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Sample records for adult human articular

  1. Adult human neural crest-derived cells for articular cartilage repair.

    PubMed

    Pelttari, Karoliina; Pippenger, Benjamin; Mumme, Marcus; Feliciano, Sandra; Scotti, Celeste; Mainil-Varlet, Pierre; Procino, Alfredo; von Rechenberg, Brigitte; Schwamborn, Thomas; Jakob, Marcel; Cillo, Clemente; Barbero, Andrea; Martin, Ivan

    2014-08-27

    In embryonic models and stem cell systems, mesenchymal cells derived from the neuroectoderm can be distinguished from mesoderm-derived cells by their Hox-negative profile--a phenotype associated with enhanced capacity of tissue regeneration. We investigated whether developmental origin and Hox negativity correlated with self-renewal and environmental plasticity also in differentiated cells from adults. Using hyaline cartilage as a model, we showed that adult human neuroectoderm-derived nasal chondrocytes (NCs) can be constitutively distinguished from mesoderm-derived articular chondrocytes (ACs) by lack of expression of specific HOX genes, including HOXC4 and HOXD8. In contrast to ACs, serially cloned NCs could be continuously reverted from differentiated to dedifferentiated states, conserving the ability to form cartilage tissue in vitro and in vivo. NCs could also be reprogrammed to stably express Hox genes typical of ACs upon implantation into goat articular cartilage defects, directly contributing to cartilage repair. Our findings identify previously unrecognized regenerative properties of HOX-negative differentiated neuroectoderm cells in adults, implying a role for NCs in the unmet clinical challenge of articular cartilage repair. An ongoing phase 1 clinical trial preliminarily indicated the safety and feasibility of autologous NC-based engineered tissues for the treatment of traumatic articular cartilage lesions. PMID:25163479

  2. The synthesis of dermatan sulphate proteoglycans by fetal and adult human articular cartilage.

    PubMed Central

    Melching, L I; Roughley, P J

    1989-01-01

    Non-aggregating dermatan sulphate proteoglycans can be extracted from both fetal and adult human articular cartilage. The dermatan sulphate proteoglycans appear to be smaller in the adult, this presumably being due to shorter glycosaminoglycan chains, and these chains contain a greater proportion of their uronic acid residues as iduronate. Both the adult and fetal dermatan sulphate proteoglycans contain a greater amount of 4-sulphation than 6-sulphation of the N-acetylgalactosamine residues, in contrast with the aggregating proteoglycans, which always show more 6-sulphation on their chondroitin sulphate chains. In the fetus the major dermatan sulphate proteoglycan to be synthesized is DS-PGI, though DS-PGII is synthesized in reasonable amounts. In the adult, however, DS-PGI synthesis is barely detectable relative to DS-PGII, which is still synthesized in substantial amounts. Purification of the dermatan sulphate proteoglycans from adult cartilage is hampered by the presence of degradation products derived from the large aggregating proteoglycans, which possess similar charge, size and density properties, but which can be distinguished by their ability to interact with hyaluronic acid. Images Fig. 1. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. PMID:2775229

  3. Comparative potential of juvenile and adult human articular chondrocytes for cartilage tissue formation in three-dimensional biomimetic hydrogels.

    PubMed

    Smeriglio, Piera; Lai, Janice H; Dhulipala, Lakshmi; Behn, Anthony W; Goodman, Stuart B; Smith, Robert L; Maloney, William J; Yang, Fan; Bhutani, Nidhi

    2015-01-01

    Regeneration of human articular cartilage is inherently limited and extensive efforts have focused on engineering the cartilage tissue. Various cellular sources have been studied for cartilage tissue engineering including adult chondrocytes, and embryonic or adult stem cells. Juvenile chondrocytes (from donors below 13 years of age) have recently been reported to be a promising cell source for cartilage regeneration. Previous studies have compared the potential of adult and juvenile chondrocytes or adult and osteoarthritic (OA) chondrocytes. To comprehensively characterize the comparative potential of young, old, and diseased chondrocytes, here we examined cartilage formation by juvenile, adult, and OA chondrocytes in three-dimensional (3D) biomimetic hydrogels composed of poly(ethylene glycol) and chondroitin sulfate. All three human articular chondrocytes were encapsulated in the 3D biomimetic hydrogels and cultured for 3 or 6 weeks to allow maturation and extracellular matrix formation. Outcomes were analyzed using quantitative gene expression, immunofluorescence staining, biochemical assays, and mechanical testing. After 3 and 6 weeks, juvenile chondrocytes showed a greater upregulation of chondrogenic gene expression than adult chondrocytes, while OA chondrocytes showed a downregulation. Aggrecan and type II collagen deposition and glycosaminoglycan accumulation were high for juvenile and adult chondrocytes but not for OA chondrocytes. Similar trend was observed in the compressive moduli of the cartilage constructs generated by the three different chondrocytes. In conclusion, the juvenile, adult and OA chondrocytes showed differential responses in the 3D biomimetic hydrogels. The 3D culture model described here may also provide a useful tool to further study the molecular differences among chondrocytes from different stages, which can help elucidate the mechanisms for age-related decline in the intrinsic capacity for cartilage repair. PMID:25054343

  4. PGE2 And Its Cognate EP Receptors Control Human Adult Articular Cartilage Homeostasis and Are Linked to the Pathophysiology of Osteoarthritis

    PubMed Central

    Li, Xin; Ellman, Michael; Muddasani, Prasuna; Wang, James H-C; Cs-Szabo, Gabriella; van Wijnen, Andre J; Im, Hee-Jeong

    2009-01-01

    Objective To elucidate the pathophysiologic links between prostaglandin E2 (PGE2) and osteoarthritis by characterizing the catabolic effects of PGE2 and its unique receptors in human adult articular chondrocytes. Methods Human adult articular chondrocytes were cultured in monolayer or alginate beads with and without PGE2 and/or agonist, antagonist of EP receptors and cytokines. Cell survival, proliferation, and total proteoglycan synthesis and accumulation were measured in alginate beads. Chondrocyte-related gene expression and PI3k/Akt signaling were assessed by real-time PCR and western blotting, respectively, using a monolayer cell culture model. Results Stimulation of human articular chondrocytes with PGE2 through the EP2 receptor (i) suppresses proteoglycan accumulation and synthesis, (ii) suppresses aggrecan gene expression, (iii) does not appreciably affect expression of matrix-degrading enzymes; and (iv) decreases the collagen II:I ratio. EP2 and EP4 receptors are expressed at higher levels in knee compared to ankle cartilage, and in a grade-dependent fashion. PGE2 titration combined with IL-1 synergistically accelerates expression of pain-associated molecules such as inducible nitric oxide synthase (iNOS) and IL-6. Finally, stimulation with exogenous PGE2 or an EP2 agonist inhibits activation of Akt that is induced by insulin-like growth factor (IGF-1). Conclusion PGE2 exerts an anti-anabolic effect on human adult articular cartilage in vitro, and EP2/4 receptor antagonists may represent effective therapeutic agents for the treatment of osteoarthritis. PMID:19180509

  5. Vitrification of intact human articular cartilage.

    PubMed

    Jomha, Nadr M; Elliott, Janet A W; Law, Garson K; Maghdoori, Babak; Forbes, J Fraser; Abazari, Alireza; Adesida, Adetola B; Laouar, Leila; Zhou, Xianpei; McGann, Locksley E

    2012-09-01

    Articular cartilage injuries do not heal and large defects result in osteoarthritis with major personal and socioeconomic costs. Osteochondral transplantation is an effective treatment for large joint defects but its use is limited by the inability to store cartilage for long periods of time. Cryopreservation/vitrification is one method to enable banking of this tissue but decades of research have been unable to successfully preserve the tissue while maintaining cartilage on its bone base - a requirement for transplantation. To address this limitation, human knee articular cartilage from total knee arthroplasty patients and deceased donors was exposed to specified concentrations of 4 different cryoprotective agents for mathematically determined periods of time at lowering temperatures. After complete exposure, the cartilage was immersed in liquid nitrogen for up to 3 months. Cell viability was 75.4 ± 12.1% determined by membrane integrity stains and confirmed with a mitochondrial assay and pellet culture documented production of sulfated glycosaminoglycans and collagen II similar to controls. This report documents successful vitrification of intact human articular cartilage on its bone base making it possible to bank this tissue indefinitely. PMID:22698720

  6. Studies on cathepsin B in human articular cartilage.

    PubMed Central

    Bayliss, M T; Ali, S Y

    1978-01-01

    The thiol proteinase cathepsin B (EC 3.4.22.1), previously called cathepsin B1, was assayed in human articular cartilage by its hydrolysis of the synthetic substrate alpha-N-benzoyl-DL-arginine 2-naphthylamide. The enzyme was activated by cysteine and EDTA and completely inhibited by iodoacetamide and HgCl2. It was also partially inhibited by whole human serum. Human osteoarthrotic cartilage had increased activity when compared with normal cartilage. Cathepsin B activity of normal cartilage was age-related, being high in juveniles and declining to low values in adult and elderly individuals. Cathepsin D and cathepsin B both exhibited a zonal variation through the cartilage depth; the surface cells appeared to contain more activity than those close to the subchondral bone. PMID:417724

  7. Human Articular Chondrocytes Express Multiple Gap Junction Proteins

    PubMed Central

    Mayan, Maria D.; Carpintero-Fernandez, Paula; Gago-Fuentes, Raquel; Martinez-de-Ilarduya, Oskar; Wang, Hong-Zhang; Valiunas, Virginijus; Brink, Peter; Blanco, Francisco J.

    2014-01-01

    Osteoarthritis (OA) is the most common joint disease and involves progressive degeneration of articular cartilage. The aim of this study was to investigate if chondrocytes from human articular cartilage express gap junction proteins called connexins (Cxs). We show that human chondrocytes in tissue express Cx43, Cx45, Cx32, and Cx46. We also find that primary chondrocytes from adults retain the capacity to form functional voltage-dependent gap junctions. Immunohistochemistry experiments in cartilage from OA patients revealed significantly elevated levels of Cx43 and Cx45 in the superficial zone and down through the next approximately 1000 μm of tissue. These zones corresponded with regions damaged in OA that also had high levels of proliferative cell nuclear antigen. An increased number of Cxs may help explain the increased proliferation of cells in clusters that finally lead to tissue homeostasis loss. Conversely, high levels of Cxs in OA cartilage reflect the increased number of adjacent cells in clusters that are able to interact directly by gap junctions as compared with hemichannels on single cells in normal cartilage. Our data provide strong evidence that OA patients have a loss of the usual ordered distribution of Cxs in the damaged zones and that the reductions in Cx43 levels are accompanied by the loss of correct Cx localization in the nondamaged areas. PMID:23416160

  8. IL-1beta, but not BMP-7 leads to a dramatic change in the gene expression pattern of human adult articular chondrocytes--portraying the gene expression pattern in two donors.

    PubMed

    Saas, J; Haag, J; Rueger, D; Chubinskaya, S; Sohler, F; Zimmer, R; Bartnik, E; Aigner, T

    2006-10-01

    Anabolic and catabolic cytokines and growth factors such as BMP-7 and IL-1beta play a central role in controlling the balance between degradation and repair of normal and (osteo)arthritic articular cartilage matrix. In this report, we investigated the response of articular chondrocytes to these factors IL-1beta and BMP-7 in terms of changes in gene expression levels. Large scale analysis was performed on primary human adult articular chondrocytes isolated from two human, independent donors cultured in alginate beads (non-stimulated and stimulated with IL-1beta and BMP-7 for 48 h) using Affymetrix gene chips (oligo-arrays). Biostatistical and bioinformatic evaluation of gene expression pattern was performed using the Resolver software (Rosetta). Part of the results were confirmed using real-time PCR. IL-1beta modulated significantly 909 out of 3459 genes detectable, whereas BMP-7 influenced only 36 out of 3440. BMP-7 induced mainly anabolic activation of chondrocytes including classical target genes such as collagen type II and aggrecan, while IL-1beta, both, significantly modulated the gene expression levels of numerous genes; namely, IL-1beta down-regulated the expression of anabolic genes and induced catabolic genes and mediators. Our data indicate that BMP-7 has only a limited effect on differentiated cells, whereas IL-1beta causes a dramatic change in gene expression pattern, i.e. induced or repressed much more genes. This presumably reflects the fact that BMP-7 signaling is effected via one pathway only (i.e. Smad-pathway) whereas IL-1beta is able to signal via a broad variety of intracellular signaling cascades involving the JNK, p38, NFkB and Erk pathways and even influencing BMP signaling. PMID:17161615

  9. Cryoprotectant kinetic analysis of a human articular cartilage vitrification protocol.

    PubMed

    Shardt, Nadia; Al-Abbasi, Khaled K; Yu, Hana; Jomha, Nadr M; McGann, Locksley E; Elliott, Janet A W

    2016-08-01

    We recently published a protocol to vitrify human articular cartilage and a method of cryoprotectant removal in preparation for transplantation. The current study's goal was to perform a cryoprotectant kinetic analysis and theoretically shorten the procedure used to vitrify human articular cartilage. First, the loading of the cryoprotectants was modeled using Fick's law of diffusion, and this information was used to predict the kinetics of cryoprotectant efflux after the cartilage sample had been warmed. We hypothesized that diffusion coefficients obtained from the permeation of individual cryoprotectants into porcine articular cartilage could be used to provide a reasonable prediction of the cryoprotectant loading and of the combined cryoprotectant efflux from vitrified human articular cartilage. We tested this hypothesis with experimental efflux measurements. Osteochondral dowels from three patients were vitrified, and after warming, the articular cartilage was immersed in 3 mL X-VIVO at 4 °C in two consecutive solutions, each for 24 h, with the solution osmolality recorded at various times. Measured equilibrium values agreed with theoretical values within a maximum of 15% for all three samples. The results showed that diffusion coefficients for individual cryoprotectants determined from experiments with 2-mm thick porcine cartilage can be used to approximate the rate of efflux of the combined cryoprotectants from vitrified human articular cartilage of similar thickness. Finally, Fick's law of diffusion was used in a computational optimization to shorten the protocol with the constraint of maintaining the theoretical minimum cryoprotectant concentration needed to achieve vitrification. The learning provided by this study will enable future improvements in tissue vitrification. PMID:27221520

  10. Genetic Inhibition of Fibroblast Growth Factor Receptor 1 in Knee Cartilage Attenuates the Degeneration of Articular Cartilage in Adult Mice

    PubMed Central

    Weng, Tujun; Yi, Lingxian; Huang, Junlan; Luo, Fengtao; Wen, Xuan; Du, Xiaolan; Chen, Qian; Deng, Chuxia; Chen, Di; Chen, Lin

    2013-01-01

    Objective Fibroblast growth factor (FGF) family members are involved in the regulation of articular cartilage homeostasis. The aim of this study was to investigate the function of FGF receptor 1 (FGFR-1) in the development of osteoarthritis (OA) and its underlying mechanisms. Methods FGFR-1 was deleted from the articular chondrocytes of adult mice in a cartilage-specific and tamoxifen-inducible manner. Two OA models (aging-associated spontaneous OA, and destabilization-induced OA), as well as an antigen-induced arthritis (AIA) model, were established and tested in Fgfr1-deficient and wild-type (WT) mice. Alterations in cartilage structure and the loss of proteoglycan were assessed in the knee joints of mice of either genotype, using these 3 arthritis models. Primary chondrocytes were isolated and the expression of key regulatory molecules was assessed quantitatively. In addition, the effect of an FGFR-1 inhibitor on human articular chondrocytes was examined. Results The gross morphologic features of Fgfr1-deficient mice were comparable with those of WT mice at both the postnatal and adult stages. The articular cartilage of 12-month-old Fgfr1-deficient mice displayed greater aggrecan staining compared to 12-month-old WT mice. Fgfr1 deficiency conferred resistance to the proteoglycan loss induced by AIA and attenuated the development of cartilage destruction after surgically induced destabilization of the knee joint. The chondroprotective effect of FGFR-1 inhibition was largely associated with decreased expression of matrix metalloproteinase 13 (MMP-13) and up-regulation of FGFR-3 in mouse and human articular chondrocytes. Conclusion Disruption of FGFR-1 in adult mouse articular chondrocytes inhibits the progression of cartilage degeneration. Down-regulation of MMP-13 expression and up-regulation of FGFR-3 levels may contribute to the phenotypic changes observed in Fgfr1-deficient mice. PMID:22833219

  11. Morphological, genetic and phenotypic comparison between human articular chondrocytes and cultured chondrocytes.

    PubMed

    Mata-Miranda, Mónica Maribel; Martinez-Martinez, Claudia María; Noriega-Gonzalez, Jesús Emmanuel; Paredes-Gonzalez, Luis Enrique; Vázquez-Zapién, Gustavo Jesús

    2016-08-01

    Articular cartilage is an avascular and aneural tissue with limited capacity for regeneration. On large articular lesions, it is recommended to use regenerative medicine strategies, like autologous chondrocyte implantation. There is a concern about morphological changes that chondrocytes suffer once they have been isolated and cultured. Due to the fact that there is little evidence that compares articular cartilage chondrocytes with cultured chondrocytes, in this research we proposed to obtain chondrocytes from human articular cartilage, compare them with themselves once they have been cultured and characterize them through genetic, phenotypic and morphological analysis. Knee articular cartilage samples of 10 mm were obtained, and each sample was divided into two fragments; a portion was used to determine gene expression, and from the other portion, chondrocytes were obtained by enzymatic disaggregation, in order to be cultured and expanded in vitro. Subsequently, morphological, genetic and phenotypic characteristics were compared between in situ (articular cartilage) and cultured chondrocytes. Obtained cultured chondrocytes were rounded in shape, possessing a large nucleus with condensed chromatin and a clear cytoplasm; histological appearance was quite similar to typical chondrocyte. The expression levels of COL2A1 and COL10A1 genes were higher in cultured chondrocytes than in situ chondrocytes; moreover, the expression of COL1A1 was almost undetectable on cultured chondrocytes; likewise, COL2 and SOX9 proteins were detected by immunofluorescence. We concluded that chondrocytes derived from adult human cartilage cultured for 21 days do not tend to dedifferentiate, maintaining their capacity to produce matrix and also retaining their synthesis capacity and morphology. PMID:27094849

  12. Telomere erosion and senescence in human articular cartilage chondrocytes.

    PubMed

    Martin, J A; Buckwalter, J A

    2001-04-01

    Aging and the degeneration of articular cartilage in osteoarthritis are distinct processes, but a strong association exists between age and the incidence and prevalence of osteoarthritis. We hypothesized that this association is due to in vivo replicative senescence, which causes age-related declines in the ability of chondrocytes to maintain articular cartilage. For this hypothesis to be tested, senescence-associated markers were measured in human articular chondrocytes from donors ranging in age from 1 to 87 years. These measures included in situ staining for senescence-associated beta-galactosidase activity, (3)H-thymidine incorporation assays for mitotic activity, and Southern blots for telomere length determinations. We found that senescence-associated beta-galactosidase activity increased with age, whereas both mitotic activity and mean telomere length declined. These findings indicate that chondrocyte replicative senescence occurs in vivo and support the hypothesis that the association between osteoarthritis and aging is due in part to replicative senescence. The data also imply that transplantation procedures performed to restore damaged articular surfaces could be limited by the inability of older chondrocytes to form new cartilage after transplantation. PMID:11283188

  13. The effects of exercise on human articular cartilage

    PubMed Central

    Eckstein, F; Hudelmaier, M; Putz, R

    2006-01-01

    The effects of exercise on articular hyaline articular cartilage have traditionally been examined in animal models, but until recently little information has been available on human cartilage. Magnetic resonance imaging now permits cartilage morphology and composition to be analysed quantitatively in vivo. This review briefly describes the methodological background of quantitative cartilage imaging and summarizes work on short-term (deformational behaviour) and long-term (functional adaptation) effects of exercise on human articular cartilage. Current findings suggest that human cartilage deforms very little in vivo during physiological activities and recovers from deformation within 90 min after loading. Whereas cartilage deformation appears to become less with increasing age, sex and physical training status do not seem to affect in vivo deformational behaviour. There is now good evidence that cartilage undergoes some type of atrophy (thinning) under reduced loading conditions, such as with postoperative immobilization and paraplegia. However, increased loading (as encountered by elite athletes) does not appear to be associated with increased average cartilage thickness. Findings in twins, however, suggest a strong genetic contribution to cartilage morphology. Potential reasons for the inability of cartilage to adapt to mechanical stimuli include a lack of evolutionary pressure and a decoupling of mechanical competence and tissue mass. PMID:16637874

  14. Mechanical properties of normal and osteoarthritic human articular cartilage.

    PubMed

    Robinson, Dale L; Kersh, Mariana E; Walsh, Nicole C; Ackland, David C; de Steiger, Richard N; Pandy, Marcus G

    2016-08-01

    Isotropic hyperelastic models have been used to determine the material properties of normal human cartilage, but there remains an incomplete understanding of how these properties may be altered by osteoarthritis. The aims of this study were to (1) measure the material constants of normal and osteoarthritic human knee cartilage using isotropic hyperelastic models; (2) determine whether the material constants correlate with histological measures of structure and/or cartilage tissue damage; and (3) quantify the abilities of two common isotropic hyperelastic material models, the neo-Hookean and Yeoh models, to describe articular cartilage contact force, area, and pressure. Small osteochondral specimens of normal and osteoarthritic condition were retrieved from human cadaveric knees and from the knees of patients undergoing total knee arthroplasty and tested in unconfined compression at loading rates and large strains representative of weight-bearing activity. Articular surface contact area and lateral deformation were measured concurrently and specimen-specific finite element models then were used to determine the hyperelastic material constants. Structural parameters were measured using histological techniques while the severity of cartilage damage was quantified using the OARSI grading scale. The hyperelastic material constants correlated significantly with OARSI grade, indicating that the mechanical properties of cartilage for large strains change with tissue damage. The measurements of contact area described anisotropy of the tissue constituting the superficial zone. The Yeoh model described contact force and pressure more accurately than the neo-Hookean model, whereas both models under-predicted contact area and poorly described the anisotropy of cartilage within the superficial zone. These results identify the limits by which isotropic hyperelastic material models may be used to describe cartilage contact variables. This study provides novel data for the

  15. Quantitative proteomic profiling of human articular cartilage degradation in osteoarthritis.

    PubMed

    Lourido, Lucía; Calamia, Valentina; Mateos, Jesús; Fernández-Puente, Patricia; Fernández-Tajes, Juan; Blanco, Francisco J; Ruiz-Romero, Cristina

    2014-12-01

    Osteoarthritis (OA) is the most common rheumatic pathology and is characterized primarily by articular cartilage degradation. Despite its high prevalence, there is no effective therapy to slow disease progression or regenerate the damaged tissue. Therefore, new diagnostic and monitoring tests for OA are urgently needed, which would also promote the development of alternative therapeutic strategies. In the present study, we have performed an iTRAQ-based quantitative proteomic analysis of secretomes from healthy human articular cartilage explants, comparing their protein profile to those from unwounded (early disease) and wounded (advanced disease) zones of osteoarthritic tissue. This strategy allowed us to identify a panel of 76 proteins that are distinctively released by the diseased tissue. Clustering analysis allowed the classification of proteins according to their different profile of release from cartilage. Among these proteins, the altered release of osteoprotegerin (decreased in OA) and periostin (increased in OA), both involved in bone remodelling processes, was verified in further analyses. Moreover, periostin was also increased in the synovial fluid of OA patients. Altogether, the present work provides a novel insight into the mechanisms of human cartilage degradation and a number of new cartilage-characteristic proteins with possible biomarker value for early diagnosis and prognosis of OA. PMID:25383958

  16. Membrane channel gene expression in human costal and articular chondrocytes

    PubMed Central

    Asmar, A.; Barrett-Jolley, R.; Werner, A.; Kelly, R.; Stacey, M.

    2016-01-01

    ABSTRACT Chondrocytes are the uniquely resident cells found in all types of cartilage and key to their function is the ability to respond to mechanical loads with changes of metabolic activity. This mechanotransduction property is, in part, mediated through the activity of a range of expressed transmembrane channels; ion channels, gap junction proteins, and porins. Appropriate expression of ion channels has been shown essential for production of extracellular matrix and differential expression of transmembrane channels is correlated to musculoskeletal diseases such as osteoarthritis and Albers-Schönberg. In this study we analyzed the consistency of gene expression between channelomes of chondrocytes from human articular and costal (teenage and fetal origin) cartilages. Notably, we found 14 ion channel genes commonly expressed between articular and both types of costal cartilage chondrocytes. There were several other ion channel genes expressed only in articular (6 genes) or costal chondrocytes (5 genes). Significant differences in expression of BEST1 and KCNJ2 (Kir2.1) were observed between fetal and teenage costal cartilage. Interestingly, the large Ca2+ activated potassium channel (BKα, or KCNMA1) was very highly expressed in all chondrocytes examined. Expression of the gap junction genes for Panx1, GJA1 (Cx43) and GJC1 (Cx45) was also observed in chondrocytes from all cartilage samples. Together, this data highlights similarities between chondrocyte membrane channel gene expressions in cells derived from different anatomical sites, and may imply that common electrophysiological signaling pathways underlie cellular control. The high expression of a range of mechanically and metabolically sensitive membrane channels suggest that chondrocyte mechanotransduction may be more complex than previously thought. PMID:27116676

  17. ROCK inhibitor prevents the dedifferentiation of human articular chondrocytes

    SciTech Connect

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

    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

  18. The collagen fibril organization in human articular cartilage.

    PubMed Central

    Minns, R J; Steven, F S

    1977-01-01

    In this scanning electron microscopic study blocks of collagen fibrils were prepared from human articular cartilage, using two techinques which selectively removed either the proteoglycans alone, or both the proteoglycans and the collagen fibrils, of the non-calcified cartilage layer. Amino acid analysis of the fibrils confirmed the purity of the collagen after proteoglycan extraction. The cartilage was scanned in four different ways: (1) normal to the articular surface, (2) in superficial sections, (3) on surfaces of blocks which had been broken in planes parallel to artificial splits make by the insertion of a pin, and (4) on fracture surfaces which traversed the calcified cartilage and the subchondral bone. Five features of the organization of the collagen fibrils were specially noted: (1) Individual fibrils within the trabeculae joined to form small fibre bundles which became grouped into larger bundles at the calcified/uncalcified interface. (2) Fibrils in the deep and middle zones which, exhibiting the characteristic surface periodicity of collagen, were generally oriented towars the articular surface in large bundles approximately 55 micronm across. (3) In the superficial zone, fibrils ran parallel to the surface. (4) The surface fibrils had random orientation, even at the bases of empty lacunae vacated by chondrocytes during specimen preparation. (5) The collagen fibrils of the lacunar walls appeared to be thinner and more closely packed than thos between the lacunae. The fine collagen fibrils associated with the lacunar walls were frequently observed to pass through a large lacunar space, resulting in the formation of two or more compartments, each of which was presumably filled with a chondrocyte in the living cartilage. Images Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 PMID:870478

  19. Expression of Angiotensin II Receptor-1 in Human Articular Chondrocytes

    PubMed Central

    Kawakami, Yuki; Matsuo, Kosuke; Murata, Minako; Yudoh, Kazuo; Nakamura, Hiroshi; Shimizu, Hiroyuki; Beppu, Moroe; Inaba, Yutaka; Saito, Tomoyuki; Kato, Tomohiro; Masuko, Kayo

    2012-01-01

    Background. Besides its involvement in the cardiovascular system, the renin-angiotensin-aldosterone (RAS) system has also been suggested to play an important role in inflammation. To explore the role of this system in cartilage damage in arthritis, we investigated the expression of angiotensin II receptors in chondrocytes. Methods. Articular cartilage was obtained from patients with osteoarthritis, rheumatoid arthritis, and traumatic fractures who were undergoing arthroplasty. Chondrocytes were isolated and cultured in vitro with or without interleukin (IL-1). The expression of angiotensin II receptor types 1 (AT1R) and 2 (AT2R) mRNA by the chondrocytes was analyzed using reverse transcription-polymerase chain reaction (RT-PCR). AT1R expression in cartilage tissue was analyzed using immunohistochemistry. The effect of IL-1 on AT1R/AT2R expression in the chondrocytes was analyzed by quantitative PCR and flow cytometry. Results. Chondrocytes from all patient types expressed AT1R/AT2R mRNA, though considerable variation was found between samples. Immunohistochemical analysis confirmed AT1R expression at the protein level. Stimulation with IL-1 enhanced the expression of AT1R/AT2R mRNA in OA and RA chondrocytes. Conclusions. Human articular chondrocytes, at least partially, express angiotensin II receptors, and IL-1 stimulation induced AT1R/AT2R mRNA expression significantly. PMID:23346400

  20. The young adult hip: extra-articular causes of hip pain and how to pick the winners

    PubMed Central

    Bray, Edward D. R.; Sherafati, Milad; Cutts, Charlotte L.

