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Sample records for adult human articular

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

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    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.

  2. Human stem cells and articular cartilage regeneration.

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    Inui, Atsuyuki; Iwakura, Takashi; Reddi, A Hari

    2012-11-05

    The regeneration of articular cartilage damaged due to trauma and posttraumatic osteoarthritis is an unmet medical need. Current approaches to regeneration and tissue engineering of articular cartilage include the use of chondrocytes, stem cells, scaffolds and signals, including morphogens and growth factors. Stem cells, as a source of cells for articular cartilage regeneration, are a critical factor for articular cartilage regeneration. This is because articular cartilage tissue has a low cell turnover and does not heal spontaneously. Adult stem cells have been isolated from various tissues, such as bone marrow, adipose, synovial tissue, muscle and periosteum. Signals of the transforming growth factor beta superfamily play critical roles in chondrogenesis. However, adult stem cells derived from various tissues tend to differ in their chondrogenic potential. Pluripotent stem cells have unlimited proliferative capacity compared to adult stem cells. Chondrogenesis from embryonic stem (ES) cells has been studied for more than a decade. However, establishment of ES cells requires embryos and leads to ethical issues for clinical applications. Induced pluripotent stem (iPS) cells are generated by cellular reprogramming of adult cells by transcription factors. Although iPS cells have chondrogenic potential, optimization, generation and differentiation toward articular chondrocytes are currently under intense investigation.

  3. Human Stem Cells and Articular Cartilage Regeneration

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    A. Hari Reddi

    2012-11-01

    Full Text Available  The regeneration of articular cartilage damaged due to trauma and posttraumatic osteoarthritis is an unmet medical need. Current approaches to regeneration and tissue engineering of articular cartilage include the use of chondrocytes, stem cells, scaffolds and signals, including morphogens and growth factors. Stem cells, as a source of cells for articular cartilage regeneration, are a critical factor for articular cartilage regeneration. This is because articular cartilage tissue has a low cell turnover and does not heal spontaneously. Adult stem cells have been isolated from various tissues, such as bone marrow, adipose, synovial tissue, muscle and periosteum. Signals of the transforming growth factor beta superfamily play critical roles in chondrogenesis. However, adult stem cells derived from various tissues tend to differ in their chondrogenic potential. Pluripotent stem cells have unlimited proliferative capacity compared to adult stem cells. Chondrogenesis from embryonic stem (ES cells has been studied for more than a decade. However, establishment of ES cells requires embryos and leads to ethical issues for clinical applications. Induced pluripotent stem (iPS cells are generated by cellular reprogramming of adult cells by transcription factors. Although iPS cells have chondrogenic potential, optimization, generation and differentiation toward articular chondrocytes are currently under intense investigation.

  4. Basic fibroblast growth factor induces matrix metalloproteinase-13 via ERK MAP kinase-altered phosphorylation and sumoylation of Elk-1 in human adult articular chondrocytes

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    Hee-Jeong Im

    2009-10-01

    Full Text Available Hee-Jeong Im,1–4 Andrew D Sharrocks,5 Xia Lin,6 Dongyao Yan,1 Jaesung Kim,1 Andre J van Wijnen,7 Robert A Hipskind81Departments of Biochemistry, 2Internal Medicine, 3Section of Rheumatology, Orthopedic Surgery, 4Rush University Medical Center, and Department of Bioengineering; University of Illinois at Chicago, IL USA; 5Faculty of Life Sciences, University of Manchester, Oxford Rd, Manchester, UK; 6Michael D DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas, USA; 7Department of Cell Biology, University of Massachusetts Medical School, Worcester, MA, USA; 8Institute De Genetique Moleculaire de Montpellier, FranceAbstract: Degradation of the extracellular matrix (ECM by matrix metalloproteinases (MMPs and release of basic fibroblast growth factor (bFGF are principal aspects of the pathology of osteoarthritis (OA. ECM disruption leads to bFGF release, which activates the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK pathway and its downstream target the Ets-like transcription factor Elk-1. Previously we demonstrated that the bFGF-ERK-Elk-1 signaling axis is responsible for the potent induction of MMP-13 in human primary articular chondrocytes. Here we report that, in addition to phosphorylation of Elk-1, dynamic posttranslational modification of Elk-1 by small ubiquitin-related modifier (SUMO serves as an important mechanism through which MMP-13 gene expression is regulated. We show that bFGF activates Elk-1 mainly through the ERK pathway and that increased phosphorylation of Elk-1 is accompanied by decreased conjugation of SUMO to Elk-1. Reporter gene assays reveal that phosphorylation renders Elk-1 competent for induction of MMP-13 gene transcription, while sumoylation has the opposite effect. Furthermore, we demonstrate that the SUMO-conjugase Ubc9 acts as a key mediator for Elk-1 sumoylation. Taken together, our results suggest that sumoylation antagonizes the phosphorylation

  5. Spontaneous Redifferentiation of Dedifferentiated Human Articular Chondrocytes on Hydrogel Surfaces

    OpenAIRE

    2010-01-01

    Chondrocytes rapidly dedifferentiate into a more fibroblastic phenotype on a two-dimensional polystyrene substratum. This impedes fundamental research on these cells as well as their clinical application. This study investigated the redifferentiation behavior of dedifferentiated chondrocytes on a hydrogel substratum. Dedifferentiated normal human articular chondrocyte–knee (NHAC-kn) cells were released from the sixth-passage monolayer cultured on a polystyrene surface. These cells were then s...

  6. ROCK inhibitor prevents the dedifferentiation of human articular chondrocytes

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    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

  7. Immortalization of human articular chondrocytes and induction of their phenotype

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    何清义; 李起鸿; 杨柳; 许建中

    2003-01-01

    Objective To immortalize human articular chondrocytes (HACs) using gene transfection and to maintain stable phenotype of transformed HACs after induction.Methods HACs were transfected with the retroviral vector pLXSN encoding human papillomavirus 16E7 (HPV16E7), and the transformed clones were sorted and proliferated. Karyotype analysis, clone forming tests and nude mice tumor forming tests were applied to check the characteristics of the transformation. Type Ⅱ collagen of transformed chondrocytes was inducted with free serum medium (FSM) supplemented with nutridoma-sp and ascorbate. Results Immortalized HACs were isolated with fifty passages achieved. The HPV16E7 transformed cells were confirmed to be benign. Induction of FSM with nutridoma-sp and ascorbate promoted type Ⅱ collagen of transformed chondrocytes to the high levels of normal chondrocytes. Conclusion HACs transformed with HPV16E7 survive for long periods in vitro, and type Ⅱ collagen can maintain stability after induction.

  8. bFGF influences human articular chondrocyte differentiation

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    Schmal, H; Zwingmann, J; Fehrenbach, M

    2007-01-01

    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...... in monolayer. bFGF-dependent cell proliferation, production of collagen type II and aggrecan were monitored 10 days after isolation. Furthermore, effect of bFGF on cell cycle, cell morphology, and mRNA expression of integrins and chondrogenic markers determined by real time PCR were analyzed. RESULTS: b...... unchanged. Supplementation of cell culture with bFGF reduced collagen type II mRNA by 49%, but increased expression of the integrin alpha(2) by 70%. bFGF did not significantly regulate the integrins alpha(1), alpha(5), alpha(10), alpha(v) and type I collagen. bFGF reduced the amount of collagen type II...

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

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    Gradišnik, Lidija; Gorenjak, Mario; Vogrin, Matjaž

    2017-01-01

    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 common and very

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

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    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

  11. Cartilage tissue engineering using pre-aggregated human articular chondrocytes

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    F Wolf

    2008-12-01

    Full Text Available In this study, we first aimed at determining whether human articular chondrocytes (HAC proliferate in aggregates in the presence of strong chondrocyte mitogens. We then investigated if the aggregated cells have an enhanced chondrogenic capacity as compared to cells cultured in monolayer. HAC from four donors were cultured in tissue culture dishes either untreated or coated with 1% agarose in the presence of TGFb-1, FGF-2 and PDGF-BB. Proliferation and stage of differentiation were assessed by measuring respectively DNA contents and type II collagen mRNA. Expanded cells were induced to differentiate in pellets or in Hyaff®-11 meshes and the formed tissues were analysed biochemically for glycosaminoglycans (GAG and DNA, and histologically by Safranin O staining. The amount of DNA in aggregate cultures increased significantly from day 2 to day 6 (by 3.2-fold, but did not further increase with additional culture time. Expression of type II collagen mRNA was about two orders of magnitude higher in aggregated HAC as compared to monolayer expanded cells. Pellets generated by aggregated HAC were generally more intensely stained for GAG than those generated by monolayer-expanded cells. Scaffolds seeded with aggregates accumulated more GAG (1.3-fold than scaffolds seeded with monolayer expanded HAC. In conclusion, this study showed that HAC culture in aggregates does not support a relevant degree of expansion. However, aggregation of expanded HAC prior to loading into a porous scaffold enhances the quality of the resulting tissues and could thus be introduced as an intermediate culture phase in the manufacture of engineered cartilage grafts.

  12. Human Adipose-Derived Mesenchymal Progenitor Cells Engraft into Rabbit Articular Cartilage

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    Wen Wang

    2015-05-01

    Full Text Available Mesenchymal stem cells (MSCs are known to have the potential for articular cartilage regeneration, and are suggested for the treatment of osteoarthritis (OA. Here, we investigated whether intra-articular injection of xenogeneic human adipose-derived mesenchymal progenitor cells (haMPCs promoted articular cartilage repair in rabbit OA model and engrafted into rabbit articular cartilage. The haMPCs were cultured in vitro, and phenotypes and differentiation characteristics of cells were evaluated. OA was induced surgically by anterior cruciate ligament transection (ACLT and medical meniscectomy of knee joints. At six weeks following surgery, hyaluronic acid (HA or haMPCs was injected into the knee joints, the contralateral knee served as normal control. All animals were sacrificed at the 16th week post-surgery. Assessments were carried out by macroscopic examination, hematoxylin/eosin (HE and Safranin-O/Fast green stainings and immunohistochemistry. The data showed that haMPC treatment promoted cartilage repair. Signals of human mitochondrial can be directly detected in haMPC treated cartilage. The haMPCs expressed human leukocyte antigen I (HLA-I but not HLA-II-DR in vivo. These results suggest that intra-articular injection of haMPCs promotes regeneration of articular cartilage in rabbit OA model, and support the notion that MPCs are transplantable between HLA-incompatible individuals.

  13. Traumatic atlantoaxial rotatory fixation associated with C2 articular facet fracture in adult patient: Case report

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    Mehdi Bellil

    2014-01-01

    Full Text Available Traumatic atlantoaxial rotatory fixation is a very rare injury in adults which is often misdiagnosed initially. Its combination with C2 fractures is predominated by dens lesions. Therapeutic management is challenging because of the difficulty to achieve optimal reduction and permanent stability. We report a rare case of traumatic atlantoaxial rotatory fixation in a 56-year-old women associated with C2 articular facet fracture successfully treated by conservative means after patient-awake manual reduction with optimal functional and radiographic outcome.

  14. Metric analysis of loading magnitudes at articular and non-articular weight-bearing surfaces in human calcaneus.

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    Mahato, Niladri Kumar; Murthy, S Sathiya Narayana

    2013-03-01

    The calcaneus is axially loaded at its articular interface with the talus. A large bulk of this load is transmitted to the ground across the non-articular tubercles at the plantar surface of the bone. A small part of the incumbent load sustained by the calcaneus is directed towards the forefoot at the calcaneo-cuboid junction. This study investigates the proportion of load distributed across the articular and non-articular surfaces of the calcaneus. The present study demonstrates strong and significant correlation between some of the load bearing variables and suggests the need for further investigations to understand the effect of angular aspects of axial loading on the calcaneus. Accounting for the relative distribution of weight across the articular and non-articular areas may enable us to appreciate the internal trabecular structure of the calcaneus in light of its clinical importance.

  15. Controversies in the management of intra-articular fractures of distal humerus in adults

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    Sudhir Babhulkar

    2011-01-01

    Full Text Available Background: The surgical approach, type of olecranon osteotomy, method of stabilization of osteotomy, type of fracture stabilization, orthogonal vs parallel plate fixation, need for transposition of ulnar nerve, place for primary total elbow replacement, and type of rehabilitation schedule after surgical fracture treatment are the controversial issues in the treatment of complex intra-articular distal humerus fractures (C2 and C3 in adults. Severe comminution, bone loss, and osteoporosis at the site of distal articular fractures of humerus often lead to unsatisfactory results due to inadequate fixation. We hereby report the outcome of a series of intracondylar fractures of the humerus treated by open reduction and internal fixation and discuss the controversies in light of published literature. Materials and Methods: One hundred and eighty-four patients of intra-articular fractures of distal humerus (C2 and C3 were operated by posterior transolecranon approach between January 1980 and December 2008. Initially, in the first part Chevron intra-articular osteotomy (n=108 was performed out of which 94 have been published in another publication. In later second part (1993 onward, extra-articular olecranon osteotomy (n=76 was routinely performed. Both columns were stably fixed by orthogonal methods; (n=174 however, during the last 2 years, in 10 patients with severe comminution with bone loss, stabilization was achieved by parallel plating. The osteotomy was routinely stabilized by tension band wiring with two parallel K-wires introduced up to the anterior ulnar cortex. The results were evaluated by the staging system of Caja et al. at a minimum follow-up of 2 years. Results: In the first part of the study (n=94, there was delayed union in 4% (n=4, with the fracture taking more than 20 weeks for union. There was delayed union of ulnar osteotomy (n=3 and failure of one tension band wiring, requiring revision. Some loss of motion was seen in 20% of

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

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    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.

  17. 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...

  18. Differences in articular-eminence inclination between medieval and contemporary human populations.

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    Kranjčić, Josip; Vojvodić, Denis; Žabarović, Domagoj; Vodanović, Marin; Komar, Daniel; Mehulić, Ketij

    2012-08-01

    The articular-eminence inclination is an important element in the biomechanics of the temporomandibular joint and the entire masticatory system; however, very little is known about this inclination in archaeological human populations. Therefore, the aim of this study was to determine the values of, in addition to the differences between, the articular-eminence inclination in medieval and contemporary human populations. The study was carried out on two dry skull groups. The first group consisted of 14 dry skulls from the medieval culture group Bijelo Brdo (BB) of East Croatia, and the other consisted of 137 recent dry skulls from the osteologic collection of the Institute of Anatomy (IA) in Zagreb. All BB skulls were dentulous, whereas the IA skulls were divided into dentulous and edentulous groups. The articular-eminence inclination was measured in relation to the Frankfurt horizontal plane on digital images of the skull's two lateral views using AutoCAD computer software. The mean value of the articular-eminence inclination in the BB sample group (49.57°) was lower, with a statistical significance (pmedieval specimens are needed to confirm the results obtained from this study.

  19. FIXATION OF ADULT EXRTA –ARTICULAR DISTAL THIRD DIA PHYSEAL FRACTURE OF HUMERUS-A PROSPECTIVE STUDY

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    Ahmed

    2013-05-01

    Full Text Available ABSTRACT : Distal humerus fracture in adult is very difficul t to treat. It is very difficult to achieve alignment, anatomical reduction, rigid fixation, im mediate mobilization and fracture union in such patient MATERIAL AND METHOD-We operate 41 patient o f close extra articular fracture of distal third of humerus, using posterior approach. 10 case s were fixed with single locking plate,6 cases by single distal multiple hole plate,12 cases by two r econstruction plate,6 cases by simple T plate,7case s by oblique metaphyseal locking plate. RESULT- Doubl e plating with reconstruction plates provide a more rigid fixation than a single-locked plate. CON CLUSION- Fixation of extra articular distal humerus, diaphyseal fracture in adult are better w ith double plating than single plating, which provide more rigid fixation with early mobilization and higher mayo elbow score

  20. A superficial hyperechoic band in human articular cartilage on ultrasonography with histological correlation: preliminary observations

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    Tae Sun Han

    2015-04-01

    Full Text Available Purpose: To demonstrate the superficial hyperechoic band (SHEB in articular cartilage by using ultrasonography (US and to assess its correlation with histological images. Methods: In total, 47 regions of interest (ROIs were analyzed from six tibial osteochondral specimens (OCSs that were obtained after total knee arthroplasty. Ultrasonograms were obtained for each OCS. Then, matching histological sections from all specimens were obtained for comparison with the ultrasonograms. Two types of histological staining were used: Safranin-O stain (SO to identify glycosaminoglycans (GAG and Masson’s trichrome stain (MT to identify collagen. In step 1, two observers evaluated whether there was an SHEB in each ROI. In step 2, the two observers evaluated which histological staining method correlated better with the SHEB by using the ImageJ software. Results: In step 1 of the analysis, 20 out of 47 ROIs showed an SHEB (42.6%, kappa=0.579. Step 2 showed that the SHEB correlated significantly better with the topographical variation in stainability in SO staining, indicating the GAG distribution, than with MT staining, indicating the collagen distribution (P<0.05, kappa=0.722. Conclusion: The SHEB that is frequently seen in human articular cartilage on high-resolution US correlated better with variations in SO staining than with variations in MT staining. Thus, we suggest that a SHEB is predominantly related to changes in GAG. Identifying an SHEB by US is a promising method for assessing the thickness of articular cartilage or for monitoring early osteoarthritis.

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

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    Zhong, Leilei; Huang, Xiaobin; Karperien, Marcel; Post, Janine N

    2015-08-14

    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.

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

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    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.

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

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    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.

  4. Innervation and functional characteristics of connective tissues, especially elastic fibers, in human fetal thoracic intervertebral articular capsule and its surroundings.

    Science.gov (United States)

    Shiraishi, Yosuke; Kobayashi, Miya; Yasui, Masaya; Ozaki, Noriyuki; Sugiura, Yasuo

    2003-05-01

    The articular capsules between the thoracic vertebrae, which have physiologically different functions from those of other levels of the vertebrae, have yet to be subjected to neuro-anatomical and fine structural analysis. In the present study, we analyzed serial frozen sections of decalcified thoracic vertebrae in human fetuses, and identified the articular capsule tissue with its unique distribution of elastic fibers. The fine structure of the elastic fibers was studied by transmission electron microscopy. In the early-stage fetus, the fibrous membrane forming the lateral intervertebral articular capsule contained abundant thin elastic fibers consisting of microfibrils. In the late-stage fetus, the lateral capsule of fibrous membrane was occupied by thick elastic fibers. A medial articular capsule, namely the ligamenta flava, contained numerous thick elastic fibers in both early and late-stage fetuses. The distributional differences in nerve fibers between early and late-stage fetuses were determined by immunostaining, using antibodies raised against protein gene product 9.5 (PGP 9.5; ubiquitin carboxyl-terminal hydrolase). Innervation by PGP 9.5 immunoreactive fibers was limited to the areas of the articular capsules near the blood vessels, which may indicate their functional relation with blood flow. No PGP 9.5 immunoreactive fibers were found in the ligamenta flava of the late-stage fetus. Innervation might be directly involved in the development of the intervertebral articular capsules in normal human fetuses.

  5. 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.

  6. A comparison of healthy human and swine articular cartilage dynamic indentation mechanics.

    Science.gov (United States)

    Ronken, S; Arnold, M P; Ardura García, H; Jeger, A; Daniels, A U; Wirz, D

    2012-05-01

    Articular cartilage is a multicomponent, poroviscoelastic tissue with nonlinear mechanical properties vital to its function. A consequent goal of repair or replacement of injured cartilage is to achieve mechanical properties in the repair tissue similar to healthy native cartilage. Since fresh healthy human articular cartilage (HC) is not readily available, we tested whether swine cartilage (SC) could serve as a suitable substitute for mechanical comparisons. To a first approximation, cartilage tissue and surgical substitutes can be evaluated mechanically as viscoelastic materials. Stiffness measurements (dynamic modulus, loss angle) are vital to function and are also a non-destructive means of evaluation. Since viscoelastic material stiffness is strongly strain rate dependent, stiffness was tested under different loading conditions related to function. Stiffness of healthy HC and SC specimens was determined and compared using two non-destructive, mm-scale indentation test modes: fast impact and slow sinusoidal deformation. Deformation resistance (dynamic modulus) and energy handling (loss angle) were determined. For equivalent anatomic locations, there was no difference in dynamic modulus. However, the HC loss angle was ~35% lower in fast impact and ~12% higher in slow sinusoidal mode. Differences seem attributable to age (young SC, older HC) but also to species anatomy and biology. Test mode-related differences in human-swine loss angle support use of multiple function-related test modes. Keeping loss angle differences in mind, swine specimens could serve as a standard of comparison for mechanical evaluation of e.g. engineered cartilage or synthetic repair materials.

  7. 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...

  8. Study on the Microstructure of Human Articular Cartilage/Bone Interface

    Institute of Scientific and Technical Information of China (English)

    Yaxiong Liu; Qin Lian; Jiankang He; Jinna Zhao; Zhongmin Jin; Dichen Li

    2011-01-01

    For improving the theory of gradient microstructure of cartilage/bone interface, human distal femurs were studied. Scanning Electron Microscope (SEM), histological sections and MicroCT were used to observe, measure and model the microstructure of cartilage/bone interface. The results showed that the cartilage/bone interface is in a hierarchical structure which is composed of four different tissue layers. The interlocking of hyaline cartilage and calcified cartilage and that of calcified cartilage and subchondral bone are in the manner of"protrusion-pore" with average diameter of 17.0 μm and 34.1 μm respectively. In addition, the cancellous bone under the cartilage is also formed by four layer hierarchical structure, and the adjacent layers are connected by bone trabecula in the shape of H, I and Y, forming a complex interwoven network structure. Finally, the simplified structure model of the cartilage/bone interface was proposed according to the natural articular cartilage/bone interface. The simplified model is a 4-layer gradient biomimetic structure, which corresponds to four different tissues of natural cartilage/bone interface. The results of this work would be beneficial to the design of bionic scaffold for the tissue engineering of articular cartilage/bone.

  9. Induction of vascular endothelial growth factor by nitric oxide in cultured human articular chondrocytes.

    Science.gov (United States)

    Turpaev, K; Litvinov, D; Dubovaya, V; Panasyuk, A; Ivanov, D; Prassolov, V

    2001-06-01

    We investigated the role of nitric oxide (NO) in the control of vascular endothelial growth factor A (VEGF) gene expression in cultured human articular chondrocytes. Cell treatment with the NO-generating compound nitrosoglutathione (GSNO) caused a significant accumulation of 4.4 kb VEGF mRNA, a major VEGF mRNA isoform expressing in chondrocytes. This is the first demonstration that NO can induce VEGF mRNA expression in chondrocytes. VEGF mRNA level was not affected in cells exposed to dibutyryl cGMP, a non-hydrolyzable analog of cGMP, suggesting that the cGMP system is not involved in NO-dependent transcriptional activation of VEGF gene. The GSNO-stimulated induction of VEGF mRNA was slightly attenuated by MAP protein kinase inhibitors PD98058 and SB203580, but was completely blocked in cells incubated with GSNO in the presence of catalase and superoxide dismutase, enzymes scavenging reactive oxygen species (ROS), or in the presence of thiol-containing antioxidants, N-acetyl cysteine and reduced glutathione. These results suggest that in articular chondrocytes the GSNO-induced VEGF gene transcriptional activation is dependent on endogenous ROS production and oxidative thiol modifications.

  10. Induction of advanced glycation end products and alterations of the tensile properties of articular cartilage

    NARCIS (Netherlands)

    Chen, A.C.; Temple, M.M.; Ng, D.M.; Verzijl, N.; Groot, J. de; TeKoppele, J.M.; Sah, R.L.

    2002-01-01

    Objective. To determine whether increasing advanced glycation end products (AGEs) in bovine articular cartilage to levels present in aged human cartilage modulates the tensile biomechanical properties of the tissue. Methods. Adult bovine articular cartilage samples were incubated in a buffer solutio

  11. The effect of oxygen tension on human articular chondrocyte matrix synthesis: integration of experimental and computational approaches.

    Science.gov (United States)

    Li, S; Oreffo, R O C; Sengers, B G; Tare, R S

    2014-09-01

    Significant oxygen gradients occur within tissue engineered cartilaginous constructs. Although oxygen tension is an important limiting parameter in the development of new cartilage matrix, its precise role in matrix formation by chondrocytes remains controversial, primarily due to discrepancies in the experimental setup applied in different studies. In this study, the specific effects of oxygen tension on the synthesis of cartilaginous matrix by human articular chondrocytes were studied using a combined experimental-computational approach in a "scaffold-free" 3D pellet culture model. Key parameters including cellular oxygen uptake rate were determined experimentally and used in conjunction with a mathematical model to estimate oxygen tension profiles in 21-day cartilaginous pellets. A threshold oxygen tension (pO2 ≈ 8% atmospheric pressure) for human articular chondrocytes was estimated from these inferred oxygen profiles and histological analysis of pellet sections. Human articular chondrocytes that experienced oxygen tension below this threshold demonstrated enhanced proteoglycan deposition. Conversely, oxygen tension higher than the threshold favored collagen synthesis. This study has demonstrated a close relationship between oxygen tension and matrix synthesis by human articular chondrocytes in a "scaffold-free" 3D pellet culture model, providing valuable insight into the understanding and optimization of cartilage bioengineering approaches.

  12. Operative management of closed intra-articular fractures of distal end of humerus in adults.

    Science.gov (United States)

    Bhattacharyya, Arunangsu; Jha, Amrish Kumar; Chatterjee, Debdutta; Ghosh, Bappaditya; Roy, Sandip Kumar; Banerjee, Debabrata

    2011-06-01

    This is a study of 60 patients with mean age of 30 years having intra-articular fracture of distal humerus of type C (AO classification). We treated these fractures by open reduction and internal fixation through transolecranon approach. Mean duration of operative time with that of injury was 10 days. In all the cases 1st the intracondylar fracture was fixed followed by reconstruction and stabilisation of medial and lateral pillar by 1/3 tubular plate and 3.5 mm dynamic compressent plate (DCP) or recon plate respectively. Minimum follow-up was of 1 year duration with average follow-up of 3 years. We could achieve 100% union with mean range of movement at the and of 1 year was 20 degree to 110 degree. Two fractures had delayed union, 5 patients had skin complications for which extended dressing was required. None of these patients required SSG or secondary suture.

  13. Reference genes for normalization of gene expression studies in human osteoarthritic articular cartilage

    Directory of Open Access Journals (Sweden)

    Gomez-Reino Juan J

    2008-01-01

    Full Text Available Abstract Background Assessment of gene expression is an important component of osteoarthritis (OA research, greatly improved by the development of quantitative real-time PCR (qPCR. This technique requires normalization for precise results, yet no suitable reference genes have been identified in human articular cartilage. We have examined ten well-known reference genes to determine the most adequate for this application. Results Analyses of expression stability in cartilage from 10 patients with hip OA, 8 patients with knee OA and 10 controls without OA were done with classical statistical tests and the software programs geNorm and NormFinder. Results from the three methods of analysis were broadly concordant. Some of the commonly used reference genes, GAPDH, ACTB and 18S RNA, performed poorly in our analysis. In contrast, the rarely used TBP, RPL13A and B2M genes were the best. It was necessary to use together several of these three genes to obtain the best results. The specific combination depended, to some extent, on the type of samples being compared. Conclusion Our results provide a satisfactory set of previously unused reference genes for qPCR in hip and knee OA This confirms the need to evaluate the suitability of reference genes in every tissue and experimental situation before starting the quantitative assessment of gene expression by qPCR.

  14. Autophagy modulates articular cartilage vesicle formation in primary articular chondrocytes.

    Science.gov (United States)

    Rosenthal, Ann K; Gohr, Claudia M; Mitton-Fitzgerald, Elizabeth; Grewal, Rupinder; Ninomiya, James; Coyne, Carolyn B; Jackson, William T

    2015-05-22

    Chondrocyte-derived extracellular organelles known as articular cartilage vesicles (ACVs) participate in non-classical protein secretion, intercellular communication, and pathologic calcification. Factors affecting ACV formation and release remain poorly characterized; although in some cell types, the generation of extracellular vesicles is associated with up-regulation of autophagy. We sought to determine the role of autophagy in ACV production by primary articular chondrocytes. Using an innovative dynamic model with a light scatter nanoparticle counting apparatus, we determined the effects of autophagy modulators on ACV number and content in conditioned medium from normal adult porcine and human osteoarthritic chondrocytes. Healthy articular chondrocytes release ACVs into conditioned medium and show significant levels of ongoing autophagy. Rapamycin, which promotes autophagy, increased ACV numbers in a dose- and time-dependent manner associated with increased levels of autophagy markers and autophagosome formation. These effects were suppressed by pharmacologic autophagy inhibitors and short interfering RNA for ATG5. Caspase-3 inhibition and a Rho/ROCK inhibitor prevented rapamycin-induced increases in ACV number. Osteoarthritic chondrocytes, which are deficient in autophagy, did not increase ACV number in response to rapamycin. SMER28, which induces autophagy via an mTOR-independent mechanism, also increased ACV number. ACVs induced under all conditions had similar ecto-enzyme specific activities and types of RNA, and all ACVs contained LC3, an autophagosome-resident protein. These findings identify autophagy as a critical participant in ACV formation, and augment our understanding of ACVs in cartilage disease and repair.

  15. Collagen metabolism of human osteoarthritic articular cartilage as modulated by bovine collagen hydrolysates.

    Directory of Open Access Journals (Sweden)

    Saskia Schadow

    Full Text Available Destruction of articular cartilage is a characteristic feature of osteoarthritis (OA. Collagen hydrolysates are mixtures of collagen peptides and have gained huge public attention as nutriceuticals used for prophylaxis of OA. Here, we evaluated for the first time whether different bovine collagen hydrolysate preparations indeed modulate the metabolism of collagen and proteoglycans from human OA cartilage explants and determined the chemical composition of oligopeptides representing collagen fragments. Using biophysical techniques, like MALDI-TOF-MS, AFM, and NMR, the molecular weight distribution and aggregation behavior of collagen hydrolysates from bovine origin (CH-Alpha®, Peptan™ B 5000, Peptan™ B 2000 were determined. To investigate the metabolism of human femoral OA cartilage, explants were obtained during knee replacement surgery. Collagen synthesis of explants as modulated by 0-10 mg/ml collagen hydrolysates was determined using a novel dual radiolabeling procedure. Proteoglycans, NO, PGE(2, MMP-1, -3, -13, TIMP-1, collagen type II, and cell viability were determined in explant cultures. Groups of data were analyzed using ANOVA and the Friedman test (n = 5-12. The significance was set to p≤0.05. We found that collagen hydrolysates obtained from different sources varied with respect to the width of molecular weight distribution, average molecular weight, and aggregation behavior. None of the collagen hydrolysates tested stimulated the biosynthesis of collagen. Peptan™ B 5000 elevated NO and PGE(2 levels significantly but had no effect on collagen or proteoglycan loss. All collagen hydrolysates tested proved not to be cytotoxic. Together, our data demonstrate for the first time that various collagen hydrolysates differ with respect to their chemical composition of collagen fragments as well as by their pharmacological efficacy on human chondrocytes. Our study underscores the importance that each collagen hydrolysate

  16. Effects of sesamin on the biosynthesis of chondroitin sulfate proteoglycans in human articular chondrocytes in primary culture.

    Science.gov (United States)

    Pothacharoen, Peraphan; Najarus, Sumet; Settakorn, Jongkolnee; Mizumoto, Shuji; Sugahara, Kazuyuki; Kongtawelert, Prachya

    2014-04-01

    Osteoarthritis (OA) is a degenerative joint disease that progressively causes a loss of joint functions and the impaired quality of life. The most significant event in OA is a high degree of degradation of articular cartilage accompanied by the loss of chondroitin sulfate-proteoglycans (CS-PGs). Recently, the chondroprotective effects of sesamin, the naturally occurring substance found in sesame seeds, have been proved in a rat model of papain-induced osteoarthritis. We hypothesized that sesamin may be associated with possible promotion of the biosynthesis of CS-PGs in human articular chondrocytes. The aim of the study was to investigate the effects of sesamin on the major CS-PG biosynthesis in primary human chondrocyte. The effects of sesamin on the gene expression of the PG core and the CS biosynthetic enzymes as well as on the secretion of glycosaminoglycans (GAGs) in monolayer and pellet culture systems of articular chondrocytes. Sesamin significantly increased the GAGs content both in culture medium and pellet matrix. Real-time-quantitative PCR showed that sesamin promoted the expression of the genes encoding the core protein (ACAN) of the major CS-PG aggrecan and the biosynthetic enzymes (XYLT1, XYLT2, CHSY1 and CHPF) required for the synthesis of CS-GAG side chains. Safranin-O staining of sesamin treated chondrocyte pellet section confirmed the high degree of GAG accumulation. These results were correlated with an increased level of secreted GAGs in the media of cultured articular chondrocytes in both culture systems. Thus, sesamin would provide a potential therapeutic strategy for treating OA patients.

  17. The human adult cardiomyocyte phenotype

    NARCIS (Netherlands)

    Bird, SD; Doevendans, PA; van Rooijen, MA; de la Riviere, AB; Hassink, RJ; Passier, R; Mummery, CL

    2003-01-01

    Aim: Determination of the phenotype of adult human atrial and ventricular myocytes based on gene expression and morphology. Methods: Atrial and ventricular cardiomyocytes were obtained from patients undergoing cardiac surgery using a modified isolation procedure. Myocytes were isolated and cultured

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

    NARCIS (Netherlands)

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

  19. Working conditions of bipolar radiofrequency on human articular cartilage repair following thermal injury during arthroscopy

    Institute of Scientific and Technical Information of China (English)

    Huang Yuelong; Zhang Yujun; Ding Xiaoquan; Liu Songyang; Sun Tiezheng

    2014-01-01

    Background The thermal injury during bipolar radiofrequercy results in chondrocyte death that limits cartilage repair.The purpose was to determine the effects of various factors of bipolar radiofrequency on human articular cartilage after thermal injury,offering suitable working conditions for bipolar radiofrequency during arthroscopy.Methods Osteochondral explants from 28 patients undergoing total knee arthroplasty (TKA) in Department of Orthopaedic,Peking University Reople's Hospital from October 2013 to May 2014,were harvested and treated using bipolar radiofrequency in a light contact mode under the following conditions:various power setting of levels 2,4 and 6; different durations of 2 seconds,5 seconds and 10 seconds; irrigation with fluids of different temperatures of 4℃,22℃,and 37℃; two different bipolar radiofrequency probes ArthroCare TriStar 50 and Paragon T2.The percentage of cell death and depth of cell death were quantified with laser confocal microscopy.The content of proteoglycan elution at different temperatures was determined by spectrophotometer at 530 nm.Results Chondrocyte mortality during the treatment time of 2 seconds and power setting of level 2 was significantly lower than that with long duration or in higher level groups (time:P=0.001; power:P=0.001).The percentage of cell death after thermal injury was gradually reduced by increasing the temperature of the irrigation solutions (P=0.003),the depth of dead chondrocytes in the 37℃ solution group was significantly less than those in the 4℃ and 22℃ groups (P=0.001).The proteoglycan elution was also gradually reduced by increasing the temperature (P=0.004).Compared with the ArthroCare TriStar 50 group,the percentage of cell death in the Paragon T2 group was significantly decreased (P=0.046).Conclusions Thermal chondroplasty with bipolar radiofrequency resulted in defined margins of chondrocyte death under controlled conditions.The least cartilage damage during thermal chondroplasty

  20. Functional Outcomes to Surgical Treatment of the Distal Humerus Intra-Articular Fractures in Adults

    Directory of Open Access Journals (Sweden)

    Abdulkadir Yýðman

    2013-11-01

    Full Text Available Aim: Displaced and intraarticular humerus distal fractures require surgical treatment.  In this study we  evaluated to functional results of the surgical treatment of distal humerus intraarticular fractures in adults. Additionally, we evaluated the factors affecting surgical outcomes. Material and Method: Between 2005 to 2010, 22 elbows of 21 patients who were operated for distal humerus intraarticular fractures were evaluated retrospectively. 11(52.4% patiens were male and 10(47.6% were female, mean age 46.2 (range 17 to 71.  Fractures were classified as type B3 for 10, type C1 for 6 and type C2 for 6 subjects according to AO classifications. We performed paralel double locking plate for 9(41%, perpendicular double plate for 2(9%, K wires and screw combination for 7(32%, and single plate for 4(18% patients. Functional assesment were performed with the MEPS and q-DASH scoring systems. Results: Mean follow-up  was 30.4(5-68 months. Fracture healing was observed in all of the patients. Mean elbow flexion of 117 (90-145 degrees and extension loss of 24.3 (0-60 were noted. 10 (47.6% patients were excellent, 6 (28.6% were good, 3 (14.3% were fair and 2(9.5% were poor according to MEPS. Mean q-DASH scores were 15 (0-69.8 in 21 patients. Good results were obtained in fractures treated with stable fixation, in early performed surgeries, and in early  started rehabilitation. Discussion: Treatment of distal humerus intraarticular fractures with anatomical reduction, stable osteosynthesis, and early rehabilitation are very important in obtaining successful outcomes. Additionally, age and fracture type are important factors to conclude good results..

  1. 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.

  2. 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

  3. Induction of advanced glycation end products and alterations of the tensile properties of articular cartilage

    OpenAIRE

    Chen, A C; Temple, M.M.; Ng, D.M.; Verzijl, N; de Groot, J.; TeKoppele, J.M.; Sah, R.L.

    2002-01-01

    Objective. To determine whether increasing advanced glycation end products (AGEs) in bovine articular cartilage to levels present in aged human cartilage modulates the tensile biomechanical properties of the tissue. Methods. Adult bovine articular cartilage samples were incubated in a buffer solution with ribose to induce the formation of AGEs or in a control solution. Portions of cartilage samples were assayed for biochemical indices of AGEs and tested to assess their tensile biomechanical p...

  4. 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 dep

  5. Green fluorescent protein as marker in chondrocytes overexpressing human insulin-like growth factor-1 for repair of articular cartilage defects in rabbits

    Institute of Scientific and Technical Information of China (English)

    ZHANG Shao-kun; LIU Yi; SONG Zhi-ming; FU Chang-feng; XU Xin-xiang

    2007-01-01

    Objective:To label the primary articular chondrocytes overexpressing human insulin-like growth factor ( hIGF-1 ) with green fluorescent protein (GFP) for repair of articular cartilage defects in rabbits. Methods:GFP cDNA was inserted into pcDNA3.1-hIGF-1 to label the expression vector.The recombinant vector,pcGI,a mammalian expression vector with multiple cloning sites under two respective cytomegalovirus promoters/enhancers,was transfected into the primary articular chondrocytes with the help of lipofectamine.After the positive cell clones were selected by G418,G418-resistant chondrocytes were cultured in medium for 4 weeks.The stable expression of hIGF-1 in the articular chondrocytes was determined by in situ hybridization and immunocytochemical analysis and the GFP was confirmed under a fluorescence microscope. Methyl thiazolyl tetrazolium (MTT) and flow cytometer methods were employed to determine the effect of transfection on proliferation of chondrocytes. Gray value was used to analyze quantitatively the expression of type Ⅱ collagen. Results:The expression of hIGF-1 and GFP was confirmed in transfected chondrocytes by in situ hybridization, immunocytochemical analysis and fluorescence microscope observation. Green articular chondrocytes overexpressing hIGF-1 could expand and maintain their chondrogenic phenotypes for more than 4 weeks.After the transfection of IGF-1,the proliferation of chondrocytes was enhanced and the chondrocytes could effectively maintain the expression of type Ⅱ collagen. Conclusions:The hIGF-1 eukaryotic expression vector containing GFP marker gene has been successfully constructed.GFP,which can be visualized in real time and in situ, is stably expressed in articular chondrocytes overexpressing hIGF-1.The labeled articular chondrocytes overexpressing hIGF-1 can be applied in cell-mediated gene therapy as well as for other biomedical purposes of transgenic chondrocytes.

  6. 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.

  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. Cannabinoid WIN-55,212-2 mesylate inhibits ADAMTS-4 activity in human osteoarthritic articular chondrocytes by inhibiting expression of syndecan-1

    Science.gov (United States)

    KONG, YING; WANG, WANCHUN; ZHANG, CHANGJIE; WU, YI; LIU, YANG; ZHOU, XIAORONG

    2016-01-01

    A central feature of osteoarthritis (OA) is the loss of articular cartilage, which is primarily attributed to cartilage breakdown. A group of metalloproteinases termed the A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) family are reported to be important in cartilage breakdown. Recent studies have suggested that ADAMTS-4 is a major contributor to the pathogenesis of OA and that syndecan-1 is closely associated with activation of ADAMTS-4 in human chondrocytes. Accumulating evidence also suggests that cannabinoids have chondroprotective effects. The current study explored the effects of synthetic cannabinoid WIN-55,212-2 mesylate (WIN-55) on the expression of syndecan-1 and ADAMTS-4, as well as ADAMTS-4 activity, in unstimulated and interleukin (IL)-1β-stimulated OA chondrocytes. Primary human OA articular chondrocytes were treated with WIN-55 in the presence or absence of IL-1β and cannabinoid receptor antagonists. The results of the present study demonstrated that WIN-55 inhibited ADAMTS-4 activity in unstimulated and IL-1β-stimulated primary human OA articular chondrocytes in a concentration-dependent manner. Cannabinoid receptor type 1 (CB1) and 2 (CB2) were constitutively expressed in human OA articular chondrocytes. Furthermore, selective CB2 antagonist, JTE907, but not selective CB1 antagonist, MJ15, abolished the inhibitory effect of WIN-55 on ADAMTS-4 activity. WIN55 inhibited the expression of syndecan-1 but not ADAMTS-4, and overexpression of syndecan-1 reversed the inhibitory effect of WIN-55 on the ADAMTS-4 activity in unstimulated and IL-1β-stimulated human OA articular chondrocytes. Despite having no significant effect on syndecan-1 gene promoter activity, WIN-55 markedly decreased the stability of syndecan-1 mRNA via CB2. In conclusion, to the best of our knowledge, the present study provides the first in vitro evidence supporting that the synthetic cannabinoid WIN-55 inhibits ADAMTS-4 activity in unstimulated and IL-1

  9. The acute effect of bipolar radiofrequency energy thermal chondroplasty on intrinsic biomechanical properties and thickness of chondromalacic human articular cartilage.

    Science.gov (United States)

    Dutcheshen, Nicholas; Maerz, Tristan; Rabban, Patrick; Haut, Roger C; Button, Keith D; Baker, Kevin C; Guettler, Joseph

    2012-08-01

    Radio frequency energy (RFE) thermal chondroplasty has been a widely-utilized method of cartilage debridement in the past. Little is known regarding its effect on tissue mechanics. This study investigated the acute biomechanical effects of bipolar RFE treatment on human chondromalacic cartilage. Articular cartilage specimens were extracted (n = 50) from femoral condyle samples of patients undergoing total knee arthroplasty. Chondromalacia was graded with the Outerbridge classification system. Tissue thicknesses were measured using a needle punch test. Specimens underwent pretreatment load-relaxation testing using a spherical indenter. Bipolar RFE treatment was applied for 45 s and the indentation protocol was repeated. Structural properties were derived from the force-time data. Mechanical properties were derived using a fibril-reinforced biphasic cartilage model. Statistics were performed using repeated measures ANOVA. Cartilage thickness decreased after RFE treatment from a mean of 2.61 mm to 2.20 mm in Grade II, II-III, and III specimens (P resistance to shear and tension could be compromised due to removal of the superficial layer and decreased fibril modulus, RFE treatment increases matrix modulus and decreases tissue permeability which may restore the load- bearing capacity of the cartilage.

  10. Imaging of Osteoarthritic Human Articular Cartilage using Fourier Transform Infrared Microspectroscopy Combined with Multivariate and Univariate Analysis.

    Science.gov (United States)

    Oinas, J; Rieppo, L; Finnilä, M A J; Valkealahti, M; Lehenkari, P; Saarakkala, S

    2016-07-21

    The changes in chemical composition of human articular cartilage (AC) caused by osteoarthritis (OA) were investigated using Fourier transform infrared microspectroscopy (FTIR-MS). We demonstrate the sensitivity of FTIR-MS for monitoring compositional changes that occur with OA progression. Twenty-eight AC samples from tibial plateaus were imaged with FTIR-MS. Hyperspectral images of all samples were combined for K-means clustering. Partial least squares regression (PLSR) analysis was used to compare the spectra with the OARSI grade (histopathological grading of OA). Furthermore, the amide I and the carbohydrate regions were used to estimate collagen and proteoglycan contents, respectively. Spectral peak at 1338 cm(-1) was used to estimate the integrity of the collagen network. The layered structure of AC was revealed using the carbohydrate region for clustering. Statistically significant correlation was observed between the OARSI grade and the collagen integrity in the superficial (r = -0.55) and the deep (r = -0.41) zones. Furthermore, PLSR models predicted the OARSI grade from the superficial (r = 0.94) and the deep (r = 0.77) regions of the AC with high accuracy. Obtained results suggest that quantitative and qualitative changes occur in the AC composition during OA progression, and these can be monitored by the use of FTIR-MS.

  11. 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.

  12. 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.

  13. 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.

  14. Chondroitin sulphate and heparan sulphate sulphation motifs and their proteoglycans are involved in articular cartilage formation during human foetal knee joint development.

    Science.gov (United States)

    Melrose, James; Isaacs, Marc D; Smith, Susan M; Hughes, Clare E; Little, Christopher B; Caterson, Bruce; Hayes, Anthony J

    2012-09-01

    Novel sulphation motifs within the glycosaminoglycan chain structure of chondroitin sulphate (CS) containing proteoglycans (PGs) are associated with sites of growth, differentiation and repair in many biological systems and there is compelling evidence that they function as molecular recognition sites that are involved in the binding, sequestration or presentation of soluble signalling molecules (e.g. morphogens, growth factors and cytokines). Here, using monoclonal antibodies 3B3(-), 4C3 and 7D4, we examine the distribution of native CS sulphation motifs within the developing connective tissues of the human foetal knee joint, both during and after joint cavitation. We show that the CS motifs have broad, overlapping distributions within the differentiating connective tissues before the joint has fully cavitated; however, after cavitation, they all localise very specifically to the presumptive articular cartilage tissue. Comparisons with the labelling patterns of heparan sulphate (HS), HS-PGs (perlecan, syndecan-4 and glypican-6) and FGF-2, molecules with known signalling roles in development, indicate that these also become localised to the future articular cartilage tissue after joint cavitation. Furthermore, they display interesting, overlapping distributions with the CS motifs, reflective of early tissue zonation. The overlapping expression patterns of these molecules at this site suggests they are involved, or co-participate, in early morphogenetic events underlying articular cartilage formation; thus having potential clinical relevance to mechanisms involved in its repair/regeneration. We propose that these CS sulphation motifs are involved in modulating the signalling gradients responsible for the cellular behaviours (proliferation, differentiation, matrix turnover) that shape the zonal tissue architecture present in mature articular cartilage.

  15. PEO-PPO-PEO Carriers for rAAV-Mediated Transduction of Human Articular Chondrocytes in Vitro and in a Human Osteochondral Defect Model.

    Science.gov (United States)

    Rey-Rico, Ana; Frisch, Janina; Venkatesan, Jagadesh Kumar; Schmitt, Gertrud; Rial-Hermida, Isabel; Taboada, Pablo; Concheiro, Angel; Madry, Henning; Alvarez-Lorenzo, Carmen; Cucchiarini, Magali

    2016-08-17

    Gene therapy is an attractive strategy for the durable treatment of human osteoarthritis (OA), a gradual, irreversible joint disease. Gene carriers based on the small human adeno-associated virus (AAV) exhibit major efficacy in modifying damaged human articular cartilage in situ over extended periods of time. Yet, clinical application of recombinant AAV (rAAV) vectors remains complicated by the presence of neutralizing antibodies against viral capsid elements in a majority of patients. The goal of this study was to evaluate the feasibility of delivering rAAV vectors to human OA chondrocytes in vitro and in an experimental model of osteochondral defect via polymeric micelles to protect gene transfer from experimental neutralization. Interaction of rAAV with micelles of linear (poloxamer PF68) or X-shaped (poloxamine T908) poly(ethylene oxide) (PEO) and poly(propylene oxide) (PPO) copolymers (PEO-PPO-PEO micelles) was characterized by means of isothermal titration calorimetry. Micelle encapsulation allowed an increase in both the stability and bioactivity of rAAV vectors and promoted higher levels of safe transgene (lacZ) expression both in vitro and in experimental osteochondral defects compared with that of free vector treatment without detrimental effects on the biological activity of the cells or their phenotype. Remarkably, protection against antibody neutralization was also afforded when delivering rAAV via PEO-PPO-PEO micelles in all systems evaluated, especially when using T908. Altogether, these findings show the potential of PEO-PPO-PEO micelles as effective tools to improve current gene-based treatments for human OA.

  16. First ex vivo study demonstrating that {sup 99m}Tc-NTP 15-5 radiotracer binds to human articular cartilage

    Energy Technology Data Exchange (ETDEWEB)

    Cachin, Florent; Culot, Damien [Jean Perrin Cancer Centre, Nuclear Medicine Department, Clermont-Ferrand (France); Universite d' Auvergne, UMR 990 INSERM, Clermont-Ferrand (France); Boisgard, Stephane [Gabriel Montpied University Hospital, Orthopaedic Surgery, Clermont-Ferrand (France); Universite d' Auvergne, UMR 990 INSERM, Clermont-Ferrand (France); Vidal, Aurelien; Auzeloux, Philippe; Madelmont, Jean-Claude; Chezal, Jean-Michel; Miot-Noirault, Elisabeth [Universite d' Auvergne, UMR 990 INSERM, Clermont-Ferrand (France); Filaire, Marc [Universite d' Auvergne, Anatomy Laboratory, Clermont-Ferrand (France); Askienazy, Serge [Cyclopharma Laboratoire, Saint-Beauzire (France)

    2011-11-15

    Preclinical data pointed to {sup 99m}Tc-NTP 15-5 as a good candidate for single photon emission computed tomography (SPECT) imaging of cartilaginous disease. We set out to investigate and quantify {sup 99m}Tc-NTP 15-5 ex vivo uptake by human articular cartilage relative to bone {sup 99m}Tc-hydroxymethylene diphosphonate (HMDP) radiotracer. Three osteoarthritic human tibial plateaux and four tibiofemoral joints were incubated with {sup 99m}Tc-NTP 15-5 and {sup 99m}Tc-HMDP for 2 h. Affinity of tracers for cartilage was determined by visual analysis of SPECT/CT acquisitions and measurement of cartilage to cortical bone uptake ratios. Cartilage to cortical bone uptake ratios were 3.90 {+-} 2.35 and 0.76 {+-} 0.24, respectively, for {sup 99m}Tc-NTP 15-5 and {sup 99m}Tc-HMDP radiotracers. Visual analysis of fused SPECT/CT slices showed selective, intense {sup 99m}Tc-NTP 15-5 accumulation in articular cartilage, whereas {sup 99m}Tc-HMDP binding was low. Interestingly, a cartilage defect visualized on CT was clearly associated with focal decreased uptake of {sup 99m}Tc-NTP 15-5. The tracer {sup 99m}Tc-NTP 15-5 is of major interest for human cartilage molecular imaging and could find clinical applications in osteoarthritis staging and monitoring. (orig.)

  17. Millicurrent stimulation of human articular chondrocytes cultivated in a collagen type-I gel and of human osteochondral explants

    Directory of Open Access Journals (Sweden)

    Silny Jiri

    2010-08-01

    Full Text Available Abstract Background Here we investigate the effect of millicurrent treatment on human chondrocytes cultivated in a collagen gel matrix and on human osteochondral explants. Methods Human chondrocytes from osteoarthritic knee joints were enzymatically released and transferred into a collagen type-I gel. Osteochondral explants and cell-seeded gel samples were cultivated in-vitro for three weeks. Samples of the verum groups were stimulated every two days by millicurrent treatment (3 mA, sinusoidal signal of 312 Hz amplitude modulated by two super-imposed signals of 0.28 Hz, while control samples remained unaffected. After recovery, collagen type-I, type-II, aggrecan, interleukin-1β, IL-6, TNFα and MMP13 were examined by immunohistochemistry and by real time PCR. Results With regard to the immunostainings 3 D gel samples and osteochondral explants did not show any differences between treatment and control group. The expression of all investigated genes of the 3 D gel samples was elevated following millicurrent treatment. While osteochondral explant gene expression of col-I, col-II and Il-1β was nearly unaffected, aggrecan gene expression was elevated. Following millicurrent treatment, IL-6, TNFα, and MMP13 gene expression decreased. In general, the standard deviations of the gene expression data were high, resulting in rarely significant results. Conclusions We conclude that millicurrent stimulation of human osteoarthritic chondrocytes cultivated in a 3 D collagen gel and of osteochondral explants directly influences cell metabolism.

  18. Disposition of human recombinant lubricin in naive rats and in a rat model of post-traumatic arthritis after intra-articular or intravenous administration.

    Science.gov (United States)

    Vugmeyster, Yulia; Wang, Qin; Xu, Xin; Harrold, John; Daugusta, Daren; Li, Jian; Zollner, Richard; Flannery, Carl R; Rivera-Bermúdez, Moisés A

    2012-03-01

    We have recently demonstrated that intra-articular (IA) administration of human recombinant lubricin, LUB:1, significantly inhibited cartilage degeneration and pain in the rat meniscal tear model of post-traumatic arthritis. In this report, we show that after a single IA injection to naïve rats and rats that underwent unilateral meniscal tear, [(125)I]LUB:1 had a tri-phasic disposition profile, with the alpha, beta, and gamma half-life estimates of 4.5 h, 1.5 days, and 2.1 weeks, respectively. We hypothesize that the terminal phase kinetics was related to [(125)I]LUB:1 binding to its ligands. [(125)I]LUB:1 was detected on articular cartilage surfaces as long as 28 days after single IA injection. Micro-autoradiography analysis suggested that [(125)I]LUB:1 tended to localize to damaged joint surfaces in rats with meniscal tear. After a single intravenous (IV) dose to rats, [(125)I]LUB:1 was eliminated rapidly from the systemic circulation, with a mean total body clearance of 154 mL/h/kg and a mean elimination half-life (t (1/2)) of 6.7 h. Overall, LUB:1 has met a desired disposition profile of a potential therapeutic intended for an IA administration: target tissue (knee) retention and fast elimination from the systemic circulation after a single IA or IV dose.

  19. Tensorial electrokinetics in articular cartilage.

    Science.gov (United States)

    Reynaud, Boris; Quinn, Thomas M

    2006-09-15

    Electrokinetic phenomena contribute to biomechanical functions of articular cartilage and underlie promising methods for early detection of osteoarthritic lesions. Although some transport properties, such as hydraulic permeability, are known to become anisotropic with compression, the direction-dependence of cartilage electrokinetic properties remains unknown. Electroosmosis experiments were therefore performed on adult bovine articular cartilage samples, whereby fluid flows were driven by electric currents in directions parallel and perpendicular to the articular surface of statically compressed explants. Magnitudes of electrokinetic coefficients decreased slightly with compression (from approximately -7.5 microL/As in the range of 0-20% compression to -6.0 microL/As in the 35-50% range) consistent with predictions of microstructure-based models of cartilage material properties. However, no significant dependence on direction of the electrokinetic coupling coefficient was detected, even for conditions where the hydraulic permeability tensor is known to be anisotropic. This contrast may also be interpreted using microstructure-based models, and provides insights into structure-function relationships in cartilage extracellular matrix and physical mediators of cell responses to tissue compression. Findings support the use of relatively simple isotropic modeling approaches for electrokinetic phenomena in cartilage and related materials, and indicate that measurement of electrokinetic properties may provide particularly robust means for clinical evaluation of cartilage matrix integrity.

