainless steel cannula with a blunt trocar inside the joint. The cannula allowed sufficient intra-articular distraction, and, at the same time, a 4.0-mm arthroscope can be inserted through the cannula to view the joint. Screws can be inserted to fix the joint under fluoroscopic guidance without changing the patient's position or removing the noninvasive distraction device and leg holder, which are often necessary during standard arthroscopic arthrodesis with noninvasive distraction. Copyright © 2014 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.

  17. Particulated articular cartilage: CAIS and DeNovo NT.

    Science.gov (United States)

    Farr, Jack; Cole, Brian J; Sherman, Seth; Karas, Vasili

    2012-03-01

    Cartilage Autograft Implantation System (CAIS; DePuy/Mitek, Raynham, MA) and DeNovo Natural Tissue (NT; ISTO, St. Louis, MO) are novel treatment options for focal articular cartilage defects in the knee. These methods involve the implantation of particulated articular cartilage from either autograft or juvenile allograft donor, respectively. In the laboratory and in animal models, both CAIS and DeNovo NT have demonstrated the ability of the transplanted cartilage cells to "escape" from the extracellular matrix, migrate, multiply, and form a new hyaline-like cartilage tissue matrix that integrates with the surrounding host tissue. In clinical practice, the technique for both CAIS and DeNovo NT is straightforward, requiring only a single surgery to affect cartilage repair. Clinical experience is limited, with short-term studies demonstrating both procedures to be safe, feasible, and effective, with improvements in subjective patient scores, and with magnetic resonance imaging evidence of good defect fill. While these treatment options appear promising, prospective randomized controlled studies are necessary to refine the indications and contraindications for both CAIS and DeNovo NT.

  18. Pathology of articular cartilage and synovial membrane from elbow joints with and without degenerative joint disease in domestic cats.

    Science.gov (United States)

    Freire, M; Meuten, D; Lascelles, D

    2014-09-01

    The elbow joint is one of the feline appendicular joints most commonly and severely affected by degenerative joint disease. The macroscopic and histopathological lesions of the elbow joints of 30 adult cats were evaluated immediately after euthanasia. Macroscopic evidence of degenerative joint disease was found in 22 of 30 cats (39 elbow joints) (73.33% cats; 65% elbow joints), and macroscopic cartilage erosion ranged from mild fibrillation to complete ulceration of the hyaline cartilage with exposure of the subchondral bone. Distribution of the lesions in the cartilage indicated the presence of medial compartment joint disease (most severe lesions located in the medial coronoid process of the ulna and medial humeral epicondyle). Synovitis scores were mild overall and correlated only weakly with macroscopic cartilage damage. Intra-articular osteochondral fragments either free or attached to the synovium were found in 10 joints. Macroscopic or histologic evidence of a fragmented coronoid process was not found even in those cases with intra-articular osteochondral fragments. Lesions observed in these animals are most consistent with synovial osteochondromatosis secondary to degenerative joint disease. The pathogenesis for the medial compartmentalization of these lesions has not been established, but a fragmented medial coronoid process or osteochondritis dissecans does not appear to play a role. © The Author(s) 2014.

  19. Changes in radiation dose with variations in human anatomy: moderately and severely obese adults.

    Science.gov (United States)

    Clark, Landon D; Stabin, Michael G; Fernald, Michael J; Brill, Aaron B

    2010-06-01

    The phantoms used in standardized dose assessment are based on a median (i.e., 50th percentile) individual of a large population, for example, adult males or females or children of a particular age. Here we describe phantoms that model instead the influence of obesity on specific absorbed fractions (SAFs) and dose factors in adults. The literature was reviewed to evaluate how individual organ sizes change with variations in body weight in mildly and severely obese adult men and women. On the basis of the literature evaluation, changes were made to our deformable reference adult male and female total-body models. Monte Carlo simulations of radiation transport were performed. SAFs for photons were generated for mildly and severely obese adults, and comparisons were made to the reference (50th) percentile SAF values. SAFs studied between the obese phantoms and the 50th percentile reference phantoms were not significantly different from the reference 50th percentile individual, with the exception of intestines irradiating some abdominal organs, because of an increase in separation between folds caused by an increase in mesenteric adipose deposits. Some low-energy values for certain organ pairs were different, possibly due only to the statistical variability of the data at these low energies. The effect of obesity on dose calculations for internal emitters is minor and may be neglected in the routine use of standardized dose estimates.

  20. Secondary knee instability caused by fracture of the stabilizing insert in a dual-articular total knee

    DEFF Research Database (Denmark)

    Boesen, Morten P; Jensen, Tim Toftgaard; Husted, Henrik

    2004-01-01

    A case of a fractured polyethylene stabilizing insert causing secondary knee instability in a Dual-articular total knee arthroplasty (TKA) is presented. A 65-year-old woman who underwent surgery with a Dual-articular TKA 4 years earlier had a well-functioning prosthesis until a fall, after which......-articular knee....

  1. Gastrointestinal absorption of plutonium and uranium in fed and fasted adult baboons and mice: application to humans

    International Nuclear Information System (INIS)

    Bhattacharyya, M.H.; Larsen, R.P.; Oldham, R.D.; Cohen, N.; Ralston, L.G.; Moretti, E.S.; Ayres, L.

    1989-01-01

    Gastrointestinal (GI) absorption values of plutonium and uranium were determined in fed and fasted adult baboons and mice. For both baboons and mice, the GI absorptions of plutonium and uranium were 10 to 20 times higher in 24 h fasted animals than in fed ones. For plutonium, GI absorption values in baboons were almost identical to those in mice for both fed and fasted conditions, and values for fed animals agreed with estimates for humans. For uranium, GI absorption values in fed and fasted baboons were 6 to 7 times higher than those in mice, and agreed well with those fed and fasted humans. For one baboon that was not given its morning meal, plutonium absorption 2 h after the start of the active phase was the same as that in the 24 h fasted animals. In contrast, for baboons that received a morning meal, plutonium absorption did not rise to the value of 24 h fasted baboons even 8 h after the meal. We conclude that GI absorption values for plutonium and uranium in adult baboons are good estimates of the values in humans and that the values for the fasted condition should be used to set standards for oral exposure of persons in the workplace. (author)

  2. Comparison of efficacy of intra-articular morphine and steroid in patients with knee osteoarthritis

    Directory of Open Access Journals (Sweden)

    Serbülent Gökhan Beyaz

    2012-01-01

    Full Text Available Introduction: Primary therapeutic aim in treatment of osteoarthritis of the knee is to relieve the pain of osteoarthritis. The aim of this study was to compare the efficacy of intra-articular triamcinolone with intra-articular morphine in pain relief due to osteoarthritis of the knee in the elderly population. Materials and Methods: Patients between 50 and 80 years of age were randomized into three groups. Group M received morphine plus bupivacaine intra-articularly, Group T received triamcinolone plus bupivacaine intra-articularly, and Group C received saline plus bupivacaine intra-articularly. Patients were evaluated before injection and in 2nd, 4th, 6th, and 12th weeks after injection. First-line supplementary analgesic was oral paracetamol 1500 mg/day. If analgesia was insufficient with paracetamol, oral dexketoprofen trometamol 50 mg/day was recommended to patients. Results: After the intra-articular injection, there was statistically significant decrease in visual analog scale (VAS scores in Groups M and T, when compared to Group C. The decrease of VAS scores seen at the first 2 weeks continued steadily up to the end of 12th week. There was a significant decrease in Groups M and T in the WOMAC scores, when compared to Group C. There was no significant difference in the WOMAC scores between morphine and steroid groups. Significantly less supplementary analgesics was used in the morphine and steroid groups. Conclusion: Intra-articular morphine was as effective as intra-articular triamcinolone for analgesia in patients with osteoarthritis knee. Intra-articular morphine is possibly a better option than intra-articular steroid as it has lesser side effects.

  3. Ectopic Human Fasciola hepatica Infection by an Adult Worm in the Mesocolon.

    Science.gov (United States)

    Kim, Ah Jin; Choi, Chang Hwan; Choi, Sun Keun; Shin, Yong Woon; Park, Yun-Kyu; Kim, Lucia; Choi, Suk Jin; Han, Jee Young; Kim, Joon Mee; Chu, Young Chae; Park, In Suh

    2015-12-01

    We report here an ectopic case of Fasciola hepatica infection confirmed by recovery of an adult worm in the mesocolon. A 56-year-old female was admitted to our hospital with discomfort and pain in the left lower quadrant of the abdomen. Abdominal CT showed 3 abscesses in the left upper quadrant, mesentery, and pelvic cavity. On surgical exploration, abscess pockets were found in the mesocolon of the sigmoid colon and transverse colon. A leaf-like worm found in the abscess pocket of the mesocolon of the left colon was diagnosed as an adult fluke of F. hepatica. Histologically, numerous eggs of F. hepatica were noted with acute and chronic granulomatous inflammations in the subserosa and pericolic adipose tissues. Conclusively, a rare case of ectopic fascioliasis has been confirmed in this study by the adult worm recovery of F. hepatica in the mesocolon.