    2015-01-01

    Hip pain in young adults is not always caused by intra-articular pathology, even in the presence of abnormal examination and imaging findings. Therefore, management of young adult hip pain requires processes that identify patients who are likely to benefit from surgical intervention. An important investigation in the diagnostic pathway is the intra-articular injection; a negative response to this should alert the surgeon to the presence of symptomatic extra-articular causes of hip pain. Our aim was to identify the proportion of patients referred with intra-articular pathology whose primary cause of pain was of extra-articular origin. A total of 143 intra-articular hip injections (local anaesthetic + corticosteroid) were performed over a 2-year period. Mean patient age was 41.95 (95% confidence interval: 39.50–44.41) years with a mean body mass index of 27 (95% confidence interval: 25.77–28.23); 26% of patients (n = 37) had no relief of symptoms after intra-articular injection. Of the patients with no relief, 81.1% (n = 30) were found to have extra-articular pathology as the cause of their pain and the remainder are under on-going investigation. Intra-articular hip injection is an important investigation in the diagnostic pathway of young adult hip pain, as it can highlight and differentiate those patients with referred pain from extra-articular pathology. This benefit may be further enhanced if injections are performed in theatres using image intensifier, under sedation, as it allows direct penetration into the joint without any local anaesthetic infiltration of surrounding tissue. The latter allows immediate objective assessment of symptom relief, eliminating the need to rely on retrospective patient recall of symptom change. PMID:27011814

  1. Localization of hyaluronic acid in human articular cartilage.

    PubMed

    Asari, A; Miyauchi, S; Kuriyama, S; Machida, A; Kohno, K; Uchiyama, Y

    1994-04-01

    To demonstrate localization of hyaluronic acid (HA) in articular cartilage of the human femur, biotinylated HA-binding region, which specifically binds HA molecules, was applied to the tissue. In sections fixed by 2% paraformaldehyde-2% glutaraldehyde, HA staining was detected in lamina splendens and chondrocytes in the middle zone. By pretreatment with trypsin, intense HA staining appeared in the extracellular matrix of the deep zone and weak staining in the superficial and middle zones. Moreover, pre-treatment with chondroitinase ABC (CHase ABC) intensely enhanced the stainability for HA in the superficial and middle zones and weakly in the deeper zone. Combined pre-treatment of trypsin with CHase ABC abolished intra- and extracellular staining for HA in all zones. By microbiochemical study, the concentrations of HA and dermatan sulfate were high in the middle zone, whereas those of chondroitin sulfate and keratan sulfate were high in the deep zone. These results suggest that HA is abundantly synthesized in and secreted from the chondrocytes, particularly in the middle zone, whereas it is largely masked by proteoglycan constituents in the extracellular matrix. PMID:8126377

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

    PubMed Central

    Wang, Wen; He, Na; Feng, Chenchen; Liu, Victor; Zhang, Luyi; Wang, Fei; He, Jiaping; Zhu, Tengfang; Wang, Shuyang; Qiao, Weiwei; Li, Suke; Zhou, Guangdong; Zhang, Li; Dai, Chengxiang; Cao, Wei

    2015-01-01

    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. PMID:26023716

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

    PubMed Central

    Bellil, Mehdi; Hadhri, Khaled; Sridi, Maamoun; Kooli, Mondher

    2014-01-01

    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. PMID:25558147

  4. Relationship of articular soft tissue contour and shape to the underlying eminence and slope profile in young adult temporomandibular joints.

    PubMed

    Pullinger, A G; Bibb, C A; Ding, X; Baldioceda, F

    1993-11-01

    This study examined whether the overall shape of the articular soft tissue overlying the posterior slope and articular eminence of the temporal bone could be predicted by the underlying osseous contour in a histologic model of 51 central sagittal sections of young adult temporomandibular joints. Articular soft tissue and bone contours were traced, and osseous landmarks identified on the basis of joint geometry. Soft tissue thickness measurements were made under low power light microscopy. Seven categories of articular soft tissue pattern were identified. The soft tissue uniformly followed the osseous contour in only one (14%). A progressive increase in soft tissue thickness from the middle of the posterior slope to the articular crest was the most common pattern (35%) but did not describe most of the sample that was more asymmetric. Pattern was poorly predicted by the shape and slope of the temporal bone outline or by dental factors that describe anterior guidance and did not relate to disk displacement. The articular soft tissue compensated for flatter eminence slopes and osseous irregularities and maintained an intact surface. This study has clinical implications for radiographic interpretation of disk space, condyle translation pathways, and the integrity of the functional articular surface. PMID:8247507

  5. Mesenchymal progenitor cell markers in human articular cartilage: normal distribution and changes in osteoarthritis

    PubMed Central

    Grogan, Shawn P; Miyaki, Shigeru; Asahara, Hiroshi; D'Lima, Darryl D; Lotz, Martin K

    2009-01-01

    Introduction Recent findings suggest that articular cartilage contains mesenchymal progenitor cells. The aim of this study was to examine the distribution of stem cell markers (Notch-1, Stro-1 and VCAM-1) and of molecules that modulate progenitor differentiation (Notch-1 and Sox9) in normal adult human articular cartilage and in osteoarthritis (OA) cartilage. Methods Expression of the markers was analyzed by immunohistochemistry (IHC) and flow cytometry. Hoechst 33342 dye was used to identify and sort the cartilage side population (SP). Multilineage differentiation assays including chondrogenesis, osteogenesis and adipogenesis were performed on SP and non-SP (NSP) cells. Results A surprisingly high number (>45%) of cells were positive for Notch-1, Stro-1 and VCAM-1 throughout normal cartilage. Expression of these markers was higher in the superficial zone (SZ) of normal cartilage as compared to the middle zone (MZ) and deep zone (DZ). Non-fibrillated OA cartilage SZ showed reduced Notch-1 and Sox9 staining frequency, while Notch-1, Stro-1 and VCAM-1 positive cells were increased in the MZ. Most cells in OA clusters were positive for each molecule tested. The frequency of SP cells in cartilage was 0.14 ± 0.05% and no difference was found between normal and OA. SP cells displayed chondrogenic and osteogenic but not adipogenic differentiation potential. Conclusions These results show a surprisingly high number of cells that express putative progenitor cell markers in human cartilage. In contrast, the percentage of SP cells is much lower and within the range of expected stem cell frequency. Thus, markers such as Notch-1, Stro-1 or VCAM-1 may not be useful to identify progenitors in cartilage. Instead, their increased expression in OA cartilage implicates involvement in the abnormal cell activation and differentiation process characteristic of OA. PMID:19500336

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

    PubMed Central

    Babhulkar, Sudhir; Babhulkar, Sushrut

    2011-01-01

    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 cases and these

  7. Biological Effects of the Plant-derived Polyphenol Resveratrol in Human Articular Cartilage and Chondrosarcoma Cells

    PubMed Central

    Im, Hee-Jeong; Li, Xin; Chen, Di; Yan, Dongyao; Kim, Jaesung; Ellman, Michael B; Stein, Gary S.; Cole, Brian; Ranjan, KC; Cs-Szabo, Gabriella; van Wijnen, Andre J

    2012-01-01

    The natural phytoestrogen resveratrol (RSV) may have therapeutic potential for arthritic conditions. RSV is chondroprotective for articular cartilage in rabbit models for arthritis, but its biological effects on human articular cartilage and chondrosarcoma cells are unknown. Effects of RSV on human articular cartilage homeostasis were studied by assessing production of matrix-degrading enzymes (MMP-13, ADAMTS-4, and ADAMTS-5), as well as proteoglycan production and synthesis. The counteractions of RSV against catabolic factors (e.g., FGF-2 or IL-1β) were examined by in vitro and ex vivo using monolayer, three-dimensional alginate beads and cartilage explants cultures, respectively. RSV improves cell viability of articular chondrocytes and effectively antagonizes cartilage-degrading protease production that was initiated by catabolic and/or anti-anabolic cytokines in human articular chondrocytes. RSV significantly also enhances BMP7-promoted proteoglycan synthesis as assessed by 35S-sulfate incorporation. Protein-DNA interaction arrays suggest that RSV inhibits the activation of transcription factors involved in inflammation and cartilage catabolic signaling pathways, including direct downstream regulators of MAPK (e.g., AP-1, PEA3) and NFκB. RSV selectively compromises survival of human chondrosarcoma cells, but not primary articular chondrocytes, revealing cell-specific activity of RSV on non-tumorigenic versus tumor-derived cells. We propose that RSV exerts its chondroprotective functions, in part, by deactivating p53-induced apoptosis in human primary chondrocytes, but not human chondrosarcoma. Our findings suggest that RSV has potential as a unique biologic treatment for both prevention and treatment of cartilage degenerative diseases. PMID:22252971

  8. Prenatal caffeine exposure induces a poor quality of articular cartilage in male adult offspring rats via cholesterol accumulation in cartilage

    PubMed Central

    Luo, Hanwen; Li, Jing; Cao, Hong; Tan, Yang; Magdalou, Jacques; Chen, Liaobin; Wang, Hui

    2015-01-01

    Epidemiological investigations indicate that osteoarthritis is associated with intrauterine growth retardation (IUGR) and abnormal cholesterol metabolism. Our previous studies showed that prenatal caffeine exposure (PCE) induced chondrogenesis retardation in IUGR offspring rats. The current study sought to investigate the effects of PCE on male IUGR offspring rats’ articular cartilage, and the mechanisms associated with abnormal cholesterol metabolism. Based on the results from both male fetal and adult fed a high-fat diet (HFD) studies of rats that experienced PCE (120 mg/kg.d), the results showed a poor quality of articular cartilage and cholesterol accumulation in the adult PCE group. Meanwhile, the serum total cholesterol and low-density lipoprotein-cholesterol concentrations were increased in adult PCE offspring. We also observed lower expression of insulin-like growth factor1 (IGF1) and impaired cholesterol efflux in adult articular cartilage. Furthermore, the expression of cartilage functional genes, components of the IGF1 signaling pathway and cholesterol efflux pathway related genes were decreased in PCE fetal cartilage. In conclusion, PCE induced a poor quality of articular cartilage in male adult offspring fed a HFD. This finding was shown to be due to cholesterol accumulation in the cartilage, which may have resulted from intrauterine reduced activity of the IGF1 signaling pathway. PMID:26639318

  9. Demonstration of fibronectin in human articular cartilage by an indirect immunoperoxidase technique.

    PubMed

    Clemmensen, I; Hølund, B; Johansen, N; Andersen, R B

    1982-01-01

    Fresh frozen tissue sections of human articular cartilage was treated without and with human testicular hyaluronidase (2 x 10(6) units/l) for 60 min at 37 degrees C and stained by the indirect immunoperoxidase technique with rabbit antihuman fibronectin. The rabbit antihuman fibronectin was purified by affinity chromatography on human fibronectin-Sepharose. Fibronectin was only found on the acellular surface of the articular cartilage in tissue sections not treated with hyaluronidase. In this surface layer, probably identical to "lamina splendens", the arrangement of fibronectin was as a membrane. No collagen was seen in this area by van Gieson staining. No staining for fibronectin was found in the cartilage matrix or in the chondrocytes. Treatment of the cartilage tissue with hyaluronidase resulted in visualization of high amount of fibronectin in the cartilage matrix, with the highest intensity around the chondrocytes. The staining of the acellular surface layer of the articular cartilage was identical with the results obtained without hyaluronidase treatment. These results indicate that articular cartilage is rich in fibronectin probably in complex with hyaluronic acid, and that the chondrocytes produce fibronectin in situ. It also demonstrates the steric hindrance of hyaluronic acid aggregates in diffusion of the antibody and the value of hyaluronidase treatment of tissue before demonstration of fibronectin. PMID:6757202

  10. Versican gene expression in human articular cartilage and comparison of mRNA splicing variation with aggrecan.

    PubMed Central

    Grover, J; Roughley, P J

    1993-01-01

    The chondrocytes in human articular cartilage from subjects of all ages express mRNAs for both of the aggregating proteoglycans aggrecan and versican, although the level of expression of versican mRNA is much lower than that of aggrecan mRNA. Aggrecan shows alternative splicing of the epidermal growth factor (EGF)-like domain within its C-terminal globular region, but there is no evidence for a major difference in situ in the relative expression of this domain with age. At all ages studied from birth to the mature adult, a greater proportion of transcripts lacked the EGF domain. The relative proportions of the two transcripts did not change upon culture and passage of isolated chondrocytes. In contrast, the neighbouring complement regulatory protein (CRP)-like domain was predominantly expressed irrespective of age, but cell culture did result in variation of the splicing of this domain. Versican possesses two EGF-like domains and one CRP-like domain, but at all ages the three domains were predominantly present in all transcripts. This situation persisted upon culture and passage of the chondrocytes. Thus, unlike aggrecan, the versican expressed by human articular cartilage does not appear to undergo alternative splicing of its C-terminal globular region, either in cartilage in situ or in chondrocytes in culture. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8484718

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

    PubMed

    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 (p<0.01), than those of the IA dentulous (61.56°), the IA edentulous (62.54°), and all the combined IA (61.99°) specimens. Because the values of the articular-eminence inclination can vary a lot with reference to the number of specimens and the different methods used for measuring, the obtained values yield only orientational information. Further investigations including a larger number of medieval specimens are needed to confirm the results obtained from this study. PMID:22721644

  12. Fibroblast growth factor receptor 1 is principally responsible for fibroblast growth factor 2-induced catabolic activities in human articular chondrocytes

    PubMed Central

    2011-01-01

    Introduction Cartilage degeneration driven by catabolic stimuli is a critical pathophysiological process in osteoarthritis (OA). We have defined fibroblast growth factor 2 (FGF-2) as a degenerative mediator in adult human articular chondrocytes. Biological effects mediated by FGF-2 include inhibition of proteoglycan production, up-regulation of matrix metalloproteinase-13 (MMP-13), and stimulation of other catabolic factors. In this study, we identified the specific receptor responsible for the catabolic functions of FGF-2, and established a pathophysiological connection between the FGF-2 receptor and OA. Methods Primary human articular chondrocytes were cultured in monolayer (24 hours) or alginate beads (21 days), and stimulated with FGF-2 or FGF18, in the presence or absence of FGFR1 (FGF receptor 1) inhibitor. Proteoglycan accumulation and chondrocyte proliferation were assessed by dimethylmethylene blue (DMMB) assay and DNA assay, respectively. Expression of FGFRs (FGFR1 to FGFR4) was assessed by flow cytometry, immunoblotting, and quantitative real-time PCR (qPCR). The distinctive roles of FGFR1 and FGFR3 after stimulation with FGF-2 were evaluated using either pharmacological inhibitors or FGFR small interfering RNA (siRNA). Luciferase reporter gene assays were used to quantify the effects of FGF-2 and FGFR1 inhibitor on MMP-13 promoter activity. Results Chondrocyte proliferation was significantly enhanced in the presence of FGF-2 stimulation, which was inhibited by the pharmacological inhibitor of FGFR1. Proteoglycan accumulation was reduced by 50% in the presence of FGF-2, and this reduction was successfully rescued by FGFR1 inhibitor. FGFR1 inhibitors also fully reversed the up-regulation of MMP-13 expression and promoter activity stimulated by FGF-2. Blockade of FGFR1 signaling by either chemical inhibitors or siRNA targeting FGFR1 rather than FGFR3 abrogated the up-regulation of matrix metalloproteinases 13 (MMP-13) and a disintegrin and

  13. The surface lamina of the articular cartilage of human zygapophyseal joints.

    PubMed

    Giles, L G

    1992-07-01

    Literature referring to the conflicting results of investigations into the possible existence and composition of the lamina splendens is reviewed. Two hundred micrometer thick histological sections from 80 human cadaveric lower lumbar zygapophyseal joint articular cartilages were examined by ordinary light and darkfield microscopy. The findings illustrate what appears to be an acellular surface lamina on the opposing cartilaginous surfaces. No speculation is made regarding the possible physiological significance of the lamina based on this anatomical study. PMID:1609968

  14. Effects of introducing cultured human chondrocytes into a human articular cartilage explant model.

    PubMed

    Secretan, Charles; Bagnall, Keith M; Jomha, Nadr M

    2010-02-01

    Articular cartilage (AC) heals poorly and effective host-tissue integration after reconstruction is a concern. We have investigated the ability of implanted chondrocytes to attach at the site of injury and to be incorporated into the decellularized host matrix adjacent to a defect in an in vitro human explant model. Human osteochondral dowels received a standardized injury, were seeded with passage 3 chondrocytes labelled with PKH 26 and compared with two control groups. All dowels were cultured in vitro, harvested at 0, 7, 14 and 28 days and assessed for chondrocyte adherence and migration into the region of decellularized tissue adjacent to the defects. Additional evaluation included cell viability, general morphology and collagen II production. Seeded chondrocytes adhered to the standardized defect and areas of lamina splendens disruption but did not migrate into the adjacent acellular region. A difference was noted in viable-cell density between the experimental group and one control group. A thin lattice-like network of matrix surrounded the seeded chondrocytes and collagen II was present. The results indicate that cultured human chondrocytes do indeed adhere to regions of AC matrix injury but do not migrate into the host tissue, despite the presence of viable cells. This human explant model is thus an effective tool for studying the interaction of implanted cells and host tissue. PMID:20012649

  15. STRUCTURE-FUNCTION RELATIONSHIPS IN OSTEOARTHRITIC HUMAN HIP JOINT ARTICULAR CARTILAGE

    PubMed Central

    Mäkelä, Janne T.A.; Huttu, Mari R.J.; Korhonen, Rami K.

    2013-01-01

    Objectives It is currently poorly known how different structural and compositional components in human articular cartilage are related to their specific functional properties at different stages of osteoarthritis (OA). The objective of this study was to characterize the structure-function relationships of articular cartilage obtained from osteoarthritic human hip joints. Methods Articular cartilage samples with their subchondral bone (n = 15) were harvested during hip replacement surgeries from human femoral necks. Stress-relaxation tests, Mankin scoring, spectroscopic and microscopic methods were used to determine the biomechanical properties, OA grade, and the composition and structure of the samples. In order to obtain the mechanical material parameters for the samples, a fibril-reinforced poroviscoelastic model was fitted to the experimental data obtained from the stress-relaxation experiments. Results The strain-dependent collagen network modulus (Efε) and the collagen orientation angle exhibited a negative linear correlation (r = −0.65, p < 0.01), while the permeability strain-dependency factor (M) and the collagen content exhibited a positive linear correlation (r = 0.56, p < 0.05). The non-fibrillar matrix modulus (Enf) also exhibited a positive linear correlation with the proteoglycan content (r = 0.54, p < 0.05). Conclusion The study suggests that increased collagen orientation angle during OA primarily impairs the collagen network and the tensile stiffness of cartilage in a strain-dependent manner, while the decreased collagen content in OA facilitates fluid flow out of the tissue especially at high compressive strains. Thus, the results provide interesting and important information of the structure-function relationships of human hip joint cartilage and mechanisms during the progression of OA. PMID:22858669

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

    PubMed

    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. PMID:26769161

  17. Chondrocyte number and proteoglycan synthesis in the aging and osteoarthritic human articular cartilage

    PubMed Central

    Bobacz, K; Erlacher, L; Smolen, J; Soleiman, A; Graninger, W

    2004-01-01

    Objective: To correlate the number of chondrocytes in healthy and osteoarthritic human articular cartilage with age, and to evaluate the influence of donor age on total proteoglycan synthesis. Methods: Chondrocytes were isolated from human articular cartilage derived from hip joints with and without osteoarthritic lesions. The cell number was normalised to cartilage sample wet weight. In addition, the influence of age on chondrocyte numbers was assessed histomorphometrically. Chondrocytes were grown as monolayer cultures for seven days in a chemically defined serum-free basal medium. Total proteoglycan synthesis was measured by [35S]sulphate incorporation into newly synthesised macromolecules. Results: Chondrocyte numbers in healthy cartilage decreased significantly with advancing age (r = –0.69, p<0.0001). In contrast to healthy specimens, chondrocyte numbers were decreased in osteoarthritic cartilage irrespective of and unrelated to age, and differed markedly, by an average of 38%, from the cell numbers found in healthy individuals (p<0.0001). Regarding synthesis of matrix macromolecules, no dependence on patients' age, either in healthy or in osteoarthritic specimens, could be observed. Conclusions: Under the experimental conditions employed, chondrocytes from healthy and osteoarthritic joints synthesised comparable amounts of cartilage macromolecules, independent of age or underlying osteoarthritic disease. Thus the decrease in chondrocyte number in aging and osteoarthritic joints could be a crucial factor in limiting tissue replenishment. PMID:15547085

  18. Micromechanical Mapping of Early Osteoarthritic Changes in the Pericellular Matrix of Human Articular Cartilage

    PubMed Central

    Wilusz, Rebecca E.; Zauscher, Stefan; Guilak, Farshid

    2013-01-01

    Objective Osteoarthritis (OA) is a degenerative joint disease characterized by the progressive loss of articular cartilage. While macroscale degradation of the cartilage extracellular matrix (ECM) has been extensively studied, microscale changes in the chondrocyte pericellular matrix (PCM) and immediate microenvironment with OA are not fully understood. The objective of this study was to quantify osteoarthritic changes in the micromechanical properties of the ECM and PCM of human articular cartilage in situ using atomic force microscopy (AFM). Method AFM elastic mapping was performed on cryosections of human cartilage harvested from both condyles of macroscopically normal and osteoarthritic knee joints. This method was used to test the hypotheses that both ECM and PCM regions exhibit a loss of mechanical properties with OA and that the size of the PCM is enlarged in OA cartilage as compared to normal tissue. Results Significant decreases were observed in both ECM and PCM moduli of 45% and 30%, respectively, on the medial condyle of OA knee joints as compared to cartilage from macroscopically normal joints. Enlargement of the PCM, as measured biomechanically, was also observed in medial condyle OA cartilage, reflecting the underlying distribution of type VI collagen in the region. No significant differences were observed in elastic moduli or their spatial distribution on the lateral condyle between normal and OA joints. Conclusion Our findings provide new evidence of significant site-specific degenerative changes in the chondrocyte micromechanical environment with OA. PMID:24025318

  19. Human metapneumovirus in adults.

    PubMed

    Haas, Lenneke E M; Thijsen, Steven F T; van Elden, Leontine; Heemstra, Karen A

    2013-01-01

    Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier. Although the virus was primarily known as causative agent of respiratory tract infections in children, HMPV is an important cause of respiratory infections in adults as well. Almost all children are infected by HMPV below the age of five; the repeated infections throughout life indicate transient immunity. HMPV infections usually are mild and self-limiting, but in the frail elderly and the immunocompromised patients, the clinical course can be complicated. Since culturing the virus is relatively difficult, diagnosis is mostly based on a nucleic acid amplification test, such as reverse transcriptase polymerase chain reaction. To date, no vaccine is available and treatment is supportive. However, ongoing research shows encouraging results. The aim of this paper is to review the current literature concerning HMPV infections in adults, and discuss recent development in treatment and vaccination. PMID:23299785

  20. Human Metapneumovirus in Adults

    PubMed Central

    Haas, Lenneke E. M.; Thijsen, Steven F. T.; van Elden, Leontine; Heemstra, Karen A.

    2013-01-01

    Human metapneumovirus (HMPV) is a relative newly described virus. It was first isolated in 2001 and currently appears to be one of the most significant and common human viral infections. Retrospective serologic studies demonstrated the presence of HMPV antibodies in humans more than 50 years earlier. Although the virus was primarily known as causative agent of respiratory tract infections in children, HMPV is an important cause of respiratory infections in adults as well. Almost all children are infected by HMPV below the age of five; the repeated infections throughout life indicate transient immunity. HMPV infections usually are mild and self-limiting, but in the frail elderly and the immunocompromised patients, the clinical course can be complicated. Since culturing the virus is relatively difficult, diagnosis is mostly based on a nucleic acid amplification test, such as reverse transcriptase polymerase chain reaction. To date, no vaccine is available and treatment is supportive. However, ongoing research shows encouraging results. The aim of this paper is to review the current literature concerning HMPV infections in adults, and discuss recent development in treatment and vaccination. PMID:23299785

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

    PubMed Central

    Li, S; Oreffo, ROC; Sengers, BG; Tare, RS

    2014-01-01

    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. Biotechnol. Bioeng. 2014;111: 1876–1885. PMID:24668194

  2. Biochemical and metabolic abnormalities in normal and osteoarthritic human articular cartilage

    SciTech Connect

    Ryu, J.; Treadwell, B.V.; Mankin, H.J.

    1984-01-01

    Incorporation of radioactive precursors into macromolecules was studied with human normal and osteoarthritic articular cartilage organ culture. Analysis of the salt extracted matrix components separated by cesium chloride buoyant density gradient centrifugation showed an increase in the specific activities of all gradient fractions prepared from the osteoarthritic cartilage. Further analysis of these fractions showed the osteoarthritic cartilage contained 5 times as much sulfate incorporated into proteoglycans, and an even greater amount of 3H-glucosamine incorporated into material sedimenting to the middle of the gradient. Greater than half of this radioactive middle fraction appears to be hyaluronate, as judged by the position it elutes from a DEAE column and its susceptibility to hyaluronidase digestion. This study supports earlier findings showing increased rates of macromolecular synthesis in osteoarthritis, and in addition, an even greater synthetic rate for hyaluronic acid is demonstrated.

  3. Curcumin synergizes with resveratrol to stimulate the MAPK signaling pathway in human articular chondrocytes in vitro.