  20. Crosslinking by advanced glycation end products increases the stiffness of the collagen network in human articular cartilage: A possible mechanism through which age is a risk factor for osteoarthritis

    NARCIS (Netherlands)

    Verzijl, N.; Groot, J. de; Zaken, C.B.; Braun-Benjamin, O.; Maroudas, A.; Bank, R.A.; Mizrahi, J.; Schalkwijk, C.G.; Thorpe, S.R.; Baynes, J.W.; Bijlsma, J.W.J.; Lafeber, F.P.J.G.; TeKoppele, J.M.

    2002-01-01

    Objective. Age is an important risk factor for osteoarthritis (OA). During aging, nonenzymatic glycation results in the accumulation of advanced glycation end products (AGEs) in cartilage collagen. We studied the effect of AGE crosslinking on the stiffness of the collagen network in human articular

  1. 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.)

  2. Angiogenic properties of adult human thymus fat.

    Science.gov (United States)

    Salas, Julián; Montiel, Mercedes; Jiménez, Eugenio; Valenzuela, Miguel; Valderrama, José Francisco; Castillo, Rafael; González, Sergio; El Bekay, Rajaa

    2009-11-01

    The endogenous proangiogenic properties of adipose tissue are well recognized. Although the adult human thymus has long been known to degenerate into fat tissue, it has never been considered as a potential source of angiogenic factors. We have investigated the expression of diverse angiogenic factors, including vascular endothelial growth factor A and B, angiopoietin 1, and tyrosine-protein kinase receptor-2 (an angiopoietin receptor), and then analyzed their physiological role on endothelial cell migration and proliferation, two relevant events in angiogenesis. The detection of the gene and protein expression of the various proteins has been performed by immunohistochemistry, Western blotting, and quantitative real-time polymerase chain reaction. We show, for the first time, that adult thymus fat produces a variety of angiogenic factors and induces the proliferation and migration of human umbilical cord endothelial cells. Based on these findings, we suggest that this fat has a potential angiogenic function that might affect thymic function and ongoing adipogenesis within the thymus.

  3. BMP receptor signaling is required for postnatal maintenance of articular cartilage.

    Directory of Open Access Journals (Sweden)

    Ryan B Rountree

    2004-11-01

    Full Text Available Articular cartilage plays an essential role in health and mobility, but is frequently damaged or lost in millions of people that develop arthritis. The molecular mechanisms that create and maintain this thin layer of cartilage that covers the surface of bones in joint regions are poorly understood, in part because tools to manipulate gene expression specifically in this tissue have not been available. Here we use regulatory information from the mouse Gdf5 gene (a bone morphogenetic protein [BMP] family member to develop new mouse lines that can be used to either activate or inactivate genes specifically in developing joints. Expression of Cre recombinase from Gdf5 bacterial artificial chromosome clones leads to specific activation or inactivation of floxed target genes in developing joints, including early joint interzones, adult articular cartilage, and the joint capsule. We have used this system to test the role of BMP receptor signaling in joint development. Mice with null mutations in Bmpr1a are known to die early in embryogenesis with multiple defects. However, combining a floxed Bmpr1a allele with the Gdf5-Cre driver bypasses this embryonic lethality, and leads to birth and postnatal development of mice missing the Bmpr1a gene in articular regions. Most joints in the body form normally in the absence of Bmpr1a receptor function. However, articular cartilage within the joints gradually wears away in receptor-deficient mice after birth in a process resembling human osteoarthritis. Gdf5-Cre mice provide a general system that can be used to test the role of genes in articular regions. BMP receptor signaling is required not only for early development and creation of multiple tissues, but also for ongoing maintenance of articular cartilage after birth. Genetic variation in the strength of BMP receptor signaling may be an important risk factor in human osteoarthritis, and treatments that mimic or augment BMP receptor signaling should be

  4. Sintomas articulares crônicos em adultos de Pelotas, Rio Grande do Sul, Brasil: prevalência e determinantes Chronic joint symptoms in adults from Pelotas, Rio Grande do Sul State, Brazil: prevalence and determinants

    Directory of Open Access Journals (Sweden)

    Vera Regina Lopes da Silva

    2009-12-01

    Full Text Available Com o objetivo de estimar a prevalência de sintomas articulares crônicos e seus determinantes, foi realizado um estudo transversal, com 2.953 adultos com 20 anos ou mais, residentes em Pelotas, Rio Grande do Sul, Brasil. Foram investigadas a presença de dor, edema ou rigidez articular, além de informações demográficas, sócio-econômicas e sobre problemas de saúde. A análise multivariável foi realizada pela regressão de Poisson. A prevalência geral de sintomas articulares crônicos foi de 36,5% (42,4% nas mulheres e 28,7% nos homens. A presença da tríade - dor, edema e rigidez articulares - foi de 14,1% e 5,5% nas mulheres e homens, respectivamente. Sintomas articulares crônicos se mostraram linearmente associados ao aumento da idade (RP: 2,9; IC95%: 2,4-3,5, do índice de massa corporal (RP: 1,6; IC95%: 1,3-2,0 e à menor escolaridade (RP: 1,5; IC95%: 1,3-1,8. Somente 6% dos homens e 18% das mulheres relataram diagnóstico médico de artrite. As prevalências gerais de limitações para atividades de vida diária e para atividades laborais, secundárias a sintomas articulares crônicos, foi de 15% e 21%, respectivamente. Os jovens e homens representam a maioria dos indivíduos com sintomas articulares crônicos subdiagnosticados.With the objective of estimating the prevalence of chronic joint symptoms and their determinants, a cross-sectional study was conducted with 2,953 adults 20 years or older in Pelotas, Rio Grande do Sul State, Brazil. Pain, swelling, and stiffness in joints were investigated, plus demographic, socioeconomic, and health-related information. Multivariate analysis was performed with Poisson regression. Overall prevalence of chronic joint symptoms was 36.5% (42.4% in women and 28.7% in men. The threefold presence of pain, swelling, and stiffness in joints was 14.1% and 5.5% in women and men, respectively. Chronic joint symptoms showed a linear association with increasing age (PR: 2.9; 95%CI: 2.4-3.5, body mass

  5. Kinematic biomechanical assessment of human articular cartilage transplants in the knee using 3-T MRI: an in vivo reproducibility study

    Energy Technology Data Exchange (ETDEWEB)

    Juras, Vladimir; Szomolanyi, Pavol [Medical University of Vienna, Department of Radiodiagnostics, MR Centre of Excellence, Vienna (Austria); Slovak Academy of Sciences, Department of Imaging Methods, Institute of Measurement Science, Bratislava (Slovakia); Ludwig Boltzmann Institute for Clinical and Experimental Traumatology, Austrian Cluster for Tissue Regeneration, Vienna (Austria); Welsch, Goetz H.; Pinker, Katja; Trattnig, Siegfried [Medical University of Vienna, Department of Radiodiagnostics, MR Centre of Excellence, Vienna (Austria); Ludwig Boltzmann Institute for Clinical and Experimental Traumatology, Austrian Cluster for Tissue Regeneration, Vienna (Austria); Millington, Steven [Royal National Orthopaedic Hospital, London, Stanmore (United Kingdom); Mamisch, Tallal C. [Inselspital, Orthopedic Surgery Department, Berne (Switzerland)

    2009-05-15

    The aims of this study were to examine the clinical feasibility and reproducibility of kinematic MR imaging with respect to changes in T{sub 2} in the femoral condyle articular cartilage. We used a flexible knee coil, which allows acquisition of data in different positions from 40 flexion to full extension during MR examinations. The reproducibility of T{sub 2} measurements was evaluated for inter-rater and inter-individual variability and determined as a coefficient of variation (CV) for each volunteer and rater. Three different volunteers were measured twice and regions of interest (ROIs) were selected by three raters at different time points. To prove the clinical feasibility of this method, 20 subjects (10 patients and 10 age- and sex-matched volunteers) were enrolled in the study. Inter-rater variability ranged from 2 to 9 and from 2 to 10% in the deep and superficial zones, respectively. Mean inter-individual variability was 7% for both zones. Different T{sub 2} values were observed in the superficial cartilage zone of patients compared with volunteers. Since repair tissue showed a different behavior in the contact zone compared with healthy cartilage, a possible marker for improved evaluation of repair tissue quality after matrix-associated autologous chondrocyte transplantation (MACT) may be available and may allow biomechanical assessment of cartilage transplants. (orig.)

  6. Condrocalcinose articular familiar Familial articular chondrocalcinosis

    Directory of Open Access Journals (Sweden)

    Mittermayer Barreto Santiago

    2004-08-01

    Full Text Available Condrocalcinose articular familiar é uma condição clínica caracterizada pela deposição de cristais de pirofosfato de cálcio no líquido sinovial e cartilagens articulares levando à artrite. Descrevemos três membros de uma família com condrocalcinose cujo quadro clínico era caracterizado por artrite intermitente em dois e artrite crônica lembrando artrite reumatóide em um. A avaliação radiológica mostrou calcificações em cartilagens de diversas articulações, particularmente de joelhos. A utilização de colchicina foi suficiente para prevenir as crises de artrite em dois pacientes e o paciente com a forma crônica necessitou uso contínuo de antiinflamatórios não-hormonais. Embora aparentemente rara no Brasil, não afastamos a possibilidade desse dado estar subestimado e sugerimos que seja realizada uma avaliação radiológica articular dos familiares de todo paciente com diagnóstico de condrocalcinose esporádica.Familial articular chondrocalcinosis is a disorder characterized by deposition of calcium pyrophosphate dihydrate crystal in synovial fluid and articular cartilage that can cause joint pain and arthritis. We have identified three members of the same family with chondrocalcinosis. The clinical features of the disease were intermittent episodes of arthritis in two patients and polyarthritis resembling rheumatoid arthritis in one member. The radiological evaluation showed calcification in several joints, particularly in cartilages of the knees. Therapy with colchicine was enough to prevent arthritic crisis in two patients and continous NSAID use was necessary to control symptoms in the last one. Familial chondrocalcinosis seems to be rare in Brazil, but we do not exclude the possibility that this figure is underestimated and suggest that in cases of sporadic chondrocalcinosis other members of the family should be fully investigated.

  7. [Intra-articular injections].

    Science.gov (United States)

    Chapelle, Ch

    2015-09-01

    It is not unusual for a specialist or general practitioner to be presented with a pathology which necessitates the use of an intra-articular injection of corticosteroids, hyaluronic acid or a local anaesthetic. It would seem to be interesting to update and to precise the techniques and methods of intraarticular injections which have appeared in recent international publications, when we know that 30 % of the injections given into the knee and so called "dry" are incorrect and, therefore, inefficient. The indication of an articular injection depends, firstly, on the diagnosis which should be done with great care; after which should be an objective analysis complete with secondary effects linked to both the injection and the product used. The conditions of asepsis, the choice of needles and quantities of the injection and even the ways of the injections should be reviewed in detail. The last studies clearly question the secondary effects of the cartilage degradations of the cortisone given as an intra-articular injection and shows its efficiency on the pain and inflammatory phenomonen in osteoarthritis. Studies on hyaluronic acid are often contradictory going from a modest result to an important pain relief but it is necessary to be aware that the objective criteria are difficult to interpret. The use of local anaesthetics in intra-articular is limited by the few indications in view of the major risk of aggravating the pre-existing lesions by the disappearing signs of pain.

  8. 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.

  9. Latent inhibition in human adults without masking.

    Science.gov (United States)

    Escobar, Martha; Arcediano, Francisco; Miller, Ralph R

    2003-09-01

    Latent inhibition refers to attenuated responding to Cue X observed when the X-outcome pairings are preceded by X-alone presentations. It has proven difficult to obtain in human adults unless the preexposure (X-alone) presentations are embedded within a masking (i.e., distracting) task. The authors hypothesized that the difficulty in obtaining latent inhibition with unmasked tasks is related to the usual training procedures, in which the preexposure and conditioning experiences are separated by a set of instructions. Experiment 1 reports latent inhibition without masking in a task in which preexposure and conditioning occur without interruption. Experiments 2 and 3 demonstrate that this attenuation in responding to target Cue X does not pass a summation test for conditioned inhibition and is context specific, thereby confirming that it is latent inhibition. Experiments 3 and 4 confirm that introducing instructions between preexposure and conditioning disrupts latent inhibition.

  10. 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.

  11. Adult neurogenesis in humans- common and unique traits in mammals.

    Directory of Open Access Journals (Sweden)

    Aurélie Ernst

    2015-01-01

    Full Text Available New neurons are continuously generated in specific regions in the adult brain. Studies in rodents have demonstrated that adult-born neurons have specific functional features and mediate neural plasticity. Data on the extent and dynamics of adult neurogenesis in adult humans are starting to emerge, and there are clear similarities and differences compared to other mammals. Why do these differences arise? And what do they mean?

  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. 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…

  14. Synoviocyte Derived-Extracellular Matrix Enhances Human Articular Chondrocyte Proliferation and Maintains Re-Differentiation Capacity at Both Low and Atmospheric Oxygen Tensions.

    Directory of Open Access Journals (Sweden)

    Thomas J Kean

    Full Text Available Current tissue engineering methods are insufficient for total joint resurfacing, and chondrocytes undergo de-differentiation when expanded on tissue culture plastic. De-differentiated chondrocytes show poor re-differentiation in culture, giving reduced glycosaminoglycan (GAG and collagen matrix accumulation. To address this, porcine synoviocyte-derived extracellular matrix and low (5% oxygen tension were assessed for their ability to enhance human articular chondrocyte expansion and maintain re-differentiation potential.Porcine synoviocyte matrices were devitalized using 3 non-detergent methods. These devitalized synoviocyte matrices were compared against tissue culture plastic for their ability to support human chondrocyte expansion. Expansion was further compared at both low (5%, and atmospheric (20% oxygen tension on all surfaces. Expanded cells then underwent chondrogenic re-differentiation in aggregate culture at both low and atmospheric oxygen tension. Aggregates were assessed for their GAG and collagen content both biochemically and histologically.Human chondrocytes expanded twice as fast on devitalized synoviocyte matrix vs. tissue culture plastic, and cells retained their re-differentiation capacity for twice the number of population doublings. There was no significant difference in growth rate between low and atmospheric oxygen tension. There was significantly less collagen type I, collagen type II, aggrecan and more MMP13 expression in cells expanded on synoviocyte matrix vs. tissue culture plastic. There were also significant effects due to oxygen tension on gene expression, wherein there was greater collagen type I, collagen type II, SOX9 and less MMP13 expression on tissue culture plastic compared to synoviocyte matrix. There was a significant increase in GAG, but not collagen, accumulation in chondrocyte aggregates re-differentiated at low oxygen tension over that achieved in atmospheric oxygen conditions

  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. The dynamics of adult neurogenesis in human hippocampus.

    Science.gov (United States)

    Ihunwo, Amadi O; Tembo, Lackson H; Dzamalala, Charles

    2016-12-01

    The phenomenon of adult neurogenesis is now an accepted occurrence in mammals and also in humans. At least two discrete places house stem cells for generation of neurons in adult brain. These are olfactory system and the hippocampus. In animals, newly generated neurons have been directly or indirectly demonstrated to generate a significant amount of new neurons to have a functional role. However, the data in humans on the extent of this process is still scanty and such as difficult to comprehend its functional role in humans. This paper explores the available data on as extent of adult hippocampal neurogenesis in humans and makes comparison to animal data.

  17. A novel rat tail collagen type-I gel for the cultivation of human articular chondrocytes in low cell density.

    Science.gov (United States)

    Muller-Rath, R; Gavénis, K; Andereya, S; Mumme, T; Schmidt-Rohlfing, B; Schneider, U

    2007-12-01

    Collagen type-I matrix systems have gained growing importance as a cartilage repair device. However, most of the established matrix systems use collagen type-I of bovine origin seeded in high cell densities. Here we present a novel collagen type-I gel system made of rat tail collagen for the cultivation of human chondrocytes in low cell densities. Rat tail collagen type-I gel (CaReS, Arthro Kinetics, Esslingen, Germany) was seeded with human passage 2 chondrocytes in different cell densities to evaluate the optimal cell number. In vitro, the proliferation factor of low density cultures was more than threefold higher compared with high density cultures. After 6 weeks of in vitro cultivation, freshly prepared chondrocytes with an initial cell density of 2x10(5) cells/mL showed a proliferation factor of 33. A cell density of 2x10(5) cells/mL was chosen for in vitro and in vivo cultivation using the common nude mouse model as an in vivo system. Chondrocytes stayed viable as a Live/Dead fluorescence assay and TUNEL staining revealed. During in vitro cultivation, passage 0 cells partly dedifferentiated morphologically. In vivo, passage 0 cells maintained the chondrocyte phenotype and demonstrated an increased synthesis of collagen type-II protein and gene expression compared to passage 2 cells. Passage 2 cells did not redifferentiate in vivo. Cultivating a cell-seeded collagen gel of bovine origin as a control (AtelocollagenTM, Koken, Tokyo, Japan) did not lead to superior results with regard to cell morphology, col-II protein production and col-II gene expression. With the CaReS collagen gel system the best quality of repair tissue was obtained by seeding freshly isolated chondrocytes.

  18. Adult Human Neurogenesis: from Microscopy to Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Amanda eSierra

    2011-04-01

    Full Text Available Neural stem cells reside in well-defined areas of the adult human brain and are capable of gene-rating new neurons throughout the life span. In rodents, it is well established that the new born neurons are involved in olfaction as well as in certain forms of memory and learning. In humans, the functional relevance of adult human neurogenesis is being investigated, in particular its implication in the etiopathology of a variety of brain disorders. Adult neurogenesis in the human brain was discovered by utilizing methodologies directly imported from the rodent research, such as immunohistological detection of proliferation and cell-type specific biomarkers in postmortem or biopsy tissue. However, in the vast majority of cases, these methods do not support longitudinal studies; thus, the capacity of the putative stem cells to form new neurons under different disease conditions cannot be tested. More recently, new technologies have been specifically developed for the detection and quantification of neural stem cells in the living human brain. These technologies rely on the use of magnetic resonance imaging, available in hospitals worldwide. Although they require further validation in rodents and primates, these new methods hold the potential to test the contribution of adult human neurogenesis to brain function in both health and disease. This review reports on the current knowledge on adult human neurogenesis. We first review the different methods available to assess human neurogenesis, both ex vivo and in vivo and then appraise the changes of adult neurogenesis in human diseases.

  19. Effects of tenoxicam and aspirin on the metabolism of proteoglycans and hyaluronan in normal and osteoarthritic human articular cartilage.

    Science.gov (United States)

    Manicourt, D H; Druetz-Van Egeren, A; Haazen, L; Nagant de Deuxchaisnes, C

    1994-01-01

    1. As nonsteroidal anti-inflammatory drugs may impair the ability of the chondrocyte to repair its damaged extracellular matrix, we explored the changes in the metabolism of newly synthesized proteoglycan (PG) and hyaluronan (HA) molecules produced by tenoxicam and aspirin in human normal cartilage explants and in osteoarthritic (OA) cartilage from age-matched donors. 2. Explants were sampled from the medial femoral condyle and were classified by use of Mankin's histological-histochemical grading system. Cartilage specimens were normal in 10 subjects, exhibited moderate OA (MOA) in 10 and had severe OA (SOA) in 10. 3. Cartilage explants were pulsed with [3H]-glucosamine and chased in the absence and in the presence of either aspirin (190 micrograms ml-1) or tenoxicam (4-16 micrograms ml-1). After papain digestion, the labelled chondroitin sulphate ([3H]-PGs) and HA([3H]-HA) molecules present in the tissue and media were purified by anion-exchange chromatography. 4. In normal cartilage as well as in explants with MOA and SOA aspirin reduced more strongly PG and HA synthesis than the loss of [3H]-HA and [3H]-PGs. 5. In normal cartilage, tenoxicam did not affect PG metabolism whereas it reduced HA synthesis in a dose-dependent manner and did not change or even increased the net loss of [3H]-HA. In contrast, in OA cartilage, tenoxicam produced a stronger reduction in the loss of [3H]-PGs than in PG synthesis and this decrease occurred at lower concentrations in cartilage with SOA (4-8 micrograms ml-1) than in cartilage with MOA (8-16 micrograms ml-1).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7889262

  20. Gustofacial and olfactofacial responses in human adults.

    Science.gov (United States)

    Weiland, Romy; Ellgring, Heiner; Macht, Michael

    2010-11-01

    Adults' facial reactions in response to tastes and odors were investigated in order to determine whether differential facial displays observed in newborns remain stable in adults who exhibit a greater voluntary facial control. Twenty-eight healthy nonsmokers (14 females) tasted solutions of PROP (bitter), NaCl (salty), citric acid (sour), sucrose (sweet), and glutamate (umami) differing in concentration (low, medium, and high) and smelled different odors (banana, cinnamon, clove, coffee, fish, and garlic). Their facial reactions were video recorded and analyzed using the Facial Action Coding System. Adults' facial reactions discriminated between stimuli with opponent valences. Unpleasant tastes and odors elicited negative displays (brow lower, upper lip raise, and lip corner depress). The pleasant sweet taste elicited positive displays (lip suck), whereas the pleasant odors did not. Unlike newborns, adults smiled with higher concentrations of some unpleasant tastes that can be regarded as serving communicative functions. Moreover, adults expressed negative displays with higher sweetness. Except for the "social" smile in response to unpleasant tastes, adults' facial reactions elicited by tastes and odors mostly correspond to those found in newborns. In conclusion, adults' facial reactions to tastes and odors appear to remain stable in their basic displays; however, some additional reactions might reflect socialization influences.

  1. Adult Literacy Education and Human Rights: A View from Afghanistan

    Science.gov (United States)

    Andersen, Susan M.; Kooij, Christina S.

    2007-01-01

    In this article, we argue that adult literacy as part of international development is an issue of both human rights and women's rights. We explore this by presenting a case study of the effects of one innovative adult literacy program in Afghanistan that places men and women, as well as various ethnicities, together in the same classroom as…

  2. Pure waterjet drilling of articular bone

    OpenAIRE

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

    2015-01-01

    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 study investigates whether drilling bony tissue with pure waterjets is feasible. Water pressures between 20 and 120 MPa with an orifice of 0.6 mm were used to create waterjets to drill blind boring...

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

    Energy Technology Data Exchange (ETDEWEB)

    Silvast, T.S.; Jurvelin, J.S.; Aula, A.S.; Lammi, M.J.; Toeyraes, J. (Dept. of Clinical Neurophysiology, Kuopio Univ. Hospital, Kuopio (Finland))

    2009-01-15

    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<0.05) in contrast agent concentration was seen in the superficial layer of spontaneously degenerated samples. Significant negative correlations were revealed between the contrast agent concentration and the superficial or full-thickness GAG content of tissue (|R|>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

  4. Differentiated human stem cells resemble fetal, not adult, β cells.

    Science.gov (United States)

    Hrvatin, Sinisa; O'Donnell, Charles W; Deng, Francis; Millman, Jeffrey R; Pagliuca, Felicia Walton; DiIorio, Philip; Rezania, Alireza; Gifford, David K; Melton, Douglas A

    2014-02-25

    Human pluripotent stem cells (hPSCs) have the potential to generate any human cell type, and one widely recognized goal is to make pancreatic β cells. To this end, comparisons between differentiated cell types produced in vitro and their in vivo counterparts are essential to validate hPSC-derived cells. Genome-wide transcriptional analysis of sorted insulin-expressing (INS(+)) cells derived from three independent hPSC lines, human fetal pancreata, and adult human islets points to two major conclusions: (i) Different hPSC lines produce highly similar INS(+) cells and (ii) hPSC-derived INS(+) (hPSC-INS(+)) cells more closely resemble human fetal β cells than adult β cells. This study provides a direct comparison of transcriptional programs between pure hPSC-INS(+) cells and true β cells and provides a catalog of genes whose manipulation may convert hPSC-INS(+) cells into functional β cells.

  5. Adult human metapneumonovirus (hMPV) pneumonia mimicking Legionnaire's disease.

    Science.gov (United States)

    Cunha, Burke A; Irshad, Nadia; Connolly, James J

    2016-01-01

    In adults hospitalized with viral pneumonias the main differential diagnostic consideration is influenza pneumonia. The respiratory viruses causing viral influenza like illnesses (ILIs), e.g., RSV may closely resemble influenza. Rarely, extrapulmonary findings of some ILIs may resemble Legionnaire's disease (LD), e.g., adenovirus, human parainfluenza virus (HPIV-3). We present a most unusual case of human metapneumonovirus pneumonia (hMPV) with some characteristic extrapulmonary findings characteristic of LD, e.g., relative bradycardia, as well as mildly elevated serum transaminases and hyphosphatemia. We believe this is the first reported case of hMPV pneumonia in a hospitalized adult that had some features of LD.

  6. 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.

  7. Oogenesis in adult mammals, including humans: a review.

    Science.gov (United States)

    Bukovsky, Antonin; Caudle, Michael R; Svetlikova, Marta; Wimalasena, Jay; Ayala, Maria E; Dominguez, Roberto

    2005-04-01

    The origin of oocytes and primary follicles in ovaries of adult mammalian females has been a matter of dispute for over 100 yr. The prevailing belief that all oocytes in adult mammalian females must persist from the fetal period of life seems to be a uniquely retrogressive reproductive mechanism requiring humans to preserve their gametes from the fetal period for several decades. The utilization of modern techniques during last 10 yr clearly demonstrates that mammalian primordial germ cells originate from somatic cell precursors. This indicates that if somatic cells are precursors of germ cells, then somatic mutations can be passed on to progeny. Mitotically active germline stem cells have been described earlier in ovaries of adult prosimian primates and recently have been reported to also be present in the ovaries of adult mice. We have earlier shown that in adult human females, mesenchymal cells in the ovarian tunica albuginea undergo a mesenchymal-epithelial transition into ovarian surface epithelium cells, which differentiate sequentially into primitive granulosa and germ cells. Recently, we have reported that these structures assemble in the deeper ovarian cortex and form new follicles to replace earlier primary follicles undergoing atresia (follicular renewal). Our current observations also indicate that follicular renewal exists in rat ovaries, and human oocytes can differentiate from ovarian surface epithelium in fetal ovaries in vivo and from adult ovaries in vitro. These reports challenge the established dogma regarding the fetal origin of eggs and primary follicles in adult mammalian ovaries. Our data indicate that the pool of primary follicles in adult human ovaries does not represent a static but a dynamic population of differentiating and regressing structures. Yet, the follicular renewal may cease at a certain age, and this may predetermine the onset of the natural menopause or premature ovarian failure. A lack of follicular renewal in aging ovaries

  8. 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...... treatments and the biological response should be reproducible and comparable to humans. This allows for a reliable translation of results to clinical studies.This study aimed at verifying the Göttingen minipig as a pre-clinical model for articular cartilage repair by testing existing clinical cartilage...

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

    Directory of Open Access Journals (Sweden)

    Minhong Wang

    2013-09-01

    Full Text Available 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 technology have been increasingly enabling and facilitating learning and knowledge-related initiatives.. They have largely extended learning opportunities through the provision of resource-rich and learner-centered environment, computer-based learning support, and expanded social interactions and networks. Papers in this special issue are representative of ongoing research on integration of technology with learning for innovation and sustainable development in higher education institutions and organizational and community environments.

  10. 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.

  11. 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

  12. Classification of primary articular chondrocalcinosis.

    Science.gov (United States)

    Zitnan, D; Sitaj, S

    1979-01-01

    Based on long-term observations the authors submit a categorization of primary (hereditary and solitary) articular chondrocalcinosis into three different sub-populations. Attention is drawn to the fact that the extent of the qualitative disorder of the articular cartilage, obviously conditioned genetically, is linked with the age factor and determines the quantitative differences of pyrophosphate arthropathy in primary chondrocalcinosis. In young age, as a rule in the third decade, severe polyarticular condrocalcinosis (first sub-population) develops which causes relatively soon invalidity, in middle age (5th and 6th decade) milder condrocalcinosis develops (second sub-population) which combines with extraarticular, tendinous and tissue calcifacations, and finally in advanced age oligoarticular chondrocalcinosis develops (third sub-population) which is usually associated with ankylosing hyperostosis of the spine. Articular chondrocalcinosis (CCA) which we described by this term as a special metabolic arthropathy which occurs in families and solitary and which we defined as a special nosological unit (35, 36,) has become generally known and firmly established in rheumatology. As ensues from numerous publications, primary (idiopathic) CCA which comprises the hereditary and solitary (sporadic) form is characterized by pyrophosphate arthropathy which develops on articular cartilages not damaged by another process (13, 25, 26, 37); on the other hand as secondary CCA we consider pyrophosphate arthropathies which are associated with metabolic, endocrine or other diseases (9, 30). The common sign of both basic forms of CCA is the presence of microcrystals of calcium pyrophosphate dihydrate (CaPD) in articular cartilages, synovial fluid, or other articular structures (capsules, tendons, ligaments), characterized originally by McCarty et al. (11, 18) and later by other authors (2, 23, 27, 32). In addition to semantic (terminological) problems there were also questions of the

  13. 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.

  14. 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.

  15. CCM2 expression during prenatal development and adult human neocortex.

    Science.gov (United States)

    Tanriover, Gamze; Sozen, Berna; Gunel, Murat; Demir, Necdet

    2011-08-01

    Cerebral cavernous malformation (CCM) is one of the most common types of vascular malformations of the central nervous system, affecting nearly one in 200 people. CCM lesions are characterized by grossly dilated vascular channels lined by a single layer of endothelium. Genetic linkage analyses have mapped three CCM loci to CCM1, CCM2 and CCM3. All three causative genes have now been identified allowing new insights into CCM pathophysiology. We focused on the CCM2 protein that might take place in blood vessel formation; we report here the expression patterns of CCM2 in prenatal development and adult human neocortex by means of immunohistochemistry and Western blot analysis. CCM2 was obviously detected in vascular endothelium and neuroglial precursor cells during development and also observed in arterial endothelium, neurons, some of the glial cells in adult neocortex. The expression patterns suggest that it could be one of the arterial markers whether this is a cause or a consequence of an altered vascular identity. CCM2 might play a role during vasculogenesis and angiogenesis during human brain development. Furthermore, with this study, CCM2 have been described for the first time in developing human neocortex.

  16. Lubrication of Articular Cartilage.

    Science.gov (United States)

    Jahn, Sabrina; Seror, Jasmine; Klein, Jacob

    2016-07-11

    The major synovial joints such as hips and knees are uniquely efficient tribological systems, able to articulate over a wide range of shear rates with a friction coefficient between the sliding cartilage surfaces as low as 0.001 up to pressures of more than 100 atm. No human-made material can match this. The means by which such surfaces maintain their very low friction has been intensively studied for decades and has been attributed to fluid-film and boundary lubrication. Here, we focus especially on the latter: the reduction of friction by molecular layers at the sliding cartilage surfaces. In particular, we discuss such lubrication in the light of very recent advances in our understanding of boundary effects in aqueous media based on the paradigms of hydration lubrication and of the synergism between different molecular components of the synovial joints (namely hyaluronan, lubricin, and phospholipids) in enabling this lubrication.

  17. Ontogeny of morningness-eveningness across the adult human lifespan

    Science.gov (United States)

    Randler, Christoph

    2016-02-01

    Sleep timing of humans can be classified alongside a continuum from early to late sleepers, with some people (larks) having an early activity, early bed, and rise times and others (owls) with a more nocturnally orientated activity. Only a few studies reported that morningness-eveningness changes significantly during the adult lifespan based on community samples. Here, I applied a different methodological approach to seek for evidence for the age-related changes in morningness-eveningness preferences by using a meta-data from all available studies. The new aspect of this cross-sectional approach is that only a few studies themselves address the age-related changes of the adult lifespan development, but that many studies are available that provide exactly the data needed. The studies came from 27 countries and included 36,939 participants. Age was highly significantly correlated with scores on the Composite Scale of Morningness ( r = 0.70). This relationship seems linear, because a linear regression explained nearly the same amount of variance compared to other models such as logarithmic, quadratic, or cubic models. The standard deviation of age correlated with the standard deviation of CSM scores ( r = 0.55), suggesting when there is much variance in age in a study; in turn, there is much variance in morningness. This meta-analytical approach shows that morningness-eveningness changes across the adult lifespan and that older age is related to higher morningness.

  18. 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.)

  19. 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

    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....... 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...

  20. 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.

  1. Neuropeptide Y in the Adult and Fetal Human Pineal Gland

    Directory of Open Access Journals (Sweden)

    Morten Møller

    2014-01-01

    Full Text Available Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally.

  2. Neuropeptide Y in the adult and fetal human pineal gland.

    Science.gov (United States)

    Møller, Morten; Phansuwan-Pujito, Pansiri; Badiu, Corin

    2014-01-01

    Neuropeptide Y was isolated from the porcine brain in 1982 and shown to be colocalized with noradrenaline in sympathetic nerve terminals. The peptide has been demonstrated to be present in sympathetic nerve fibers innervating the pineal gland in many mammalian species. In this investigation, we show by use of immunohistochemistry that neuropeptide Y is present in nerve fibers of the adult human pineal gland. The fibers are classical neuropeptidergic fibers endowed with large boutons en passage and primarily located in a perifollicular position with some fibers entering the pineal parenchyma inside the follicle. The distance from the immunoreactive terminals to the pinealocytes indicates a modulatory function of neuropeptide Y for pineal physiology. Some of the immunoreactive fibers might originate from neurons located in the brain and be a part of the central innervation of the pineal gland. In a series of human fetuses, neuropeptide Y-containing nerve fibers was present and could be detected as early as in the pineal of four- to five-month-old fetuses. This early innervation of the human pineal is different from most rodents, where the innervation starts postnatally.

  3. Early reversal cells in adult human bone remodeling

    DEFF Research Database (Denmark)

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

    2016-01-01

    . 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...... through electron microscopy and analysis of molecular markers. Periosteoclastic reversal cells show direct contacts with the osteoclasts and with the demineralized resorption debris. These early reversal cells show (1) ¾-collagen fragments typically generated by extracellular collagenases of the MMP...... family, (2) MMP-13 (collagenase-3) and (3) the endocytic collagen receptor uPARAP/Endo180. The prevalence of these markers was lower in the later reversal cells, which are located near the osteoid surfaces and morphologically resemble mature bone-forming osteoblasts. In conclusion, this study...

  4. 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

  5. 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.

  6. Footprint-free human induced pluripotent stem cells from articular cartilage with redifferentiation capacity: a first step toward a clinical-grade cell source.

    Science.gov (United States)

    Boreström, Cecilia; Simonsson, Stina; Enochson, Lars; Bigdeli, Narmin; Brantsing, Camilla; Ellerström, Catharina; Hyllner, Johan; Lindahl, Anders

    2014-04-01

    Human induced pluripotent stem cells (iPSCs) are potential cell sources for regenerative medicine; however, clinical applications of iPSCs are restricted because of undesired genomic modifications associated with most reprogramming protocols. We show, for the first time, that chondrocytes from autologous chondrocyte implantation (ACI) donors can be efficiently reprogrammed into iPSCs using a nonintegrating method based on mRNA delivery, resulting in footprint-free iPSCs (no genome-sequence modifications), devoid of viral factors or remaining reprogramming molecules. The search for universal allogeneic cell sources for the ACI regenerative treatment has been difficult because making chondrocytes with high matrix-forming capacity from pluripotent human embryonic stem cells has proven challenging and human mesenchymal stem cells have a predisposition to form hypertrophic cartilage and bone. We show that chondrocyte-derived iPSCs can be redifferentiated in vitro into cartilage matrix-producing cells better than fibroblast-derived iPSCs and on par with the donor chondrocytes, suggesting the existence of a differentiation bias toward the somatic cell origin and making chondrocyte-derived iPSCs a promising candidate universal cell source for ACI. Whole-genome single nucleotide polymorphism array and karyotyping were used to verify the genomic integrity and stability of the established iPSC lines. Our results suggest that RNA-based technology eliminates the risk of genomic integrations or aberrations, an important step toward a clinical-grade cell source for regenerative medicine such as treatment of cartilage defects and osteoarthritis.

  7. Low oxygen tension stimulates redifferentiation of dedifferentiated adult human nasal chondrocytes

    NARCIS (Netherlands)

    Malda, J.; Blitterswijk, van C.A.; Geffen, van M.; Martens, D.E.; Tramper, J.; Riesle, J.

    2004-01-01

    Objective: To determine the effect of dissolved oxygen tension (DO) on the redifferentiation of dedifferentiated adult human nasal septum chondrocytes cultured as pellets. Design: After isolation, human nasal chondrocytes were expanded in monolayer culture, which resulted in their dedifferentiation.

  8. Low oxygen tension stimulates the redifferentiation of dedifferentiated adult human nasal chondrocytes

    NARCIS (Netherlands)

    Malda, J.; Blitterswijk, van C.A.; Geffen, van M.; Martens, D.E.; Tramper, J.; Riesle, J.

    2004-01-01

    Objective: To determine the effect of dissolved oxygen tension (DO) on the redifferentiation of dedifferentiated adult human nasal septum chondrocytes cultured as pellets. - Design: After isolation, human nasal chondrocytes were expanded in monolayer culture, which resulted in their dedifferentiati

  9. Comprehensive cellular-resolution atlas of the adult human brain.

    Science.gov (United States)

    Ding, Song-Lin; Royall, Joshua J; Sunkin, Susan M; Ng, Lydia; Facer, Benjamin A C; Lesnar, Phil; Guillozet-Bongaarts, Angie; McMurray, Bergen; Szafer, Aaron; Dolbeare, Tim A; Stevens, Allison; Tirrell, Lee; Benner, Thomas; Caldejon, Shiella; Dalley, Rachel A; Dee, Nick; Lau, Christopher; Nyhus, Julie; Reding, Melissa; Riley, Zackery L; Sandman, David; Shen, Elaine; van der Kouwe, Andre; Varjabedian, Ani; Write, Michelle; Zollei, Lilla; Dang, Chinh; Knowles, James A; Koch, Christof; Phillips, John W; Sestan, Nenad; Wohnoutka, Paul; Zielke, H Ronald; Hohmann, John G; Jones, Allan R; Bernard, Amy; Hawrylycz, Michael J; Hof, Patrick R; Fischl, Bruce; Lein, Ed S

    2016-11-01

    Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole-brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high-resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and 1,356 large-format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto- and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127-3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

  10. Adult human liver mesenchymal progenitor cells express phenylalanine hydroxylase.

    Science.gov (United States)

    Baruteau, Julien; Nyabi, Omar; Najimi, Mustapha; Fauvart, Maarten; Sokal, Etienne

    2014-09-01

    Phenylketonuria (PKU) is one of the most prevalent inherited metabolic diseases and is accountable for a severe encephalopathy by progressive intoxication of the brain by phenylalanine. This results from an ineffective L-phenylalanine hydroxylase enzyme (PAH) due to a mutated phenylalanine hydroxylase (PAH) gene. Neonatal screening programs allow an early dietetic treatment with restrictive phenylalanine intake. This diet prevents most of the neuropsychological disabilities but remains challenging for lifelong compliance. Adult-derived human liver progenitor cells (ADHLPC) are a pool of precursors that can differentiate into hepatocytes. We aim to study PAH expression and PAH activity in a differenciated ADHLPC. ADHLPC were isolated from human hepatocyte primary culture of two different donors and differenciated under specific culture conditions. We demonstrated the high expression of PAH and a large increase of PAH activity in differenciated LPC. The age of the donor, the cellular viability after liver digestion and cryopreservation affects PAH activity. ADHLPC might therefore be considered as a suitable source for cell therapy in PKU.

  11. Analgesic effects of intra-articular botulinum toxin Type B in a murine model of chronic degenerative knee arthritis pain

    Directory of Open Access Journals (Sweden)

    Stephanie Anderson

    2010-09-01

    Full Text Available Stephanie Anderson1,2, Hollis Krug1,2, Christopher Dorman1, Pari McGarraugh1, Sandra Frizelle1, Maren Mahowald1,21Rheumatology Section, Veteran’s Affairs Medical Center, Minneapolis, Minnesota; 2Division of Rheumatology and Autoimmune Diseases, University of Minnesota Medical School, Minneapolis, Minnesota, USAObjective: To evaluate the analgesic effectiveness of intra-articular botulinum toxin Type B (BoNT/B in a murine model of chronic degenerative arthritis pain.Methods and materials: Chronic arthritis was produced in adult C57Bl6 mice by intra-articular injection of Type IV collagenase into the left knee. Following induction of arthritis, the treatment group received intra-articular BoNT/B. Arthritic control groups were treated with intra-articular normal saline or sham injections. Pain behavior testing was performed prior to arthritis, after induction of arthritis, and following treatments. Pain behavior measures included analysis of gait impairment (spontaneous pain behavior and joint tenderness evaluation (evoked pain response. Strength was measured as ability to grasp and cling.Results: Visual gait analysis showed significant impairment of gait in arthritic mice that improved 43% after intra-articular BoNT/B, demonstrating a substantial articular analgesic effect. Joint tenderness, measured with evoked pain response scores, increased with arthritis induction and decreased 49.5% after intra-articular BoNT/B treatment. No improvement in visual gait scores or decrease in evoked pain response scores were found in the control groups receiving intra-articular normal saline or sham injections. Intra-articular BoNT/B was safe, and no systemic effects or limb weakness was noted.Conclusions: This study is the first report of intra-articular BoNT/B for analgesia in a murine model of arthritis pain. The results of this study validate prior work using intra-articular neurotoxins in murine models. Our findings show chronic degenerative arthritis

  12. Estabilidade articular: abordagem biomecânica

    OpenAIRE

    Alex Sandra Oliveira de Cerqueira Soares

    2015-01-01

    A instabilidade articular é responsável pelo desenvolvimento de lesões degenerativas incapacitantes que comprometem o desempenho funcional. Compreender os processos desenvolvidos para estabilização dinâmica articular é um desafio para pesquisadores das mais diversas áreas. O presente estudo propõe o uso da abordagem Biomecânica para reconhecer os mecanismos relacionadas ao processo de estabilização dinâmica articular, por meio de três diferentes condições experimentais. No experimento 1 foi a...

  13. Features of hand-foot crawling behavior in human adults.

    Science.gov (United States)

    Maclellan, M J; Ivanenko, Y P; Cappellini, G; Sylos Labini, F; Lacquaniti, F

    2012-01-01

    Interlimb coordination of crawling kinematics in humans shares features with other primates and nonprimate quadrupeds, and it has been suggested that this is due to a similar organization of the locomotor pattern generators (CPGs). To extend the previous findings and to further explore the neural control of bipedal vs. quadrupedal locomotion, we used a crawling paradigm in which healthy adults crawled on their hands and feet at different speeds and at different surface inclinations (13°, 27°, and 35°). Ground reaction forces, limb kinematics, and electromyographic (EMG) activity from 26 upper and lower limb muscles on the right side of the body were collected. The EMG activity was mapped onto the spinal cord in approximate rostrocaudal locations of the motoneuron pools to characterize the general features of cervical and lumbosacral spinal cord activation. The spatiotemporal pattern of spinal cord activity significantly differed between quadrupedal and bipedal gaits. In addition, participants exhibited a large range of kinematic coordination styles (diagonal vs. lateral patterns), which is in contrast to the stereotypical kinematics of upright bipedal walking, suggesting flexible coupling of cervical and lumbosacral pattern generators. Results showed strikingly dissimilar directional horizontal forces for the arms and legs, considerably retracted average leg orientation, and substantially smaller sacral vs. lumbar motoneuron activity compared with quadrupedal gait in animals. A gradual transition to a more vertical body orientation (increasing the inclination of the treadmill) led to the appearance of more prominent sacral activity (related to activation of ankle plantar flexors), typical of bipedal walking. The findings highlight the reorganization and adaptation of CPG networks involved in the control of quadrupedal human locomotion and a high specialization of the musculoskeletal apparatus to specific gaits.

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

    Directory of Open Access Journals (Sweden)

    Nadja Larsen

    Full Text Available 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. 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-encoded amplicon pyrosequencing of the V4 region of the 16S rRNA gene. The proportions of phylum Firmicutes and class Clostridia were significantly reduced in the diabetic group compared to the control group (P = 0.03. Furthermore, the ratios of Bacteroidetes to Firmicutes as well as the ratios of Bacteroides-Prevotella group to C. coccoides-E. rectale group correlated positively and significantly with plasma glucose concentration (P = 0.04 but not with BMIs. Similarly, class Betaproteobacteria was highly enriched in diabetic compared to non-diabetic persons (P = 0.02 and positively correlated with plasma glucose (P = 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 to control metabolic diseases by modifying the gut microbiota.

  15. Photogrammetric analysis of the articular surface of the distal radius.

    Science.gov (United States)

    Ege, A; Seker, D Z; Tuncay, I; Duran, Z

    2004-01-01

    Three-dimensional measurements made using photogrammetry have recently gained popularity with the development of real-time detection facilities and up-to-date equipment. The modelling of human bones presents a particular challenge as the measurements required are difficult to obtain, especially from uneven surfaces. In this study, the articular surfaces of 12 radius bones were evaluated using photogrammetry to obtain three-dimensional coordinates of certain points. Morphometric characteristics of the digital topography of the articular surface were analysed using three-dimensional data from more than 200 points for each specimen. The coronal plane curve, from the tip of the styloid process to the centre of the distal radioulnar articular notch, was found to be similar to the fourth degree polynomial function. A mathematical expression representing the sagittal curve passing through scapholunate border could not be found. Close-range photogrammetry is a safe and precise technique that can provide reliable, reproducible and accurate data for evaluating complex morphological surfaces.

  16. Imaging of intra-articular osteoid osteoma

    Energy Technology Data Exchange (ETDEWEB)

    Allen, S.D.; Saifuddin, A. E-mail: asaifuddin@aol.com

    2003-11-01

    Intra-articular osteoid osteoma accounts for approximately 13% of all osteoid osteomas and presents as a monoarthropathy. Radiographs commonly do not identify the nidus, and in this event, MRI is likely to be the next imaging investigation. MRI may show a variety of appearances depending upon the age of the lesion. This article illustrates the imaging features of intra-articular osteoid osteoma, with emphasis on MRI. CT remains the investigation of choice for identifying the nidus.

  17. Human herpesvirus 8 seropositivity among sexually active adults in Uganda.

    Directory of Open Access Journals (Sweden)

    Fatma M Shebl

    Full Text Available INTRODUCTION: Sexual transmission of human herpesvirus 8 (HHV8 has been implicated among homosexual men, but the evidence for sexual transmission among heterosexual individuals is controversial. We investigated the role of sexual transmission of HHV8 in a nationally representative sample in Uganda, where HHV8 infection is endemic and transmitted mostly during childhood. MATERIALS AND METHODS: The study population was a subset of participants (n = 2681 from a population-based HIV/AIDS serobehavioral survey of adults aged 15-59 years conducted in 2004/2005. High risk for sexual transmission was assessed by questionnaire and serological testing for HIV and herpes simplex virus 2. Anti-HHV8 antibodies were measured using two enzyme immunoassays targeting synthetic peptides from the K8.1 and orf65 viral genes. The current study was restricted to 2288 sexually active adults. ORs and 95% CIs for HHV8 seropositivity were estimated by fitting logistic regression models with a random intercept using MPLUS and SAS software. RESULTS: The weighted prevalence of HHV8 seropositivity was 56.2%, based on 1302 seropositive individuals, and it increased significantly with age (P(trend<0.0001. In analyses adjusting for age, sex, geography, education, and HIV status, HHV8 seropositivity was positively associated with reporting two versus one marital union (OR:1.52, 95% CI: 1.17-1.97 and each unit increase in the number of children born (OR: 1.04, 95% CI: 1.00-1.08, and was inversely associated with ever having used a condom (OR: 0.64, 95% CI: 0.45-0.89. HHV8 seropositivity was not associated with HIV (P = 0.660 or with herpes simplex virus 2 (P = 0.732 seropositivity. Other sexual variables, including lifetime number of sexual partners or having had at least one sexually transmitted disease, and socioeconomic variables were unrelated to HHV8 seropositivity. CONCLUSION: Our findings are compatible with the conclusion that sexual transmission of HHV8 in

  18. Immunoreactivity of thymosin beta 4 in human foetal and adult genitourinary tract

    Science.gov (United States)

    Nemolato, S.; Cabras, T.; Fanari, M.U.; Cau, F.; Fanni, D.; Gerosa, C.; Manconi, B.; Messana, I.; Castagnola, M.; Faa, G.

    2010-01-01

    Thymosin beta 4 (Tβ4) is a member of the beta-thymosins family, a family of peptides playing essential roles in many cellular functions. Our recent studies suggested Tβ4 plays a key role in the development of human salivary glands and the gastrointestinal tract. The aim of this study was to analyse the presence of Tβ4 in the human adult and foetal genitourinary tract. Immunolocalization of Tβ4 was studied in autoptic samples of kidney, bladder, uterus, ovary, testicle and prostate obtained from four human foetuses and four adults. Presence of the peptide was observed in cells of different origin: in surface epithelium, in gland epithelial cells and in the interstitial cells. Tβ4 was mainly found in adult and foetal bladder in the transitional epithelial cells; in the adult endometrium, glands and stromal cells were immunoreactive for the peptide; Tβ4 was mainly localized in the glands of foetal prostate while, in the adults a weak Tβ4 reactivity was restricted to the stroma. In adult and foetal kidney, Tβ4 reactivity was restricted to ducts and tubules with completely spared glomeruli; a weak positivity was observed in adult and foetal oocytes; immunoreactivity was mainly localized in the interstitial cells of foetal and adult testis. In this study, we confirm that Tβ4 could play a relevant role during human development, even in the genitourinary tract, and reveal that immunoreactivity for this peptide may change during postnatal and adult life. PMID:21263742

  19. A century of trends in adult human height

    DEFF Research Database (Denmark)

    Sørensen, Thorkild Ingvor A; Zimmermann, Esther

    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...

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

    Science.gov (United States)

    Sandberg, Cecilie Jonsgar; Vik-Mo, Einar O; Behnan, Jinan; Helseth, Eirik; Langmoen, Iver A

    2014-01-01

    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 fate.

  1. HISTOLOGICAL SEXUAL DIFFERENCES IN ADULT HUMAN PARATHYROID GLANDS

    Directory of Open Access Journals (Sweden)

    Fating Anita

    2014-07-01

    Full Text Available CONTEXT (BACKGROUND: Increasing problems of calcium deficiency with physiological conditions like pregnancy, lactation etc. it becomes the need of time to focus attention towards these glands as one of the essential entity. Hence we have undertaken this study to have an idea about normal variation in the gland as per sex. AIMS: To reveal sexual differences in adult human parathyroid glands. METHODS AND MATERIAL: Parathyroid glands from 25 autopsied cases of 20 to 59 years were studied after staining with Hematoxylin & Eosin, Masson’s Trichrome & Reticulin stains. STATISTICAL ANALYSIS: Data is analyzed on statistical software intercooled STATA version 8.0. Data was presented in mean± standard deviation & categorical variables were expressed in percentages. Comparison of oxyphil scores in male & female was done by unpaired‘t’ test. P < 0.05 was taken as statistical significance. RESULTS: Stroma composed of short often branching reticular fibres along with blood vessels and fat cells. By statistical examination the amount of fat was more in case of females than in males of same age groups. Oxyphil cells being less numerous than chief cells were distinguished by their dark eosinophilic, granular cytoplasm and were arranged mostly in closely packed groups without interstitial fat in between the cells. Oxyphil cells also found as placed singly among chief cells. It was also observed as continuous masses or anastomosing columns. As compared with males oxyphil cells are more in females. CONCLUSIONS: By statistical analysis 1 Percentage of stromal fat in case of females was slightly greater than in males of same age group. 2 The score of oxyphil cells in females was double to more than triple as compared to male score of same age group. 3 This study is clinically important as hormonal changes occurs early in females than in males and it is in favor of providing supplementary calcium with D3 along with minimal dose of estrogen as age advances in

  2. Response to: Comment on "Human adult neurogenesis across the ages: An immunohistochemical study".

    Science.gov (United States)

    Dennis, C V; Suh, L S; Rodriguez, M L; Kril, J J; Sutherland, G T

    2017-02-20

    It is with great interest that we read the comment by Marucci [1] referring to our publication "Human adult neurogenesis across the ages: An immunohistochemical study" [2]. Since the seminal paper of Eriksson et al. in 1998, human adult neurogenesis has become a major area of research in neuroscience [3]. Although an age-related decline in human adult neurogenesis is not disputed, opinions differ on the functional significance of the residual neuroblasts. This article is protected by copyright. All rights reserved.

  3. Brain stem auditory evoked responses in human infants and adults

    Science.gov (United States)

    Hecox, K.; Galambos, R.

    1974-01-01

    Brain stem evoked potentials were recorded by conventional scalp electrodes in infants (3 weeks to 3 years of age) and adults. The latency of one of the major response components (wave V) is shown to be a function both of click intensity and the age of the subject; this latency at a given signal strength shortens postnatally to reach the adult value (about 6 msec) by 12 to 18 months of age. The demonstrated reliability and limited variability of these brain stem electrophysiological responses provide the basis for an optimistic estimate of their usefulness as an objective method for assessing hearing in infants and adults.

  4. STRUCTURAL ANALYSIS OF ARTICULAR CARTILAGE OF THE HIP JOINT USING FINITE ELEMENT METHOD

    Directory of Open Access Journals (Sweden)

    Robert Karpiński

    2016-09-01

    Full Text Available The paper presents the results of a preliminary study on the structural analysis of the hip joint, taking into account changes in the mechanical properties of the articular cartilage of the joint. Studies have been made due to the need to determine the tension distribution occurring in the cartilage of the human hip. These distribution are the starting point for designing custom made human hip prosthesis. Basic anatomy, biomechanical analysis of the hip joint and articular cartilage are introduced. The mechanical analysis of the hip joint model is conducted. Final results of analysis are presented. Main conclusions of the study are: the capability of absorbing loads by articular cartilage of the hip joint is preliminary determined as decreasing with increasing degenerations of the cartilage and with age of a patient. Without further information on changes of cartilage’s mechanical parameters in time it is hard to determine the nature of relation between mentioned capability and these parameters.

  5. Morphological method for the diagnosis of human adult type hypolactasia.

    OpenAIRE

    Maiuri, L; M. Rossi; V. Raia; Paparo, F; Coletta, S; Mazzeo, F; Breglia, A; Auricchio, S

    1994-01-01

    The primary adult type hypolactasia is the most common form of genetically determined disaccharidase deficiency. This study examined a large and homogeneous population of the south of Italy: surgical biopsy specimens of proximal jejunum from 178 adult subjects have been assayed for disaccharidase activities; the expression of lactase protein and lactase activity has also been investigated on tissue sections by immunomorphological and enzymohistochemical techniques. Histograms of lactase to su...

  6. 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.

  7. 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.