  4. Comparative study of the chondrogenic potential of human bone marrow stromal cells, neonatal chondrocytes and adult chondrocytes

    International Nuclear Information System (INIS)

    Saha, Sushmita; Kirkham, Jennifer; Wood, David; Curran, Stephen; Yang, Xuebin

    2010-01-01

    Research highlights: → This study has characterised three different cell types under conditions similar to those used for autologous chondrocyte implantation (ACI) for applications in cartilage repair/regeneration. → Compared for the first time the chondrogenic potential of neonatal chondrocytes with human bone marrow stromal cells (HBMSCs) and adult chondrocytes. → Demonstrated that adult chondrocytes hold greatest potential for use in ACI based on their higher proliferation rates, lower alkaline phosphatise activity and enhanced expression of chondrogenic genes. → Demonstrated the need for chondroinduction as a necessary pre-requisite to efficient chondrogenesis in vitro and, by extrapolation, for cell based therapy (e.g. ACI or cartilage tissue engineering). -- Abstract: Cartilage tissue engineering is still a major clinical challenge with optimisation of a suitable source of cells for cartilage repair/regeneration not yet fully addressed. The aims of this study were to compare and contrast the differences in chondrogenic behaviour between human bone marrow stromal cells (HBMSCs), human neonatal and adult chondrocytes to further our understanding of chondroinduction relative to cell maturity and to identify factors that promote chondrogenesis and maintain functional homoeostasis. Cells were cultured in monolayer in either chondrogenic or basal medium, recapitulating procedures used in existing clinical procedures for cell-based therapies. Cell doubling time, morphology and alkaline phosphatase specific activity (ALPSA) were determined at different time points. Expression of chondrogenic markers (SOX9, ACAN and COL2A1) was compared via real time polymerase chain reaction. Amongst the three cell types studied, HBMSCs had the highest ALPSA in basal culture and lowest ALPSA in chondrogenic media. Neonatal chondrocytes were the most proliferative and adult chondrocytes had the lowest ALPSA in basal media. Gene expression analysis revealed a difference in the

  5. Comparative study of the chondrogenic potential of human bone marrow stromal cells, neonatal chondrocytes and adult chondrocytes

    Energy Technology Data Exchange (ETDEWEB)

    Saha, Sushmita [Biomaterials and Tissue Engineering Group, Leeds Dental Institute, University of Leeds, LS29LU (United Kingdom); Kirkham, Jennifer [Biomineralisation Group, Leeds Dental Institute, University of Leeds, LS29LU (United Kingdom); NIHR Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Chapel Allerton Hospital, Leeds LS74SA (United Kingdom); Wood, David [Biomaterials and Tissue Engineering Group, Leeds Dental Institute, University of Leeds, LS29LU (United Kingdom); Curran, Stephen [Smith and Nephew Research Centre, YO105DF (United Kingdom); Yang, Xuebin, E-mail: X.B.Yang@leeds.ac.uk [Biomaterials and Tissue Engineering Group, Leeds Dental Institute, University of Leeds, LS29LU (United Kingdom); NIHR Leeds Musculoskeletal Biomedical Research Unit, University of Leeds, Chapel Allerton Hospital, Leeds LS74SA (United Kingdom)

    2010-10-22

    Research highlights: {yields} This study has characterised three different cell types under conditions similar to those used for autologous chondrocyte implantation (ACI) for applications in cartilage repair/regeneration. {yields} Compared for the first time the chondrogenic potential of neonatal chondrocytes with human bone marrow stromal cells (HBMSCs) and adult chondrocytes. {yields} Demonstrated that adult chondrocytes hold greatest potential for use in ACI based on their higher proliferation rates, lower alkaline phosphatise activity and enhanced expression of chondrogenic genes. {yields} Demonstrated the need for chondroinduction as a necessary pre-requisite to efficient chondrogenesis in vitro and, by extrapolation, for cell based therapy (e.g. ACI or cartilage tissue engineering). -- Abstract: Cartilage tissue engineering is still a major clinical challenge with optimisation of a suitable source of cells for cartilage repair/regeneration not yet fully addressed. The aims of this study were to compare and contrast the differences in chondrogenic behaviour between human bone marrow stromal cells (HBMSCs), human neonatal and adult chondrocytes to further our understanding of chondroinduction relative to cell maturity and to identify factors that promote chondrogenesis and maintain functional homoeostasis. Cells were cultured in monolayer in either chondrogenic or basal medium, recapitulating procedures used in existing clinical procedures for cell-based therapies. Cell doubling time, morphology and alkaline phosphatase specific activity (ALPSA) were determined at different time points. Expression of chondrogenic markers (SOX9, ACAN and COL2A1) was compared via real time polymerase chain reaction. Amongst the three cell types studied, HBMSCs had the highest ALPSA in basal culture and lowest ALPSA in chondrogenic media. Neonatal chondrocytes were the most proliferative and adult chondrocytes had the lowest ALPSA in basal media. Gene expression analysis revealed

  6. Comparative digital cartilage histology for human and common osteoarthritis models

    Directory of Open Access Journals (Sweden)

    Pedersen DR

    2013-02-01

    Full Text Available Douglas R Pedersen, Jessica E Goetz, Gail L Kurriger, James A MartinDepartment of Orthopaedics and Rehabilitation, University of Iowa, Iowa City, IA, USAPurpose: This study addresses the species-specific and site-specific details of weight-bearing articular cartilage zone depths and chondrocyte distributions among humans and common osteoarthritis (OA animal models using contemporary digital imaging tools. Histological analysis is the gold-standard research tool for evaluating cartilage health, OA severity, and treatment efficacy. Historically, evaluations were made by expert analysts. However, state-of-the-art tools have been developed that allow for digitization of entire histological sections for computer-aided analysis. Large volumes of common digital cartilage metrics directly complement elucidation of trends in OA inducement and concomitant potential treatments.Materials and methods: Sixteen fresh human knees, 26 adult New Zealand rabbit stifles, and 104 bovine lateral plateaus were measured for four cartilage zones and the cell densities within each zone. Each knee was divided into four weight-bearing sites: the medial and lateral plateaus and femoral condyles.Results: One-way analysis of variance followed by pairwise multiple comparisons (Holm–Sidak method at a significance of 0.05 clearly confirmed the variability between cartilage depths at each site, between sites in the same species, and between weight-bearing articular cartilage definitions in different species.Conclusion: The present study clearly demonstrates multisite, multispecies differences in normal weight-bearing articular cartilage, which can be objectively quantified by a common digital histology imaging technique. The clear site-specific differences in normal cartilage must be taken into consideration when characterizing the pathoetiology of OA models. Together, these provide a path to consistently analyze the volume and variety of histologic slides necessarily generated

  7. Changes in concentrations of haemostatic and inflammatory biomarkers in synovial fluid after intra-articular injection of lipopolysaccharide in horses

    DEFF Research Database (Denmark)

    Andreassen, Stine Mandrup; Vinther, Anne Mette Lindberg; Nielsen, Søren Saxmose

    2017-01-01

    BACKGROUND: Septic arthritis is a common and potentially devastating disease characterized by severe intra-articular (IA) inflammation and fibrin deposition. Research into equine joint pathologies has focused on inflammation, but recent research in humans suggests that both haemostatic and inflam......BACKGROUND: Septic arthritis is a common and potentially devastating disease characterized by severe intra-articular (IA) inflammation and fibrin deposition. Research into equine joint pathologies has focused on inflammation, but recent research in humans suggests that both haemostatic...... and inflammatory pathways are activated in the joint compartment in arthritic conditions. The aim of this study was to characterize the IA haemostatic and inflammatory responses in horses with experimental lipopolysaccharide (LPS)-induced joint inflammation. Inflammation was induced by IA injection of LPS into one...... antebrachiocarpal joint of six horses. Horses were evaluated clinically with subjective grading of lameness, and blood and synovial fluid (SF) samples were collected at post injection hours (PIH) -120, -96, -24, 0, 2, 4, 8, 16, 24, 36, 48, 72 and 144. Total protein (TP), white blood cell counts (WBC), serum amyloid...

  8. Isolation of mineralizing Nestin+ Nkx6.1+ vascular muscular cells from the adult human spinal cord

    Directory of Open Access Journals (Sweden)

    Guillon Hélène

    2011-10-01

    Full Text Available Abstract Background The adult central nervous system (CNS contains different populations of immature cells that could possibly be used to repair brain and spinal cord lesions. The diversity and the properties of these cells in the human adult CNS remain to be fully explored. We previously isolated Nestin+ Sox2+ neural multipotential cells from the adult human spinal cord using the neurosphere method (i.e. non adherent conditions and defined medium. Results Here we report the isolation and long term propagation of another population of Nestin+ cells from this tissue using adherent culture conditions and serum. QPCR and immunofluorescence indicated that these cells had mesenchymal features as evidenced by the expression of Snai2 and Twist1 and lack of expression of neural markers such as Sox2, Olig2 or GFAP. Indeed, these cells expressed markers typical of smooth muscle vascular cells such as Calponin, Caldesmone and Acta2 (Smooth muscle actin. These cells could not differentiate into chondrocytes, adipocytes, neuronal and glial cells, however they readily mineralized when placed in osteogenic conditions. Further characterization allowed us to identify the Nkx6.1 transcription factor as a marker for these cells. Nkx6.1 was expressed in vivo by CNS vascular muscular cells located in the parenchyma and the meninges. Conclusion Smooth muscle cells expressing Nestin and Nkx6.1 is the main cell population derived from culturing human spinal cord cells in adherent conditions with serum. Mineralization of these cells in vitro could represent a valuable model for studying calcifications of CNS vessels which are observed in pathological situations or as part of the normal aging. In addition, long term propagation of these cells will allow the study of their interaction with other CNS cells and their implication in scar formation during spinal cord injury.

  9. Relative influence of human harvest, carnivores, and weather on adult female elk survival across western North America

    Science.gov (United States)

    Brodie, Jedediah; Johnson, Heather; Mitchell, Michael; Zager, Peter; Proffitt, Kelly; Hebblewhite, Mark; Kauffman, Matthew; Johnson, Bruce; Bissonette, John; Bishop, Chad; Gude, Justin; Herbert, Jeff; Hersey, Kent R.; Hurley, Mark; Lukacs, Paul M.; McCorquodale, Scott; McIntire, Eliot; Nowak, Josh; Sawyer, Hall; Smith, Douglas; White, P.J.

    2013-01-01

    Well-informed management of harvested species requires understanding how changing ecological conditions affect demography and population dynamics, information that is lacking for many species. We have limited understanding of the relative influence of carnivores, harvest, weather and forage availability on elk Cervus elaphus demography, despite the ecological and economic importance of this species. We assessed adult female survival, a key vital rate for population dynamics, from 2746 radio-collared elk in 45 populations across western North America that experience wide variation in carnivore assemblage, harvest, weather and habitat conditions. Proportional hazard analysis revealed that 'baseline' (i.e. not related to human factors) mortality was higher with very high winter precipitation, particularly in populations sympatric with wolves Canis lupus. Mortality may increase via nutritional stress and heightened vulnerability to predation in snowy winters. Baseline mortality was unrelated to puma Puma concolor presence, forest cover or summer forage productivity. Cause-specific mortality analyses showed that wolves and all carnivore species combined had additive effects on baseline elk mortality, but only reduced survival by baseline adult female elk mortality from wolves in years with high winter precipitation could affect elk abundance as winters across the western US become drier and wolves recolonize portions of the region. In the absence of human harvest, wolves had additive, although limited, effects on mortality. However, human harvest, and its apparent use by managers to offset predation, primarily controls overall variation in adult female mortality. Altering harvest quotas is thus a strong tool for offsetting impacts of carnivore recolonization and shifting weather patterns on elk across western North America.