    PubMed

    Shakibaei, Mehdi; Mobasheri, Ali; Buhrmann, Constanze

    2011-05-01

    The mitogen-activated protein kinase (MAPK) pathway is stimulated in differentiated chondrocytes and is an important signaling cascade for chondrocyte differentiation and survival. Pro-inflammatory cytokines such as interleukin 1β (IL-1β) play important roles in the pathogenesis of osteoarthritis (OA) and rheumatoid arthritis (RA). In this study, we investigated whether curcumin and resveratrol can synergistically inhibit the catabolic effects of IL-1β, specifically the inhibition of the MAPK and subsequent apoptosis in human articular chondrocytes. Chondrocytes were either left untreated or treated with 10 ng/ml IL-1β or 1 μM U0126, a specific inhibitor of MAPK pathway alone for the indicated time periods or pre-treated with 10 μM curcumin, 10 μM resveratrol or 10 μM resveratrol and 10 μM curcumin for 4 h followed by co-treatment with 10 ng/ml IL-1β or 1 μM U0126 and 10 μM resveratrol, 10 μM curcumin or 10 μM resveratrol and 10 μM curcumin for the indicated time periods. Cultures were evaluated by immunoblotting and transmission electron microscopy. Incubation of chondrocytes with IL-1β resulted in induction of apoptosis, downregulation of β1-integrins and the extracellular signal-regulated kinase 1/2 (Erk1/2). Interestingly, U0126 induced apoptosis and blocked the above-mentioned proteins in a similar way to IL-1β. Furthermore, curcumin and resveratrol inhibited IL-1β- or U0126-induced apoptosis and downregulation of β1-integrins and Erk1/2 in human articular chondrocytes. These results suggest that combining these two natural compounds activates MEK/Erk signaling, a pathway that is involved in the maintenance of chondrocyte differentiation and survival. PMID:21484156

  4. Alterations in endogenous osteogenic protein-1 with degeneration of human articular cartilage.

    PubMed

    Merrihew, Charis; Kumar, Bhavna; Heretis, Katherine; Rueger, David C; Kuettner, Klaus E; Chubinskaya, Susan

    2003-09-01

    A synchronized balance between synthesis and breakdown of extracellular matrix (ECM) molecules in normal articular cartilage is disturbed in osteoarthritis (OA). The focus of our study is the anabolic factor, osteogenic protein-1 (OP-1) that is expressed in articular cartilage and is able to induce the synthesis of ECM components. The major aim was to investigate both qualitatively and quantitatively endogenous OP-1 in normal, degenerative, and OA cartilage. Normal and degenerative cartilage was obtained at autopsies from femoral condyles of human organ donors with no documented history of joint disease; OA cartilage was obtained from patients undergoing joint arthroplasty. Appearance of donor cartilage was evaluated by Collins scale, where normal cartilage is assigned grades 0-1, and degenerated cartilage is assigned grades 2-4. OP-1 mRNA expression was assessed by RT-PCR; OP-1 protein (pro- and active forms) was qualitatively analyzed by Western blotting and quantified by OP-1 ELISA. The highest levels of OP-1 expression (mRNA and protein) were detected in normal cartilage of grade 0. The concentration of OP-1 protein was about 50 ng per gram cartilage dry weight. With the progression of cartilage degeneration (increased Collins grades and OA) OP-1 protein was down-regulated up to 9-fold. These changes affected primarily the active form of OP-1. OP-1 message also declined in cartilages with the increase of degenerative changes. In conclusion, an overall decrease in endogenous OP-1 in degenerated and OA tissue suggests that OP-1 could be one of the factors responsible for normal homeostasis and matrix integrity in cartilage. PMID:12919879

  5. Characterization of proteoglycans isolated from associative extracts of human articular cartilage.

    PubMed Central

    Vilím, V; Fosang, A J

    1993-01-01

    Approx. 10% of the total proteoglycan content of normal young human articular cartilage was extracted under associative conditions with Dulbecco's PBS. Proteoglycans isolated from the extract by Q-Sepharose chromatography were separated by gel chromatography and characterized by gradient gel SDS/PAGE and immunoblotting. Three species of small proteoglycans, two main populations of aggrecan and a population of its smaller fragments were identified. The major populations of aggrecan contained chondroitin sulphate chains, all or part of the N-terminal G1 and G2 domains and, therefore, intact keratan sulphate domains. The larger population was estimated by gradient SDS/PAGE to have a molecular mass of approx. 600 kDa or greater. The second population had an apparent molecular mass of approx. 300-600 kDa. Core proteins derived from these populations of proteoglycans separated on SDS/PAGE into several clusters of bands in the range from 120 to approx. 360 kDa. The extract further contained smaller fragments which lacked chondroitin sulphate but reacted with antibodies against keratan sulphate, and against epitopes present in the G2 domain of aggrecan. The presence of the G2 domain in a broad range of populations of decreasing size indicated extensive cleavage of the aggrecan core protein within its chondroitin sulphate domain. These findings suggest that fragmentation of aggrecan probably occurs in vivo in normal articular cartilage of young individuals. Associative extracts also contained decorin, biglycan and fibromodulin. These were resolved from aggrecan by gel chromatography and identified by immunodetection. Images Figure 2 Figure 4 Figure 5 Figure 6 Figure 7 PMID:8328959

  6. The ontogeny of talo-crural appositional articular morphology among catarrhine taxa: adult shape reflects substrate use.

    PubMed

    Turley, Kevin; Frost, Stephen R

    2014-07-01

    The upper ankle joint forms a single articular plane between organism and the foot and substrate. Singular warp analysis shows that its shape reflects substrate use. This study explores whether the differences in shape are genetic with a developmental trajectory evident during ontogeny or epigenetic and the result of substrate use by the individual. A total of 418 matched distal tibial and proximal talar landmarked surfaces from adult and subadult specimens from 12 diverse catarrhine taxa were studied. Specimens were grouped by molar eruption (M1, M2, and M3) for comparative analysis. Generalized Procrustes analysis, multivariate regression, relative warp analysis, singular warp analysis, and permutation tests were used. Singular warp analysis for the entire cohort was highly significant in the first singular warp, with the adult taxa sorting by substrate use. All 173 subadults clustered with an adult "arboreal" shape profile. Among Hominoidea, adults (M3) sorted by substrate use with Pan paniscus and Hylobatidae assuming an "arboreal" shape separate from Pan troglodytes and the remaining taxa with "terrestrial" shape. Cercopithecoid adults sorted by substrate use as well, with the M3 specimens of Papio hamadryas and Macaca thibetana demonstrating a "terrestrial" shape. Differences in mode of locomotion did not affect the findings in the first singular warp. Results confirmed the convergence of talo-crural shape among superfamilies based on substrate use and divergence in shape within Pan and Macaca, based on substrate use. The shape differences among adults (M3) are consistent with a plastic response to the behavioral stimulus of substrate use. PMID:24842582

  7. A comparative study of articular cartilage thickness in the stifle of animal species used in human pre-clinical studies compared to articular cartilage thickness in the human knee.

    PubMed

    Frisbie, D D; Cross, M W; McIlwraith, C W

    2006-01-01

    Histological measurements of the thickness of non-calcified and calcified cartilage, as well as the subchondral bone plate in five locations on the femoral trochlea and medial femoral condyles of species were used in preclinical studies of articular cartilage and compared to those of the human knee. Cadaver specimens were obtained of six human knees, as well as six equine, six goat, six dog, six sheep and six rabbit stifle joints (the animal equivalent of the human knee). Specimens were taken from the lateral trochlear ridge, medial trochlear ridge and medial femoral condyle. After histopathological processing, the thickness of non-calcified and calcified cartilage layers, as well as the subchondral bone plate, was measured. Average articular cartilage thickness over five locations were 2.2-2.5 mm for human, 0.3 mm for rabbit, 0.4-0.5 mm for sheep, 0.6-1.3 mm for dog, 0.7-1.5 mm for goat and 1.5-2 mm for horse. The horse provides the closest approximation to humans in terms of articular cartilage thickness, and this approximation is considered relevant in pre-clinical studies of cartilage healing. PMID:16971996

  8. Prediction of the human thoracic and lumbar articular facet joint morphometry from radiographic images

    PubMed Central

    Kunkel, Maria E; Schmidt, Hendrik; Wilke, Hans-Joachim

    2011-01-01

    The articular facet joints (AFJ) play an important role in the biomechanics of the spine. Although it is well known that some AFJ dimensions (e.g. facet height/width or facet angles) play a major role in spinal deformities such as scoliosis, little is known about statistical correlations between these dimensions and the size of the vertebral bodies. Such relations could allow patient-specific prediction of AFJ morphometry from a few dimensions measurable by X-ray. This would be of clinical interest and could also provide parameters for mathematical modeling of the spine. Our purpose in this study was to generate prediction equations for 20 parameters of the human thoracic and lumbar AFJ from T1 to L4 as a function of only one given parameter, the vertebral body height posterior (VBHP). Linear and nonlinear regression analyses were performed with published anatomical data, including linear and angular dimensions of the AFJ and vertebral body heights, to find the best functions to describe the correlations between these parameters. Third-order polynomial regressions, in contrast to the linear, exponential and logarithmic regressions, provided moderate to high correlations between the AFJ parameters and vertebral body heights; e.g. facet height superior and interfacet width (R2, 0.605–0.880); facet height inferior, interfacet height and sagittal/transverse angle superior (R2, 0.875–0.973). Different correlations were found for facet width and transverse angle inferior in the thoracic (R2, 0.703–0.930) and lumbar (R2, 0.457–0.892) regions. A set of 20 prediction equations for AFJ parameters was generated (P-values < 0.005, anova). Comparison of the AFJ predictions with experimental data indicated mean percent errors < 13%, with the exception of the thoracolumbar junction (T12–L1). It was possible to establish useful predictions for human thoracic and lumbar AFJ dimensions based on the size of the vertebral bodies. The generated set of equations allows the

  9. Age-related changes in the content of the C-terminal region of aggrecan in human articular cartilage.

    PubMed Central

    Dudhia, J; Davidson, C M; Wells, T M; Vynios, D H; Hardingham, T E; Bayliss, M T

    1996-01-01

    The content of the C-terminal region of aggrecan was investigated in samples of articular cartilage from individuals ranging in age from newborn to 65 years. This region contains the globular G3 domain which is known to be removed from aggrecan in mature cartilage, probably by proteolytic cleavage, but the age-related changes in its abundance in human cartilage have not been described previously. The analysis was performed by immunosorbant assay using an antiserum (JD5) against recombinant amino acid residues of human aggrecan, on crude extracts of cartilage without further purification of aggrecan. The results showed that the content of the C-terminal region decreased with age relative to the G1 domain content (correlation coefficient = 0.463). This represented a 92% fall in the content of this region of the molecule from newborn to 65 years of age. furthermore, when the G1 content of the cartilage extracts was corrected to only include the G1 attached to aggrecan and to exclude the G1 fragments which accumulate as a by-product of normal aggrecan turnover (free G1), the age-related decrease in the C-terminal region remained very pronounced. Analysis by composite agarose/PAGE showed that the number of subpopulations of aggrecan resolved increased from one in newborn to three in adult cartilage. All of these reacted with an antiserum to the human G1 domain, but only the slowest migrating species reacted with the C-terminal region antiserum (JD5). Similar analysis by SDS/PAGE confirmed the presence of high-molecular-mass (200 kDa) proteins reactive with JD5, but no reactive fragments of lower electrophoretic mobility were detected. In contrast, when probed with the antiserum to the human G1 domain, the immunoblots showed protein species corresponding to the free G1 and G1-G2 fragments, which were present at high concentrations in adult cartilage. The results suggest that the loss of the C-terminal region is not directly part of the process of aggrecan turnover, but

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

    PubMed

    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. PMID:25869133

  11. External fixation of intra-articular fracture of the distal radius in young and old adults.

    PubMed

    Huch, K; Hünerbein, M; Meeder, P J

    1996-01-01

    Forty patients (18-89 years old, mean 58 years) with comminuted intra-articular fractures of the distal radial end (AO-type C 2 or C 3) treated with external fixation could be followed for an average of 2.3 years. After 3 weeks, the distraction was released, and after another 3 weeks, the device was removed. Complications seen were one malunion, one radial shaft fracture caused by excentric drilling of a Schanz screw, one Sudeck atrophy, and one subcutaneous pin-track infection. Radial and ulnar deviations were reduced to 52% and 71% of the untreated wrist, whereas the range of motion in the other planes reached about 80% or more of the healthy side. In all, 82.5% of the patients showed good or excellent radiological and functional results. This study demonstrates that external fixation of distal radial C 2 and 3 fractures for 6 weeks results in good recovery for young patients and elderly patients with osteoporosis. PMID:8775708

  12. Differential regulation and expression of hyaluronan synthases in human articular chondrocytes, synovial cells and osteosarcoma cells.

    PubMed Central

    Recklies, A D; White, C; Melching, L; Roughley, P J

    2001-01-01

    Recently three isoforms of hyaluronan synthase (HAS), the enzyme responsible for hyaluronate/hyaluronan (HA) biosynthesis, have been cloned, allowing us to study their expression pattern. Our objective was to determine which of the HAS isoenzymes were expressed in human articular chondrocytes, synovial fibroblasts and osteosarcoma cells, whether their expression could be modulated by growth factors (insulin-like growth factor-1, basic fibroblast growth factor and transforming growth factor (TGF-beta1) and cytokines [interleukin 1beta1 (IL-1beta)], and whether changes in the rate of HA synthesis by the cells correlated with changes in mRNA levels for one or more of the HAS isoforms. All three HAS isoforms were found to be expressed in the cultured cells analysed in this study, although the relative proportions varied for each cell type. HAS2 mRNA was usually predominant in chondrocytes, whereas synovial cells contained increased amounts of HAS1. HAS3 was always the least abundant message. The rapidly growing osteosarcoma cells contained almost exclusively HAS2 message. HAS usage in uncultured cartilage and synovial tissues was similar to that in the cultured cells, with HAS2 message being the predominant species in cartilage and HAS1 usually being the predominant species in synovium. HA synthesis was stimulated by the growth factors, but the extent of the response was cell-type specific. Synovial cells responded particularly well to IL-1beta, and showed a unique synergistic response when IL-1beta was used in combination with TGF-beta1. This response was much reduced in articular chondrocytes and absent in the osteosarcoma cells. Analysis of changes in HAS message levels indicated that there was often no correlation with the changes in HA secretion following exposure to growth factors. Although HAS-1 mRNA was increased in synovial cells after exposure to TGF-beta1/IL-1beta, the magnitude of the change was far less than the effect on HA synthesis. Our data thus

  13. Dermatan sulphate proteoglycans of human articular cartilage. The properties of dermatan sulphate proteoglycans I and II.

    PubMed Central

    Roughley, P J; White, R J

    1989-01-01

    Dermatan sulphate proteoglycans were purified from juvenile human articular cartilage, with a yield of about 2 mg/g wet wt. of cartilage. Both dermatan sulphate proteoglycan I (DS-PGI) and dermatan sulphate proteoglycan II (DS-PGII) were identified and the former was present in greater abundance. The two proteoglycans could not be resolved by agarose/polyacrylamide-gel electrophoresis, but could be resolved by SDS/polyacrylamide-gel electrophoresis, which indicated average Mr values of 200,000 and 98,000 for DS-PGI and DS-PGII respectively. After digestion with chondroitin ABC lyase the Mr values of the core proteins were 44,000 for DS-PGI and 43,000 and 47,000 for DS-PGII, with the smaller core protein being predominant in DS-PGII. Sequence analysis of the N-terminal 20 amino acid residues reveals the presence of a single site for the potential substitution of dermatan sulphate at residue 4 of DS-PGII and two such sites at residues 5 and 10 for DS-PGI. Images Fig. 1. Fig. 2. PMID:2590169

  14. Multiparametric MRI Assessment of Human Articular Cartilage Degeneration: Correlation with Quantitative Histology and Mechanical Properties

    PubMed Central

    Rautiainen, Jari; Nissi, Mikko J.; Salo, Elli-Noora; Tiitu, Virpi; Finnilä, Mikko A.J.; Aho, Olli-Matti; Saarakkala, Simo; Lehenkari, Petri; Ellermann, Jutta; Nieminen, Miika T.

    2014-01-01

    Purpose To evaluate the sensitivity of quantitative MRI techniques (T1, T1,Gd, T2, continous wave (CW) T1ρ dispersion, adiabatic T1ρ, adiabatic T2ρ, RAFF and inversion-prepared magnetization transfer (MT)) for assessment of human articular cartilage with varying degrees of natural degeneration. Methods Osteochondral samples (n = 14) were obtained from the tibial plateaus of patients undergoing total knee replacement. MRI of the specimens was performed at 9.4 T and the relaxation time maps were evaluated in the cartilage zones. For reference, quantitative histology, OARSI grading and biomechanical measurements were performed and correlated with MRI findings. Results All MRI parameters, except T1,Gd, showed statistically significant differences in tangential and full-thickness ROIs between early and advanced osteoarthritis (OA) groups, as classified by OARSI grading. CW-T1ρ showed significant dispersion in all ROIs and featured classical laminar structure of cartilage with spin-lock powers below 1000 Hz. Adiabatic T1ρ, T2ρ, CW-T1ρ, MT and RAFF correlated strongly with OARSI grade and biomechanical parameters. Conclusion MRI parameters were able to differentiate between early and advanced OA. Furthermore, rotating frame methods, namely adiabatic T1ρ, adiabatic T2ρ, CW-T1ρ and RAFF, as well as MT experiment correlated strongly with biomechanical parameters and OARSI grade, suggesting high sensitivity of the parameters for cartilage degeneration. PMID:25104181

  15. Human articular cartilage in osteoarthrosis. I. The matrix. Transmission electron microscopic study.

    PubMed

    Montella, A; Manunta, A; Espa, E; Gasparini, G; De Santis, E; Gulisano, M

    1992-01-01

    The present research has been carried out with the aim of contributing to the understanding of morphological changes in human articular cartilage during osteoarthrosis and to evaluate the usefulness of TEM in this application. Only the matrix was examined in this first phase of study. Fragments from the femoral head of 20 patients subjected total hip arthroplasis, were studied by TEM after treatment with current procedures. The images obtained were considered observing the division of cartilage into superficial, intermediate and deep layers. Patients were divided according to the gravity of their clinical conditions. The least severe forms of pathology seem to involve only the superficial layer, which quickly loses the lamina splendens and may be affected by rarefactions of the matrix, which becomes fissured, while the deep layers are only slightly involved. During the later stages, the pathology progresses with irregularity of disposition and size of the collagen fibres and an increase in the number and size of fissures. The intermediate layer shows architectural disorder in the collagen fibres, even reaching the deep layer. The interfibrillar distance appears greater. As pathology progresses, the superficial layer tends to disappear, while the successive layers undergo progressive alteration in disposition and size of the collagen fibres. Globular aggregations of various dimensions and electron density similar to collagen are present in the deep layer. PMID:1288443

  16. Effects of Hyaluronic Acid and γ–Globulin Concentrations on the Frictional Response of Human Osteoarthritic Articular Cartilage

    PubMed Central

    Son, Kyeong-Min; Thompson, Mark S.; Park, Sungchan; Chang, Jun-Dong; Nam, Ju-Suk; Park, Seonghun; Lee, Sang-Soo

    2014-01-01

    Synovial fluid plays an important role in lubricating synovial joints. Its main constituents are hyaluronic acid (HA) and γ–globulin, acting as boundary lubricants for articular cartilage. The aim of the study was to demonstrate the concentration-dependent effect of HA and γ–globulin on the boundary-lubricating ability of human osteoarthritis (OA) cartilage. Normal, early and advance stage articular cartilage samples were obtained from human femoral heads and in presence of either HA or γ–globulin, cartilage frictional coefficient (µ) was measured by atomic force microscopy (AFM). In advanced stage OA, the cartilage superficial layer was observed to be completely removed and the damaged cartilage surface showed a higher µ value (∼0.409) than the normal cartilage surface (∼0.119) in PBS. Adsorbed HA and γ–globulin molecules significantly improved the frictional behavior of advanced OA cartilage, while they were ineffective for normal and early OA cartilage. In advanced-stage OA, the concentration-dependent frictional response of articular cartilage was observed with γ–globulin, but not with HA. Our result suggested that HA and γ–globulin may play a significant role in improving frictional behavior of advanced OA cartilage. During early-stage OA, though HA and γ–globulin had no effect on improving frictional behavior of cartilage, however, they might contribute to disease modifying effects of synovial fluid as observed in clinical settings. PMID:25426992

  17. Age-related changes in the composition, the molecular stoichiometry and the stability of proteoglycan aggregates extracted from human articular cartilage.

    PubMed Central

    Wells, Terri; Davidson, Catherine; Mörgelin, Matthias; Bird, Joseph L E; Bayliss, Michael T; Dudhia, Jayesh

    2003-01-01

    The heterogeneity of the components of proteoglycan aggregates, their stoichiometry within the aggregate and the aggregates' stability was investigated in normal human articular cartilage specimens (age-range newborn to 63 years). Proteoglycans were extracted from tissue by sequentially extracting them with PBS alone, PBS containing oligosaccharides of hyaluronan, and PBS containing solutions of increasing guanidinium chloride concentration (1 M, 2 M, 3 M and 4 M). A high proportion of each of the components of the proteoglycan aggregate, i.e. uronic acid, sulphated glycosaminoglycan, hyaluronan binding domain of aggrecan (G1-domain), link protein (LP) and hyaluronan, was extracted from immature cartilage by PBS alone and PBS containing oligosaccharides of hyaluronan. This was in marked contrast to adult cartilage, which required high concentrations of guanidinium chloride for the efficient extraction of these components. The molar ratios of total G1-domain:LP and the G1-domain associated with aggrecan:LP also differed markedly between immature and mature cartilage and between each of the sequential extracts. The concentration of LP was less than that of the G1-domain in all extracts of cartilage from individuals over 13 years, but this was particularly noticeable in the 1 M guanidinium chloride extracts, and it was surmised that a deficiency in LP produces unstable aggregates in situ. The fragmentation of LP, which is known to occur with advancing age, did not influence the extractability of LP, and fragments were present in each of the sequential extracts. Therefore the generally accepted model of proteoglycan aggregation presented in the literature, which is mostly derived from analysis of immature animal cartilage, cannot be used to describe the structure and organization of aggregates in adult human articular cartilage, where a heterogeneous population of complexes exist that have varying degrees of stability. PMID:12431185

  18. Characterization and Localization of Citrullinated Proteoglycan Aggrecan in Human Articular Cartilage

    PubMed Central

    Glant, Tibor T.; Ocsko, Timea; Markovics, Adrienn; Szekanecz, Zoltan; Katz, Robert S.; Rauch, Tibor A.; Mikecz, Katalin

    2016-01-01

    Background Rheumatoid arthritis (RA) is an autoimmune disease of the synovial joints. The autoimmune character of RA is underscored by prominent production of autoantibodies such as those against IgG (rheumatoid factor), and a broad array of joint tissue-specific and other endogenous citrullinated proteins. Anti-citrullinated protein antibodies (ACPA) can be detected in the sera and synovial fluids of RA patients and ACPA seropositivity is one of the diagnostic criteria of RA. Studies have demonstrated that RA T cells respond to citrullinated peptides (epitopes) of proteoglycan (PG) aggrecan, which is one of the most abundant macromolecules of articular cartilage. However, it is not known if the PG molecule is citrullinated in vivo in human cartilage, and if so, whether citrulline-containing neoepitopes of PG (CitPG) can contribute to autoimmunity in RA. Methods CitPG was detected in human cartilage extracts using ACPA+ RA sera in dot blot and Western blot. Citrullination status of in vitro citrullinated recombinant G1 domain of human PG (rhG1) was confirmed by antibody-based and chemical methods, and potential sites of citrullination in rhG1 were explored by molecular modeling. CitPG-specific serum autoantibodies were quantified by enzyme-linked immunosorbent assays, and CitPG was localized in osteoarthritic (OA) and RA cartilage using immunohistochemistry. Findings Sera from ACPA+ RA patients reacted with PG purified from normal human cartilage specimens. PG fragments (mainly those containing the G1 domain) from OA or RA cartilage extracts were recognized by ACPA+ sera but not by serum from ACPA- individuals. ACPA+ sera also reacted with in vitro citrullinated rhG1 and G3 domain-containing fragment(s) of PG. Molecular modeling suggested multiple sites of potential citrullination within the G1 domain. The immunohistochemical localization of CitPG was different in OA and RA cartilage. Conclusions CitPG is a new member of citrullinated proteins identified in human

  19. Regeneration of Articular Cartilage Surface: Morphogens, Cells, and Extracellular Matrix Scaffolds.

    PubMed

    Sakata, Ryosuke; Iwakura, Takashi; Reddi, A Hari

    2015-10-01

    The articular cartilage is a well-organized tissue for smooth and friction-free joint movement for locomotion in animals and humans. Adult articular cartilage has a very low self-regeneration capacity due to its avascular nature. The regeneration of articular cartilage surface is critical to prevent the progression to osteoarthritis (OA). Although various joint resurfacing procedures in experimental articular cartilage defects have been developed, no standardized clinical protocol has yet been established. The three critical ingredients for tissue regeneration are morphogens and growth factors, cells, and scaffolds. The concepts based on the regeneration triad have been extensively investigated in animal models. However, these studies in animal models have demonstrated variable results and outcomes. An optimal animal model must precisely mimic and model the sequence of events in articular cartilage regeneration in human. In this article, the progress and remaining challenges in articular cartilage regeneration in animal models are reviewed. The role of individual morphogens and growth factors in cartilage regeneration has been investigated. In normal articular cartilage homeostasis, morphogens and growth factors function sequentially in tissue regeneration. Mesenchymal stem cell-based repair of articular cartilage defects, performed with or without various growth factors and scaffolds, has been widely attempted in animal models. Stem cells, including embryonic and adult stem cells and induced pluripotent stem cells, have also been reported as attractive cell sources for articular cartilage surface regeneration. Several studies with regard to scaffolds have been advanced, including recent investigations based on nanomaterials, functional mechanocompatible scaffolds, multilayered scaffolds, and extracellular matrix scaffolds for articular cartilage surface regeneration. Continuous refinement of animal models in chondral and osteochondral defects provide opportunities

  20. The Relationship between MR Parameters and Biomechanical Quantities of Loaded Human Articular Cartilage in Osteoarthritis: An In-Vitro Study

    NASA Astrophysics Data System (ADS)

    Juráš, V.; Szomolányi, P.; Gäbler, S.; Frollo, I.; Trattnig, S.

    2009-01-01

    The aim of this study was to assess the changes in MRI parameters during applied load directly in MR scanner and correlate these changes with biomechanical parameters of human articular cartilage. Cartilage explants from patients who underwent total knee replacement were examined in the micro-imaging system in 3T scanner. Respective MRI parameters (T1 without- and T1 with contrast agent as a marker of proteoglycan content, T2 as a marker of collagen network anisotropy and ADC as a measure of diffusivity) were calculated in pre- and during compression state. Subsequently, these parameters were compared to the biomechanical properties of articular cartilage, instantaneous modulus (I), equilibrium modulus (Eq) and time of tissue relaxation (τ). Significant load-induced changes of T2 and ADC were recorded. High correlation between T1Gd and I (r = 0.6324), and between ADC and Eq (r = -0.4884) was found. Multi-parametric MRI may have great potential in analyzing static and dynamic biomechanical behavior of articular cartilage in early stages of osteoarthritis (OA).

  1. In vivo articular cartilage deformation: noninvasive quantification of intratissue strain during joint contact in the human knee

    PubMed Central

    Chan, Deva D.; Cai, Luyao; Butz, Kent D.; Trippel, Stephen B.; Nauman, Eric A.; Neu, Corey P.

    2016-01-01

    The in vivo measurement of articular cartilage deformation is essential to understand how mechanical forces distribute throughout the healthy tissue and change over time in the pathologic joint. Displacements or strain may serve as a functional imaging biomarker for healthy, diseased, and repaired tissues, but unfortunately intratissue cartilage deformation in vivo is largely unknown. Here, we directly quantified for the first time deformation patterns through the thickness of tibiofemoral articular cartilage in healthy human volunteers. Magnetic resonance imaging acquisitions were synchronized with physiologically relevant compressive loading and used to visualize and measure regional displacement and strain of tibiofemoral articular cartilage in a sagittal plane. We found that compression (of 1/2 body weight) applied at the foot produced a sliding, rigid-body displacement at the tibiofemoral cartilage interface, that loading generated subject- and gender-specific and regionally complex patterns of intratissue strains, and that dominant cartilage strains (approaching 12%) were in shear. Maximum principle and shear strain measures in the tibia were correlated with body mass index. Our MRI-based approach may accelerate the development of regenerative therapies for diseased or damaged cartilage, which is currently limited by the lack of reliable in vivo methods for noninvasive assessment of functional changes following treatment. PMID:26752228

  2. In vivo articular cartilage deformation: noninvasive quantification of intratissue strain during joint contact in the human knee

    NASA Astrophysics Data System (ADS)

    Chan, Deva D.; Cai, Luyao; Butz, Kent D.; Trippel, Stephen B.; Nauman, Eric A.; Neu, Corey P.