  8. Preliminary study on articular cartilage MRI T1ρimaging in normal adults%正常膝关节软骨MRI T1ρ序列表现初步研究

    Institute of Scientific and Technical Information of China (English)

    李智慧; 陆勇; 蒋梅花; 杜联军; 丁晓毅; 严福华

    2014-01-01

    Objective To compare the performance of MRI T1ρand three-dimensional fat suppressed fasts poiled gradient echo (3D-FS-SPGR) sequence in normal knee articular cartilage, investigate the feasibility of T 1ρsequence for assessing cartilage, and evaluate the MRI T1ρdifference between deep and superficial layer of normal knee articular cartilage. Methods A total of 26 healthy volunteers confirmed by clinician and radiologist were enrolled, which included 11 males and 15 females;aged 15-65 years old with mean age of 31.69. The performance of MRI T1ρand 3D-FS-SPGR sequence were analyzed. The knee cartilage was divided into 6 segments:patellar cartilage, trochlear cartilage, medial and lateral femoral condyle cartilage, medial and lateral tibial cartilage. The MRI signal intensity of cartilage, subchondral bone, and the background noise was measured on the T 1ρfirst echo images and the same location 3D-FS-SPGR images. The cartilage/subchondral bone contrast ratio(CNR) and the cartilage ratio(SNR) were compared by paired t-test. The thickest cartilage of 6 segments was selected and the T 1ρvalues of deep layer and superficial layer were measured by the same pixel values. The T1ρ values were compared by paired t-test, and P < 0.05 was considered statistically significant. Results ①The mean value of CNR and SNR in T1ρsequence on the first echo image was significantly higher than those of 3D-FS-SPGR sequence, with CNR being 29.88 ± 10.00 vs 12.08 ± 3.08(t=23.09, P=0.000) and SNR being 34.70 ± 11.16 vs 14.18 ± 3.46(t=23.929, P=0.000).②The mean T1ρvalue of the superficial layer [(43.23 ± 6.78) ms] was significantly higher than that of the deep layer[(29.12 ± 8.07) ms](t=-24.687, P=0 .000). Conclusion It is demonstrated that T1ρsequence could be used for clinical evaluation of cartilage, and the collagen fiber is arranged more closely in the superficial layer than in the deep layer.%目的:比较正常膝关节软骨MRI T1ρ和三

  9. Adult human case of toxocariasis with pulmonary migratory infiltrate and eosinophilia

    Directory of Open Access Journals (Sweden)

    Považan Đorđe

    2011-01-01

    Full Text Available Introduction. Toxocariasis is a zoonosis which is in Serbia characterized with a very high infection rate of dogs and excessive contamination of the soil with the eggs of Toxocara canis, the agent of the disease. Toxocara-induced infections have in recent years been established in a few hundreds of children, but toxocariasis has rather rarely been diagnosed in adults. Case report. We reported toxocariasis (visceral larva migrans in an adult, manifested by migratory pulmonary infiltrates and positive serological test finding to Toxocara. Conclusion. Human toxocariasis is a rare disease in adults, therefore it should be considered in adult patients presented with eosinophilia and migratory pulmonary infiltrates.

  10. Development of artificial articular cartilage

    Indian Academy of Sciences (India)

    Biswajit Bera

    2009-10-01

    The present study describes the development of artificial articular cartilage on the basis of mimicking structural gel properties and mechanical gel properties of natural articular cartilage. It is synthesized from PVA/Si nanocomposite containing 20% Tetra ethoxy silane (TEOS) by sol–gel method. 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 underlying bone with high bond strength.

  11. 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...... 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....... Stimulus–response curves were constructed by recording the intensity of the reported phosphenes evoked in the contralateral visual field at range of TMS intensities. Phosphene measurements revealed that MD produced a rapid and robust decrease in cortical excitability relative to a control condition without...

  12. "Adult Education Is about Human Being in All Its Aspects"

    Science.gov (United States)

    Stanistreet, Paul

    2011-01-01

    Derek Legge, who celebrated his 95th birthday at the end of last month, is one of the most dedicated and influential of the largely unsung heroes of the adult education movement in Britain. As modesty is one of the many qualities with which his friends and colleagues credit him, he is certain to shrink from the description, but there is little…

  13. Intra-articular angiolipoma of the knee: a case report

    Directory of Open Access Journals (Sweden)

    Nishimori Makoto

    2010-04-01

    Full Text Available Abstract We report a case of intra-articular angiolipoma of the knee. This case report describes our experience in excising an intra-articular angiolipoma of the knee joint. Complete resection under arthroscopy was performed in a 30-year-old man. Two years after the surgery, no evidence of recurrence was seen. Intra-articular angiolipomas should be considered in the differential diagnosis of intra-articular masses in adolescents with recurrent hemarthrosis without trauma.

  14. Geometry of the articular facets of the lateral atlanto-axial joints in the case of occipitalization.

    Science.gov (United States)

    Ryniewicz, A M; Skrzat, J; Ryniewicz, A; Ryniewicz, W; Walocha, J

    2010-08-01

    This study investigates if atlanto-occipital fusion affects the size and geometrical configuration of the articular facets of the atlanto-axial joint. Morphometric analysis was performed on the male adult skull, the occipital bone of which is assimilated with the first cervical vertebrae (the atlas). The perimeter, Feret's diameter, surface area, and circularity of the inferior articular fa-cets were measured. However, we did not observe significant bilateral differences in size of the inferior articular facets of the assimilated atlas compared to normal first cervical vertebrae. Geometrical conformation of the articular facets of the atlas and axis was assessed using a coordinate measuring machine (PMM - 12106, Leitz). The results obtained from this machine indicated that the inferior articular facets of the assimilated atlas presented asymmetrical orientation compared to the normal anatomy of the atlas. Hence, in the case of occipitalization, the gap between the articulating facets of the atlas and the axis was measured to be greater than in the normal atlanto-axial joint. Computer assisted tomography was applied to visualise the anatomical relationship between the inferior articular facets of the assimilated atlas and the corresponding facets located on the axis. In this case, radiographic examination revealed that the bilaterally articulating facets (inferior and superior) showed disproportion in their adjustment within the lateral atlanto-axial joints. Thus, we concluded that the fusion of the atlas with the occipital bone altered the geometry of the inferior articular facets of the atlas and influenced the orientation of the superior articular facets of the axis.

  15. Preparation of Articular Cartilage Specimens for Scanning Electron Microscopy.

    Science.gov (United States)

    Stupina, T A

    2016-08-01

    We developed and adapted a technology for preparation of articular cartilage specimens for scanning electron microscopy. The method includes prefixation processing, fixation, washing, and dehydration of articular cartilage specimens with subsequent treatment in camphene and air-drying. The technological result consists in prevention of deformation of the articular cartilage structures. The method is simpler and cheaper than the known technologies.

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

    NARCIS (Netherlands)

    Ramachandran, S.D.; Schirmer, K.; Munst, B.; Heinz, S.; Ghafoory, S.; Wolfl, S.; Simon-Keller, K.; Marx, A.; Oie, C.I.; Ebert, M.P.; Walles, H.; Braspenning, J.C.; Breitkopf-Heinlein, K.

    2015-01-01

    In this study we used differentiated adult human upcyte(R) cells for the in vitro generation of liver organoids. Upcyte(R) cells are genetically engineered cell strains derived from primary human cells by lenti-viral transduction of genes or gene combinations inducing transient proliferation capacit

  17. An Inventory of Skills and Attitudes Necessary for a Career in Human Services/Adult Care.

    Science.gov (United States)

    Broadbent, William

    This document is an inventory of skills identified as necessary by professionals in the human services field specializing in adult care. It is intended as a mechanism whereby educators can compare that which they teach against what the human services industry feels is relevant. Introductory material discusses the process of the occupational…

  18. Intra-Articular Lubricin Gene Therapy for Post-Traumatic Arthritis

    Science.gov (United States)

    2015-09-01

    develop a survival animal model of intra-articular fracture (IAF) in which all major pathophysiological attributes of corresponding human clinical...Y, Gandhi V, Prasad M, Yu W, Wang X, Zhu Q, et al. Distribution of small integrin-binding ligand, N-linked glycoproteins (SIBLING) in the condylar

  19. Intra-articular Implantation of Mesenchymal Stem Cells, Part 2

    Science.gov (United States)

    Kraeutler, Matthew J.; Mitchell, Justin J.; Chahla, Jorge; McCarty, Eric C.; Pascual-Garrido, Cecilia

    2017-01-01

    Knee osteoarthritis (OA) after partial or total meniscectomy is a prevalent issue that patients must face. Various methods of replacing meniscal tissue have been studied to avoid this progression, including meniscal allograft transplantation, meniscal scaffolds, and synthetic meniscus replacement. Studies have shown that meniscal scaffolds may improve symptoms but have not been shown to prevent progression of OA. Recently, mesenchymal stem cells (MSCs) have been proposed as a possible biological therapy for meniscal regeneration. Several animal studies and 1 human study have evaluated the effect of transplanting MSCs into the knee joint after partial meniscectomy. The purpose of this review was to assess the outcomes of intra-articular transplantation of MSCs on meniscal regeneration in animals and humans after partial meniscectomy. Limited results from animal studies suggest that there is some potential for intra-articular injection of MSCs for the regeneration of meniscal tissue. However, further studies are necessary to determine the quality of regenerated meniscal tissue through histological and biomechanical testing. PMID:28203596

  20. A century of trends in adult human height

    DEFF Research Database (Denmark)

    Damsgaard, Camilla T.; 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....

  1. Binge Drinking Effects on EEG in Young Adult Humans

    Directory of Open Access Journals (Sweden)

    Kelly E. Courtney

    2010-05-01

    Full Text Available Young adult (N = 96 university students who varied in their binge drinking history were assessed by electroencephalography (EEG recording during passive viewing. Groups consisted of male and female non-binge drinkers (>1 to 5/4 drinks/ounces in under two hours, low-binge drinkers (5/4–7/6 drinks/ounces in under two hours, and high-binge drinkers (≥ 10 drinks/ounces in under two hours, who had been drinking alcohol at their respective levels for an average of 3 years. The non- and low-binge drinkers exhibited less spectral power than the high-binge drinkers in the delta (0–4 Hz and fast-beta (20–35 Hz bands. Binge drinking appears to be associated with a specific pattern of brain electrical activity in young adults that may reflect the future development of alcoholism.

  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. Regeneration of Articular Cartilage in Lizard Knee from Resident Stem/Progenitor Cells.

    Science.gov (United States)

    Alibardi, Lorenzo

    2015-09-01

    The epiphysis of femur and tibia in the lizard Podarcis muralis can extensively regenerate after injury. The process involves the articular cartilage and metaphyseal (growth) plate after damage. The secondary ossification center present between the articular cartilage and the growth plate is replaced by cartilaginous epiphyses after about one month of regeneration at high temperature. The present study analyzes the origin of the chondrogenic cells from putative stem cells located in the growing centers of the epiphyses. The study is carried out using immunocytochemistry for the detection of 5BrdU-labeled long retaining cells and for the localization of telomerase, an enzyme that indicates stemness. The observations show that putative stem cells retaining 5BrdU and positive for telomerase are present in the superficial articular cartilage and metaphyseal growth plate located in the epiphyses. This observation suggests that these areas represent stem cell niches lasting for most of the lifetime of lizards. In healthy long bones of adult lizards, the addition of new chondrocytes from the stem cells population in the articular cartilage and the metaphyseal growth plate likely allows for slow, continuous longitudinal growth. When the knee is injured in the adult lizard, new populations of chondrocytes actively producing chondroitin sulfate proteoglycan are derived from these stem cells to allow for the formation of completely new cartilaginous epiphyses, possibly anticipating the re-formation of secondary centers in later stages. The study suggests that in this lizard species, the regenerative ability of the epiphyses is a pre-adaptation to the regeneration of the articular cartilage.

  4. Regeneration of Articular Cartilage in Lizard Knee from Resident Stem/Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Lorenzo Alibardi

    2015-09-01

    Full Text Available The epiphysis of femur and tibia in the lizard Podarcis muralis can extensively regenerate after injury. The process involves the articular cartilage and metaphyseal (growth plate after damage. The secondary ossification center present between the articular cartilage and the growth plate is replaced by cartilaginous epiphyses after about one month of regeneration at high temperature. The present study analyzes the origin of the chondrogenic cells from putative stem cells located in the growing centers of the epiphyses. The study is carried out using immunocytochemistry for the detection of 5BrdU-labeled long retaining cells and for the localization of telomerase, an enzyme that indicates stemness. The observations show that putative stem cells retaining 5BrdU and positive for telomerase are present in the superficial articular cartilage and metaphyseal growth plate located in the epiphyses. This observation suggests that these areas represent stem cell niches lasting for most of the lifetime of lizards. In healthy long bones of adult lizards, the addition of new chondrocytes from the stem cells population in the articular cartilage and the metaphyseal growth plate likely allows for slow, continuous longitudinal growth. When the knee is injured in the adult lizard, new populations of chondrocytes actively producing chondroitin sulfate proteoglycan are derived from these stem cells to allow for the formation of completely new cartilaginous epiphyses, possibly anticipating the re-formation of secondary centers in later stages. The study suggests that in this lizard species, the regenerative ability of the epiphyses is a pre-adaptation to the regeneration of the articular cartilage.

  5. Body weight independently affects articular cartilage catabolism.

    Science.gov (United States)

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

    2015-06-01

    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. Key pointsWalking for 30 minutes with adjustments in body weight (normal body weight, +40% and -40% body weight) significantly influences articular cartilage catabolism, measured via serum COMP concentration.Compared to baseline levels, walking with +40% body weight and normal body weight both elicited significant increases in

  6. CB1 cannabinoid receptor enrichment in the ependymal region of the adult human spinal cord

    OpenAIRE

    Beatriz Paniagua-Torija; Angel Arevalo-Martin; Isidro Ferrer; Eduardo Molina-Holgado; Daniel Garcia-Ovejero

    2015-01-01

    Cannabinoids are involved in the regulation of neural stem cell biology and their receptors are expressed in the neurogenic niches of adult rodents. In the spinal cord of rats and mice, neural stem cells can be found in the ependymal region, surrounding the central canal, but there is evidence that this region is largely different in adult humans: lacks a patent canal and presents perivascular pseudorosettes, typically found in low grade ependymomas. Using Laser Capture Microdissection, Taqma...

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

    Science.gov (United States)

    Liu, He; Song, Ni

    2016-01-01

    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. PMID:27375363

  8. A century of trends in adult human height

    OpenAIRE

    Bentham, J; Di Cesare, M; Stevens, G.A.; Zhou, B.; Bixby, H.; Cowan, M.; Fortunato, L.; Hajifathalian, K; Lu, Y.; Riley, L. M.; Kontis, V.; Paciorek, C. J.; Ezzati, M; Abdeen, Z. A. (Ziad A.); Hamid, Z. A.

    2016-01-01

    Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain 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, ...

  9. Rate and adaptation effects on the auditory evoked brainstem response in human newborns and adults.

    Science.gov (United States)

    Lasky, R E

    1997-09-01

    Auditory evoked brainstem response (ABR) latencies increased and amplitudes decreased with increasing stimulus repetition rate for human newborns and adults. The wave V latency increases were larger for newborns than adults. The wave V amplitude decreases were smaller for newborns than adults. These differences could not be explained by developmental differences in frequency responsivity. The transition from the unadapted to the fully adapted response was less rapid in newborns than adults at short (= 10 ms) inter stimulus intervals (ISIs). At longer ISIs (= 20 ms) there were no developmental differences in the transition to the fully adapted response. The newborn transition occurred in a two stage process. The rapid initial stage observed in adults and newborns was complete by about 40 ms. A second slower stage was observed only in newborns although it has been observed in adults in other studies (Weatherby and Hecox, 1982; Lightfoot, 1991; Lasky et al., 1996). These effects were replicated at different stimulus intensities. After the termination of stimulation the return to the wave V unadapted response took nearly 500 ms in newborns. Neither the newborn nor the adult data can be explained by forward masking of one click on the next click. These results indicate human developmental differences in adaptation to repetitive auditory stimulation at the level of the brainstem.

  10. A century of trends in adult human height.

    Science.gov (United States)

    2016-07-26

    Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain 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.

  11. Tenascin and aggrecan expression by articular chondrocytes is influenced by interleukin 1ß: a possible explanation for the changes in matrix synthesis during osteoarthritis

    OpenAIRE

    Pfander, D; HEINZ, N.; Rothe, P; Carl, H.; Swoboda, B

    2004-01-01

    Objective: To analyse the distribution patterns of tenascin and proteoglycans in normal and osteoarthritic cartilage, and to determine the effect of interleukin 1ß (IL1ß) on aggrecan and tenascin expression by human articular chondrocytes in vitro.

  12. 骨形态发生蛋白与碱性成纤维细胞生长因子联合修复软骨缺损的效果评价%Effects of recombinant human bone morphogenetic protein combined with basic fibroblast growth factor on the repair of articular cartilage defects

    Institute of Scientific and Technical Information of China (English)

    朱国华; 蔡建平; 郭翠玲; 廖家新; 刘勇; 罗洪涛; 许国华; 胡红涛

    2012-01-01

    背景:多种细胞生长因子在骨软骨代谢过程中的协同作用越来越受到重视,但目前复合细胞生长因子修复软骨缺损报道较少,且修复效果尚无定论.目的:探讨骨形态发生蛋白和碱性成纤维细胞生长因子联合应用修复关节软骨缺损的效果.方法:24 只日本大耳白兔建立骨软骨缺损模型后随机等分为4 组,对照组缺损处仅填塞明胶海绵,其他3 组在对照组基础上,缺损处分别注射骨形态发生蛋白和碱性成纤维细胞生长因子、骨形态发生蛋白、碱性成纤维细胞生长因子.结果与结论:大体观察显示联合应用2 种细胞因子后,软骨缺损面基本修复但稍不平整,单独使用其中1 种细胞因子缺损面未完全修复,对照组无明显修复.联合应用2 种细胞因子缺损部位软骨细胞数多于其他3 组(P < 0.05),且Ⅱ型胶原免疫组化染色深于其他组.提示联合应用骨形态发生蛋白和碱性成纤维细胞生长因子可以促进关节软骨损伤的修复,疗效优于单独应用骨形态发生蛋白或碱性成纤维细胞生长因子.%BACKGROUND: The synergy of various cell growth factors attracts more and more attention in the course of cartilage metabolism.However, there are few reports of repairing cartilage defects with combined cell growth factors, and the effect remains unknown atpresent.OBJECTIVE: To study the repairing effect of recombinant human bone morphogenetic protein (rhBMP) combined with basicfibroblast growth factor (bFGF) on articular cartilage defects.METHODS: After the model of articular cartilage defects was made, 24 Japan big-eared white rabbits were randomly divided intofour groupsforintervention: rhBMP combined with bFGF (group A), single rhBMP (group B), single bFGF (group C), the fourthgroup was without injection and just filled with gelatin sponge (group D).RESULTS AND CONCLUSION: In general observation, articular cartilage defects were basically repaired but slightly

  13. The human traffickers and exploitation of children and young adults.

    Directory of Open Access Journals (Sweden)

    Sara Scala

    2012-06-01

    Full Text Available The article focuses on the traffic of children, who are kidnapped, cheated and purchased by their families to be exploited in many ways. These victims have severe mental and physical traumas. Many of them, slaves of their exploiters, remain invisible and live their lifes without fundamental rights and without any kind of support or help. The traffic in human beings is a new kind of slavery, which acts in the dark, is criminal and involves different subjects of different ages, different nationalities and generations. The traffic in human beings is managed by transnational criminal organizations and is a disturbing and growing phenomena around the world.

  14. 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...

  15. The landscape of genomic imprinting across diverse adult human tissues

    Science.gov (United States)

    Baran, Yael; Subramaniam, Meena; Biton, Anne; Tukiainen, Taru; Tsang, Emily K.; Rivas, Manuel A.; Pirinen, Matti; Gutierrez-Arcelus, Maria; Smith, Kevin S.; Kukurba, Kim R.; Zhang, Rui; Eng, Celeste; Torgerson, Dara G.; Urbanek, Cydney; Li, Jin Billy; Rodriguez-Santana, Jose R.; Burchard, Esteban G.; Seibold, Max A.; MacArthur, Daniel G.; Montgomery, Stephen B.; Zaitlen, Noah A.; Lappalainen, Tuuli

    2015-01-01

    Genomic imprinting is an important regulatory mechanism that silences one of the parental copies of a gene. To systematically characterize this phenomenon, we analyze tissue specificity of imprinting from allelic expression data in 1582 primary tissue samples from 178 individuals from the Genotype-Tissue Expression (GTEx) project. We characterize imprinting in 42 genes, including both novel and previously identified genes. Tissue specificity of imprinting is widespread, and gender-specific effects are revealed in a small number of genes in muscle with stronger imprinting in males. IGF2 shows maternal expression in the brain instead of the canonical paternal expression elsewhere. Imprinting appears to have only a subtle impact on tissue-specific expression levels, with genes lacking a systematic expression difference between tissues with imprinted and biallelic expression. In summary, our systematic characterization of imprinting in adult tissues highlights variation in imprinting between genes, individuals, and tissues. PMID:25953952

  16. 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 melanocyte cultures could be reproduced on human skin.

  17. 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

    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...... to control metabolic diseases by modifying the gut microbiota....... = 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...

  18. 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. 

  19. The minor collagens in articular cartilage

    DEFF Research Database (Denmark)

    Luo, Yunyun

    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...

  20. The human traffickers and exploitation of children and young adults.

    OpenAIRE

    2012-01-01

    The article focuses on the traffic of children, who are kidnapped, cheated and purchased by their families to be exploited in many ways. These victims have severe mental and physical traumas. Many of them, slaves of their exploiters, remain invisible and live their lifes without fundamental rights and without any kind of support or help. The traffic in human beings is a new kind of slavery, which acts in the dark, is criminal and involves different subjects of different ages, different nation...

  1. Adult human neural stem cell therapeutics: Currentdevelopmental status and prospect

    Institute of Scientific and Technical Information of China (English)

    Hyun Nam; Kee-Hang Lee; Do-Hyun Nam; Kyeung Min Joo

    2015-01-01

    Over the past two decades, regenerative therapies usingstem cell technologies have been developed for variousneurological diseases. Although stem cell therapy is anattractive option to reverse neural tissue damage and torecover neurological deficits, it is still under developmentso as not to show significant treatment effects in clinicalsettings. In this review, we discuss the scientific andclinical basics of adult neural stem cells (aNSCs), andtheir current developmental status as cell therapeuticsfor neurological disease. Compared with other typesof stem cells, aNSCs have clinical advantages, suchas limited proliferation, inborn differentiation potentialinto functional neural cells, and no ethical issues. Inspite of the merits of aNSCs, difficulties in the isolationfrom the normal brain, and in the in vitro expansion,have blocked preclinical and clinical study using aNSCs.However, several groups have recently developed noveltechniques to isolate and expand aNSCs from normaladult brains, and showed successful applications ofaNSCs to neurological diseases. With new technologiesfor aNSCs and their clinical strengths, previous hurdlesin stem cell therapies for neurological diseases could beovercome, to realize clinically efficacious regenerativestem cell therapeutics.

  2. 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.

  3. Articular cartilage repair and the evolving role of regenerative medicine

    Directory of Open Access Journals (Sweden)

    Pieter K Bos

    2010-10-01

    Full Text Available Pieter K Bos1, Marloes L van Melle1, Gerjo JVM van Osch1,21Department of Orthopaedic Surgery, Erasmus MC, Rotterdam, the Netherlands; 2Department of Otorhinolaryngology, Erasmus MC, Rotterdam, the NetherlandsAbstract: Among the growing applications of regenerative medicine, clinical articular cartilage repair has now been used for 2 decades and forms a successful example of translational medicine. Cartilage is characterized by a limited intrinsic repair capacity following injury. Articular cartilage defects cause symptoms, are not spontaneously repaired, and are generally believed to result in early osteoarthritis. Marrow stimulation techniques, osteochondral transplantation, and cell-based therapies, such as autologous chondrocyte implantation (ACI and use of mesenchymal stem cells (MSCs, are used for tissue regeneration, symptom relief, and prevention of further joint degeneration. The exact incidence of cartilage defects and the natural outcome of joints with these lesions are unclear. Currently available cartilage repair techniques are designed for defect treatment in otherwise healthy joints and limbs, mostly in young adults. The natural history studies presented in this review estimated that the prevalence of cartilage lesions in this patient group ranges from 5% to 11%. The background and results from currently available randomized clinical trials of the three mostly used cartilage repair techniques are outlined in this review. Osteochondral transplantation, marrow stimulation, and ACI show improvement of symptoms with an advantage for cell-based techniques, but only a suggestion that risk for joint degeneration can be reduced. MSCs, characterized by their good proliferative capacity and the potential to differentiate into different mesenchymal lineages, form an attractive alternative cell source for cartilage regeneration. Moreover, MSCs provide a regenerative microenvironment by the secretion of bioactive factors. This trophic activity

  4. Concept Maps: Practice Applications in Adult Education and Human Resource Development

    Science.gov (United States)

    Daley, Barbara J.

    2010-01-01

    Concept maps can be used as both a cognitive and constructivist learning strategy in teaching and learning in adult education and human resource development. The maps can be used to understand course readings, analyze case studies, develop reflective thinking and enhance research skills. The creation of concept maps can also be supported by the…

  5. 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…

  6. 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).…

  7. 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…

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

    DEFF Research Database (Denmark)

    Swales, Nathalie; Martens, Geert A; Bonné, Stefan

    2012-01-01

    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....

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

    NARCIS (Netherlands)

    ZIJLSTRA, WG; MEEUWSENVANDERROEST, WP

    1991-01-01

    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

  10. Treatment of Human-Caused Trauma: Attrition in the Adult Outcomes Research

    Science.gov (United States)

    Matthieu, Monica; Ivanoff, Andre

    2006-01-01

    Attrition or dropout is the failure of a participant to complete, comply, or the prematurely discontinuation or discharge from treatment, resulting in lost data and affecting outcomes. This review of 10 years of adult posttraumatic stress disorder (PTSD) treatment outcome literature specific to Criterion A events of human origin examines how…

  11. 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…

  12. Emotions and Human Concern: Adult Education and the Philosophical Thought of Martha Nussbaum

    Science.gov (United States)

    Plumb, Donovan

    2014-01-01

    This article argues that philosopher Martha Nussbaum's reflections on the role of the emotions in human flourishing can contribute in important ways to our understanding of the emotions in adult education contexts. The article summarises Nussbaum's exploration of the contributions of classical philosophers like Socrates, Aristotle, and…

  13. Mature astrocytes in the adult human neocortex express the early neuronal marker doublecortin.

    NARCIS (Netherlands)

    Verwer, R.W.H.; Sluiter, A.A.; Balesar, R.A.; Baayen, J.C.; Noske, D.P.; Dirven, C.M.; Wouda, J.; van Dam, A.M.; Lucassen, P.J.; Swaab, D.F.

    2007-01-01

    Doublecortin (DCX) is a microtubule-associated protein expressed by migrating neuroblasts and is considered to be a reliable marker of neurogenesis. DCX has been used to study the relation between neurogenesis in adult human brain and neurological and neurodegenerative disease processes in the searc

  14. Increased presence of capillaries next to remodeling sites in adult human cancellous bone

    DEFF Research Database (Denmark)

    Kristensen, Helene Bjoerg; Andersen, Thomas Levin; Marcussen, Niels;

    2013-01-01

    by pericytes. Furthermore, the BRC canopy cells were found to express SMA. These ordered distributions support the existence of an osteogenic-vascular interface in adult human cancellous bone. The organization of this interface fits the current knowledge on the mode of action of vasculature on osteogenesis...

  15. Canonical Genetic Signatures of the Adult Human Brain

    Science.gov (United States)

    Hawrylycz, Michael; Miller, Jeremy A.; Menon, Vilas; Feng, David; Dolbeare, Tim; Guillozet-Bongaarts, Angela L.; Jegga, Anil G.; Aronow, Bruce J.; Lee, Chang-Kyu; Bernard, Amy; Glasser, Matthew F.; Dierker, Donna L.; Menche, Jörge; Szafer, Aaron; Collman, Forrest; Grange, Pascal; Berman, Kenneth A.; Mihalas, Stefan; Yao, Zizhen; Stewart, Lance; Barabási, Albert-László; Schulkin, Jay; Phillips, John; Ng, Lydia; Dang, Chinh; Haynor, David R.; Jones, Allan; Van Essen, David C.; Koch, Christof; Lein, Ed

    2015-01-01

    The structure and function of the human brain are highly stereotyped, implying a conserved molecular program responsible for its development, cellular structure, and function. We applied a correlation-based metric of “differential stability” (DS) to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing meso-scale genetic organization. The highest DS genes are highly biologically relevant, with enrichment for brain-related biological annotations, disease associations, drug targets, and literature citations. Using high DS genes we identified 32 anatomically diverse and reproducible gene expression signatures, which represent distinct cell types, intracellular components, and/or associations with neurodevelopmental and neurodegenerative disorders. Genes in neuron-associated compared to non-neuronal networks showed higher preservation between human and mouse; however, many diversely-patterned genes displayed dramatic shifts in regulation between species. Finally, highly consistent transcriptional architecture in neocortex is correlated with resting state functional connectivity, suggesting a link between conserved gene expression and functionally relevant circuitry. PMID:26571460

  16. 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... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted...

  17. 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... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults conducted...

  18. 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…

  19. CD133+ adult human retinal cells remain undifferentiated in Leukaemia Inhibitory Factor (LIF

    Directory of Open Access Journals (Sweden)

    Mayer Eric J

    2009-02-01

    Full Text Available Abstract Background CD133 is a cell surface marker of haematopoietic stem and progenitor cells. Leukaemia inhibitory factor (LIF, sustains proliferation and not differentiation of embryonic stem cells. We used CD133 to purify adult human retinal cells and aimed to determine what effect LIF had on these cultures and whether they still had the ability to generate neurospheres. Methods Retinal cell suspensions were derived from adult human post-mortem tissue with ethical approval. With magnetic automated cell sorting (MACS CD133+ retinal cells were enriched from post mortem adult human retina. CD133+ retinal cell phenotype was analysed by flow cytometry and cultured cells were observed for proliferative capacity, neuropshere generation and differentiation with or without LIF supplementation. Results We demonstrated purification (to 95% of CD133+ cells from adult human postmortem retina. Proliferating cells were identified through BrdU incorporation and expression of the proliferation markers Ki67 and Cyclin D1. CD133+ retinal cells differentiated whilst forming neurospheres containing appropriate lineage markers including glia, neurons and photoreceptors. LIF maintained CD133+ retinal cells in a proliferative and relatively undifferentiated state (Ki67, Cyclin D1 expression without significant neurosphere generation. Differentiation whilst forming neurospheres was re-established on LIF withdrawal. Conclusion These data support the evidence that CD133 expression characterises a population of cells within the resident adult human retina which have progenitor cell properties and that their turnover and differentiation is influenced by LIF. This may explain differences in retinal responses observed following disease or injury.

  20. [Indirect articular lymphography using Tc 99m-labeled Dextran in animals].

    Science.gov (United States)

    Albuquerque, M; Pedroso de Lima, J; Cardoso, A; Mendes, F; Pires, J; Canha, N; Branco, R

    1990-01-01

    Looking for a standardization of the articular lymphoscintigraphy, an experimental research was conducted on 14 dogs injected in the ankle, with 2.5 mCi of 99m Tc-labeled dextran (P.M. = 70,000). Good scintigraphic images of the lymphatic system have been obtained. After having collected blood samples during the experimentation as well as aliquots of organs and of tissues, after the necropsy of the animal, it was verified that the 99m Tc-labeled dextran was useful for quantitative studies of the articular lymphatic drainage. The activities attained, in the drainage lymph nodes of injected articulation, are 152 times superior to those obtained in the kidney and one gramma of popliteal ganglion was 8929 times more active than one gramma of blood. The dextran 70,000, widely used in our clinical routine, can be injected to the human being, without any risk, and it may be the tracer which permits studies of the articular lymphatic drainage and the usage of the lymphoscintigraphy, already in expansion in many other Medicine branches, in the articular studies, nowadays.

  1. Effects of low-intensity pulsed ultrasound in repairing injured articular cartilage

    Institute of Scientific and Technical Information of China (English)

    JIA Xiao-lin; CHEN Wen-zhi; ZHOU Kun; WANG Zhi-biao

    2005-01-01

    Objective: To investigate the effects of low-intensity pulsed ultrasound in repairing injured articular cartilage. Methods: Ten adult New Zealand rabbits with bilateral full-thickness osteochondral defects on the cartilage surface of intercondylar fossas were used in this study. The wounds in the left knees were treated with low-intensity pulsed ultrasound as the experimental group. The right knees received no treatment as the control group. All the animals were killed at 8 weeks after injury and the tissues in the wounds were collected for gross appearance grading, histological grading and proteoglycan quantity. Results: The scores of the gross appearance grades, histological grades and the optical density of toluidine blue of the tissues in the experimental group were significantly higher than those of the controls at 8 weeks after injury (P<0.05). Conclusions: Low-intensity pulsed ultrasound can accelerate the repair of injured articular cartilage.

  2. Neural-Competent Cells of Adult Human Dermis Belong to the Schwann Lineage

    Science.gov (United States)

    Etxaniz, Usue; Pérez-San Vicente, Adrián; Gago-López, Nuria; García-Dominguez, Mario; Iribar, Haizea; Aduriz, Ariane; Pérez-López, Virginia; Burgoa, Izaskun; Irizar, Haritz; Muñoz-Culla, Maider; Vallejo-Illarramendi, Ainara; Leis, Olatz; Matheu, Ander; Martín, Angel G.; Otaegui, David; López-Mato, María Paz; Gutiérrez-Rivera, Araika; MacLellan, Robb; Izeta, Ander

    2014-01-01

    Summary Resident neural precursor cells (NPCs) have been reported for a number of adult tissues. Understanding their physiological function or, alternatively, their activation after tissue damage or in vitro manipulation remains an unsolved issue. Here, we investigated the source of human dermal NPCs in adult tissue. By following an unbiased, comprehensive approach employing cell-surface marker screening, cell separation, transcriptomic characterization, and in vivo fate analyses, we found that p75NTR+ precursors of human foreskin can be ascribed to the Schwann (CD56+) and perivascular (CD56−) cell lineages. Moreover, neural differentiation potential was restricted to the p75NTR+CD56+ Schwann cells and mediated by SOX2 expression levels. Double-positive NPCs were similarly obtained from human cardiospheres, indicating that this phenomenon might be widespread. PMID:25418723

  3. Neural-Competent Cells of Adult Human Dermis Belong to the Schwann Lineage

    Directory of Open Access Journals (Sweden)

    Usue Etxaniz

    2014-11-01

    Full Text Available Resident neural precursor cells (NPCs have been reported for a number of adult tissues. Understanding their physiological function or, alternatively, their activation after tissue damage or in vitro manipulation remains an unsolved issue. Here, we investigated the source of human dermal NPCs in adult tissue. By following an unbiased, comprehensive approach employing cell-surface marker screening, cell separation, transcriptomic characterization, and in vivo fate analyses, we found that p75NTR+ precursors of human foreskin can be ascribed to the Schwann (CD56+ and perivascular (CD56− cell lineages. Moreover, neural differentiation potential was restricted to the p75NTR+CD56+ Schwann cells and mediated by SOX2 expression levels. Double-positive NPCs were similarly obtained from human cardiospheres, indicating that this phenomenon might be widespread.

  4. Neural-competent cells of adult human dermis belong to the Schwann lineage.

    Science.gov (United States)

    Etxaniz, Usue; Pérez-San Vicente, Adrián; Gago-López, Nuria; García-Dominguez, Mario; Iribar, Haizea; Aduriz, Ariane; Pérez-López, Virginia; Burgoa, Izaskun; Irizar, Haritz; Muñoz-Culla, Maider; Vallejo-Illarramendi, Ainara; Leis, Olatz; Matheu, Ander; Martín, Angel G; Otaegui, David; López-Mato, María Paz; Gutiérrez-Rivera, Araika; MacLellan, Robb; Izeta, Ander

    2014-11-11

    Resident neural precursor cells (NPCs) have been reported for a number of adult tissues. Understanding their physiological function or, alternatively, their activation after tissue damage or in vitro manipulation remains an unsolved issue. Here, we investigated the source of human dermal NPCs in adult tissue. By following an unbiased, comprehensive approach employing cell-surface marker screening, cell separation, transcriptomic characterization, and in vivo fate analyses, we found that p75NTR(+) precursors of human foreskin can be ascribed to the Schwann (CD56(+)) and perivascular (CD56(-)) cell lineages. Moreover, neural differentiation potential was restricted to the p75NTR(+)CD56(+) Schwann cells and mediated by SOX2 expression levels. Double-positive NPCs were similarly obtained from human cardiospheres, indicating that this phenomenon might be widespread.

  5. 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....

  6. Intra-Articular Osteoid Osteoma Mimicking Juvenile Arthritis

    Directory of Open Access Journals (Sweden)

    Sidi Yaya Traore

    2014-01-01

    Full Text Available In case of intra-articular osteoid osteoma, misdiagnosis as juvenile arthritis may occur, delaying adequate treatment. We report cases of intra-articular osteoid osteomas in children that were misdiagnosed and initially inappropriately treated with intra-articular corticoid injection. Diagnosis of osteoid osteoma was finally given by CT-scan and appropriate treatment by radiofrequency ablation or surgical ablation was performed. Clinicians and radiologists should be aware of the potentially confusing clinical and imaging findings associated with intra-articular osteoid osteoma.

  7. 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.

  8. Ultrastructural Evidence of Exosome Secretion by Progenitor Cells in Adult Mouse Myocardium and Adult Human Cardiospheres

    Directory of Open Access Journals (Sweden)

    Lucio Barile

    2012-01-01

    Full Text Available The demonstration of beneficial effects of cell therapy despite the persistence of only few transplanted cells in vivo suggests secreted factors may be the active component of this treatment. This so-called paracrine hypothesis is supported by observations that culture media conditioned by progenitor cells contain growth factors that mediate proangiogenic and cytoprotective effects. Cardiac progenitor cells in semi-suspension culture form spherical clusters (cardiospheres that deliver paracrine signals to neighboring cells. A key component of paracrine secretion is exosomes, membrane vesicles that are stored intracellularly in endosomal compartments and are secreted when these structures fuse with the cell plasma membrane. Exosomes have been identified as the active component of proangiogenic effects of bone marrow CD34+ stem cells in mice and the regenerative effects of embryonic mesenchymal stem cells in infarcted hearts in pigs and mice. Here, we provide electron microscopic evidence of exosome secretion by progenitor cells in mouse myocardium and human cardiospheres. Exosomes are emerging as an attractive vector of paracrine signals delivered by progenitor cells. They can be stored as an “off-the-shelf” product. As such, exosomes have the potential for circumventing many of the limitations of viable cells for therapeutic applications in regenerative medicine.

  9. Binding of furosemide to albumin isolated from human fetal and adult serum.

    Science.gov (United States)

    Viani, A; Cappiello, M; Silvestri, D; Pacifici, G M

    1991-01-01

    Albumin was isolated from pooled fetal serum from 58 placentas obtained at normal delivery at term and from pooled adult plasma from 8 individuals. Albumin isolation was carried out by means of PEG precipitation followed by ion-exchange chromatography on DEAE-Sephadex A 50 and then on SP-Sephadex C 50. The electrophoresis on SDS-polyacrylamide gels showed only one spot that comigrated with commercial human albumin. Binding to albumin was measured by equilibrium dialysis of an aliquot of albumin solution (0.7 ml) against the same volume of 0.13 M sodium orthophosphate buffer (pH 7.4). At a total concentration of 2 micrograms/ml (therapeutic range), the unbound fraction of furosemide was 2.71% (fetal albumin) and 2.51% (adult albumin). Two classes of binding sites for furosemide were observed in fetal and adult albumin. The number of binding sites (moles of furosemide per mole of albumin) was 1.22 (fetal albumin) and 1.58 (adult albumin) for the high-affinity site and 2.97 (fetal albumin) and 3.25 (adult albumin) for the low-affinity site. The association constants (M-1) were 3.1 X 10(4) (fetal albumin) and 2.6 X 10(4) (adult albumin) for the high-affinity set of sites and 0.83 X 10(4) (fetal albumin) and 1.0 X 10(4) (adult albumin) low-affinity site. The displacement of furosemide from albumin was studied with therapeutic concentrations of several drugs. Valproic acid, salicylic acid, azapropazone and tolbutamide had the highest displacing effects which were significantly higher with fetal than with adult albumin.

  10. CB1 cannabinoid receptor enrichment in the ependymal region of the adult human spinal cord.

    Science.gov (United States)

    Paniagua-Torija, Beatriz; Arevalo-Martin, Angel; Ferrer, Isidro; Molina-Holgado, Eduardo; Garcia-Ovejero, Daniel

    2015-12-04

    Cannabinoids are involved in the regulation of neural stem cell biology and their receptors are expressed in the neurogenic niches of adult rodents. In the spinal cord of rats and mice, neural stem cells can be found in the ependymal region, surrounding the central canal, but there is evidence that this region is largely different in adult humans: lacks a patent canal and presents perivascular pseudorosettes, typically found in low grade ependymomas. Using Laser Capture Microdissection, Taqman gene expression assays and immunohistochemistry, we have studied the expression of endocannabinoid system components (receptors and enzymes) at the human spinal cord ependymal region. We observe that ependymal region is enriched in CB1 cannabinoid receptor, due to high CB1 expression in GFAP+ astrocytic domains. However, in human spinal cord levels that retain central canal patency we found ependymal cells with high CB1 expression, equivalent to the CB1(HIGH) cell subpopulation described in rodents. Our results support the existence of ependymal CB1(HIGH) cells across species, and may encourage further studies on this subpopulation, although only in cases when central canal is patent. In the adult human ependyma, which usually shows central canal absence, CB1 may play a different role by modulating astrocyte functions.

  11. The adult macaque spinal cord central canal zone contains proliferative cells and closely resembles the human.

    Science.gov (United States)

    Alfaro-Cervello, Clara; Cebrian-Silla, Arantxa; Soriano-Navarro, Mario; Garcia-Tarraga, Patricia; Matías-Guiu, Jorge; Gomez-Pinedo, Ulises; Molina Aguilar, Pilar; Alvarez-Buylla, Arturo; Luquin, Maria-Rosario; Garcia-Verdugo, Jose Manuel

    2014-06-01

    The persistence of proliferative cells, which could correspond to progenitor populations or potential cells of origin for tumors, has been extensively studied in the adult mammalian forebrain, including human and nonhuman primates. Proliferating cells have been found along the entire ventricular system, including around the central canal, of rodents, but little is known about the primate spinal cord. Here we describe the central canal cellular composition of the Old World primate Macaca fascicularis via scanning and transmission electron microscopy and immunohistochemistry and identify central canal proliferating cells with Ki67 and newly generated cells with bromodeoxyuridine incorporation 3 months after the injection. The central canal is composed of uniciliated, biciliated, and multiciliated ependymal cells, astrocytes, and neurons. Multiciliated ependymal cells show morphological characteristics similar to multiciliated ependymal cells from the lateral ventricles, and uniciliated and biciliated ependymal cells display cilia with large, star-shaped basal bodies, similar to the Ecc cells described for the rodent central canal. Here we show that ependymal cells with one or two cilia, but not multiciliated ependymal cells, proliferate and give rise to new ependymal cells that presumably remain in the macaque central canal. We found that the infant and adult human spinal cord contains ependymal cell types that resemble those present in the macaque. Interestingly, a wide hypocellular layer formed by bundles of intermediate filaments surrounded the central canal both in the monkey and in the human, being more prominent in the stenosed adult human central canal.

  12. Human and monkey striatal interneurons are derived from the medial ganglionic eminence but not from the adult subventricular zone.

    Science.gov (United States)

    Wang, Congmin; You, Yan; Qi, Dashi; Zhou, Xing; Wang, Lei; Wei, Song; Zhang, Zhuangzhi; Huang, Weixi; Liu, Zhidong; Liu, Fang; Ma, Lan; Yang, Zhengang

    2014-08-13

    In adult rodent and monkey brains, newly born neurons in the subventricular zone (SVZ) in the wall of the lateral ventricle migrate into the olfactory bulb (OB) via the rostral migratory stream (RMS). A recent study reported that interneurons are constantly generating in the adult human striatum from the SVZ. In contrast, by taking advantage of the continuous expression of Sp8 from the neuroblast stage through differentiation into mature interneurons, we found that the adult human SVZ does not generate new interneurons for the striatum. In the adult human SVZ and RMS, very few neuroblasts were observed, and most of them expressed the transcription factor Sp8. Neuroblasts in the adult rhesus monkey SVZ-RMS-OB pathway also expressed Sp8. In addition, we observed that Sp8 was expressed by most adult human and monkey OB interneurons. However, very few Sp8+ cells were in the adult human striatum. This suggests that neuroblasts in the adult human SVZ and RMS are likely destined for the OB, but not for the striatum. BrdU-labeling results also revealed few if any newly born neurons in the adult rhesus monkey striatum. Finally, on the basis of transcription factor expression, we provide strong evidence that the vast majority of interneurons in the human and monkey striatum are generated from the medial ganglionic eminence during embryonic developmental stages, as they are in rodents. We conclude that, although a small number of neuroblasts exist in the adult human SVZ, they do not migrate into the striatum and become mature striatal interneurons.

  13. Expression of hypoxia-inducible factor 2 alpha and vascular endothelial growth factor in chondrocytes of articular cartilages in human osteoarthritis%骨关节炎关节软骨细胞中低氧诱导因子2α及血管内皮生长因子的表达

    Institute of Scientific and Technical Information of China (English)

    刘丰; 彭昊; 周建林; 方洪松; 邓爽; 杨骁; 翁金清

    2015-01-01

    BACKGROUND:Studies have found that vascular endothelial growth factor and hypoxia inducible factor are involved in the development process of osteoarthritis, but their correlation is rarely reported. OBJECTIVE:To observe the expression and correlation of hypoxia inducible factor-2α and vascular endothelial growth factor in chondrocytes of articular cartilages in human osteoarthritis. METHODS: Articular cartilage specimens were colected from 50 patients with knee osteoarthritis undergoing total knee joint replacement. According to the joint Kelgren-Lawrance (K-L) X-ray grouping classification standard, there were 18 cases of K-LIII level and 32 cases of K-LIV level. Besides, articular cartilage specimens from 10 patients undergoing amputation for legs tumor or traffic accident served as control group. Hematoxylin-eosin staining, Safranin O-Fast Green staining and Mankin scoring were performed to observe and evaluate the histological characteristics of articular cartilages of each group, immunohistochemical staining was conducted to detect the expression of hypoxia inducible factor-2α and vascular endothelial growth factor in chondrocytes of articular cartilages, and their correlations were analyzed. RESULTS AND CONCLUSION:The Mankin score of K-LIV group was significantly higher than those of K-LIII group and control group. Immunohistochemical staining revealed that the number of chondrocytes with positive expression of hypoxia inducible factor-2α or vascular endothelial growth factor in K-LIV group was significantly higher than that in K-LIII group and control group (P < 0.05). The expression of hypoxia inducible factor-2α and vascular endothelial growth factor increased in chondrocytes of articular cartilages of osteoarthritis patients, and to up-regulate the expression of vascular endothelial growth factor may be the regulatory mechanism of hypoxia inducible factor-2αinthe pathogenesis of osteoarthritis.%背景:已有研究发现血管内皮生长因子

  14. PET imaging of neurogenic activity in the adult brain: Toward in vivo imaging of human neurogenesis.

    Science.gov (United States)

    Tamura, Yasuhisa; Kataoka, Yosky

    2017-01-01

    Neural stem cells are present in 2 neurogenic regions, the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus (DG), and continue to generate new neurons throughout life. Adult hippocampal neurogenesis is linked to a variety of psychiatric disorders such as depression and anxiety, and to the therapeutic effects of antidepressants, as well as learning and memory. In vivo imaging for hippocampal neurogenic activity may be used to diagnose psychiatric disorders and evaluate the therapeutic efficacy of antidepressants. However, these imaging techniques remain to be established until now. Recently, we established a quantitative positron emission tomography (PET) imaging technique for neurogenic activity in the adult brain with 3'-deoxy-3'-[(18)F]fluoro-L-thymidine ([(18)F]FLT) and probenecid, a drug transporter inhibitor in blood-brain barrier. Moreover, we showed that this PET imaging technique can monitor alterations in neurogenic activity in the hippocampus of adult rats with depression and following treatment with an antidepressant. This PET imaging method may assist in diagnosing depression and in monitoring the therapeutic efficacy of antidepressants. In this commentary, we discuss the possibility of in vivo PET imaging for neurogenic activity in adult non-human primates and humans.

  15. Identification and characterization of neuroblasts in the subventricular zone and rostral migratory stream of the adult human brain

    Institute of Scientific and Technical Information of China (English)

    Congmin Wang; Qiangqiang Zhang; Yue Zhang; Rui Chen; Hongjun Song; Zhengang Yang; Fang Liu; Ying-Ying Liu; Cai-Hong Zhao; Yan You; Lei Wang; Jingxiao Zhang; Bin Wei; Tong Ma

    2011-01-01

    It is of great interest to identify new neurons in the adult human brain,but the persistence of neurogenesis in the subventricular zone (SVZ) and the existence of the rostral migratory stream (RMS)-like pathway in the adult human forebrain remain highly controversial.In the present study,we have described the general configuration of the RMS in adult monkey,fetal human and adult human brains.We provide evidence that neuroblasts exist continuously in the anterior ventral SVZ and RMS of the adult human brain.The neuroblasts appear singly or in pairs without forming chains; they exhibit migratory morphologies and co-express the immature neuronal markers doublecortin,polysialylated neural cell adhesion molecule and βI-tubulin.Few of these neuroblasts appear to be actively proliferating in the anterior ventral SVZ but none in the RMS,indicating that neuroblasts distributed along the RMS are most likely derived from the ventral SVZ.Interestingly,no neuroblasts are found in the adult human olfactory bulb.Taken together,our data suggest that the SVZ maintains the ability to produce neuroblasts in the adult human brain.

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

    OpenAIRE

    Biskup, Christian; Dunnen, Steven den; Kerkhoffs, Gino M. M. J.; Kraaij, Gert; Tuijthof, Gabrielle 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 study investigates whether drilling bony tissue with pure waterjets is feasible. Water pressures between 20 and 120 MPa with an orifice of 0.6 mm were used to create waterjets to drill blind boring...

  17. 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

  18. Normalizing the environment recapitulates adult human immune traits in laboratory mice.

    Science.gov (United States)

    Beura, Lalit K; Hamilton, Sara E; Bi, Kevin; Schenkel, Jason M; Odumade, Oludare A; Casey, Kerry A; Thompson, Emily A; Fraser, Kathryn A; Rosato, Pamela C; Filali-Mouhim, Ali; Sekaly, Rafick P; Jenkins, Marc K; Vezys, Vaiva; Haining, W Nicholas; Jameson, Stephen C; Masopust, David

    2016-04-28

    Our current understanding of immunology was largely defined in laboratory mice, partly because they are inbred and genetically homogeneous, can be genetically manipulated, allow kinetic tissue analyses to be carried out from the onset of disease, and permit the use of tractable disease models. Comparably reductionist experiments are neither technically nor ethically possible in humans. However, there is growing concern that laboratory mice do not reflect relevant aspects of the human immune system, which may account for failures to translate disease treatments from bench to bedside. Laboratory mice live in abnormally hygienic specific pathogen free (SPF) barrier facilities. Here we show that standard laboratory mouse husbandry has profound effects on the immune system and that environmental changes produce mice with immune systems closer to those of adult humans. Laboratory mice--like newborn, but not adult, humans--lack effector-differentiated and mucosally distributed memory T cells. These cell populations were present in free-living barn populations of feral mice and pet store mice with diverse microbial experience, and were induced in laboratory mice after co-housing with pet store mice, suggesting that the environment is involved in the induction of these cells. Altering the living conditions of mice profoundly affected the cellular composition of the innate and adaptive immune systems, resulted in global changes in blood cell gene expression to patterns that more closely reflected the immune signatures of adult humans rather than neonates, altered resistance to infection, and influenced T-cell differentiation in response to a de novo viral infection. These data highlight the effects of environment on the basal immune state and response to infection and suggest that restoring physiological microbial exposure in laboratory mice could provide a relevant tool for modelling immunological events in free-living organisms, including humans.

  19. [Extra-articular manifestations of seronegative spondylarthritis].

    Science.gov (United States)

    Cammelli, Daniele

    2006-05-01

    Seronegative spondylarthritis are frequently characterised by extra-articular manifestations. They are frequently in recurrent uveitis. Between the cutaneous manifestations should be mentioned erythema nodosum, typical of inflammatory bowel diseases, and keratoderma blenorrhagicum, in the Reiter's syndrome. Cardiac complications in ankylosing spondylitis (AS) include aortic valvular regurgitation and arrhythmia and, more rarely, mitral valvulopathy, cardiomyopathy and pericarditis. Pulmonary involvement in AS includes ventilatory restrictive syndrome and fibro-bullous disease of the apex. Vertebral osteoporosis is a very important extra-articular manifestation because of the possibility of spontaneous fractures of the vertebrae. Central neurological manifestations include medullary compression from cervical sub-luxation while the most important peripheral involvements are lumbar stenosis and the cauda equina syndrome. Type AA amyloidosis is a rare late complication of the AS, possible cause of death especially in patients with aggressive disease. Kidney complications can be observed as consequences of prolonged anti-inflammatory therapy, but the most frequent renal complications are amyloidosis and mesangial IgA segmental and focal glomerulonephritis.

  20. Toward patient-specific articular contact mechanics.

    Science.gov (United States)

    Ateshian, Gerard A; Henak, Corinne R; Weiss, Jeffrey A

    2015-03-18

    The mechanics of contacting cartilage layers is fundamentally important to understanding the development, homeostasis and pathology of diarthrodial joints. Because of the highly nonlinear nature of both the materials and the contact problem itself, numerical methods such as the finite element method are typically incorporated to obtain solutions. Over the course of five decades, we have moved from an initial qualitative understanding of articular cartilage material behavior to the ability to perform complex, three-dimensional contact analysis, including multiphasic material representations. This history includes the development of analytical and computational contact analysis methods that now provide the ability to perform highly nonlinear analyses. Numerical implementations of contact analysis based on the finite element method are rapidly advancing and will soon enable patient-specific analysis of joint contact mechanics using models based on medical image data. In addition to contact stress on the articular surfaces, these techniques can predict variations in strain and strain through the cartilage layers, providing the basis to predict damage and failure. This opens up exciting areas for future research and application to patient-specific diagnosis and treatment planning applied to a variety of pathologies that affect joint function and cartilage homeostasis.

  1. Rapid Increase in Neural Conduction Time in the Adult Human Auditory Brainstem Following Sudden Unilateral Deafness.

    Science.gov (United States)

    Maslin, M R D; Lloyd, S K; Rutherford, S; Freeman, S; King, A; Moore, D R; Munro, K J

    2015-10-01

    Individuals with sudden unilateral deafness offer a unique opportunity to study plasticity of the binaural auditory system in adult humans. Stimulation of the intact ear results in increased activity in the auditory cortex. However, there are no reports of changes at sub-cortical levels in humans. Therefore, the aim of the present study was to investigate changes in sub-cortical activity immediately before and after the onset of surgically induced unilateral deafness in adult humans. Click-evoked auditory brainstem responses (ABRs) to stimulation of the healthy ear were recorded from ten adults during the course of translabyrinthine surgery for the removal of a unilateral acoustic neuroma. This surgical technique always results in abrupt deafferentation of the affected ear. The results revealed a rapid (within minutes) reduction in latency of wave V (mean pre = 6.55 ms; mean post = 6.15 ms; p < 0.001). A latency reduction was also observed for wave III (mean pre = 4.40 ms; mean post = 4.13 ms; p < 0.001). These reductions in response latency are consistent with functional changes including disinhibition or/and more rapid intra-cellular signalling affecting binaurally sensitive neurons in the central auditory system. The results are highly relevant for improved understanding of putative physiological mechanisms underlying perceptual disorders such as tinnitus and hyperacusis.