  10. Attenuation of the progression of articular cartilage degeneration by inhibition of TGF-β1 signaling in a mouse model of osteoarthritis.

    Science.gov (United States)

    Chen, Rebecca; Mian, Michelle; Fu, Martin; Zhao, Jing Ying; Yang, Liang; Li, Yefu; Xu, Lin

    2015-11-01

    Transforming growth factor beta 1 (TGF-β1) is implicated in osteoarthritis. We therefore studied the role of TGF-β1 signaling in the development of osteoarthritis in a developmental stage-dependent manner. Three different mouse models were investigated. First, the Tgf-β receptor II (Tgfbr2) was specifically removed from the mature cartilage of joints. Tgfbr2-deficient mice were grown to 12 months of age and were then euthanized for collection of knee and temporomandibular joints. Second, Tgfbr2-deficient mice were subjected to destabilization of the medial meniscus (DMM) surgery. Knee joints were then collected from the mice at 8 and 16 weeks after the surgery. Third, wild-type mice were subjected to DMM at the age of 8 weeks. Immediately after the surgery, these mice were treated with the Tgfbr2 inhibitor losartan for 8 weeks and then euthanized for collection of knee joints. All joints were characterized for evidences of articular cartilage degeneration. Initiation or acceleration of articular cartilage degeneration was not observed by the genetic inactivation of Tgfbr2 in the joints at the age of 12 months. In fact, the removal of Tgfbr2 and treatment with losartan both delayed the progression of articular cartilage degeneration induced by DMM compared with control littermates. Therefore, we conclude that inhibition of Tgf-β1 signaling protects adult knee joints in mice against the development of osteoarthritis. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  11. Relative influence of human harvest, carnivores, and weather on adult female elk survival across western North America

    Science.gov (United States)

    Brodie, Jedediah; Johnson, Heather; Mitchell, Michael; Zager, Peter; Proffitt, Kelly; Hebblewhite, Mark; Kauffman, Matthew; Johnson, Bruce; Bissonette, John; Bishop, Chad; Gude, Justin; Herbert, Jeff; Hersey, Kent R.; Hurley, Mark; Lukacs, Paul M.; McCorquodale, Scott; McIntire, Eliot; Nowak, Josh; Sawyer, Hall; Smith, Douglas; White, P.J.

    2013-01-01

    Well-informed management of harvested species requires understanding how changing ecological conditions affect demography and population dynamics, information that is lacking for many species. We have limited understanding of the relative influence of carnivores, harvest, weather and forage availability on elk Cervus elaphus demography, despite the ecological and economic importance of this species. We assessed adult female survival, a key vital rate for population dynamics, from 2746 radio-collared elk in 45 populations across western North America that experience wide variation in carnivore assemblage, harvest, weather and habitat conditions. Proportional hazard analysis revealed that 'baseline' (i.e. not related to human factors) mortality was higher with very high winter precipitation, particularly in populations sympatric with wolves Canis lupus. Mortality may increase via nutritional stress and heightened vulnerability to predation in snowy winters. Baseline mortality was unrelated to puma Puma concolor presence, forest cover or summer forage productivity. Cause-specific mortality analyses showed that wolves and all carnivore species combined had additive effects on baseline elk mortality, but only reduced survival by <2%. When human factors were included, ‘total’ adult mortality was solely related to harvest; the influence of native carnivores was compensatory. Annual total mortality rates were lowest in populations sympatric with both pumas and wolves because managers reduced female harvest in areas with abundant or diverse carnivores. Mortality from native carnivores peaked in late winter and early spring, while harvest-induced mortality peaked in autumn. The strong peak in harvest-induced mortality during the autumn hunting season decreased as the number of native carnivore species increased. Synthesis and applications. Elevated baseline adult female elk mortality from wolves in years with high winter precipitation could affect elk abundance as

  12. Defining the role of common variation in the genomic and biological architecture of adult human height

    NARCIS (Netherlands)