    2016-01-01

    The in vivo measurement of articular cartilage deformation is essential to understand how mechanical forces distribute throughout the healthy tissue and change over time in the pathologic joint. Displacements or strain may serve as a functional imaging biomarker for healthy, diseased, and repaired tissues, but unfortunately intratissue cartilage deformation in vivo is largely unknown. Here, we directly quantified for the first time deformation patterns through the thickness of tibiofemoral articular cartilage in healthy human volunteers. Magnetic resonance imaging acquisitions were synchronized with physiologically relevant compressive loading and used to visualize and measure regional displacement and strain of tibiofemoral articular cartilage in a sagittal plane. We found that compression (of 1/2 body weight) applied at the foot produced a sliding, rigid-body displacement at the tibiofemoral cartilage interface, that loading generated subject- and gender-specific and regionally complex patterns of intratissue strains, and that dominant cartilage strains (approaching 12%) were in shear. Maximum principle and shear strain measures in the tibia were correlated with body mass index. Our MRI-based approach may accelerate the development of regenerative therapies for diseased or damaged cartilage, which is currently limited by the lack of reliable in vivo methods for noninvasive assessment of functional changes following treatment.

  3. In vivo articular cartilage deformation: noninvasive quantification of intratissue strain during joint contact in the human knee.

    PubMed

    Chan, Deva D; Cai, Luyao; Butz, Kent D; Trippel, Stephen B; Nauman, Eric A; Neu, Corey P

    2016-01-01

    The in vivo measurement of articular cartilage deformation is essential to understand how mechanical forces distribute throughout the healthy tissue and change over time in the pathologic joint. Displacements or strain may serve as a functional imaging biomarker for healthy, diseased, and repaired tissues, but unfortunately intratissue cartilage deformation in vivo is largely unknown. Here, we directly quantified for the first time deformation patterns through the thickness of tibiofemoral articular cartilage in healthy human volunteers. Magnetic resonance imaging acquisitions were synchronized with physiologically relevant compressive loading and used to visualize and measure regional displacement and strain of tibiofemoral articular cartilage in a sagittal plane. We found that compression (of 1/2 body weight) applied at the foot produced a sliding, rigid-body displacement at the tibiofemoral cartilage interface, that loading generated subject- and gender-specific and regionally complex patterns of intratissue strains, and that dominant cartilage strains (approaching 12%) were in shear. Maximum principle and shear strain measures in the tibia were correlated with body mass index. Our MRI-based approach may accelerate the development of regenerative therapies for diseased or damaged cartilage, which is currently limited by the lack of reliable in vivo methods for noninvasive assessment of functional changes following treatment. PMID:26752228

  4. Arts & Humanities in Adult Education.

    ERIC Educational Resources Information Center

    Word's Worth: A Quarterly Newsletter of the Lifelong Learning Network, 1998

    1998-01-01

    This issue of a quarterly newsletter on lifelong learning focuses on the theme of the arts and humanities in adult literacy education. The following articles are included: (1) "In Defense of a Practical Education" (Earl Shorris); (2) "From the Program Director" (Elizabeth Bryant McCrary); (3) "Vermont Council on the Humanities: Book Discussion…

  5. Fibroblast Growth Factor–2 Promotes Catabolism Via FGFR1–Ras–Raf–MEK1/2–ERK1/2 Axis That Coordinates With the PKCδ Pathway in Human Articular Chondrocytes

    PubMed Central

    Yan, Dongyao; Chen, Di; Im, Hee-Jeong

    2013-01-01

    Fibroblast growth factor 2 (FGF-2) has been found to play an anti-anabolic and/or a catabolic role in adult human articular cartilage via regulation of multiple signaling pathways. Upon FGF-2 stimulation, a molecular crosstalk between the mitogen activated protein kinase (MAPK) and protein kinase C δ (PKCδ) pathways are initiated, where PKCδ positively regulates downstream MAPK signaling. In this study, we explored the relationship between fibroblast growth factor receptor 1 (FGFR1), Ras, and PKCδ in FGF-2 signaling in human articular chondrocytes. Pathway-specific inhibition using both chemical inhibitors and siRNA targeting FGFR1 demonstrated that, upon FGF-2 stimulation, FGFR1 controlled both Ras and PKCδ activation, which converged on the Raf-MEK1/2-ERK1/2 axis. No crosstalk was observed between Ras and PKCδ. Quantitative PCR analyses revealed that both Ras and PKCδ contributed to FGF-2-mediated upregulation of MMP-13, ADAMTS5, and repression of aggrecan gene. Correspondingly, FGF-2-mediated proteoglycan loss was effectively reversed by individual pathway-specific inhibitor of Ras, PKCδ, and ERK1/2 in both 3-dimensional alginate bead culture and cartilage organ culture systems. Our findings suggest that FGFR1 interacts with FGF-2 and then activates Ras and PKCδ, which concertedly drive MAPK signaling to mediate biological effects of FGF-2. Such an integration of dual inputs constitutes a novel mechanism of FGF-2 signaling cascade in human articular chondrocytes. PMID:22488450

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

    PubMed Central

    2013-01-01

    -nonspecific alkaline phosphatase, was upregulated in OA chondrocytes isolated from CaC crystal-containing cartilages. Conclusions CaC crystal deposition is a widespread phenomenon in human OA articular cartilage involving the entire knee cartilage including macroscopically normal and less weight-bearing zones. Cartilage calcification is associated with altered expression of genes involved in the mineralisation process. PMID:24004678

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

    PubMed Central

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

    2012-01-01

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

  8. In vitro determination of biomechanical properties of human articular cartilage in osteoarthritis using multi-parametric MRI

    NASA Astrophysics Data System (ADS)

    Juras, Vladimir; Bittsansky, Michal; Majdisova, Zuzana; Szomolanyi, Pavol; Sulzbacher, Irene; Gäbler, Stefan; Stampfl, Jürgen; Schüller, Georg; Trattnig, Siegfried

    2009-03-01

    The objective of this study was to evaluate the correlations between MR parameters and the biomechanical properties of naturally degenerated human articular cartilage. Human cartilage explants from the femoral condyles of patients who underwent total knee replacement were evaluated on a micro-imaging system at 3 T. To quantify glycosaminoglycan (GAG) content, delayed gadolinium-enhanced MRI of the cartilage (dGEMRIC) was used. T2 maps were created by using multi-echo, multi-slice spin echo sequences with six echoes: 15, 30, 45, 60, 75, and 90 ms. Data for apparent diffusion constant (ADC) maps were obtained from pulsed gradient spin echo (PGSE) sequences with five b-values: 10.472, 220.0, 627.0, 452.8, 724.5, and 957.7. MR parameters were correlated with mechanical parameters (instantaneous ( I) and equilibrium ( Eq) modulus and relaxation time ( τ)), and the OA stage of each cartilage specimen was determined by histological evaluation of hematoxylin-eosin stained slices. For some parameters, a high correlation was found: the correlation of T1Gd vs Eq ( r = 0.8095), T1Gd vs I/ Eq ( r = -0.8441) and T1Gd vs τ ( r = 0.8469). The correlation of T2 and ADC with selected biomechanical parameters was not statistically significant. In conclusion, GAG content measured by dGEMRIC is highly related to the selected biomechanical properties of naturally degenerated articular cartilage. In contrast, T2 and ADC were unable to estimate these properties. The results of the study imply that some MR parameters can non-invasively predict the biomechanical properties of degenerated articular cartilage.

  9. Three-Dimensional Scaffold-Free Fusion Culture: the Way to Enhanced Chondrogenesis of in vitro Propagated Human Articular Chondrocytes

    PubMed Central

    Lehmann, M.; Martin, F.; Mannigel, K.; Kaltschmidt, K.; Sack, U.; Anderer, U.

    2013-01-01

    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-β2) 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-β2 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. PMID:24441184

  10. The significance of using pooled human serum in human articular cartilage tissue engineering.

    PubMed

    Azmi, B; Aminuddin, B S; Sharaf, I; Samsudin, O C; Munirah, S; Chua, K H; Ruszymah, B H I

    2004-05-01

    Animal serum is commonly used in chondrocytes culture expansion to promote cell proliferation and shorten the time lag before new tissue reconstruction is possible. However, animal serum is not suitable for regeneration of clinical tissue because it has potential risk of viral and prion related disease transmission particularly mad cow disease and foreign protein contamination that can stimulate immune reaction leading to graft rejection. In this context, human serum as homologous supplement has a greater potential as growth promoting agents for human chondrocytes culture. PMID:15468795

  11. Trabecular trajectory in the articular processes of the human fourth cervical vertebra

    PubMed Central

    HERRERA, M.; PANCHÓN, A.; PEREZ-BACETE, M.

    2001-01-01

    The articular processes (AP) of the neural arch have been implicated in weight transmission through the cervical spine. To analyse the mechanism of weight transmission in the AP, we studied the direction of forces within it, in particular, the pattern of trabecular trajectories. Twenty-two AP from C4 vertebrae were studied in anatomical sections, and corresponding photoelastic models from selected sections were constructed and analysed. Anatomical and photoelastic findings show the subarticular spongiosa of the superior articular process (SAP) to be orthogonally arranged with vertical and oblique trabeculae in the direction of compressive forces and additional trabeculae always oriented perpendicular to the former. Vertical and oblique trabeculae are divided into rostral, middle and posterior groups. Rostral and middle trabeculae end in the anterior wall of the SAP and the transitional zone with the pedicle. Posterior trabeculae end in the subarticular spongiosa of the inferior articular process (IAP). The findings relating to trabecular trajectories in the SAP differ from previous descriptions and instead suggest that a part of the weight forces distributed within the AP transmit to the subchondral zone of the IAP. Knowledge of the trajectorial architecture of the AP may contribute to refining finite element analytical models for investigating its weight-bearing function. PMID:11554512

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

    PubMed Central

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

    2013-01-01

    Bovine lactoferricin (LfcinB) is a heparan sulfate-binding peptide with multiple bioactivities. In human articular cartilage, LfcinB antagonizes interleukin-1 β (IL-1β) and fibroblast growth factor 2 (FGF-2) in proteoglycan metabolism, catabolic protease expression, and induction of pro-inflammatory mediators. LfcinB specifically activates ERK1/2, p38 and Akt, but whether these signaling pathways control the expression of LfcinB target genes remained unknown. In this report, we characterized a novel aspect of LfcinB-mediated genetic response in human articular chondrocytes, tissue inhibitor of metalloproteinase 3 (TIMP-3) induction. Inhibition of individual signaling pathways revealed that ERK1/2 functions as the major pathway in TIMP-3 expression, whereas Akt plays a minor role. Further investigation identified Sp1 as a critical transcriptional activator in TIMP-3 regulation, and Sp1 activity is modulated by ERK1/2, not Akt. Comparative quantification indicates significant downregulation of TIMP-3 occurs in OA chondrocytes, suggesting a beneficial role of LfcinB in OA pathogenesis. Our results collectively provide new insights into the mechanism of action of LfcinB, and support the candidacy of LfcinB as a chondroprotective agent. PMID:23313877

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

    PubMed Central

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

    2014-01-01

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

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

    PubMed Central

    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.

    2015-01-01

    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. PMID:26569221

  15. Inhibition of Histone Deacetylases Antagonized FGF2 and IL-1β Effects on MMP Expression in Human Articular Chondrocytes

    PubMed Central

    Wang, Xibin; Song, Yingjie; Jacobi, Jennifer L.; Tuan, Rocky S.

    2013-01-01

    Fibroblast growth factor – 2 (FGF2) and interleukin – 1β IL-1β) stimulate the expression of matrix metalloproteinases (MMPs) in articular chondrocytes, which may contribute to cartilage degradation and development of osteoarthritis. Histone deacetylases (HDACs) have recently been implicated in the regulation of MMP gene expression. To investigate the functional involvement of HDACs in the signaling pathway of FGF2 and IL-1β, we examined the effects of HDAC inhibition on activities of FGF2 or IL-1β on gene expression of MMP-1, MMP-3, MMP-13, a disintegrin and metalloproteinase with thrombospondin motifs – 5 (ADAMTS5), collagen type II, and aggrecan. Human articular chondrocyte cultures were treated with FGF2 or IL-1β in the presence or absence of HDAC inhibitor (trichostatin A, TSA). Gene expression levels after treatments were assessed using quantitative real time PCR. Results showed that FGF2 and IL-1β both increased MMP-1 and -13 expression, while IL-1βalso increased MMP-3 mRNA levels. These effects were attenuated in the presence of TSA in a dose dependent manner. In contrast to the effects on MMPs, FGF2 decreased mRNA levels of ADAMTS–5, which was not affected by HDAC inhibition. FGF2, IL-1β, and TSA inhibited expression of aggrecan, while TSA also decreased mRNA levels of collagen type II. These findings showed that HDAC inhibition antagonized FGF2 and IL-1β induced MMP expression. Combination of FGF2 and the HDAC inhibitor decreases both anabolic and catabolic genes, which may slow the cartilage turnover and be beneficial for maintaining cartilage integrity. PMID:19107653

  16. Expression of extracellular matrix molecules typical of articular cartilage in the human scapholunate interosseous ligament

    PubMed Central

    Milz, S; Aktas, T; Putz, R; Benjamin, M

    2006-01-01

    The scapholunate interosseous ligament (SLIL) connects the scaphoid and lunate bones and plays a crucial role in carpal kinematics. Its rupture leads to carpal instability and impairment of radiocarpal joint function. As the ligament is one of the first structures affected in rheumatoid arthritis, we conducted an immunohistochemical study of cadaveric tissue to determine whether it contains known autoantigens for rheumatoid arthritis. We immunolabelled the ligament from one hand in 12 cadavers with monoclonal antibodies directed against a wide range of extracellular matrix (ECM) molecules associated with both fibrous and cartilaginous tissues. The labelling profile has also enabled us to comment on how the molecular composition of the ligament relates to its mechanical function. All regions of the ligament labelled for types I, III and VI collagens, chondroitin 4 and 6 sulphates, keratan sulphate, dermatan sulphate, versican, tenascin and cartilage oligomeric matrix protein (COMP). However, both entheses labelled strongly for type II collagen, aggrecan and link protein and were distinctly fibrocartilaginous. In some regions, the ligament attached to bone via a region of hyaline cartilage that was continuous with articular cartilage. Labelling for cartilage molecules in the midsubstance was most evident dorsally. We conclude that the SLIL has an ECM which is typical of other highly fibrocartilaginous ligaments that experience both tensile load and shear. The presence of aggrecan, link protein, COMP and type II collagen could explain why the ligament may be a target for autoantigenic destruction in some forms of rheumatoid arthritis. PMID:16761970

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

    PubMed

    Kong, Ying; Wang, Wanchun; Zhang, Changjie; Wu, Yi; Liu, Yang; Zhou, Xiaorong

    2016-06-01

    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

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

    PubMed Central

    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

  19. Proteomic and redox-proteomic evaluation of homogentisic acid and ascorbic acid effects on human articular chondrocytes.

    PubMed

    Braconi, Daniela; Laschi, Marcella; Taylor, Adam M; Bernardini, Giulia; Spreafico, Adriano; Tinti, Laura; Gallagher, James A; Santucci, Annalisa

    2010-11-01

    Alkaptonuria (AKU) is a rare genetic disease associated with the accumulation of homogentisic acid (HGA) and its oxidized/polymerized products in connective tissues up to the deposition of melanin-like pigments (ochronosis). Since little is known on the effects of HGA and its metabolites on articular cells, we carried out a proteomic and redox-proteomic analysis to investigate how HGA and ascorbic acid (ASC) affect the human chondrocytic protein repertoire. We settled up an in vitro model using a human chondrocytic cell line to evaluate the effects of 0.33 mM HGA, alone or combined with ASC. We found that HGA and ASC significantly affect the levels of proteins with specific functions in protein folding, cell organization and, notably, stress response and cell defense. Increased protein carbonyls levels were found either in HGA or ASC treated cells, and evidences produced in this paper support the hypothesis that HGA-induced stress might be mediated by protein oxidation. Our finding can lay the basis towards the settling up of more sophisticated models to study AKU and ochronosis. PMID:20665660

  20. Quantification of aggrecan and link-protein mRNA in human articular cartilage of different ages by competitive reverse transcriptase-PCR.

    PubMed Central

    Bolton, M C; Dudhia, J; Bayliss, M T

    1996-01-01

    A competitive reverse transcriptase-PCR (RT-PCR) assay has been developed for the quantification of particular mRNA species in human articular cartilage. Competitor RNA species were synthesized that differed from the amplified target sequence only by the central insertion of an EcoRI restriction site. By using known amounts of synthetic target and competitor RNA, it was shown that competitor RNA molecules designed in this way are reverse-transcribed and amplified with equal efficiency to the target of interest. Furthermore quantification could be performed during the plateau phase of the PCR, which was necessary when using ethidium bromide fluorescence as a detection system. The inhibition of aggrecan and link-protein mRNA expression by interleukin 1 or tumour necrosis factor in monolayers of human articular chondrocytes quantified by this competitive RT-PCR method compared favourably with Northern hybridization studies. The main advantage of this technique is that it can be used to quantify levels of mRNA with RNA extracted directly from 100 mg wet weight of human articular cartilage. Age-related changes in aggrecan and link-protein mRNA were therefore quantified in human articular cartilage directly after dissection from the joint. The concentration of link-protein mRNA was higher in immature cartilage than in mature cartilage when expressed relative to the amount of glyceraldehyde-3-phosphate dehydrogenase mRNA, but no age-related changes were observed in aggrecan mRNA expression. The ratio of aggrecan to link-protein mRNA was higher in mature cartilage than in immature tissue. These age-related differences in the molecular stoichiometry of aggrecan and link-protein mRNA might have implications with respect to the regulation of the formation and the stability of the proteoglycan aggregates in cartilage. PMID:8912686

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

    PubMed

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

    2016-01-01

    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. PMID:27445254

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

    PubMed

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

    2016-10-15

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

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

    PubMed Central

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

    2016-01-01

    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. PMID:27445254

  4. Articular Osteochondrosis: A Comparison of Naturally-Occurring Human and Animal Disease

    PubMed Central

    McCoy, Annette M; Toth, Ferenc; Dolvik, Nils I; Ekman, Stina; Ellermann, Jutta; Olstad, Kristin; Ytrehus, Bjornar; Carlson, Cathy S

    2013-01-01

    Background Osteochondrosis (OC) is a common developmental orthopedic disease affecting both humans and animals. Despite increasing recognition of this disease among children and adolescents, its pathogenesis is incompletely understood because clinical signs are often not apparent until lesions have progressed to end-stage, and examination of cadaveric early lesions is not feasible. In contrast, both naturally-occurring and surgically-induced animal models of disease have been extensively studied, most notably in horses and swine, species in which OC is recognized to have profound health and economic implications. The potential for a translational model of human OC has not been recognized in the existing human literature. Objective The purpose of this review is to highlight the similarities in signalment, predilection sites and clinical presentation of naturally-occurring OC in humans and animals and to propose a common pathogenesis for this condition across species. Study Design Review Methods The published human and veterinary literature for the various manifestations of OC was reviewed. Peer-reviewed original scientific articles and species-specific review articles accessible in PubMed (US National Library of Medicine) were eligible for inclusion. Results A broad range of similarities exists between OC affecting humans and animals, including predilection sites, clinical presentation, radiographic/MRI changes, and histological appearance of the end stage lesion, suggesting a shared pathogenesis across species. Conclusion This proposed shared pathogenesis for OC between species implies that naturally-occurring and surgically-induced models of OC in animals may be useful in determining risk factors and for testing new diagnostic and therapeutic interventions that can be used in humans. PMID:23954774

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

    PubMed Central

    Stromps, Jan-Philipp; Paul, Nora Emilie; Rath, Björn; Nourbakhsh, Mahtab; Bernhagen, Jürgen; Pallua, Norbert

    2014-01-01

    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. PMID:25019085

  6. Direct Assessment of Articular Cartilage and Underlying Subchondral Bone Reveals a Progressive Gene Expression Change in Human Osteoarthritic Knees

    PubMed Central

    Chou, Ching-Heng; Lee, Chian-Her; Lu, Liang-Suei; Song, I-Wen; Chuang, Hui-Ping; Kuo, San-Yuan; Wu, Jer-Yuarn; Chen, Yuan-Tsong; Kraus, Virginia Byers; Wu, Chia-Chun; Lee, Ming Ta Michael

    2013-01-01

    Objective To evaluate the interaction of articular cartilage (AC) and subchondral bone (SB) through analysis of osteoarthritis (OA)-related genes of site-matched tissue. Design We developed a novel method for isolating site-matched overlying AC and underlying SB from three and four regions of interest respectively from the human knee tibial plateau (n=50). For each site, the severity of cartilage changes of OA were assessed histologically, and the severity of bone abnormalities were assessed by microcomputed tomography. An RNA isolation procedure was optimized that yielded high quality RNA from site-matched AC and SB tibial regions. Q-PCR analysis was performed to evaluate gene expression of 61 OA-associated genes for correlation with cartilage integrity and bone structure parameters. Results A total of 27 (44%) genes were coordinately up or down regulated in both tissues. The expression levels of 19 genes were statistically significantly correlated with the severity of AC degeneration and changes of SB structure; these included: ADAMTS1, ASPN, BMP6, BMPER, CCL2, CCL8, COL5A1, COL6A3, COL7A1, COL16A1, FRZB, GDF10, MMP3, OGN, OMD, POSTN, PTGES, TNFSF11 and WNT1. Conclusions These results provide a strategy for identifying targets whose modification may have the potential to ameliorate pathological alterations and progression of disease in both AC and SB simultaneously. In addition, this is the first study, to our knowledge, to overcome the major difficulties related to isolation of high quality RNA from site-matched joint tissues. We expect this method to facilitate advances in our understanding of the coordinated molecular responses of the whole joint organ. PMID:23220557

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

    PubMed

    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. PMID:26573959

  8. Stability of housekeeping genes in human intervertebral disc, endplate and articular cartilage cells in multiple conditions for reliable transcriptional analysis.

    PubMed

    Lopa, S; Ceriani, C; Cecchinato, R; Zagra, L; Moretti, M; Colombini, A

    2016-01-01

    Quantitative gene expression analysis is widely used to evaluate the expression of specific tissue markers. To obtain reliable data it is essential to select stable housekeeping genes whose expression is not influenced by the anatomical origin of cells or by the culture conditions. No studies have evaluated housekeeping gene stability in intervertebral disc (IVD) cells and only few studies using cartilaginous endplate (CEP) and articular cartilage (AC) cells are present in the literature. We analysed the stability of four candidate housekeeping genes (GAPDH, TBP, YWHAZ and RPL13A) in human cells isolated from nucleus pulposus (NP) and annulus fibrosus (AF), CEP and AC. Cell isolation, expansion, cryoconservation, and differentiation in 3D pellets were tested. GeNorm, NormFinder, BestKeeper tools and the comparative ΔCt method were used to evaluate housekeeping gene stability. In each cell population, TBP alone or combined with YWHAZ was identified as the best normaliser in both monolayer and 3D pellets. GAPDH was the best performer only for AC cells in monolayer. In most culture conditions considering groups of two or more cell types, TBP was the most stable and YWHAZ was the second choice. GAPDH was the best performer only in 3D pellets with factors for AC and AF combined with CEP cells. RPL13A was the most stable only for AF with CEP cells at isolation. Our findings will be useful to properly design the experimental set-up of studies involving IVD, CEP or AC cells in different culture conditions, in order to obtain accurate and high quality data from quantitative gene expression analysis. PMID:27232666

  9. Age-related changes in the sulphation of the chondroitin sulphate linkage region from human articular cartilage aggrecan.

    PubMed Central

    Lauder, R M; Huckerby, T N; Brown, G M; Bayliss, M T; Nieduszynski, I A

    2001-01-01

    The chondroitin sulphate (CS) linkage regions have been isolated from human articular cartilage aggrecan (from 10- to 72-year-olds) by chondroitin ABC endolyase digestion and size-exclusion chromatography. Linkage region hexasaccharides have been characterized and their abundance estimated by high-pH anion-exchange chromatography. The basic structure for the CS linkage region oligosaccharides identified from human aggrecan is as follows: DeltaUA(beta1-3)GalNAc[0S/4S/6S](beta1-4)GlcA(beta1-3)Gal[0S/6S](beta1-3)Gal(beta1-4)Xyl, where DeltaUA represents 4,5-unsaturated hexuronic acid, 4S and 6S represent an O-ester sulphate group on C-4 and C-6 respectively, and 0S represents zero sulphation. There are significant age-related changes in the abundance of the various N-acetylgalactosamine (GalNAc) sulphation forms identified, occurring up to approx. 20 years old. During the period from 10 to 20 years old the level of GalNAc 6-sulphation at the linkage region increases from approx. 43% to approx. 75%, while there is a corresponding reduction in unsulphated (approx. 30% to approx. 20%) and 4-sulphated (approx. 25% to approx. 6%) GalNAc residues. There is also an increase in the incidence of linkage region galactose 6-sulphation (approx. 2% to approx. 10%) which was only observed in linkage regions with GalNAc 6-sulphation. Beyond 20 years old there are few changes in the relative abundance of these GalNAc sulphation variants; however, there is a slight increase in the abundance of 6-sulphation between approx. 20 years old and approx. 40 years old and a slight decrease in its abundance beyond approx. 40 years old. Our data show that in the majority of chains from tissues of all ages the GalNAc residue closest to the linkage region is 6-sulphated, but the level of GalNAc 6-sulphation within the linkage region is lower than the average level observed within the repeat region. PMID:11513754

  10. A novel keratan sulphate domain preferentially expressed on the large aggregating proteoglycan from human articular cartilage is recognized by the monoclonal antibody 3D12/H7.

    PubMed Central

    Fischer, D C; Haubeck, H D; Eich, K; Kolbe-Busch, S; Stöcker, G; Stuhlsatz, H W; Greiling, H

    1996-01-01

    Monoclonal antibodies (mAbs) were prepared against aggrecan which has been isolated from human articular cartilage and purified by several chromatographic steps. One of these mAbs, the aggrecan-specific mAb 3D12/H7, was selected for further characterization. The data presented indicate that this mAb recognizes a novel domain of keratan sulphate chains from aggrecan: (1) immunochemical staining of aggrecan is abolished by treatment with keratanase/keratanase II, but not with keratanase or chondroitin sulphate lyase AC/ABC; (2) after chemical deglycosylation of aggrecan no staining of the core-protein was observed; (3) different immunochemical reactivity was observed against keratan sulphates from articular cartilage, intervertebral disc and cornea for the mAbs 3D12/H7 and 5D4. For further characterization of the epitope, reduced and 3H-labelled keratan sulphate chains were prepared. In an IEF-gel-shift assay it was shown that the 3H-labelled oligosaccharides obtained after keratanase digestion of reduced and 3H-labelled keratan sulphate chains were recognized by the mAb 3D12/H7. Thus it can be concluded that the mAb 3D12/H7 recognizes an epitope in the linkage region present in, at least some, keratan sulphate chains of the large aggregating proteoglycan from human articular cartilage. Moreover, this domain seems to be expressed preferentially on those keratan sulphate chains which occur in the chondroitin sulphate-rich region of aggrecan, since the antibody does not recognize the keratan sulphate-rich region obtained after combined chondroitinase AC/ABC and trypsin digestion of aggrecan. PMID:8836155

  11. A novel keratan sulphate domain preferentially expressed on the large aggregating proteoglycan from human articular cartilage is recognized by the monoclonal antibody 3D12/H7.