  2. Urinary concentrations of parabens in Chinese young adults: implications for human exposure.

    Science.gov (United States)

    Ma, Wan-Li; Wang, Lei; Guo, Ying; Liu, Li-Yan; Qi, Hong; Zhu, Ning-Zheng; Gao, Chong-Jing; Li, Yi-Fan; Kannan, Kurunthachalam

    2013-10-01

    Parabens are widely used as preservatives in foods, cosmetics, and pharmaceuticals. However, recent studies have indicated that high and systemic exposure to parabens can be harmful to human health. Although a few studies have reported urinary paraben levels in western countries, studies on paraben exposure in the Chinese population are limited. China is currently a major producer of parabens in the world. In this study, 109 urine samples collected from Chinese young adults (approximately 20 years old) were analyzed for five parabens (methyl-, ethyl-, propyl-, butyl-, and benzyl-parabens) by high-performance liquid chromatography-tandem mass spectrometry. Methyl-, propyl-, and ethyl-parabens were the three major paraben analogues found in all (100%) samples. The concentration of the sum of the five parabens ranged from 0.82 to 728 ng/mL with a geometric mean value of 17.4 ng/mL. Urinary concentration of parabens was 2-fold greater in females than in males. Based on the measured urinary concentrations, daily intake of parabens by the Chinese young adults was estimated and compared with those reported for United States adults. The estimated daily intakes (EDIurine) of parabens were 18.4 and 40.8 μg/kg bw/day for Chinese males and females, respectively, values that were lower than those reported for United States adults (74.7 μg/kg bw/day). Based on the reported concentrations of parabens in foods from China and the United States, the contribution of dietary intake to EDIurine was estimated to be 5.5, 2.6, and 0.42% for Chinese males, Chinese females, and United States adults, respectively, which indicates the significance of nondietary sources of parabens to human exposures.

  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 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 those with more advanced changes

  4. Comparative immunolocalisation of perlecan with collagen II and aggrecan in human foetal, newborn and adult ovine joint tissues demonstrates perlecan as an early developmental chondrogenic marker.

    Science.gov (United States)

    Smith, Susan M; Shu, Cindy; Melrose, James

    2010-09-01

    We undertook a comparative immunolocalisation study on type II collagen, aggrecan and perlecan in a number of 12- to 14-week-old human foetal and postnatal (7-19 months) ovine joints including finger, toe, knee, elbow, hip and shoulder. This demonstrated that perlecan followed a virtually identical immunolocalisation pattern to that of type II collagen in the foetal tissues, but a slightly divergent localisation pattern in adult tissues. Aggrecan was also localised in the cartilaginous joint tissues, which were clearly delineated by toluidine blue staining and the type II collagen immunolocalisations. It was also present in the capsular joint tissues and in ligaments and tendons in the joint, which stained poorly or not at all with toluidine blue. In higher power microscopic views, antibodies to perlecan also stained small blood vessels in the synovial lining tissues of the joint capsule; however, this was not discernable in low power macroscopic views where the immunolocalisation of perlecan to pericellular regions of cells within the cartilaginous rudiments was a predominant feature. Perlecan was also evident in small blood vessels in stromal connective tissues associated with the cartilage rudiments and with occasional nerves in the vicinity of the joint tissues. Perlecan was expressed by rounded cells in the enthesis attachment points of tendons to bone and in rounded cells in the inner third of the meniscus, which stained prominently with type II collagen and aggrecan identifying the chondrogenic background of these cells and local compressive loads. Flattened cells within the tendon and in the surface laminas of articular cartilages and the meniscus did not express perlecan. Collected evidence presented herein, therefore, indicates that besides being a basement membrane component, perlecan is also a marker of chondrogenic cells in prenatal cartilages. In postnatal cartilages, perlecan displayed a pericellular localisation pattern rather than the territorial

  5. Comparison of human growth hormone products' cost in pediatric and adult patients. A budgetary impact model.

    Science.gov (United States)

    Bazalo, Gary R; Joshi, Ashish V; Germak, John

    2007-09-01

    We assessed the economic impact to the United States payer of recombinant human growth hormone (rhGH) utilization, comparing the relative dosage efficiency of marketed pen-based and vial-based products in a pediatric and in an adult population. A budgetary impact model calculated drug costs based on product waste and cost. Waste was the difference between prescribed dose, based on patient weight, and actual delivered dose, based on dosing increments and maximum deliverable dose for pens and a fixed-percent waste as derived from the literature for vials. Annual wholesale acquisition costs were calculated based upon total milligrams delivered, using a daily dose of 0.03 mg/kg for pediatric patients and 0.016 mg/kg for adults. Total annual drug costs were compared for two scenarios: 1) a product mix based on national market share and 2) restricting use to the product with lowest waste. Based on the literature, waste for each vial product was 23 percent. Among individual pens, waste was highest for Humatrope 24 mg (19.5 percent pediatric, 14.3 percent adult) and lowest for Norditropin Nordi-Flex 5 mg (1.1 percent pediatric, 1 percent adult). Restricting use to the brand with least waste (Norditropin), compared to national product share mix, resulted in a 10.2 percent reduction in annual pediatric patient cost from $19,026 to $17,089 and an 8 percent reduction in annual adult patient cost from $24,099 to $22,161. We concluded that pen delivery systems result in less waste than vial and syringe. Considering all approved delivery systems, Norditropin resulted in the least product waste and lower annual patient cost for both pediatric and adult populations.

  6. Isoforms of Hsp70-binding human LDL in adult Schistosoma mansoni worms.

    Science.gov (United States)

    Pereira, Adriana S A; Cavalcanti, Marília G S; Zingali, Russolina B; Lima-Filho, José L; Chaves, Maria E C

    2015-03-01

    Schistosoma mansoni is one of the most common parasites infecting humans. They are well adapted to the host, and this parasite's longevity is a consequence of effective escape from the host immune system. In the blood circulation, lipoproteins not only help to conceal the worm from attack by host antibodies but also act as a source of lipids for S. mansoni. Previous SEM studies showed that the low-density lipoprotein (LDL) particles present on the surface of adult S. mansoni worms decreased in size when the incubation time increased. In this study, immunocytochemical and proteomic analyses were used to locate and identify S. mansoni binding proteins to human plasma LDL. Ultrathin sections of adult worms were cut transversely from the anterior, medial and posterior regions of the parasite. Immunocytochemical experiments revealed particles of gold in the tegument, muscle region and spine in male worms and around vitelline cells in females. Immunoblotting and 2D-electrophoresis using incubations with human serum, anti-LDL antibodies and anti-chicken IgG peroxidase conjugate were performed to identify LDL-binding proteins in S. mansoni. Analysis of the binding proteins using LC-MS identified two isoforms of the Hsp70 chaperone in S. mansoni. Hsp70 is involved in the interaction with apoB in the cytoplasm and its transport to the endoplasmic reticulum. However, further studies are needed to clarify the functional role of Hsp70 in S. mansoni, mainly related to the interaction with human LDL.

  7. Induction of oligodendrocyte differentiation from adult human fibroblast-derived induced pluripotent stem cells.

    Science.gov (United States)

    Ogawa, Shin-ichiro; Tokumoto, Yasuhito; Miyake, Jun; Nagamune, Teruyuki

    2011-08-01

    Induced pluripotent stem cells (iPSCs) prepared from somatic cells might become a novel therapeutic tool in regenerative medicine, especially for the central nervous system (CNS). In this study, we attempted to induce O4-positive (O4(+)) oligodendrocytes from adult human fibroblast-derived iPSCs in vitro. We used two adult human iPSC cell lines, 201B7 and 253G1. 201B7 was induced by four-gene transduction (oct4, sox2, klf4, c-myc), and 253G1 was induced by three-gene transduction (oct4, sox2, klf4). We treated these cells with two in vitro oligodendrocyte-directed differentiation protocols that were optimized for human embryonic stem cells. One protocol used platelet-derived growth factor as the major mitogen for oligodendrocyte lineage cells, and the other protocol used epidermal growth factor (EGF) as the mitogen. Although the differentiation efficiency was low (less than 0.01%), we could induce O4(+) oligodendrocytes from 253G1 cells using the EGF-dependent differentiation protocol. This is the first report of the in vitro induction of oligodendrocytes differentiation from human iPSCs.

  8. Adult education as a human right: The Latin American context and the ecopedagogic perspective

    Science.gov (United States)

    Gadotti, Moacir

    2011-08-01

    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 as technical. All along the history of contemporary education it is essential to highlight the importance of the CONFINTEA conferences for the construction of an expanded vision of this concept. Adult education is understood as a human right. The right to education does not end when a person has reached the so-called "proper" age; it continues to be a right for the duration of everyone's entire life. This article explores Paulo Freire's contribution, particularly the methodology of MOVA (Youth and Adult Literacy Movement). It also presents the ecopedagogic perspective, which was inspired by Paulo Freire's legacy. Finally, this article stresses the need to support a long-term policy for adult education, following the recommendations of the Civil Society International Forum (FISC) and CONFINTEA VI, both held in Belém, Brazil, in 2009.

  9. Functional bracing for comminuted extra-articular fractures of the distal third of the humerus.

    Science.gov (United States)

    Sarmiento, A; Horowitch, A; Aboulafia, A; Vangsness, C T

    1990-03-01

    From 1982 to 1987 we treated 85 extra-articular comminuted distal third humeral fractures in adults with prefabricated plastic braces. Of these, 15% were open fractures and 18% had initial peripheral nerve injury. On average, the sleeve was applied 12 days after injury and used for 10 weeks. There was 96% union, with no infections. All nerve injuries resolved or were improving at the latest examination. At union there was varus deformity averaging 9 degrees in 81% of patients, but loss of range of movement was minimal and functional results were good.

  10. 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

  11. Effects of intra articular tramadol on articular cartilage and synovium of rats

    Directory of Open Access Journals (Sweden)

    Musa Kola

    2015-12-01

    Full Text Available Objective: To investigate the effects of intra articular tramadol injection on articular cartilage and synovium in rat knee joint. Methods: After Animal Ethical Committee approval, a total of 20 Sprague-Dawley rats were used and divided into 4 groups. Each group was composed of 5 rats. 0.2 ml of tramadol HCl was injected into the right knee joints and left knee joints of all the rats were considered as control. Control side joints received saline injection. Rats were sacrificed with ketamin on 1st, 7th, 14th and 21st days and knee joints were removed. Obtained tissue samples were decalcified and were dyed with Hematoxylin-eosin and Masson’s trichrome stain and examined by light microscopy for the presence of inflammation in periarticular area and synovia. Results: Congestion of synovial veins and perivascular cell infiltration were observed in tramadol group on days 1 and 7 (P < 0.05. The inflammation process was replaced by fibrosis on day 14 and fibrosis was significantly decreased on day 21. Conclusion: Intra articular tramadol should be used cautiously, keeping in mind that it may cause synovial inflammation in early phases and fibrosis in late phases. J Clin Exp Invest 2015; 6 (4: 337-342

  12. Extrasynaptic location of laminin beta 2 chain in developing and adult human skeletal muscle

    DEFF Research Database (Denmark)

    Wewer, U M; Thornell, L E; Loechel, F;

    1997-01-01

    We have investigated the distribution of the laminin beta 2 chain (previously s-laminin) in human fetal and adult skeletal muscle and compared it to the distribution of laminin beta 1. Immunoblotting and transfection assays were used to characterize a panel of monoclonal and polyclonal antibodies...... to the laminin beta 2 chain. We found that laminin beta 1 chain was detected at all times during development from 10 weeks of gestation. Laminin beta 2 chain was first detected in 15 to 22-week-old fetal skeletal muscle as distinct focal immunoreactivity in the sarcolemmal basement membrane area of some...... myofibers. In the adult skeletal muscle, laminin beta 2 chain immunoreactivity was found along the entire perimeter of each of the individual myofibers in a large series of different muscles studied. Laminin beta 2 chain was similarly found in the skeletal muscle basement membranes in patients with Duchenne...

  13. 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.

  14. 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.

  15. [Familial articular chondrocalcinosis: study of an Alsatian family].

    Science.gov (United States)

    Netter, P; Loeuille, D; Jouzeau, J Y; Gillet, P; Peterschmitt, J; Pourel, J; Gaucher, A

    2001-01-01

    Familial articular chondrocalcinosis is a chronic articular disease characterized by acute intermittent attacks of arthritis, presence of calcium pyrophosphate dihydrate crystal in synovial fluid, cartilage and periarticular soft tissue and by x rays calcium deposition in articular cartilage. A family originating from Alsace, with an autosomal dominant transmission has been studied. As in English and Argentinean families, a linkage to the short arm of chromosome 5p has been found. These results suggest that a defective gene at this location may be related to the chondrocalcinosis in these families.

  16. Three-dimensional dental arch curvature in human adolescents and adults.

    Science.gov (United States)

    Ferrario, V F; Sforza, C; Poggio, C E; Serrao, G; Colombo, A

    1999-04-01

    The three-dimensional arrangement of dental cusps and incisal edges in human dentitions has been reported to fit the surface of a sphere (the curve of Monson), with a radius of about 4 inches in adults. The objective of the current study was to compare the three-dimensional curvature of the mandibular dental arch in healthy permanent dentitions of young adults and adolescents. The mandibular casts of 50 adults (aged 19 to 22 years) and 20 adolescents (aged 12 to 14 years) with highly selected sound dentitions that were free from temporomandibular joint problems were obtained. The three coordinates of cusp tips excluding the third molars were digitized with a three-dimensional digitizer, and used to derive a spherical model of the curvature of the occlusal surfaces. From the best interpolating sphere, the radii of the left and right curves of Spee (quasi-sagittal plane) and of molar curve of Wilson (frontal plane) were computed. Mandibular arch size (interdental distances) was also calculated. The occlusal curvature of the mandibular arch was not significantly influenced by sex, although a significant effect of age was found (Student t, P curves of Spee, and curve of Wilson in the molar area were about 101 mm in adults, and about 80 mm in adolescents. Arch size was not influenced by either sex or age. The different curvatures of the occlusal plane in adolescents and adults may be explained by a progressive rotation of the major axis of the teeth moving the occlusal plane toward a more buccal position. These dental movements should be performed in a frontal plane on an anteroposterior axis located next to the dental crown.

  17. Effects of dexamethasone on proliferation, differentiation and apoptosis of adult human osteoblasts in vitro

    Institute of Scientific and Technical Information of China (English)

    杨林; 陶天遵; 王新婷; 杜宁; 陈伟珍; 陶树清; 王志成; 吴丽萍

    2003-01-01

    Objective To observe the effects of dexamethasone on proliferation, differentiation and apoptosis of adult human osteoblasts in vitro. Methods Iliac trabecular bone specimens were obtained from adult patients undergoing necessary surgery. After the bone pieces were digested with collagenase-trypsin, osteoblasts were released and incubated at 37℃ in a relative humidity of 95% and 5% CO2. Then, the cells were purified, and their passages were given DMEM-F12 and fetal bovine serum medium. Subsequently, 10-8 mol/L dexamethasone was added into the culture medium to incubate the osteoblasts for three days, and the cells from control groups were incubated without any drugs. All cells were observed continually with phase contrast microscope and transmission electron microscope. Finally, apoptosis was detected by the use of terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) and biochemical indices, alkaline phosphatase (ALP) and osteocalcin (OCN) were used to determine the effects of dexamethasone on proliferation, differentiation and apoptosis of adult osteoblasts in vitro. Results In the adult osteoblasts obtained by collagenase-trypsin digestion, it achieved high survial, stable biochemical indices and excellent purification. Under the condition of dexamethasone 10-8 mol/L and osteoblasts 10 000/ml, there was significant promotion of ALP and OCN secretion without cell apoptosis.Conclusions Dexamethasone has a significant effect on the proliferation and differentiation of adult osteoblasts in vitro without apoptosis, and dexamethasone at the suggested concentration can be used as positive control in drug studies for osteoporosis treatment.

  18. Human tau expression reduces adult neurogenesis in a mouse model of tauopathy.

    Science.gov (United States)

    Komuro, Yutaro; Xu, Guixiang; Bhaskar, Kiran; Lamb, Bruce T

    2015-06-01

    Accumulation of hyperphosphorylated and aggregated microtubule-associated protein tau (MAPT) is a central feature of a class of neurodegenerative diseases termed tauopathies. Notably, there is increasing evidence that tauopathies, including Alzheimer's disease, are also characterized by a reduction in neurogenesis, the birth of adult neurons. However, the exact relationship between hyperphosphorylation and aggregation of MAPT and neurogenic deficits remains unclear, including whether this is an early- or late-stage disease marker. In the present study, we used the genomic-based hTau mouse model of tauopathy to examine the temporal and spatial regulation of adult neurogenesis during the course of the disease. Surprisingly, hTau mice exhibited reductions in adult neurogenesis in 2 different brain regions by as early as 2 months of age, before the development of robust MAPT pathology in this model. This reduction was found to be due to reduced proliferation and not because of enhanced apoptosis in the hippocampus. At these same time points, hTau mice also exhibited altered MAPT phosphorylation with neurogenic precursors. To examine whether the effects of MAPT on neurogenesis were cell autonomous, neurospheres prepared from hTau animals were examined in vitro, revealing a growth deficit when compared with non-transgenic neurosphere cultures. Taken together, these studies provide evidence that altered adult neurogenesis is a robust and early marker of altered, cell-autonomous function of MAPT in the hTau mouse mode of tauopathy and that altered adult neurogenesis should be examined as a potential marker and therapeutic target for human tauopathies.

  19. Isolation and culture of adult human microglia within mixed glial cultures for functional experimentation and high-content analysis.

    Science.gov (United States)

    Smith, Amy M; Gibbons, Hannah M; Lill, Claire; Faull, Richard L M; Dragunow, Mike

    2013-01-01

    Microglia are thought to be involved in diseases of the adult human brain as well as normal aging processes. While neonatal and rodent microglia are often used in studies investigating microglial function, there are important differences between rodent microglia and their adult human counterparts. Human brain tissue provides a unique and valuable tool for microglial cell and molecular biology. Routine protocols can now enable use of this culture method in many laboratories. Detailed protocols and advice for culture of human brain microglia are provided here. We demonstrate the protocol for culturing human adult microglia within a mixed glial culture and use a phagocytosis assay as an example of the functional studies possible with these cells as well as a high-content analysis method of quantification.

  20. Early reversal cells in adult human bone remodeling: osteoblastic nature, catabolic functions and interactions with osteoclasts.

    Science.gov (United States)

    Abdelgawad, Mohamed Essameldin; Delaisse, Jean-Marie; Hinge, Maja; Jensen, Pia Rosgaard; Alnaimi, Ragad Walid; Rolighed, Lars; Engelholm, Lars H; Marcussen, Niels; Andersen, Thomas Levin

    2016-06-01

    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 through electron microscopy and analysis of molecular markers. Periosteoclastic reversal cells show direct contacts with the osteoclasts and with the demineralized resorption debris. These early reversal cells show (1) ¾-collagen fragments typically generated by extracellular collagenases of the MMP family, (2) MMP-13 (collagenase-3) and (3) the endocytic collagen receptor uPARAP/Endo180. The prevalence of these markers was lower in the later reversal cells, which are located near the osteoid surfaces and morphologically resemble mature bone-forming osteoblasts. In conclusion, this study demonstrates that reversal cells colonizing bone surfaces right after resorption are osteoblast-lineage cells, and extends to adult human bone remodeling their role in rendering eroded surfaces osteogenic.

  1. 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.

  2. 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

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

    Science.gov (United States)

    Nemolato, S.; Van Eyken, P.; Cabras, T.; Cau, F.; Fanari, M.U.; Locci, A.; Fanni, D.; Gerosa, C.; Messana, I.; Castagnola, M.; Faa, G.

    2011-01-01

    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. PMID:22073372

  4. 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.

  5. [Structure of the articular cartilage in the middle aged].

    Science.gov (United States)

    Kop'eva, T N; Mul'diiarov, P Ia; Bel'skaia, O B; Pastel', V B

    1983-10-01

    In persons 17-83 years of age having no articular disorders 39 samples of the patellar articular cartilage, the articulated surface and the femoral head have been studied histochemically, histometrically and electron microscopically. Age involution of the articular cartilage is revealed after 40 years of age as a progressive decrease in chondrocytes density in the superficial and (to a less degree) in the intermediate zones. This is accompanied with a decreasing number of 3- and 4-cellular lacunae and with an increasing number of unicellular and hollow lacunae. In some chondrocytes certain distrophic and necrotic changes are revealed. In the articular matrix the zone with the minimal content of glycosaminoglycans becomes thicker and keratansulfate content in the territorial matrix of the cartilage deep zone grows large.

  6. Selection of apoptotic cell specific human antibodies from adult bone marrow.

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    Caroline Grönwall

    Full Text Available Autoreactive antibodies that recognize neo-determinants on apoptotic cells in mice have been proposed to have protective, homeostatic and immunoregulatory properties, although our knowledge about the equivalent antibodies in humans has been much more limited. In the current study, human monoclonal antibodies with binding specificity for apoptotic cells were isolated from the bone marrow of healthy adults using phage display technology. These antibodies were shown to recognize phosphorylcholine (PC-associated neo-determinants. Interestingly, three of the four identified apoptotic cell-specific antibody clones were encoded by VH3 region rearrangements with germline or nearly germline configuration without evidence of somatic hypermutation. Importantly, the different identified antibody clones had diverse heavy chain CDR3 and deduced binding surfaces as suggested by structure modeling. This may suggest a potentially great heterogeneity in human antibodies recognizing PC-related epitopes on apoptotic cells. To re-construct the postulated structural format of the parental anti-PC antibody, the dominant clone was also expressed as a recombinant human polymeric IgM, which revealed a substantially increased binding reactivity, with dose-dependent and antigen-inhibitable binding of apoptotic cells. Our findings may have implication for improved prognostic testing and therapeutic interventions in human inflammatory disease.

  7. Differential DNA Methylation Regions in Adult Human Sperm following Adolescent Chemotherapy: Potential for Epigenetic Inheritance

    Science.gov (United States)

    Shnorhavorian, Margarett; Schwartz, Stephen M.; Stansfeld, Barbara; Sadler-Riggleman, Ingrid; Beck, Daniel

    2017-01-01

    Background The potential that adolescent chemotherapy can impact the epigenetic programming of the germ line to influence later life adult fertility and promote epigenetic inheritance was investigated. Previous studies have demonstrated a number of environmental exposures such as abnormal nutrition and toxicants can promote sperm epigenetic changes that impact offspring. Methods Adult males approximately ten years after pubertal exposure to chemotherapy were compared to adult males with no previous exposure. Sperm were collected to examine differential DNA methylation regions (DMRs) between the exposed and control populations. Gene associations and correlations to genetic mutations (copy number variation) were also investigated. Methods and Findings A signature of statistically significant DMRs was identified in the chemotherapy exposed male sperm. The DMRs, termed epimutations, were found in CpG desert regions of primarily 1 kilobase size. Observations indicate adolescent chemotherapy exposure can promote epigenetic alterations that persist in later life. Conclusions This is the first observation in humans that an early life chemical exposure can permanently reprogram the spermatogenic stem cell epigenome. The germline (i.e., sperm) epimutations identified suggest chemotherapy has the potential to promote epigenetic inheritance to the next generation. PMID:28146567

  8. The Frictional Coefficient of Bovine Knee Articular Cartilage

    Institute of Scientific and Technical Information of China (English)

    Qian Shan-hua; Ge Shi-rong; Wang Qing-liang

    2006-01-01

    The normal displacement of articular cartilage was measured under load and in sliding, and the coefficient of friction during sliding was measured using a UMT-2 Multi-Specimen Test System. The maximum normal displacement under load and the start-up frictional coefficient have similar tendency of variation with loading time. The sliding speed does not significantly influence the frictional coefficient of articular cartilage.

  9. Reduced Expression of Cytoskeletal and Extracellular Matrix Genes in Human Adult Retinal Pigment Epithelium Cells Exposed to Simulated Microgravity

    DEFF Research Database (Denmark)

    Corydon, Thomas J; Mann, Vivek; Slumstrup, Lasse;

    2016-01-01

    BACKGROUND/AIMS: Microgravity (µg) has adverse effects on the eye of humans in space. The risk of visual impairment is therefore one of the leading health concerns for NASA. The impact of µg on human adult retinal epithelium (ARPE-19) cells is unknown. METHODS: In this study we investigated the i...

  10. Reprogramming of adult human neural stem cells into induced pluripotent stem cells

    Institute of Scientific and Technical Information of China (English)

    XIE Li-qian; SUN Hua-ping; WANG Tian; TANG Hai-liang; WANG Pu; ZHU Jian-hong; YAO Zheng-wei

    2013-01-01

    Background Since an effective method for generating induced pluripotent stem cells (iPSCs) from human neural stem cells (hNSCs) can offer us a promising tool for studying brain diseases,here we reported direct reprogramming of adult hNSCs into iPSCs by retroviral transduction of four defined factors.Methods NSCs were successfully isolated and cultured from the hippocampus tissue of epilepsy patients.When combined with four factors (OCT3/4,SOX2,KLF4,and c-MYC),iPSCs colonies were successfully obtained.Results Morphological characterization and specific genetic expression confirmed that these hNSCs-derived iPSCs showed embryonic stem cells-like properties,which include the ability to differentiate into all three germ layers both in vitro and in vivo.Conclusion Our method would be useful for generating human iPSCs from NSCs and provide an important tool for studying neurological diseases.

  11. HUMANIZATION VISIT FAMILY IN AN ADULT ICU SOUTHEAST OF MATO GROSSO

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    Vagner Nascimento

    2012-01-01

    Full Text Available This is a pilot project, using the theoretical and philosophical Leininger. The project will be developed in a municipality hospital in southeastern of Mato Grosso, in the period between January and March 2012, in order to humanize the family visits of the internal customers of Adult Intensive Care Unit. To carry out the project activities will use the listing of the original guidelines proposed by the Paulista School of Medicine of sectors closed to visitors. The need to intervene in this dynamic, customer-service family, there was a lack of humane view of the team with the family, sometimes for not recognizing the family as a therapeutic tool in intensive care. Thus, neglecting the health of the family, who likewise, need special care, intensive care.

  12. D-type cyclins in adult human testis and testicular cancer

    DEFF Research Database (Denmark)

    Bartkova, J; Rajpert-de Meyts, E; Skakkebaek, N E

    1999-01-01

    on immunohistochemical and immunochemical analysis of human adult testis and 32 testicular tumours to examine the differential expression and abundance of cyclins D1, D2, and D3 in relation to cell type, proliferation, differentiation, and malignancy. In normal testis, the cell type-restricted expression patterns were...... D2 but not D1 or D3, while the invasive testicular tumours showed variable positivity for cyclins D2 and D3, but rarely D1. An unexpected correlation with differentiation rather than proliferation was found particularly for cyclin D3 in teratomas, a conceptually significant observation confirmed...... by massive up-regulation of cyclin D3 in the human teratocarcinoma cell line NTera2/D1 induced to differentiate along the neuronal lineage. These results suggest a possible involvement of cyclin D2 in the early stages of testicular oncogenesis and the striking examples of proliferation-independent expression...

  13. Difference of Sodium Currents between Pediatric and Adult Human Atrial Myocytes: Evidence for Developmental Changes of Sodium Channels

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    Benzhi Cai, Xiaoqin Mu, Dongmei Gong, Shulin Jiang, Jianping Li, Qingxin Meng, Yunlong Bai, Yanju Liu, Xinyue Wang, Xueying Tan, Baofeng Yang, Yanjie Lu

    2011-01-01

    Full Text Available Voltage-gated calcium currents and potassium currents were shown to undergo developmental changes in postnatal human and animal cardiomocytes. However, so far, there is no evidence whether sodium currents also presented the developmental changes in postnatal human atrial cells. The aim of this study was to observe age-related changes of sodium currents between pediatric and adult atrial myocytes. Human atrial myocytes were acutely isolated and the whole-cell patch clamp technique was used to record sodium currents isolated from pediatric and adult atrial cardiomocytes. The peak amplitude of sodium currents recorded in adult atrial cells was significantly larger than that in pediatric atrial myocytes. However, there was no significant difference of the activation voltage for peak sodium currents between two kinds of atrial myocytes. The time constants for the activation and inactivation of sodium currents were smaller in adult atria than pediatric atria. The further study revealed that the voltage-dependent inactivation of sodium currents were more slow in adult atrial cardiomyocytes than pediatric atrial cells. A significant difference was also observed in the recovery process of sodium channel from inactivation. In summary, a few significant differences were demonstrated in sodium currents characteristics between pediatric and adult atrial myocytes, which indicates that sodium currents in human atria also undergo developmental changes.

  14. Essential Microenvironment for Thymopoiesis is Preserved in Human Adult and Aged Thymus

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    J. Shiraishi

    2003-01-01

    Full Text Available Normal human thymuses at various ages were immunohistologically examined in order to determine whether adult or aged thymus maintained the microenvironment for the T cell development and thymopoiesis was really ongoing. To analyze the thymic microenvironment, two monoclonal antibodies (MoAb were employed. One is MoAb to IL-1 receptor (IL-1R recognizing medullary and subcapsular cortical epithelial cells of normal infant human thymus. The other is UH-1 MoAb recognizing thymic epithelial cells within the cortex, which are negative with IL-1R-MoAb. Thymus of subjects over 20 years of age was split into many fragments and dispersed in the fatty tissue. However, the microenvironment of each fragment was composed of both IL-1R positive and UH-1 positive epithelial cells, and the UH-1 positive portion was populated with lymphocytes showing a follicle-like appearance. Lymphocytes in these follicle-like portions were mostly CD4+CD8+ double positive cells and contained many proliferating cells as well as apoptotic cells. Thus these follicle-like portions in adult and aged thymus were considered to be functioning as cortex as in infant thymus. Proliferative activity of thymocytes in the thymic cortex and the follicle-like portions definitely declined with advance of age, while incidence of apoptotic thymocytes increased with aging.

  15. Psychometric testing of the Revised Humane Caring Scale for adult patients in Singapore.

    Science.gov (United States)

    Goh, Mien Li; Ang, Emily N K; Chan, Yiong-Huak; He, Hong-Gu; Vehviläinen-Julkunen, Katri

    2015-09-01

    In this study, we examined the validity and reliability of the Revised Humane Caring Scale as used by adult patients in a tertiary hospital in Singapore. A three-phase descriptive quantitative study was conducted. In phase I, an expert panel of nurses and inpatients examined the content validity of the scale; phase II comprised a pilot study on 20 patients; and in phase III, a large-scale study on 235 patients was implemented to test the internal consistency of the scale. The results revealed that the content validity index of the scale ranged from 0.856 to 1, and the scale had a high inter-rater agreement kappa value of 0.940. Cronbach's alpha ranged from 0.798 to 0.877 in phase II, and from 0.579 to 0.760 in phase III, respectively. The Revised Humane Caring Scale revealed good content validity and an acceptable level of internal consistency. The scale is an acceptable measurement tool for evaluating adult patients' satisfaction during hospitalization.

  16. Adult human nasal mesenchymal-like stem cells restore cochlear spiral ganglion neurons after experimental lesion.

    Science.gov (United States)

    Bas, Esperanza; Van De Water, Thomas R; Lumbreras, Vicente; Rajguru, Suhrud; Goss, Garrett; Hare, Joshua M; Goldstein, Bradley J

    2014-03-01

    A loss of sensory hair cells or spiral ganglion neurons from the inner ear causes deafness, affecting millions of people. Currently, there is no effective therapy to repair the inner ear sensory structures in humans. Cochlear implantation can restore input, but only if auditory neurons remain intact. Efforts to develop stem cell-based treatments for deafness have demonstrated progress, most notably utilizing embryonic-derived cells. In an effort to bypass limitations of embryonic or induced pluripotent stem cells that may impede the translation to clinical applications, we sought to utilize an alternative cell source. Here, we show that adult human mesenchymal-like stem cells (MSCs) obtained from nasal tissue can repair spiral ganglion loss in experimentally lesioned cochlear cultures from neonatal rats. Stem cells engraft into gentamicin-lesioned organotypic cultures and orchestrate the restoration of the spiral ganglion neuronal population, involving both direct neuronal differentiation and secondary effects on endogenous cells. As a physiologic assay, nasal MSC-derived cells engrafted into lesioned spiral ganglia demonstrate responses to infrared laser stimulus that are consistent with those typical of excitable cells. The addition of a pharmacologic activator of the canonical Wnt/β-catenin pathway concurrent with stem cell treatment promoted robust neuronal differentiation. The availability of an effective adult autologous cell source for inner ear tissue repair should contribute to efforts to translate cell-based strategies to the clinic.

  17. Distortion product otoacoustic emission suppression tuning curves in human adults and neonates.

    Science.gov (United States)

    Abdala, C; Sininger, Y S; Ekelid, M; Zeng, F G

    1996-09-01

    Distortion product otoacoustic emission (DPOAE) iso-suppression tuning curves (STC) were generated in 15 normal-hearing adults and 16 healthy term-born neonates for three f2 frequencies. The 2f1-f2 DPOAE was elicited using f2/f1 = 1.2, LI = 1.2, LI = 65 and L2 = 50 dB SPL. A suppressor tone was presented at frequencies ranging from 1 octave below to 1/4 octave above f2 and varied in level until DPOAE amplitude was reduced by 6 dB. The suppressor level required for 6 dB suppression was plotted as function of suppressor frequency to generate a DPOAE STC. Forward-masked psychoacoustic tuning curves (PTC) were obtained for three of the adult subjects. Results indicate that DPOAE STCs are stable and show minimal inter- and intra-subject variability. The tip of the STC is consistently centered around the f2 region and STCs are similar in shape, width (Q10) and slope to VIIIth-nerve TCs. PTCs and STCs measured in the same subject showed similar trends, although PTCs had narrower width and steeper slope. Neonatal STCs were recorded at 3000 and 6000 Hz only and were comparable in shape, width and slope to adult STCs. Results suggest: (1) suppression of the 2f1-f2 DPOAE may provide an indirect measure of cochlear frequency resolution in humans and (2) cochlear tuning, and associated active processes in the cochlea, are mature by term birth for at least mid- and high-frequencies. These results provide significant impetus for continued study of DPOAE suppression as a means of evaluating cochlear frequency resolution in humans.

  18. High individual consistency in fear of humans throughout the adult lifespan of rural and urban burrowing owls.

    Science.gov (United States)

    Carrete, Martina; Tella, José L

    2013-12-17

    Human-induced rapid environmental changes challenge individuals by creating evolutionarily novel scenarios, where species encounter novel enemies, the new species sometimes being humans themselves. However, little is known about how individuals react to human presence, specifically whether they are able to habituate to human presence, as frequently assumed, or are selected based on their fear of humans. We tested whether fear of humans (measured as flight initiation distance in a diurnal owl) is reduced through habituation to human presence (plasticity) or whether it remains unchanged throughout the individuals' life. Results show an unusually high level of individual consistency in fear of humans throughout the adult lifespan of both rural (r = 0.96) and urban (r = 0.90) birds, lending no support to habituation. Further research should assess the role of inter-individual variability in fear of humans in shaping the distribution of individuals and species in an increasingly humanized world.

  19. 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.

  20. An animal model of adult T-cell leukemia: humanized mice with HTLV-1-specific immunity.

    Science.gov (United States)

    Tezuka, Kenta; Xun, Runze; Tei, Mami; Ueno, Takaharu; Tanaka, Masakazu; Takenouchi, Norihiro; Fujisawa, Jun-ichi

    2014-01-16

    Human T-cell leukemia virus type 1 (HTLV-1) is causally associated with adult T-cell leukemia (ATL), an aggressive T-cell malignancy with a poor prognosis. To elucidate ATL pathogenesis in vivo, a variety of animal models have been established; however, the mechanisms driving this disorder remain poorly understood due to deficiencies in each of these animal models. Here, we report a novel HTLV-1-infected humanized mouse model generated by intra-bone marrow injection of human CD133(+) stem cells into NOD/Shi-scid/IL-2Rγc null (NOG) mice (IBMI-huNOG mice). Upon infection, the number of CD4(+) human T cells in the periphery increased rapidly, and atypical lymphocytes with lobulated nuclei resembling ATL-specific flower cells were observed 4 to 5 months after infection. Proliferation was seen in both CD25(-) and CD25(+) CD4 T cells with identical proviral integration sites; however, a limited number of CD25(+)-infected T-cell clones eventually dominated, indicating an association between clonal selection of infected T cells and expression of CD25. Additionally, HTLV-1-specific adaptive immune responses were induced in infected mice and might be involved in the control of HTLV-1-infected cells. Thus, the HTLV-1-infected IBMI-huNOG mouse model successfully recapitulated the development of ATL and may serve as an important tool for investigating in vivo mechanisms of ATL leukemogenesis and evaluating anti-ATL drug and vaccine candidates.

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

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    Sarada Devi Ramachandran

    Full Text Available 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.

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

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    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.

  3. Sustained Engraftment of Cryopreserved Human Bone Marrow CD34(+) Cells in Young Adult NSG Mice.

    Science.gov (United States)

    Wiekmeijer, Anna-Sophia; Pike-Overzet, Karin; Brugman, Martijn H; Salvatori, Daniela C F; Egeler, R Maarten; Bredius, Robbert G M; Fibbe, Willem E; Staal, Frank J T

    2014-06-01

    Hematopoietic stem cells (HSCs) are defined by their ability to repopulate the bone marrow of myeloablative conditioned and/or (lethally) irradiated recipients. To study the repopulating potential of human HSCs, murine models have been developed that rely on the use of immunodeficient mice that allow engraftment of human cells. The NSG xenograft model has emerged as the current standard for this purpose allowing for engraftment and study of human T cells. Here, we describe adaptations to the original NSG xenograft model that can be readily implemented. These adaptations encompass use of adult mice instead of newborns and a short ex vivo culture. This protocol results in robust and reproducible high levels of lympho-myeloid engraftment. Immunization of recipient mice with relevant antigen resulted in specific antibody formation, showing that both T cells and B cells were functional. In addition, bone marrow cells from primary recipients exhibited repopulating ability following transplantation into secondary recipients. Similar results were obtained with cryopreserved human bone marrow samples, thus circumventing the need for fresh cells and allowing the use of patient derived bio-bank samples. Our findings have implications for use of this model in fundamental stem cell research, immunological studies in vivo and preclinical evaluations for HSC transplantation, expansion, and genetic modification.

  4. Characterization of pancreatic stem cells derived from adult human pancreas ducts by fluorescence activated cell sorting

    Institute of Scientific and Technical Information of China (English)

    Han-Tso Lin; Shih-Hwa Chiou; Chung-Lan Kao; Yi-Ming Shyr; Chien-Jen Hsu; Yih-Wen Tarng; Larry L-T Ho; Ching-Fai Kwok; Hung-Hai Ku

    2006-01-01

    AIM: To isolate putative pancreatic stem cells (PSCs)from human adult tissues of pancreas duct using serumfree, conditioned medium. The characterization of surface phenotype of these PSCs was analyzed by flow cytometry. The potential for pancreatic lineage and the capability of β-cell differentiation in these PSCs were evaluated as well.METHODS: By using serum-free medium supplemented with essential growth factors, we attempted to isolate the putative PSCs which has been reported to express nestin and pdx-1. The MatrigelTM was employed to evaluate the differential capacity of isolated cells. Dithizone staining, insulin content/secretion measurement, and immunohistochemistry staining were used to monitor the differentiation. Fluorescence activated cell sorting (FACS)was used to detect the phenotypic markers of putative PSCs.RESULTS: A monolayer of spindle-like cells was cultivated. The putative PSCs expressed pdx-1 and nestin.They were also able to differentiate into insulin-, glucagon-, and somatostatin-positive cells. The spectrum of phenotypic markers in PSCs was investigated; a similarity was revealed when using human bone marrow-derived stem cells as the comparative experiment, such as CD29,CD44, CD49, CD50, CD51, CD62E, PDGFR-α, CD73 (SH2),CD81, CD105(SH3).CONCLUSION: In this study, we successfully isolated PSCs from adult human pancreatic duct by using serumfree medium. These PSCs not only expressed nestin and pdx-1 but also exhibited markers attributable to mesenchymal stem cells. Although work is needed to elucidate the role of these cells, the application of these PSCs might be therapeutic strategies for diabetes mellitus.

  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. 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.

  7. Extensive neuronal differentiation of human neural stem cell grafts in adult rat spinal cord.

    Directory of Open Access Journals (Sweden)

    Jun Yan

    2007-02-01

    Full Text Available BACKGROUND: Effective treatments for degenerative and traumatic diseases of the nervous system are not currently available. The support or replacement of injured neurons with neural grafts, already an established approach in experimental therapeutics, has been recently invigorated with the addition of neural and embryonic stem-derived precursors as inexhaustible, self-propagating alternatives to fetal tissues. The adult spinal cord, i.e., the site of common devastating injuries and motor neuron disease, has been an especially challenging target for stem cell therapies. In most cases, neural stem cell (NSC transplants have shown either poor differentiation or a preferential choice of glial lineages. METHODS AND FINDINGS: In the present investigation, we grafted NSCs from human fetal spinal cord grown in monolayer into the lumbar cord of normal or injured adult nude rats and observed large-scale differentiation of these cells into neurons that formed axons and synapses and established extensive contacts with host motor neurons. Spinal cord microenvironment appeared to influence fate choice, with centrally located cells taking on a predominant neuronal path, and cells located under the pia membrane persisting as NSCs or presenting with astrocytic phenotypes. Slightly fewer than one-tenth of grafted neurons differentiated into oligodendrocytes. The presence of lesions increased the frequency of astrocytic phenotypes in the white matter. CONCLUSIONS: NSC grafts can show substantial neuronal differentiation in the normal and injured adult spinal cord with good potential of integration into host neural circuits. In view of recent similar findings from other laboratories, the extent of neuronal differentiation observed here disputes the notion of a spinal cord that is constitutively unfavorable to neuronal repair. Restoration of spinal cord circuitry in traumatic and degenerative diseases may be more realistic than previously thought, although major

  8. 普通接骨板与锁定接骨板治疗成人闭合性跟骨关节内骨折疗效对比%Clinical analysis of open reduction and internal fixation with unlocking plate or locking plate for treatment of adult in-tra-articular calcaneal fractures

    Institute of Scientific and Technical Information of China (English)

    曲绍东; 杨占辉; 史宏伟; 石明国; 张立军; 贾文杰; 苏庆军

    2015-01-01

    Objective To analyze the effect of open reduction and internal fixation (ORIF) with unlocking plate or locking plate for treatment of adult intra-articular calcaneal fracture. Methods 68 cases of calcaneal fracture,including 72 feet in 56 males (4 males were bilateral) and 12 females,with the average age of 35 years (ranging from 18 to 71), were en-rolled. According to Sanders' classification,15 feet were classified as type Ⅱ,46 feet were classified as type Ⅲ, and 11 feet were classified as type Ⅳ. 44 feet were treated with unlocking plate for calcaneal fracture in group A , 28 feet were treated with locking plate for calcaneal fracture in group B. The cases of existing ipsilateral lower limb fracture, ipsilateral vascular injury, and ipsilateral lower limb open injury were excluded. Results The wounds of 64 feet healed piemarily,5 feet were delayed healing. The soft tissue coloboma of 3 feet delayed until pedicle flap transfered. The B(o)hler angle of two groups were significantly different between preoperation and postoperation, but there were no significant differences in B(o)hler angle between two groups. 64 feet in 63 cases were followed up for 12~26 months. According to the AOFAS Ankle-Hindfoot Scale ,49 feet scored 90~100 points,13 feet scored 75~89 points and 2 feet scored 50~74 points. The excellent and good rate was 96.9%. Conclusion ORIF with unlocking plate or locking plate are all effective methods to treat the calcaneal fracture , there are no significant dif-ferences in curative effect between the two methods.%目的 分析普通接骨板与锁定接骨板治疗成人闭合性跟骨骨折的临床疗效. 方法 本组跟骨骨折68例(72足),男56例,女12例,4例男性为双侧. 年龄18~71岁,平均35岁. 应用Sanders分型,其中Ⅱ型15足,Ⅲ型46足,Ⅳ型11足.其中应用非锁定跟骨接骨板治疗44足(A组),应用锁定跟骨接骨板治疗28足(B组).排除术前合并同侧下肢骨折、同侧血管损伤及同

  9. Gene expression profiling of embryonic human neural stem cells and dopaminergic neurons from adult human substantia nigra.

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    Hany E S Marei

    Full Text Available Neural stem cells (NSC with self-renewal and multipotent properties serve as an ideal cell source for transplantation to treat neurodegenerative insults such as Parkinson's disease. We used Agilent's and Illumina Whole Human Genome Oligonucleotide Microarray to compare the genomic profiles of human embryonic NSC at a single time point in culture, and a multicellular tissue from postmortem adult substantia nigra (SN which are rich in dopaminergic (DA neurons. We identified 13525 up-regulated genes in both cell types of which 3737 (27.6% genes were up-regulated in the hENSC, 4116 (30.4% genes were up-regulated in the human substantia nigra dopaminergic cells, and 5672 (41.93% were significantly up-regulated in both cell population. Careful analysis of the data that emerged using DAVID has permitted us to distinguish several genes and pathways that are involved in dopaminergic (DA differentiation, and to identify the crucial signaling pathways that direct the process of differentiation. The set of genes expressed more highly at hENSC is enriched in molecules known or predicted to be involved in the M phase of the mitotic cell cycle. On the other hand, the genes enriched in SN cells include a different set of functional categories, namely synaptic transmission, central nervous system development, structural constituents of the myelin sheath, the internode region of axons, myelination, cell projection, cell somata, ion transport, and the voltage-gated ion channel complex. Our results were also compared with data from various databases, and between different types of arrays, Agilent versus Illumina. This approach has allowed us to confirm the consistency of our obtained results for a large number of genes that delineate the phenotypical differences of embryonic NSCs, and SN cells.

  10. How illusory is the solitaire illusion? Assessing the degree of misperception of numerosity in adult humans

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    Christian Agrillo

    2016-10-01

    Full Text Available The Solitaire illusion occurs when the spatial arrangement of items influences the subjective estimation of their quantity. Unlike other illusory phenomena frequently reported in humans and often also in non-human animals, evidence of the Solitaire illusion in species other than humans remains weak. However, before concluding that this perceptual bias affects quantity judgments differently in human and non-human animals, further investigations on the strength of the Solitaire illusion is required. To date, no study has assessed the exact misperception of numerosity generated by the Solitaire arrangement, and the possibility exists that the numerical effects generated by the illusion are too subtle to be detected by non-human animals.The present study investigated the strength of this illusion in adult humans. In a relative numerosity task, participants were required to select which array contained more blue items in the presence of two arrays made of identical blue and yellow items. Participants perceived the Solitaire illusion as predicted, overestimating the Solitaire array with centrally clustered blue items as more numerous than the Solitaire array with blue items on the perimeter. Their performance in the presence of the Solitaire array was similar to that observed in control trials with numerical ratios larger than 0.67, suggesting that the illusory array produces a substantial overestimation of the number of blue items in one array relative to the other. This aspect was more directly investigated in a numerosity identification task in which participants were required to estimate the number of blue items when single arrays were presented one at a time. In the presence of the Solitaire array, participants slightly overestimated the number of items when they were centrally located while they underestimated the number of items when those items were located on the perimeter. Items located on the perimeter were perceived to be 76% as numerous

  11. Nicotine alters MicroRNA expression and hinders human adult stem cell regenerative potential.

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    Ng, Tsz Kin; Carballosa, Carlos M; Pelaez, Daniel; Wong, Hoi Kin; Choy, Kwong Wai; Pang, Chi Pui; Cheung, Herman S

    2013-03-01

    Adult stem cells are critical for the healing process in regenerative medicine. However, cigarette smoking inhibits stem cell recruitment to tissues and delays the wound-healing process. This study investigated the effect of nicotine, a major constituent in the cigarette smoke, on the regenerative potentials of human mesenchymal stem cells (MSC) and periodontal ligament-derived stem cells (PDLSC). The cell proliferation of 1.0 μM nicotine-treated MSC and PDLSC was significantly reduced when compared to the untreated control. Moreover, nicotine also retarded the locomotion of these adult stem cells. Furthermore, their osteogenic differentiation capabilities were reduced in the presence of nicotine as evidenced by gene expression (RUNX2, ALPL, BGLAP, COL1A1, and COL1A2), calcium deposition, and alkaline phosphatase activity analyses. In addition, the microRNA (miRNA) profile of nicotine-treated PDLSC was altered; suggesting miRNAs might play an important role in the nicotine effects on stem cells. This study provided the possible mechanistic explanations on stem cell-associated healing delay in cigarette smoking.

  12. Pertussis toxin activates adult and neonatal naive human CD4+ T lymphocytes.

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    Tonon, Sandrine; Badran, Bassam; Benghiat, Fleur Samantha; Goriely, Stanislas; Flamand, Véronique; Willard-Gallo, Karen; Willems, Fabienne; Goldman, Michel; De Wit, Dominique

    2006-07-01

    Pertussis toxin (PTX) is known to be mitogenic for T lymphocytes, but its direct action on naive human T cells has not been specified. Herein, we show that PTX induces the proliferation of purified adult CD45RA(+)CD4(+) T cells independently of its ADP-ribosyltransferase activity. PTX directly induces TNF-alpha and IL-2 mRNA expression, modulates the level of several cell surface receptors and induces Forkhead box p3 (Foxp3) protein accumulation in naive CD4(+) T cells. Addition of autologous dendritic cells was found to be required for the production of high levels of IFN-gamma by PTX-stimulated naive T cells. These effects of PTX occurred in conjunction with activation of NF-kappaB and NFAT transcription factors. Overall, responses of neonatal CD4(+) T cells to PTX were similar to those of adult CD45RA(+)CD4(+) naive T cells except for their blunted CD40 ligand up-regulation. We suggest that the adjuvant properties of PTX during primary cell-mediated immune responses involve a direct action on naive T lymphocytes in addition to activation of antigen-presenting cells.

  13. Morphological variations of a jugular foramen in North Indian human adult skulls

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    Ruchira Sethi

    2011-01-01

    Full Text Available Aims: To assess the size and bridging patterns of jugular foramina of adult human skulls. Materials and Methods: The study was conducted on 56 adult North - Indian skulls procured from Department of Anatomy of Santosh Medical College, Ghaziabad. The jugular foramina were observed by naked eye and with magnifying lens to assess the variations in size and bridging patterns. Results: The jugular foramen was larger on the right side in 53.5% skulls and on the left side in 7.1% skulls. In the remaining skulls (39.4% it was equal on both sides. Complete tripartite division was observed in 10.7% cases. Incomplete division was seen in 7.1% cases on right side and 3.5% cases on the left side. Incomplete division was never observed bilaterally. An additional accessory foramen was observed to be communicating with posterior condylar canal. Conclusion: The variations observed in present study are of immense value to ENT surgeons while performing middle ear surgeries for various jugular foramen tumors. Also, the bridging patterns cause compression to structures passing through this foramen hence accentuating the clinical presentations of Glomus jugulare.

  14. Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells.

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    Yamada, Mitsutoshi; Johannesson, Bjarki; Sagi, Ido; Burnett, Lisa Cole; Kort, Daniel H; Prosser, Robert W; Paull, Daniel; Nestor, Michael W; Freeby, Matthew; Greenberg, Ellen; Goland, Robin S; Leibel, Rudolph L; Solomon, Susan L; Benvenisty, Nissim; Sauer, Mark V; Egli, Dieter

    2014-06-26

    The transfer of somatic cell nuclei into oocytes can give rise to pluripotent stem cells that are consistently equivalent to embryonic stem cells, holding promise for autologous cell replacement therapy. Although methods to induce pluripotent stem cells from somatic cells by transcription factors are widely used in basic research, numerous differences between induced pluripotent stem cells and embryonic stem cells have been reported, potentially affecting their clinical use. Because of the therapeutic potential of diploid embryonic stem-cell lines derived from adult cells of diseased human subjects, we have systematically investigated the parameters affecting efficiency of blastocyst development and stem-cell derivation. Here we show that improvements to the oocyte activation protocol, including the use of both kinase and translation inhibitors, and cell culture in the presence of histone deacetylase inhibitors, promote development to the blastocyst stage. Developmental efficiency varied between oocyte donors, and was inversely related to the number of days of hormonal stimulation required for oocyte maturation, whereas the daily dose of gonadotropin or the total number of metaphase II oocytes retrieved did not affect developmental outcome. Because the use of concentrated Sendai virus for cell fusion induced an increase in intracellular calcium concentration, causing premature oocyte activation, we used diluted Sendai virus in calcium-free medium. Using this modified nuclear transfer protocol, we derived diploid pluripotent stem-cell lines from somatic cells of a newborn and, for the first time, an adult, a female with type 1 diabetes.

  15. Differential Oxidative Stress Induced by Dengue Virus in Monocytes from Human Neonates, Adult and Elderly Individuals

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    Valero, Nereida; Mosquera, Jesús; Añez, Germán; Levy, Alegria; Marcucci, Rafael; de Mon, Melchor Alvarez

    2013-01-01

    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. PMID:24069178

  16. Schistosoma mansoni Sambon, 1907: morphometric differences between adult worms from sympatric rodent and human isolates

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    Neves Renata Heisler

    1998-01-01

    Full Text Available A computer software for image analysis (IMAGE PRO PLUS, MEDIA CYBERNETICS was utilized in male and females adult worms, aiming the morphological characterization of Schistosoma mansoni samples isolated from a slyvatic rodent, Nectomys squamipes, and humans in Sumidouro, Rio de Janeiro, Brazil and recovered from Mus musculus C3H/He. The following characters for males's testicular lobes were analyzed: number, area, density, larger and smaller diameter, longer and shorter axis and perimeter and extension; for females: area, longer and shorter axis, larger and smaller diameter and perimeter of the eggs and spine; oral and ventral suckers area and distance between them in both sex were determined. By the analysis of variance (one way ANOVA significant differences (p<0.05 were observed in all studied characters, except for the density of testicular lobes. Significant differences (p<0.05 were detected for all characters in the female worms. Data ratify that sympatric isolates present phenotypic differences and the adult female characters are useful for the proper identification of S. mansoni isolates.

  17. A STUDY OF NEURONAL PROFILE OF INFERIOR OLIVARY NUCLEAR COMPLEX IN FOETAL AND ADULT HUMAN MEDULLA

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    B.Narasinga Rao

    2013-09-01

    Full Text Available Abstract: Background: ION receives proprioceptive impulses from spino-olivary tract and conveys the fibers to the cerebellum through olivo-cerebellar tract. There is paucity of data in human olivary complex, hence the present study is done. Materials And Methods: 15 adult brains and 25 fetuses of different gestations were perfused with 10% formalin and processed for histological examination. Results: Rounded cells have been seen infiltrating the entire field. at 16 weeks of gestation. Segregation of neurons into principal, medial, and dorsal accessory olivary nuclei at 20 wks gestation. Discussion: Neuron differentiation into oval, round, multipolar types has begun at 40 wks gestation. Neurons in the olivary subdivisions are grouped in separate clusters as per Ramon y Cajal,1909; Scheibel and Scheibel, 1955, Bowman and King, 1973. Multipolar neurons dominated in adult inferior olivary nucleus. Conclusion:The greater development of neurons is a consequence of finer regulation of various movements of hands and finger associated with movement of head and eyes

  18. Early developmental gene enhancers affect subcortical volumes in the adult human brain.

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    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 Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc.

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

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    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.

  20. Fetal and adult hematopoietic stem cells give rise to distinct T cell lineages in humans.

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    Mold, Jeff E; Venkatasubrahmanyam, Shivkumar; Burt, Trevor D; Michaëlsson, Jakob; Rivera, Jose M; Galkina, Sofiya A; Weinberg, Kenneth; Stoddart, Cheryl A; McCune, Joseph M

    2010-12-17

    Although the mammalian immune system is generally thought to develop in a linear fashion, findings in avian and murine species argue instead for the developmentally ordered appearance (or "layering") of distinct hematopoietic stem cells (HSCs) that give rise to distinct lymphocyte lineages at different stages of development. Here we provide evidence of an analogous layered immune system in humans. Our results suggest that fetal and adult T cells are distinct populations that arise from different populations of HSCs that are present at different stages of development. We also provide evidence that the fetal T cell lineage is biased toward immune tolerance. These observations offer a mechanistic explanation for the tolerogenic properties of the developing fetus and for variable degrees of immune responsiveness at birth.