    A.R. Wood (Andrew); T. Esko (Tõnu); J. Yang (Jian); S. Vedantam (Sailaja); T.H. Pers (Tune); S. Gustafsson (Stefan); A.Y. Chu (Audrey Y); K. Estrada Gil (Karol); J. Luan; Z. Kutalik; N. Amin (Najaf); M.L. Buchkovich (Martin); D.C. Croteau-Chonka (Damien); F.R. Day (Felix); Y. Duan (Yanan); M. Fall (Magnus); R.S.N. Fehrmann (Rudolf); T. Ferreira (Teresa); A.U. Jackson (Anne); J. Karjalainen (Juha); K.S. Lo (Ken Sin); A. Locke (Adam); R. Mägi (Reedik); E. Mihailov (Evelin); E. Porcu (Eleonora); J.C. Randall (Joshua); A. Scherag (Andre); A.A.E. Vinkhuyzen (Anna A.); H.J. Westra (Harm-Jan); T.W. Winkler (Thomas W.); T. Workalemahu (Tsegaselassie); J.H. Zhao (Jing Hua); D. Absher (Devin); E. Albrecht (Eva); J. Baron (Jeffrey); M. Beekman (Marian); A. Demirkan (Ayşe); G.B. Ehret (Georg); B. Feenstra; M.F. Feitosa (Mary Furlan); K. Fischer (Krista); R.M. Fraser (Ross); A. Goel (Anuj); J. Gong (Jian); A.E. Justice (Anne); S. Kanoni (Stavroula); M.E. Kleber (Marcus); K. Kristiansson (Kati); U. Lim (Unhee); V. Lotay (Vaneet); J.C. Lui (Julian C); M. Mangino (Massimo); I.M. Leach (Irene Mateo); M.C. Medina-Gomez (Carolina); M.A. Nalls (Michael); A.S. Dimas (Antigone); C. Palmer (Cameron); D. Pasko (Dorota); S. Pechlivanis (Sonali); I. Prokopenko (Inga); J.S. Ried (Janina); S. Ripke (Stephan); D. Shungin (Dmitry); A. Stancáková (Alena); R.J. Strawbridge (Rona); Y.J. Sung (Yun Ju); T. Tanaka (Toshiko); A. Teumer (Alexander); S. Trompet (Stella); S.W. Van Der Laan (Sander W.); J. van Setten (Jessica); J.V. van Vliet-Ostaptchouk (Jana); Z. Wang (Zhaoming); L. Yengo (Loic); W. Zhang (Weihua); U. Afzal (Uzma); J. Ärnlöv (Johan); G.M. Arscott (Gillian M.); S. Bandinelli (Stefania); A. Barrett (Angela); C. Bellis (Claire); A.J. Bennett (Amanda); C. Berne (Christian); M. Blüher (Matthias); J.L. Bolton (Jennifer); Y. Böttcher (Yvonne); H.A. Boyd; M. Bruinenberg (M.); B.M. Buckley (Brendan M.); S. Buyske (Steven); I.H. Caspersen (Ida H.); P.S. Chines (Peter); R. Clarke (Robert); S. Claudi-Boehm (Simone); M.N. Cooper (Matthew); E.W. Daw (E Warwick); P.A. De Jong (Pim A); J. Deelen (Joris); G. Delgado; J.C. Denny (Josh C); R.A.M. Dhonukshe-Rutten (Rosalie); M. Dimitriou (Maria); A.S.F. Doney (Alex); M. Dörr (Marcus); N. Eklund (Niina); E. Eury (Elodie); L. Folkersen (Lasse); M. Garcia (Melissa); F. Geller (Frank); V. Giedraitis (Vilmantas); A. Go (Attie); H. Grallert (Harald); T.B. Grammer (Tanja B); J. Gräßler (Jürgen); H. Grönberg (Henrik); L.C.P.G.M. de Groot (Lisette); C.J. Groves (Christopher J.); J. Haessler (Jeff); P. Hall (Per); T. Haller (Toomas); G. Hallmans (Göran); M. Hannemann (Mario); C.A. Hartman (Catharina); M. Hassinen (Maija); C. Hayward (Caroline); N.L. Heard-Costa (Nancy); Q. Helmer (Quinta); G. Hemani; A.K. Henders (Anjali); H.L. Hillege (Hans); M.A. Hlatky (Mark); W. Hoffmann (Wolfgang); P. Hoffmann (Per); O.L. Holmen (Oddgeir); J.J. Houwing-Duistermaat (Jeanine); T. Illig (Thomas); A. Isaacs (Aaron); A.L. James (Alan); J. Jeff (Janina); B. Johansen (Berit); A. Johansson (Åsa); G.J. Jolley (Jason); T. Juliusdottir (Thorhildur); M.J. Junttila (Juhani); M.M.L. Kho (Marcia); L. Kinnunen (Leena); N. Klopp (Norman); T. Kocher; W. Kratzer (Wolfgang); P. Lichtner (Peter); L. Lind (Lars); J. Lindström (Jaana); S. Lobbens (Stéphane); M. Lorentzon (Mattias); Y. Lu (Yingchang); V. Lyssenko (Valeriya); P.K. Magnusson (Patrik); A. Mahajan (Anubha); M. Maillard (Marc); W.L. McArdle (Wendy); C.A. McKenzie (Colin A.); S. McLachlan (Stela); P.J. McLaren (Paul J); C. Menni (Cristina); S. Merger (Sigrun); L. Milani (Lili); A. Moayyeri (Alireza); K.L. Monda (Keri); M.A. Morken (Mario); G. Müller (Gabriele); M. Müller-Nurasyid (Martina); A.W. Musk (Arthur); N. Narisu (Narisu); M. Nauck (Matthias); I.M. Nolte (Ilja M.); M.M. Nöthen (Markus); L. Oozageer (Laticia); S. Pilz (Stefan); N.W. Rayner (Nigel William); F. Renström (Frida); N.R. Robertson (Neil R.); L.M. Rose (Lynda M.); R. Roussel (Ronan); S. Sanna (Serena); H. Scharnagl (Hubert); S. Scholtens (Salome); F.R. Schumacher (Fredrick R); H. Schunkert (Heribert); R.A. Scott (Robert); J.S. Sehmi (Joban); T. Seufferlein (Thomas); J. Shi (Jianxin); K. Silventoinen (Karri); J.H. Smit (Johannes); G.D. Smith; J. Smolonska (Joanna); A. Stanton (Alice); K. Stirrups (Kathy); D.J. Stott (David J); H.M. Stringham (Heather); J. Sundstrom (Johan); M. Swertz (Morris); A.C. Syvanen; B. Tayo (Bamidele); G. Thorleifsson (Gudmar); J.P. Tyrer (Jonathan); S. Van Dijk (Suzanne); N.M. van Schoor (Natasja); N. van der Velde (Nathalie); D. van Heemst (Diana); F.V.A. Van Oort (Floor V A); S.H.H.M. Vermeulen (Sita); N. Verweij (Niek); J.M. Vonk (Judith M); L. Waite (Lindsay); M. Waldenberger (Melanie); R. Wennauer (Roman); L.R. Wilkens (Lynne R.); C. Willenborg (Christina); T. Wilsgaard (Tom); M.K. Wojczynski (Mary ); A. Wong (Andrew); A. Wright (Alan); Q. Zhang (Qunyuan); D. Arveiler (Dominique); S.J.L. Bakker (Stephan); J. Beilby (John); R.N. Bergman (Richard); S.M. Bergmann (Sven); R. Biffar; J. Blangero (John); D.I. Boomsma (Dorret); S.R. Bornstein (Stefan R.); P. Bovet (Pascal); P. Brambilla (Paolo); M.J. Brown (Morris); H. Campbell (Harry); M. Caulfield (Mark); A. Chakravarti (Aravinda); F.S. Collins (Francis); D.C. Crawford (Dana); L.A. Cupples (Adrienne); J. Danesh (John); U. de Faire (Ulf); H.M. den Ruijter (Hester ); R. Erbel (Raimund); J. Erdmann (Jeanette); J. Eriksson; M. Farrall (Martin); E. Ferrannini (Ele); J. Ferrieres (Jean); I. Ford; N.G. Forouhi (Nita); T. Forrester (Terrence); R.T. Gansevoort (Ron); P.V. Gejman (Pablo); C. Gieger (Christian); A. Golay (Alain); R.F. Gottesman (Rebecca); V. Gudnason (Vilmundur); U. Gyllensten (Ulf); D.W. Haas (David W); A.S. Hall (Alistair); T.B. Harris (Tamara); A.T. Hattersley (Andrew); A.C. Heath (Andrew C); C. Hengstenberg (Christian); A.A. Hicks (Andrew); L.A. Hindorff (Lucia A); A. Hingorani (Aroon); A. Hofman (Albert); G.K. Hovingh (Kees); S.E. Humphries (Steve E.); S.C. Hunt (Steven); E. Hypponen (Elina); K.B. Jacobs (Kevin); M.-R. Jarvelin (Marjo-Riitta); P. Jousilahti (Pekka); A. Jula (Antti); J. Kaprio (Jaakko); J.J.P. Kastelein (John); M.H. Kayser (Manfred); F. Kee (Frank); S. Keinanen-Kiukaanniemi (Sirkka); L.A.L.M. Kiemeney (Bart); J.S. Kooner (Jaspal S.); C. Kooperberg (Charles); S. Koskinen (Seppo); P. Kovacs (Peter); A. Kraja (Aldi); M. Kumari (Meena); J. Kuusisto (Johanna); T.A. Lakka (Timo); C. Langenberg (Claudia); L. Le Marchand (Loic); T. Lehtimäki (Terho); S. Lupoli (Sara); P.A. Madden; S. Männistö (Satu); P. Manunta (Paolo); A. Marette (Andre'); T.C. Matise (Tara C.); B. McKnight (Barbara); T. Meitinger (Thomas); F.L. Moll (Frans); G.W. Montgomery (Grant W.); A.D. Morris (Andrew); A.P. Morris (Andrew); J.C. Murray (Jeffrey); M. Nelis (Mari); C. Ohlsson (Claes); A.J. Oldehinkel (Albertine); K.K. Ong (Ken K.); W.H. Ouwehand (Willem); G. Pasterkamp (Gerard); A. Peters (Annette); P.P. Pramstaller (Peter Paul); J.F. Price (Jackie F.); L. Qi (Lu); O. Raitakari (Olli); T. Rankinen (Tuomo); D.C. Rao (Dabeeru C.); T.K. Rice (Treva K.); M.D. Ritchie (Marylyn D.); I. Rudan (Igor); V. Salomaa (Veikko); N.J. Samani (Nilesh); J. Saramies (Jouko); M.A. Sarzynski (Mark A.); P.E.H. Schwarz (Peter E. H.); S. Sebert (Sylvain); P. Sever (Peter); A.R. Shuldiner (Alan); J. Sinisalo (Juha); V. Steinthorsdottir (Valgerdur); R.P. Stolk; J.-C. Tardif (Jean-Claude); A. Tönjes (Anke); A. Tremblay (Angelo); E. Tremoli (Elena); J. Virtamo (Jarmo); M.-C. Vohl (Marie-Claude); P. Amouyel (Philippe); F.W. Asselbergs (Folkert W.); T.L. Assimes (Themistocles); M. Bochud (Murielle); B.O. Boehm (Bernhard); E.A. Boerwinkle (Eric); E.P. Bottinger (Erwin P.); C. Bouchard (Claude); S. Cauchi (Stéphane); J.C. Chambers (John C.); S.J. Chanock (Stephen); R.S. Cooper (Richard S.); P.I.W. de Bakker (Paul); G.V. Dedoussis (George); L. Ferrucci (Luigi); P.W. Franks; P. Froguel (Philippe); L. Groop (Leif); C.A. Haiman (Christopher); A. Hamsten (Anders); M.G. Hayes (M. Geoffrey); J. Hui (Jennie); D. Hunter (David); K. Hveem (Kristian); J.W. Jukema (Jan Wouter); R.C. Kaplan (Robert); M. Kivimaki (Mika); D. Kuh (Diana); M. Laakso (Markku); Y. Liu (YongMei); N.G. Martin (Nicholas); W. März (Winfried); M. Melbye (Mads); S. Moebus (Susanne); P. Munroe (Patricia); I. Njølstad (Inger); B.A. Oostra (Ben); C.N.A. Palmer (Colin); N.L. Pedersen (Nancy L.); M. Perola (Markus); L. Perusse (Louis); U. Peters (Ulrike); J.E. Powell (Joseph); C. Power (Christine); T. Quertermous (Thomas); R. Rauramaa (Rainer); E. Reinmaa (Eva); P.M. Ridker (Paul); F. Rivadeneira Ramirez (Fernando); J.I. Rotter (Jerome I.); T. Saaristo (Timo); D. Saleheen; D. Schlessinger (David); P.E. Slagboom (P Eline); H. Snieder (Harold); T.D. Spector (Timothy); K. Strauch (Konstantin); M. Stumvoll (Michael); J. Tuomilehto (Jaakko); M. Uusitupa (Matti); P. van der Harst (Pim); H. Völzke (Henry); M. Walker (Mark); N.J. Wareham (Nick); H. Watkins (Hugh); H.E. Wichmann (Heinz Erich); J.F. Wilson (James F); P. Zanen (Pieter); P. Deloukas (Panagiotis); I.M. Heid (Iris); C.M. Lindgren (Cecilia); K.L. Mohlke (Karen); E.K. Speliotes (Elizabeth); U. Thorsteinsdottir (Unnur); I.E. Barroso (Inês); C.S. Fox (Caroline S.); K.E. North (Kari); D.P. Strachan (David P.); J.S. Beckmann (Jacques); S.I. Berndt (Sonja); M. Boehnke (Michael); I.B. Borecki (Ingrid); M.I. McCarthy (Mark); A. Metspalu (Andres); J-A. Zwart (John-Anker); A.G. Uitterlinden (André); C.M. van Duijn (Cornelia); L. Franke (Lude); C.J. Willer (Cristen); A. Price (Alkes); G. Lettre (Guillaume); R.J.F. Loos (Ruth); M.N. Weedon (Michael); E. Ingelsson (Erik); J.R. O´Connell; G.R. Abecasis (Gonçalo); D.I. Chasman (Daniel); D. Anderson (Denise); M.E. Goddard (Michael); P.M. Visscher (Peter); J.N. Hirschhorn (Joel); T.M. Frayling (Timothy)

    2014-01-01

    textabstractUsing genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated

  13. The breaking and making of healthy adult human skeletal muscle in vivo

    DEFF Research Database (Denmark)

    Mackey, Abigail L.; Kjaer, Michael

    2017-01-01

    and highlights the importance of the basement membrane in the process of regeneration. In addition, it provides insight into parallels between the regeneration of adult skeletal muscle in mouse and man, confirming that this model may be a useful tool in investigating myofibre and matrix formation, as well...

  14. Using "The Simpsons" to Teach Humanities with Gen X and Gen Y Adult Students

    Science.gov (United States)

    Fink, Maxwell A.; Foote, Deborah C.

    2007-01-01

    Many educators lament the UNESCO study showing that by the time the average teen graduates from high school he or she has spent more than fifteen thousand hours watching television and only eleven thousand in the classroom (Gorebel, 1998). Rather than regretting this "condition," colleges, universities, and educators of adults and children should…

  15. Mass Entertainment and Human Survival: Television's Potential for Prosocial Effects on Adults.

    Science.gov (United States)

    Loye, David

    Psychosocial adaptations are sometimes affected by experiences that are ordinarily considered to be amusements. In 1974, a field study was undertaken by the Program on Psychosocial Adaptation and the Future to determine if it is possible to measure the effect of television on adult viewers. A sample of 260 couples, controlled for demographic…

  16. Hiding and Searching Strategies of Adult Humans in a Virtual and a Real-Space Room

    Science.gov (United States)

    Talbot, Katherine J.; Legge, Eric L. G.; Bulitko, Vadim; Spetch, Marcia L.