    PubMed

    Fischer, D C; Haubeck, H D; Eich, K; Kolbe-Busch, S; Stöcker, G; Stuhlsatz, H W; Greiling, H

    1996-09-15

    Monoclonal antibodies (mAbs) were prepared against aggrecan which has been isolated from human articular cartilage and purified by several chromatographic steps. One of these mAbs, the aggrecan-specific mAb 3D12/H7, was selected for further characterization. The data presented indicate that this mAb recognizes a novel domain of keratan sulphate chains from aggrecan: (1) immunochemical staining of aggrecan is abolished by treatment with keratanase/keratanase II, but not with keratanase or chondroitin sulphate lyase AC/ABC; (2) after chemical deglycosylation of aggrecan no staining of the core-protein was observed; (3) different immunochemical reactivity was observed against keratan sulphates from articular cartilage, intervertebral disc and cornea for the mAbs 3D12/H7 and 5D4. For further characterization of the epitope, reduced and 3H-labelled keratan sulphate chains were prepared. In an IEF-gel-shift assay it was shown that the 3H-labelled oligosaccharides obtained after keratanase digestion of reduced and 3H-labelled keratan sulphate chains were recognized by the mAb 3D12/H7. Thus it can be concluded that the mAb 3D12/H7 recognizes an epitope in the linkage region present in, at least some, keratan sulphate chains of the large aggregating proteoglycan from human articular cartilage. Moreover, this domain seems to be expressed preferentially on those keratan sulphate chains which occur in the chondroitin sulphate-rich region of aggrecan, since the antibody does not recognize the keratan sulphate-rich region obtained after combined chondroitinase AC/ABC and trypsin digestion of aggrecan. PMID:8836155

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

    PubMed

    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. PMID:27404480

  13. Physiological assessment of in vivo human knee articular cartilage using sodium MR imaging at 1.5 T.

    PubMed

    Hani, Ahmad Fadzil Mohd; Kumar, Dileep; Malik, Aamir Saeed; Razak, Ruslan

    2013-09-01

    Osteoarthritis is a common joint disorder that is most prevalent in the knee joint. Knee osteoarthritis (OA) can be characterized by the gradual loss of articular cartilage (AC). Formation of lesion, fissures and cracks on the cartilage surface has been associated with degenerative AC and can be measured by morphological assessment. In addition, loss of proteoglycan from extracellular matrix of the AC can be measured at early stage of cartilage degradation by physiological assessment. In this case, a biochemical phenomenon of cartilage is used to assess the changes at early degeneration of AC. In this paper, a method to measure local sodium concentration in AC due to proteoglycan has been investigated. A clinical 1.5-T magnetic resonance imaging (MRI) with multinuclear spectroscopic facility is used to acquire sodium images and quantify local sodium content of AC. An optimised 3D gradient-echo sequence with low echo time has been used for MR scan. The estimated sodium concentration in AC region from four different data sets is found to be ~225±19mmol/l, which matches the values that has been reported for the normal AC. This study shows that sodium images acquired at clinical 1.5-T MRI system can generate an adequate quantitative data that enable the estimation of sodium concentration in AC. We conclude that this method is potentially suitable for non-invasive physiological (sodium content) measurement of articular cartilage. PMID:23731535

  14. BMP Receptor Signaling Is Required for Postnatal Maintenance of Articular Cartilage

    PubMed Central

    2004-01-01

    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 investigated as a possible

  15. How human gait responds to muscle impairment in total knee arthroplasty patients: Muscular compensations and articular perturbations.

    PubMed

    Ardestani, Marzieh M; Moazen, Mehran

    2016-06-14

    Post-surgical muscle weakness is prevalent among patients who undergo total knee arthroplasty (TKA). We conducted a probabilistic multi-body dynamics (MBD) to determine whether and to what extent habitual gait patterns of TKA patients may accommodate strength deficits in lower extremity muscles. We analyzed muscular and articular compensations in response to various muscle impairments, and the minimum muscle strength requirements needed to preserve TKA gait patterns in its habitual status. Muscle weakness was simulated by reducing the strength parameter of muscle models in MBD analysis. Using impaired models, muscle and joint forces were calculated and compared versus those from baseline gait i.e. TKA habitual gait before simulating muscle weakness. Comparisons were conducted using a relatively new statistical approach for the evaluation of gait waveforms, i.e. Spatial Parameter Mapping (SPM). Principal component analysis was then conducted on the MBD results to quantify the sensitivity of every joint force component to individual muscle impairment. The results of this study contain clinically important, although preliminary, suggestions. Our findings suggested that: (1) hip flexor and ankle plantar flexor muscles compensated for hip extensor weakness; (2) hip extensor, hip adductor and ankle plantar flexor muscles compensated for hip flexor weakness; (3) hip and knee flexor muscles responded to hip abductor weakness; (4) knee flexor and hip abductor balanced hip adductor impairment; and (5) knee extensor and knee flexor weakness were compensated by hip extensor and hip flexor muscles. Future clinical studies are required to validate the results of this computational study. PMID:27063251

  16. Insulin-Like Growth Factor (IGF) Binding Protein-3 (IGFBP-3) is Closely Associated with the Chondrocyte Nucleus in Human Articular Cartilage

    PubMed Central

    EB, Hunziker; E, Kapfinger; J, Martin; J, Buckwalter; TI, Morales

    2008-01-01

    Objective The Insulin-like Growth Factor-I (IGF-I) is critically involved in the control of cartilage matrix metabolism. It is well known that its binding protein-3 (IGFBP-3) is increased during osteoarthritis (OA), but its function(s) is not known. In other cells, IGFBP-3 can regulate IGF-I action in the extracellular environment and can also act independently inside the cell; this includes transcriptional gene control in the nucleus. These studies were undertaken to localize IGFBP-3 in human articular cartilage, particularly within cells. Design Cartilage was dissected from human femoral heads derived from arthroplasty for OA, and OA grade assessed by histology. Tissue slices were further characterized by extraction and assay of IGFBPs by IGF Ligand blot (LB) and by ELISA. Immunohistochemistry (IHC) for IGF-I and IGFBP-3 was performed on cartilage from donors with mild, moderate and severe OA. Indirect fluorescence and immunogold labeling IHC studies were included. Results LBs of chondrocyte lysates showed a strong signal for IGFBP-3. IHC of femoral cartilage sections at all OA stages showed IGF-I and IGFBP-3 matrix stain particularly in the top zones, and closely associated with most cells. A prominent perinuclear/nuclear IGFBP-3 signal was seen. Controls using non-immune sera or antigen-blocked antibody showed negative or strongly reduced stain. In frozen sections of human ankle cartilage, immunofluorescent IGFBP-3 stain co-localized with the nuclear DAPI stain in greater than 90% of the cells. Immunogold IHC of thin sections and TEM immunogold microscopy of ultra-thin sections showed distinct intra-nuclear staining. Conclusions IGFBP-3 in human cartilage is located in the matrix and within chondrocytes in the cytoplasm and nuclei. This new data indicates that the range of IGFBP-3 actions in articular cartilage is likely to include IGF independent roles and opens the door to studies of its nuclear actions, including the possible regulation of hormone receptors

  17. Activation patterns of mono- and bi-articular arm muscles as a function of force and movement direction of the wrist in humans

    PubMed Central

    van Bolhuis, B M; Gielen, C C A M; van Ingen Schenau, G J

    1998-01-01

    In order to explain the task-dependent activation of muscles, we have investigated the hypothesis that mono- and bi-articular muscles have a different functional role in the control of multijoint movements. According to this hypothesis, bi-articular muscles are activated in a way to control the direction of external force. The mono-articular muscles are thought to be activated to contribute to joint torque mainly during shortening movements.To investigate this hypothesis, surface electromyographic (EMG) recordings were obtained from several mono- and bi-articular arm muscles during voluntary slow movements of the wrist in a horizontal plane against an external force. The direction of force produced at the wrist and the direction of movement of the wrist were varied independently.The results revealed distinct differences between the activation patterns of mono- and bi-articular muscles. The activation of the bi-articular muscles was not affected by movement direction, but appeared to vary exclusively with the direction of force.The mono-articular muscles showed significantly more EMG activity for movements in a specific direction, which equalled the movement direction corresponding to the largest shortening velocity of the muscle. The EMG activity decreased gradually for movements in other directions. This direction-dependent activation appeared to be independent of the direction of the external force. PMID:9490859

  18. Assessment of chemical species of lead accumulated in tidemarks of human articular cartilage by X-ray absorption near-edge structure analysis

    PubMed Central

    Meirer, Florian; Pemmer, Bernhard; Pepponi, Giancarlo; Zoeger, Norbert; Wobrauschek, Peter; Sprio, Simone; Tampieri, Anna; Goettlicher, Joerg; Steininger, Ralph; Mangold, Stefan; Roschger, Paul; Berzlanovich, Andrea; Hofstaetter, Jochen G.; Streli, Christina

    2011-01-01

    A highly specific accumulation of the toxic element lead was recently measured in the transition zone between non-calcified and calcified normal human articular cartilage. This transition zone, the so-called ‘tidemark’, is considered to be an active calcification front of great clinical importance. However, little is known about the mechanisms of accumulation and the chemical form of Pb in calcified cartilage and bone. Using spatially resolved X-ray absorption near-edge structure analysis (µ-XANES) at the Pb L 3-edge, the chemical state of Pb in the osteochondral region was investigated. The feasibility of the µ-XANES set-up at the SUL-X beamline (ANKA synchrotron light source) was tested and confirmed by comparing XANES spectra of bulk Pb-reference compounds recorded at both the XAS and the SUL-X beamline at ANKA. The µ-XANES set-up was then used to investigate the tidemark region of human bone (two patella samples and one femoral head sample). The spectra recorded at the tidemark and at the trabecular bone were found to be highly correlated with the spectra of synthetic Pb-doped carbonated hydroxyapatite, suggesting that in both of these very different tissues Pb is incorporated into the hydroxyapatite structure. PMID:21335911

  19. Rethinking Adult Literacy Programs: A Humanities-Based Curriculum.

    ERIC Educational Resources Information Center

    Anania, Joanne

    The Roosevelt University Humanities Enrichment Program tries to acknowledge the adult part of adult literacy. Its instructional materials are of interest and value to the adult student and, therefore, provide incentives for reading and discussion instead of serving merely as skill-building exercises. The materials are drawn from literature,…

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

    NASA Astrophysics Data System (ADS)

    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.

  1. Adult Education and Human Resource Development: A Symbiotic Relationship?

    ERIC Educational Resources Information Center

    Grubb, Robert E.; Hemby, K. Virginia; Conerly-Stewart, Donna L.

    1998-01-01

    Top-ranked competencies for graduate education in human resources development (HRD) identified by 55 (of 195) HRD practitioners were adult learning, presentation, facilitation, needs assessment, and human relations. Seven of the top 10 were allied with adult education graduate program content. (SK)

  2. Encephalitis-Associated Human Metapneumovirus Pneumonia in Adult, Australia

    PubMed Central

    Mateevici, Cristina; Lin, Belinda; Chandra, Ronil V.; Chong, Victor H.T.

    2015-01-01

    Human metapneumovirus pneumonia, most commonly found in children, was diagnosed in an adult with encephalitis. This case suggests that testing for human metapneumovirus RNA in nasopharyngeal aspirate and cerebrospinal fluid samples should be considered in adults with encephalitis who have a preceding respiratory infection, PMID:26488420

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

    ERIC Educational Resources Information Center

    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…

  4. A large-molecular-weight polyanion, synthesized via ring-opening metathesis polymerization, as a lubricant for human articular cartilage.

    PubMed

    Wathier, Michel; Lakin, Benjamin A; Bansal, Prashant N; Stoddart, Stephanie S; Snyder, Brian D; Grinstaff, Mark W

    2013-04-01

    A large-molecular-weight polyanion is found to possess lubricating properties for cartilage. The polyanion, sodium poly(7-oxanorbornene-2-carboxylate), is synthesized by ring-opening metathesis polymerization of methyl 5-oxanorbornene-2-carboxylate. When dissolved in aqueous solution and applied to the surface of human cartilage it reduces the friction at the interface and acts as a lubricant. Its performance is similar to that of synovial fluid and superior to those of saline and Synvisc in an ex vivo human cartilage plug-on-plug model. The polymer is also not readily degraded by hyaluronidase or cytotoxic to human chondrocytes in vitro. As such, this polymer is a new type of viscosupplement, and the results provide insight into the design requirements for synthesizing highly efficacious synthetic biolubricants. PMID:23496043

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

    PubMed Central

    Kiga, N.; Tojyo, I.; Matsumoto, T.; Hiraishi, Y.; Shinohara, Y.; Fujita, S.

    2010-01-01

    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 fibroblast-like 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. PMID:20819773

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

    PubMed Central

    Kean, Thomas J.; Dennis, James E.

    2015-01-01

    Background 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. Methods 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. Results 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. Conclusions

  7. Adult Human Neurogenesis: From Microscopy to Magnetic Resonance Imaging

    PubMed Central

    Sierra, Amanda; Encinas, Juan M.; Maletic-Savatic, Mirjana

    2011-01-01

    Neural stem cells reside in well-defined areas of the adult human brain and are capable of generating 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. PMID:21519376

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

    PubMed Central

    Neumann, Alexander J.; Gardner, Oliver F. W.; Williams, Rebecca; Alini, Mauro; Archer, Charles W.; Stoddart, Martin J.

    2015-01-01

    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 represent a

  9. Phytoestrogen Metabolism by Adult Human Gut Microbiota.

    PubMed

    Gaya, Pilar; Medina, Margarita; Sánchez-Jiménez, Abel; Landete, José Mᵃ

    2016-01-01

    Phytoestrogens are plant-derived polyphenols with a structure similar to human estrogens. The three main groups of phytoestrogens, isoflavones, ellagitannins, and lignans, are transformed into equol, urolithins, and enterolignans, respectively, by bacteria. These metabolites have more estrogenic/antiestrogenic and antioxidant activities than their precursors, and they are more bioavailable. The aim of this study was to analyze the metabolism of isoflavones, lignans and ellagitannins by gut microbiota, and to study the possible correlation in the metabolism of these three groups of phytoestrogens. In vitro fermentation experiments were performed with feces samples from 14 healthy adult volunteers, and metabolite formation was measured by HPLC-PAD and HPLC-ESI/MS. Only the microbiota of one subject produced equol, while most of them showed production of O-desmethylangolensin (O-DMA). Significant inter-subject differences were observed in the metabolism of dihydrodaidzein and dihydrogenistein, while the glucoside isoflavones and their aglycones showed less variability, except for glycitin. Most subjects produced urolithins M-5 and E. Urolithin D was not detected, while uroltithin B was found in half of the individuals analyzed, and urolithins A and C were detected in two and four subjects, respectively. Enterolactone was found in all subjects, while enterodiol only appeared in five. Isoflavone metabolism could be correlated with the metabolism of lignans and ellagitannins. However, the metabolism of ellagitannins and lignans could not be correlated. This the first study where the metabolism of the three groups together of phytoestrogen, isoflavones, lignans, and ellagitannins by gut microbiota is analyzed. PMID:27517891

  10. Developing Resourceful Humans. Adult Education within the Economic Context.

    ERIC Educational Resources Information Center

    Burton, Lynn Elen, Ed.

    This book, which explores the shifting paradigm from human resource development to developing resourceful humans, establishes the historical position of adult education within the economic context, discusses human capital propositions, and examines the learning dimensions of economic and educational change. The following chapters are included:…

  11. Why Teach the Humanities to Adult Basic Education Students?

    ERIC Educational Resources Information Center

    Mocker, Donald W., Ed.; Jones, William C., Ed.

    The publication contains an article on curriculum selection in adult basic education (ABE), three presentations on the humanities and ABE, and a concluding commentary. An introductory article, "Criteria for Selecting Curriculum in Adult Basic Education" by Donald Mocker, emphasizes the need for broader criteria for selection of ABE curriculum.…

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

    ERIC Educational Resources Information Center

    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…

  13. Humanizing Adult Education Research: Five Stories from the 1930's.

    ERIC Educational Resources Information Center

    Hilton, Ronald

    Taken from the author's doctoral dissertation, this award-winning monograph describes a method for humanizing educational research in adult education and provides five stories of adult education efforts in the 1930's as examples of such research. The method described suggests valuing qualitative data as much as quantitative in the field of…

  14. Technology and the Adult Degree Program: The Human Element

    ERIC Educational Resources Information Center

    Rodriquez, Frank G.; Nash, Susan Smith

    2004-01-01

    While technology has for many years been a critical component in programs for adults and calls to mind sophisticated gadgetry with expensive price tags, it is often the nexus where technology and humans intersect that proves most critical to the success and quality of adult degree programs.

  15. A comparative study of bifidobacteria in human babies and adults

    PubMed Central

    KHONSARI, Shadi; SUGANTHY, Mayuran; BURCZYNSKA, Beata; DANG, Vu; CHOUDHURY, Manika; PACHENARI, Azra

    2015-01-01

    The composition and diversity of the gut microbiota are known to be different between babies and adults. The aim of this project was to compare the level of bifidobacteria between babies and adults and to investigate the influence of lifestyle factors on the level of this bacterium in the gut. During this study, the levels of bifidobacteria in 10 human babies below 2 years of age were compared with that of 10 human adults above 40 years. The level of bifidobacteria proved to be significantly higher in babies in comparison with adults. This investigation concluded that a combination of several factors, such as age, diet, and BMI, has an important effect on the level of bifidobacteria in adults, while in babies, a combination of diet and age may influence the level of intestinal bifidobacteria. PMID:27200263

  16. A comparative study of bifidobacteria in human babies and adults.

    PubMed

    Khonsari, Shadi; Suganthy, Mayuran; Burczynska, Beata; Dang, Vu; Choudhury, Manika; Pachenari, Azra

    2016-01-01

    The composition and diversity of the gut microbiota are known to be different between babies and adults. The aim of this project was to compare the level of bifidobacteria between babies and adults and to investigate the influence of lifestyle factors on the level of this bacterium in the gut. During this study, the levels of bifidobacteria in 10 human babies below 2 years of age were compared with that of 10 human adults above 40 years. The level of bifidobacteria proved to be significantly higher in babies in comparison with adults. This investigation concluded that a combination of several factors, such as age, diet, and BMI, has an important effect on the level of bifidobacteria in adults, while in babies, a combination of diet and age may influence the level of intestinal bifidobacteria. PMID:27200263

  17. Quantitative analysis of the mRNA expression levels of BCL2 and BAX genes in human osteoarthritis and normal articular cartilage: An investigation into their differential expression.

    PubMed

    Karaliotas, Georgios I; Mavridis, Konstantinos; Scorilas, Andreas; Babis, George C

    2015-09-01

    Osteoarthritis (OA) is primarily characterized by articular cartilage degeneration and chondrocyte loss. Although the role of apoptosis in cartilage pathobiology remains to be elucidated, the apoptotic B‑cell CLL/lymphoma 2 (BCL2) gene family is considered to be involved in OA. The purpose of the present study was to quantitatively analyze the mRNA expression profiles of the BCL2‑associated X protein (BAX) and BCL2 genes in human OA and in normal cartilage. Cartilage tissue samples were obtained from 78 patients undergoing total knee arthroplasty for OA (OA group) and orthopedic interventions for causes other than OA (control group). Total RNA was isolated from the cartilage tissue specimens and reverse transcribed into cDNA. A highly sensitive and specific reverse transcription quantitative polymerase chain reaction assay was developed for quantification of the mRNA levels of BAX and BCL2, using beta‑2 microglobulin as an endogenous control for normalization purposes. Gene expression analysis was performed using the comparative Ct (2(‑ΔΔCt)) method. The mRNA expression of BAX presented an increasing trend in the OA group compared with the control group, although without statistically significace (P=0.099). By contrast, the expression ratio of BCL2/BAX was found to be significantly decreased (2.76‑fold) in the OA group compared with the normal cartilage control group (P=0.022). A notable 4.6‑fold overexpression of median mRNA levels of BAX was also observed in patients with stage III OA compared with the control (P=0.034), while the BCL2/BAX ratio was markedly (2.5‑fold) decreased (P=0.024). A marked positive correlation was observed between the mRNA levels of BAX and BCL2 in the control group (r(s)=0.728; P<0.001), which was also present in the OA group, although to a lesser degree (r(s)=0.532; P<0.001). These results further implicate apoptosis in the pathogenesis of OA, through molecular mechanisms, which include the aberrant expression of the

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

    PubMed Central

    Platano, Daniela; Cattini, Luca; Trisolino, Giovanni; Mariani, Erminia; Borzì, Rosa Maria

    2015-01-01

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

  19. Hereditary uricemia and articular gout in chickens.

    PubMed

    Cole, R K; Austic, R E

    1980-05-01

    Ten generations of selection for uricemia and articular gout have led to the development of the HUA line which is characterized by a threefold increase in plasma level of uric acid when compared to the control LUA line, even when fed diets containing normal levels of protein. Articular gout results in many cases, especially among adult males fed a normal breeder diet. Restriction protein level of the diet delays or prevents the development of articular gout in mature males of the HUA line. The data suggest that relatively few genes are responsible for the defect in renal transport of uric acid which underlies the uricemia and gout. The association of lower levels of uric acid with dominant white plumage color suggests a linkage of a major recessive gene for the I gene. Ambient temperature, because of its effect on food consumption, influences the level of uric acid in blood plasma. The HUA line and its control (LUA line), both sex-linked dwarfs, would appear to provide an excellent animal model for the experimental study of gout in man. PMID:7393846

  20. Homology of lubricin and superficial zone protein (SZP): products of megakaryocyte stimulating factor (MSF) gene expression by human synovial fibroblasts and articular chondrocytes localized to chromosome 1q25.

    PubMed

    Jay, G D; Tantravahi, U; Britt, D E; Barrach, H J; Cha, C J

    2001-07-01

    We have previously identified megakaryocyte stimulating factor (MSF) gene expression by synovial fibroblasts as the origin of lubricin in the synovial cavity. Lubricin is a mucinous glycoprotein responsible for the boundary lubrication of articular cartilage. MSF has a significant homology to vitronectin and is composed of 12 exons. RNA was purified from human synovial fibroblasts and articular chondrocytes grown in vitro from tissue explants obtained from subjects without degenerative joint disease. RT-PCR was used with multiple complimentary primer pairs spanning the central mucin expressing exon 6 of the MSF gene and individual exons on both the N- and C-terminal sides of exon 6. Exons 2, 4 and 5 appear to be variably expressed by synovial fibroblasts and articular chondrocytes. Lubricating mucin, in the form of MSF, is expressed by both chondrocytes and synovial fibroblasts in vitro. Both lubricin and superficial zone protein (SZP), a related proteoglycan, share a similar primary structure but could differ in post-translational modifications with O-linked oligosaccharides which are predominant in lubricin and with limited amounts chondroitin and keratan sulfate found in SZP. Since most of the MSF exons are involved in the expression of lubricating mucin, a strong homology to vitronectin persists. It is therefore appropriate to consider that both SZP and lubricin occupy a new class of biomolecules termed tribonectins. Screening of a human genome bacterial artificial chromsome (BAC) library with a cDNA primer pair complimentary for exon 6 identified two clones. Both clones were complimentary for chromosome 1q25 by in situ hybridization. This same locus was previously implicated in camptodactyl-arthropathy-pericarditis syndrome (CAP) by genetic mapping. It is hypothesized that CAP, a large joint arthropathy, may be associated with ineffective boundary lubrication provided by synovial fluid. PMID:11518279

  1. Humanities and the Adult Learner in an Information Society.

    ERIC Educational Resources Information Center

    Myers, Dale; Kamholtz, Jonathan

    Humanities courses have often been given little attention in continuing education for adults, possibly because they have been viewed as not "practical" or not "job-oriented" enough in our career-oriented, technologically advanced society. However, the humanities should be an integral part of our culture and of the lives of educated persons--a…

  2. Towards Regeneration of Articular Cartilage

    PubMed Central

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

    2014-01-01

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

  3. Postnatal development of collagen structure in ovine articular cartilage

    PubMed Central

    2010-01-01

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

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

    PubMed

    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. PMID:26988110

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

    PubMed Central

    2012-01-01

    Background The energy requirement of species at each trophic level in an ecological pyramid is a function of the number of organisms and their average mass. Regarding human populations, although considerable attention is given to estimating the number of people, much less is given to estimating average mass, despite evidence that average body mass is increasing. We estimate global human biomass, its distribution by region and the proportion of biomass due to overweight and obesity. Methods For each country we used data on body mass index (BMI) and height distribution to estimate average adult body mass. We calculated total biomass as the product of population size and average body mass. We estimated the percentage of the population that is overweight (BMI > 25) and obese (BMI > 30) and the biomass due to overweight and obesity. Results In 2005, global adult human biomass was approximately 287 million tonnes, of which 15 million tonnes were due to overweight (BMI > 25), a mass equivalent to that of 242 million people of average body mass (5% of global human biomass). Biomass due to obesity was 3.5 million tonnes, the mass equivalent of 56 million people of average body mass (1.2% of human biomass). North America has 6% of the world population but 34% of biomass due to obesity. Asia has 61% of the world population but 13% of biomass due to obesity. One tonne of human biomass corresponds to approximately 12 adults in North America and 17 adults in Asia. If all countries had the BMI distribution of the USA, the increase in human biomass of 58 million tonnes would be equivalent in mass to an extra 935 million people of average body mass, and have energy requirements equivalent to that of 473 million adults. Conclusions Increasing population fatness could have the same implications for world food energy demands as an extra half a billion people living on the earth. PMID:22709383

  6. Expression of tmp21 in normal adult human tissues

    PubMed Central

    Xie, Jian; Yang, Yuan; Li, Jianbo; Hou, Jing; Xia, Kun; Song, Weihong; Liu, Shengchun

    2014-01-01

    TMP21, known as p23 protein, is one important member of the p24 protein families. The degradation of TMP21 is mediated by the ubiquitin-proteasome pathway, as with the other presenilin-associated γ-secretase complex members. NFAT plays a very important role in regulation of human TMP21 gene expression. Compared with the function of TMP21, the studies about the distribution of this protein in human tissues are limited. We collected 19 normal adult human tissues from a healthy adult man died in a traffic accident and did examination of all the tissues collected for ICH, western blot and RT-PCR. It was shown that the expression of TMP21 is at high levels in heart, liver, lung, kidney and adrenal gland; moderate levels in brain, pancreas, prostate gland, testicle, small intestine, colon, stomach, gall bladder, thyroid gland and trachea; low levels in skeletal muscle, skin and lymphonodus. TMP21 is widely existed in normal adult human tissues. The current study provided for the first time a comprehensive expression of TMP21 in normal adult human tissues. It will benefit on helping in the design and interpretation of future studies focused on expounding the function of TMP21. PMID:25356171

  7. [Articular cartilage regeneration using scaffold].