  1. Differentiation of adult human bone marrow mesenchymal stem cells into Schwann-like cells in vitro

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    YANG Li-ye; ZHENG Jia-kun; WANG Chao-yang; LI Wen-yu

    2005-01-01

    Objective: To investigate the differentiative capability of adult human bone marrow mesenchymal stem cells (BMSCs) into Schwann-like cells. Methods: Bone marrows were aspirated from healthy donors and mononuclear cells were separated by Percoll lymphocytes separation liquid (1.073 g/ml) with centrifugation, cells were cultured in DMEM/F12 (1:1) medium containing 10% fetal bovine serum (FBS), 20 ng/ml epidermal growth factor (EGF) and 20 ng/ml basic fibroblast growth factor (bFGF). Cells of passage 1 were identified with immunocytochemistry. Conclusions: Bone marrow contains the stem cells with the ability of differentiating into Schwann-like cells, which may represent an alternative stem cell sources for neural transplantation.

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

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    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.

  3. Human embryonic and fetal mesenchymal stem cells differentiate toward three different cardiac lineages in contrast to their adult counterparts.

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    Ramkisoensing, Arti A; Pijnappels, Daniël A; Askar, Saïd F A; Passier, Robert; Swildens, Jim; Goumans, Marie José; Schutte, Cindy I; de Vries, Antoine A F; Scherjon, Sicco; Mummery, Christine L; Schalij, Martin J; Atsma, Douwe E

    2011-01-01

    Mesenchymal stem cells (MSCs) show unexplained differences in differentiation potential. In this study, differentiation of human (h) MSCs derived from embryonic, fetal and adult sources toward cardiomyocytes, endothelial and smooth muscle cells was investigated. Labeled hMSCs derived from embryonic stem cells (hESC-MSCs), fetal umbilical cord, bone marrow, amniotic membrane and adult bone marrow and adipose tissue were co-cultured with neonatal rat cardiomyocytes (nrCMCs) or cardiac fibroblasts (nrCFBs) for 10 days, and also cultured under angiogenic conditions. Cardiomyogenesis was assessed by human-specific immunocytological analysis, whole-cell current-clamp recordings, human-specific qRT-PCR and optical mapping. After co-culture with nrCMCs, significantly more hESC-MSCs than fetal hMSCs stained positive for α-actinin, whereas adult hMSCs stained negative. Furthermore, functional cardiomyogenic differentiation, based on action potential recordings, was shown to occur, but not in adult hMSCs. Of all sources, hESC-MSCs expressed most cardiac-specific genes. hESC-MSCs and fetal hMSCs contained significantly higher basal levels of connexin43 than adult hMSCs and co-culture with nrCMCs increased expression. After co-culture with nrCFBs, hESC-MSCs and fetal hMSCs did not express α-actinin and connexin43 expression was decreased. Conduction velocity (CV) in co-cultures of nrCMCs and hESC-MSCs was significantly higher than in co-cultures with fetal or adult hMSCs. In angiogenesis bioassays, only hESC-MSCs and fetal hMSCs were able to form capillary-like structures, which stained for smooth muscle and endothelial cell markers.Human embryonic and fetal MSCs differentiate toward three different cardiac lineages, in contrast to adult MSCs. Cardiomyogenesis is determined by stimuli from the cellular microenvironment, where connexin43 may play an important role.

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

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    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.

  5. Neurophysiological basis for neurogenic-mediated articular cartilage anabolism alteration.

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    Gouze-Decaris, E; Philippe, L; Minn, A; Haouzi, P; Gillet, P; Netter, P; Terlain, B

    2001-01-01

    This study was designed to investigate the pathways involved in neurogenic-mediated articular cartilage damage triggered by a nonsystemic distant subcutaneous or intra-articular inflammation. The cartilage damage was assessed 24 h after subcutaneous or intra-articular complete Freund's adjuvant (CFA) injection measuring patellar proteoglycan (PG) synthesis (ex vivo [Na(2)(35)SO(4)] incorporation) in 96 Wistar rats. Unilateral subcutaneous or intra-articular injection of CFA induced significant decrease (25-29%) in PG synthesis in both patellae. Chronic administration of capsaicin (50 mg. kg(-1). day(-1) during 4 days), which blunted the normal response of C fiber stimulation, prevented the bilateral significant decrease in cartilage synthesis. Similarly, intrathecal injection of MK-801 (10 nmol/day during 5 days), which blocked the glutamatergic synaptic transmission at the dorsal horn of signal originating in primary afferent C fibers, eliminated the CFA-induced PG synthesis decrease in both patellae. Chemical sympathectomy, induced by guanethidine (12.5 mg. kg(-1). day(-1) during 6 wk), also prevented PG synthesis alteration. Finally, compression of the spinal cord at the T3-T5 level had a similar protective effect on the reduction of [Na(2)(35)SO(4)] incorporation. It is concluded that the signal that triggers articular cartilage synthesis damage induced by a distant local inflammation 1) is transmitted through the afferent C fibers, 2) makes glutamatergic synaptic connections with the preganglionic neurons of the sympathetic system, and 3) involves spinal and supraspinal pathways.

  6. The Functions of BMP3 in Rabbit Articular Cartilage Repair

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    Zhe Zhang

    2015-10-01

    Full Text Available Bone morphogenetic proteins (BMPs play important roles in skeletal development and repair. Previously, we found fibroblast growth factor 2 (FGF2 induced up-regulation of BMP2, 3, 4 in the process of rabbit articular cartilage repair, which resulted in satisfactory repair effects. As BMP2/4 show a clearly positive effect for cartilage repair, we investigated the functions of BMP3 in rabbit articular cartilage repair. In this paper, we find that BMP3 inhibits the repair of partial-thickness defect of articular cartilage in rabbit by inducing the degradation of extracellular matrix, interfering with the survival of chondrocytes surrounding the defect, and directly inhibiting the expression of BMP2 and BMP4. Meanwhile BMP3 suppress the repair of full-thickness cartilage defect by destroying the subchondral bone through modulating the proliferation and differentiation of bone marrow stem cells (BMSCs, and directly increasing the expression of BMP4. Although BMP3 has different functions in the repair of partial and full-thickness defects of articular cartilage in rabbit, the regulation of BMP expression is involved in both of them. Together with our previous findings, we suggest the regulation of the BMP signaling pathway by BMP3 is essential in articular cartilage repair.

  7. The Effects of Vitamin D3 on Proliferation and Apoptosis of Primary Cultured Chondrocytes from Human Articular Cartilage%活性维生素D3对体外原代培养人骨关节炎软骨细胞的影响

    Institute of Scientific and Technical Information of China (English)

    张良; 郭艾

    2012-01-01

    Objective To obtain articular chondrocyte from patients with osteoarthritis by primary culture,to explore the relationship between different concentrate [1, 25-(OH)2D3]and proliferation, apoptosis of chondrocytes. Methods Human articular chondrocytes were obtained by modified digestive method with enzyme in vitro and inden-tified by alkaline phosphatase (AKP) staining. OA Chondrocytes were cultured in medium with different concentrate [1,25-(OH)2D3]. MMT method was used to assay proliferation of chondrocytes. Optical density(OD) at 490nm was determined by ELISA. Flow cytometry was used to assay the apoptosis ratio at different time point. Results 10~5 u-mol/L[l ,25-(OH)2D3]can promote the proliferation of chondrocytes obviously,and the proper react time point is 48 hour(P<0. 01). At the same time 10-5 umol/L[1, 25-(OH)2D3]can inhibit the apoptosis ratio obviously at 48 hour time point. Conclusion To promote the proliferation and inhibit the apoptosis of OA chondrocytes in vitro,the better concentration of [1,25-(OH)2D3]is 1×10-5 umol/L. 48 hour after[1,25-(OH)2D3]added is the best time for the experiment objective.%目的 探讨不同浓度的1α,25二羟基维生素D3[1,25 -(OH)2D3]对体外培养的人骨关节炎患者关节软骨细胞的增殖及凋亡率的影响.方法 酶二步消化法体外分离培养人软骨细胞,以碱性磷酸酶染色法鉴定.加入不同剂量的[1,25 (OH)2D3],通过噻唑蓝比色试验检测细胞存活和增殖情况,以及用流式细胞仪检测软骨细胞在不同药物浓度、不同作用时间的凋亡率.结论 [1,25 (OH)2D3]作用于入骨关节炎软骨细胞的最佳作用浓度为1×10-5umol/L,最佳作用时间点为48h.高浓度的[1,25-(OH)2D3]能明显促进细胞坏死,极低浓度的[1,25 -(OH)2D3]对软骨细胞增殖、凋亡无明显影响.

  8. Oct4 expression in adult human stem cells: evidence in support of the stem cell theory of carcinogenesis.

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    Tai, Mei-Hui; Chang, Chia-Cheng; Kiupel, Matti; Webster, Joshua D; Olson, L Karl; Trosko, James E

    2005-02-01

    The Oct3/4 gene, a POU family transcription factor, has been noted as being specifically expressed in embryonic stem cells and in tumor cells but not in cells of differentiated tissues. With the ability to isolate adult human stem cells it became possible to test for the expression of Oct3/4 gene in adult stem cells and to test the stem cell theory of carcinogenesis. Using antibodies and PCR primers we tested human breast, liver, pancreas, kidney, mesenchyme and gastric stem cells, the cancer cell lines HeLa and MCF-7 and human, dog and rat tumors for Oct4 expression. The results indicate that adult human stem cells, immortalized non-tumorigenic cells and tumor cells and cell lines, but not differentiated cells, express Oct4. Oct4 is expressed in a few cells found in the basal layer of human skin epidermis. The data demonstrate that adult stem cells maintain expression of Oct4, consistent with the stem cell hypothesis of carcinogenesis.

  9. Empirical evaluation of the inter-relationship of articular elements involved in the pathoanatomy of knee osteoarthritis using Magnetic Resonance Imaging

    Directory of Open Access Journals (Sweden)

    Yoshioka Hiroshi

    2009-10-01

    Full Text Available Abstract Background 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. Methods 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. Results 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 Conclusion 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 findings to clinically relevant outcomes such as pain and function.

  10. 24R,25-Dihydroxyvitamin D3 Protects against Articular Cartilage Damage following Anterior Cruciate Ligament Transection in Male Rats

    Science.gov (United States)

    Boyan, Barbara D.; Hyzy, Sharon L.; Pan, Qingfen; Scott, Kayla M.; Coutts, Richard D.; Healey, Robert; Schwartz, Zvi

    2016-01-01

    Osteoarthritis (OA) in humans is associated with low circulating 25-hydroxyvitamin D3 [25(OH)D3]. In vitamin D replete rats, radiolabeled 24R,25-dihydroxyvitamin D3 [24R,25(OH)2D3] accumulates in articular cartilage following injection of [3H]-25(OH)D3. Previously, we showed that 24R,25(OH)2D3 blocks chondrocyte apoptosis via phospholipase D and p53, suggesting a role for 24R,25(OH)2D3 in maintaining cartilage health. We examined the ability of 24R,25(OH)2D3 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(OH)2D3 or 1α,25(OH)2D3. 24R,25(OH)2D3 but not 1α,25(OH)2D3 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(OH)2D3 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(OH)2D3 had less articular cartilage damage and levels of inflammatory mediators. These results indicate that 24R,25(OH)2D3 protects against OA, and suggest that it may be a therapeutic approach for preventing trauma-induced osteoarthritis. PMID:27575371

  11. REGENERATION OF ARTICULAR CARTILAGE UNDER THE IMPLANTATION OF BONE MATRIX

    Directory of Open Access Journals (Sweden)

    Yuri M. Iryanov, Nikolay A. Kiryanov, Olga V. Dyuriagina , Tatiana Yu. Karaseva, Evgenii A. Karasev

    2015-07-01

    Full Text Available Background: The damage or loss of articular cartilage is costly medical problem. The purpose of this work – morphological analysis of reparative chondrogenesis when implanted in the area of the knee joint cartilage of granulated mineralized bone matrix. Material and Methods: The characteristic features of the knee cartilage regeneration studied experimentally in pubertal Wistar rats after modeling a marginal perforated defect and implantation of granulated mineralized bone matrix obtained according to original technology without heat and demineralizing processing into the injury zone. Results: This biomaterial established to have pronounced chondro- and osteoinductive properties, and to provide prolonged activation of reparative process, accelerated organotypical remodeling and restoration of the articular cartilage injured. Conclusion: The data obtained demonstrate the efficacy of МВМ in clinical practice for the treatment of diseases and injuries of the articular cartilage.

  12. 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.

  13. Evidence of progenitor cells of glandular and myoepithelial cell lineages in the human adult female breast epithelium: a new progenitor (adult stem) cell concept.

    Science.gov (United States)

    Boecker, Werner; Buerger, Horst

    2003-10-01

    Although experimental data clearly confirm the existence of self-renewing mammary stem cells, the characteristics of such progenitor cells have never been satisfactorily defined. Using a double immunofluorescence technique for simultaneous detection of the basal cytokeratin 5, the glandular cytokeratins 8/18 and the myoepithelial differentiation marker smooth muscle actin (SMA), we were able to demonstrate the presence of CK5+ cells in human adult breast epithelium. These cells have the potential to differentiate to either glandular (CK8/18+) or myoepithelial cells (SMA+) through intermediary cells (CK5+ and CK8/18+ or SMA+). We therefore proceeded on the assumption that the CK5+ cells are phenotypically and behaviourally progenitor (committed adult stem) cells of human breast epithelium. Furthermore, we furnish evidence that most of these progenitor cells are located in the luminal epithelium of the ductal lobular tree. Based on data obtained in extensive analyses of proliferative breast disease lesions, we have come to regard usual ductal hyperplasia as a progenitor cell-derived lesion, whereas most breast cancers seem to evolve from differentiated glandular cells. Double immunofluorescence experiments provide a new tool to characterize phenotypically progenitor (adult stem) cells and their progenies. This model has been shown to be of great value for a better understanding not only of normal tissue regeneration but also of proliferative breast disease. Furthermore, this model provides a new tool for unravelling further the regulatory mechanisms that govern normal and pathological cell growth.

  14. The Inhibitory Effect of Salmon Calcitonin on Tri-Iodothyronine Induction of Early Hypertrophy in Articular Cartilage

    OpenAIRE

    Pingping Chen-An; Kim Vietz Andreassen; Kim Henriksen; Yadong Li; Morten Asser Karsdal; Anne-Christine Bay-Jensen

    2012-01-01

    OBJECTIVE: Salmon calcitonin has chondroprotective effect both in vitro and in vivo, and is therefore being tested as a candidate drug for cartilage degenerative diseases. Recent studies have indicated that different chondrocyte phenotypes may express the calcitonin receptor (CTR) differentially. We tested for the presence of the CTR in chondrocytes from tri-iodothyronin (T3)-induced bovine articular cartilage explants. Moreover, investigated the effects of human and salmon calcitonin on the ...

  15. Tissue-specific mutation accumulation in human adult stem cells during life

    Science.gov (United States)

    Blokzijl, Francis; de Ligt, Joep; Jager, Myrthe; Sasselli, Valentina; Roerink, Sophie; Sasaki, Nobuo; Huch, Meritxell; Boymans, Sander; Kuijk, Ewart; Prins, Pjotr; Nijman, Isaac J.; Martincorena, Inigo; Mokry, Michal; Wiegerinck, Caroline L.; Middendorp, Sabine; Sato, Toshiro; Schwank, Gerald; Nieuwenhuis, Edward E. S.; Verstegen, Monique M. A.; van der Laan, Luc J. W.; de Jonge, Jeroen; Ijzermans, Jan N. M.; Vries, Robert G.; van de Wetering, Marc; Stratton, Michael R.; Clevers, Hans; Cuppen, Edwin; van Boxtel, Ruben

    2016-10-01

    The gradual accumulation of genetic mutations in human adult stem cells (ASCs) during life is associated with various age-related diseases, including cancer. Extreme variation in cancer risk across tissues was recently proposed to depend on the lifetime number of ASC divisions, owing to unavoidable random mutations that arise during DNA replication. However, the rates and patterns of mutations in normal ASCs remain unknown. Here we determine genome-wide mutation patterns in ASCs of the small intestine, colon and liver of human donors with ages ranging from 3 to 87 years by sequencing clonal organoid cultures derived from primary multipotent cells. Our results show that mutations accumulate steadily over time in all of the assessed tissue types, at a rate of approximately 40 novel mutations per year, despite the large variation in cancer incidence among these tissues. Liver ASCs, however, have different mutation spectra compared to those of the colon and small intestine. Mutational signature analysis reveals that this difference can be attributed to spontaneous deamination of methylated cytosine residues in the colon and small intestine, probably reflecting their high ASC division rate. In liver, a signature with an as-yet-unknown underlying mechanism is predominant. Mutation spectra of driver genes in cancer show high similarity to the tissue-specific ASC mutation spectra, suggesting that intrinsic mutational processes in ASCs can initiate tumorigenesis. Notably, the inter-individual variation in mutation rate and spectra are low, suggesting tissue-specific activity of common mutational processes throughout life.

  16. Large-Scale Identification of Coregulated Enhancer Networks in the Adult Human Brain

    Directory of Open Access Journals (Sweden)

    Marit W. Vermunt

    2014-10-01

    Full Text Available Understanding the complexity of the human brain and its functional diversity remain a major challenge. Distinct anatomical regions are involved in an array of processes, including organismal homeostasis, cognitive functions, and susceptibility to neurological pathologies, many of which define our species. Distal enhancers have emerged as key regulatory elements that acquire histone modifications in a cell- and species-specific manner, thus enforcing specific gene expression programs. Here, we survey the epigenomic landscape of promoters and cis-regulatory elements in 136 regions of the adult human brain. We identify a total of 83,553 promoter-distal H3K27ac-enriched regions showing global characteristics of brain enhancers. We use coregulation of enhancer elements across many distinct regions of the brain to uncover functionally distinct networks at high resolution and link these networks to specific neuroglial functions. Furthermore, we use these data to understand the relevance of noncoding genomic variations previously linked to Parkinson’s disease incidence.

  17. 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.

  18. 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

  19. 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.

  20. Effect of the N-terminal residues on the quaternary dynamics of human adult hemoglobin

    Science.gov (United States)

    Chang, Shanyan; Mizuno, Misao; Ishikawa, Haruto; Mizutani, Yasuhisa

    2016-05-01

    The protein dynamics of human hemoglobin following ligand photolysis was studied by time-resolved resonance Raman spectroscopy. The time-resolved spectra of two kinds of recombinant hemoglobin expressed in Escherichia coli, normal recombinant hemoglobin and the α(V1M)/β(V1M) double mutant, were compared with those of human adult hemoglobin (HbA) purified from blood. A frequency shift of the iron-histidine stretching [ν(Fe-His)] band was observed in the time-resolved spectra of all three hemoglobin samples, indicative of tertiary and quaternary changes in the protein following photolysis. The spectral changes of the α(V1M)/β(V1M) double mutant were distinct from those of HbA in the tens of microseconds region, whereas the spectral changes of normal recombinant hemoglobin were similar to those of HbA isolated from blood. These results demonstrated that a structural change in the N-termini is involved in the second step of the quaternary structure change of hemoglobin. We discuss the implications of these results for understanding the allosteric pathway of HbA.

  1. Identification of candidate antigens from adult stages of Toxocara canis for the serodiagnosis of human toxocariasis

    Directory of Open Access Journals (Sweden)

    Patrícia Longuinhos Peixoto

    2011-03-01

    Full Text Available In the present work, we identified adult Toxocara canis antigens through sodium dodecyl sulfate-polyacrylamide gel electrophoresis for potential use in human toxocariasis immunodiagnosis. The sensitivity and specificity of several semi-purified antigens, as well as their cross-reactivity with other parasitic infections, were assessed by IgM and IgG-enzime linked immunosorbent assay. Whilst we found that the crude extract of the parasite presented limited sensitivity, specificity and high cross-reactivity against other parasites, we identified 42, 58, 68 and 97-kDa semi-purified antigens as the most promising candidates for immunodiagnosis. Moreover, the 58 and 68-kDa antigens presented the lowest IgM cross-reactivity. When tested as a combination, a mixture of the 58 and 68-kDa antigens presented 100% sensitivity and specificity, as well as minor cross-reactivity. Although the combination of the 42, 58, 68 and 97-kDa antigens presented 100% sensitivity at a dilution of 1:40, the low specificity and high cross-reactivity observed suggested a limited use for diagnostic purposes. Our data suggested that the 58 and 68-kDa antigens might be most suitable for the immunodiagnosis of human toxocariasis.

  2. Redifferentiation of adult human β cells expanded in vitro by inhibition of the WNT pathway.

    Directory of Open Access Journals (Sweden)

    Ayelet Lenz

    Full Text Available In vitro expansion of adult human islet β cells is an attractive solution for the shortage of tissue for cell replacement therapy of type 1 diabetes. Using a lineage tracing approach we have demonstrated that β-cell-derived (BCD cells rapidly dedifferentiate in culture and can proliferate for up to 16 population doublings. Dedifferentiation is associated with changes resembling epithelial-mesenchymal transition (EMT. The WNT pathway has been shown to induce EMT and plays key roles in regulating replication and differentiation in many cell types. Here we show that BCD cell dedifferentiation is associated with β-catenin translocation into the nucleus and activation of the WNT pathway. Inhibition of β-catenin expression in expanded BCD cells using short hairpin RNA resulted in growth arrest, mesenchymal-epithelial transition, and redifferentiation, as judged by activation of β-cell gene expression. Furthermore, inhibition of β-catenin expression synergized with redifferentiation induced by a combination of soluble factors, as judged by an increase in the number of C-peptide-positive cells. Simultaneous inhibition of the WNT and NOTCH pathways also resulted in a synergistic effect on redifferentiation. These findings, which were reproducible in cells derived from multiple human donors, suggest that inhibition of the WNT pathway may contribute to a therapeutically applicable way for generation of functional insulin-producing cells following ex-vivo expansion.

  3. Expression of Bcl-2 in adult human brain regions with special reference to neurodegenerative disorders.

    Science.gov (United States)

    Vyas, S; Javoy-Agid, F; Herrero, M T; Strada, O; Boissiere, F; Hibner, U; Agid, Y

    1997-07-01

    The expression of the protooncogene bcl-2, an inhibitor of apoptosis in various cells, was examined in the adult human brain. Several experimental criteria were used to verify its presence; mRNA was analyzed by northern blot with parallel experiments in mouse tissues, by RNase protection, and by in situ hybridization histochemistry. Bcl-2 protein was detected by western blot analysis and immunohistochemistry. Two bcl-2 mRNA species were identified in the human brain. The pattern of distribution of bcl-2 mRNA at the cellular level showed labeling in neurons but not glia. The in situ hybridization signal was stronger in the pyramidal neurons of the cerebral cortex and in the cholinergic neurons of the nucleus basalis of Meynert than in the Purkinje neurons of the cerebellum. Both melanized and nonmelanized neurons were labeled in the substantia nigra. In the striatum, bcl-2 mRNA was detected in some but not all neurons. In the regions examined for Bcl-2 protein, the expression pattern correlated with the mRNA results. In patients with Alzheimer's and Parkinson's diseases, quantification of bcl-2 mRNA in the nucleus basalis of Meynert and substantia nigra, respectively, showed that the expression was unaltered compared with controls, raising the possibility that the expression of other components of apoptosis is modulated.

  4. Human prefrontal cortex phospholipids containing docosahexaenoic acid increase during normal adult aging, whereas those containing arachidonic acid decrease.

    Science.gov (United States)

    Norris, Sarah E; Friedrich, Michael G; Mitchell, Todd W; Truscott, Roger J W; Else, Paul L

    2015-04-01

    Membrane phospholipids make up a substantial portion of the human brain, and changes in their amount and composition are thought to play a role in the pathogenesis of age-related neurodegenerative disease. Nevertheless, little is known about the changes that phospholipids undergo during normal adult aging. This study examined changes in phospholipid composition in the mitochondrial and microsomal membranes of human dorsolateral prefrontal cortex over the adult life span. The largest age-related changes were an increase in the abundance of both mitochondrial and microsomal phosphatidylserine 18:0_22:6 by approximately one-third from age 20 to 100 years and a 25% decrease in mitochondrial phosphatidylethanolamine 18:0_20:4. Generally, increases were seen with age in phospholipids containing docosahexaenoic acid across both membrane fractions, whereas phospholipids containing either arachidonic or adrenic acid decreased with age. These findings suggest a gradual change in membrane lipid composition over the adult life span.

  5. Adult growth hormone (GH)-deficient patients demonstrate heterogeneity between childhood onset and adult onset before and during human GH treatment. Adult Growth Hormone Deficiency Study Group

    DEFF Research Database (Denmark)

    Attanasio, A F; Lamberts, S W; Matranga, A M

    1997-01-01

    -deficient adult patients have been compared. The first 6 months comprised randomized, double-blind treatment with GH or placebo, then all patients were GH-treated for a further 12 months. At baseline the height, body weight, body mass index, lean body mass, and waist/hip ratio of AO patients were significantly (P...

  6. Canine articular cartilage regeneration using mesenchymal stem cells seeded on platelet rich fibrin

    Science.gov (United States)

    Shams Asenjan, K.; Dehdilani, N.; Parsa, H.

    2017-01-01

    Objectives Mesenchymal stem cells have the ability to differentiate into various cell types, and thus have emerged as promising alternatives to chondrocytes in cell-based cartilage repair methods. The aim of this experimental study was to investigate the effect of bone marrow derived mesenchymal stem cells combined with platelet rich fibrin on osteochondral defect repair and articular cartilage regeneration in a canine model. Methods Osteochondral defects were created on the medial femoral condyles of 12 adult male mixed breed dogs. They were either treated with stem cells seeded on platelet rich fibrin or left empty. Macroscopic and histological evaluation of the repair tissue was conducted after four, 16 and 24 weeks using the International Cartilage Repair Society macroscopic and the O’Driscoll histological grading systems. Results were reported as mean and standard deviation (sd) and compared at different time points between the two groups using the Mann-Whitney U test, with a value regeneration. It is postulated that platelet rich fibrin creates a suitable environment for proliferation and differentiation of stem cells by releasing endogenous growth factors resulting in creation of a hyaline-like reparative tissue. Cite this article: D. Kazemi, K. Shams Asenjan, N. Dehdilani, H. Parsa. Canine articular cartilage regeneration using mesenchymal stem cells seeded on platelet rich fibrin: Macroscopic and histological assessments. Bone Joint Res 2017;6:98–107. DOI: 10.1302/2046-3758.62.BJR-2016-0188.R1. PMID:28235767

  7. Intra-articular block for knee arthroscopy: a study on 41 patients

    Directory of Open Access Journals (Sweden)

    Emami A

    2009-07-01

    Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: During recent three decades, parallel to the improvement of arthroscopic techniques, intra-articular block by direct injection of anesthetics into the joint has been used in knee arthroscopy. In this study the efficacy of intra- articular block by complex of bupivacaine, lidocaine and adrenaline in knee arthroscopy has been assessed. "n"nMethods: Forty one healthy adults (age range: 18-55 years with knee problems selected for diagnostic arthroscopy. Anesthesia was induced by direct injection of 10ml 2% bupivacaine, 10ml 0.5% lidocaine plus 1/100000 adrenaline into the knee joint.  Duration of operation and volume of serum used for irrigation during the procedure; pain and analgesics requirement, during and after arthroscopy; VAS (Visual Analogue Scale score, at time of discharge from recovery and also patient's and surgeon's satisfaction were assessed. "n"n Results: Sixty eight percent and 29% of cases reported mild and moderate degree of pain perception during arthroscopy, respectively, and only one case for which general anesthesia was performed, reported severe pain. VAS mean was 2.78. Seventy eight percent of cases and the surgeon in 80% of procedures had excellent or good satisfaction with

  8. GH safety workshop position paper: A critical appraisal of recombinant human GH therapy in children and adults

    Science.gov (United States)

    Recombinant human Growth Hormone (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, t...

  9. 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.

  10. El concepto de contacto articular alternativo de la rodilla

    OpenAIRE

    1994-01-01

    La observación radioscópica de la interlínea articular de rodillas de cadáveres sin anomalías anatómicas durante movimientos de abducción y adducción, realizada en estudios previos del autor, permitió apreciar la aparición de pérdida de contacto entre las superficies articulares mediales o laterales respectivamente. El presente artículo tuvo como objetivo rememorar dichos estudios y documentar las apreciaciones visuales mediante el análisis de neumoartrografías seriada...

  11. Serum-free media for articular chondrocytes in vitro expansion

    Institute of Scientific and Technical Information of China (English)

    SHAO Xin-xin; Neil A.Duncan; LIN Lin; FU Xin; ZHANG Ji-ying; YU Chang-long

    2013-01-01

    Background In vitro chondrocyte expansion is a major challenge in cell-based therapy for human articular cartilage repair.Classical culture conditions usually use animal serum as a medium supplement,which raises a number of undesirable questions.In the present study,two kinds of defined,serum-free media were developed to expand chondrocytes in monolayer culture for the purpose of cartilage tissue engineering.Methods Bovine chondrocytes were expanded in serum-free media supplemented with fibroblast growth factor-2 and platelet-derived growth factor or fibroblast growth factor-2 and insulin-like growth factor.Expansion culture in a conventional 10% fetal bovine serum (FBS) medium served as control.Fibronectin coating was used to help cell adhesion in serum-free medium.Next,in vitro three-dimensional pellet culture was used to evaluate the chondrocyte capacity.Cell pellets were expanded in different media to re-express the differentiated phenotype (re-differentiation) and to form cartilaginous tissue.The pellets were assessed by glycosaminoglycans contents,collagen II,collagen I and collagen X immunohistological staining.Results Chondrocytes cultured in serum-free media showed no proliferation difference than cells grown with 10% FBS medium.In addition,chondrocytes expanded in both serum-free media expressed more differentiated phenotypes at the end of monolayer culture,as indicated by higher gene expression ratios of collagen type Ⅱ to collagen type Ⅰ.Pellets derived from chondrocytes cultured in both serum-free media displayed comparable chondrogenic capacities to pellets from cells expanded in 10% FBS medium.Conclusion These findings provide alternative culture approaches for chondrocytes in vitro expansion,which may benefit the clinical use of autologous chondrocytes implantation.

  12. Suppression of adverse angiogenesis in an albumin-based hydrogel for articular cartilage and intervertebral disc regeneration

    Directory of Open Access Journals (Sweden)

    B Scholz

    2010-07-01

    Full Text Available An injectable polyethylene glycol-crosslinked albumin gel (AG supplemented with hyaluronic acid as a matrix for autologous chondrocyte implantation was evaluated with regard to its impact on angiogenesis. Healthy articular cartilage and intervertebral discs (IVD are devoid of blood vessels, whereas pathological blood vessel formation augments degeneration of both theses tissues. In contrast to human endothelial cells, primary human articular chondrocytes encapsulated in the AG retained their viability. Endothelial cells did not adhere to the gel surface to a significant extent nor did they proliferate in vitro. The AG did not release any diffusible toxic components. Contrary to MatrigelTM employed as positive control, the AG prevented endothelial chemoinvasion in Transwell filter assays even in the presence of a chemotactic gradient of vascular endothelial growth factor. In ovo, the AG exhibited a barrier function for blood vessels of the chick chorioallantoic membrane. Subcutaneous implantation of human IVD chondrocytes enclosed in the albumin gel into immunodeficient mice revealed a complete lack of angiogenesis inside the gel after two weeks. At the same time, the IVD chondrocytes within the gel remained vital and displayed a characteristic gene expression pattern as judged from aggrecan, collagen type I and type II mRNA levels. In summary, aiming at articular cartilage and IVD regeneration the albumin gel promises to be a beneficial implant matrix for chondrocytes simultaneously exhibiting non-permissive properties for adverse endothelial cells.

  13. Development of human white matter fiber pathways: From newborn to adult ages.

    Science.gov (United States)

    Cohen, Andrew H; Wang, Rongpin; Wilkinson, Molly; MacDonald, Patrick; Lim, Ashley R; Takahashi, Emi

    2016-05-01

    Major long-range white matter pathways (cingulum, fornix, uncinate fasciculus [UF], inferior fronto-occipital fasciculus [IFOF], inferior longitudinal fasciculus [ILF], thalamocortical [TC], and corpus callosal [CC] pathways) were identified in eighty-three healthy humans ranging from newborn to adult ages. We tracked developmental changes using high-angular resolution diffusion MR tractography. Fractional anisotropy (FA), apparent diffusion coefficient, number, length, and volume were measured in pathways in each subject. Newborns had fewer, and more sparse, pathways than those of the older subjects. FA, number, length, and volume of pathways gradually increased with age and reached a plateau between 3 and 5 years of age. Data were further analyzed by normalizing with mean adult values as well as with each subject's whole brain values. Comparing subjects of 3 years old and under to those over 3 years old, the studied pathways showed differential growth patterns. The CC, bilateral cingulum, bilateral TC, and the left IFOF pathways showed significant growth both in volume and length, while the bilateral fornix, bilateral ILF and bilateral UF showed significant growth only in volume. The TC and CC took similar growth patterns with the whole brain. FA values of the cingulum and IFOF, and the length of ILF showed leftward asymmetry. The fornix, ILF and UF occupied decreased space compared to the whole brain during development with higher FA values, likely corresponding to extensive maturation of the pathways compared to the mean whole brain maturation. We believe that the outcome of this study will provide an important database for future reference.

  14. Clonal analysis of the differentiation potential of human adipose-derived adult stem cells.

    Science.gov (United States)

    Guilak, Farshid; Lott, Kristen E; Awad, Hani A; Cao, Qiongfang; Hicok, Kevin C; Fermor, Beverley; Gimble, Jeffrey M

    2006-01-01

    Pools of human adipose-derived adult stem (hADAS) cells can exhibit multiple differentiated phenotypes under appropriate in vitro culture conditions. Because adipose tissue is abundant and easily accessible, hADAS cells offer a promising source of cells for tissue engineering and other cell-based therapies. However, it is unclear whether individual hADAS cells can give rise to multiple differentiated phenotypes or whether each phenotype arises from a subset of committed progenitor cells that exists within a heterogeneous population. The goal of this study was to test the hypothesis that single hADAS are multipotent at a clonal level. hADAS cells were isolated from liposuction waste, and ring cloning was performed to select cells derived from a single progenitor cell. Forty-five clones were expanded through four passages and then induced for adipogenesis, osteogenesis, chondrogenesis, and neurogenesis using lineage-specific differentiation media. Quantitative differentiation criteria for each lineage were determined using histological and biochemical analyses. Eighty one percent of the hADAS cell clones differentiated into at least one of the lineages. In addition, 52% of the hADAS cell clones differentiated into two or more of the lineages. More clones expressed phenotypes of osteoblasts (48%), chondrocytes (43%), and neuron-like cells (52%) than of adipocytes (12%), possibly due to the loss of adipogenic ability after repeated subcultures. The findings are consistent with the hypothesis that hADAS cells are a type of multipotent adult stem cell and not solely a mixed population of unipotent progenitor cells. However, it is important to exercise caution in interpreting these results until they are validated using functional in vivo assays.

  15. Extensive epigenetic reprogramming in human somatic tissues between fetus and adult

    Directory of Open Access Journals (Sweden)

    Yuen Ryan KC

    2011-05-01

    Full Text Available Abstract Background Development of human tissue is influenced by a combination of intrinsic biological signals and extrinsic environmental stimuli, both of which are mediated by epigenetic regulation, including DNA methylation. However, little is currently known of the normal acquisition or loss of epigenetic markers during fetal and postnatal development. Results The DNA methylation status of over 1000 CpGs located in the regulatory regions of nearly 800 genes was evaluated in five somatic tissues (brain, kidney, lung, muscle and skin from eight normal second-trimester fetuses. Tissue-specific differentially methylated regions (tDMRs were identified in 195 such loci. However, comparison with corresponding data from trisomic fetuses (five trisomy 21 and four trisomy 18 revealed relatively few DNA methylation differences associated with trisomy, despite such conditions having a profound effect on development. Of interest, only 17% of the identified fetal tDMRs were found to maintain this same tissue-specific DNA methylation in adult tissues. Furthermore, 10% of the sites analyzed, including sites associated with imprinted genes, had a DNA methylation difference of >40% between fetus and adult. This plasticity of DNA methylation over development was further confirmed by comparison with similar data from embryonic stem cells, with the most altered methylation levels being linked to domains with bivalent histone modifications. Conclusions Most fetal tDMRs seem to reflect transient DNA methylation changes during development rather than permanent epigenetic signatures. The extensive tissue-specific and developmental-stage specific nature of DNA methylation will need to be elucidated to identify abnormal patterns of DNA methylation associated with abnormal development or disease.

  16. A comparison of epithelial and neural properties in progenitor cells derived from the adult human ciliary body and brain.

    Science.gov (United States)

    Moe, Morten C; Kolberg, Rebecca S; Sandberg, Cecilie; Vik-Mo, Einar; Olstorn, Havard; Varghese, Mercy; Langmoen, Iver A; Nicolaissen, Bjørn

    2009-01-01

    Cells isolated from the ciliary body (CB) of the adult human eye possess properties of retinal stem/progenitor cells and can be propagated as spheres in culture. As these cells are isolated from a non-neural epithelium which has neuroepithelial origin, they may have both epithelial and neural lineages. Since it is the properties of neural progenitor cells that are sought after in a future scenario of autotransplantation, we wanted to directly compare human CB spheres with neurospheres derived from the human subventricular zone (SVZ), which is the best characterized neural stem cell niche in the CNS of adults. The CB epithelium was dissected from donor eyes (n = 8). Biopsies from the ventricular wall were harvested during neurosurgery due to epilepsy (n = 7). CB and SVZ tissue were also isolated from Brown Norwegian rats. Dissociated single cells were cultivated in a sphere-promoting medium and passaged every 10-30 days. Fixed spheres were studied by immunohistochemistry, quantitative RT-PCR and scanning/transmission electron microscopy. We found that both CB and SVZ spheres contained a mixed population of cells embedded in extracellular matrix. CB spheres, in contrast to SVZ neurospheres, contained pigmented cells with epithelial morphology that stained for cytokeratins (3/12 + 19), were connected through desmosomes and tight-junctions and produced PEDF. Markers of neural progenitors (nestin, Sox-2, GFAP) were significantly lower expressed in human CB compared to SVZ spheres, and nestin positive cells in the CB spheres also contained pigment. There was higher expression of EGF and TGF-beta receptors in human CB spheres, and a comparative greater activation of the canonical Wnt pathway. These results indicate that adult human CB spheres contain progenitor cells with epithelial properties and limited expression of neural progenitor markers compared to CNS neurospheres. Further studies mapping the regulation between epithelial and neural properties in the adult human

  17. Severe Community-Acquired Pneumonia Caused by Human Adenovirus in Immunocompetent Adults: A Multicenter Case Series.

    Directory of Open Access Journals (Sweden)

    Dingyu Tan

    Full Text Available Severe community-acquired pneumonia (CAP caused by human adenovirus (HAdV, especially HAdV type 55 (HAdV-55 in immunocompetent adults has raised increasing concerns. Clinical knowledge of severe CAP and acute respiratory distress syndrome induced by HAdV-55 is still limited, though the pathogen has been fully characterized by whole-genome sequencing.We conducted a multicentre retrospective review of all consecutive patients with severe CAP caused by HAdV in immunocompetent adults admitted to the Emergency Department Intensive Care Unit of two hospitals in Northern China between February 2012 and April 2014. Clinical, laboratory, radiological characteristics, treatments and outcomes of these patients were collected and analyzed.A total of 15 consecutive severe CAP patients with laboratory-confirmed adenovirus infections were included. The median age was 30 years and all cases were identified during the winter and spring seasons. HAdV-55 was the most frequently (11/15 detected HAdV type. Persistent high fever, cough and rapid progression of dyspnea were typically reported in these patients. Significantly increased pneumonia severity index (PSI, respiratory rate, and lower PaO2/FiO2, hypersensitive CRP were reported in non-survivors compared to survivors (P = 0.013, 0.022, 0.019 and 0.026, respectively. The rapid development of bilateral consolidations within 10 days after illness onset were the most common radiographic finding, usually accompanied by adjacent ground glass opacities and pleural effusions. Total mortality was 26.7% in this study. Corticosteroids were prescribed to 14 patients in this report, but the utilization rate between survivors and non-survivors was not significant.HAdV and the HAdV-55 sub-type play an important role among viral pneumonia pathogens in hospitalized immunocompetent adults in Northern China. HAdV should be tested in severe CAP patients with negative bacterial cultures and a lack of response to antibiotic

  18. [Morphology of the ganglion cervicale superius in human fetuses and an adult].

    Science.gov (United States)

    Hara, I; Tanuma, K; Suzuki, K

    1993-10-01

    Morphology of the ganglion cervicale superius (GCS) was studied on 16 sides of 10 human fetuses and the 2 sides of an adult cadaver with a binocular stereomicroscope. The obtained results were as follows. GCS is fusiform on 8 sides, takes the form of an eggplant on 3 sides, and is weakly constricted on 7 sides. The GCS was symmetrical in 2 cases. The GCS lay slightly above the first cervical vertebra and extended downward to the superior half of the second cervical vertebra on 11 sides of fetuses. The level in the adult is lower than in the fetuses by one vertebra. The nervus caroticus internus (CI), originating from the superior pole of the GCS as a cephalic prolongation, comprises one bundle on 14 sides, and splits into 2 bundles in the original position on 4 sides. The Nn. carotici externi (CE) arise from the medial part of the superior half of the GCS with several roots (the average number of roots: 3.4) on 17 sides. The CE communicates with the Rami pharyngei of the N. vagus and the N. laryngeus superior. The Rr. laryngopharyngei arise from CE on many sides. The N. jugularis originates from the laterosuperior side of GCS with one to three branches. On a few sides, the N. jugularis communicates with the N. vagus and the N. hypoglossus. The communicating branch between the Ggl. inferius of the N. vagus and the GCS was observed in all cases. The communicating branch between the R. ventralis of the Nn. cervicales and GCS is found in all sides, and the lower limit of the branch is at the ansa from C3 to C4. The Rr. laryngopharyngei (RL) arise from the medial part of the GCS with several branches near the CE, or it may arise from the CE or from both the GCS and the CE, and join with the N. laryngeus superior (laryngeal branch of RL:RL1), the Plexus pharyngeus (pharyngeal branch of RL:RL2) and CE (RL1 and RL2). It is found in a few sides that RL directly extends to the pharyngeal and laryngeal portions. The N. cardiacus cervicalis superior (CS), which originates from

  19. 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)

  20. Morphometric study of sacral hiatus in adult human Egyptian sacra: Their significance in caudal epidural anesthesia

    Directory of Open Access Journals (Sweden)

    Mohamed S Mustafa

    2012-01-01

    Full Text Available Background: The reliability and success of caudal epidural anesthesia depends on anatomic variations of sacral hiatus (SH as observed by various authors. SH is an important landmark during caudal epidural block (CEB.The purpose of the present study was to clarify the morphometric characteristics of the SH in human Egyptian dry sacra and pelvic radiographs and identification of nearest ony landmarks to permit correct and uncomplicated caudal epidural accesses. Methods: The present study was done on 46 human adult Egyptian dry sacra. The maximum height, midventral curved length, and maximum breadth of each sacrum were measured and sacral and curvature indices were calculated. According to sacral indices, sacra were divided into 2 groups (22 male and 24 female sacra. SH was evaluated in each sacrum according to its shape, level of its apex, and base according to sacral and coccygeal vertebrae, length, anteroposterior (AP diameter at its apex, and transverse width at its base. Linear distances were measured between the apex of SH and second sacral foramina, right and left superolateral sacral crests. The distance between the 2 superolateral sacral crests also was measured. Results: The most common types of SH were the inverted U and inverted V (in male and inverted V and dumbbell shaped (in female. Absent SH was observed in male group only. The most common location of SH apex was at the level of S4 in all groups of dry sacra and S3 in all groups of lumbosacral spine radiographs, whereas S5 was the common level of its base. The mean SH length, transverse width of its base, and AP diameter of its apex were 2.1±0.80, 1.7±0.26, and 0.48±0.19 cm. Female sacra showed narrower SH apex than male. The distance between the S2 foramen and the apex of the SH was 4.1±1.14, 3.67±1.21, and 4.48±1.01 cm in total, female and male sacra, respectively. Conclusion: Sacrum and SH showed morphometric variations in adult Egyptians. The equilateral triangle is an

  1. Morphological Study: Ultrastructural Aspects of Articular Cartilage and Subchondral Bone in Patients Affected by Post-Traumatic Shoulder Instability.

    Science.gov (United States)

    Baudi, Paolo; Catani, Fabio; Rebuzzi, Manuela; Ferretti, Marzia; Smargiassi, Alberto; Campochiaro, Gabriele; Serafini, Fabio; Palumbo, Carla

    2016-12-16

    Post-traumatic shoulder instability is a frequent condition in active population, representing one of most disabling pathologies, due to altered balance involving joints. No data are so far available on early ultrastructural osteo-chondral damages, associated with the onset of invalidating pathologies, like osteoarthritis-OA. Biopsies of glenoid articular cartilage and sub-chondral bone were taken from 10 adult patients underwent arthroscopic stabilization. Observations were performed under Transmission Electron Microscopy-TEM in tangential, arcuate and radial layers of the articular cartilage and in the sub-chondral bone. In tangential and arcuate layers chondrocytes display normal and very well preserved ultrastructure, probably due to the synovial liquid supply; otherwise, throughout the radial layer (un-calcified and calcified) chondrocytes show various degrees of degeneration; occasionally, in the radial layer evidences of apoptosis/autophagy were also observed. Concerning sub-chondral bone, osteocytes next to the calcified cartilage also show signs of degeneration, while osteocytes farther from the osteo-chondral border display normal ultrastructure, probably due to the bone vascular supply. The ultrastructural features of the osteo-chondral complex are not age-dependent. This study represents the first complete ultrastructural investigation of the articular osteo-chondral complex in shoulder instability, evaluating the state of preservation/viability of both chondrocytes and osteocytes throughout the successive layers of articular cartilage and sub-chondral bone. Preliminary observations here collected represent the morphological basis for further deepening of pathogenesis related to shoulder instability, enhancing the relationship between cell shape and microenvironment; in particular, they could be useful in understanding if the early surgical treatment in shoulder instability could avoid the onset of OA. Anat Rec, 300:12-15, 2017. © 2016 Wiley

  2. Chondrogenic potential of articular chondrocytes depends on their original location

    NARCIS (Netherlands)

    Bekkers, Joris E J; Saris, Daniel B F; Tsuchida, Anika Iris; van Rijen, Mattie H P; Dhert, Wouter J A; Creemers, Laura B

    2014-01-01

    OBJECTIVE: This study aimed to investigate the regenerative capacity of chondrocytes derived from debrided defect cartilage and healthy cartilage from different regions in the joint to determine the best cell source for regenerative cartilage therapies. METHODS: Articular cartilage was obtained from

  3. 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 outc

  4. The epidemiology of extra-articular manifestations in ankylosing spondylitis

    DEFF Research Database (Denmark)

    Stolwijk, Carmen; Essers, Ivette; van Tubergen, Astrid

    2015-01-01

    OBJECTIVE: To assess the incidence and risks of common extra-articular manifestations (EAMs), that is, acute anterior uveitis (AAU), psoriasis and inflammatory bowel disease (IBD), in patients with ankylosing spondylitis (AS) compared with population-based controls. METHODS: All incident patients...

  5. 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 micromovemen...

  6. Computational aspects in mechanical modeling of the articular cartilage tissue.

    Science.gov (United States)

    Mohammadi, Hadi; Mequanint, Kibret; Herzog, Walter

    2013-04-01

    This review focuses on the modeling of articular cartilage (at the tissue level), chondrocyte mechanobiology (at the cell level) and a combination of both in a multiscale computation scheme. The primary objective is to evaluate the advantages and disadvantages of conventional models implemented to study the mechanics of the articular cartilage tissue and chondrocytes. From monophasic material models as the simplest form to more complicated multiscale theories, these approaches have been frequently used to model articular cartilage and have contributed significantly to modeling joint mechanics, addressing and resolving numerous issues regarding cartilage mechanics and function. It should be noted that attentiveness is important when using different modeling approaches, as the choice of the model limits the applications available. In this review, we discuss the conventional models applicable to some of the mechanical aspects of articular cartilage such as lubrication, swelling pressure and chondrocyte mechanics and address some of the issues associated with the current modeling approaches. We then suggest future pathways for a more realistic modeling strategy as applied for the simulation of the mechanics of the cartilage tissue using multiscale and parallelized finite element method.

  7. Evidence for a negative Pasteur effect in articular cartilage.

    Science.gov (United States)

    Lee, R B; Urban, J P

    1997-01-01

    Uptake of external glucose and production of lactate were measured in freshly-excised bovine articular cartilage under O2 concentrations ranging from 21% (air) to zero (N2-bubbled). Anoxia (O2 concentration Pasteur effect in bovine articular cartilage. Anoxia also suppressed glycolysis in articular cartilage from horse, pig and sheep. Inhibitors acting on the glycolytic pathway (2-deoxy-D-glucose, iodoacetamide or fluoride) strongly decreased aerobic lactate production and ATP concentration, consistent with the belief that articular cartilage obtains its principal supply of ATP from substrate-level phosphorylation in glycolysis. Azide or cyanide lowered the ATP concentration in aerobic cartilage to approximately the same extent as did anoxia but, because glycolysis (lactate production) was also inhibited by these treatments, the importance of any mitochondrial ATP production could not be assessed. A negative Pasteur effect would make chondrocytes particularly liable to suffer a shortage of energy under anoxic conditions. Incorporation of [35S]sulphate into proteoglycan was severely curtailed by treatments, such as anoxia, which decreased the intracellular concentration of ATP.

  8. Surgery for extra-articular trismus : a systematic review

    NARCIS (Netherlands)

    Bouman, M A; Dijkstra, P U; Reintsema, H; Roodenburg, J L N; Werker, P M N

    2015-01-01

    The aim of this systematic review was to identify operations that are used to improve mouth opening in patients with extra-articular trismus (caused by cancer and its treatment, oral submucous fibrosis, or noma) and to find out if they work. We searched the electronic databases PubMed, Embase, Cinah

  9. Surgery for extra-articular trismus : a systematic review

    NARCIS (Netherlands)

    Bouman, M. A.; Dijkstra, P. U.; Reintsema, H.; Roodenburg, J. L. N.; Werkera, P. M. N.

    2016-01-01

    The aim of this systematic review was to identify operations that are used to improve mouth opening in patients with extra-articular trismus (caused by cancer and its treatment, oral submucous fibrosis, or noma) and to find out if they work. We searched the electronic databases PubMed, Embase, Cinah

  10. Doxycycline inhibits collagen synthesis by differentiated articular chondrocytes.

    NARCIS (Netherlands)

    TeKoppele, J.M.; Beekman, B.; Verzijl, N.; Koopman, J.L.; Groot, J. de; Bank, R.A.

    1998-01-01

    Doxycycline (DOX) profoundly inhibited collagen synthesis by differentiated articular chondrocytes. At 25 microM, the rate of collagen synthesis was suppressed by more than 50% without affecting cell proliferation (DNA levels) and general protein synthesis (35S-Met and 35S-Cys incorporation). Steady

  11. 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....

  12. Deformable adult human phantoms for radiation protection dosimetry: anthropometric data representing size distributions of adult worker populations and software algorithms

    Science.gov (United States)

    Hum Na, Yong; Zhang, Binquan; Zhang, Juying; Caracappa, Peter F.; Xu, X. George

    2010-07-01

    Computational phantoms representing workers and patients are essential in estimating organ doses from various occupational radiation exposures and medical procedures. Nearly all existing phantoms, however, were purposely designed to match internal and external anatomical features of the Reference Man as defined by the International Commission on Radiological Protection (ICRP). To reduce uncertainty in dose calculations caused by anatomical variations, a new generation of phantoms of varying organ and body sizes is needed. This paper presents detailed anatomical data in tables and graphs that are used to design such size-adjustable phantoms representing a range of adult individuals in terms of the body height, body weight and internal organ volume/mass. Two different sets of information are used to derive the phantom sets: (1) individual internal organ size and volume/mass distribution data derived from the recommendations of the ICRP in Publications 23 and 89 and (2) whole-body height and weight percentile data from the National Health and Nutrition Examination Survey (NHANES 1999-2002). The NHANES height and weight data for 19 year old males and females are used to estimate the distributions of individuals' size, which is unknown, that corresponds to the ICRP organ and tissue distributions. This paper then demonstrates the usage of these anthropometric data in the development of deformable anatomical phantoms. A pair of phantoms—modeled entirely in mesh surfaces—of the adult male and female, RPI-adult male (AM) and RPI-adult female (AF) are used as the base for size-adjustable phantoms. To create percentile-specific phantoms from these two base phantoms, organ surface boundaries are carefully altered according to the tabulated anthropometric data. Software algorithms are developed to automatically match the organ volumes and masses with desired values. Finally, these mesh-based, percentile-specific phantoms are converted into voxel-based phantoms for Monte

  13. Deformable adult human phantoms for radiation protection dosimetry: anthropometric data representing size distributions of adult worker populations and software algorithms

    Energy Technology Data Exchange (ETDEWEB)

    Na, Yong Hum; Xu, X George [Biomedical Engineering, Rensselaer Polytechnic Institute, Troy, NY 12180 (United States); Zhang Binquan; Zhang Juying; Caracappa, Peter F, E-mail: xug2@rpi.ed [Nuclear Engineering and Engineering Physics, Rensselaer Polytechnic Institute, Troy, NY 12180 (United States)

    2010-07-07

    Computational phantoms representing workers and patients are essential in estimating organ doses from various occupational radiation exposures and medical procedures. Nearly all existing phantoms, however, were purposely designed to match internal and external anatomical features of the Reference Man as defined by the International Commission on Radiological Protection (ICRP). To reduce uncertainty in dose calculations caused by anatomical variations, a new generation of phantoms of varying organ and body sizes is needed. This paper presents detailed anatomical data in tables and graphs that are used to design such size-adjustable phantoms representing a range of adult individuals in terms of the body height, body weight and internal organ volume/mass. Two different sets of information are used to derive the phantom sets: (1) individual internal organ size and volume/mass distribution data derived from the recommendations of the ICRP in Publications 23 and 89 and (2) whole-body height and weight percentile data from the National Health and Nutrition Examination Survey (NHANES 1999-2002). The NHANES height and weight data for 19 year old males and females are used to estimate the distributions of individuals' size, which is unknown, that corresponds to the ICRP organ and tissue distributions. This paper then demonstrates the usage of these anthropometric data in the development of deformable anatomical phantoms. A pair of phantoms-modeled entirely in mesh surfaces-of the adult male and female, RPI-adult male (AM) and RPI-adult female (AF) are used as the base for size-adjustable phantoms. To create percentile-specific phantoms from these two base phantoms, organ surface boundaries are carefully altered according to the tabulated anthropometric data. Software algorithms are developed to automatically match the organ volumes and masses with desired values. Finally, these mesh-based, percentile-specific phantoms are converted into voxel-based phantoms for Monte

  14. 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.

  15. Open-Porous Hydroxyapatite Scaffolds for Three-Dimensional Culture of Human Adult Liver Cells

    Directory of Open Access Journals (Sweden)

    Anthony Finoli

    2016-01-01

    Full Text Available Liver cell culture within three-dimensional structures provides an improved culture system for various applications in basic research, pharmacological screening, and implantable or extracorporeal liver support. Biodegradable calcium-based scaffolds in such systems could enhance liver cell functionality by providing endothelial and hepatic cell support through locally elevated calcium levels, increased surface area for cell attachment, and allowing three-dimensional tissue restructuring. Open-porous hydroxyapatite scaffolds were fabricated and seeded with primary adult human liver cells, which were embedded within or without gels of extracellular matrix protein collagen-1 or hyaluronan. Metabolic functions were assessed after 5, 15, and 28 days. Longer-term cultures exhibited highest cell numbers and liver specific gene expression when cultured on hydroxyapatite scaffolds in collagen-1. Endothelial gene expression was induced in cells cultured on scaffolds without extracellular matrix proteins. Hydroxyapatite induced gene expression for cytokeratin-19 when cells were cultured in collagen-1 gel while culture in hyaluronan increased cytokeratin-19 gene expression independent of the use of scaffold in long-term culture. The implementation of hydroxyapatite composites with extracellular matrices affected liver cell cultures and cell differentiation depending on the type of matrix protein and the presence of a scaffold. The hydroxyapatite scaffolds enable scale-up of hepatic three-dimensional culture models for regenerative medicine applications.