    2009-01-01

    Adults searched for or cached three objects in nine hiding locations in a virtual room or a real-space room. In both rooms, the locations selected by participants differed systematically between searching and hiding. Specifically, participants moved farther from origin and dispersed their choices more when hiding objects than when searching for…

  17. Adult Education as a Human Right: The Latin American Context and the Ecopedagogic Perspective

    Science.gov (United States)

    Gadotti, Moacir

    2011-01-01

    This article presents the concept and practice of adult education as a key issue for Brazil and other Latin American countries, both for formal and non-formal education in the public and private sectors. It includes citizen education focused on democratisation of society and sustainable development. The concept is pluralist and ideological as well…

  18. 21st Century African Philosophy of Adult and Human Resource Education in Southern Africa

    Science.gov (United States)

    Mutamba, Charlene

    2012-01-01

    This paper will attempt to define a philosophy of adult education for the purpose of workforce development in Southern Africa. The different influences such as Ubuntu and communalism, indigenous education, diversity western philosophy, globalization and technology are explored in the context of the Southern African region.

  19. Defining the role of common variation in the genomic and biological architecture of adult human height

    NARCIS (Netherlands)

    Wood, Andrew R.; Esko, Tonu; Yang, Jian; Vedantam, Sailaja; Pers, Tune H.; Gustafsson, Stefan; Chu, Audrey Y.; Estrada, Karol; Luan, Jian'an; Kutalik, Zoltán; Amin, Najaf; Buchkovich, Martin L.; Croteau-Chonka, Damien C.; Day, Felix R.; Duan, Yanan; Fall, Tove; Fehrmann, Rudolf; Ferreira, Teresa; Jackson, Anne U.; Karjalainen, Juha; Lo, Ken Sin; Locke, Adam E.; Mägi, Reedik; Mihailov, Evelin; Porcu, Eleonora; Randall, Joshua C.; Scherag, André; Vinkhuyzen, Anna A. E.; Westra, Harm-Jan; Winkler, Thomas W.; Workalemahu, Tsegaselassie; Zhao, Jing Hua; Absher, Devin; Albrecht, Eva; Anderson, Denise; Baron, Jeffrey; Beekman, Marian; Demirkan, Ayse; Ehret, Georg B.; Feenstra, Bjarke; Feitosa, Mary F.; Fischer, Krista; Fraser, Ross M.; Goel, Anuj; Gong, Jian; Justice, Anne E.; Kanoni, Stavroula; Kleber, Marcus E.; Kristiansson, Kati; Lim, Unhee; Lotay, Vaneet; Lui, Julian C.; Mangino, Massimo; Mateo Leach, Irene; Medina-Gomez, Carolina; Nalls, Michael A.; Nyholt, Dale R.; Palmer, Cameron D.; Pasko, Dorota; Pechlivanis, Sonali; Prokopenko, Inga; Ried, Janina S.; Ripke, Stephan; Shungin, Dmitry; Stancáková, Alena; Strawbridge, Rona J.; Sung, Yun Ju; Tanaka, Toshiko; Teumer, Alexander; Trompet, Stella; van der Laan, Sander W.; van Setten, Jessica; van Vliet-Ostaptchouk, Jana V.; Wang, Zhaoming; Yengo, Loïc; Zhang, Weihua; Afzal, Uzma; Arnlöv, Johan; Arscott, Gillian M.; Bandinelli, Stefania; Barrett, Amy; Bellis, Claire; Bennett, Amanda J.; Berne, Christian; Blüher, Matthias; Bolton, Jennifer L.; Böttcher, Yvonne; Boyd, Heather A.; Bruinenberg, Marcel; Buckley, Brendan M.; Buyske, Steven; Caspersen, Ida H.; Chines, Peter S.; Clarke, Robert; Claudi-Boehm, Simone; Cooper, Matthew; Daw, E. Warwick; de Jong, Pim A.; Deelen, Joris; Delgado, Graciela; Denny, Josh C.; Dhonukshe-Rutten, Rosalie; Dimitriou, Maria; Doney, Alex S. F.; Dörr, Marcus; Eklund, Niina; Eury, Elodie; Folkersen, Lasse; Garcia, Melissa E.; Geller, Frank; Giedraitis, Vilmantas; Go, Alan S.; Grallert, Harald; Grammer, Tanja B.; Gräßler, Jürgen; Grönberg, Henrik; de Groot, Lisette C. P. G. M.; Groves, Christopher J.; Haessler, Jeffrey; Hall, Per; Haller, Toomas; Hallmans, Goran; Hannemann, Anke; Hartman, Catharina A.; Hassinen, Maija; Hayward, Caroline; Heard-Costa, Nancy L.; Helmer, Quinta; Hemani, Gibran; Henders, Anjali K.; Hillege, Hans L.; Hlatky, Mark A.; Hoffmann, Wolfgang; Hoffmann, Per; Holmen, Oddgeir; Houwing-Duistermaat, Jeanine J.; Illig, Thomas; Isaacs, Aaron; James, Alan L.; Jeff, Janina; Johansen, Berit; Johansson, Åsa; Jolley, Jennifer; Juliusdottir, Thorhildur; Junttila, Juhani; Kho, Abel N.; Kinnunen, Leena; Klopp, Norman; Kocher, Thomas; Kratzer, Wolfgang; Lichtner, Peter; Lind, Lars; Lindström, Jaana; Lobbens, Stéphane; Lorentzon, Mattias; Lu, Yingchang; Lyssenko, Valeriya; Magnusson, Patrik K. E.; Mahajan, Anubha; Maillard, Marc; McArdle, Wendy L.; McKenzie, Colin A.; McLachlan, Stela; McLaren, Paul J.; Menni, Cristina; Merger, Sigrun; Milani, Lili; Moayyeri, Alireza; Monda, Keri L.; Morken, Mario A.; Müller, Gabriele; Müller-Nurasyid, Martina; Musk, Arthur W.; Narisu, Narisu; Nauck, Matthias; Nolte, Ilja M.; Nöthen, Markus M.; Oozageer, Laticia; Pilz, Stefan; Rayner, Nigel W.; Renstrom, Frida; Robertson, Neil R.; Rose, Lynda M.; Roussel, Ronan; Sanna, Serena; Scharnagl, Hubert; Scholtens, Salome; Schumacher, Fredrick R.; Schunkert, Heribert; Scott, Robert A.; Sehmi, Joban; Seufferlein, Thomas; Shi, Jianxin; Silventoinen, Karri; Smit, Johannes H.; Smith, Albert Vernon; Smolonska, Joanna; Stanton, Alice V.; Stirrups, Kathleen; Stott, David J.; Stringham, Heather M.; Sundström, Johan; Swertz, Morris A.; Syvänen, Ann-Christine; Tayo, Bamidele O.; Thorleifsson, Gudmar; Tyrer, Jonathan P.; van Dijk, Suzanne; van Schoor, Natasja M.; van der Velde, Nathalie; van Heemst, Diana; van Oort, Floor V. A.; Vermeulen, Sita H.; Verweij, Niek; Vonk, Judith M.; Waite, Lindsay L.; Waldenberger, Melanie; Wennauer, Roman; Wilkens, Lynne R.; Willenborg, Christina; Wilsgaard, Tom; Wojczynski, Mary K.; Wong, Andrew; Wright, Alan F.; Zhang, Qunyuan; Arveiler, Dominique; Bakker, Stephan J. L.; Beilby, John; Bergman, Richard N.; Bergmann, Sven; Biffar, Reiner; Blangero, John; Boomsma, Dorret I.; Bornstein, Stefan R.; Bovet, Pascal; Brambilla, Paolo; Brown, Morris J.; Campbell, Harry; Caulfield, Mark J.; Chakravarti, Aravinda; Collins, Rory; Collins, Francis S.; Crawford, Dana C.; Cupples, L. Adrienne; Danesh, John; de Faire, Ulf; den Ruijter, Hester M.; Erbel, Raimund; Erdmann, Jeanette; Eriksson, Johan G.; Farrall, Martin; Ferrannini, Ele; Ferrières, Jean; Ford, Ian; Forouhi, Nita G.; Forrester, Terrence; Gansevoort, Ron T.; Gejman, Pablo V.; Gieger, Christian; Golay, Alain; Gottesman, Omri; Gudnason, Vilmundur; Gyllensten, Ulf; Haas, David W.; Hall, Alistair S.; Harris, Tamara B.; Hattersley, Andrew T.; Heath, Andrew C.; Hengstenberg, Christian; Hicks, Andrew A.; Hindorff, Lucia A.; Hingorani, Aroon D.; Hofman, Albert; Hovingh, G. Kees; Humphries, Steve E.; Hunt, Steven C.; Hypponen, Elina; Jacobs, Kevin B.; Jarvelin, Marjo-Riitta; Jousilahti, Pekka; Jula, Antti M.; Kaprio, Jaakko; Kastelein, John J. P.; Kayser, Manfred; Kee, Frank; Keinanen-Kiukaanniemi, Sirkka M.; Kiemeney, Lambertus A.; Kooner, Jaspal S.; Kooperberg, Charles; Koskinen, Seppo; Kovacs, Peter; Kraja, Aldi T.; Kumari, Meena; Kuusisto, Johanna; Lakka, Timo A.; Langenberg, Claudia; Le Marchand, Loic; Lehtimäki, Terho; Lupoli, Sara; Madden, Pamela A. F.; Männistö, Satu; Manunta, Paolo; Marette, André; Matise, Tara C.; McKnight, Barbara; Meitinger, Thomas; Moll, Frans L.; Montgomery, Grant W.; Morris, Andrew