    PubMed

    Ishimoto, Yoshiyuki; Hattori, Koji; Ohgushi, Hajime

    2008-12-01

    The self-healing capacity of articular cartilage for repair is limited. For articular cartilage injury, several surgical techniques are used in clinical practice, namely drilling, abrasion arthroplasty, microfracture, or autologous osteochondral grafting, while various methods of autologous chondrocyte transplantation to cartilage defect sites have been reported since 1990s. In a case of chondrocyte transplantation to cartilage defect site, the use of proper scaffold is important. Currently, collagen gel or PLGA is used widely as a scaffold. PMID:19043192

  8. Late Pleistocene adult mortality patterns and modern human establishment

    PubMed Central

    Trinkaus, Erik

    2011-01-01

    The establishment of modern humans in the Late Pleistocene, subsequent to their emergence in eastern Africa, is likely to have involved substantial population increases, during their initial dispersal across southern Asia and their subsequent expansions throughout Africa and into more northern Eurasia. An assessment of younger (20–40 y) versus older (>40 y) adult mortality distributions for late archaic humans (principally Neandertals) and two samples of early modern humans (Middle Paleolithic and earlier Upper Paleolithic) provides little difference across the samples. All three Late Pleistocene samples have a dearth of older individuals compared with Holocene ethnographic/historical samples. They also lack older adults compared with Holocene paleodemographic profiles that have been critiqued for having too few older individuals for subsistence, social, and demographic viability. Although biased, probably through a combination of preservation, age assessment, and especially Pleistocene mobility requirements, these adult mortality distributions suggest low life expectancy and demographic instability across these Late Pleistocene human groups. They indicate only subtle and paleontologically invisible changes in human paleodemographics with the establishment of modern humans; they provide no support for a life history advantage among early modern humans. PMID:21220336

  9. Novel surface markers directed against adult human gallbladder

    PubMed Central

    Galivo, Feorillo H.; Dorrell, Craig S.; Grompe, Maria; Zhong, Yong-Ping; Streeter, Philip; Grompe, Markus

    2015-01-01

    Novel cell surface-reactive monoclonal antibodies generated against extrahepatic biliary cells were developed for the isolation and characterization of different cell subsets from normal adult human gallbladder. Eleven antigenically distinct gallbladder subpopulations were isolated by fluorescence-activated cell sorting. They were classified into epithelial, mesenchymal, and pancreatobiliary (PDX1+SOX9+) subsets based on gene expression profiling. These antigenically distinct human gallbladder cell subsets could potentially also reflect different functional properties in regards to bile physiology, cell renewal and plasticity. Three of the novel monoclonal antibodies differentially labeled archival sections of primary carcinoma of human gallbladder relative to normal tissue. The novel monoclonal antibodies described herein enable the identification and characterization of antigenically diverse cell subsets within adult human gallbladder and are putative tumor biomarkers. PMID:26079872

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

    PubMed

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

    2015-01-01

    A variety of age-related differences in the innate and adaptive immune systems have been proposed to contribute to the increased susceptibility to infection of human neonates and older adults. The emergence of RNA sequencing (RNA-seq) provides an opportunity to obtain an unbiased, comprehensive, and quantitative view of gene expression differences in defined cell types from different age groups. An examination of ex vivo human monocyte responses to lipopolysaccharide stimulation or Listeria monocytogenes infection by RNA-seq revealed extensive similarities between neonates, young adults, and older adults, with an unexpectedly small number of genes exhibiting statistically significant age-dependent differences. By examining the differentially induced genes in the context of transcription factor binding motifs and RNA-seq data sets from mutant mouse strains, a previously described deficiency in interferon response factor-3 activity could be implicated in most of the differences between newborns and young adults. Contrary to these observations, older adults exhibited elevated expression of inflammatory genes at baseline, yet the responses following stimulation correlated more closely with those observed in younger adults. Notably, major differences in the expression of constitutively expressed genes were not observed, suggesting that the age-related differences are driven by environmental influences rather than cell-autonomous differences in monocyte development. PMID:26147648

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

    PubMed

    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. PMID:26890418

  12. Dendritic cells in humans--from fetus to adult.

    PubMed

    McGovern, Naomi; Chan, Jerry K Y; Ginhoux, Florent

    2015-02-01

    The human immune system evolves continuously during development from the embryo into the adult, reflecting the ever-changing environment and demands of our body. This ability of our immune system to sense external cues and adapt as we develop is just as important in the early tolerogenic environment of the fetus, as it is in the constantly pathogen-challenged adult. Dendritic cells (DCs), the professional antigen-sensing and antigen-presenting components of the immune system, play a crucial role in this process where they act as sentinels, both initiating and regulating immune responses. Here, we provide an overview of the human immune system in the developing fetus and the adult, with a focus on DC ontogeny and function during these discrete but intimately linked life stages. PMID:25323843

  13. Expansion of Multipotent Stem Cells from the Adult Human Brain

    PubMed Central

    Murrell, Wayne; Palmero, Emily; Bianco, John; Stangeland, Biljana; Joel, Mrinal; Paulson, Linda; Thiede, Bernd; Grieg, Zanina; Ramsnes, Ingunn; Skjellegrind, Håvard K.; Nygård, Ståle; Brandal, Petter; Sandberg, Cecilie; Vik-Mo, Einar; Palmero, Sheryl; Langmoen, Iver A.

    2013-01-01

    The discovery of stem cells in the adult human brain has revealed new possible scenarios for treatment of the sick or injured brain. Both clinical use of and preclinical research on human adult neural stem cells have, however, been seriously hampered by the fact that it has been impossible to passage these cells more than a very few times and with little expansion of cell numbers. Having explored a number of alternative culturing conditions we here present an efficient method for the establishment and propagation of human brain stem cells from whatever brain tissue samples we have tried. We describe virtually unlimited expansion of an authentic stem cell phenotype. Pluripotency proteins Sox2 and Oct4 are expressed without artificial induction. For the first time multipotency of adult human brain-derived stem cells is demonstrated beyond tissue boundaries. We characterize these cells in detail in vitro including microarray and proteomic approaches. Whilst clarification of these cells’ behavior is ongoing, results so far portend well for the future repair of tissues by transplantation of an adult patient’s own-derived stem cells. PMID:23967194

  14. The adult human brain harbors multipotent perivascular mesenchymal stem cells.

    PubMed

    Paul, Gesine; Özen, Ilknur; Christophersen, Nicolaj S; Reinbothe, Thomas; Bengzon, Johan; Visse, Edward; Jansson, Katarina; Dannaeus, Karin; Henriques-Oliveira, Catarina; Roybon, Laurent; Anisimov, Sergey V; Renström, Erik; Svensson, Mikael; Haegerstrand, Anders; Brundin, Patrik

    2012-01-01

    Blood vessels and adjacent cells form perivascular stem cell niches in adult tissues. In this perivascular niche, a stem cell with mesenchymal characteristics was recently identified in some adult somatic tissues. These cells are pericytes that line the microvasculature, express mesenchymal markers and differentiate into mesodermal lineages but might even have the capacity to generate tissue-specific cell types. Here, we isolated, purified and characterized a previously unrecognized progenitor population from two different regions in the adult human brain, the ventricular wall and the neocortex. We show that these cells co-express markers for mesenchymal stem cells and pericytes in vivo and in vitro, but do not express glial, neuronal progenitor, hematopoietic, endothelial or microglial markers in their native state. Furthermore, we demonstrate at a clonal level that these progenitors have true multilineage potential towards both, the mesodermal and neuroectodermal phenotype. They can be epigenetically induced in vitro into adipocytes, chondroblasts and osteoblasts but also into glial cells and immature neurons. This progenitor population exhibits long-term proliferation, karyotype stability and retention of phenotype and multipotency following extensive propagation. Thus, we provide evidence that the vascular niche in the adult human brain harbors a novel progenitor with multilineage capacity that appears to represent mesenchymal stem cells and is different from any previously described human neural stem cell. Future studies will elucidate whether these cells may play a role for disease or may represent a reservoir that can be exploited in efforts to repair the diseased human brain. PMID:22523602

  15. Human Service Planning as a Collective Adult Learning Experience.

    ERIC Educational Resources Information Center

    Wright, Joan

    Based on a study by the Department of Community Service Education, Cornell University, to evaluate human service planning (HSP) nationwide, this paper discusses the premises that HSP may be defined as community learning and that the community (according to the Robert Boyd and Jerold Apps model for adult education) is both a beneficiary of and…

  16. [The existence vomeronasal organ in adult humans].

    PubMed

    Rapiejko, Piotr; Zielnik-Jurkiewicz, Beata; Wojdas, Andrzej; Ratajczak, Jan; Jurkiewicz, Dariusz

    2007-01-01

    The influence of chemical substances (feromones) on human emotional and physical condition has fascinated psychologists, sexuologists and laryngologists since centurie. Literature conveys inconsistent information on vomeronasal organ (VNO) occurrence in humans. This organ is often called Jacobson's, and 2 symmetrical openings leading into it, located on both sides of septum, are called Ruyasch's ducts. The aim of the study was to analyze vomeronasal organ occurrence in humans in relation to age and sex. The study was conducted in a group of 634 patients, aged 18-80 years. All patients underwent routine ENT examination including rhinoscopy, nasal cavity examination with usage of 2.5x magnification lens (surgical glasses) and surgical microscope with 10x magnification. All persons had nasal cavities examined endoscopically. Every time presence of vomeronasal organ openings, along with localization, size and symmetry of these was noted. Subjects, who presented Jacobson's organ, were asked to fill a questionnaire concerning influence of smells on erotic sensations. Vomeronasal organ was fund in 312 persons, that is 49.21%. In 83.65% of cases vomeronasal organ opening size was smaller than 0.2 mm, what restricted its visibility to usage of magnifying lens, microscope, or endoscope. In 16.34% of cases only vomeronasal organ ducts openings were well visible in routine rhinoscopy without magnification. Vomeronasal organ was found more often in men than women. VNO was significantly more rare in patients with nasal septal deviation. In these cases, vomeronasal organ was usually found unilaterally, in all the cases on the concave side of deviated nasal septum. PMID:18260256

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

    PubMed Central

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

    2006-01-01

    In the human and equine species, different kinds of free floating intra-articular particles are related to certain disorders. Osteochondral fragments formed during osteochondrosis dissecans are the most common finding in the equine species, whereas in humans rice bodies due to rheumatoid arthritis are more frequent. Herein we report a third type of floating body inside the stifle of an adult draught horse stallion, in macroscopic appearance similar to articular rice bodies known in humans. As revealed by histologic examination, the two particles consist of polypoid degenerated structures derived from synovial villi. Their formation was probably induced by ischemia. PMID:16434856

  18. Telocytes of the human adult trigeminal ganglion.

    PubMed

    Rusu, Mugurel Constantin; Cretoiu, Dragos; Vrapciu, Alexandra Diana; Hostiuc, Sorin; Dermengiu, Dan; Manoiu, Vasile Sorin; Cretoiu, Sanda Maria; Mirancea, Nicolae

    2016-06-01

    Telocytes (TCs) are typically defined as cells with telopodes by their ultrastructural features. Their presence was reported in various organs, however little is known about their presence in human trigeminal ganglion. To address this issue, samples of trigeminal ganglia were tested by immunocytochemistry for CD34 and examined by transmission electron microscopy (TEM). We found that TCs are CD34 positive and form networks within the ganglion in close vicinity to microvessels and nerve fibers around the neuronal-glial units (NGUs). TEM examination confirmed the existence of spindle-shaped and bipolar TCs with one or two telopodes measuring between 15 to 53 μm. We propose that TCs are cells with stemness capacity which might contribute in regeneration and repair processes by: modulation of the stem cell activity or by acting as progenitors of other cells present in the normal tissue. In addition, further studies are needed to establish if they might influence the neuronal circuits. PMID:27147447

  19. Human pancreatic polypeptide in children and young adults.

    PubMed

    Hanukoglu, A; Chalew, S; Kowarski, A A

    1990-01-01

    Measurement of human pancreatic polypeptide may be useful for assessment of gastrointestinal function, integrity of the parasympathetic nervous system or screening for endocrine neoplasia. In adults hPP levels have been reported to increase with age. However hPP levels throughout childhood have not been well characterized in comparison with the adult range. We studied fasting human pancreatic polypeptide (hPP) from 45 pediatric patients, from infancy - 15 years, and 18 older adolescents and adults aged 16-45 years. The mean hPP level of children (233 +/- 147 pg/ml) was significantly higher than that (113 +/- 35 pg/ml) of adults (P less than .0001). There was no difference in mean hPP levels of children with normal growth hormone secretion compared to growth hormone deficient patients. There was no effect of gender or body mass index on hPP levels. We conclude that fasting hPP levels must be interpreted with respect to the age of the subject, children particularly, in that preteens may have higher fasting levels than older teenagers and adults. PMID:2307392

  20. Human Adult Cortical Reorganization and Consequent Visual Distortion

    PubMed Central

    Dilks, Daniel D.; Serences, John T.; Rosenau, Benjamin J.; Yantis, Steven; McCloskey, Michael

    2009-01-01

    Neural and behavioral evidence for cortical reorganization in the adult somatosensory system after loss of sensory input (e.g., amputation) has been well documented. In contrast, evidence for reorganization in the adult visual system is far less clear: neural evidence is the subject of controversy, behavioral evidence is sparse, and studies combining neural and behavioral evidence have not previously been reported. Here, we report converging behavioral and neuroimaging evidence from a stroke patient (B.L.) in support of cortical reorganization in the adult human visual system. B.L.’s stroke spared the primary visual cortex (V1), but destroyed fibers that normally provide input to V1 from the upper left visual field (LVF). As a consequence, B.L. is blind in the upper LVF, and exhibits distorted perception in the lower LVF: stimuli appear vertically elongated, toward and into the blind upper LVF. For example, a square presented in the lower LVF is perceived as a rectangle extending upward. We hypothesized that the perceptual distortion was a consequence of cortical reorganization in V1. Extensive behavioral testing supported our hypothesis, and functional magnetic resonance imaging (fMRI) confirmed V1 reorganization. Together, the behavioral and fMRI data show that loss of input to V1 after a stroke leads to cortical reorganization in the adult human visual system, and provide the first evidence that reorganization of the adult visual system affects visual perception. These findings contribute to our understanding of the human adult brain’s capacity to change and has implications for topics ranging from learning to recovery from brain damage. PMID:17804619

  1. The development and evaluation of individualized templates to assist transoral C2 articular mass or transpedicular screw placement in TARP-IV procedures: adult cadaver specimen study

    PubMed Central

    Li, Xue-Shi; Wu, Zeng-Hui; Xia, Hong; Ma, Xiang-Yang; Ai, Fu-Zhi; Zhang, Kai; Wang, Jian-Hua; Mai, Xiao-Hong; Yin, Qing-Shui

    2014-01-01

    OBJECTIVES: The transoral atlantoaxial reduction plate system treats irreducible atlantoaxial dislocation from transoral atlantoaxial reduction plate-I to transoral atlantoaxial reduction plate-III. However, this system has demonstrated problems associated with screw loosening, atlantoaxial fixation and concealed or manifest neurovascular injuries. This study sought to design a set of individualized templates to improve the accuracy of anterior C2 screw placement in the transoral atlantoaxial reduction plate-IV procedure. METHODS: A set of individualized templates was designed according to thin-slice computed tomography data obtained from 10 human cadavers. The templates contained cubic modules and drill guides to facilitate transoral atlantoaxial reduction plate positioning and anterior C2 screw placement. We performed 2 stages of cadaveric experiments with 2 cadavers in stage one and 8 in stage two. Finally, guided C2 screw placement was evaluated by reading postoperative computed tomography images and comparing the planned and inserted screw trajectories. RESULTS: There were two cortical breaching screws in stage one and three in stage two, but only the cortical breaching screws in stage one were ranked critical. In stage two, the planned entry points and the transverse angles of the anterior C2 screws could be simulated, whereas the declination angles could not be simulated due to intraoperative blockage of the drill bit and screwdriver by the upper teeth. CONCLUSIONS: It was feasible to use individualized templates to guide transoral C2 screw placement. Thus, these drill templates combined with transoral atlantoaxial reduction plate-IV, may improve the accuracy of transoral C2 screw placement and reduce related neurovascular complications. PMID:25518033

  2. Intra-articular injection of Torin 1 reduces degeneration of articular cartilage in a rabbit osteoarthritis model

    PubMed Central

    Cheng, N-T.; Cui, Y-P.

    2016-01-01

    Objectives Recent studies have shown that systemic injection of rapamycin can prevent the development of osteoarthritis (OA)-like changes in human chondrocytes and reduce the severity of experimental OA. However, the systemic injection of rapamycin leads to many side effects. The purpose of this study was to determine the effects of intra-articular injection of Torin 1, which as a specific inhibitor of mTOR which can cause induction of autophagy, is similar to rapamycin, on articular cartilage degeneration in a rabbit osteoarthritis model and to investigate the mechanism of Torin 1’s effects on experimental OA. Methods Collagenase (type II) was injected twice into both knees of three-month-old rabbits to induce OA, combined with two intra–articular injections of Torin 1 (400 nM). Degeneration of articular cartilage was evaluated by histology using the Mankin scoring system at eight weeks after injection. Chondrocyte degeneration and autophagosomes were observed by transmission electron microscopy. Matrix metallopeptidase-13 (MMP-13) and vascular endothelial growth factor (VEGF) expression were analysed by quantitative RT-PCR (qPCR).Beclin-1 and light chain 3 (LC3) expression were examined by Western blotting. Results Intra-articular injection of Torin 1 significantly reduced degeneration of the articular cartilage after induction of OA. Autophagosomes andBeclin-1 and LC3 expression were increased in the chondrocytes from Torin 1-treated rabbits. Torin 1 treatment also reduced MMP-13 and VEGF expression at eight weeks after collagenase injection. Conclusion Our results demonstrate that intra-articular injection of Torin 1 reduces degeneration of articular cartilage in collagenase-induced OA, at least partially by autophagy activation, suggesting a novel therapeutic approach for preventing cartilage degeneration and treating OA. Cite this article: N-T. Cheng, A. Guo, Y-P. Cui. Intra-articular injection of Torin 1 reduces degeneration of articular cartilage in a

  3. Adult human sarcomas. II. Medical oncology.

    PubMed

    Sinkovics, Joseph G

    2007-02-01

    Human sarcoma cells can be killed by radio- and chemotherapy, but tumor cells acquiring resistance frequently kill the patient. A keen understanding of the intracellular course of oncogenic cascades leads to the discovery of small molecular inhibitors of the involved phosphorylated kinases. Targeted therapy complements chemotherapy. Oncogene silencing is feasible by small interfering RNA. The restoration of some of the mutated or deleted tumor-suppressor genes (p53, Rb, PTEN, hSNF, INK/ARF and WT) by demethylation or reacetylation of their histones has been accomplished. Genetically engineered or naturally oncolytic viruses selectively lyse tumors and leave healthy tissues intact. Adeno- or retroviral vectors deliver genes of immunological costimulators, tumor antigens, chemo- or cytokines and/or tumor-suppressor proteins into tumor (sarcoma) cells. Suicide gene delivery results in apoptosis induction. Genes of enzymes that target prodrugs as their substrates render tumor cells highly susceptible to chemotherapy, with the prodrug to be targeted intracellularly. It will be combinations of sophisticated surgical removal of the nonencapsulated and locally invasive primary sarcomas, advanced forms of radiotherapy to the involved sites and immunotherapy with sarcoma vaccines that will cure primary sarcomas. Adoptive immunotherapy with immune lymphocytes will be operational in metastatic disease only when populations of regulatory T cells are controlled. Targeted therapy with small molecular inhibitors of oncogene cascades, the driving forces of sarcoma cells, alteration of the tumor stroma from a supportive to a tumor-hostile environment, reactivation or replacement of wild-type tumor-suppressor genes, and radio-chemotherapy (with much reduced toxicity) will eventually accomplish the cure of metastatic sarcomas. PMID:17288529

  4. Fracture of articular cartilage.

    PubMed

    Chin-Purcell, M V; Lewis, J L

    1996-11-01

    Crack formation and propagation is a significant element of the degeneration process in articular cartilage. In order to understand this process, and separate the relative importance of structural overload and material failure, methods for measuring the fracture toughness of cartilage are needed. In this paper, two such methods are described and used to measure fracture properties of cartilage from the canine patella. A modified single edge notch (MSEN) specimen was used to measure J, and a trouser tear test was used to measure T, both measures of fracture toughness with units of kN/m. A pseudo-elastic modulus was also obtained from the MSEN test. Several potential error sources were examined, and results for the MSEN test compared with another method for measuring the fracture parameter for urethane rubber. Good agreement was found. The two test methods were used to measure properties of cartilage from the patellae of 12 canines: 4-9 specimens from each of 12 patellae, with 5 right-left pairs were tested. Values of J ranged from 0.14-1.2 kN/m. J values correlated with T and were an average of 1.7 times larger than T. A variety of failure responses was seen in the MSEN tests, consequently a grade of 0 to 3 was assigned to each test, where 0 represented a brittle-like crack with minimal opening and 3 represented plastic flow with no crack formation. The initial cracks in 12/82 specimens did not propagate and were assigned to grade 3. The method for reducing data in the MSEN test assumed pseudo-elastic response and could not be used for the grade 3 specimens. Stiffness did not correlate with J. Neither J nor T was statistically different between right-left pairs, but varied between animals. The test methods appear useful for providing a quantitative measure of fracture toughness for cartilage and other soft materials. PMID:8950659

  5. Perivascular mesenchymal progenitors in human fetal and adult liver.

    PubMed

    Gerlach, Jörg C; Over, Patrick; Turner, Morris E; Thompson, Robert L; Foka, Hubert G; Chen, William C W; Péault, Bruno; Gridelli, Bruno; Schmelzer, Eva

    2012-12-10

    The presence of mesenchymal stem cells (MSCs) has been described in various organs. Pericytes possess a multilineage differentiation potential and have been suggested to be one of the developmental sources for MSCs. In human liver, pericytes have not been defined. Here, we describe the identification, purification, and characterization of pericytes in human adult and fetal liver. Flow cytometry sorting revealed that human adult and fetal liver contains 0.56%±0.81% and 0.45%±0.39% of CD146(+)CD45(-)CD56(-)CD34(-) pericytes, respectively. Of these, 41% (adult) and 30% (fetal) were alkaline phosphatase-positive (ALP(+)). In situ, pericytes were localized around periportal blood vessels and were positive for NG2 and vimentin. Purified pericytes could be cultured extensively and had low population doubling times. Immunofluorescence of cultures demonstrated that cells were positive for pericyte and mesenchymal cell markers CD146, NG2, CD90, CD140b, and vimentin, and negative for endothelial, hematopoietic, stellate, muscle, or liver epithelial cell markers von Willebrand factor, CD31, CD34, CD45, CD144, CD326, CK19, albumin, α-fetoprotein, CYP3A7, glial fibrillary acid protein, MYF5, and Pax7 by gene expression; myogenin and alpha-smooth muscle actin expression were variable. Fluorescence-activated cell sorting analysis of cultures confirmed surface expression of CD146, CD73, CD90, CD10, CD13, CD44, CD105, and ALP and absence of human leukocyte antigen-DR. In vitro differentiation assays demonstrated that cells possessed robust osteogenic and myogenic, but low adipogenic and low chondrogenic differentiation potentials. In functional in vitro assays, cells had typical mesenchymal strong migratory and invasive activity. In conclusion, human adult and fetal livers harbor pericytes that are similar to those found in other organs and are distinct from hepatic stellate cells. PMID:22931482

  6. Ultrastructural characteristics of human adult and infant cerebral cortical neurons.

    PubMed Central

    Ong, W Y; Garey, L J

    1991-01-01

    Biopsy specimens of human cerebral cortex from three adults and two infants were studied by correlating their light microscopic features in semithin sections with their ultrastructural characteristics. There was good tissue preservation, due to a minimum delay between obtaining the specimens and fixation. Pyramidal cells had a prominent apical dendrite, fine heterochromatin clumps in the nucleus and generally small numbers of cytoplasmic organelles, except for numerous free ribosomes in some of the large pyramids of Layers III to VI. Non-pyramidal cells lacked an apical dendrite and were further classified, on size and ultrastructure, into small, medium and large types. Large numbers of asymmetrical and symmetrical synapses were present in the neuropil but very few axosomatic synapses were found in the human cerebral cortex compared with subhuman primates and other mammals. Some symmetrical synapses were characterised by the presence of wide pre- and postsynaptic densities. The same general features of the adult cortex were also encountered in the infant, with certain exceptions. Many of the infant neurons had less densely packed heterochromatin, but greater numbers of free ribosomes, compared with the adult, and lipofuscin was absent. There was a total absence of myelinated fibres from the infant cortex; more large diameter dendrites were present than in the adult and axosomatic synapses were commoner. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 PMID:2050578

  7. Development of artificial articular cartilage.

    PubMed

    Oka, M; Ushio, K; Kumar, P; Ikeuchi, K; Hyon, S H; Nakamura, T; Fujita, H

    2000-01-01

    Attempts have been made to develop an artificial articular cartilage on the basis of a new viewpoint of joint biomechanics in which the lubrication and load-bearing mechanisms of natural and artificial joints are compared. Polyvinyl alcohol hydrogel (PVA-H), 'a rubber-like gel', was investigated as an artificial articular cartilage and the mechanical properties of this gel were improved through a new synthetic process. In this article the biocompatibility and various mechanical properties of the new improved PVA-H is reported from the perspective of its usefulness as an artificial articular cartilage. As regards lubrication, the changes in thickness and fluid pressure of the gap formed between a glass plate and the specimen under loading were measured and it was found that PVA-H had a thicker fluid film under higher pressures than polyethylene (PE) did. The momentary stress transmitted through the specimen revealed that PVA-H had a lower peak stress and a longer duration of sustained stress than PE, suggesting a better damping effect. The wear factor of PVA-H was approximately five times that of PE. Histological studies of the articular cartilage and synovial membranes around PVA-H implanted for 8-52 weeks showed neither inflammation nor degenerative changes. The artificial articular cartilage made from PVA-H could be attached to the underlying bone using a composite osteochondral device made from titanium fibre mesh. In the second phase of this work, the damage to the tibial articular surface after replacement of the femoral surface in dogs was studied. Pairs of implants made of alumina, titanium or PVA-H on titanium fibre mesh were inserted into the femoral condyles. The two hard materials caused marked pathological changes in the articular cartilage and menisci, but the hydrogel composite replacement caused minimal damage. The composite osteochondral device became rapidly attached to host bone by ingrowth into the supporting mesh. The clinical implications of

  8. Engineering lubrication in articular cartilage.

    PubMed

    McNary, Sean M; Athanasiou, Kyriacos A; Reddi, A Hari

    2012-04-01

    Despite continuous progress toward tissue engineering of functional articular cartilage, significant challenges still remain. Advances in morphogens, stem cells, and scaffolds have resulted in enhancement of the bulk mechanical properties of engineered constructs, but little attention has been paid to the surface mechanical properties. In the near future, engineered tissues will be able to withstand and support the physiological compressive and tensile forces in weight-bearing synovial joints such as the knee. However, there is an increasing realization that these tissue-engineered cartilage constructs will fail without the optimal frictional and wear properties present in native articular cartilage. These characteristics are critical to smooth, pain-free joint articulation and a long-lasting, durable cartilage surface. To achieve optimal tribological properties, engineered cartilage therapies will need to incorporate approaches and methods for functional lubrication. Steady progress in cartilage lubrication in native tissues has pushed the pendulum and warranted a shift in the articular cartilage tissue-engineering paradigm. Engineered tissues should be designed and developed to possess both tribological and mechanical properties mirroring natural cartilage. In this article, an overview of the biology and engineering of articular cartilage structure and cartilage lubrication will be presented. Salient progress in lubrication treatments such as tribosupplementation, pharmacological, and cell-based therapies will be covered. Finally, frictional assays such as the pin-on-disk tribometer will be addressed. Knowledge related to the elements of cartilage lubrication has progressed and, thus, an opportune moment is provided to leverage these advances at a critical step in the development of mechanically and tribologically robust, biomimetic tissue-engineered cartilage. This article is intended to serve as the first stepping stone toward future studies in functional

  9. Engineering Lubrication in Articular Cartilage

    PubMed Central

    McNary, Sean M.; Athanasiou, Kyriacos A.