  16. Constrained Total Energy Expenditure and Metabolic Adaptation to Physical Activity in Adult Humans.

    Science.gov (United States)

    Pontzer, Herman; Durazo-Arvizu, Ramon; Dugas, Lara R; Plange-Rhule, Jacob; Bovet, Pascal; Forrester, Terrence E; Lambert, Estelle V; Cooper, Richard S; Schoeller, Dale A; Luke, Amy

    2016-02-08

    Current obesity prevention strategies recommend increasing daily physical activity, assuming that increased activity will lead to corresponding increases in total energy expenditure and prevent or reverse energy imbalance and weight gain [1-3]. Such Additive total energy expenditure models are supported by exercise intervention and accelerometry studies reporting positive correlations between physical activity and total energy expenditure [4] but are challenged by ecological studies in humans and other species showing that more active populations do not have higher total energy expenditure [5-8]. Here we tested a Constrained total energy expenditure model, in which total energy expenditure increases with physical activity at low activity levels but plateaus at higher activity levels as the body adapts to maintain total energy expenditure within a narrow range. We compared total energy expenditure, measured using doubly labeled water, against physical activity, measured using accelerometry, for a large (n = 332) sample of adults living in five populations [9]. After adjusting for body size and composition, total energy expenditure was positively correlated with physical activity, but the relationship was markedly stronger over the lower range of physical activity. For subjects in the upper range of physical activity, total energy expenditure plateaued, supporting a Constrained total energy expenditure model. Body fat percentage and activity intensity appear to modulate the metabolic response to physical activity. Models of energy balance employed in public health [1-3] should be revised to better reflect the constrained nature of total energy expenditure and the complex effects of physical activity on metabolic physiology.

  17. Analysis of Pregnancy-Associated Plasma Protein A Production in Human Adult Cardiac Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Piera D’Elia

    2013-01-01

    Full Text Available IGF-binding proteins (IGFBPs and their proteases regulate IGFs bioavailability in multiple tissues. Pregnancy-associated plasma protein A (PAPP-A is a protease acting by cleaving IGFBP2, 4, and 5, regulating local bioavailability of IGFs. We have previously shown that IGFs and IGFBPs are produced by human adult cardiac progenitor cells (haCPCs and that IGF-1 exerts paracrine therapeutic effects in cardiac cell therapy with CPCs. Using immunofluorescence and enzyme immunoassays, we firstly report that PAPP-A is produced and secreted in surprisingly high amounts by haCPCs. In particular, the homodimeric, enzymatically active, PAPP-A is secreted in relevant concentrations in haCPC-conditioned media, while the enzymatically inactive PAPPA/proMBP complex is not detectable in the same media. Furthermore, we show that both homodimeric PAPP-A and proMBP can be detected as cell associated, suggesting that the previously described complex formation at the cell surface does not occur easily, thus positively affecting IGF signalling. Therefore, our results strongly support the importance of PAPP-A for the IGFs/IGFBPs/PAPP-A axis in CPCs biology.

  18. Open-Porous Hydroxyapatite Scaffolds for Three-Dimensional Culture of Human Adult Liver Cells.

    Science.gov (United States)

    Finoli, Anthony; Schmelzer, Eva; Over, Patrick; Nettleship, Ian; Gerlach, Joerg C

    2016-01-01

    Liver cell culture within three-dimensional structures provides an improved culture system for various applications in basic research, pharmacological screening, and implantable or extracorporeal liver support. Biodegradable calcium-based scaffolds in such systems could enhance liver cell functionality by providing endothelial and hepatic cell support through locally elevated calcium levels, increased surface area for cell attachment, and allowing three-dimensional tissue restructuring. Open-porous hydroxyapatite scaffolds were fabricated and seeded with primary adult human liver cells, which were embedded within or without gels of extracellular matrix protein collagen-1 or hyaluronan. Metabolic functions were assessed after 5, 15, and 28 days. Longer-term cultures exhibited highest cell numbers and liver specific gene expression when cultured on hydroxyapatite scaffolds in collagen-1. Endothelial gene expression was induced in cells cultured on scaffolds without extracellular matrix proteins. Hydroxyapatite induced gene expression for cytokeratin-19 when cells were cultured in collagen-1 gel while culture in hyaluronan increased cytokeratin-19 gene expression independent of the use of scaffold in long-term culture. The implementation of hydroxyapatite composites with extracellular matrices affected liver cell cultures and cell differentiation depending on the type of matrix protein and the presence of a scaffold. The hydroxyapatite scaffolds enable scale-up of hepatic three-dimensional culture models for regenerative medicine applications.

  19. Immunomodulatory properties of human adult and fetal multipotent mesenchymal stem cells.

    Science.gov (United States)

    Chen, Pei-Min; Yen, Men-Luh; Liu, Ko-Jiunn; Sytwu, Huey-Kang; Yen, B-Linju

    2011-07-18

    In recent years, a large number of studies have contributed to our understanding of the immunomodulatory mechanisms used by multipotent mesenchymal stem cells (MSCs). Initially isolated from the bone marrow (BM), MSCs have been found in many tissues but the strong immunomodulatory properties are best studied in BM MSCs. The immunomodulatory effects of BM MSCs are wide, extending to T lymphocytes and dendritic cells, and are therapeutically useful for treatment of immune-related diseases including graft-versus-host disease as well as possibly autoimmune diseases. However, BM MSCs are very rare cells and require an invasive procedure for procurement. Recently, MSCs have also been found in fetal-stage embryo-proper and extra-embryonic tissues, and these human fetal MSCs (F-MSCs) have a higher proliferative profile, and are capable of multilineage differentiation as well as exert strong immunomodulatory effects. As such, these F-MSCs can be viewed as alternative sources of MSCs. We review here the current understanding of the mechanisms behind the immunomodulatory properties of BM MSCs and F-MSCs. An increase in our understanding of MSC suppressor mechanisms will offer insights for prevalent clinical use of these versatile adult stem cells in the near future.

  20. Prebiotic effects of almonds and almond skins on intestinal microbiota in healthy adult humans.

    Science.gov (United States)

    Liu, Zhibin; Lin, Xiuchun; Huang, Guangwei; Zhang, Wen; Rao, Pingfan; Ni, Li

    2014-04-01

    Almonds and almond skins are rich in fiber and other components that have potential prebiotic properties. In this study we investigated the prebiotic effects of almond and almond skin intake in healthy humans. A total of 48 healthy adult volunteers consumed a daily dose of roasted almonds (56 g), almond skins (10 g), or commercial fructooligosaccharides (8 g) (as positive control) for 6 weeks. Fecal samples were collected at defined time points and analyzed for microbiota composition and selected indicators of microbial activity. Different strains of intestinal bacteria had varying degrees of growth sensitivity to almonds or almond skins. Significant increases in the populations of Bifidobacterium spp. and Lactobacillus spp. were observed in fecal samples as a consequence of almond or almond skin supplementation. However, the populations of Escherichia coli did not change significantly, while the growth of the pathogen Clostridum perfringens was significantly repressed. Modification of the intestinal microbiota composition induced changes in bacterial enzyme activities, specifically a significant increase in fecal β-galactosidase activity and decreases in fecal β-glucuronidase, nitroreductase and azoreductase activities. Our observations suggest that almond and almond skin ingestion may lead to an improvement in the intestinal microbiota profile and a modification of the intestinal bacterial activities, which would induce the promotion of health beneficial factors and the inhibition of harmful factors. Thus we believe that almonds and almond skins possess potential prebiotic properties.

  1. 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.

  2. The Effectiveness of Ultrasound-Guided Steroid Injection for Femoroacetabular Impingement: A Comparison between the Extra-Articular and Intra-Articular Approaches

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Chang Ho; Lee, Joon Woo [Dept. of Radiology, Seoul National University Bundang Hospital, Seongnam (Korea, Republic of)

    2013-03-15

    To assess the effectiveness of pain control using ultrasound-guided steroid injection by the extra-articular and intra-articular approaches to femoroacetabular impingement patients. From September through December 2010, 18 patients with clinical suspicion of femoroacetabular impingement syndrome underwent ultrasound-guided steroid and local anesthetics injection: a total of 20 cases, including 16 cases of ipsilateral and 2 cases of bilateral injection. Extra-articular or intra-articular approach was selected for each patient, randomly and alternately. Nine cases were performed by extra-articular approach and 11 cases were performed by intra-articular approach. Every patient was observed in the outpatient clinic and visual analogue scale (VAS) was taken and compared before and after the procedure in all patients. Pre-injection average VAS value of extra-articular approached cases was 5.22 {+-} 1.99 and post-injection average VAS value was 4.11 {+-} 1.96, which is statistically insignificant (p < 0.156). The average VAS value of intra-articular approached cases was decreased from 5.72 {+-} 2.15 to 2.91 {+-} 2.30 after injection, which is statistically significant (p < 0.006). Ultrasound guided intra-articular approached steroid and local anesthetics injection could be effective in controlling pain for patients with femoroacetabular impingement syndrome.

  3. Occurrence of artificial sweeteners in human liver and paired blood and urine samples from adults in Tianjin, China and their implications for human exposure.

    Science.gov (United States)

    Zhang, Tao; Gan, Zhiwei; Gao, Chuanzi; Ma, Ling; Li, Yanxi; Li, Xiao; Sun, Hongwen

    2016-09-14

    In this study, acesulfame (ACE), saccharin (SAC) and cyclamate (CYC) were found in all paired urine and blood samples collected from healthy adults, with mean values of 4070, 918 and 628 ng mL(-1), respectively, in urine and 9.03, 20.4 and 0.72 ng mL(-1), respectively, in blood. SAC (mean: 84.4 ng g(-1)) and CYC (4.29 ng g(-1)) were detectable in all liver samples collected from liver cancer patients, while ACE was less frequently detected. Aspartame (ASP) was not found in any analyzed human sample, which can be explained by the fact that this chemical metabolized rapidly in the human body. Among all adults, significantly positive correlations between SAC and CYC levels were observed (p < 0.001), regardless of human matrices. Nevertheless, no significant correlations between concentrations of SAC (or CYC) and ACE were found in any of the human matrices. Our results suggest that human exposure to SAC and CYC is related, whereas ACE originates from a discrete source. Females (or young adults) were exposed to higher levels of SAC and CYC than males (or elderly). The mean renal clearance of SAC was 730 mL per day per kg in adults, which was significantly (p < 0.001) lower than those for CYC (10 800 mL per day per kg) and ACE (10 300 mL per day per kg). The average total daily intake of SAC and ACE was 9.27 and 33.8 μg per kg bw per day, respectively.

  4. Intrastriatal transplantation of adult human neural crest-derived stem cells improves functional outcome in parkinsonian rats.

    Science.gov (United States)

    Müller, Janine; Ossig, Christiana; Greiner, Johannes F W; Hauser, Stefan; Fauser, Mareike; Widera, Darius; Kaltschmidt, Christian; Storch, Alexander; Kaltschmidt, Barbara

    2015-01-01

    Parkinson's disease (PD) is considered the second most frequent and one of the most severe neurodegenerative diseases, with dysfunctions of the motor system and with nonmotor symptoms such as depression and dementia. Compensation for the progressive loss of dopaminergic (DA) neurons during PD using current pharmacological treatment strategies is limited and remains challenging. Pluripotent stem cell-based regenerative medicine may offer a promising therapeutic alternative, although the medical application of human embryonic tissue and pluripotent stem cells is still a matter of ethical and practical debate. Addressing these challenges, the present study investigated the potential of adult human neural crest-derived stem cells derived from the inferior turbinate (ITSCs) transplanted into a parkinsonian rat model. Emphasizing their capability to give rise to nervous tissue, ITSCs isolated from the adult human nose efficiently differentiated into functional mature neurons in vitro. Additional successful dopaminergic differentiation of ITSCs was subsequently followed by their transplantation into a unilaterally lesioned 6-hydroxydopamine rat PD model. Transplantation of predifferentiated or undifferentiated ITSCs led to robust restoration of rotational behavior, accompanied by significant recovery of DA neurons within the substantia nigra. ITSCs were further shown to migrate extensively in loose streams primarily toward the posterior direction as far as to the midbrain region, at which point they were able to differentiate into DA neurons within the locus ceruleus. We demonstrate, for the first time, that adult human ITSCs are capable of functionally recovering a PD rat model.

  5. Cultured human embryonic neocortical cells survive and grow in infarcted cavities of adult rat brains and interconnect with host brain

    Institute of Scientific and Technical Information of China (English)

    ZENG Jin-sheng; YU Jian; CUI Chun-mei; ZHAO Zhan; HONG Hua; SHENG Wen-li; TAO Yu-qian; LI Ling; HUANG Ru-xun

    2005-01-01

    Background There are no reports on exnografting cultured human fetal neocortical cells in this infracted cavities of adult rat brains. This study was undertaken to observe whether cultured human cortical neurons and astrocytes can survive and grow in the infarcted cavities of adult rat brains and whether they interconnect with host brains.Methods The right middle cerebral artery was ligated distal to the striatal branches in 16 adult stroke-prone renovascular hypertensive rats. One week later, cultured cells from human embryonic cerebral cortexes were stereotaxically transferred to the infarcted cavity of 11 rats. The other 5 rats receiving sham transplants served as controls. For immunosuppression, all transplanted rats received intraperitoneal injection of cyclosporine A daily starting on the day of grafting. Immunohistochemistry for glial fibrillary acidic protein (GFAP), synaptophysin, neurofilament, and microtubule associated protein-2 (MAP-2) was performed on brain sections perfused in situ 8 weeks after transplantation.Results Grafts in the infarcted cavities of 6 of 10 surviving rats consisted of bands of neurons with an immature appearance, bundles of fibers, and GFAP-immunopositive astrocytes, which were unevenly distributed. The grafts were rich in synaptophysin, neurofilament, and MAP2-positive neurons with long processes. The graft/host border was diffuse with dendrites apparently bridging over to the host brain, into which neurofilament immunopositive fibers protruded. Conclusion Cultured human fetal brain cells can survive and grow in the infarcted cavities of immunodepressed rats and integrate with the host brain.

  6. 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.

  7. Postmortem Adult Human Microglia Proliferate in Culture to High Passage and Maintain Their Response to Amyloid-β

    Science.gov (United States)

    Guo, Ling; Rezvanian, Aras; Kukreja, Lokesh; Hoveydai, Ramez; Bigio, Eileen H.; Mesulam, M.-Marsel; El Khoury, Joseph; Geula, Changiz

    2016-01-01

    Microglia are immune cells of the brain that display a range of functions. Most of our knowledge about microglia biology and function is based on cells from the rodent brain. Species variation in the complexity of the brain and differences in microglia response in the primate when compared with the rodent, require use of adult human microglia in studies of microglia biology. While methods exist for isolation of microglia from postmortem human brains, none allow culturing cells to high passage. Thus cells from the same case could not be used in parallel studies and multiple conditions. Here we report a method, which includes use of growth factors such as granulocyte macrophage colony stimulating factor, for successful culturing of adult human microglia from postmortem human brains up to 28 passages without significant loss of proliferation. Such cultures maintained their phenotype, including uptake of the scavenger receptor ligand acetylated low density lipoprotein and response to the amyloid-β peptide, and were used to extend in vivo studies in the primate brain demonstrating that inhibition of microglia activation protects neurons from amyloid-β toxicity. Significantly, microglia cultured from brains with pathologically confirmed Alzheimer’s disease displayed the same characteristics as microglia cultured from normal aged brains. The method described here provides the scientific community with a new and reliable tool for mechanistic studies of human microglia function in health from childhood to old age, and in disease, enhancing the relevance of the findings to the human brain and neurodegenerative conditions. PMID:27567845

  8. 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

  9. 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.

  10. FASH and MASH: female and male adult human phantoms based on polygon mesh surfaces: I. Development of the anatomy

    Energy Technology Data Exchange (ETDEWEB)

    Cassola, V F; Kramer, R; Khoury, H J [Department of Nuclear Energy, Federal University of Pernambuco, Avenida Prof. Luiz Freire, 1000, CEP 50740-540, Recife (Brazil); De Melo Lima, V J [Department of Anatomy, Federal University of Pernambuco, Avenida Prof. Moraes Rego, 1235, CEP 50670-901, Recife (Brazil)], E-mail: rkramer@uol.com.br

    2010-01-07

    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{sub A}M and female RPI{sub A}F phantoms shows differences with respect to the material used, to the software and concepts applied, and to the anatomies created.

  11. Protocol to isolate a large amount of functional oligodendrocyte precursor cells from the cerebral cortex of adult mice and humans.

    Directory of Open Access Journals (Sweden)

    Eva María Medina-Rodríguez

    Full Text Available During development, oligodendrocytes are generated from oligodendrocyte precursor cells (OPCs, a cell type that is a significant proportion of the total cells (3-8% in the adult central nervous system (CNS of both rodents and humans. Adult OPCs are responsible for the spontaneous remyelination that occurs in demyelinating diseases like Multiple Sclerosis (MS and they constitute an interesting source of cells for regenerative therapy in such conditions. However, there is little data regarding the neurobiology of adult OPCs isolated from mice since an efficient method to isolate them has yet to be established. We have designed a protocol to obtain viable adult OPCs from the cerebral cortex of different mouse strains and we have compared its efficiency with other well-known methods. In addition, we show that this protocol is also useful to isolate functional OPCs from human brain biopsies. Using this method we can isolate primary cortical OPCs in sufficient quantities so as to be able to study their survival, maturation and function, and to facilitate an evaluation of their utility in myelin repair.

  12. The Effects of Supplemental Intra-Articular Lubricin and Hyaluronic Acid on the Progression of Post-Traumatic Arthritis in the Anterior Cruciate Ligament Deficient Rat Knee

    Science.gov (United States)

    Teeple, Erin; Elsaid, Khaled A.; Jay, Gregory D.; Zhang, Ling; Badger, Gary J.; Akelman, Matthew; Bliss, Thomas F.; Fleming, Braden C.

    2010-01-01

    Background Lubricin and hyaluronic acid lubricate articular cartilage and prevent wear. Because lubricin loss occurs following ACL injury, intra-articular lubricin injections may reduce cartilage damage in the ACL deficient knee. Purpose To determine if lubricin and/or hyaluronic acid supplementation will reduce cartilage damage in the ACL deficient knee. Study Design Controlled laboratory study Methods 36 male rats, 3 months old, underwent unilateral ACL transection. They were randomized to four treatments: 1) saline (PBS), 2) hyaluronic acid (HA), 3) purified human lubricin (LUB), and 4) LUB and HA (LUB+HA). Intra-articular injections were given twice weekly for four weeks starting one week after surgery. Knees were harvested one week following final injection. Radiographs of each limb and synovial fluid lavages were obtained at harvest. Histology was performed to assess cartilage damage using Safranin O/Fast green staining. Radiographs were scored for the severity of joint degeneration using the modified Kellgren-Lawrence scale. Synovial fluid levels of sulfated glycosaminoglycan, collagen II breakdown, IL-1β, TNF-α and lubricin were measured using ELISA. Results Treatment with LUB or LUB+HA significantly decreased radiographic and histologic scores of cartilage damage (p=0.039, p=0.015, respectively) when compared to the PBS and HA conditions. There was no evidence of an effect of HA nor was the LUB effect HA dependent suggesting that the addition of HA did not further reduce damage. The synovial fluid of knees treated with LUB had significantly more lubricin in the synovial fluid at euthanasia, though there were no differences in the other cartilage metabolism biomarkers. Conclusions Supplemental intra-articular LUB reduced cartilage damage in the ACL transected rat knee 6 weeks after injury, while treatment with HA did not. Clinical Relevance Although longer-term studies are needed, intra-articular supplementation (tribosupplementation) with lubricin

  13. Application of Jean Piaget's theory of human development for nursing children in an adult intensive therapy unit.

    Science.gov (United States)

    Green, A

    1991-12-01

    Piaget (1964) believed that interaction with the environment has a large part to play in human development. Matthew (1986) states that in an ideal world critically ill children should be cared for by staff trained in paediatrics, within designated paediatric intensive therapy units. Unfortunately, there are only 28 paediatric intensive therapy units in Great Britain (CMA Medical Data, 1987), consequently each year a third of children requiring intensive care are admitted to adult intensive therapy units (ITU). A knowledge and understanding of developmental psychology can therefore be beneficial to nurses in assessing which stage of development a child has reached, in order to plan the correct level of stimulation, and hence facilitate progress rather than regression in the accomplishment of developmental tasks. The psychological and social processes involved in Jean Piaget's (1896-1980) theory of human development are discussed with regard to nursing children requiring intubation and ventilation in an adult ITU.

  14. 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

    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......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...

  15. Condensed cellular seeded collagen gel as an improved biomaterial for tissue engineering of articular cartilage.

    Science.gov (United States)

    Mueller-Rath, Ralf; Gavénis, Karsten; Andereya, Stefan; Mumme, Torsten; Albrand, Monique; Stoffel, Marcus; Weichert, Dieter; Schneider, Ulrich

    2010-01-01

    Three-dimensional autologous chondrocyte implantation based on collagen gel as matrix scaffold has become a clinically applied treatment for focal defects of articular cartilage. However, the low biomechanical properties of collagen gel makes intraoperative handling difficult and creates the risk of early damages to the vulnerable implant. The aim of the study was to create a stabilized form of collagen gel and to evaluate its biomechanical and biochemical properties.Collagen type-I gel was seeded with human articular chondrocytes. 20 samples were subject to condensation which was achieved mechanically by compression and filtration. Control samples were left uncondensed. From both types of gels 10 samples were used for initial biomechanical evaluation by means of unconfined compression and 10 samples were cultivated under standard conditions in vitro. Following cultivation the samples were evaluated by conventional histology and immunohistochemistry. The proliferation rate was calculated and matrix gene expression was quantified by real-time PCR.The biomechanical tests revealed a higher force carrying capacity of the condensed specimens. Strain rate dependency and relaxation was seen in both types of collagen gel representing viscoelastic material properties. Cells embedded within the condensed collagen gel were able to produce extracellular matrix proteins and showed proliferation.Condensed collagen gel represents a mechanically improved type of biomaterial which is suitable for three-dimensional autologous chondrocyte implantation.

  16. Stem cells and other innovative intra-articular therapies for osteoarthritis: what does the future hold?

    Directory of Open Access Journals (Sweden)

    Singh Jasvinder A

    2012-05-01

    Full Text Available Abstract Osteoarthritis (OA, the most common type of arthritis in the world, is associated with suffering due to pain, productivity loss, decreased mobility and quality of life. Systemic therapies available for OA are mostly symptom modifying and have potential gastrointestinal, renal, hepatic, and cardiac side effects. BMC Musculoskeletal Disorders recently published a study showing evidence of reparative effects demonstrated by homing of intra-articularly injected autologous bone marrow stem cells in damaged cartilage in an animal model of OA, along with clinical and radiographic benefit. This finding adds to the growing literature showing the potential benefit of intra-articular (IA bone marrow stem cells. Other emerging potential IA therapies include IL-1 receptor antagonists, conditioned autologous serum, botulinum toxin, and bone morphogenetic protein-7. For each of these therapies, trial data in humans have been published, but more studies are needed to establish that they are safe and effective. Several additional promising new OA treatments are on the horizon, but challenges remain to finding safe and effective local and systemic therapies for OA. Please see related article: http://www.biomedcentral.com/1471-2474/12/259

  17. Chondrocytes, Mesenchymal Stem Cells, and Their Combination in Articular Cartilage Regenerative Medicine.

    Science.gov (United States)

    Nazempour, A; Van Wie, B J

    2016-05-01

    Articular cartilage (AC) is a highly organized connective tissue lining, covering the ends of bones within articulating joints. Its highly ordered structure is essential for stable motion and provides a frictionless surface easing load transfer. AC is vulnerable to lesions and, because it is aneural and avascular, it has limited self-repair potential which often leads to osteoarthritis. To date, no fully successful treatment for osteoarthritis has been reported. Thus, the development of innovative therapeutic approaches is desperately needed. Autologous chondrocyte implantation, the only cell-based surgical intervention approved in the United States for treating cartilage defects, has limitations because of de-differentiation of articular chondrocytes (AChs) upon in vitro expansion. De-differentiation can be abated if initial populations of AChs are co-cultured with mesenchymal stem cells (MSCs), which not only undergo chondrogenesis themselves but also support chondrocyte vitality. In this review we summarize studies utilizing AChs, non-AChs, and MSCs and compare associated outcomes. Moreover, a comprehensive set of recent human studies using chondrocytes to direct MSC differentiation, MSCs to support chondrocyte re-differentiation and proliferation in co-culture environments, and exploratory animal intra- and inter-species studies are systematically reviewed and discussed in an innovative manner allowing side-by-side comparisons of protocols and outcomes. Finally, a comprehensive set of recommendations are made for future studies.

  18. 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…

  19. Development and application of human adult stem or progenitor cell organoids

    NARCIS (Netherlands)

    Rookmaaker, Maarten B; Schutgens, Frans; Verhaar, Marianne C; Clevers, Hans

    2015-01-01

    Adult stem or progenitor cell organoids are 3D adult-organ-derived epithelial structures that contain self-renewing and organ-specific stem or progenitor cells as well as differentiated cells. This organoid culture system was first established in murine intestine and subsequently developed for sever

  20. Effect on the disability index of adult patients with benign paroxysmal positional vertigo using vestibular rehabilitation and human movement

    OpenAIRE

    Chaverri Flores, Sofía; Chaverri Polini, Julián; Mora Campos, Andrea

    2007-01-01

    Objective: determine the effect on the disability index of adult patients with benign paroxysmal positional vertigo (BPPV) using vestibular rehabilitation therapy (VRT) and human movement. Subjects: six subjects with an average age of 49.5 ± 14.22 years who have been diagnosed with benign paroxysmal positional vertigo by an otolaryngologist. Instruments: the Dizziness Handicap Inventory and a questionnaire to determine impact on the quality of life of patients with this pathology (Ceballos an...

  1. Hybrid mathematical model of cardiomyocyte turnover in the adult human heart.

    Directory of Open Access Journals (Sweden)

    Jeremy A Elser

    Full Text Available RATIONALE: The capacity for cardiomyocyte regeneration in the healthy adult human heart is fundamentally relevant for both myocardial homeostasis and cardiomyopathy therapeutics. However, estimates of cardiomyocyte turnover rates conflict greatly, with a study employing C14 pulse-chase methodology concluding 1% annual turnover in youth declining to 0.5% with aging and another using cell population dynamics indicating substantial, age-increasing turnover (4% increasing to 20%. OBJECTIVE: Create a hybrid mathematical model to critically examine rates of cardiomyocyte turnover derived from alternative methodologies. METHODS AND RESULTS: Examined in isolation, the cell population analysis exhibited severe sensitivity to a stem cell expansion exponent (20% variation causing 2-fold turnover change and apoptosis rate. Similarly, the pulse-chase model was acutely sensitive to assumptions of instantaneous incorporation of atmospheric C14 into the body (4-fold impact on turnover in young subjects while numerical restrictions precluded otherwise viable solutions. Incorporating considerations of primary variable sensitivity and controversial model assumptions, an unbiased numerical solver identified a scenario of significant, age-increasing turnover (4-6% increasing to 15-22% with age that was compatible with data from both studies, provided that successive generations of cardiomyocytes experienced higher attrition rates than predecessors. CONCLUSIONS: Assignment of histologically-observed stem/progenitor cells into discrete regenerative phenotypes in the cell population model strongly influenced turnover dynamics without being directly testable. Alternatively, C14 trafficking assumptions and restrictive models in the pulse-chase model artificially eliminated high-turnover solutions. Nevertheless, discrepancies among recent cell turnover estimates can be explained and reconciled. The hybrid mathematical model provided herein permits further examination of

  2. 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

  3. Restricted 12p Amplification and RAS Mutation in Human Germ Cell Tumors of the Adult Testis

    Science.gov (United States)

    Roelofs, Helene; Mostert, Marijke C.; Pompe, Kirsten; Zafarana, Gaetano; van Oorschot, Monique; van Gurp, Ruud J. H. L. M.; Gillis, Ad J. M.; Stoop, Hans; Beverloo, Berna; Oosterhuis, J. Wolter; Bokemeyer, Carsten; Looijenga, Leendert H. J.

    2000-01-01

    Human testicular germ-cell tumors of young adults (TGCTs), both seminomas and nonseminomas, are characterized by 12p overrepresentation, mostly as isochromosomes, of which the biological and clinical significance is still unclear. A limited number of TGCTs has been identified with an additional high-level amplification of a restricted region of 12p including the K-RAS proto-oncogene. Here we show that the incidence of these restricted 12p amplifications is ∼8% in primary TGCTs. Within a single cell formation of i(12p) and restricted 12p amplification is mutually exclusive. The borders of the amplicons cluster in short regions, and the amplicon was never found in the adjacent carcinoma in situ cells. Seminomas with the restricted 12p amplification virtually lacked apoptosis and the tumor cells showed prolonged in vitro survival like seminoma cells with a mutated RAS gene. However, no differences in proliferation index between these different groups of seminomas were found. Although patients with a seminoma containing a homogeneous restricted 12p amplification presented at a significantly younger age than those lacking it, the presence of a restricted 12p amplification/RAS mutation did not predict the stage of the disease at clinical presentation and the treatment response of primary seminomas. In 55 primary and metastatic tumors from 44 different patients who failed cisplatinum-based chemotherapy, the restricted 12p amplification and RAS mutations had the same incidence as in the consecutive series of responding patients. These data support the model that gain of 12p in TGCTs is related to invasive growth. It allows tumor cells, in particular those showing characteristics of early germ cells (ie, the seminoma cells), to survive outside their specific microenvironment. Overexpression of certain genes on 12p probably inhibits apoptosis in these tumor cells. However, the copy numbers of the restricted amplification of 12p and K-RAS mutations do not predict response

  4. Study origin of germ cells and formation of new primary follicles in adult human and rat ovaries.

    Science.gov (United States)

    Bukovsky, Antonin; Gupta, Satish K; Virant-Klun, Irma; Upadhyaya, Nirmala B; Copas, Pleas; Van Meter, Stuart E; Svetlikova, Marta; Ayala, Maria E; Dominguez, Roberto

    2008-01-01

    The central thesis regarding the human ovaries is that, although primordial germ cells in embryonal ovaries are of extraovarian origin, those generated during the fetal period and in postnatal life are derived from the ovarian surface epithelium (OSE) bipotent cells. With the assistance of immune system-related cells, secondary germ cells and primitive granulosa cells originate from OSE stem cells in the fetal and adult human gonads. Fetal primary follicles are formed during the second trimester of intrauterine life, prior to the end of immune adaptation, possibly to be recognized as self-structures and renewed later. With the onset of menarche, a periodical oocyte and follicular renewal emerges to replace aging primary follicles and ensure that fresh eggs for healthy babies are always available during the prime reproductive period. The periodical follicular renewal ceases between 35 and 40 yr of age, and the remaining primary follicles are utilized during the premenopausal period until exhausted. However, the persisting oocytes accumulate genetic alterations and may become unsuitable for ovulation and fertilization. The human OSE stem cells preserve the character of embryonic stem cells, and they may produce distinct cell types, including new eggs in vitro, particularly when derived from patients with premature ovarian failure or aging and postmenopausal ovaries. Our observations also indicate that there are substantial differences in follicular renewal between adult human and rat ovaries. As part of this chapter, we present in detail protocols utilized to analyze oogenesis in humans and to study interspecies differences when compared to the ovaries of rat females.

  5. Protocadherin 11X/Y a human-specific gene pair: an immunohistochemical survey of fetal and adult brains.

    Science.gov (United States)

    Priddle, Thomas H; Crow, Tim J

    2013-08-01

    Protocadherins 11X and 11Y are cell adhesion molecules of the δ1-protocadherin family. Pcdh11X is present throughout the mammalian radiation; however, 6 million years ago (MYA), a reduplicative translocation of the Xq21.3 block onto what is now human Yp11 created the Homo sapiens-specific PCDH11Y. Therefore, modern human females express PCDH11X whereas males express both PCDH11X and PCDH11Y. PCDH11X/Y has been subject to accelerated evolution resulting in human-specific changes to both proteins, most notably 2 cysteine substitutions in the PCDH11X ectodomain that may alter binding characteristics. The PCDH11X/Y gene pair is postulated to be critical to aspects of human brain evolution related to the neural correlates of language. Therefore, we raised antibodies to investigate the temporal and spatial expression of PCDH11X/Y in cortical and sub-cortical areas of the human fetal brain between 12 and 34 postconceptional weeks. We then used the antibodies to determine if this expression was consistent in a series of adult brains. PCDH11X/Y immunoreactivity was detectable at all developmental stages. Strong expression was detected in the fetal neocortex, ganglionic eminences, cerebellum, and inferior olive. In the adult brain, the cerebral cortex, hippocampal formation, and cerebellum were strongly immunoreactive, with expression also detectable in the brainstem.

  6. Differences in compact bone tissue microscopic structure between adult humans (Homo sapiens) and Assam macaques (Macaca assamensis).

    Science.gov (United States)

    Nganvongpanit, Korakot; Phatsara, Manussabhorn; Settakorn, Jongkolnee; Mahakkanukrauh, Pasuk

    2015-09-01

    This study investigated the osteon structure of adult humans and Assam macaques, which served as a nonhuman primate model, to find an adequate key for species identification. Samples of compact bone from humans (n=5) and Assam macaques (n=5) - including humerus (n=20), radius (n=20), ulna (n=20), femur (n=20), tibia (n=20) and fibula (n=20) - were processed using conventional histological techniques. 100 secondary osteons from each sample were evaluated under light microscopy. Parameter measurements included: diameter, perimeter and area of Haversian canal and osteon; distance between centers of Haversian canals; and ratio between diameter of Haversian canal and osteon. Four parameters, including diameters and areas of Haversian canal and osteon, demonstrated significantly higher (P<0.05) values in humans than in Assam macaques. Therefore, compact bone microstructure could thus be used as a potential tool to differentiate human and nonhuman primates.

  7. One intra-articular injection of hyaluronan prevents cell death and improves cell metabolism in a model of injured articular cartilage in the rabbit

    NARCIS (Netherlands)

    Jansen, Edwin J. P.; Ernans, Pieter J.; Douw, Conny M.; Guidemond, Nick A.; Van Rhijn, Lodewijk W.; Bulstra, Sjoerd K.; Kuijer, Roell

    2008-01-01

    The purpose of this study was to determine the effect of one intra-articular injection of hyaluronan on chondrocyte death and metabolism in injured cartilage. Twenty-three 6-month-old rabbits received partial-thickness articular cartilage defects created on each medial femoral condyle. In order to e

  8. Epidemiology of extra-articular manifestations in rheumatoid arthritis.

    Science.gov (United States)

    Turesson, C; Jacobsson, L T H

    2004-01-01

    Extra-articular RA (ExRA) includes a wide variety of disease manifestations. Although rheumatologists in general are aware that such events are clinically important, the heterogeneity of available data, including discrepancies in case definitions, has complicated constructive discussions on this aspect of the RA disease phenotype. In recent years, there has been a growing recognition of the importance of co-morbidity in patients with RA. ExRA manifestations are not uncommon, explain excess mortality in RA and are predicted by smoking and autoantibodies. Further studies of the mechanisms underlying these associations are likely to be important in improving our understanding of the systemic nature of RA. This article discusses the methodological issues involved in the study of ExRA manifestations, presents suggested criteria that have been used in clinical studies, and reviews important surveys of the epidemiology of extra-articular RA.

  9. 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.

  10. The biochemical content of articular cartilage: an original MRI approach.

    Science.gov (United States)

    Loeuille, Damien; Olivier, Pierre; Watrin, Astrid; Grossin, Laurent; Gonord, Patrick; Guillot, Geneviève; Etienne, Stéphanie; Blum, Alain; Netter, Patrick; Gillet, Pierre

    2002-01-01

    The MR aspect of articular cartilage, that reflects the interactions between protons and macromolecular constituents, is affected by the intrinsic tissue structure (water content, the content of matrix constituents, collagen network organization), imager characteristics, and acquisition parameters. On the T1-weighted sequences, the bovine articular cartilage appears as an homogeneous tissue in high signal intensity, whatever the age of animals considered, whereas on the T2-weighted sequences, the articular bovine cartilage presents variations of its imaging pattern (laminar appearance) well correlated to the variations of its histological and biochemical structure. The T2 relaxation time measurement (T2 mapping), which reflects quantitatively the signal intensity variations observed on T2 weighted sequences, is a way to evaluate more precisely the modifications of cartilage structure during the aging and maturation processes (rat's study). This technique so far confined to experimental micro-imagers is now developed on clinical imagers. Consequently, it may permit to depict the early stages of osteoarthritic disease (OA) or to evaluate the chondroprotective effect of drugs.

  11. Sonographic evaluation of femoral articular cartilage in the knee

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Sung Hwan [College of Medicine, Hallym University, Seoul (Korea, Republic of); Kong Keun Young; Chung, Hye Won; Choi, Young Ho; Song, Yeong Wook; Kang, Heung Sik [College of Medicine and the Institute of Radiation Medicine, Seoul National University, Seoul (Korea, Republic of)

    2000-06-01

    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)

  12. Ultrasonic quantitation of superficial degradation of articular cartilage.

    Science.gov (United States)

    Saarakkala, Simo; Töyräs, Juha; Hirvonen, Jani; Laasanen, Mikko S; Lappalainen, Reijo; Jurvelin, Jukka S

    2004-06-01

    Ultrasound (US) has been suggested as a means for the quantitative detection of early osteoarthrotic changes in articular cartilage. In this study, the ability of quantitative US 2-D imaging (20 MHz) to reveal superficial changes in bovine articular cartilage after mechanical or enzymatic degradation was investigated in vitro. Mechanical degradation was induced by grinding samples against an emery paper with the grain size of 250 microm, 106 microm, 45 microm or 23 microm. For enzymatic degradation, samples were digested with collagenase, trypsin or chondroitinase ABC. Variations of the US reflection coefficient induced by the degradation were investigated. Furthermore, two novel parameters, the US roughness index (URI) and the spatial variation of the US reflection coefficient (SVR), were established to quantitate the integrity of the cartilage surface. Statistically significant decreases (p < 0.05) in US reflection coefficient were observed after mechanical degradations or enzymatic digestion with collagenase. Increases (p < 0.05) in URI were also revealed after these treatments. We conclude that quantitative US imaging may be used to detect collagen disruption and increased roughness in the articular surface. These structural damages are typical of early osteoarthrosis.

  13. Vulnerability of the Superficial Zone of Immature Articular Cartilage to Compressive Injury

    Energy Technology Data Exchange (ETDEWEB)

    Rolauffs, R.; Muehleman, C; Li, J; Kurz, B; Kuettner, K; Frank, E; Grodzinsky, A

    2010-01-01

    The zonal composition and functioning of adult articular cartilage causes depth-dependent responses to compressive injury. In immature cartilage, shear and compressive moduli as well as collagen and sulfated glycosaminoglycan (sGAG) content also vary with depth. However, there is little understanding of the depth-dependent damage caused by injury. Since injury to immature knee joints most often causes articular cartilage lesions, this study was undertaken to characterize the zonal dependence of biomechanical, biochemical, and matrix-associated changes caused by compressive injury. Disks from the superficial and deeper zones of bovine calves were biomechanically characterized. Injury to the disks was achieved by applying a final strain of 50% compression at 100%/second, followed by biomechanical recharacterization. Tissue compaction upon injury as well as sGAG density, sGAG loss, and biosynthesis were measured. Collagen fiber orientation and matrix damage were assessed using histology, diffraction-enhanced x-ray imaging, and texture analysis. Injured superficial zone disks showed surface disruption, tissue compaction by 20.3 {+-} 4.3% (mean {+-} SEM), and immediate biomechanical impairment that was revealed by a mean {+-} SEM decrease in dynamic stiffness to 7.1 {+-} 3.3% of the value before injury and equilibrium moduli that were below the level of detection. Tissue areas that appeared intact on histology showed clear textural alterations. Injured deeper zone disks showed collagen crimping but remained undamaged and biomechanically intact. Superficial zone disks did not lose sGAG immediately after injury, but lost 17.8 {+-} 1.4% of sGAG after 48 hours; deeper zone disks lost only 2.8 {+-} 0.3% of sGAG content. Biomechanical impairment was associated primarily with structural damage. The soft superficial zone of immature cartilage is vulnerable to compressive injury, causing superficial matrix disruption, extensive compaction, and textural alteration, which results

  14. Autophagy is required for self-renewal and differentiation of adult human stem cells

    Institute of Scientific and Technical Information of China (English)

    Souzan Salemi; Shida Yousefi; Mihai A Constantinescu; Martin F Fey; Hans-Uwe Simon

    2012-01-01

    Dear Editor,Patients receiving anticancer therapy usually suffer from side effects,such as loss of hair,epithelial barrier defects,and myelosuppression,which,however,are usually reversible when the therapy is discontinued.Although this clinical experience suggests that adult stem cells may survive such therapeutic interventions,the underlying molecular regulatory mechanisms are poorly understood.Such regulatory mechanisms also seem to protect adult stem cells from acquiring mutations,which could lead to additional tumorigenesis.

  15. Uptake of dietary milk miRNAs by adult humans: a validation study [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Amanda Auerbach

    2016-04-01

    Full Text Available Breast milk is replete with nutritional content as well as nucleic acids including microRNAs (miRNAs. In a recent report, adult humans who drank bovine milk appeared to have increased circulating levels of miRNAs miR-29b-3p and miR-200c-3p. Since these miRNAs are homologous between human and cow, these results could be explained by xeno-miRNA influx, endogenous miRNA regulation, or both. More data were needed to validate the results and explore for additional milk-related alterations in circulating miRNAs. Samples from the published study were obtained, and 223 small RNA features were profiled with a custom OpenArray, followed by individual quantitative PCR assays for selected miRNAs. Additionally, small RNA sequencing (RNA-seq data obtained from plasma samples of the same project were analyzed to find human and uniquely bovine miRNAs. OpenArray revealed no significantly altered miRNA signals after milk ingestion, and this was confirmed by qPCR. Plasma sequencing data contained no miR-29b or miR-200c reads and no intake-consistent mapping of uniquely bovine miRNAs. In conclusion, the results do not support transfer of dietary xenomiRs into the circulation of adult humans.

  16. Transferability and fine-mapping of genome-wide associated loci for adult height across human populations.

    Directory of Open Access Journals (Sweden)

    Daniel Shriner

    Full Text Available Human height is the prototypical polygenic quantitative trait. Recently, several genetic variants influencing adult height were identified, primarily in individuals of East Asian (Chinese Han or Korean or European ancestry. Here, we examined 152 genetic variants representing 107 independent loci previously associated with adult height for transferability in a well-powered sample of 1,016 unrelated African Americans. When we tested just the reported variants originally identified as associated with adult height in individuals of East Asian or European ancestry, only 8.3% of these loci transferred (p-values or = 0.3 with the reported variants, the transferability rate increased to 54.1%. The transferability rate was 70.8% for associations originally reported as genome-wide significant and 38.0% for associations originally reported as suggestive. An additional 23 loci were significantly associated but failed to transfer because of directionally inconsistent effects. Six loci were associated with adult height in all three groups. Using differences in linkage disequilibrium patterns between HapMap CEU or CHB reference data and our African American sample, we fine-mapped these six loci, improving both the localization and the annotation of these transferable associations.

  17. Immunohistochemical localization of cyclooxygenase-1 and cyclooxygenase-2 in the human fetal and adult male reproductive tracts.

    Science.gov (United States)

    Kirschenbaum, A; Liotta, D R; Yao, S; Liu, X H; Klausner, A P; Unger, P; Shapiro, E; Leav, I; Levine, A C

    2000-09-01

    The first rate-limiting step in the conversion of arachidonic acid to PGs is catalyzed by cyclooxygenase (Cox). Two isoforms of Cox have been identified, Cox-1 (constitutively expressed) and Cox-2 (inducible form), which are the products of two different genes. In this study we describe the immunohistochemical localization of Cox-1 and -2 in the human male fetal and adult reproductive tracts. There was no Cox-1 expression in fetal samples (prostate, seminal vesicles, or ejaculatory ducts), and only minimal expression in adult tissues. There was no expression of Cox-2 in the fetal prostate. In a prepubertal prostate there was some Cox-2 expression that localized exclusively to the smooth muscle cells of the transition zone. In adult hyperplastic prostates, Cox-2 was strongly expressed in smooth muscle cells, with no expression in the luminal epithelial cells. Cox-2 was strongly expressed in epithelial cells of both fetal and adult seminal vesicles and ejaculatory ducts. The Cox-2 staining intensity in the fetal ejaculatory ducts during various times of gestation correlated with previously reported testosterone production rates by the fetal testis. These data indicate that Cox-2 is the predominant isoform expressed in the fetal male reproductive tract, and its expression may be regulated by androgens. The distinct cell type-specific expression patterns of Cox-2 in the prostate (smooth muscle) vs. the seminal vesicles and ejaculatory ducts (epithelium) may reflect the different roles of PGs in these tissues.

  18. 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

  19. 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

  20. The ependymal region of the adult human spinal cord differs from other species and shows ependymoma-like features.

    Science.gov (United States)

    Garcia-Ovejero, Daniel; Arevalo-Martin, Angel; Paniagua-Torija, Beatriz; Florensa-Vila, José; Ferrer, Isidro; Grassner, Lukas; Molina-Holgado, Eduardo

    2015-06-01

    Several laboratories have described the existence of undifferentiated precursor cells that may act like stem cells in the ependyma of the rodent spinal cord. However, there are reports showing that this region is occluded and disassembled in humans after the second decade of life, although this has been largely ignored or interpreted as a post-mortem artefact. To gain insight into the patency, actual structure, and molecular properties of the adult human spinal cord ependymal region, we followed three approaches: (i) with MRI, we estimated the central canal patency in 59 control subjects, 99 patients with traumatic spinal cord injury, and 26 patients with non-traumatic spinal cord injuries. We observed that the central canal is absent from the vast majority of individuals beyond the age of 18 years, gender-independently, throughout the entire length of the spinal cord, both in healthy controls and after injury; (ii) with histology and immunohistochemistry, we describe morphological properties of the non-lesioned ependymal region, which showed the presence of perivascular pseudorosettes, a common feature of ependymoma; and (iii) with laser capture microdissection, followed by TaqMan® low density arrays, we studied the gene expression profile of the ependymal region and found that it is mainly enriched in genes compatible with a low grade or quiescent ependymoma (53 genes); this region is enriched only in 14 genes related to neurogenic niches. In summary, we demonstrate here that the central canal is mainly absent in the adult human spinal cord and is replaced by a structure morphologically and molecularly different from that described for rodents and other primates. The presented data suggest that the ependymal region is more likely to be reminiscent of a low-grade ependymoma. Therefore, a direct translation to adult human patients of an eventual therapeutic potential of this region based on animal models should be approached with caution.

  1. Depth-varying density and organization of chondrocytes in immature and mature bovine articular cartilage assessed by 3d imaging and analysis

    Science.gov (United States)

    Jadin, Kyle D.; Wong, Benjamin L.; Bae, Won C.; Li, Kelvin W.; Williamson, Amanda K.; Schumacher, Barbara L.; Price, Jeffrey H.; Sah, Robert L.

    2005-01-01

    Articular cartilage is a heterogeneous tissue, with cell density and organization varying with depth from the surface. The objectives of the present study were to establish a method for localizing individual cells in three-dimensional (3D) images of cartilage and quantifying depth-associated variation in cellularity and cell organization at different stages of growth. Accuracy of nucleus localization was high, with 99% sensitivity relative to manual localization. Cellularity (million cells per cm3) decreased from 290, 310, and 150 near the articular surface in fetal, calf, and adult samples, respectively, to 120, 110, and 50 at a depth of 1.0 mm. The distance/angle to the nearest neighboring cell was 7.9 microm/31 degrees , 7.1 microm/31 degrees , and 9.1 microm/31 degrees for cells at the articular surface of fetal, calf, and adult samples, respectively, and increased/decreased to 11.6 microm/31 degrees , 12.0 microm/30 degrees , and 19.2 microm/25 degrees at a depth of 0.7 mm. The methodologies described here may be useful for analyzing the 3D cellular organization of cartilage during growth, maturation, aging, degeneration, and regeneration.

  2. En bloc joystick reduction of a comminuted intra-articular distal radius fracture: a technical trick.

    Science.gov (United States)

    Siegall, Evan; Ziran, Bruce

    2014-08-01

    A patient with a 1-month-old intra-articular distal radius fracture (treated closed in a splint) presented with an unacceptable degree of pain and stiffness caused by shortening and dorsal angulation of the distal radius. The fracture was comminuted with 4 or 5 distinct fragments, several involving the articular surface. Surgical correction was attempted. During the procedure, it was noted that, though the distal radius was shortened and angulated, there was actually acceptable congruity of the articular surface itself, despite the intra-articular nature of the fracture. Bone quality was poor and healing incomplete. Thus, we were concerned the currently congruous articular surface would fall apart with manipulation. Given this situation, we used a unique scaffolding technique with Kirschner wires placed in perpendicular fashion to both hold the articular surface intact and manipulate it en bloc. This technique is a simple way to turn a complex fracture into an easily reduced 2-part fracture.

  3. A classical brown adipose tissue mRNA signature partly overlaps with brite in the supraclavicular region of adult humans

    DEFF Research Database (Denmark)

    Jespersen, Naja Zenius; Larsen, Therese Juhlin; Peijs, Lone;

    2013-01-01

    . A similar mRNA expression profile was observed when comparing isolated human adipocytes from BAT and white adipose tissue (WAT) depots, differentiated in vitro. In conclusion, our data suggest that human BAT might consist of both classical brown and recruitable brite adipocytes, an observation important......Human brown adipose tissue (BAT) has been detected in adults but was recently suggested to be of brite/beige origin. We collected BAT from the supraclavicular region in 21 patients undergoing surgery for suspected cancer in the neck area and assessed the gene expression of established murine...... markers for brown, brite/beige, and white adipocytes. We demonstrate that a classical brown expression signature, including upregulation of miR-206, miR-133b, LHX8, and ZIC1 and downregulation of HOXC8 and HOXC9, coexists with an upregulation of two newly established brite/beige markers, TBX1 and TMEM26...

  4. Comparison of the Immunogenicity and Reactogenicity of Cervarix and Gardasil Human Papillomavirus Vaccines in HIV-Infected Adults

    DEFF Research Database (Denmark)

    Nielsen, Lars Toft; Storgaard, Merete; Müller, Martin;

    2013-01-01

    Objectives. To compare the immunogenicity and reactogenicity of Cervarix(®) or Gardasil(®) Human Papillomavirus (HPV) vaccines in HIV-infected adults.Methods. A double-blind, controlled trial randomizing HIV-positive adults to receive three doses of Cervarix(®) or Gardasil(®) at 0, 1.5 and 6 months.......Results. Ninety-two participants were included in the study. Anti-HPV-18 antibody titers were higher in the Cervarix(®) group compared with the Gardasil(®) group at 7 and 12 months. No significant differences in anti-HPV-16 antibody titers were found among vaccine groups. Among Cervarix(®) vaccinees, women had.......Conclusions. Both vaccines were immunogenic and well tolerated. Compared with Gardasil(®), Cervarix(®) induced superior vaccine responses among HIV-infected women whereas in HIV-infected men the difference in immunogenicity was less pronounced....

  5. Intra-articular osteoid osteoma at the femoral trochlea treated with osteochondral autograft transplantation

    Science.gov (United States)

    Leeman, Joshua J; Motamedi, Daria; Wildman-Tobriner, Ben; O’Donnell, Richard J; Link, Thomas M

    2016-01-01

    We present the case of an intra-articular osteoid osteoma at the femoral trochlea. Intra-articular osteoid osteoma can present a diagnostic challenge both clinically and with imaging because it presents differently from the classic cortical osteoid osteoma. Given the lesion’s proximity to overlying cartilage, the patient underwent resection of the lesion with osteochondral autograft transplantation at the surgical defect. A comprehensive literature review and discussion of intra-articular osteoma will be provided. PMID:27761182

  6. Pluripotency of adult stem cells derived from human and rat pancreas

    Science.gov (United States)

    Kruse, C.; Birth, M.; Rohwedel, J.; Assmuth, K.; Goepel, A.; Wedel, T.

    Adult stem cells are undifferentiated cells found within fully developed tissues or organs of an adult individuum. Until recently, these cells have been considered to bear less self-renewal ability and differentiation potency compared to embryonic stem cells. In recent studies an undifferentiated cell type was found in primary cultures of isolated acini from exocrine pancreas termed pancreatic stellate cells. Here we show that pancreatic stellate-like cells have the capacity of extended self-renewal and are able to differentiate spontaneously into cell types of all three germ layers expressing markers for smooth muscle cells, neurons, glial cells, epithelial cells, chondrocytes and secretory cells (insulin, amylase). Differentiation and subsequent formation of three-dimensional cellular aggregates (organoid bodies) were induced by merely culturing pancreatic stellate-like cells in hanging drops. These cells were developed into stable, long-term, in vitro cultures of both primary undifferentiated cell lines as well as organoid cultures. Thus, evidence is given that cell lineages of endodermal, mesodermal, and ectodermal origin arise spontaneously from a single adult undifferentiated cell type. Based on the present findings it is assumed that pancreatic stellate-like cells are a new class of lineage uncommitted pluripotent adult stem cells with a remarkable self-renewal ability and differentiation potency. The data emphasize the versatility of adult stem cells and may lead to a reappraisal of their use for the treatment of inherited disorders or acquired degenerative diseases.