D.; Morris, Andrew P.; Murray, Jeffrey C.; Nelis, Mari; Ohlsson, Claes; Oldehinkel, Albertine J.; Ong, Ken K.; Ouwehand, Willem H.; Pasterkamp, Gerard; Peters, Annette; Pramstaller, Peter P.; Price, Jackie F.; Qi, Lu; Raitakari, Olli T.; Rankinen, Tuomo; Rao, D. C.; Rice, Treva K.; Ritchie, Marylyn; Rudan, Igor; Salomaa, Veikko; Samani, Nilesh J.; Saramies, Jouko; Sarzynski, Mark A.; Schwarz, Peter E. H.; Sebert, Sylvain; Sever, Peter; Shuldiner, Alan R.; Sinisalo, Juha; Steinthorsdottir, Valgerdur; Stolk, Ronald P.; Tardif, Jean-Claude; Tönjes, Anke; Tremblay, Angelo; Tremoli, Elena; Virtamo, Jarmo; Vohl, Marie-Claude; Amouyel, Philippe; Asselbergs, Folkert W.; Assimes, Themistocles L.; Bochud, Murielle; Boehm, Bernhard O.; Boerwinkle, Eric; Bottinger, Erwin P.; Bouchard, Claude; Cauchi, Stéphane; Chambers, John C.; Chanock, Stephen J.; Cooper, Richard S.; de Bakker, Paul I. W.; Dedoussis, George; Ferrucci, Luigi; Franks, Paul W.; Froguel, Philippe; Groop, Leif C.; Haiman, Christopher A.; Hamsten, Anders; Hayes, M. Geoffrey; Hui, Jennie; Hunter, David J.; Hveem, Kristian; Jukema, J. Wouter; Kaplan, Robert C.; Kivimaki, Mika; Kuh, Diana; Laakso, Markku; Liu, Yongmei; Martin, Nicholas G.; März, Winfried; Melbye, Mads; Moebus, Susanne; Munroe, Patricia B.; Njølstad, Inger; Oostra, Ben A.; Palmer, Colin N. A.; Pedersen, Nancy L.; Perola, Markus; Pérusse, Louis; Peters, Ulrike; Powell, Joseph E.; Power, Chris; Quertermous, Thomas; Rauramaa, Rainer; Reinmaa, Eva; Ridker, Paul M.; Rivadeneira, Fernando; Rotter, Jerome I.; Saaristo, Timo E.; Saleheen, Danish; Schlessinger, David; Slagboom, P. Eline; Snieder, Harold; Spector, Tim D.; Strauch, Konstantin; Stumvoll, Michael; Tuomilehto, Jaakko; Uusitupa, Matti; van der Harst, Pim; Völzke, Henry; Walker, Mark; Wareham, Nicholas J.; Watkins, Hugh; Wichmann, H.-Erich; Wilson, James F.; Zanen, Pieter; Deloukas, Panos; Heid, Iris M.; Lindgren, Cecilia M.; Mohlke, Karen L.; Speliotes, Elizabeth K.; Thorsteinsdottir, Unnur; Barroso, Inês; Fox, Caroline S.; North, Kari E.; Strachan, David P.; Beckmann, Jacques S.; Berndt, Sonja I.; Boehnke, Michael; Borecki, Ingrid B.; McCarthy, Mark I.; Metspalu, Andres; Stefansson, Kari; Uitterlinden, André G.; van Duijn, Cornelia M.; Franke, Lude; Willer, Cristen J.; Price, Alkes L.; Lettre, Guillaume; Loos, Ruth J. F.; Weedon, Michael N.; Ingelsson, Erik; O'Connell, Jeffrey R.; Abecasis, Goncalo R.; Chasman, Daniel I.; Goddard, Michael E.; Visscher, Peter M.; Hirschhorn, Joel N.; Frayling, Timothy M.; McCarty, Catherine A.; Starren, Justin; Peissig, Peggy; Berg, Richard; Rasmussen, Luke; Linneman, James; Miller, Aaron; Choudary, Vidhu; Chen, Lin; Waudby, Carol; Kitchner, Terrie; Reeser, Jonathan; Fost, Norman; Wilke, Russell A.; Chisholm, Rex L.; Avila, Pedro C.; Greenland, Philip; Hayes, M. Geoff; Kho, Abel; Kibbe, Warren A.; Lemke, Amy A.; Lowe, William L.; Smith, Maureen E.; Wolf, Wendy A.; Pacheco, Jennifer A.; Thompson, William K.; Humowiecki, Joel; Law, May; Chute, Christopher; Kullo, Iftikar; Koenig, Barbara; de Andrade, Mariza; Bielinski, Suzette; Pathak, Jyotishman; Savova, Guergana; Wu, Joel; Henriksen, Joan; Ding, Keyue; Hart, Lacey; Palbicki, Jeremy; Larson, Eric B.; Newton, Katherine; Ludman, Evette; Spangler, Leslie; Hart, Gene; Carrell, David; Jarvik, Gail; Crane, Paul; Burke, Wylie; Fullerton, Stephanie Malia; Trinidad, Susan Brown; Carlson, Chris; Hutchinson, Fred; McDavid, Andrew; Roden, Dan M.; Clayton, Ellen; Haines, Jonathan L.; Masys, Daniel R.; Churchill, Larry R.; Cornfield, Daniel; Crawford, Dana; Darbar, Dawood; Denny, Joshua C.; Malin, Bradley A.; Ritchie, Marylyn D.; Schildcrout, Jonathan S.; Xu, Hua; Ramirez, Andrea Havens; Basford, Melissa; Pulley, Jill; Alizadeh, Behrooz Z.; de Boer, Rudolf A.; Boezen, H. Marike; van der Klauw, Melanie M.; Navis, Gerjan; Ormel, Johan; Postma, Dirkje S.; Rosmalen, Judith G. M.; Slaets, Joris P.; Wolffenbuttel, Bruce H. R.; Wijmenga, Cisca; Kathiresan, Sekar; Voight, Benjamin F.; Purcell, Shaun; Musunuru, Kiran; Ardissino, Diego; Mannucci, Pier M.; Anand, Sonia; Engert, James C.; Reilly, Muredach P.; Rader, Daniel J.; Morgan, Thomas; Spertus, John A.; Stoll, Monika; Girelli, Domenico; McKeown, Pascal P.; Patterson, Chris C.; Siscovick, David S.; O'Donnell, Christopher J.; Elosua, Roberto; Peltonen, Leena; Schwartz, Stephen M.; Melander, Olle; Altshuler, David; Merlini, Pier Angelica; Berzuini, Carlo; Bernardinelli, Luisa; Peyvandi, Flora; Tubaro, Marco; Celli, Patrizia; Ferrario, Maurizio; Fetiveau, Raffaela; Marziliano, Nicola; Casari, Giorgio; Galli, Michele; Ribichini, Flavio; Rossi, Marco; Bernardi, Francesco; Zonzin, Pietro; Piazza, Alberto; Yee, Jean; Friedlander, Yechiel; Marrugat, Jaume; Lucas, Gavin; Subirana, Isaac; Sala, Joan; Ramos, Rafael; Meigs, James B.; Williams, Gordon; Nathan, David M.; MacRae, Calum A.; Havulinna, Aki S.; Berglund, Goran; Asselta, Rosanna; Duga, Stefano; Spreafico, Marta; Daly, Mark J.; Nemesh, James; Korn, Joshua M.; McCarroll, Steven A.; Surti, Aarti; Guiducci, Candace; Gianniny, Lauren; Mirel, Daniel; Parkin, Melissa; Burtt, Noel; Gabriel, Stacey B.; Thompson, John R.; Braund, Peter S.; Wright, Benjamin J.; Balmforth, Anthony J.; Ball, Stephen G.; Schunkert, I. Heribert; Linsel-Nitschke, Patrick; Lieb, Wolfgang; Ziegler, Andreas; König, Inke R.; Fischer, Marcus; Stark, Klaus; Grosshennig, Anika; Preuss, Michael; Schreiber, Stefan; Ouwehand, Willem; Scholz, Michael; Cambien, Francois; Goodall, Alison; Li, Mingyao; Chen, Zhen; Wilensky, Robert; Matthai, William; Qasim, Atif; Hakonarson, Hakon H.; Devaney, Joe; Burnett, Mary-Susan; Pichard, Augusto D.; Kent, Kenneth M.; Satler, Lowell; Lindsay, Joseph M.; Waksman, Ron; Knouff, Christopher W.; Waterworth, Dawn M.; Walker, Max C.; Mooser, Vincent; Epstein, Stephen E.; Scheffold, Thomas; Berger, Klaus; Huge, Andreas; Martinelli, Nicola; Olivieri, Oliviero; Corrocher, Roberto; Hólm, Hilma; Do, Ron; Xie, Changchun; Siscovick, David; Matise, Tara; Buyske, Steve; Higashio, Julia; Williams, Rasheeda; Nato, Andrew; Ambite, Jose Luis; Deelman, Ewa; Manolio, Teri; Hindorff, Lucia; Heiss, Gerardo; Taylor, Kira; Franceschini, Nora; Avery, Christy; Graff, Misa; Lin, Danyu; Quibrera, Miguel; Cochran, Barbara; Kao, Linda; Umans, Jason; Cole, Shelley; MacCluer, Jean; Person, Sharina; Pankow, James; Gross, Myron; Fornage, Myriam; Durda, Peter; Jenny, Nancy; Patsy, Bruce; Arnold, Alice; Buzkova, Petra; Haines, Jonathan; Murdock, Deborah; Glenn, Kim; Brown-Gentry, Kristin; Thornton-Wells, Tricia; Dumitrescu, Logan; Bush, William S.; Mitchell, Sabrina L.; Goodloe, Robert; Wilson, Sarah; Boston, Jonathan; Malinowski, Jennifer; Restrepo, Nicole; Oetjens, Matthew; Fowke, Jay; Zheng, Wei; Spencer, Kylee; Pendergrass, Sarah; Le Marchand, Loïc; Wilkens, Lynne; Park, Lani; Tiirikainen, Maarit; Kolonel, Laurence; Cheng, Iona; Wang, Hansong; Shohet, Ralph; Haiman, Christopher; Stram, Daniel; Henderson, Brian; Monroe, Kristine; Schumacher, Fredrick; Anderson, Garnet; Prentice, Ross; LaCroix, Andrea; Wu, Chunyuan; Carty, Cara; Rosse, Stephanie; Young, Alicia; Haessler, Jeff; Kocarnik, Jonathan; Lin, Yi; Jackson, Rebecca; Duggan, David; Kuller, Lew