    2012-01-01

    Despite continuous progress toward tissue engineering of functional articular cartilage, significant challenges still remain. Advances in morphogens, stem cells, and scaffolds have resulted in enhancement of the bulk mechanical properties of engineered constructs, but little attention has been paid to the surface mechanical properties. In the near future, engineered tissues will be able to withstand and support the physiological compressive and tensile forces in weight-bearing synovial joints such as the knee. However, there is an increasing realization that these tissue-engineered cartilage constructs will fail without the optimal frictional and wear properties present in native articular cartilage. These characteristics are critical to smooth, pain-free joint articulation and a long-lasting, durable cartilage surface. To achieve optimal tribological properties, engineered cartilage therapies will need to incorporate approaches and methods for functional lubrication. Steady progress in cartilage lubrication in native tissues has pushed the pendulum and warranted a shift in the articular cartilage tissue-engineering paradigm. Engineered tissues should be designed and developed to possess both tribological and mechanical properties mirroring natural cartilage. In this article, an overview of the biology and engineering of articular cartilage structure and cartilage lubrication will be presented. Salient progress in lubrication treatments such as tribosupplementation, pharmacological, and cell-based therapies will be covered. Finally, frictional assays such as the pin-on-disk tribometer will be addressed. Knowledge related to the elements of cartilage lubrication has progressed and, thus, an opportune moment is provided to leverage these advances at a critical step in the development of mechanically and tribologically robust, biomimetic tissue-engineered cartilage. This article is intended to serve as the first stepping stone toward future studies in functional

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

    PubMed

    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. PMID:20032473

  11. How long have adult humans been consuming milk?

    PubMed

    Gerbault, Pascale; Roffet-Salque, Mélanie; Evershed, Richard P; Thomas, Mark G

    2013-12-01

    Lactase is the enzyme that breaks down the milk sugar lactose, and in most mammals, including most humans, lactase activity is down-regulated after the weaning period is completed. However, in about 35% of adults worldwide, lactase continues to be expressed throughout adulthood, a feature termed lactase persistence (LP). Genetic evidence indicates that LP is a recent human adaptation, and its current geographic distribution correlates with the relative historical importance of dairying in different human populations. Investigating archaeological evidence for fresh milk consumption has proved crucial in building an account of the joint evolution of LP and dairying. A powerful technique for investigating food processing, including milk processing, in ancient populations is lipid residue analysis on archaeological pottery. We review here the archaeological and genetic evidence available that have contributed to a better understanding of the gene-culture co-evolution of LP and dairying. PMID:24339181

  12. PRP and Articular Cartilage: A Clinical Update

    PubMed Central

    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

  13. 3D Hydrogel Scaffolds for Articular Chondrocyte Culture and Cartilage Generation.

    PubMed

    Smeriglio, Piera; Lai, Janice H; Yang, Fan; Bhutani, Nidhi

    2015-01-01

    Human articular cartilage is highly susceptible to damage and has limited self-repair and regeneration potential. Cell-based strategies to engineer cartilage tissue offer a promising solution to repair articular cartilage. To select the optimal cell source for tissue repair, it is important to develop an appropriate culture platform to systematically examine the biological and biomechanical differences in the tissue-engineered cartilage by different cell sources. Here we applied a three-dimensional (3D) biomimetic hydrogel culture platform to systematically examine cartilage regeneration potential of juvenile, adult, and osteoarthritic (OA) chondrocytes. The 3D biomimetic hydrogel consisted of synthetic component poly(ethylene glycol) and bioactive component chondroitin sulfate, which provides a physiologically relevant microenvironment for in vitro culture of chondrocytes. In addition, the scaffold may be potentially used for cell delivery for cartilage repair in vivo. Cartilage tissue engineered in the scaffold can be evaluated using quantitative gene expression, immunofluorescence staining, biochemical assays, and mechanical testing. Utilizing these outcomes, we were able to characterize the differential regenerative potential of chondrocytes of varying age, both at the gene expression level and in the biochemical and biomechanical properties of the engineered cartilage tissue. The 3D culture model could be applied to investigate the molecular and functional differences among chondrocytes and progenitor cells from different stages of normal or aberrant development. PMID:26484414

  14. 3D Hydrogel Scaffolds for Articular Chondrocyte Culture and Cartilage Generation

    PubMed Central

    Yang, Fan; Bhutani, Nidhi

    2015-01-01

    Human articular cartilage is highly susceptible to damage and has limited self-repair and regeneration potential. Cell-based strategies to engineer cartilage tissue offer a promising solution to repair articular cartilage. To select the optimal cell source for tissue repair, it is important to develop an appropriate culture platform to systematically examine the biological and biomechanical differences in the tissue-engineered cartilage by different cell sources. Here we applied a three-dimensional (3D) biomimetic hydrogel culture platform to systematically examine cartilage regeneration potential of juvenile, adult, and osteoarthritic (OA) chondrocytes. The 3D biomimetic hydrogel consisted of synthetic component poly(ethylene glycol) and bioactive component chondroitin sulfate, which provides a physiologically relevant microenvironment for in vitro culture of chondrocytes. In addition, the scaffold may be potentially used for cell delivery for cartilage repair in vivo. Cartilage tissue engineered in the scaffold can be evaluated using quantitative gene expression, immunofluorescence staining, biochemical assays, and mechanical testing. Utilizing these outcomes, we were able to characterize the differential regenerative potential of chondrocytes of varying age, both at the gene expression level and in the biochemical and biomechanical properties of the engineered cartilage tissue. The 3D culture model could be applied to investigate the molecular and functional differences among chondrocytes and progenitor cells from different stages of normal or aberrant development. PMID:26484414

  15. Role of uppermost superficial surface layer of articular cartilage in the lubrication mechanism of joints

    PubMed Central

    KUMAR, P.; OKA, M.; TOGUCHIDA, J.; KOBAYASHI, M.; UCHIDA, E.; NAKAMURA, T.; TANAKA, K.

    2001-01-01

    The uppermost superficial surface layer of articular cartilage, the ‘lamina splendens’ which provides a very low friction lubrication surface in articular joints, was investigated using atomic force microscopy (AFM). Complementary specimens were also observed under SEM at −10 °C without dehydration or sputter ion coating. Fresh adult pig osteochondral specimens were prepared from the patellas of pig knee joints and digested with the enzymes, hyaluronidase, chondroitinase ABC and alkaline protease. Friction coefficients between a pyrex glass plate and the osteochondral specimens digested by enzymes as well as natural (undigested) specimens were measured, using a thrust collar apparatus. Normal saline, hyaluronic acid (HA) and a mixture of albumin, globulin, HA (AGH) were used as lubrication media. The surface irregularities usually observed in SEM studies were not apparent under AFM. The articular cartilage surface was resistant to hyaluronidase and also to chondroitinase ABC, but a fibrous structure was exhibited in alkaline protease enzymes-digested specimens. AFM analysis revealed that the thickness of the uppermost superficial surface layer of articular cartilage was between 800 nm and 2 μm in adult pig articular cartilage. The coefficient of friction (c.f.) was significantly higher in chondroitinase ABC and alkaline protease enzymes digested specimens. Generally, in normal saline lubrication medium, c.f. was higher in comparison to HA and AGH lubrication media. The role of the uppermost, superficial surface layer of articular cartilage in the lubrication mechanism of joints is discussed. PMID:11554503

  16. Role of uppermost superficial surface layer of articular cartilage in the lubrication mechanism of joints.

    PubMed

    Kumar, P; Oka, M; Toguchida, J; Kobayashi, M; Uchida, E; Nakamura, T; Tanaka, K

    2001-09-01

    The uppermost superficial surface layer of articular cartilage, the 'lamina splendens' which provides a very low friction lubrication surface in articular joints, was investigated using atomic force microscopy (AFM). Complementary specimens were also observed under SEM at -10 degrees C without dehydration or sputter ion coating. Fresh adult pig osteochondral specimens were prepared from the patellas of pig knee joints and digested with the enzymes, hyaluronidase, chondroitinase ABC and alkaline protease. Friction coefficients between a pyrex glass plate and the osteochondral specimens digested by enzymes as well as natural (undigested) specimens were measured, using a thrust collar apparatus. Normal saline, hyaluronic acid (HA) and a mixture of albumin, globulin, HA (AGH) were used as lubrication media. The surface irregularities usually observed in SEM studies were not apparent under AFM. The articular cartilage surface was resistant to hyaluronidase and also to chondroitinase ABC, but a fibrous structure was exhibited in alkaline protease enzymes-digested specimens. AFM analysis revealed that the thickness of the uppermost superficial surface layer of articular cartilage was between 800 nm and 2 microm in adult pig articular cartilage. The coefficient of friction (c.f.) was significantly higher in chondroitinase ABC and alkaline protease enzymes digested specimens. Generally, in normal saline lubrication medium, c.f. was higher in comparison to HA and AGH lubrication media. The role of the uppermost, superficial surface layer of articular cartilage in the lubrication mechanism of joints is discussed. PMID:11554503

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

    NASA Astrophysics Data System (ADS)

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

    PubMed

    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. PMID:26715354

  19. Colonies in engineered articular cartilage express superior differentiation.

    PubMed

    Selvaratnam, L; Abd Rahim, S; Kamarul, T; Chan, K Y; Sureshan, S; Penafort, R; Ng, C L L

    2005-07-01

    In view of poor regeneration potential of the articular cartilage, in-vitro engineering of cartilage tissue offers a promising option for progressive joint disease. This study aims to develop a biologically engineered articular cartilage for autologous transplantation. The initial work involved determination of chondrocyte yield and viability, and morphological analysis. Cartilage was harvested from the knee, hip and shoulder joints of adult New Zealand white rabbits and chondrocytes were isolated by enzymatic digestion of the extra-cellular matrix before serial cultivation in DMEM/Ham's F12 media as monolayer cultures. No differences were noted in cell yield. Although chondrocytes viability was optimal (>93%) following harvest from native cartilage, their viability tended to be lowered on passaging. Chondrocytes aggregated in isogenous colonies comprising ovoid cells with intimate intracellular contacts and readily exhibited Safranin-O positive matrix; features typically associated with articular cartilage in-vivo. However, chondrocytes also existed concurrently in scattered bipolar/multipolar forms lacking Safranin-O expression. Therefore, early data demonstrated successful serial culture of adult chondrocytes with differentiated morphology seen in established chondrocyte colonies synthesizing matrix proteoglycans. PMID:16381284

  20. Cohort Programming and Learning: Improving Educational Experiences for Adult Learners. Professional Practices in Adult Education and Human Resource Development Series.

    ERIC Educational Resources Information Center

    Saltiel, Iris M.; Russo, Charline S.

    This book, which is intended for adult educators and human resource developers, presents guidelines for using the principles of cohort programming and learning to improve adult learners' educational experiences. The following are among the topics covered in the book's eight chapters: (1) cohort programming and learning (cohort programs defined;…

  1. Assessing Adult Learning: A Guide for Practitioners. Revised Edition. Professional Practices in Adult Education and Human Resource Development Series.

    ERIC Educational Resources Information Center

    Moran, Joseph J.

    This book, which is intended for adult educators and human resource developers, presents guidelines for assessing adult learning. The following are among the topics covered in the book's eight chapters: (1) basic principles of informal assessment (relationship between learning and assessment activities; sequencing learning and assessment…

  2. Unique multipotent cells in adult human mesenchymal cell populations

    PubMed Central

    Kuroda, Yasumasa; Kitada, Masaaki; Wakao, Shohei; Nishikawa, Kouki; Tanimura, Yukihiro; Makinoshima, Hideki; Goda, Makoto; Akashi, Hideo; Inutsuka, Ayumu; Niwa, Akira; Shigemoto, Taeko; Nabeshima, Yoko; Nakahata, Tatsutoshi; Nabeshima, Yo-ichi; Fujiyoshi, Yoshinori; Dezawa, Mari

    2010-01-01

    We found adult human stem cells that can generate, from a single cell, cells with the characteristics of the three germ layers. The cells are stress-tolerant and can be isolated from cultured skin fibroblasts or bone marrow stromal cells, or directly from bone marrow aspirates. These cells can self-renew; form characteristic cell clusters in suspension culture that express a set of genes associated with pluripotency; and can differentiate into endodermal, ectodermal, and mesodermal cells both in vitro and in vivo. When transplanted into immunodeficient mice by local or i.v. injection, the cells integrated into damaged skin, muscle, or liver and differentiated into cytokeratin 14-, dystrophin-, or albumin-positive cells in the respective tissues. Furthermore, they can be efficiently isolated as SSEA-3(+) cells. Unlike authentic ES cells, their proliferation activity is not very high and they do not form teratomas in immunodeficient mouse testes. Thus, nontumorigenic stem cells with the ability to generate the multiple cell types of the three germ layers can be obtained through easily accessible adult human mesenchymal cells without introducing exogenous genes. These unique cells will be beneficial for cell-based therapy and biomedical research. PMID:20421459

  3. Multipotent progenitor cells isolated from adult human pancreatic tissue.

    PubMed

    Todorov, I; Nair, I; Ferreri, K; Rawson, J; Kuroda, A; Pascual, M; Omori, K; Valiente, L; Orr, C; Al-Abdullah, I; Riggs, A; Kandeel, F; Mullen, Y

    2005-10-01

    The supply of islet cells is a limiting factor for the widespread application of islet transplantation of type-1 diabetes. Islets constitute 1% to 2% of pancreatic tissue, leaving approximately 98% as discard after islet isolation and purification. In this report we present our data on the isolation of multipotent progenitor cells from discarded adult human pancreatic tissue. The collected cells from discarded nonislet fractions, after enzymatic digestion and gradient purification of islets, were dissociated for suspension culture in a serum-free medium. The cell clusters grown to a size of 100 to 150 mum contained cells staining for stage-specific embryonic antigens, but not insulin or C-peptide. To direct cell differentiation toward islets, clusters were recultured in a pancreatic differentiation medium. Insulin and C-peptide-positive cells by immunocytochemistry appeared within a week, reaching over 10% of the cell population. Glucagon and somatostatin-positive cells were also detected. The cell clusters were found to secrete insulin in response to glucose stimulation. Cells from the same clusters also had the capacity for differentiation into neural cells, as documented by staining for neural and glial cell markers when cultured as monolayers in media containing neurotrophic factors. These data suggest that multipotent pancreatic progenitor cells exist within the human pancreatic tissue that is typically discarded during islet isolation procedures. These adult progenitor cells can be successfully differentiated into insulin-producing cells, and thus they have the potential for treatment of type-1 diabetes mellitus. PMID:16298614

  4. Safety, Biodistribution, and Efficacy of an AAV-5 Vector Encoding Human Interferon-Beta (ART-I02) Delivered via Intra-Articular Injection in Rhesus Monkeys with Collagen-Induced Arthritis.

    PubMed

    Bevaart, Lisette; Aalbers, Caroline J; Vierboom, Michel P M; Broekstra, Niels; Kondova, Ivanela; Breedveld, Elia; Hauck, Bernd; Wright, J Fraser; Tak, Paul Peter; Vervoordeldonk, Margriet J

    2015-06-01

    Preclinical studies to assess biodistribution, safety, and initial efficacy of ART-I02, an adeno-associated type 5 (rAAV5) vector expressing human interferon β (hIFN-β), were performed in a total of 24 rhesus monkeys with collagen-induced arthritis. All monkeys were naïve or showed limited neutralizing antibody (Nab) titers to AAV5 at the start of the study. Animals were injected with a single intra-articular dose of ART-I02 or placebo, consisting of 3.2×10(13) vg (Dose A=maximum feasible dose), 4.58×10(12) vg (Dose B), or placebo in the first affected finger joint, the ipsilateral knee, and ankle joint at the same time point. Animals were monitored for clinical parameters and well-being with a maximum of 4 weeks, with the option that the severity of arthritis could necessitate an earlier time point of sacrifice. No adverse events were noted after injection of ART-I02. No abnormalities were observed after histological evaluation of all organs. At both dose levels, immunohistochemical staining indicated expression of hIFN-β. In animals injected with Dose A, we observed stabilization or a reduction in swelling in the finger joint in which vector was administered. The highest copy numbers of vector DNA were detected in synovial tissue of the injected joint and the draining lymph node of the injected knee. High titers of Nab to rAAV5 were observed at the end of the study. Five monkeys developed an rAAV5-specific T-cell response. Two monkeys developed Nab to hIFN-β. In conclusion, intra-articular injection of ART-I02 was well-tolerated and did not induce adverse events. After administration of Dose A of ART-I02, we observed a beneficial effect on joint swelling, substantiated by decreased histological inflammation and bone erosion scores. A GMP vector for clinical application has been manufactured and is currently being tested in GLP rodent studies, with the aim to move forward to a clinical trial. PMID:26086763

  5. Ultrasound evaluation of site-specific effect of simulated microgravity on articular cartilage.

    PubMed

    Wang, Qing; Zheng, Yong-Ping; Wang, Xiao-Yun; Huang, Yan-Ping; Liu, Mu-Qing; Wang, Shu-Zhe; Zhang, Zong-Kang; Guo, Xia

    2010-07-01

    Space flight induces acute changes in normal physiology in response to the microgravity environment. Articular cartilage is subjected to high loads under a ground reaction force on Earth. The objectives of this study were to investigate the site dependence of morphological and ultrasonic parameters of articular cartilage and to examine the site-specific responses of articular cartilage to simulated microgravity using ultrasound biomicroscopy (UBM). Six rats underwent tail suspension (simulated microgravity) for four weeks and six other rats were kept under normal Earth gravity as controls. Cartilage thickness, ultrasound roughness index (URI), integrated reflection coefficient (IRC) and integrated backscatter coefficient (IBC) of cartilage tissues, as well as histological degeneration were measured at the femoral head (FH), medial femoral condyle (MFC), lateral femoral condyle (LFC), patello-femoral groove (PFG) and patella (PAT). The results showed site dependence not significant in all UBM parameters except cartilage thickness (p < 0.01) in the control specimens. Only minor changes in articular cartilage were induced by 4-week tail suspension, although there were significant decreases in cartilage thickness at the MFC and PAT (p < 0.05) and a significant increase in URI at the PAT (p < 0.01). This study suggested that the 4-week simulated microgravity had only mild effects on femoral articular cartilage in the rat model. This information is useful for human spaceflight and clinical medicine in improving understanding of the effect of microgravity on articular cartilage. However, the effects of longer duration microgravity experience on articular cartilage need further investigation. PMID:20620696

  6. Inter- and intra-specific scaling of articular surface areas in the hominoid talus

    PubMed Central

    Parr, William C H; Chatterjee, Helen J; Soligo, Christophe

    2011-01-01

    The morphology of postcranial articular surfaces is expected to reflect their weight-bearing properties, as well as the stability and mobility of the articulations to which they contribute. Previous studies have mainly confirmed earlier predictions of isometric scaling between articular surface areas and body mass; the exception to this is ‘male-type’, convex articular surface areas, which may scale allometrically due to differences in locomotor strategies within the analysed samples. In the present study, we used new surface scanning technology to quantify more accurately articular surface areas and to test those predictions within the talus of hominoid primates, including modern humans. Our results, contrary to predictions, suggest that there are no generalised rules of articular scaling within the talus of hominoids. Instead, we suggest that articular scaling patterns are highly context-specific, depending on the role of each articulation during locomotion, as well as taxon- and sex-specific differences in locomotion and ontogenetic growth trajectories within any given sample. While this may prove problematic for inferring body mass based on articular surface area, it also offers new opportunities of gaining substantial insights into the locomotor patterns of extinct species. PMID:21323919

  7. The Biomechanics of the Pediatric and Adult Human Thoracic Spine

    PubMed Central

    Lopez-Valdes, Francisco J.; Lau, Sabrina; Riley, Patrick; Lamp, John; Kent, Richard

    2011-01-01

    A growing body of literature points out the relevance of the thoracic spine dynamics in understanding the thorax-restraint interaction as well as in determining the kinematics of the head and cervical spine. This study characterizes the dynamic response in bending of eight human spinal specimens (4 pediatric: ages 7 and 15 years, 4 adult: ages 48 and 52 years) from two sections along the thoracic spine (T2–T4 and T7–T9). Each specimen consisted of three vertebral bodies connected by the corresponding intervertebral discs. All ligaments were preserved in the preparation with the exception of the inter-transverse ligament. Specimens were exposed to a series of five dynamic bending ramp-and-hold tests with varying amplitudes at a nominal rate of 2 rad/s. After this battery of tests, failure experiments were conducted. The 7-year-old specimen showed the lowest tolerance to a moment (T2–T4: 12.1 Nm; T7–T9: 11.6 Nm) with no significant reduction of the relative rotation between the vertebrae. The 15-year-old failure tolerance was comparable to that of the adult specimens. Failure of the adult specimens occurred within a wide range at the T2–T4 thoracic section (23.3 Nm- 53.0 Nm) while it was circumscribed to the interval 48.3 Nm-52.5 Nm for the T7–T9 section. The series of dynamic ramp-and-hold were used to assess two different scaling methods (mass scaling and SAE scaling). Neither method was able to capture the stiffness, peak moment and relaxation characteristics exhibited by the pediatric specimens. PMID:22105396

  8. Gender specificity of sucrose induced analgesia in human adults.

    PubMed

    Bhattacharjee, Manasi; Bhatia, Renu; Mathur, Rashmi

    2007-01-01

    Sweet, palatable substances such as sucrose are reported to calm infants undergoing routine investigative procedures. The analgesic effect persists in pre pubertal children and adults with a hint of gender dependent variation in the analgesic response. The present study was therefore designed to explore gender specificity of sucrose induced analgesia in adult volunteers utilizing the nociceptive flexion reflex, an objective tool for pain assessment. Nociceptive flexion reflex was recorded, both before and after (up to 15 min) ingestion of 100 ml of 25% sucrose solution in 6 male and 6 female volunteers. In the male volunteers the maximum amplitude of the response was 20.8 +/- 7.7 microV before sucrose ingestion and 22.6 +/- 9.1 microV, 6.6 +/- 0.7 microV, 6.2 +/- 1.1 microV, 7.5 +/- 0.9 microV at 0, 5, 10 and 15 minutes post sucrose ingestion respectively. In female volunteers, the maximum amplitude of the response was 33.7 +/- 17.7 microV before sucrose ingestion and 43.6 +/- 17.2 microV, 7.1 +/- 1.2 microV, 25.9 +/- 16.1 microV, 50.6 +/- 16.3 microV at the same time intervals post sucrose ingestion. The maximum amplitude values were significantly lower in the males at 10 and 15 minutes after sucrose ingestion (P < 0.05). This is the first objective report of gender specificity in sucrose induced analgesia in adult humans. The gender dependent variation in sucrose induced analgesia is prolonged in male (15 min) and short lived in female (5 min) volunteers. This knowledge may have important implications in pain management. PMID:18476396

  9. The relationship between the temporomandibular joint capsule, articular disc and jaw muscles.

    PubMed Central

    Schmolke, C

    1994-01-01

    The anatomy of the temporomandibular joint capsule and its possible relationships to other structures near the joint are not fully understood. A 3-dimensional analysis based on sagittal, frontal and horizontal serial sections through the human temporomandibular joint region was therefore undertaken. Capsular elements which directly connect the temporal bone with the mandible were seen only on the lateral side of the joint. In the posterior, anterior and medial regions of the joint the upper and lower laminae of the articular disc are attached separately either to the temporal bone or to the mandibular condyle. The shaping of the articular cavities and the texture of the joint capsule permit movements of the articular disc predominantly in the anteromedial direction. On the entire medial side of the joint the articular disc and its capsular attachments are in close contact with the fascia of the lateral pterygoid muscle whereby a small portion of the upper head of this muscle inserts directly into the anteromedial part of the articular disc. Thus both the upper and the lower heads of the lateral pterygoid muscle are likely to influence the position of the articular disc directly during temporomandibular joint movements. Laterally, the articular disc is attached to the fascia of the masseter muscle, and part of the lateral ligament inserts into the temporalis fascia. Since these attachments are relatively weak, neither the temporalis nor the masseter muscles are considered to act directly on the articular disc; instead, via afferents from muscle spindles, they may take part in signalling the position of the temporomandibular joint components, including that of the articular disc. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 Fig. 5 PMID:8014124

  10. Extra and Intra-articular Synovial Chondromatosis.

    PubMed

    Chaudhary, R K; Banskota, B; Rijal, S; Banskota, A K

    2015-01-01

    Synovial chondromatosis is not so rare intra-articular condition secondary to synovial metaplasia, that affects the knee joint. Extra-articular synovial chondromatosis however is an extremely rare condition that usually involves the synovial sheath or bursa of the foot or hand. We present two cases of synovial chondromatosis, one intra and one extra-articular. The first case was a 25 year old lady who presented with pain, swelling and restricted range of motion of left knee and was found to have an intra-articular synovial chondromatosis which was treated successfully by joint debridement. The second case was that of a 22 year old man who presented with right knee pain and was diagnosed to have an extra-articular synovial chondromatosis of his right medial hamstring tendon sheath, excision of which resulted in complete relief of symptoms. PMID:27549506

  11. Human herpesvirus 7 is a constitutive inhabitant of adult human saliva.

    PubMed Central

    Wyatt, L S; Frenkel, N

    1992-01-01

    We report the frequent isolation of human herpesvirus 7 from the saliva of healthy adults. Virus isolates recovered from different individuals exhibited minimal restriction enzyme polymorphism, which was mostly confined to heterogeneous (het) sequences in the genome. DNAs of isolates recovered from the same individual over a period of several months showed the same characteristic het fragments, indicating the stability of the het sequences upon virus replication and shedding in vivo. In contrast to the results of previous reports, human herpesvirus 6, the causative agent of roseola infantum, could not be isolated from the saliva specimens, raising questions regarding oral transmission of human herpesvirus 6 and human herpesvirus 7 to young children. Images PMID:1348548

  12. Exchange delays and impulsive choice in adult humans.

    PubMed

    Hyten, C; Madden, G J; Field, D P

    1994-09-01

    Choice responding by adult humans in a discrete-trial task was examined as a function of conditions that manipulated either the delay to point delivery or the delay between points and their exchange for money. In point-delay conditions, subjects chose between an "impulsive" alternative that provided a small amount of points immediately and a "self-control" alternative that provided a larger amount of points delayed by 15, 30, or 60 s. Points were exchanged for money immediately following the session. Subjects preferred the self-control alternative. In exchange-delay conditions, subjects chose between a small amount of points exchangeable for money immediately following the session and a larger amount of points exchangeable for money after 1 day, 3 weeks, or 6 weeks. A self-control preference observed for all subjects in the 1-day exchange-delay condition reversed to exclusive impulsive preference for 4 of the 6 subjects when choice conditions involved exchange delays of 3 or 6 weeks. These results show that human choice is sensitive to the manipulation of exchange delays and that impulsive preference can be obtained with exchange delays on the order of weeks. PMID:7964366

  13. Simultaneous characterization of progenitor cell compartments in adult human liver.

    PubMed

    Porretti, Laura; Cattaneo, Alessandra; Colombo, Federico; Lopa, Raffaella; Rossi, Giorgio; Mazzaferro, Vincenzo; Battiston, Carlo; Svegliati-Baroni, Gianluca; Bertolini, Francesco; Rebulla, Paolo; Prati, Daniele

    2010-01-01

    The human liver is a complex tissue consisting of epithelial, endothelial, hematopoietic, and mesenchymal elements that probably derive from multiple lineage-committed progenitors, but no comprehensive study aimed at identifying and characterizing intrahepatic precursors has yet been published. Cell suspensions for this study were obtained by enzymatic digestion of liver specimens taken from 20 patients with chronic liver disease and 13 multiorgan donors. Stem and progenitor cells were first isolated, amplified, and characterized ex vivo according to previously validated methods, and then optimized flow cytometry was used to assess their relative frequencies and characterize their immunophenotypes in the clinical specimens. Stem and progenitor cells committed to hematopoietic, endothelial, epithelial, and mesenchymal lineages were clearly identifiable in livers from both healthy and diseased subjects. Within the mononuclear liver cell compartment, epithelial progenitors [epithelial cell adhesion molecule (EpCAM)(+)/CD49f(+)/CD29(+)/CD45(-)] accounted for 2.7-3.5% whereas hematopoietic (CD34(+)/CD45(+)), endothelial [vascular endothelial growth factor-2 (KDR)(+)/CD146(+)/CD45(-)], and mesenchymal [CD73(+)/CD105(+)/CD90 (Thy-1)(+)/CD45 (-)] stem cells and progenitors accounted for smaller fractions (0.02-0.6%). The patients' livers had higher percentages of hematopoietic and endothelial precursors than those of the donors. In conclusion, we identified and characterized precursors committed to four different lineages in adult human liver. We also optimized a flow cytometry approach that will be useful in exploring the contribution of these cells to the pathogenesis of liver disease. PMID:19960544

  14. A biokinetic model for systemic technetium in adult humans

    SciTech Connect

    Leggett, Richard Wayne; Giussani, Augusto

    2015-04-10

    The International Commission on Radiological Protection (ICRP) currently is updating its biokinetic and dosimetric models for internally deposited radionuclides. Technetium (Tc), the lightest element that exists only in radioactive form, has two important isotopes from the standpoint of potential risk to humans: the long-lived isotope 99Tm(T1/2=2.1x105 y) is present in high concentration in nuclear waste, and the short-lived isotope 99mTc (T1/2=6.02 h) is the most commonly used radionuclide in diagnostic nuclear medicine. This paper reviews data on the biological behavior of technetium and proposes a biokinetic model for systemic technetium in the adult human body for use in radiation protection. Compared with the ICRP s current occupational model for systemic technetium, the proposed model provides a more realistic description of the paths of movement of technetium in the body; provides greater consistency with experimental and medical data; and, for most radiosensitive organs, yields substantially different estimates of cumulative activity (total radioactive decays within the organ) following uptake of 99Tm or 99mTc to blood.