  7. VEGF gene expression in adult human thymus fat: a correlative study with hypoxic induced factor and cyclooxygenase-2.

    Directory of Open Access Journals (Sweden)

    Francisco Tinahones

    Full Text Available UNLABELLED: It is well known that the adult human thymus degenerates into fat tissue; however, it has never been considered as a potential source of angiogenic factors. Recently, we have described that this fat (TAT produces angiogenic factors and induces human endothelial cell proliferation and migration, indicating its potential angiogenic properties. DESIGN: Adult thymus fat and subcutaneous adipose tissue specimens were obtained from 28 patients undergoing cardiac surgery, making this tissue readily available as a prime source of adipose tissue. We focused our investigation on determining VEGF gene expression and characterizing the different genes, mediators of inflammation and adipogenesis, and which are known to play a relevant role in angiogenesis regulation. RESULTS: We found that VEGF-A was the isoform most expressed in TAT. This expression was accompanied by an upregulation of HIF-1alpha, COX-2 and HO-1 proteins, and by increased HIF-1 DNA binding activity, compared to SAT. Furthermore, we observed that TAT contains a high percentage of mature adipocytes, 0.25% of macrophage cells, 15% of endothelial cells and a very low percentage of thymocyte cells, suggesting the cellular variability of TAT, which could explain the differences in gene expression observed in TAT. Subsequently, we showed that the expression of genes known as adipogenic mediators, including PPARgamma1/gamma2, FABP-4 and adiponectin was similar in both TAT and SAT. Moreover the expression of these latter genes presented a significantly positive correlation with VEGF, suggesting the potential association between VEGF and the generation of adipose tissue in adult thymus. CONCLUSION: Here we suggest that this fat has a potential angiogenic function related to ongoing adipogenesis, which substitutes immune functions within the adult thymus. The expression of VEGF seems to be associated with COX-2, HO-1 and adipogenesis related genes, suggesting the importance that this new

  8. VEGF Gene Expression in Adult Human Thymus Fat: A Correlative Study with Hypoxic Induced Factor and Cyclooxigenase-2

    Science.gov (United States)

    Tinahones, Francisco; Salas, Julian; Mayas, María Dolores; Ruiz-Villalba, Adrian; Macias-Gonzalez, Manuel; Garrido-Sanchez, Lourdes; DeMora, Manuel; Moreno-Santos, Inmaculada; Bernal, Rosa; Cardona, Fernando; Bekay, Rajaa El

    2009-01-01

    It is well known that the adult human thymus degenerates into fat tissue; however, it has never been considered as a potential source of angiogenic factors. Recently, we have described that this fat (TAT) produces angiogenic factors and induces human endothelial cell proliferation and migration, indicating its potential angiogenic properties. Design Adult thymus fat and subcutaneous adipose tissue specimens were obtained from 28 patients undergoing cardiac surgery, making this tissue readily available as a prime source of adipose tissue. We focused our investigation on determining VEGF gene expression and characterizing the different genes, mediators of inflammation and adipogenesis, and which are known to play a relevant role in angiogenesis regulation. Results We found that VEGF-A was the isoform most expressed in TAT. This expression was accompanied by an upregulation of HIF-1α, COX-2 and HO-1 proteins, and by increased HIF-1 DNA binding activity, compared to SAT. Furthermore, we observed that TAT contains a high percentage of mature adipocytes, 0.25% of macrophage cells, 15% of endothelial cells and a very low percentage of thymocyte cells, suggesting the cellular variability of TAT, which could explain the differences in gene expression observed in TAT. Subsequently, we showed that the expression of genes known as adipogenic mediators, including PPARγ1/γ2, FABP-4 and adiponectin was similar in both TAT and SAT. Moreover the expression of these latter genes presented a significantly positive correlation with VEGF, suggesting the potential association between VEGF and the generation of adipose tissue in adult thymus. Conclusion Here we suggest that this fat has a potential angiogenic function related to ongoing adipogenesis, which substitutes immune functions within the adult thymus. The expression of VEGF seems to be associated with COX-2, HO-1 and adipogenesis related genes, suggesting the importance that this new fat has acquired in research in relation to

  9. 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.

  10. Effects of Articular Cartilage Constituents on Phosphotungstic Acid Enhanced Micro-Computed Tomography

    Science.gov (United States)

    Karhula, Sakari S.; Finnilä, Mikko A.; Lammi, Mikko J.; Ylärinne, Janne H.; Kauppinen, Sami; Rieppo, Lassi; Pritzker, Kenneth P. H.; Nieminen, Heikki J.; Saarakkala, Simo

    2017-01-01

    Contrast-enhanced micro-computed tomography (CEμCT) with phosphotungstic acid (PTA) has shown potential for detecting collagen distribution of articular cartilage. However, the selectivity of the PTA staining to articular cartilage constituents remains to be elucidated. The aim of this study was to investigate the dependence of PTA for the collagen content in bovine articular cartilage. Adjacent bovine articular cartilage samples were treated with chondroitinase ABC and collagenase to degrade the proteoglycan and the collagen constituents in articular cartilage, respectively. Enzymatically degraded samples were compared to the untreated samples using CEμCT and reference methods, such as Fourier-transform infrared imaging. Decrease in the X-ray attenuation of PTA in articular cartilage and collagen content was observed in cartilage depth of 0–13% and deeper in tissue after collagen degradation. Increase in the X-ray attenuation of PTA was observed in the cartilage depth of 13–39% after proteoglycan degradation. The X-ray attenuation of PTA-labelled articular cartilage in CEμCT is associated mainly with collagen content but the proteoglycans have a minor effect on the X-ray attenuation of the PTA-labelled articular cartilage. In conclusion, the PTA labeling provides a feasible CEμCT method for 3D characterization of articular cartilage. PMID:28135331

  11. Decreases in Phospholipids Containing Adrenic and Arachidonic Acids Occur in the Human Hippocampus over the Adult Lifespan.

    Science.gov (United States)

    Hancock, Sarah E; Friedrich, Michael G; Mitchell, Todd W; Truscott, Roger J W; Else, Paul L

    2015-09-01

    One of the biggest risk factors for developing Alzheimer's disease is advanced age. Despite several studies examining changes to phospholipids in the hippocampus during the pathogenesis of Alzheimer's disease, little is known regarding changes to phospholipids in this region during normal adult aging. This study examined the phospholipid composition of the mitochondrial and microsomal membranes of the human hippocampus from post-mortem tissue of neurologically normal subjects aged between 18 and 104 years. Many of the age-related changes found were in low-to-moderately abundant phospholipids in both membrane fractions, with decreases with age being seen in many phospholipids containing either adrenic or arachidonic acid. The most abundant phospholipid of this type was phosphatidylethanolamine 18:0_22:4, which decreased in both the mitochondrial and microsomal membranes by approximately 20% from ages 20 to 100. Subsequent decreases with age were seen in total adrenic and arachidonic acid in the phospholipids of both membrane fractions, but not in either fatty acid specifically within the phosphatidylethanolamine class. Increases with age were seen in the hippocampus for mitochondrial phosphatidylserine 18:0_22:6. This is the first report of changes to molecular phospholipids of the human hippocampus over the adult lifespan, with this study also providing a comprehensive profile of the phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine phospholipids of the human hippocampus.

  12. Migrating neuroblasts in the adult human brain: a stream reduced to a trickle

    Institute of Scientific and Technical Information of China (English)

    Miriam E van Strien; Simone A van den Berge; Elly M Hol

    2011-01-01

    It has long been thought that neurogenesis (birth of neurons) in the mammalian brain only occurs while the central nervous system is still developing.Although the first indications to the contrary already appeared in the 1960s,it took more than 30 years for the neuroscience community to accept that the mammalian adult brain also generates new neurons.Today it is completely accepted that neurogenesis occurs in two mammalian adult brain areas,the subventricular zone (SVZ) near the lateral ventricles and the subgranular zone in the hippocampus.

  13. 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.

  14. Adult human glia, pericytes and meningeal fibroblasts respond similarly to IFNy but not to TGFβ1 or M-CSF.

    Directory of Open Access Journals (Sweden)

    Amy M Smith

    Full Text Available The chemokine Interferon gamma-induced protein 10 (IP-10 and human leukocyte antigen (HLA are widely used indicators of glial activation and neuroinflammation and are up-regulated in many brain disorders. These inflammatory mediators have been widely studied in rodent models of brain disorders, but less work has been undertaken using human brain cells. In this study we investigate the regulation of HLA and IP-10, as well as other cytokines and chemokines, in microglia, astrocytes, pericytes, and meningeal fibroblasts derived from biopsy and autopsy adult human brain, using immunocytochemistry and a Cytometric Bead Array. Interferonγ (IFNγ increased microglial HLA expression, but contrary to data in rodents, the anti-inflammatory cytokine transforming growth factor β1 (TGFβ1 did not inhibit this increase in HLA, nor did TGFβ1 affect basal microglial HLA expression or IFNγ-induced astrocytic HLA expression. In contrast, IFNγ-induced and basal microglial HLA expression, but not IFNγ-induced astrocytic HLA expression, were strongly inhibited by macrophage colony stimulating factor (M-CSF. IFNγ also strongly induced HLA expression in pericytes and meningeal fibroblasts, which do not basally express HLA, and this induction was completely blocked by TGFβ1, but not affected by M-CSF. In contrast, TGFβ1 did not block the IFNγ-induced increase in IP-10 in pericytes and meningeal fibroblasts. These results show that IFNγ, TGFβ1 and M-CSF have species- and cell type-specific effects on human brain cells that may have implications for their roles in adult human brain inflammation.

  15. Identifying protective Streptococcus pyogenes vaccine antigens recognized by both B and T cells in human adults and children

    DEFF Research Database (Denmark)

    Mortensen, Rasmus; Nissen, Thomas Nørrelykke; Fredslund, Sine

    2016-01-01

    No commercial vaccine exists against Group A streptococci (GAS; Streptococcus pyogenes) and only little is known about anti-GAS protective immunity. In our effort to discover new protective vaccine candidates, we selected 21 antigens based on an in silico evaluation. These were all well......-conserved among different GAS strains, upregulated in host-pathogen interaction studies, and predicted to be extracellular or associated with the surface of the bacteria. The antigens were tested for both antibody recognition and T cell responses in human adults and children. The antigenicity of a selected group...

  16. 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; 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

  17. Low/Negative Expression of PDGFR-α Identifies the Candidate Primary Mesenchymal Stromal Cells in Adult Human Bone Marrow

    DEFF Research Database (Denmark)

    Li, Hongzhe; Ghazanfari, Roshanak; Zacharaki, Dimitra;

    2014-01-01

    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...... exhibited high levels of genes associated with mesenchymal lineages and HSC supportive function. Moreover, lin(-)/CD45(-)/CD271(+)/CD140a(low/-) cells effectively mediated the ex vivo expansion of transplantable CD34(+) hematopoietic stem cells. Taken together, these data indicate that CD140a is a key...

  18. 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.

  19. 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…

  20. 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; Chun, Audrey Y.; Estrada, Karol; Luan, Jian'an; Kutalik, Zoltan; 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.; Maegi, Reedik; Mihailov, Evelin; Porcu, Eleonora; Randall, Joshua C.; Scherag, Andre; 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; Stancakova, 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, Loic; Zhang, Weihua; Afzal, Uzma; Arnloev, Johan; Arscott, Gillian M.; Bandinelli, Stefania; Barrett, Amy; Bellis, Claire; Bennett, Amanda J.; Berne, Christian; Blueher, Matthias; Bolton, Jennifer L.; Boettcher, 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.; Doerr, Marcus; Eklund, Niina; Eury, Elodie; Folkersen, Lasse; Garcia, Melissa E.; Geller, Frank; Giedraitis, Vilmantas; Go, Alan S.; Grallert, Harald; Grammer, Tanja B.; Graessler, Juergen; Groenberg, 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, Bent; Johansson, Asa; Jolley, Jennifer; Juliusdottir, Thorhildur; Junttila, Juhani; Kho, Abel N.; Kinnunen, Leena; Klopp, Norman; Kocher, Thomas; Kratzer, Wolfgang; Lichtner, Peter; Lind, Lars; Lindstroem, Jaana; Lobbens, Stephane; 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.; Mueller, Gabriele; Mueller-Nurasyid, Martina; Musk, Arthur W.; Narisu, Narisu; Nauck, Matthias; Nolte, Ilja M.; Noethen, 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; Shin, Jianxin; Silventoinen, Karri; Smit, Johannes H.; Smith, Albert Vernon; Smolonska, Joanna; Stanton, Alice V.; Stirrups, Kathleen; Stott, David J.; Stringham, Heather M.; Sundstrom, Johan; Swertz, Morris A.; Syvanen, 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; Ferrieres, 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; Lehtimaki, Terho; Lupoli, Sara; Madden, Pamela A. F.; Mannisto, Satu; Manunta, Paolo; Marette, Andre; 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; Toenjes, 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, Stephane; 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.; Maerz, Winfried; Melbye, Mads; Moebus, Susanne; Munroe, Patricia B.; Njolstad, Inger; Oostra, Ben A.; Palmer, Colin N. A.; Pedersen, Nancy L.; Perola, Markus; Perusse, 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; Voelzke, 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, Ines; 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, Andre 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.

    2014-01-01

    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 similar to 2,000,

  1. 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; D. Absher (Devin); E. Albrecht (Eva); D. Anderson (David); 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 H.); 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); 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 B.); 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. 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 (Cock); 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); 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 1/42,

  2. 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.

  3. Effects of Balsamodendron mukul Gum Resin Extract on Articular Cartilage in Papain-induced Osteoarthritis.

    Science.gov (United States)

    Manjhi, Jayanand; Gupta, Maneesh; Sinha, Anvesha; Rawat, Beena; Rai, Durg V

    2016-07-01

    Context • Osteoarthritis (OA) is one of the most prevalent chronic diseases of the musculoskeleton, causing functional disability among older adults. Management of OA includes conventional pharmacological treatments consisting primarily of nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, physiotherapy, and surgical procedures. The medications are not ideal therapeutic agents; NSAIDs in particular can cause serious side effects. Objective • The study was conducted to investigate the effects of Balsamodendron mukul (BDM) gum resin extract on cartilage damage and microstructural changes in the subchondral bone of rats with papain-induced, osteoarthritic knee joints. Design • The authors designed a parallel randomized, controlled study to examine the effects of 3 concentrations of BDM on OA in a murine model. Setting • The present study was undertaken at the research laboratory, Faculty of Biological Engineering, Shobhit University (Modipuram, Meerut, India). Intervention • OA was induced by intra-articular injections of 0.2 mL of 4% papain solution and 0.1 mL of 0.03 M cysteine through the patellar ligament using a 26-gauge, 1.27-cm needle. The rats in the sham group received same volume of isotonic sodium chloride solution. The rats were divided into 6 groups : (1) control group-fresh rats, with ages and genders similar to those of the other groups but with no induction of OA and no treatments; (2) sham group-rats receiving a sham induction of OA using an intra-articular injection of saline of the same volume as the papain given to all OA rats but no treatments; (3) OA group-rats induced with OA but receiving no treatments; (4) OA + BDM (10%) group-rats induced with OA that received a 10% dose of BDM; (5) OA + BDM (20%) group-rats induced with OA that received a 20% dose of BDM; and (6) OA + BDM (40%) group-rats induced with OA that received a 40% dose of BDM. Rats in the treatment groups were fed their respective doses of BDM extract for 30 d

  4. Acute anterior uveitis and other extra-articular manifestations of spondyloarthritis

    Science.gov (United States)

    Mitulescu, TC; Popescu, C; Naie, A; Predeţeanu, D; Popescu, V; Alexandrescu, C; Voinea, LM

    2015-01-01

    Background: Spondyloarthritis (SpA) is associated with an array of peripheral manifestations. Our study aims to evaluate extra-articular manifestations of SpA in a Romanian academic clinical setting and to observe their associations with different disease measures. Methods: The study was designed to note the extra-articular manifestations of SpA patients in a cross-sectional and retrospective manner. Records included demographics, inflammation markers, SpA clinical characteristics, treatment regimes, associated osteoporosis and cardiovascular morbidity. Data were assessed by using appropriate non-parametric tests. Results: A total of 126 SpA patients were included. The most common extra-articular manifestations were skin involvement in the form of psoriasis (34.1%), eye involvement in the form of acute anterior uveitis (8.7%) and dactylitis (7.2%). Compared to patients with no record of uveitis, uveitis-affected cases were more frequently males, more frequently diagnosed with ankylosing spondylitis, but less frequently dyslipidemic and diagnosed with psoriasis. Psoriasis-affected patients were older and had a higher prevalence of peripheral SpA diagnosis, but a lower prevalence of radiographic sacroiliitis. Conclusions:Acute anterior uveitis in SpA predominantly affects males with AS. This is relevant both to clinical and fundamental science, since its management requires both ophthalmology and rheumatology clinical settings. Psoriasis was associated more frequently with peripheral SpA. Abbreviations: AHT = arterial hypertension, AS = ankylosing spondylitis, ASAS = Assessment in SpondyloArthritis international Society, aSpA = axial spondyloarthritis, BASFI = Bath Ankylosing Spondylitis Functional Index, BASDAI = Bath Ankylosing Spondylitis Disease Activity Index, CRP = C-reactive protein, ESR = erythrocyte sedimentation rate, DM2 = type 2 diabetes mellitus, HLA = human leukocyte antigen, IBD = inflammatory bowel disease, MRI = magnetic resonance imaging, m

  5. Metabolic Effects of Avocado/Soy Unsaponifiables on Articular Chondrocytes

    Directory of Open Access Journals (Sweden)

    Louis Lippiello

    2008-01-01

    Full Text Available Avocado/soy unsaponifiable (ASU components are reported to have a chondroprotective effect by virtue of anti-inflammatory and proanabolic effects on articular chondrocytes. The identity of the active component(s remains unknown. In general, sterols, the major component of unsaponifiable plant material have been demonstrated to be anti-inflammatory in vitro and in animal models. These studies were designed to clarify whether the sterol content of ASU preparations were the primary contributors to biological activity in articular chondrocytes. ASU samples were analyzed by high pressure liquid chromatography (HPLC and GC mass spectrometry. The sterol content was normalized between diverse samples prior to in vitro testing on bovine chondrocytes. Anabolic activity was monitored by uptake of 35-sulfate into proteoglycans and quantitation of labeled hydroxyproline and proline content after incubation with labeled proline. Anti-inflammatory activity was assayed by measuring reduction of interleukin-1 (IL-1-induced synthesis of PGE2 and metalloproteases and release of label from tissue prelabeled with S-35.All ASU samples exerted a similar time-dependent up-regulation of 35-sulfate uptake in bovine cells reaching a maximum of greater than 100% after 72 h at sterol doses of 1–10 μg/ml. Non-collagenous protein (NCP and collagen synthesis were similarly up-regulated. All ASU were equally effective in dose dependently inhibiting IL-1-induced MMP-3 activity (23–37%, labeled sulfate release (15–23% and PGE2 synthesis (45–58%. Up-regulation of glycosaminoglycan and collagen synthesis and reduction of IL-1 effects in cartilage are consistent with chondroprotective activity. The similarity of activity of ASU from diverse sources when tested at equal sterol levels suggests sterols are important for biologic effects in articular chondrocytes.

  6. Biochemical composition of the superficial layer of articular cartilage.

    Science.gov (United States)

    Crockett, R; Grubelnik, A; Roos, S; Dora, C; Born, W; Troxler, H

    2007-09-15

    To gain more information on the mechanism of lubrication in articular joints, the superficial layer of bovine articular cartilage was mechanically removed in a sheet of ice that formed on freezing the cartilage. Freeze-dried samples contained low concentrations of chondroitin sulphate and protein. Analysis of the protein by SDS PAGE showed that the composition of the sample was comparable to that of synovial fluid (SF). Attenuated total reflection infrared (ATR-IR) spectroscopy of the dried residue indicated that the sample contained mostly hyaluronan. Moreover, ATR-IR spectroscopy of the upper layer of the superficial layer, adsorbed onto silicon, showed the presence of phospholipids. A gel could be formed by mixing hyaluronan and phosphatidylcholine in water with mechanical properties similar to those of the superficial layer on cartilage. Much like the superficial layer of natural cartilage, the surface of this gel became hydrophobic on drying out. Thus, it is proposed that the superficial layer forms from hyaluronan and phospholipids, which associate by hydrophobic interactions between the alkyl chains of the phospholipids and the hydrophobic faces of the disaccharide units in hyaluronan. This layer is permeable to material from the SF and the cartilage, as shown by the presence of SF proteins and chondroitin sulphate. As the cartilage dries out after removal from the joint, the phospholipids migrate towards the surface of the superficial layer to reduce the surface tension. It is also proposed that the highly efficient lubrication in articular joints can, at least in part, be attributed to the ability of the superficial layer to adsorb and hold water on the cartilage surface, thus creating a highly viscous boundary protection.

  7. Progression of articular cartilage degeneration after application of muscle stretch.

    Science.gov (United States)

    Dias, Carolina Náglio Kalil; Renner, Adriana Frias; dos Santos, Anderson Amaro; Vasilceac, Fernando Augusto; Mattiello, Stela Márcia

    2012-01-01

    The aim of study was to evaluate the progression of the ankle articular cartilage alterations after a post-immobilization muscle stretching. Twenty-nine Wistar rats were separated into five groups: C--control, S--stretched, SR--stretch recovery, IS--immobilized and stretched, and ISR--immobilized stretched recovery. The immobilization was maintained for 4 weeks and the left ankle was then stretched manually through a full dorsal flexion for 10 times for 60 s with a 30 s interval between each 60 s period, 7 days/week for 3 weeks. The recovery period was of 7 weeks. At the end of the experiment, the left ankles were removed, processed in paraffin, and stained in hematoxylin-eosin and safranin O. Two blinded observers evaluated the articular cartilage using the Mankin grading system (cellularity, chondrocyte cloning, and proteoglycan content) through light microscopy, and performed the morphometry (cellularity, total thickness, non-calcified thickness, and calcified thickness measures). Both the Mankin grading system and the morphometric analysis showed that the ISR group presented the most increased cellularity among the groups. The IS and SR groups showed the highest proteoglycan loss, and the ISR group showed the same content of proteoglycan observed in the C group. No significant differences were found in the chondrocyte cloning, the total cartilage thickness, the non-calcified cartilage thickness, and the calcified cartilage thickness among the groups. The results suggest that the cartilage can recover the proteoglycan loss caused by immobilization and stretching, probably because of the increased chondrocyte density. Therefore, the ankle articular cartilage responded as to repair the metabolic deficits.

  8. Metabolic Effects of Avocado/Soy Unsaponifiables on Articular Chondrocytes

    Science.gov (United States)

    Nardo, Joseph V.; Harlan, Robert; Chiou, Tiffany

    2008-01-01

    Avocado/soy unsaponifiable (ASU) components are reported to have a chondroprotective effect by virtue of anti-inflammatory and proanabolic effects on articular chondrocytes. The identity of the active component(s) remains unknown. In general, sterols, the major component of unsaponifiable plant material have been demonstrated to be anti-inflammatory in vitro and in animal models. These studies were designed to clarify whether the sterol content of ASU preparations were the primary contributors to biological activity in articular chondrocytes. ASU samples were analyzed by high pressure liquid chromatography (HPLC) and GC mass spectrometry. The sterol content was normalized between diverse samples prior to in vitro testing on bovine chondrocytes. Anabolic activity was monitored by uptake of 35-sulfate into proteoglycans and quantitation of labeled hydroxyproline and proline content after incubation with labeled proline. Anti-inflammatory activity was assayed by measuring reduction of interleukin-1 (IL-1)-induced synthesis of PGE2 and metalloproteases and release of label from tissue prelabeled with S-35.All ASU samples exerted a similar time-dependent up-regulation of 35-sulfate uptake in bovine cells reaching a maximum of greater than 100% after 72 h at sterol doses of 1–10 μg/ml. Non-collagenous protein (NCP) and collagen synthesis were similarly up-regulated. All ASU were equally effective in dose dependently inhibiting IL-1-induced MMP-3 activity (23–37%), labeled sulfate release (15–23%) and PGE2 synthesis (45–58%). Up-regulation of glycosaminoglycan and collagen synthesis and reduction of IL-1 effects in cartilage are consistent with chondroprotective activity. The similarity of activity of ASU from diverse sources when tested at equal sterol levels suggests sterols are important for biologic effects in articular chondrocytes. PMID:18604259

  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. Developmental changes of prefrontal activation in humans: a near-infrared spectroscopy study of preschool children and adults.

    Directory of Open Access Journals (Sweden)

    Yuki Kawakubo

    Full Text Available Previous morphological studies indicated that development of the human prefrontal cortex (PFC appears to continue into late adolescence. Although functional brain imaging studies have sought to determine the time course of functional development of the PFC, it is unclear whether the developmental change occurs after adolescence to adulthood and when it achieves a peak because of the narrow or discontinuous range in the participant's age. Moreover, previous functional studies have not focused on the anterior frontal region, that is, the frontopolar regions (BA9/10. Thus, the present study investigated the developmental change in frontopolar PFC activation associated with letter fluency task by using near-infrared spectroscopy (NIRS, in subjects from preschool children to adults. We analyzed the relative concentration of hemoglobin (ΔHb in the prefrontal cortex measured during the activation task in 48 typically-developing children and adolescents and 22 healthy adults. Consistent with prior morphological studies, we found developmental change with age in the children/adolescents. Moreover, the average Δoxy-Hb in adult males was significantly larger than that in child/adolescent males, but was not true for females. These data suggested that functional development of the PFC continues into late adolescence. Although the developmental change of the frontopolar PFC was independent of gender from childhood to adolescence, in adulthood a gender difference was shown.

  11. Cardiac mechanics in patients with human immunodeficiency virus: a study of systolic myocardial deformation in children and young adults.

    Science.gov (United States)

    Al-Naami, Ghassan; Kiblawi, Fuad; Kest, Helen; Hamdan, Ayman; Myridakis, Dorothy

    2014-08-01

    Human immunodeficiency virus (HIV) infection causes dysfunction of different organ systems. Myocardial diastolic dysfunction has been reported previously in an adult HIV population. Our aim was to study myocardial strain in children and young adults infected by HIV who have apparently normal ejection fraction. Forty HIV-infected patients (mean age 20.6 ± 1.5 years) with normal ejection fraction and 55 matched normal controls (mean age 17 ± 1.5 years) were studied by two-dimensional echocardiogram. The images were stored then exported to velocity vector imaging software for analysis. Measures considered were left-ventricular peak global systolic strain (LV S) and strain rate (LV SR) as well as right-ventricular peak global systolic strain (RV S) and strain rate (RV SR). Circumferential measures of the left ventricle included the following: LV circumferential peak global systolic strain (LV circ S), strain rate (LV circ SR), radial velocity (LV rad vel), and rotational velocity (LV rot vel) at the level of the mitral valve. Statistical significance was set at p strain and strain rate in children and young adults. Normal ejection fraction might be attributed to preserved circumferential myocardial deformation. Strain and strain rate may help identify HIV patients at high risk for cardiac dysfunction and allow early detection of silent myocardial depression.

  12. Relation between shape of the articular eminence and disc displacement in the temporomandibular joint

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Heung Ki; Hwang, Eui Hwan; Lee, Sang Rae [Kyung Hee Univ. College of Dentistry, Seoul (Korea, Republic of)

    2001-09-15

    To investigate the hypothesis that the morphology of the articular eminence of the temporomandibular joint is a predisposing factor for disc displacement. MR images of 126 temporomandibular joints in 94 patients were analyzed to assess for morphology of the articular eminence and disc displacement. The displaced disc was further categorized as disc displacement with reduction (DDWR) and disc displacement without reduction (DDWOR). The morphology of the articular eminence was classified into four types; box, sigmoid, flattened, and deformed. The relationship between the four types of shape of the articular eminence and the two types of disc position was assessed. In the DDWR and DDWOR groups, the morphology of articular eminence were a box type in 40.5%, a sigmoid type in 30.2%, a flattened type in 24.6%, and a deformed type in 4.7%. The box type of the articular eminence were 34.3% in the DDWR group and 42.9% in the DDWOR group. The sigmoid type of the articular eminence were 34.3% in the DDWR group and 28.6% in the DDWOR group. The flattened type of the articular eminence were 28.6% in the DDWR group and 23.1% in the DDWOR group. The deformed type of the articular eminence were 2.9% in the DDWR group and 5.5% in the DDWOR group. Disc displacement in more likely to be found in the temporomandibular joints with a box-shaped articular eminence. It can be considered that shape of the articular eminence is related to the development of disc displacement.

  13. Extra-articular Synovial Chondromatosis Eroding and Penetrating the Acromion

    Science.gov (United States)

    El Rassi, George; Matta, Jihad; Hijjawi, Ayman; Khair, Ousama Abou; Fahs, Sara

    2015-01-01

    Synovial chondromatosis of the shoulder is an uncommon disorder. It usually affects the glenohumeral joint and is characterized by metaplasia of the synovium leading to the formation of osteochondral loose bodies. Few cases of extra-articular subacromial synovial chondromatosis involving the rotator cuff tendon have been reported in the literature. The treatment of previously reported cases consisted of open bursectomy and removal of loose bodies. We report a case of subacromial synovial chondromatosis without rotator cuff involvement but with severe erosion and fracture of the acromion. Treatment consisted of shoulder arthroscopy to remove all loose bodies, total bursectomy, and debridement of the acromion. Potential benefits of arthroscopy were also evaluated. PMID:26697302

  14. Contact characteristics of articular surfaces for talus during gait-a finite element analysis%正常步态下距骨关节面接触特征的有限元分析

    Institute of Scientific and Technical Information of China (English)

    卢昌怀; 余斌; 陈辉强; 林庆荣

    2011-01-01

    [目的]通过有限元法分析正常步态下距骨各关节面软骨应力变化,了解各关节面软骨应力分布的生物力学特征.[方法]利用正常男性的足踝部螺旋 CT 扫描数据,运用三维建模软件,建立足踝部三维几何模型,并对其进行有限元网格划分,分析正常步态下距骨各关节面接触应力及 Von Mises 应力分布.[结果]建立包括骨、软骨、韧带在内的正常人体足踝部三维有限元模型,共21 865 个节点、73 440 个单元,较客观地反映了人体足踝的解剖结构和力学特性.不同位相距骨各关节面接触应力及 Von Mises 应力分布区域和应力值不同.[结论]采用有限元法分析关节软骨应力的生物力学特征是一种可行、有效的方法.%[ Objective] To construct a three- dimensional finite element model (FEM) of normal adult human ankle in order to supply a digital platform for biomechanical research of talar cartilage stress during gait, and understand the stress distribution of cartilage biomechanical characteristics. [ Methods] A three - dimensional FEM of normal adult human ankle was established through helical CT images and meshed, for analysis of contact pressure and Von Mises stress distribution of cartilage during gait. [ Results] An ankle model was constructed including bones, cartilage, ligaments, which was composed of 21 865 nodes, 73 440 elements. The articular surface contact stress and the Von Mises stress distribution and stress values were different in different stance phases. [ Conclusion] The application of FEM is valid and reasonable. It could be optimized by the interference of anatomical data and biomechanical experiments and used in further articular cartilage biomechanics research.

  15. Shape variability of the adult human acetabulum and acetabular fossa related to sex and age by geometric morphometrics. Implications for adult age estimation.

    Science.gov (United States)

    San-Millán, Marta; Rissech, Carme; Turbón, Daniel

    2017-03-01

    This study aims to explore shape variability of the acetabulum during the human adult life span, in relation to sex and age. The human acetabular shape was analysed in 682 os coxae from three different documented skeletal collections from the Iberian Peninsula. Two landmarks and thirty-two sliding semi-landmarks were used for the geometric morphometric procedures and a clock-wise standard was used for orientation. The 180° meridian (6:00) line was positioned over the midpoint of the acetabular notch and 36 reference points in 10° increments along the rim were marked. Data showed that size, sex and age significantly influence acetabular shape variation. Sex differences were significant in individuals younger than 65 years old and were characterised by males exhibiting relatively extended acetabular rim profiles from 10:00 to 1:00, narrower acetabular notches, and reduced acetabular fossae. In addition, three main age-related changes occurred to the acetabular shape in both sexes: outer acetabular profile modification, with extension from 10:00 to 1:00 and reduction from 7:00 to 9:00, acetabular notch narrowing, and acetabular fossa reduction. The age-related changes that were observed are shared by both sexes and seem to be related to bone production associated with age. Specifically, age appears to affect the entire border of the lunate surface: the acetabular rim, both acetabular horns, and the outer edge of the acetabular fossa. Furthermore, shape data confirmed the clover-leaf shape of the acetabular fossa in both males and females. These results improve our understanding of acetabular shape, and assist in refining age-estimation methods and enhancing hip surgery and rehabilitation.

  16. The critical role of UDP-galactose-4-epimerase in osteoarthritis: modulating proteoglycans synthesis of the articular chondrocytes.

    Science.gov (United States)

    Wen, Yinxian; Qin, Jun; Deng, Yu; Wang, Hui; Magdalou, Jacques; Chen, Liaobin

    2014-10-03

    UDP-galactose-4-epimerase (GALE) is a key enzyme catalyzing the interconversion of UDP-glucose and UDP-galactose, as well as UDP-N-acetylglucosamine and UDP-N-acetylgalactosamine, which are all precursors for the proteoglycans (PGs) synthesis. However, whether GALE is essential in cartilage homeostasis remains unknown. Therefore, we investigated the role of GALE in PGs synthesis of human articular chondrocytes, the GALE expression in OA, and the regulation of GALE expression by interleukin-1beta (IL-1β). Silencing GALE gene with specific siRNAs resulted in a markedly inhibition of PGs synthesis in human articular chondrocytes. GALE protein levels were also decreased in both human and rat OA cartilage, thus leading to losses of PGs contents. Moreover, GALE mRNA expression was stimulated by IL-1β in early phase, but suppressed in late phase, while the suppression of GALE expression induced by IL-1β was mainly mediated by stress-activated protein kinase/c-Jun N-terminal kinase pathway. These data indicated a critical role of GALE in maintaining cartilage homeostasis, and suggested that GALE inhibition might contribute to OA progress.

  17. Expression of nestin, mesothelin and epithelial membrane antigen (EMA) in developing and adult human meninges and meningiomas.

    Science.gov (United States)

    Petricevic, Josko; Forempoher, Gea; Ostojic, Ljerka; Mardesic-Brakus, Snjezana; Andjelinovic, Simun; Vukojevic, Katarina; Saraga-Babic, Mirna

    2011-11-01

    The spatial and temporal pattern of appearance of nestin, epithelial membrane antigen (EMA) and mesothelin proteins was immunohistochemically determined in the cells of normal developing and adult human meninges and meningiomas. Human meninges developed as two mesenchymal condensations in the head region. The simple squamous epithelium on the surface of leptomeninges developed during mesenchymal to epithelial transformation. Nestin appeared for the first time in week 7, EMA in week 8, while mesothelin appeared in week 22 of development. In the late fetal period and after birth, nestin expression decreased, whereas expression of EMA and mesothelin increased. EMA appeared in all surface epithelial cells and nodules, while mesothelin was found only in some of them. In adult meninges, all three proteins were predominantly localized in the surface epithelium and meningeal nodules. In meningothelial meningiomas (WHO grade I), EMA was detected in all tumor cells except in the endothelial cells, mesothelin characterized nests of tumor cells, while nestin was found predominantly in the walls of blood vessels. The distribution pattern of those proteins in normal meningeal and tumor cells indicates that nestin might characterize immature cells, while EMA and mesothelin appeared in maturing epithelial cells. Neoplastic transformation of these specific cell lineages contributes to the cell population in meningiomas.

  18. Activation of GPER-1 estradiol receptor downregulates production of testosterone in isolated rat Leydig cells and adult human testis.

    Directory of Open Access Journals (Sweden)

    Laurent Vaucher

    Full Text Available PURPOSE: Estradiol (E2 modulates testicular functions including steroidogenesis, but the mechanisms of E2 signaling in human testis are poorly understood. GPER-1 (GPR30, a G protein-coupled membrane receptor, mediates rapid genomic and non-genomic response to estrogens. The aim of this study was to evaluate GPER-1 expression in the testis, and its role in estradiol dependent regulation of steroidogenesis in isolated rat Leydig cells and human testis. MATERIALS AND METHODS: Isolated Leydig cells (LC from adult rats and human testicular tissue were used in this study. Expression and localization studies of GPER-1 were performed with qRT-PCR, immunofluorescence, immunohistochemistry and Western Blot. Luteinizing Hormone (LH -stimulated, isolated LC were incubated with estradiol, G-1 (GPER-1-selective agonist, and estrogen receptor antagonist ICI 182,780. Testosterone production was measured with radioimmunoassay. LC viability after incubation with G-1 was measured using 3-(4,5-dimethylthiazol-2-yl-5-(3-carboxymethoxyphenyl-2-(4-sulfophenyl-2H-tetrazolium, inner salt (MTS assay. RESULTS: GPER-1 mRNA is abundantly expressed in rat LC and human testis. Co-localization experiments showed high expression levels of GPER-1 protein in LC. E2-dependent activation of GPER-1 lowers testosterone production in isolated rats LCs and in human testis, with statistically and clinically significant drops in testosterone production by 20-30% as compared to estradiol-naïve LC. The exposure to G-1 does not affect viability of isolated LCs. CONCLUSIONS: Our results indicate that activation of GPER-1 lowers testosterone levels in the rat and human testis. The expression of GPER-1 in human testis, which lack ERα, makes it an exciting target for developing new agents affecting testosterone production in men.

  19. Human tau expression reduces adult neurogenesis in a mouse model of tauopathy

    OpenAIRE

    Komuro, Yutaro; Xu, Guixiang; Bhaskar, Kiran; Lamb, Bruce T.

    2015-01-01

    Accumulation of hyperphosphorylated and aggregated microtubule-associated protein tau (MAPT) is a central feature of a class of neurodegenerative diseases termed tauopathies. Notably, there is increasing evidence that tauopathies, including Alzheimer's disease, are also characterized by a reduction in neurogenesis, the birth of adult neurons. However, the exact relationship between hyperphosphorylation and aggregation of MAPT and neurogenic deficits remains unclear, including whether this is ...

  20. 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.

  1. Effect of nitric oxide synthase inhibitor on proteoglycan metabolism in repaired articular cartilage in rabbits

    Institute of Scientific and Technical Information of China (English)

    孙炜; 金大地; 王吉兴; 秦立赟; 刘晓霞

    2003-01-01

    Objective: To study the effect of nitric oxide synthase inhibitor, S-methyl thiocarbamate (SMT), on proteoglycan metabolism in repaired articular cartilage in rabbits. Methods: Twenty-four male New Zealand white rabbits, aged 8 months and weighing 2.5 kg±0.2 kg, were used in this study. Cartilage defects in full thickness were created on the intercondylar articular surface of bilateral femurs of all the rabbits. Then the rabbits were randomly divided into 3 groups (n=8 in each group). The defects in one group were filled with fibrin glue impregnated with recombinant human bone morphogenetic protein-2 (rhBMP-2, BMP group), in one group with fibrin glue impregnated with rhBMP-2 and hypodermic injection with SMT (SMT group) and in the other group with nothing (control group). All the animals were killed at one year postoperatively. The tissue sections were stained with safranine O-fast green and analyzed by Quantiment 500 system to determine the content of glycosaminoglycan through measuring the percentage of safranine O-stained area, the thickness of cartilages and the mean gray scale (average stain intensity). Radiolabelled sodium sulphate (Na235SO4) was used to assess the proteoglycan synthesis. Results: At one year postoperatively, the percentage of safranine O-stained area, the mean gray scale and the cartilage thickness of the repaired tissues in SMT group were significantly higher than those of BMP group (P<0.01) and the control group (P<0.05). Result of incorporation of Na235SO4 showed that the proteoglycan synthesis in SMT group was higher than those of BMP group and the control group (P<0.01). Conclusions: SMT, a nitric oxide synthase inhibitor, can significantly increase the content of glycosaminoglycan and proteoglycan synthesis, and computer-based image analysis is a reliable method for evaluating proteoglycan metabolism.

  2. Pseudomonas aeruginosa septic arthritis of knee after intra-articular ozone injection.

    Science.gov (United States)

    Seyman, Derya; Ozen, Nevgun Sepin; Inan, Dilara; Ongut, Gozde; Ogunc, Dilara

    2012-07-01

    We describe a case of septic arthritis caused by Pseudomonas aeruginosa in an immunocompetent patient following intra-articular ozone injection into the knee. To the best of our knowledge, and after considering the current literature,we believe this case is unique as no other reports of septic arthritis caused by P. aeruginosa following intra-articular ozone injection has been made.

  3. [Systematization of the articular surfaces of the carpometacarpal joints (author's transl)].

    Science.gov (United States)

    el Bacha, A; Maillot, C

    1977-01-01

    A study, done on 100 hands, of the systematization of the articular surfaces of the carpometacarpal joints, clearly delineates the variability of circumference, dimesions, and relief of the articular facets. An attempt to draw general conclusions from this morphological study, in terms of arthrokinetics, leads to an understanding of the nature of the joints and the movements that are performed at this site.

  4. Detailed Analysis of the Articular Domain in Patients with Primary Sjögren Syndrome

    NARCIS (Netherlands)

    Arends, Suzanne; Meiners, Petra M; Moerman, Rada V; Vissink, Arjan; Spijkervet, Frederik K L; Kroese, Frans G M; Brouwer, Elisabeth; Bootsma, Hendrika

    2017-01-01

    OBJECTIVE: We used the 28-joint Disease Activity Score (DAS28) and the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) articular domain to assess the effect of rituximab (RTX) and abatacept (ABA) on articular involvement in primary Sjögren syndrome (pSS). METHOD

  5. Luxación intra-articular de rótula Intra-articular dislocation of patella

    OpenAIRE

    2006-01-01

    Presentamos el caso de una paciente de 73 años de edad que, tras una caída accidental en las escaleras, sufrió una luxación intra-articular aguda de rótula de la rodilla izquierda. Esta luxación excepcional presentaba incarceración del polo proximal rotuliano en el surco intercondíleo femoral. Se realizó reducción bajo anestesia general debido al dolor y contractura muscular en los intentos de reducción sin anestesia. Realizamos revision quirúrgica que descartó lesiones asociadas del aparato ...

  6. Non-linear model for compression tests on articular cartilage.

    Science.gov (United States)

    Grillo, Alfio; Guaily, Amr; Giverso, Chiara; Federico, Salvatore

    2015-07-01

    Hydrated soft tissues, such as articular cartilage, are often modeled as biphasic systems with individually incompressible solid and fluid phases, and biphasic models are employed to fit experimental data in order to determine the mechanical and hydraulic properties of the tissues. Two of the most common experimental setups are confined and unconfined compression. Analytical solutions exist for the unconfined case with the linear, isotropic, homogeneous model of articular cartilage, and for the confined case with the non-linear, isotropic, homogeneous model. The aim of this contribution is to provide an easily implementable numerical tool to determine a solution to the governing differential equations of (homogeneous and isotropic) unconfined and (inhomogeneous and isotropic) confined compression under large deformations. The large-deformation governing equations are reduced to equivalent diffusive equations, which are then solved by means of finite difference (FD) methods. The solution strategy proposed here could be used to generate benchmark tests for validating complex user-defined material models within finite element (FE) implementations, and for determining the tissue's mechanical and hydraulic properties from experimental data.

  7. Topographic matching of distal radius and proximal fibula articular surface for distal radius osteoarticular reconstruction.

    Science.gov (United States)

    Zhang, H; Chen, S; Wang, Z; Guo, Y; Liu, B; Tong, D

    2016-07-01

    During osteoarticular reconstruction of the distal radius with the proximal fibula, congruity between the two articular surfaces is an important factor in determining the quality of the outcome. In this study, a three-dimensional model and a coordinate transformation algorithm were developed on computed tomography scanning. Articular surface matching was performed and parameters for the optimal position were determined quantitatively. The mean radii of best-fit spheres of the articular surfaces of the distal radius and proximal fibula were compared quantitatively. The radial inclination and volar tilt following reconstruction by an ipsilateral fibula graft, rather than the contralateral, best resembles the values of the native distal radius. Additionally, the ipsilateral fibula graft reconstructed a larger proportion of the distal radius articular surface than did the contralateral. The ipsilateral proximal fibula graft provides a better match for the reconstruction of the distal radius articular surface than the contralateral, and the optimal position for graft placement is quantitatively determined.

  8. Extra-articular hip impingement: a narrative review of the literature

    Science.gov (United States)

    Cheatham, Scott W.

    2016-01-01

    There is growing subgroup of patients with poor outcomes after hip arthroscopy for intra-articular pathology suggesting unrecognized cause(s) of impingement may exist. Extra-articular hip impingement (EHI) is an emerging group of conditions that have been associated with intra-articular causes of impingement and may be an unrecognized source of pain. EHI is caused by abnormal contact between the extra-articular regions of the proximal femur and pelvis. This review discusses the most common forms for EHI including: central iliopsoas impingement, subspine impingement, ischiofemoral impingement, and greater trochanteric-pelvic impingement. The clinical presentation of each pathology will be discussed since EHI conditions share similar clinical features as the intra-articular pathology but also contain some unique characteristics. PMID:27069266

  9. A Western diet ecological module identified from the 'humanized' mouse microbiota predicts diet in adults and formula feeding in children.

    Science.gov (United States)

    Siddharth, Jay; Holway, Nicholas; Parkinson, Scott J

    2013-01-01

    The interplay between diet and the microbiota has been implicated in the growing frequency of chronic diseases associated with the Western lifestyle. However, the complexity and variability of microbial ecology in humans and preclinical models has hampered identification of the molecular mechanisms underlying the association of the microbiota in this context. We sought to address two key questions. Can the microbial ecology of preclinical models predict human populations? And can we identify underlying principles that surpass the plasticity of microbial ecology in humans? To do this, we focused our study on diet; perhaps the most influential factor determining the composition of the gut microbiota. Beginning with a study in 'humanized' mice we identified an interactive module of 9 genera allied with Western diet intake. This module was applied to a controlled dietary study in humans. The abundance of the Western ecological module correctly predicted the dietary intake of 19/21 top and 21/21 of the bottom quartile samples inclusive of all 5 Western and 'low-fat' diet subjects, respectively. In 98 volunteers the abundance of the Western module correlated appropriately with dietary intake of saturated fatty acids, fat-soluble vitamins and fiber. Furthermore, it correlated with the geographical location and dietary habits of healthy adults from the Western, developing and third world. The module was also coupled to dietary intake in children (and piglets) correlating with formula (vs breast) feeding and associated with a precipitous development of the ecological module in young children. Our study provides a conceptual platform to translate microbial ecology from preclinical models to humans and identifies an ecological network module underlying the association of the gut microbiota with Western dietary habits.

  10. A Western diet ecological module identified from the 'humanized' mouse microbiota predicts diet in adults and formula feeding in children.

    Directory of Open Access Journals (Sweden)

    Jay Siddharth

    Full Text Available The interplay between diet and the microbiota has been implicated in the growing frequency of chronic diseases associated with the Western lifestyle. However, the complexity and variability of microbial ecology in humans and preclinical models has hampered identification of the molecular mechanisms underlying the association of the microbiota in this context. We sought to address two key questions. Can the microbial ecology of preclinical models predict human populations? And can we identify underlying principles that surpass the plasticity of microbial ecology in humans? To do this, we focused our study on diet; perhaps the most influential factor determining the composition of the gut microbiota. Beginning with a study in 'humanized' mice we identified an interactive module of 9 genera allied with Western diet intake. This module was applied to a controlled dietary study in humans. The abundance of the Western ecological module correctly predicted the dietary intake of 19/21 top and 21/21 of the bottom quartile samples inclusive of all 5 Western and 'low-fat' diet subjects, respectively. In 98 volunteers the abundance of the Western module correlated appropriately with dietary intake of saturated fatty acids, fat-soluble vitamins and fiber. Furthermore, it correlated with the geographical location and dietary habits of healthy adults from the Western, developing and third world. The module was also coupled to dietary intake in children (and piglets correlating with formula (vs breast feeding and associated with a precipitous development of the ecological module in young children. Our study provides a conceptual platform to translate microbial ecology from preclinical models to humans and identifies an ecological network module underlying the association of the gut microbiota with Western dietary habits.

  11. Coma in fatal adult human malaria is not caused by cerebral oedema

    Directory of Open Access Journals (Sweden)

    Pongponratn Emsri

    2011-09-01

    Full Text Available Abstract Background The role of brain oedema in the pathophysiology of cerebral malaria is controversial. Coma associated with severe Plasmodium falciparum malaria is multifactorial, but associated with histological evidence of parasitized erythrocyte sequestration and resultant microvascular congestion in cerebral vessels. To determine whether these changes cause breakdown of the blood-brain barrier and resultant perivascular or parenchymal cerebral oedema, histology, immunohistochemistry and image analysis were used to define the prevalence of histological patterns of oedema and the expression of specific molecular pathways involved in water balance in the brain in adults with fatal falciparum malaria. Methods The brains of 20 adult Vietnamese patients who died of severe malaria were examined for evidence of disrupted vascular integrity. Immunohistochemistry and image analysis was performed on brainstem sections for activation of the vascular endothelial growth factor (VEGF receptor 2 and expression of the aquaporin 4 (AQP4 water channel protein. Fibrinogen immunostaining was assessed as evidence of blood-brain barrier leakage and perivascular oedema formation. Correlations were performed with clinical, biochemical and neuropathological parameters of severe malaria infection. Results The presence of oedema, plasma protein leakage and evidence of VEGF signalling were heterogeneous in fatal falciparum malaria and did not correlate with pre-mortem coma. Differences in vascular integrity were observed between brain regions with the greatest prevalence of disruption in the brainstem, compared to the cortex or midbrain. There was a statistically non-significant trend towards higher AQP4 staining in the brainstem of cases that presented with coma (P = .02. Conclusions Histological evidence of cerebral oedema or immunohistochemical evidence of localised loss of vascular integrity did not correlate with the occurrence of pre-mortem coma in adults with

  12. Adult hippocampal neurogenesis reduces memory interference in humans: opposing effects of aerobic exercise and depression

    Directory of Open Access Journals (Sweden)

    Nicolas eDéry

    2013-04-01

    Full Text Available Since the remarkable discovery of adult neurogenesis in the mammalian hippocampus, considerable effort has been devoted to unraveling the functional significance of these new neurons. Our group has proposed that a continual turnover of neurons in the DG could contribute to the development of event-unique memory traces that act to reduce interference between highly similar inputs. To test this theory, we implemented a continuous recognition task containing some objects that were repeated across trials as well as some objects that were highly similar, but not identical, to ones previously observed. The similar objects, termed lures, overlap substantially with previously viewed stimuli, and thus, may require hippocampal neurogenesis in order to avoid catastrophic interference. Lifestyle factors such as aerobic exercise and stress have been shown to impact the local neurogenic microenvironment, leading to enhanced and reduced levels of DG neurogenesis, respectively. Accordingly, we hypothesized that healthy young adults who take part in a long-term aerobic exercise regime would demonstrate enhanced performance on the visual pattern separation task, specifically at correctly categorizing lures as similar. Indeed, those who experienced a proportionally large change in fitness demonstrated a significantly greater improvement in their ability to correctly identify lure stimuli as similar. Conversely, we expected that those who score high on depression scales, an indicator of chronic stress, would exhibit selective deficits at appropriately categorizing lures. As expected, those who scored high on the Beck Depression Inventory (BDI were significantly worse than those with relatively lower BDI scores at correctly identifying lures as similar, while performance on novel and repeated stimuli was identical. Taken together, our results support the hypothesis that adult-born neurons in the DG contribute to the orthogonalization of incoming information.

  13. 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....

  14. Proteolytic processing of anti-Müllerian hormone differs between human fetal testes and adult ovaries

    DEFF Research Database (Denmark)

    Mamsen, Linn; Petersen, TS; Jeppesen, JV

    2015-01-01

    From early embryonic life, anti-Müllerian hormone (AMH) is produced by Sertoli cells and is essential for male sex differentiation. In females, AMH is produced by immature granulosa cells (GCs) but a definitive function in females is uncertain. We have assessed the cellular localization...... and specificity of a panel of five novel high-affinity AMH monoclonal antibodies. Two recognize the mature C-terminal form of AMH, whereas three recognize the active pro-mature form of AMH in human tissue. The antibodies were tested on fetal male testicular and mesonephric tissue aged 8-19 weeks post conception...... (pc), fetal male serum aged 16-26 weeks pc and human immature GCs by immunofluorescence, immunohistochemistry, ELISA and western blotting. The active pro-mature forms of AMH were expressed in both Sertoli cells from human fetal testis and human immature GCs. In contrast, the mature C-terminal form...

  15. [Animal experiment studies on the effect of intra-articular injections of antiphlogistic-antirheumatic agents on articular cartilage in vivo].

    Science.gov (United States)

    Kalbhen, D A; Schauer, M; Wentsche, B

    1978-01-01

    Animal experiments have shown that weekly intraarticular injections of various antiphlogistic/antirheumatic drugs into the knee joint induce progressive degenerative alterations in joint cartilage. The observed degenerations and destructions are most similar to the pathophysiology of osteoarthrosis in humans. By X-ray and macroscopic techniques the degenerative processes can be studied qualitatively and quantitatively. A decrease of joint space is a sensitive and early indicator of osteoarthrosis and showed that 10 weeks after intraarticular application of Ibuprofen, Phenylbutazone, Oxyphenbutazone, Flufenamic acid, Niflumic acid, Na-salicylate, Clofezone, Bumadizone and Dexamethasone the degenerative alterations in the injected knee joints were more severe than by applications of Chloroquine,D-penicillamine, Salicylamide and Indometacin. The degenerative effect on articular cartilage by the investigated drugs can be explained by their inhibitory potency on anabolic metabolism of connective tissue. The results of our animal experiments lead to the conclusion, that antiinflammatory drugs may also in man induce or accelerate degenerative joint diseases especially after long term treatment with high doses of these drugs.

  16. Intra-articular injection of tenoxicam in rats: assessment of the local effects on the articular cartilage and synovium.

    Science.gov (United States)

    Ozyuvaci, H; Bilgic, B; Ozyuvaci, E; Altan, A; Altug, T; Karaca, C

    2004-01-01

    This study investigated the possible local adverse effects of intra-articular administration of tenoxicam in the rat knee joint. A total of 50 rats were given 0.25 ml of a standard preparation of tenoxicam by injection into the right knee joint and 0.25 ml of 0.9% saline solution by injection into the left knee joint as a control. Groups of 10 rats were killed 24 h, 48 h, 7 days, 14 days and 21 days after tenoxicam administration. Two rats were sham operated; one was killed on the first day and the other on the second day after this procedure. All the joints were prepared and sectioned for histological examination. Tissue loss and oedema were observed in the specimens obtained 24 h and 48 h after treatment with tenoxicam. No pathological changes were observed in the 7-day, 14-day and 21-day specimens, or in the control joints. Caution should be exercised when using intra-articular tenoxicam for post-operative analgesia.

  17. Expression of the neurotrophin receptors Trk A and Trk B in adult human astrocytoma and glioblastoma

    Indian Academy of Sciences (India)

    Shashi Wadhwa; Tapas C Nag; Anupam Jindal; Rahul Kushwaha; Ashok K Mahapatra; Chitra Sarkar

    2003-03-01

    Neurotrophins and their receptors of the Trk family play a critical role in proliferation, differentiation and survival of the developing neurons. There are reports on their expression in neoplasms too, namely, the primitive neuroectodermal tumours of childhood, and in adult astrocytic gliomas. The involvement of Trk receptors in tumour pathogenesis, if any, is not known. With this end in view, the present study has examined 10 tumour biopsy samples (identified as astrocytoma, pilocytic astrocytoma and glioblastoma) and peritumoral brain tissue of adult patients, for the presence of Trk A and Trk B receptors, by immunohistochemistry. The nature of the tumour samples was also confirmed by their immunoreactivity (IR) to glial fibrillary acidic protein. In the peritumoral brain tissue, only neurons showed IR for Trk A and Trk B. On the contrary, in the tumour sections, the IR to both receptors was localized in the vast majority of glia and capillary endothelium. There was an obvious pattern of IR in these gliomas: high levels of IR were present in the low-grade (type I and II) astrocytoma; whereas in the advanced malignant forms (WHO grade IV giant cell glioblastoma and glioblastoma multiforme) the IR was very weak. These findings suggest that Trk A and Trk B are involved in tumour pathogenesis, especially in the early stage, and may respond to signals that elicit glial proliferation, and thus contribute to progression towards malignancy.

  18. The structure and function of the pericellular matrix of articular cartilage.

    Science.gov (United States)

    Wilusz, Rebecca E; Sanchez-Adams, Johannah; Guilak, Farshid

    2014-10-01

    Chondrocytes in articular cartilage are surrounded by a narrow pericellular matrix (PCM) that is both biochemically and biomechanically distinct from the extracellular matrix (ECM) of the tissue. While the PCM was first observed nearly a century ago, its role is still under investigation. In support of early hypotheses regarding its function, increasing evidence indicates that the PCM serves as a transducer of biochemical and biomechanical signals to the chondrocyte. Work over the past two decades has established that the PCM in adult tissue is defined biochemically by several molecular components, including type VI collagen and perlecan. On the other hand, the biomechanical properties of this structure have only recently been measured. Techniques such as micropipette aspiration, in situ imaging, computational modeling, and atomic force microscopy have determined that the PCM exhibits distinct mechanical properties as compared to the ECM, and that these properties are influenced by specific PCM components as well as disease state. Importantly, the unique relationships among the mechanical properties of the chondrocyte, PCM, and ECM in different zones of cartilage suggest that this region significantly influences the stress-strain environment of the chondrocyte. In this review, we discuss recent advances in the measurement of PCM mechanical properties and structure that further increase our understanding of PCM function. Taken together, these studies suggest that the PCM plays a critical role in controlling the mechanical environment and mechanobiology of cells in cartilage and other cartilaginous tissues, such as the meniscus or intervertebral disc.