    2014-01-01

    Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700

  20. Repair of articular cartilage defects by tissue-engineered cartilage constructed with adipose-derived stem cells and acellular cartilaginous matrix in rabbits.

    Science.gov (United States)

    Wang, Z J; An, R Z; Zhao, J Y; Zhang, Q; Yang, J; Wang, J B; Wen, G Y; Yuan, X H; Qi, X W; Li, S J; Ye, X C

    2014-06-18

    After injury, inflammation, or degeneration, articular cartilage has limited self-repair ability. We aimed to explore the feasibility of repair of articular cartilage defects with tissue-engineered cartilage constructed by acellular cartilage matrices (ACMs) seeded with adipose-derived stem cells (ADSCs). The ADSCs were isolated from 3-month-old New Zealand albino rabbit by using collagenase and cultured and amplified in vitro. Fresh cartilage isolated from adult New Zealand albino rabbit were freeze-dried for 12 h and treated with Triton X-100, DNase, and RNase to obtain ACMs. ADSCs were seeded in the acellular cartilaginous matrix at 2x10(7)/mL, and cultured in chondrogenic differentiation medium for 2 weeks to construct tissue-engineered cartilage. Twenty-four New Zealand white rabbits were randomly divided into A, B, and C groups. Engineered cartilage was transplanted into cartilage defect position of rabbits in group A, group B obtained ACMs, and group C did not receive any transplants. The rabbits were sacrificed in week 12. The restored tissue was evaluated using macroscopy, histology, immunohistochemistry, and transmission electron microscopy (TEM). In the tissue-engineered cartilage group (group A), articular cartilage defects of the rabbits were filled with chondrocyte-like tissue with smooth surface. Immunohistochemistry showed type II-collagen expression and Alcian blue staining was positive. TEM showed chondrocytes in the recesses, with plenty of secretary matrix particles. In the scaffold group (group B), the defect was filled with fibrous tissue. No repaired tissue was found in the blank group (group C). Tissue-engineered cartilage using ACM seeded with ADSCs can help repair articular cartilage defects in rabbits.

  1. Intra-Articular Viscosupplementation With Hylan G-F 20 To Treat Osteoarthritis of the Knee

    Science.gov (United States)

    2005-01-01

    Executive Summary Objective To assess the effectiveness and cost-effectiveness of hylan G-F 20 as a substitute for existing treatments for pain due to osteoarthritis (OA) of the knee, other viscosupplementation devices, and/or as an adjunct to conventional therapy. Hylan G-F 20 (brand name Synvisc, which is manufactured by Genzyme) is a high molecular weight derivative of hyaluronan, a component of joint synovial fluid. It acts as a lubricant and shock absorber. It is administered by injection into the joint space to treat pain associated with OA of the knee. Although the injection procedure is an insured service in Ontario, the device, hylan G-F 20, is not. Clinical Need Osteoarthritis is prevalent in 10% to 12% of Ontario adults, and exceeds 40% in Ontario residents aged 65 years and older. About one-half of these people have mild, moderate, or severe OA of the knee. Conventional treatment involves a combination of nonpharmacological management (e.g., weight loss, exercise, social support, and patient education), drugs, (e.g., acetaminophen, COX-2 inhibitors, nonsteroidal anti-inflammatory drugs with/without misoprostol, intra-articular glucocorticoids, opioids, and topical analgesics) and surgical interventions, such as debridement and total knee replacement, when pharmacological management fails. The growing burden of OA of the knee in the aging Ontario population combined with recent safety concerns about COX-2 inhibitors and long wait times for total joint replacement is placing pressure on the demand for new, effective technologies to manage the pain of OA. The Technology Hylan G-F 20 is derived from rooster comb hyaluronan (HA). At the time of writing, eight viscosupplement hyaluronic products are licensed in Canada. Hylan G-F 20 is distinguished from the other products by its chemical structure (i.e., cross-linked hyaluronan, hence hylan) and relatively higher molecular weight, which may bestow greater therapeutic viscoelastic properties. A complete

  2. The influence of rAAV2-mediated SOX2 delivery into neonatal and adult human RPE cells; a comparative study.

    Science.gov (United States)

    Ezati, Razie; Etemadzadeh, Azadeh; Soheili, Zahra-Soheila; Samiei, Shahram; Ranaei Pirmardan, Ehsan; Davari, Malihe; Najafabadi, Hoda Shams

    2018-02-01

    Cell replacement is a promising therapy for degenerative diseases like age-related macular degeneration (AMD). Since the human retina lacks regeneration capacity, much attention has been directed toward persuading for cells that can differentiate into retinal neurons. In this report, we have investigated reprogramming of the human RPE cells and concerned the effect of donor age on the cellular fate as a critical determinant in reprogramming competence. We evaluated the effect of SOX2 over-expression in human neonatal and adult RPE cells in cultures. The coding region of human SOX2 gene was cloned into adeno-associated virus (AAV2) and primary culture of human neonatal/adult RPE cells were infected by recombinant virus. De-differentiation of RPE to neural/retinal progenitor cells was investigated by quantitative real-time PCR and ICC for neural/retinal progenitor cells' markers. Gene expression analysis showed 80-fold and 12-fold over-expression for SOX2 gene in infected neonatal and adult hRPE cells, respectively. The fold of increase for Nestin in neonatal and adult hRPE cells was 3.8-fold and 2.5-fold, respectively. PAX6 expression was increased threefold and 2.5-fold in neonatal/adult treated cultures. Howbeit, we could not detect rhodopsin, and CHX10 expression in neonatal hRPE cultures and expression of rhodopsin in adult hRPE cells. Results showed SOX2 induced human neonatal/adult RPE cells to de-differentiate toward retinal progenitor cells. However, the increased number of PAX6, CHX10, Thy1, and rhodopsin positive cells in adult hRPE treated cultures clearly indicated the considerable generation of neuro-retinal terminally differentiated cells. © 2017 Wiley Periodicals, Inc.

  3. Parallel assessment of the effects of bisphenol A and several of its analogs on the adult human testis.

    Science.gov (United States)

    Desdoits-Lethimonier, C; Lesné, L; Gaudriault, P; Zalko, D; Antignac, J P; Deceuninck, Y; Platel, C; Dejucq-Rainsford, N; Mazaud-Guittot, S; Jégou, B

    2017-07-01

    Are bisphenol A (BPA) and BPA analogs (BPA-A) safe for male human reproductive function? The endocrine function of human testes explants [assessed by measuring testosterone and insulin-like factor 3 (INSL3)] was impacted by exposure of the human adult testis explants to BPA/BPA-A. The few epidemiologic studies performed suggest that bisphenols have potential endocrine disruptive properties, but they did not identify clear and direct patterns of endocrine disruption. Adult human testis explants in culture were exposed to BPA and the analogs bisphenol F (BPF), bisphenol S (BPS), bisphenol E (BPE), bisphenol B (BPB) and bisphenol A diglycidyl ether (BADGE) at 10-9-10-5 M for 24 or 48 h. Human adult testes were obtained from prostate cancer patients who had no hormone therapy, or from multiorgan donors. After ex vivo exposure to the investigated bisphenols, the measured outcomes were related to histopathology (gross morphology and germ cell viability determined by anti-caspase three immunohistochemistry), and the levels of testosterone, INSL3 and inhibin B were measured using immunoassays. The levels of mRNA encoding key enzymes of bisphenol biotransformation were investigated by quantitative PCR: UGT2B15 UDP (glucuronosyltransferase two family, polypeptide B15), GUSB (glucuronidase beta), SULT1A1 and 3 (sulfotransferase family 1 A member 1 and 3) and STS (steroid sulfatase). A significant dose-dependent inhibition was found between testosterone levels measured in the culture medium and concentrations of BPA (P = 0.00778 at 24 h and P = 0.0291 at 48 h), BPE (P = 0.039) and BPF (P = 0.00663). The observed BPA and BPA-A-induced inhibition of testosterone production varied according to duration of exposure and BPA/BPA-A concentrations. BPA (10-9 M; P bisphenols. N/A. Environmental compounds cannot be deliberately administered to men, justifying the use of an ex vivo approach. A relatively low number of testes samples were available for analysis (n = 3, except for

  4. Contrast agent enhanced pQCT of articular cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Kallioniemi, A S [Department of Physics, University of Kuopio, POB 1627, 70211 Kuopio (Finland); Jurvelin, J S [Department of Physics, University of Kuopio, POB 1627, 70211 Kuopio (Finland); Nieminen, M T [Department of Diagnostic Radiology, POB 50, 90029 OYS, Oulu University Hospital, Oulu (Finland); Lammi, M J [Department of Anatomy, Institute of Biomedicine, University of Kuopio, POB 1627, 70211 Kuopio (Finland); Toeyraes, J [Department of Physics, University of Kuopio, POB 1627, 70211 Kuopio (Finland)

    2007-02-21

    The delayed gadolinium enhanced MRI of cartilage (dGEMRIC) technique is the only non-invasive means to estimate proteoglycan (PG) content in articular cartilage. In dGEMRIC, the anionic paramagnetic contrast agent gadopentetate distributes in inverse relation to negatively charged PGs, leading to a linear relation between T{sub 1,Gd} and spatial PG content in tissue. In the present study, for the first time, contrast agent enhanced peripheral quantitative computed tomography (pQCT) was applied, analogously to dGEMRIC, for the quantitative detection of spatial PG content in cartilage. The suitability of two anionic radiographic contrast agents, gadopentetate and ioxaglate, to detect enzymatically induced PG depletion in articular cartilage was investigated. First, the interrelationships of x-ray absorption, as measured with pQCT, and the contrast agent solution concentration were investigated. Optimal contrast agent concentrations for the following experiments were selected. Second, diffusion rates for both contrast agents were investigated in intact (n = 3) and trypsin-degraded (n 3) bovine patellar cartilage. The contrast agent concentration of the cartilaginous layer was measured prior to and 2-27 h after immersion. Optimal immersion time for the further experiments was selected. Third, the suitability of gadopentetate and ioxaglate enhanced pQCT to detect the enzymatically induced specific PG depletion was investigated by determining the contrast agent concentrations and uronic acid and water contents in digested and intact osteochondral samples (n = 16). After trypsin-induced PG loss (-70%, p < 0.05) the penetration of gadopentetate and ioxaglate increased (p < 0.05) by 34% and 48%, respectively. Gadopentetate and ioxaglate concentrations both showed strong correlation (r = -0.95, r -0.94, p < 0.01, respectively) with the uronic acid content. To conclude, contrast agent enhanced pQCT provides a technique to quantify PG content in normal and experimentally

  5. Contrast agent enhanced pQCT of articular cartilage

    Science.gov (United States)

    Kallioniemi, A. S.; Jurvelin, J. S.; Nieminen, M. T.; Lammi, M. J.; Töyräs, J.