  19. Insulin-producing cells from adult human bone marrow mesenchymal stem cells control streptozotocin-induced diabetes in nude mice.

    Science.gov (United States)

    Gabr, Mahmoud M; Zakaria, Mahmoud M; Refaie, Ayman F; Ismail, Amani M; Abou-El-Mahasen, Mona A; Ashamallah, Sylvia A; Khater, Sherry M; El-Halawani, Sawsan M; Ibrahim, Rana Y; Uin, Gan Shu; Kloc, Malgorzata; Calne, Roy Y; Ghoneim, Mohamed A

    2013-01-01

    Harvesting, expansion, and directed differentiation of human bone marrow-derived mesenchymal stem cells (BM-MSCs) could provide an autologous source of surrogate β-cells that would alleviate the limitations of availability and/or allogenic rejection following pancreatic or islet transplantation. Bone marrow cells were obtained from three adult type 2 diabetic volunteers and three nondiabetic donors. After 3 days in culture, adherent MSCs were expanded for two passages. At passage 3, differentiation was carried out in a three-staged procedure. Cells were cultured in a glucose-rich medium containing several activation and growth factors. Cells were evaluated in vitro by flow cytometry, immunolabeling, RT-PCR, and human insulin and c-peptide release in responses to increasing glucose concentrations. One thousand cell clusters were inserted under the renal capsule of diabetic nude mice followed by monitoring of their diabetic status. At the end of differentiation, ∼5-10% of cells were immunofluorescent for insulin, c-peptide or glucagon; insulin, and c-peptide were coexpressed. Nanogold immunolabeling for electron microscopy demonstrated the presence of c-peptide in the rough endoplasmic reticulum. Insulin-producing cells (IPCs) expressed transcription factors and genes of pancreatic hormones similar to those expressed by pancreatic islets. There was a stepwise increase in human insulin and c-peptide release by IPCs in response to increasing glucose concentrations. Transplantation of IPCs into nude diabetic mice resulted in control of their diabetic status for 3 months. The sera of IPC-transplanted mice contained human insulin and c-peptide but negligible levels of mouse insulin. When the IPC-bearing kidneys were removed, rapid return of diabetic state was noted. BM-MSCs from diabetic and nondiabetic human subjects could be differentiated without genetic manipulation to form IPCs that, when transplanted, could maintain euglycemia in diabetic mice for 3 months

  20. Comparative analysis of gene expression profiles of hip articular cartilage between non-traumatic necrosis and osteoarthritis.

    Science.gov (United States)

    Wang, Wenyu; Liu, Yang; Hao, Jingcan; Zheng, Shuyu; Wen, Yan; Xiao, Xiao; He, Awen; Fan, Qianrui; Zhang, Feng; Liu, Ruiyu

    2016-10-10

    Hip cartilage destruction is consistently observed in the non-traumatic osteonecrosis of femoral head (NOFH) and accelerates its bone necrosis. The molecular mechanism underlying the cartilage damage of NOFH remains elusive. In this study, we conducted a systematically comparative study of gene expression profiles between NOFH and osteoarthritis (OA). Hip articular cartilage specimens were collected from 12 NOFH patients and 12 controls with traumatic femoral neck fracture for microarray (n=4) and quantitative real-time PCR validation experiments (n=8). Gene expression profiling of articular cartilage was performed using Agilent Human 4×44K Microarray chip. The accuracy of microarray experiment was further validated by qRT-PCR. Gene expression results of OA hip cartilage were derived from previously published study. Significance Analysis of Microarrays (SAM) software was applied for identifying differently expressed genes. Gene ontology (GO) and pathway enrichment analysis were conducted by Gene Set Enrichment Analysis software and DAVID tool, respectively. Totally, 27 differently expressed genes were identified for NOFH. Comparing the gene expression profiles of NOFH cartilage and OA cartilage detected 8 common differently expressed genes, including COL5A1, OGN, ANGPTL4, CRIP1, NFIL3, METRNL, ID2 and STEAP1. GO comparative analysis identified 10 common significant GO terms, mainly implicated in apoptosis and development process. Pathway comparative analysis observed that ECM-receptor interaction pathway and focal adhesion pathway were enriched in the differently expressed genes of both NOFH and hip OA. In conclusion, we identified a set of differently expressed genes, GO and pathways for NOFH articular destruction, some of which were also involved in the hip OA. Our study results may help to reveal the pathogenetic similarities and differences of cartilage damage of NOFH and hip OA.

  1. Strategies for human-driven robot comprehension of spatial descriptions by older adults in a robot fetch task.

    Science.gov (United States)

    Carlson, Laura; Skubic, Marjorie; Miller, Jared; Huo, Zhiyu; Alexenko, Tatiana

    2014-07-01

    This contribution presents a corpus of spatial descriptions and describes the development of a human-driven spatial language robot system for their comprehension. The domain of application is an eldercare setting in which an assistive robot is asked to "fetch" an object for an elderly resident based on a natural language spatial description given by the resident. In Part One, we describe a corpus of naturally occurring descriptions elicited from a group of older adults within a virtual 3D home that simulates the eldercare setting. We contrast descriptions elicited when participants offered descriptions to a human versus robot avatar, and under instructions to tell the addressee how to find the target versus where the target is. We summarize the key features of the spatial descriptions, including their dynamic versus static nature and the perspective adopted by the speaker. In Part Two, we discuss critical cognitive and perceptual processing capabilities necessary for the robot to establish a common ground with the human user and perform the "fetch" task. Based on the collected corpus, we focus here on resolving the perspective ambiguity and recognizing furniture items used as landmarks in the descriptions. Taken together, the work presented here offers the key building blocks of a robust system that takes as input natural spatial language descriptions and produces commands that drive the robot to successfully fetch objects within our eldercare scenario.

  2. Predictors of adult humans' self-control and impulsiveness for food reinforcers.

    Science.gov (United States)

    Forzano, L B; Logue, A W

    1992-08-01

    Humans vary in the degree to which they demonstrate self-control--choice of larger, more delayed over smaller, less delayed reinforcers. When reinforcers consist of food, individual human subjects' choice behavior varies from virtually exclusive self-control to exclusive impulsiveness. The present experiment, using 26 men and 26 women subjects, explored some possible sources of this individual variation through assessing the correlation of behaviors exhibited in the self-control paradigm with various subject characteristics. The results suggest that self-control is negatively related to individuals' reported susceptibility to hunger (Factor 3 of the Three-Factor Eating Questionnaire) and positively related to overall rating of juice desirability, but not to gender or to various measures of caloric deprivation or personality. Relatively high self-perceived levels of food deprivation may decrease self-control, whereas assigning a relatively high value to the reinforcer may increase self-control. Both tendencies would have been adaptive for evolving humans.

  3. Attitudes of young adults to prenatal screening and genetic correction for human attributes and psychiatric conditions.

    Science.gov (United States)

    Milner, K K; Collins, E E; Connors, G R; Petty, E M

    1998-03-05

    With recent advances in DNA technology, questions have arisen as to how this technology should be appropriately used. In this article, results obtained from a survey designed to elicit attitudes of college students to prenatal testing and gene therapy for human attributes and psychiatric conditions are reported. The eleven hypothetical disease phenotypes included schizophrenia, alcoholism, tendency toward violent behavior, attention deficit/hyperactivity disorder, depression requiring medical treatment, obesity, involvement in "dangerous" sports activities, homosexuality, borderline normal IQ (80-100), proportional short stature, and inability to detect perfect pitch. Most students supported prenatal genetic testing for psychiatric disorders and behavior that might result in harm to others (i.e., tendency towards violent behavior) and found prenatal genetic testing for human attributes less desirable. However, the lack of unilateral agreement or disagreement toward any one condition or attribute suggests the potential difficulties ahead in the quest for guidelines for the application of new technologies available to manipulate the human genome.

  4. Transmitted drug-resistance in human immunodeficiency virus-infected adult population in El Salvador, Central America.

    Science.gov (United States)

    Holguín, Á; Yebra, G; Martín, L; de Pineda, A T; Ruiz, L E; Quezada, A Y; Nieto, A I; Escobar, G

    2013-12-01

    El Salvador harbours one of the largest Central American human immunodeficiency virus (HIV) epidemics, but few studies have analysed it in depth. Here, we describe the presence of transmitted drug resistance (TDR) and HIV variants in the HIV-infected adult population in El Salvador. Dried blood spots from 119 HIV-infected antiretroviral-naive adults attended in El Salvador were collected in 2011. The TDR was assessed according to the list recommended by the WHO. HIV-1 variants were described using phylogeny. Pol sequences could be amplified in 88 patients (50.6% men), with a mean age of 35 years. Almost all (96.7%) were infected with HIV through sexual practice and 58.7% were recently diagnosed. The mean CD4(+) count was 474 cells/mm(3) and 43.1% and 15.5% of patients showed moderate (100 000 copies/mL in 24.7% of patients and Salvador, lower than in other Central American studies. Periodical studies are essential to monitor and prevent TDR emergence in low-income and middle-income regions. Also, more efforts are needed to promote early diagnosis and prevention of infection in El Salvador.

  5. Genotyping of human rhinovirus in adult patients with acute respiratory infections identified predominant infections of genotype A21

    Science.gov (United States)

    Ren, Lili; Yang, Donghong; Ren, Xianwen; Li, Mingkun; Mu, Xinlin; Wang, Qi; Cao, Jie; Hu, Ke; Yan, Chunliang; Fan, Hongwei; Li, Xiangxin; Chen, Yusheng; Wang, Ruiqin; An, Fucheng; An, Shuchang; Luo, Ming; Wang, Ying; Xiao, Yan; Xiang, Zichun; Xiao, Yan; Li, Li; Huang, Fang; Jin, Qi; Gao, Zhancheng; Wang, Jianwei

    2017-01-01

    Human rhinovirus (HRV) is an important causative agent of acute respiratory tract infections (ARTIs). The roles of specific HRV genotypes in patients suffering from ARTIs have not been well established. We recruited 147 adult inpatients with community-acquired pneumonia (CAP) and 291 adult outpatients with upper ARTIs (URTIs). Respiratory pathogens were screened via PCR assays. HRV was detected in 42 patients, with 35 species A, five B and two C. Seventeen genotypes were identified, and HRV-A21 ranked the highest (9/42, 21.4%). The HRV-A21-positive infections were detected in four patients with CAP and in five with URTIs, all without co-infections. The HRV-A21 genome sequenced in this study contained 12 novel coding polymorphisms in viral protein (VP) 1, VP2 EF loop, VP3 knob and 3D regions. The infections of HRV-A21 virus obtained in this study could not be neutralized by antiserum of HRV-A21 prototype strain (VR-1131), indicating remarkable antigenic variation. Metagenomic analysis showed the HRV-A21 reads were dominant in bronchoalveolar lavage fluid of the three HRV-A21-positive patients with severe CAP, in which two dead. Our results highlight an unexpected infection of genotype HRV-A21 in the clinic, indicating the necessity of precise genotyping and surveillance of HRVs to improve the clinical management of ARTIs. PMID:28128353

  6. The presence and absence of lymphatic vessels in the adult human intervertebral disc: relation to disc pathology

    Energy Technology Data Exchange (ETDEWEB)

    Kliskey, Karolina; Williams, Kelly; Yu, J.; Urban, Jill; Athanasou, Nick [University of Oxford, Nuffield Department of Orthopaedic, Rheumatology and Musculoskeletal Science, Oxford (United Kingdom); Jackson, David [Weatherall Institute of Molecular Medicine, Human Immunology Unit, Oxford (United Kingdom)

    2009-12-15

    Although the normal adult human intervertebral disc is considered to be avascular, vascularised cellular fibrous tissue can be found in pathological conditions involving the disc such as disc herniation. Whether lymphatics vessels form a component of this reparative tissue is not known as the presence or absence of lymphatics in herniated and normal disc tissue is not known. We examined spinal tissues and discectomy specimens for the presence of lymphatics. The examination used immunohistochemistry to identify the specific lymphatic endothelial cell markers, podoplanin and LYVE1. Lymphatic vessels were not found in the nucleus pulposus or annulus fibrosus of intact, non-herniated lumbar and thoracic discs but were present in the surrounding ligaments. Ingrowth of fibrous tissue was seen in 73% of herniated disc specimens of which 36% contained LYVE1+/podoplanin + lymphatic vessels. Lymphatic vessels were not seen in the sacrum and coccyx or biopsies of four sacrococcygeal chordomas, but they were noted in surrounding extra-osseous fat and fibrous tissue at the edge of the infiltrating tumour. Our findings indicate that lymphatic vessels are not present in the normal adult intervertebral disc but that, when there is extrusion of disc material into surrounding soft tissue, there is ingrowth of reparative fibrous tissue containing lymphatic vessels. Our findings also indicate that chordoma, a tumour of notochordal origin, spreads to regional lymph nodes via lymphatics in para-spinal soft tissues. (orig.)

  7. GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults

    Science.gov (United States)

    Allen, D B; Backeljauw, P; Bidlingmaier, M; Biller, B M K; Boguszewski, M; Burman, P; Butler, G; Chihara, K; Christiansen, J; Cianfarani, S; Clayton, P; Clemmons, D; Cohen, P; Darendeliler, F; Deal, C; Dunger, D; Erfurth, E M; Fuqua, J S; Grimberg, A; Haymond, M; Higham, C; Ho, K; Hoffman, A R; Hokken-Koelega, A; Johannsson, G; Juul, A; Kopchick, J; Lee, P; Pollak, M; Radovick, S; Robison, L; Rosenfeld, R; Ross, R J; Savendahl, L; Saenger, P; Toft Sorensen, H; Stochholm, K; Strasburger, C; Swerdlow, A; Thorner, M

    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 statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement. PMID:26563978

  8. GH safety workshop position paper: a critical appraisal of recombinant human GH therapy in children and adults.

    Science.gov (United States)

    Allen, D B; Backeljauw, P; Bidlingmaier, M; Biller, B M K; Boguszewski, M; Burman, P; Butler, G; Chihara, K; Christiansen, J; Cianfarani, S; Clayton, P; Clemmons, D; Cohen, P; Darendeliler, F; Deal, C; Dunger, D; Erfurth, E M; Fuqua, J S; Grimberg, A; Haymond, M; Higham, C; Ho, K; Hoffman, A R; Hokken-Koelega, A; Johannsson, G; Juul, A; Kopchick, J; Lee, P; Pollak, M; Radovick, S; Robison, L; Rosenfeld, R; Ross, R J; Savendahl, L; Saenger, P; Toft Sorensen, H; Stochholm, K; Strasburger, C; Swerdlow, A; Thorner, M

    2016-02-01

    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 statement highlighted a number of areas for on-going surveillance of long-term safety, including cancer risk, impact on glucose homeostasis, and use of high dose pharmacological rhGH treatment. Over the intervening years, there have been a number of publications addressing the safety of rhGH with regard to mortality, cancer and cardiovascular risk, and the need for long-term surveillance of the increasing number of adults who were treated with rhGH in childhood. Against this backdrop of interest in safety, the European Society of Paediatric Endocrinology (ESPE), the GRS, and the Pediatric Endocrine Society (PES) convened a meeting to reappraise the safety of rhGH. The ouput of the meeting is a concise position statement.

  9. Validation of case-finding algorithms derived from administrative data for identifying adults living with human immunodeficiency virus infection.

    Directory of Open Access Journals (Sweden)

    Tony Antoniou

    Full Text Available OBJECTIVE: We sought to validate a case-finding algorithm for human immunodeficiency virus (HIV infection using administrative health databases in Ontario, Canada. METHODS: We constructed 48 case-finding algorithms using combinations of physician billing claims, hospital and emergency room separations and prescription drug claims. We determined the test characteristics of each algorithm over various time frames for identifying HIV infection, using data abstracted from the charts of 2,040 randomly selected patients receiving care at two medical practices in Toronto, Ontario as the reference standard. RESULTS: With the exception of algorithms using only a single physician claim, the specificity of all algorithms exceeded 99%. An algorithm consisting of three physician claims over a three year period had a sensitivity and specificity of 96.2% (95% CI 95.2%-97.9% and 99.6% (95% CI 99.1%-99.8%, respectively. Application of the algorithm to the province of Ontario identified 12,179 HIV-infected patients in care for the period spanning April 1, 2007 to March 31, 2009. CONCLUSIONS: Case-finding algorithms generated from administrative data can accurately identify adults living with HIV. A relatively simple "3 claims in 3 years" definition can be used for assembling a population-based cohort and facilitating future research examining trends in health service use and outcomes among HIV-infected adults in Ontario.

  10. Suicidal ideation and suicide attempts among human immunodeficiency virus-infected adults: differences in risk factors and their implications.

    Science.gov (United States)

    Kang, Cho Ryok; Bang, Ji Hwan; Cho, Sung-Il; Kim, Kui Nam; Lee, Hee-Jin; Ryu, Bo Yeong; Cho, Soo Kyung; Lee, Young Hwa; Oh, Myoung-Don; Lee, Jong-Koo

    2016-01-01

    Many studies have investigated risk factors for suicidal ideation and suicide attempt; however, most have failed to show differences in risk factors between suicidal ideation and suicide attempt among the human immunodeficiency virus (HIV)-infected population. This study was designed to identify differences in risk factors between suicidal ideation and suicide attempts among HIV-infected adults in Seoul. A face-to-face survey of 457 HIV-infected adults was conducted by the Seoul Metropolitan Government in 2013. Multivariate logistic regression analysis was used to identify factors associated with suicidal ideation and suicide attempt. Among 422 participants, 44% had suicidal ideation, and 11% had suicide attempts. The independent risk factors for suicidal ideation were young and middle age, living with someone, history of AIDS-defining opportunistic disease, history of treatment for depression, lower social support, and psychological status. Beneficiaries of National Medical Aid, economic barriers to treatment, history of treatment for depression, and lower psychological status were independently associated with suicide attempts. Patients with HIV in Korea were treated without cost in some centers. Thus, experiencing an economic barrier to treatment might be due in part to ignorance of HIV care policies. Our findings indicate that suicide attempts are associated with socioeconomic factors and information inequality regarding medical care. In conclusion, suicidal ideation closely associated with the psychosocial factors, whereas suicide attempt demonstrates a stronger association with socioeconomic factors. Suicide prevention measures should be implemented to provide information to help HIV-infected patients.

  11. A physical mechanism for coupling bone resorption and formation in adult human bone

    DEFF Research Database (Denmark)

    Andersen, Thomas Levin; Sondergaard, Teis Esben; Skorzynska, Katarzyna Ewa

    2009-01-01

    During skeletal remodeling, pre-osteoclasts and pre-osteoblasts are targeted to critical sites of the bone to resorb and reconstruct bone matrix, respectively. Coordination of site-specific recruitment of these two cell types is a prerequisite to maintain the specific architecture of each bone...... within strict limits throughout adult life. Here, we determined that the bone marrow microanatomy adjacent to remodeling areas is a central player in this process. By using histomorphometry and multiple immunostainings, we demonstrated in biopsies exhibiting coupled bone resorption and formation...... that osteoclasts and osteoblasts on the bone surface were always covered by a canopy of flat cells expressing osteoblast markers. In contrast, in biopsies in which this canopy was disrupted, bone formation was deficient. Three-dimensional visualizations revealed that this canopy covered the entire remodeling site...

  12. Theoretical study of interactions between human adult hemoglobin and acetate ion by polarizable force field and fragmentation quantum chemistry methods

    Institute of Scientific and Technical Information of China (English)

    YAN XiuFen; JIANG Nan; MA Jing

    2009-01-01

    A series of theoretical approaches,including conventional FF03 and FF03-based polarization model,as well as the generalized energy-based fragmentation (GEBF) quantum chemistry method,have been applied to investigate the interactions between acetate ion (CH_3COO~-) and the α-subunit of human adult hemoglobin (designated as Hb-α) at four binding sites (Lys16,Lys90,Arg92,and Lys127),respectively.The FF03-based polarizable force fields show that the interaction energies between the CH_3COO~-group and Hb-α follow the trend of Arg92>Lys127>Lys90>Lys16.The complexation of CH_3COO~-with Hb-α is governed by the long-range electrostatic interactions and steric effect.

  13. Theoretical study of interactions between human adult hemoglobin and acetate ion by polarizable force field and fragmentation quantum chemistry methods

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    A series of theoretical approaches,including conventional FF03 and FF03-based polarization model,as well as the generalized energy-based fragmentation(GEBF) quantum chemistry method,have been applied to investigate the interactions between acetate ion(CH3COO-) and the α-subunit of human adult hemoglobin(designated as Hb-α) at four binding sites(Lys16,Lys90,Arg92,and Lys127),respectively.The FF03-based polarizable force fields show that the interaction energies between the CH3COO-group and Hb-α follow the trend of Arg92>Lys127>Lys90>Lys16.The complexation of CH3COO-with Hb-α is governed by the long-range electrostatic interactions and steric effect.

  14. Human fetal cardiac progenitors: The role of stem cells and progenitors in the fetal and adult heart.

    Science.gov (United States)

    Bulatovic, Ivana; Månsson-Broberg, Agneta; Sylvén, Christer; Grinnemo, Karl-Henrik

    2016-02-01

    The human fetal heart is formed early during embryogenesis as a result of cell migrations, differentiation, and formative blood flow. It begins to beat around gestation day 22. Progenitor cells are derived from mesoderm (endocardium and myocardium), proepicardium (epicardium and coronary vessels), and neural crest (heart valves, outflow tract septation, and parasympathetic innervation). A variety of molecular disturbances in the factors regulating the specification and differentiation of these cells can cause congenital heart disease. This review explores the contribution of different cardiac progenitors to the embryonic heart development; the pathways and transcription factors guiding their expansion, migration, and functional differentiation; and the endogenous regenerative capacity of the adult heart including the plasticity of cardiomyocytes. Unfolding these mechanisms will become the basis for understanding the dynamics of specific congenital heart disease as well as a means to develop therapy for fetal as well as postnatal cardiac defects and heart failure.

  15. Role of the Subunits Interactions in the Conformational Transitions in Adult Human Hemoglobin: an Explicit Solvent Molecular Dynamics Study

    CERN Document Server

    Yusuff, Olaniyi K; Bussi, Giovanni; Raugei, Simone

    2012-01-01

    Hemoglobin exhibits allosteric structural changes upon ligand binding due to the dynamic interactions between the ligand binding sites, the amino acids residues and some other solutes present under physiological conditions. In the present study, the dynamical and quaternary structural changes occurring in two unligated (deoxy-) T structures, and two fully ligated (oxy-) R, R2 structures of adult human hemoglobin were investigated with molecular dynamics. It is shown that, in the sub-microsecond time scale, there is no marked difference in the global dynamics of the amino acids residues in both the oxy- and the deoxy- forms of the individual structures. In addition, the R, R2 are relatively stable and do not present quaternary conformational changes within the time scale of our simulations while the T structure is dynamically more flexible and exhibited the T\\rightarrow R quaternary conformational transition, which is propagated by the relative rotation of the residues at the {\\alpha}1{\\beta}2 and {\\alpha}2{\\b...

  16. 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

  17. 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

    9 months, with preservation of the ability to release insulin in response to glucose stimulation. Replacement of calf serum with serum from normal human subjects did not affect B-cell survival, but resulted in elevated insulin values partly due to lower insulin degrading activity. Thus the described...

  18. Genetic and environmental influences on adult human height across birth cohorts from 1886 to 1994

    DEFF Research Database (Denmark)

    Jelenkovic, Aline; Hur, Yoon-Mi; Sund, Reijo;

    2016-01-01

    Human height variation is determined by genetic and environmental factors, but it remains unclear whether their influences differ across birth-year cohorts. We conducted an individual-based pooled analysis of 40 twin cohorts including 143,390 complete twin pairs born 1886-1994. Although genetic v...

  19. Relationship between Human Gut Microbiota and Interleukin 6 Levels in Overweight and Obese Adults

    Science.gov (United States)

    Background: Gut microbial diversity and abundance can profoundly impact human health. Research has shown that obese individuals are likely to have altered microbiota compared to lean individuals. Obesity is often considered a pro-inflammatory state, however the relationship between microbiota and i...

  20. Remodeling of the adult human vitreous and vitreoretinal interface : a dynamic process

    NARCIS (Netherlands)

    Ponsioen, Theodorus Leonardus

    2008-01-01

    The vitreous body (or vitreous) of the human eye is an almost acellular, transparent loose-meshed connective tissue consisting mainly of water (99%) and of just 0.1% macromolecules, such as glycosaminoglycans (e.g. hyaluronan), proteoglycans, glycoproteins (such as opticin), collagens, and noncollag

  1. Low Proliferation and Differentiation Capacities of Adult Hippocampal Stem Cells Correlate with Memory Dysfunction in Humans

    Science.gov (United States)

    Coras, Roland; Siebzehnrubl, Florian A.; Pauli, Elisabeth; Huttner, Hagen B.; Njunting, Marleisje; Kobow, Katja; Villmann, Carmen; Hahnen, Eric; Neuhuber, Winfried; Weigel, Daniel; Buchfelder, Michael; Stefan, Hermann; Beck, Heinz; Steindler, Dennis A.; Blumcke, Ingmar

    2010-01-01

    The hippocampal dentate gyrus maintains its capacity to generate new neurons throughout life. In animal models, hippocampal neurogenesis is increased by cognitive tasks, and experimental ablation of neurogenesis disrupts specific modalities of learning and memory. In humans, the impact of neurogenesis on cognition remains unclear. Here, we…

  2. Gene × Smoking Interactions on Human Brain Gene Expression: Finding Common Mechanisms in Adolescents and Adults

    Science.gov (United States)

    Wolock, Samuel L.; Yates, Andrew; Petrill, Stephen A.; Bohland, Jason W.; Blair, Clancy; Li, Ning; Machiraju, Raghu; Huang, Kun; Bartlett, Christopher W.

    2013-01-01

    Background: Numerous studies have examined gene × environment interactions (G × E) in cognitive and behavioral domains. However, these studies have been limited in that they have not been able to directly assess differential patterns of gene expression in the human brain. Here, we assessed G × E interactions using two publically available datasets…

  3. [Gait analysis after intra-articular calcaneus fractures].

    Science.gov (United States)

    Siegmeth, A; Petje, G; Mittlmeier, T; Vécsei, V

    1996-01-01

    We retrospectively compared 20 patients with displaced intra-articular calcaneal fractures by clinical assessment and dynamic pedography. Eleven were treated operatively, 9 conservatively. The purpose was to identify differences in post-traumatic gait performance and to correlate the pedographic data to a clinical score to show its reliability. Twenty individuals without a history of foot injuries were used as a control group. Both groups had restricted motion in the subtalar joint, increased hindfoot and midfoot loading and decreased forefoot loading. Furthermore, they showed prolonged contact phases and an impaired ability to speed up gait during the toe-off phase. Load transfer from the hindfoot to the forefoot showed typical distribution patterns. The operatively treated group showed better functional results with fewer subjective complaints.

  4. Contact mechanics of articular cartilage layers asymptotic models

    CERN Document Server

    Argatov, Ivan

    2015-01-01

    This book presents a comprehensive and unifying approach to articular contact mechanics with an emphasis on frictionless contact interaction of thin cartilage layers. The first part of the book (Chapters 1–4) reviews the results of asymptotic analysis of the deformational behavior of thin elastic and viscoelastic layers. A comprehensive review of the literature is combined with the authors’ original contributions. The compressible and incompressible cases are treated separately with a focus on exact solutions for asymptotic models of frictionless contact for thin transversely isotropic layers bonded to rigid substrates shaped like elliptic paraboloids. The second part (Chapters 5, 6, and 7) deals with the non-axisymmetric contact of thin transversely isotropic biphasic layers and presents the asymptotic modelling methodology for tibio-femoral contact. The third part of the book consists of Chapter 8, which covers contact problems for thin bonded inhomogeneous transversely isotropic elastic layers, and Cha...

  5. Effects of Cryoprotective Agents on the Bovine Articular Chondrocyte Viability

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    Cryopreservation is the process of choice for long term preservation of cells and tissues. In this study, the effects of cryoprotective agents, dimethyl sulfoxide(DMSO), glycerol and 1,2-propanediol on the bovine articular chondrocyte viability were examined experimentally. The CPA was added at the concentrations of 0. 6. 0.9, 1.2 and 1.5 mol/I and at 4℃ and 37℃ and removed at 37℃ in one-step. CPA stepwise addition and removal at 0. 6 and 1. 2 mol/L and at 37℃ was also tested as an alternative protocol. Cell volume excursion during DMSO addition and removal was estimated and correlated well with cell survival rates. Solution makeup affects cell survival rate and a stepwise protocol can improve the cell survival rates significantly.

  6. Multiphysical modelling of fluid transport through osteo-articular media

    Directory of Open Access Journals (Sweden)

    Thibault Lemaire

    2010-03-01

    Full Text Available In this study, a multiphysical description of fluid transport through osteo-articular porous media is presented. Adapted from the model of Moyne and Murad, which is intended to describe clayey materials behaviour, this multiscale modelling allows for the derivation of the macroscopic response of the tissue from microscopical information. First the model is described. At the pore scale, electrohydrodynamics equations governing the electrolyte movement are coupled with local electrostatics (Gauss-Poisson equation, and ionic transport equations. Using a change of variables and an asymptotic expansion method, the macroscopic description is carried out. Results of this model are used to show the importance of couplings effects on the mechanotransduction of compact bone remodelling.Neste estudo uma descrição multifísica do transporte de fluidos em meios porosos osteo articulares é apresentada. Adaptado a partir do modelo de Moyne e Murad proposto para descrever o comportamento de materiais argilosos a modelagem multiescala permite a derivação da resposta macroscópica do tecido a partir da informação microscópica. Na primeira parte o modelo é apresentado. Na escala do poro as equações da eletro-hidrodinâmica governantes do movimento dos eletrolitos são acopladas com a eletrostática local (equação de Gauss-Poisson e as equações de transporte iônico. Usando uma mudança de variáveis e o método de expansão assintótica a derivação macroscópica é conduzida. Resultados do modelo proposto são usados para salientar a importância dos efeitos de acoplamento sobre a transdução mecânica da remodelagem de ossos compactados.

  7. Tratamiento farmacológico invasivo articular en la artrosis

    Directory of Open Access Journals (Sweden)

    D. Benítez Pareja

    2016-04-01

    Full Text Available La degeneración de las articulaciones axiales y periféricas va unida al propio envejecimiento del ser humano. Es responsable del dolor e impotencia funcional, y su fisiopatología es compleja y no del todo conocida. El denominador común en la artrosis es la degeneración del cartílago articular, junto a otras alteraciones secundarias. Su abordaje y manejo del dolor supone todo un reto para las Unidades del Dolor. Históricamente, el tratamiento intervencionista se llevó a cabo mediante infiltraciones a ciegas de diferentes sustancias que alivian el dolor. En la actualidad, la fluoroscopia, y más recientemente los ultrasonidos, son los métodos de elección para la guía de nuestros procedimientos. En cuanto a los fármacos utilizados más comúnmente en nuestras técnicas invasivas articulares destacaremos el ácido hialurónico (AH y el plasma rico en plaquetas (PRP. Los esteroides siguen siendo, en prácticamente todos los estudios, el estándar de oro o fármaco de referencia y sobre los que se comparan el resto de familias de fármacos. Una exploración exhaustiva del paciente, y un algoritmo de decisiones en cuanto a la decisión de realización de estas técnicas, se antoja necesario, adecuándose a cada lugar de trabajo.

  8. Partial rotator cuff injury in athletes: bursal or articular?

    Directory of Open Access Journals (Sweden)

    Cassiano Diniz Carvalho

    2015-08-01

    Full Text Available ABSTRACTA painful shoulder is a very common complaint among athletes, especially in the case of those in sports involving throwing. Partial lesions of the rotator cuff may be very painful and cause significant functional limitation to athletes' sports practice. The incidence of partial lesions of the cuff is variable (13-37%. It is difficult to make the clinical and radiological diagnosis, and this condition should be borne in mind in the cases of all athletes who present symptoms of rotator cuff syndrome, including in patients who are diagnosed only with tendinopathy. OBJECTIVE: To evaluate the epidemiological behavior of partial lesions of the rotator cuff in both amateur and professional athletes in different types of sports. METHODS: We evaluated 720 medical files on athletes attended at the shoulder service of the Discipline of Sports Medicine at the Sports Traumatology Center, Federal University of São Paulo. The majority of them were men (65%. Among all the patients, 83 of them were diagnosed with partial lesions of the rotator cuff, by means of ultrasonography or magnetic resonance, or in some cases using both. We applied the binomial test to compare the proportions found. RESULT: It was observed that intra-articular lesions predominated (67.6% and that these occurred more frequently in athletes in sports involving throwing (66%. Bursal lesions occurred in 32.4% of the athletes, predominantly in those who did muscle building (75%. CONCLUSION: Intra-articular lesions are more frequent than bursal lesions and they occur predominantly in athletes in sports involving throwing, while bursal lesions were more prevalent in athletes who did muscle building.

  9. Extra-Articular Manifestations of Rheumatoid Arthritis, Now

    Directory of Open Access Journals (Sweden)

    Paloma Vela

    2014-06-01

    Full Text Available Rheumatoid arthritis (RA is a chronic systemic inflammatory disease, characterised by polyarthritis and extra-articular organ disease, including rheumatoid nodules, ophthalmologic manifestations, cardiopulmonary disease, vasculitis, neuropathy, glomerulonephritis, Felty’s syndrome, and amyloidosis. Extra-articular manifestations of RA (ExRA occur in 17.8–40.9% of RA patients, 1.5–21.5% of them presenting as severe forms and usually associated with increased morbidity and mortality. They can develop at any time during the course of the disease, even in the early stages, and are associated with certain predisposing factors, such as the presence of rheumatoid factor, smoking, and long-standing severe disease. Rheumatoid nodules, the most common ExRA, have been found to be associated with the development of severe features, such as vasculitis, rheumatoid lung disease, pericarditis, and pleuritis, especially in those patients who develop them within 2 years from RA diagnosis. There is no uniformity in the definition of the term ExRA, which limits comparability between different studies. Several recent surveys suggest a lower frequency, probably due to a better control of disease activity. Diagnosis of ExRA is a challenge for clinicians, given its variable and complex presentation, and the lack of specific diagnostic tests; it must be based on clinical recognition and exclusion of other causes of the signs and symptoms. Furthermore, management continues to be difficult with a bad prognosis in many conditions. This article reviews the clinical aspects of major ExRA, focusing on incidence, clinical features, and therapeutic approaches, and how modern immunosuppressive therapy can change the outcome.

  10. Foetal and postnatal equine articular cartilage development: magnetic resonance imaging and polarised light microscopy

    Directory of Open Access Journals (Sweden)

    C Cluzel

    2013-08-01

    Full Text Available Adult articular cartilage (AC has a well described multizonal collagen structure. Knowledge of foetal AC organisation and development may provide a prototype for cartilage repair strategies, and improve understanding of structural changes in developmental diseases such as osteochondrosis (OC. The objective of this study was to describe normal development of the spatial architecture of the collagen network of equine AC using 1.5 T magnetic resonance imaging (MRI and polarised light microscopy (PLM, at sites employed for cartilage repair studies or susceptible to OC. T2-weighted fast-spin echo (FSE sequences and PLM assessment were performed on distal femoral epiphyses of equine foetuses, foals and adults. Both MRI and PLM revealed an early progressive collagen network zonal organisation of the femoral epiphyses, beginning at 4 months of gestation. PLM revealed that the collagen network of equine foetal AC prior to birth was already organised into an evident anisotropic layered structure that included the appearance of a dense tangential zone in the superficial AC in the youngest specimens, with the progressive development of an underlying transitional zone. A third, increasingly birefringent, radial layer developed in the AC from 6 months of gestation. Four laminae were observed on the MR images in the last third of gestation. These included not only the AC but also the superficial growth plate of the epiphysis. These findings provide novel data on normal equine foetal cartilage collagen development, and may serve as a template for cartilage repair studies in this species or a model for developmental studies of OC.

  11. Tenascin and aggrecan expression by articular chondrocytes is influenced by interleukin 1ß: a possible explanation for the changes in matrix synthesis during osteoarthritis

    Science.gov (United States)

    Pfander, D; Heinz, N; Rothe, P; Carl, H; Swoboda, B

    2004-01-01

    Objective: To analyse the distribution patterns of tenascin and proteoglycans in normal and osteoarthritic cartilage, and to determine the effect of interleukin 1ß (IL1ß) on aggrecan and tenascin expression by human articular chondrocytes in vitro. Methods: Normal and osteoarthritic cartilage and bone samples were obtained during total knee replacements or necropsies. After fixation and decalcification, paraffin embedded specimens were sectioned perpendicular to the surface. Specimens were graded according to Mankin and subdivided into those with normal, and mild, moderate, and severe osteoarthritic lesions. Serial sections were immunostained for tenascin. Tenascin expression by healthy and osteoarthritic chondrocytes was quantified by real time polymerase chain reaction (PCR). Furthermore, in cell culture experiments, human articular chondrocytes were treated with 0.1 or 10 ng/ml IL1ß. Real time PCR analyses of aggrecan and tenascin transcripts (normalised 18S rRNA) were conducted to determine the effect of IL1ß on later mRNA levels. Results: Tenascin was immunodetected in normal and osteoarthritic cartilage. In osteoarthritic cartilage increased tenascin staining was found. Tenascin was found specifically in upper OA cartilage showing a strong reduction of proteoglycans. Greatly increased tenascin transcript levels were detected in osteoarthritic cartilage compared with healthy articular cartilage. IL1ß treatment of articular chondrocytes in vitro significantly increased tenascin transcripts (~200% of control) and strongly reduced aggrecan mRNA levels (~42% of control). Conclusions: During progression of osteoarthritis the switch in matrix synthesis occurs mainly in upper osteoarthritic cartilage. Furthermore, changes in synthesis patterns of osteoarthritic chondrocytes may be significantly influenced by IL1ß, probably diffusing from the joint cavity within the upper osteoarthritic cartilage. PMID:14962956

  12. FASH and MASH: female and male adult human phantoms based on polygon mesh surfaces: II. Dosimetric calculations

    Energy Technology Data Exchange (ETDEWEB)

    Kramer, R; Cassola, V F; Khoury, H J [Department of Nuclear Energy, Federal University of Pernambuco, Avenida Prof. Luiz Freire, 1000, CEP 50740-540, Recife (Brazil); Vieira, J W [Federal Institute of Education, Science and Technology of Pernambuco, Recife (Brazil); De Melo Lima, V J [Department of Anatomy, Federal University of Pernambuco, Recife (Brazil); Robson Brown, K [Imaging Laboratory, Department of Archaeology and Anthropology, University of Bristol, Bristol (United Kingdom)], E-mail: rkramer@uol.com.br

    2010-01-07

    Female and male adult human phantoms, called FASH (Female Adult meSH) and MASH (Male Adult meSH), have been developed in the first part of this study using 3D animation software and anatomical atlases to replace the image-based FAX06 and the MAX06 voxel phantoms. 3D modelling methods allow for phantom development independent from medical images of patients, volunteers or cadavers. The second part of this study investigates the dosimetric implications for organ and tissue equivalent doses due to the anatomical differences between the new and the old phantoms. These differences are mainly caused by the supine position of human bodies during scanning in order to acquire digital images for voxel phantom development. Compared to an upright standing person, in image-based voxel phantoms organs are often coronally shifted towards the head and sometimes the sagittal diameter of the trunk is reduced by a gravitational change of the fat distribution. In addition, volumes of adipose and muscle tissue shielding internal organs are sometimes too small, because adaptation of organ volumes to ICRP-based organ masses often occurs at the expense of general soft tissues, such as adipose, muscle or unspecified soft tissue. These effects have dosimetric consequences, especially for partial body exposure, such as in x-ray diagnosis, but also for whole body external exposure and for internal exposure. Using the EGSnrc Monte Carlo code, internal and external exposure to photons and electrons has been simulated with both pairs of phantoms. The results show differences between organ and tissue equivalent doses for the upright standing FASH/MASH and the image-based supine FAX06/MAX06 phantoms of up to 80% for external exposure and up to 100% for internal exposure. Similar differences were found for external exposure between FASH/MASH and REGINA/REX, the reference voxel phantoms of the International Commission on Radiological Protection. Comparison of effective doses for external photon

  13. FASH and MASH: female and male adult human phantoms based on polygon mesh surfaces: II. Dosimetric calculations

    Science.gov (United States)

    Kramer, R.; Cassola, V. F.; Khoury, H. J.; Vieira, J. W.; de Melo Lima, V. J.; Robson Brown, K.

    2010-01-01

    Female and male adult human phantoms, called FASH (Female Adult meSH) and MASH (Male Adult meSH), have been developed in the first part of this study using 3D animation software and anatomical atlases to replace the image-based FAX06 and the MAX06 voxel phantoms. 3D modelling methods allow for phantom development independent from medical images of patients, volunteers or cadavers. The second part of this study investigates the dosimetric implications for organ and tissue equivalent doses due to the anatomical differences between the new and the old phantoms. These differences are mainly caused by the supine position of human bodies during scanning in order to acquire digital images for voxel phantom development. Compared to an upright standing person, in image-based voxel phantoms organs are often coronally shifted towards the head and sometimes the sagittal diameter of the trunk is reduced by a gravitational change of the fat distribution. In addition, volumes of adipose and muscle tissue shielding internal organs are sometimes too small, because adaptation of organ volumes to ICRP-based organ masses often occurs at the expense of general soft tissues, such as adipose, muscle or unspecified soft tissue. These effects have dosimetric consequences, especially for partial body exposure, such as in x-ray diagnosis, but also for whole body external exposure and for internal exposure. Using the EGSnrc Monte Carlo code, internal and external exposure to photons and electrons has been simulated with both pairs of phantoms. The results show differences between organ and tissue equivalent doses for the upright standing FASH/MASH and the image-based supine FAX06/MAX06 phantoms of up to 80% for external exposure and up to 100% for internal exposure. Similar differences were found for external exposure between FASH/MASH and REGINA/REX, the reference voxel phantoms of the International Commission on Radiological Protection. Comparison of effective doses for external photon

  14. Quantitative analysis of DNA methylation at all human imprinted regions reveals preservation of epigenetic stability in adult somatic tissue

    Directory of Open Access Journals (Sweden)

    Woodfine Kathryn

    2011-01-01

    Full Text Available Abstract Background Genes subject to genomic imprinting are mono-allelically expressed in a parent-of-origin dependent manner. Each imprinted locus has at least one differentially methylated region (DMR which has allele specific DNA methylation and contributes to imprinted gene expression. Once DMRs are established, they are potentially able to withstand normal genome reprogramming events that occur during cell differentiation and germ-line DMRs are stably maintained throughout development. These DMRs, in addition to being either maternally or paternally methylated, have differences in whether methylation was acquired in the germ-line or post fertilization and are present in a variety of genomic locations with different Cytosine-phosphate guanine (CpG densities and CTCF binding capacities. We therefore examined the stability of maintenance of DNA methylation imprints and determined the normal baseline DNA methylation levels in several adult tissues for all imprinted genes. In order to do this, we first developed and validated 50 highly specific, quantitative DNA methylation pyrosequencing assays for the known DMRs associated with human imprinted genes. Results Remarkable stability of the DNA methylation imprint was observed in all germ-line DMRs and paternally methylated somatic DMRs (which maintained average methylation levels of between 35% - 65% in all somatic tissues, independent of gene expression. Maternally methylated somatic DMRs were found to have more variation with tissue specific methylation patterns. Most DMRs, however, showed some intra-individual variability for DNA methylation levels in peripheral blood, suggesting that more than one DMR needs to be examined in order to get an overall impression of the epigenetic stability in a tissue. The plasticity of DNA methylation at imprinted genes was examined in a panel of normal and cancer cell lines. All cell lines showed changes in DNA methylation, especially at the paternal germ

  15. Chronic septic arthritis of the adult hip: Computed tomographic features

    Energy Technology Data Exchange (ETDEWEB)

    Resnik, C.S.; Ammann, A.M.; Walsh, J.W.

    1987-10-01

    Abnormalities on computed tomography (CT) are described in 12 adults in whom septic arthritis of the hip was diagnosed. Presenting symptoms varied, as did CT findings. Soft tissue abnormalities ranged from intra-articular effusion to large abscess formation, and bone changes ranged from minimal erosion of articular surfaces to gross destruction of the proximal femur and acetabulum. CT can be helpful in the evaluation of septic arthritis of the hip because of its superior demonstration of soft tissue detail. An accurate diagnosis can be established in unsuspected cases and can be confirmed when clinical indicators are vague.

  16. Regional-specific effects of ovarian hormone loss on synaptic plasticity in adult human APOE targeted replacement mice.

    Directory of Open Access Journals (Sweden)

    Rebecca C Klein

    Full Text Available The human apolipoprotein ε4 allele (APOE4 has been implicated as one of the strongest genetic risk factors associated with Alzheimer's disease (AD and in influencing normal cognitive functioning. Previous studies have demonstrated that mice expressing human apoE4 display deficits in behavioral and neurophysiological outcomes compared to those with apoE3. Ovarian hormones have also been shown to be important in modulating synaptic processes underlying cognitive function, yet little is known about how their effects are influenced by apoE. In the current study, female adult human APOE targeted replacement (TR mice were utilized to examine the effects of human APOE genotype and long-term ovarian hormone loss on synaptic plasticity in limbic regions by measuring dendritic spine density and electrophysiological function. No significant genotype differences were observed on any outcomes within intact mice. However, there was a significant main effect of genotype on total spine density in apical dendrites in the hippocampus, with post-hoc t-tests revealing a significant reduction in spine density in apoE3 ovariectomized (OVX mice compared to sham operated mice. There was also a significant main effect of OVX on the magnitude of LTP, with post-hoc t-tests revealing a decrease in apoE3 OVX mice relative to sham. In contrast, apoE4 OVX mice showed increased synaptic activity relative to sham. In the lateral amygdala, there was a significant increase in total spine density in apoE4 OVX mice relative to sham. This increase in spine density was consistent with a significant increase in spontaneous excitatory activity in apoE4 OVX mice. These findings suggest that ovarian hormones differentially modulate synaptic integrity in an apoE-dependent manner within brain regions that are susceptible to neurophysiological dysfunction associated with AD.

  17. Age-Dependent Changes in Geometry, Tissue Composition and Mechanical Properties of Fetal to Adult Cryopreserved Human Heart Valves.

    Science.gov (United States)

    van Geemen, Daphne; Soares, Ana L F; Oomen, Pim J A; Driessen-Mol, Anita; Janssen-van den Broek, Marloes W J T; van den Bogaerdt, Antoon J; Bogers, Ad J J C; Goumans, Marie-José T H; Baaijens, Frank P T; Bouten, Carlijn V C

    2016-01-01

    There is limited information about age-specific structural and functional properties of human heart valves, while this information is key to the development and evaluation of living valve replacements for pediatric and adolescent patients. Here, we present an extended data set of structure-function properties of cryopreserved human pulmonary and aortic heart valves, providing age-specific information for living valve replacements. Tissue composition, morphology, mechanical properties, and maturation of leaflets from 16 pairs of structurally unaffected aortic and pulmonary valves of human donors (fetal-53 years) were analyzed. Interestingly, no major differences were observed between the aortic and pulmonary valves. Valve annulus and leaflet dimensions increase throughout life. The typical three-layered leaflet structure is present before birth, but becomes more distinct with age. After birth, cell numbers decrease rapidly, while remaining cells obtain a quiescent phenotype and reside in the ventricularis and spongiosa. With age and maturation-but more pronounced in aortic valves-the matrix shows an increasing amount of collagen and collagen cross-links and a reduction in glycosaminoglycans. These matrix changes correlate with increasing leaflet stiffness with age. Our data provide a new and comprehensive overview of the changes of structure-function properties of fetal to adult human semilunar heart valves that can be used to evaluate and optimize future therapies, such as tissue engineering of heart valves. Changing hemodynamic conditions with age can explain initial changes in matrix composition and consequent mechanical properties, but cannot explain the ongoing changes in valve dimensions and matrix composition at older age.

  18. Trans-active factors controlling the IL-2 gene in adult human T-cell subsets

    Directory of Open Access Journals (Sweden)

    A. Mouzaki

    1992-01-01

    Full Text Available IL-2 secretion in total or subsets of PHA/PMA-stimulated PBMC-derived human T-lymphocytes was monitored and found to be largely due to CD4+CD8− cells. The presence and functional state of transcription factors (TF was assessed by protein-DNA interaction assays and functional transactivation experiments in the Xenopts oocyte system, modulating IL-2 transcription by injection of proteins. The results reveal that CD4+CD8− cells contain both, functional silencer in their resting, and positive TF in their activated states while the CD4+CD8− group contains only non-functional positive TF. This demonstrates that the on/off switch of IL-2 transcription is based on the same mechanism in primary T-lymphocytes of mouse spleen and in peripheral human CD4+CD8− cells.

  19. The impact of Body Worlds on adult visitors' knowledge on human anatomy: A preliminary study.

    Science.gov (United States)

    Fonseca, Guilherme R B C; Finn, Gabrielle M

    2016-05-01

    Body Worlds is an anatomical exhibition that shows human remains to the public. It has been considered controversial since it raises ethical tensions and issues. However, organizers and supporters of Body Worlds have claimed the exhibition is intended to promote visitors' understanding over the human body. Despite these claims, no studies were found that support or refute the hypothesis that a visit to Body Worlds increases the public's objective knowledge on human anatomy. Consequently, the objective of this study was to determine the impact of Body Worlds on anatomical knowledge. We constructed and delivered a questionnaire to both a previsit random sample and a postvisit random sample of visitors of Body Worlds' event Facets of Life, in Berlin. The questionnaire was available in both English and German languages and contained (a) basic sociodemographic questions and (b) a valid and reliable anatomy quiz. The quiz consisted of 16 multiple-choice questions that assessed the ability to identify the location of major anatomical structures on the human body. Average scores achieved on the quiz by the postvisit sample (X¯= 9.08, s = 2.48, n = 164) were significantly higher (unpaired t = 3.3957, P = 0.0008) than those achieved by the previsit sample (X¯= 8.11, s = 2.69, n = 167). Our results suggest that a visit to Body Worlds' event Facets of Life may have a beneficial effect in anatomical knowledge. However, further studies with better empirical designs and fewer limitations are needed to confirm our results.

  20. Lamins regulate cell trafficking and lineage maturation of adult human hematopoietic cells

    OpenAIRE

    Shin, Jae-Won; Spinler, Kyle R.; Swift, Joe; Chasis, Joel A.; Mohandas, Narla; Discher, Dennis E.

    2013-01-01

    Comparing human blood cell types, nuclear diversity is visually striking but unexplained: quasi-spherical nuclei in stem/progenitor cells and T cells contrast with multilobed nuclei in neutrophils, giant nuclei in megakaryocytes, and anuclear erythrocytes. We hypothesized broad roles for the major nuclear structure proteins—lamins—and developed mass spectrometry-calibrated intracellular flow cytometry to quantify lamin-A:B ratios. This ratio controls both nuclear viscoelasticity and cell traf...

  1. Habituation of adult Magellanic penguins to human visitation as expressed through behavior and corticosterone secretion.

    Science.gov (United States)

    Walker, Brian G; Boersma, P Dee; Wingfield, John C

    2006-02-01

    Ecotourism is increasing worldwide; hence, it is important to know how wildlife are affected behaviorally and physiologically by human visitation. We studied the effects of human visitation on the Magellanic Penguins (Spheniscus magellanicus) at Punta Tombo, Argentina, by monitoring changes in defensive head turns and plasma corticosterone (a hormone secreted in response to stress) for penguins with and without a history of tourist visitation. Habituation to human visitation was rapid. In penguins with no previous exposure to tourists, the number of defensive head turns and level of plasma corticosterone decreased significantly within 5 days of one 15-minute visit/day. Penguins living in tourist-visited and undisturbed areas secreted more corticosterone when captured and restrained than penguins visited by a person. Penguins in tourist areas, however did not show as strong a corticosterone response to capture and restraint as did penguins in areas without tourists. This difference was due to a decreased capability of the adrenocortical tissue to secrete corticosterone in tourist-visited birds. Although our data show no direct negative effects of tourism on Magellanic Penguins at Punta Tombo, consequences of a modification of physiological capabilities (e.g., adrenocortical function) may not become apparent until much later in life. The physiological differences between tourist-visited and undisturbed groups of Magellanic Penguins emphasize the importance of monitoring the effects of anthropogenic disturbances on wildlife at multiple levels.

  2. An intra-articular salmon calcitonin-based nanocomplex reduces experimental inflammatory arthritis.

    Science.gov (United States)

    Ryan, Sinéad M; McMorrow, Jason; Umerska, Anita; Patel, Hetal B; Kornerup, Kristin N; Tajber, Lidia; Murphy, Evelyn P; Perretti, Mauro; Corrigan, Owen I; Brayden, David J

    2013-04-28

    Prolonged inappropriate inflammatory responses contribute to the pathogenesis of rheumatoid arthritis (RA) and to aspects of osteoarthritis (OA). The orphan nuclear receptor, NR4A2, is a key regulator and potential biomarker for inflammation and represents a potentially valuable therapeutic target. Both salmon calcitonin (sCT) and hyaluronic acid (HA) attenuated activated mRNA expression of NR4A1, NR4A2, NR4A3, and matrix metalloproteinases (MMPs) 1, 3 and 13 in three human cell lines: SW1353 chondrocytes, U937 and THP-1 monocytes. Ad-mixtures of sCT and HA further down-regulated expression of NR4A2 compared to either agent alone at specific concentrations, hence the rationale for their formulation in nanocomplexes (NPs) using chitosan. The sCT released from NP stimulated cAMP production in human T47D breast cancer cells expressing sCT receptors. When NP were injected by the intra-articular (I.A.) route to the mouse knee during on-going inflammatory arthritis of the K/BxN serum transfer model, joint inflammation was reduced together with NR4A2 expression, and local bone architecture was preserved. These data highlight remarkable anti-inflammatory effects of sCT and HA at the level of reducing NR4A2 mRNA expression in vitro. Combining them in NP elicits anti-arthritic effects in vivo following I.A. delivery.

  3. Two adult human voxel phantoms based on polygon mesh surfaces; Dois fantomas construidos a partir de superficies mesh representando uma mulher adulta e um homem adulto

    Energy Technology Data Exchange (ETDEWEB)

    Cassola, Vagner F.; Kramer, Richard; Khoury, Helen J. [Universidade Federal de Pernambuco (UFPE), Recife (Brazil). Dept. de Energia Nuclear], e-mail: rkramer@uol.com.br; Lima, Vanildo J.M. [Universidade Federal de Pernambuco (UFPE), Recife (Brazil). Dept. de Anatomia

    2010-03-15

    Among computational models used in radiation protection, voxel phantoms based on computer tomographic (CT), nuclear magnetic resonance (NMR) or colour photographic images, became very popular in recent years. Although being a true to nature representation of the scanned individual the scanning 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 anatomy of a person in upright standing position, which in turn can influence absorbed or equivalent dose estimates. This study proposes a method for human phantom design using tools recently developed in the areas of computer graphics and animated films and applies them to the creation and modeling of artificial 3D human organs and tissues. Two models, a male and a female adult human phantom have been developed based on anatomical atlases, observ