    2007-02-01

    The delayed gadolinium enhanced MRI of cartilage (dGEMRIC) technique is the only non-invasive means to estimate proteoglycan (PG) content in articular cartilage. In dGEMRIC, the anionic paramagnetic contrast agent gadopentetate distributes in inverse relation to negatively charged PGs, leading to a linear relation between T1,Gd and spatial PG content in tissue. In the present study, for the first time, contrast agent enhanced peripheral quantitative computed tomography (pQCT) was applied, analogously to dGEMRIC, for the quantitative detection of spatial PG content in cartilage. The suitability of two anionic radiographic contrast agents, gadopentetate and ioxaglate, to detect enzymatically induced PG depletion in articular cartilage was investigated. First, the interrelationships of x-ray absorption, as measured with pQCT, and the contrast agent solution concentration were investigated. Optimal contrast agent concentrations for the following experiments were selected. Second, diffusion rates for both contrast agents were investigated in intact (n = 3) and trypsin-degraded (n = 3) bovine patellar cartilage. The contrast agent concentration of the cartilaginous layer was measured prior to and 2-27 h after immersion. Optimal immersion time for the further experiments was selected. Third, the suitability of gadopentetate and ioxaglate enhanced pQCT to detect the enzymatically induced specific PG depletion was investigated by determining the contrast agent concentrations and uronic acid and water contents in digested and intact osteochondral samples (n = 16). After trypsin-induced PG loss (-70%, p < 0.05) the penetration of gadopentetate and ioxaglate increased (p < 0.05) by 34% and 48%, respectively. Gadopentetate and ioxaglate concentrations both showed strong correlation (r = -0.95, r = -0.94, p < 0.01, respectively) with the uronic acid content. To conclude, contrast agent enhanced pQCT provides a technique to quantify PG content in normal and experimentally

  6. Contrast agent enhanced pQCT of articular cartilage

    International Nuclear Information System (INIS)

    Kallioniemi, A S; Jurvelin, J S; Nieminen, M T; Lammi, M J; Toeyraes, J

    2007-01-01

    The delayed gadolinium enhanced MRI of cartilage (dGEMRIC) technique is the only non-invasive means to estimate proteoglycan (PG) content in articular cartilage. In dGEMRIC, the anionic paramagnetic contrast agent gadopentetate distributes in inverse relation to negatively charged PGs, leading to a linear relation between T 1,Gd and spatial PG content in tissue. In the present study, for the first time, contrast agent enhanced peripheral quantitative computed tomography (pQCT) was applied, analogously to dGEMRIC, for the quantitative detection of spatial PG content in cartilage. The suitability of two anionic radiographic contrast agents, gadopentetate and ioxaglate, to detect enzymatically induced PG depletion in articular cartilage was investigated. First, the interrelationships of x-ray absorption, as measured with pQCT, and the contrast agent solution concentration were investigated. Optimal contrast agent concentrations for the following experiments were selected. Second, diffusion rates for both contrast agents were investigated in intact (n = 3) and trypsin-degraded (n 3) bovine patellar cartilage. The contrast agent concentration of the cartilaginous layer was measured prior to and 2-27 h after immersion. Optimal immersion time for the further experiments was selected. Third, the suitability of gadopentetate and ioxaglate enhanced pQCT to detect the enzymatically induced specific PG depletion was investigated by determining the contrast agent concentrations and uronic acid and water contents in digested and intact osteochondral samples (n = 16). After trypsin-induced PG loss (-70%, p < 0.05) the penetration of gadopentetate and ioxaglate increased (p < 0.05) by 34% and 48%, respectively. Gadopentetate and ioxaglate concentrations both showed strong correlation (r = -0.95, r -0.94, p < 0.01, respectively) with the uronic acid content. To conclude, contrast agent enhanced pQCT provides a technique to quantify PG content in normal and experimentally degraded

  7. Human intestinal tissue with adult stem cell properties derived from pluripotent stem cells

    NARCIS (Netherlands)

    Forster, Ryan; Chiba, Kunitoshi; Schaeffer, Lorian; Regalado, Samuel G; Lai, Christine S; Gao, Qing; Kiani, Samira; Farin, Henner F; Clevers, Hans; Cost, Gregory J; Chan, Andy; Rebar, Edward J; Urnov, Fyodor D; Gregory, Philip D; Pachter, Lior; Jaenisch, Rudolf; Hockemeyer, Dirk

    2014-01-01

    Genetically engineered human pluripotent stem cells (hPSCs) have been proposed as a source for transplantation therapies and are rapidly becoming valuable tools for human disease modeling. However, many applications are limited due to the lack of robust differentiation paradigms that allow for the

  8. Fatty acid oxidation in the human fetus: implications for fetal and adult disease

    NARCIS (Netherlands)

    Oey, Nadia A.; Ruiter, Jos P. N.; Attié-Bitach, Tania; Ijlst, Lodewijk; Wanders, Ronald J. A.; Wijburg, Frits A.

    2006-01-01

    Studies in the last few years have shown a remarkably high activity of fatty acid oxidation (FAO) enzymes in human placenta. We have recently shown mRNA expression as well as enzymatic activity of long-chain FAO enzymes in the human embryo and fetus. In this study we show activity of the FAO enzymes

  9. Detection of human bocavirus from children and adults with acute respiratory tract illness in Guangzhou, southern China

    Directory of Open Access Journals (Sweden)

    Liu Wen-Kuan

    2011-12-01

    Full Text Available Abstract Background Human bocavirus (HBoV is a newly discovered parvovirus associated with acute respiratory tract illness (ARTI and gastrointestinal illness. Our study is the first to analyze the characteristics of HBoV-positive samples from ARTI patients with a wide age distribution from Guangzhou, southern China. Methods Throat swabs (n=2811 were collected and analyzed from children and adults with ARTI over a 13-month period. The HBoV complete genome from a 60 year-old female patient isolate was also determined. Results HBoV DNA was detected in 65/2811 (2.3% samples, of which 61/1797 were from children (Mycoplasma pneumoniae had the highest frequency of 16.9% (11/65. Upper and lower respiratory tract illness were common symptoms, with 19/65 (29.2% patients diagnosed with pneumonia by chest radiography. All four adult patients had systemic influenza-like symptoms. Phylogenetic analysis of the complete genome revealed a close relationship with other HBoVs, and a more distant relationship with HBoV2 and HBoV3. Conclusions HBoV was detected from children and adults with ARTI from Guangzhou, southern China. Elderly people were also susceptive to HBoV. A single lineage of HBoV was detected among a wide age distribution of patients with ARTI.

  10. A Rare Case of Human Coronavirus 229E Associated with Acute Respiratory Distress Syndrome in a Healthy Adult

    Directory of Open Access Journals (Sweden)

    Foula Vassilara

    2018-01-01

    Full Text Available Human coronavirus 229E (HCoV-229E is one of the first coronavirus strains being described. It is linked to common cold symptoms in healthy adults. Younger children and the elderly are considered vulnerable to developing lower respiratory tract infections (LRTIs. In particular, immunocompromised patients have been reported with severe and life-threatening LRTIs attributed to HCoV-229E. We report for the first time a case of LRTI and acute respiratory distress syndrome developed in a healthy adult with no comorbidities and HCoV-229E strain identified as the only causative agent. A 45-year-old female with a clear medical history presented with fever, cough, and headache. Respiratory tract infection was diagnosed, and empirical antibiotics were started. Within two days, she developed bilateral pleural effusions, diffuse consolidations, and ground glass opacities involving all lung fields. She needed immediate oxygen supply, while ABGs deteriorated and chest imaging and PaO2/FiO2 indicated ARDS. Early administration of systemic corticosteroids led to gradual clinical improvement. Multiplex PCR from nasal secretions was positive only for HCoV-229E and negative for multiple other pathogens. It remains to be elucidated how an immunocompetent adult developed a life-threatening LRTI caused by a “benign considered” coronavirus strain, the HCoV-229E.

  11. Procedures for ambient-pressure and tympanometric tests of aural acoustic reflectance and admittance in human infants and adults

    Science.gov (United States)

    Keefe, Douglas H.; Hunter, Lisa L.; Feeney, M. Patrick; Fitzpatrick, Denis F.

    2015-01-01

    Procedures are described to measure acoustic reflectance and admittance in human adult and infant ears at frequencies from 0.2 to 8 kHz. Transfer functions were measured at ambient pressure in the ear canal, and as down- or up-swept tympanograms. Acoustically estimated ear-canal area was used to calculate ear reflectance, which was parameterized by absorbance and group delay over all frequencies (and pressures), with substantial data reduction for tympanograms. Admittance measured at the probe tip in adults was transformed into an equivalent admittance at the eardrum using a transmission-line model for an ear canal with specified area and ear-canal length. Ear-canal length was estimated from group delay around the frequency above 2 kHz of minimum absorbance. Illustrative measurements in ears with normal function are described for an adult, and two infants at 1 month of age with normal hearing and a conductive hearing loss. The sensitivity of this equivalent eardrum admittance was calculated for varying estimates of area and length. Infant-ear patterns of absorbance peaks aligned in frequency with dips in group delay were explained by a model of resonant canal-wall mobility. Procedures will be applied in a large study of wideband clinical diagnosis and monitoring of middle-ear and cochlear function. PMID:26723319

  12. Preservation of beta cell function in adult human pancreatic islets for several months in vitro

    DEFF Research Database (Denmark)

    Brunstedt, J; Andersson, A; Frimodt-Møller, C

    1979-01-01

    Islets of Langerhans were isolated from four human kidney donors, aged 16 to 21 years by the collagenase method described for isolation of rodent islets. So far the human islets have been kept in tissue culture, without attachment, in medium RPMI 1640 supplemented with 10% calf serum for more tha...... technique presents a valuable tool for studying chronic effects of metabolites and hormones on islet function, as well as for islet storage prior to transplantation into humans.......Islets of Langerhans were isolated from four human kidney donors, aged 16 to 21 years by the collagenase method described for isolation of rodent islets. So far the human islets have been kept in tissue culture, without attachment, in medium RPMI 1640 supplemented with 10% calf serum for more than...

  13. Growth Hormone Safety Workshop Position Paper: a critical appraisal of recombinant human growth hormone therapy in children and adults

    DEFF Research Database (Denmark)

    Allen, David B; Backeljauw, Philippe; Bidlingmaier, Martin

    2015-01-01

    Recombinant human GH (rhGH) has been in use for 30 years, and over that time its safety and efficacy in children and adults has been subject to considerable scrutiny. In 2001, a statement from the GH Research Society (GRS) concluded that 'for approved indications, GH is safe'; however, the statem...... (PES) convened a meeting to r