  15. A biokinetic model for systemic technetium in adult humans

    DOE PAGESBeta

    Leggett, Richard Wayne; Giussani, Augusto

    2015-04-10

    The International Commission on Radiological Protection (ICRP) currently is updating its biokinetic and dosimetric models for internally deposited radionuclides. Technetium (Tc), the lightest element that exists only in radioactive form, has two important isotopes from the standpoint of potential risk to humans: the long-lived isotope 99Tm(T1/2=2.1x105 y) is present in high concentration in nuclear waste, and the short-lived isotope 99mTc (T1/2=6.02 h) is the most commonly used radionuclide in diagnostic nuclear medicine. This paper reviews data on the biological behavior of technetium and proposes a biokinetic model for systemic technetium in the adult human body for use in radiation protection.more » Compared with the ICRP s current occupational model for systemic technetium, the proposed model provides a more realistic description of the paths of movement of technetium in the body; provides greater consistency with experimental and medical data; and, for most radiosensitive organs, yields substantially different estimates of cumulative activity (total radioactive decays within the organ) following uptake of 99Tm or 99mTc to blood.« less

  16. Ossified Ligamentum Longitudinale Anterius in Adult Human Dry Vertebrae

    PubMed Central

    Venumadhav, Nelluri; KS, Siddaraju

    2014-01-01

    Background: The ligamentum longitudinale anterius is a broad and strong band of fibrous tissue that runs along the anterior surfaces of the bodies of the vertebrae. Aim: The study was undertaken to evaluate the incidence of ossified ligamentum longitudinale anterius in adult dry human vertebra. Materials and Methods: This study was carried out on 95 sets of dry human vertebral columns irrespective of age and sex at Mayo Institute of Medical Sciences- Barabanki,-UP, Melaka Manipal Medical College-Manipal University and Department of Anatomy, KMCT Medical College, Manassery- Calicut, India. All the sets of vertebral columns were macroscopically inspected for the ossified ligamentum longitudinale anterius. Results: It was observed that out of 95 sets of vertebral columns, 27 (28.42%) vertebral columns showed ossification. Out of 27 vertebral columns, 17 (17.89%) vertebral columns showed segmental type of ossification, 2 (2.11%) vertebral columns showed continuous type of ossification and 8 (8.42%) vertebral columns showed mixed type of ossification at different vertebral level. Conclusion: Such type of ossification will affect the biomechanics of the spine and may result in stiff neck, low back pain, dysphagia, odynophagia, compression of the brachial plexus, aphonia, immobility or mucosal thickening of larynx. Hence, knowledge of such abnormalities should be kept in mind to minimise serious complications in any surgical intervention or investigative procedures in the region. PMID:25302180

  17. Professional Fulfillment and Satisfaction of US and Canadian Adult Education and Human Resource Development Faculty

    ERIC Educational Resources Information Center

    Peterson, Shari L.; Wiesenberg, Faye

    2004-01-01

    This comparative study explored the professional fulfillment and job satisfaction of US and Canadian college and university faculty in the fields of Adult Education and Human Resource Development. In Autumn 2001, we disseminated electronically "The Adult Education and Human Resource Development Faculty Survey" to a selected sample of Canadian and…

  18. Delphinidin inhibits IL-1β-induced activation of NF-κB by modulating the phosphorylation of IRAK-1Ser376 in human articular chondrocytes

    PubMed Central

    Haseeb, Abdul; Chen, Dongxing

    2013-01-01

    Objective. In OA, there is enhanced expression of pro-inflammatory cytokines such as IL-1β in the affected joint. Delphinidin, an anthocyanidin found in pigmented fruits and vegetables, has been shown to possess anti-inflammatory and antioxidant properties. In the present study we determined whether delphinidin would inhibit the IL-1β-induced activation of NF-κB in human chondrocytes and determined the mechanism of its action. Methods. PGE2 levels and activation of NF-κB p65 in human OA chondrocytes were determined by ELISA-based assays. Protein expression of cyclo-oxygenase-2 (COX-2) and phosphorylation of kinases was determined by western immunoblotting. Expression level of mRNAs was determined by TaqMan assays. Results. Delphinidin inhibited IL-1β-induced expression of COX-2 and production of PGE2 in human chondrocytes. Delphinidin also inhibited IL-1β-mediated phosphorylation of IL-1 receptor-associated kinase-1Ser376, phosphorylation of IKKα/β, expression of IKKβ, degradation of IκBα, and activation and nuclear translocation of NF-κB/p65. Phosphorylation of TGF-β-activated kinase 1 was not observed but NF-κB-inducing kinase (NIK) was phosphorylated and phosphorylation of NIK was blocked by delphinidin in IL-1β-treated human chondrocytes. Conclusion. These data identify delphinidin as a novel inhibitor of IL-1β-induced production of cartilage-degrading molecule PGE2 via inhibition of COX-2 expression and provide new insight into the mechanism of its action. Our results also identify inhibition of IRAK1Ser376 phosphorylation by delphinidin in IL-1β-induced activation of NF-κB in human chondrocytes. Given the important role played by IL-1β-induced NF-κB activation, COX-2 expression and PGE2 production in OA, our results may have important implications for the development of novel therapeutic strategies for the prevention/treatment of OA. PMID:23392593

  19. The Adult Learner. The Definitive Classic in Adult Education and Human Resource Development. Fifth Edition.

    ERIC Educational Resources Information Center

    Knowles, Malcolm S.; Holton, Elwood F., III; Swanson, Richard A.

    This book examines the core principles of adult learning and the roots of andragogy, advances in adult learning, and practice in adult learning. The following are among the topics discussed in the book's 17 chapters: importance of learning theory; theories of learning (concept of part and whole models of development, theories based on elemental…

  20. Adult somatic stem cells in the human parasite, Schistosoma mansoni

    PubMed Central

    Collins, James J.; Wang, Bo; Lambrus, Bramwell G.; Tharp, Marla; Iyer, Harini; Newmark, Phillip A.

    2013-01-01

    Summary Schistosomiasis is among the most prevalent human parasitic diseases, affecting more than 200 million people worldwide1. The etiological agents of this disease are trematode flatworms (Schistosoma) that live and lay eggs within the vasculature of the host. These eggs lodge in host tissues, causing inflammatory responses that are the primary cause of morbidity. Because these parasites can live and reproduce within human hosts for decades2, elucidating the mechanisms that promote their longevity is of fundamental importance. Although adult pluripotent stem cells, called neoblasts, drive long-term homeostatic tissue maintenance in long-lived free-living flatworms3,4 (e.g., planarians), and neoblast-like cells have been described in some parasitic tapeworms5, little is known about whether similar cell types exist in any trematode species. Here, we describe a population of neoblast-like cells in the trematode Schistosoma mansoni. These cells resemble planarian neoblasts morphologically and share their ability to proliferate and differentiate into derivatives of multiple germ layers. Capitalizing on available genomic resources6,7 and RNAseq-based gene expression profiling, we find that these schistosome neoblast-like cells express a fibroblast growth factor receptor ortholog. Using RNA interference we demonstrate that this gene is required for the maintenance of these neoblast-like cells. Our observations suggest that adaptation of developmental strategies shared by free-living ancestors to modern-day schistosomes likely contributed to the success of these animals as long-lived obligate parasites. We expect that future studies deciphering the function of these neoblast-like cells will have important implications for understanding the biology of these devastating parasites. PMID:23426263

  1. Extra-articular Manifestations in Rheumatoid Arthritis

    PubMed Central

    Cojocaru, Manole; Cojocaru, Inimioara Mihaela; Silosi, Isabela; Vrabie, Camelia Doina; Tanasescu, R

    2010-01-01

    ABSTRACT Rheumatoid arthritis (RA) is a systemic autoimmune disease whose main characteristic is persistent joint inflammation that results in joint damage and loss of function. Although RA is more common in females, extra-articular manifestations of the disease are more common in males. The extra-articular manifestations of RA can occur at any age after onset. It is characterised by destructive polyarthritis and extra-articular organ involvement, including the skin, eye, heart, lung, renal, nervous and gastrointestinal systems. The frequence of extra-articular manifestations in RA differs from one country to another. Extra-articular organ involvement in RA is more frequently seen in patients with severe, active disease and is associated with increased mortality. Incidence and frequence figures for extra-articular RA vary according to study design. Extra-articular involvement is more likely in those who have RF and/or are HLA-DR4 positive. Occasionally, there are also systemic manifestations such as vasculitis, visceral nodules, Sjögren's syndrome, or pulmonary fibrosis present. Nodules are the most common extra-articular feature, and are present in up to 30%; many of the other classic features occur in 1% or less in normal clinic settings. Sjögren's syndrome, anaemia of chronic disease and pulmonary manifestations are relatively common – in 6-10%, are frequently present in early disease and are all related to worse outcomes measures of rheumatoid disease in particular functional impairment and mortality. The occurrence of these systemic manifestations is a major predictor of mortality in patients with RA. This paper focuses on extra-articular manifestations, defined as diseases and symptoms not directly related to the locomotor system. PMID:21977172

  2. Metric analysis of basal sphenoid angle in adult human skulls

    PubMed Central

    Netto, Dante Simionato; Nascimento, Sergio Ricardo Rios; Ruiz, Cristiane Regina

    2014-01-01

    Objective To analyze the variations in the angle basal sphenoid skulls of adult humans and their relationship to sex, age, ethnicity and cranial index. Methods The angles were measured in 160 skulls belonging to the Museum of the Universidade Federal de São Paulo Department of Morphology. We use two flexible rules and a goniometer, having as reference points for the first rule the posterior end of the ethmoidal crest and dorsum of the sella turcica, and for the second rule the anterior margin of the foramen magnum and clivus, measuring the angle at the intersection of two. Results The average angle was 115.41°, with no statistical correlation between the value of the angle and sex or age. A statistical correlation was noted between the value of the angle and ethnicity, and between the angle and the horizontal cranial index. Conclusions The distribution of the angle basal sphenoid was the same in sex, and there was correlation between the angle and ethnicity, being the proportion of non-white individuals with an angle >125° significantly higher than that of whites with an angle >125°. There was correlation between the angle and the cranial index, because skulls with higher cranial index tend to have higher basiesfenoidal angle too. PMID:25295452

  3. Degenerative lesions in the articular cartilage after meniscectomy: preliminary experimental study in dogs.

    PubMed

    Berjon, J J; Munuera, L; Calvo, M

    1991-03-01

    Articular cartilage degeneration was studied in an experimental model including 68 knees of adult dogs on which five different types of medial meniscectomy had been performed with a followup period of 10 to 450 days. The results were assessed by macroscopic, radiologic, and histologic methods. The degenerative lesions increased proportionally to the amount of meniscal tissue resected and the duration of observation. These lesions proved to be more intense at the tibial plateau compared to the femoral condyle. For both joint surfaces the predominant location was the central zone. Considering the degenerative process by the articular cartilage after total meniscectomy, maximum preservation of meniscal tissue is recommended. PMID:2002520

  4. Proteoglycans of human articular cartilage. Identification of several populations of large and small proteoglycans and of hyaluronic acid-binding proteins in successive cartilage extracts.

    PubMed Central

    Vilim, V; Krajickova, J

    1991-01-01

    Two specimens of human articulage were successively extracted with solutions of phosphate-buffered saline (PBS), 7 M-urea and 4 M-guanidine hydrochloride (Gdn-HCl). Proteoglycans from individual extracts were fractionated by DEAE-Sephacel chromatography and gel chromatography on Sephacryl S-400. The presence of three populations of large proteoglycans was demonstrated in all three extracts by composite agarose/polyacrylamide-gel electrophoresis (CAPAGE). The population corresponding to the fastest CAPAGE band of aggregating proteoglycans was shown to be extremely polydisperse, having Mr (as estimated by SDS/PAGE) decreasing continuously from more than 300,000 to the size corresponding to 'free' hyaluronic acid-binding region (HABR) (about 70,000). A rather polydisperse set of HABR-containing fragments which spanned a broad range of sizes, and also differed in their keratan sulphate contents, was isolated from both 7 M-urea and 4 M-Gdn-HCl extracts. PBS and 7 M-urea extracts, but not the Gdn-HCl extract, further contained small proteoglycans, identified as fast-migrating bands on CAPAGE electrophoretograms. One of those small species was recognized with an antibody against the small proteoglycan PG II; the other two remain to be positively identified. However, the glycosaminoglycan of the small species which was present exclusively in the PBS extract was identified as keratan sulphate; this species may thus belong to the family of small keratan sulphate-containing proteolygans. Images Fig. 4. Fig. 5. Fig. 6. Fig. 7. PMID:1705114

  5. PEP-1-FK506BP12 inhibits matrix metalloproteinase expression in human articular chondrocytes and in a mouse carrageenan-induced arthritis model

    PubMed Central

    Hwang, Hyun Sook; Park, In Young; Kim, Dae Won; Choi, Soo Young; Jung, Young Ok; Kim, Hyun Ah

    2015-01-01

    The 12 kDa FK506-binding protein (FK506BP12), an immunosuppressor, modulates T cell activation via calcineurin inhibition. In this study, we investigated the ability of PEP-1-FK506BP12, consisting of FK506BP12 fused to the protein transduction domain PEP-1 peptide, to suppress catabolic responses in primary human chondrocytes and in a mouse carrageenan-induced paw arthritis model. Western blotting and immunofluorescence analysis showed that PEP-1-FK506BP12 efficiently penetrated chondrocytes and cartilage explants. In interleukin-1β (IL-1β)-treated chondrocytes, PEP-1-FK506BP12 significantly suppressed the expression of catabolic enzymes, including matrix metalloproteinases (MMPs)-1, -3, and -13 in addition to cyclooxygenase-2, at both the mRNA and protein levels, whereas FK506BP12 alone did not. In addition, PEP-1-FK506BP12 decreased IL-1β-induced phosphorylation of the mitogen-activated protein kinase (MAPK) complex (p38, JNK, and ERK) and the inhibitor kappa B alpha. In the mouse model of carrageenan-induced paw arthritis, PEP-1-FK506BP12 suppressed both carrageenan-induced MMP-13 production and paw inflammation. PEP-1-FK506BP12 may have therapeutic potential in the alleviation of OA progression. [BMB Reports 2015; 48(7): 407-412] PMID:25887750

  6. PEP-1-FK506BP12 inhibits matrix metalloproteinase expression in human articular chondrocytes and in a mouse carrageenan-induced arthritis model.

    PubMed

    Hwang, Hyun Sook; Park, In Young; Kim, Dae Won; Choi, Soo Young; Jung, Young Ok; Kim, Hyun Ah

    2015-07-01

    The 12 kDa FK506-binding protein (FK506BP12), an immunosuppressor, modulates T cell activation via calcineurin inhibition. In this study, we investigated the ability of PEP-1-FK506BP12, consisting of FK506BP12 fused to the protein transduction domain PEP-1 peptide, to suppress catabolic responses in primary human chondrocytes and in a mouse carrageenan-induced paw arthritis model. Western blotting and immunofluorescence analysis showed that PEP-1-FK506BP12 efficiently penetrated chondrocytes and cartilage explants. In interleukin-1β (IL-1β)-treated chondrocytes, PEP-1-FK506BP12 significantly suppressed the expression of catabolic enzymes, including matrix metalloproteinases (MMPs)-1, -3, and -13 in addition to cyclooxygenase-2, at both the mRNA and protein levels, whereas FK506BP12 alone did not. In addition, PEP-1-FK506BP12 decreased IL-1β-induced phosphorylation of the mitogen-activated protein kinase (MAPK) complex (p38, JNK, and ERK) and the inhibitor kappa B alpha. In the mouse model of carrageenan-induced paw arthritis, PEP-1-FK506BP12 suppressed both carrageenan-induced MMP-13 production and paw inflammation. PEP-1-FK506BP12 may have therapeutic potential in the alleviation of OA progression. PMID:25887750

  7. Effects of vimentin disruption on the mechanoresponses of articular chondrocyte.

    PubMed

    Chen, Cheng; Yin, Li; Song, Xiongbo; Yang, Hao; Ren, Xiang; Gong, Xiaoyuan; Wang, Fuyou; Yang, Liu

    2016-01-01

    Human articular cartilage is subjected to repetitive mechanical loading during life time. As the only cellular component of articular cartilage, chondrocytes play a key role in the mechanotransduction within this tissue. The mechanoresponses of chondrocytes are largely determined by the cytoskeleton. Vimentin intermediate filaments, one of the major cytoskeletal components, have been shown to regulate chondrocyte phenotype. However, the contribution of vimentin in chondrocyte mechanoresponses remains less studied. In this study, we seeded goat articular chondrocytes on a soft polyacrylamide gel, and disrupted the vimentin cytoskeleton using acrylamide. Then we applied a transient stretch or compression to the cells, and measured the changes of cellular stiffness and traction forces using Optical Magnetic Twisting Cytometry and Traction Force Microscopy, respectively. In addition, to study the effects of vimentin disruption on the intracellular force generation, we treated the cells with a variety of reagents that are known to increase or decrease cytoskeletal tension. We found that, after a compression, the contractile moment and cellular stiffness were not affected in untreated chondrocytes, but were decreased in vimentin-disrupted chondrocytes; after a stretch, vimentin-disrupted chondrocytes showed a lower level of fluidization-resolidification response compared to untreated cells. Moreover, vimentin-disrupted chondrocytes didn't show much difference to control cells in responding to reagents that target actin and ROCK pathway, but showed a weaker response to histamine and isoproterenol. These findings confirmed chondrocyte vimentin as a major contributor in withstanding compressive loading, and its minor role in regulating cytoskeletal tension. PMID:26616052

  8. Supporting Biomaterials for Articular Cartilage Repair

    PubMed Central

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

    2012-01-01

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

  9. Electrochemically Preadsorbed Collagen Promotes Adult Human Mesenchymal Stem Cell Adhesion.

    PubMed

    Benavidez, Tomás E; Wechsler, Marissa E; Farrer, Madeleine M; Bizios, Rena; Garcia, Carlos D

    2016-01-01

    The present article reports on the effect of electric potential on the adsorption of collagen type I (the most abundant component of the organic phase of bone) onto optically transparent carbon electrodes (OTCE) and its mediation on subsequent adhesion of adult, human, mesenchymal stem cells (hMSCs). For this purpose, adsorption of collagen type I was investigated as a function of the protein concentration (0.01, 0.1, and 0.25 mg/mL) and applied potential (open circuit potential [OCP; control], +400, +800, and +1500 mV). The resulting substrate surfaces were characterized using spectroscopic ellipsometry, atomic force microscopy, and cyclic voltammetry. Adsorption of collagen type I onto OTCE was affected by the potential applied to the sorbent surface and the concentration of protein. The higher the applied potential and protein concentration, the higher the adsorbed amount (Γcollagen). It was also observed that the application of potential values higher than +800 mV resulted in the oxidation of the adsorbed protein. Subsequent adhesion of hMSCs on the OTCEs (precoated with the collagen type I films) under standard cell culture conditions for 2 h was affected by the extent of collagen preadsorbed onto the OTCE substrates. Specifically, enhanced hMSCs adhesion was observed when the Γcollagen was the highest. When the collagen type I was oxidized (under applied potential equal to +1500 mV), however, hMSCs adhesion was decreased. These results provide the first correlation between the effects of electric potential on protein adsorption and subsequent modulation of anchorage-dependent cell adhesion. PMID:26549607

  10. Characterization of cutaneous and articular sensory neurons

    PubMed Central

    da Silva Serra, Ines; Husson, Zoé; Bartlett, Jonathan D.

    2016-01-01

    Background A wide range of stimuli can activate sensory neurons and neurons innervating specific tissues often have distinct properties. Here, we used retrograde tracing to identify sensory neurons innervating the hind paw skin (cutaneous) and ankle/knee joints (articular), and combined immunohistochemistry and electrophysiology analysis to determine the neurochemical phenotype of cutaneous and articular neurons, as well as their electrical and chemical excitability. Results Immunohistochemistry analysis using RetroBeads as a retrograde tracer confirmed previous data that cutaneous and articular neurons are a mixture of myelinated and unmyelinated neurons, and the majority of both populations are peptidergic. In whole-cell patch-clamp recordings from cultured dorsal root ganglion neurons, voltage-gated inward currents and action potential parameters were largely similar between articular and cutaneous neurons, although cutaneous neuron action potentials had a longer half-peak duration (HPD). An assessment of chemical sensitivity showed that all neurons responded to a pH 5.0 solution, but that acid-sensing ion channel (ASIC) currents, determined by inhibition with the nonselective acid-sensing ion channel antagonist benzamil, were of a greater magnitude in cutaneous compared to articular neurons. Forty to fifty percent of cutaneous and articular neurons responded to capsaicin, cinnamaldehyde, and menthol, indicating similar expression levels of transient receptor potential vanilloid 1 (TRPV1), transient receptor potential ankyrin 1 (TRPA1), and transient receptor potential melastatin 8 (TRPM8), respectively. By contrast, significantly more articular neurons responded to ATP than cutaneous neurons. Conclusion This work makes a detailed characterization of cutaneous and articular sensory neurons and highlights the importance of making recordings from identified neuronal populations: sensory neurons innervating different tissues have subtly different properties

  11. A comparison of erythrocyte glutathione S-transferase activity from human foetuses and adults.

    PubMed Central

    Strange, R C; Johnston, J D; Coghill, D R; Hume, R

    1980-01-01

    Glutathione S-transferase activity was measured in partially purified haemolysates of erythrocytes from human foetuses and adults. Enzyme activity was present in erythrocytes obtained between 12 and 40 weeks of gestation. The catalytic properties of the enzyme from foetal cells were similar to those of the enzyme from adult erythrocytes, indicating that probably only one form of the erythrocytes enzyme exists throughout foetal and adult life. PMID:7396875

  12. Human paraoxonase polymorphism: Hungarian population studies in children and adults.

    PubMed

    Szabó, I; Róna, K; Czinner, A; Gachályi, B

    1991-06-01

    The paraoxonase phenotype distribution pattern was studied in a Hungarian population of 102 children and 100 adults. All the subjects were of Caucasian origin and are not related. The adult population showed the trimodality in phenotype distribution similar to other European population data. The gene frequencies obtained were statistically not significantly different either. There was no correlation between the activity of serum paraoxonase and activity of cholinesterase, sex, age and body weight. The phenotype distribution was trimodal in the children's population too. There was a significant difference in gene frequency, however, compared to data from adult population. PMID:1651288

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

    NASA Technical Reports Server (NTRS)

    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.

  14. Reaching beyond the United States: Adventures in International Adult Education and Human Resource Development

    ERIC Educational Resources Information Center

    Henschke, John A.

    2005-01-01

    In this article, the author shares his experience of how travel and adult education merged, for him, into a major emphasis in international adult education (AE) and human resource development (HRD). International ventures have been some of the most exciting and learning-filled aspects of the author's career in AE and HRD. His involvement in…

  15. Adult Continuing Education and Human Resource Development: Present Competitors, Potential Partners

    ERIC Educational Resources Information Center

    Smith, Douglas H.

    2006-01-01

    Adult Continuing Education (ACE) and Human Resource Development (HRD) have grown tremendously in the last quarter century. ACE experienced tremendous growth in the 60s and 70s, with over 17 million attending colleges and universities, and local school and community adult education programs by the end of the 1970s. More ACE programs were started…

  16. Articular cartilage: structure and regeneration.

    PubMed

    Becerra, José; Andrades, José A; Guerado, Enrique; Zamora-Navas, Plácido; López-Puertas, José M; Reddi, A Hari

    2010-12-01

    Articular cartilage (AC) has no or very low ability of self-repair, and untreated lesions may lead to the development of osteoarthritis. One method that has been proven to result in long-term repair or isolated lesions is autologous chondrocyte transplantation. However, first generation of these cells' implantation has limitations, and introducing new effective cell sources can improve cartilage repair. AC provides a resilient and compliant articulating surface to the bones in diarthrodial joints. It protects the joint by distributing loads applied to it, so preventing potentially damaging stress concentrations on the bone. At the same time it provides a low-friction-bearing surface to enable free movement of the joint. AC may be considered as a visco- or poro-elastic fiber-composite material. Fibrils of predominantly type II collagen provide tensile reinforcing to a highly hydrated proteoglycan gel. The tissue typically comprises 70% water and it is the structuring and retention of this water by the proteoglycans and collagen that is largely responsible for the remarkable ability of the tissue to support compressive loads. PMID:20836752

  17. Newborn human skin fibroblasts senesce in vitro without acquiring adult growth factor requirements

    SciTech Connect

    Wharton, W.

    1984-01-01

    Cultures of human fibroblasts were prepared from chest skin obtained either from newborns (less than 3 months old) or adults (more than 35 years old) and maintained in vitro until they senesced. Adult cells grew logarithmically in medium supplemented with whole blood serum but not with platelet-poor plasma. Early passage cells obtained from newborns grew equally well in either plasma- or serum-supplemented medium. The difference in growth factor requirements between adult and newborn cells persisted through the lifespan of the cells; i.e., newborn cells did not develop adult hormonal requirements when maintained in culture. Thus, in vitro cellular aging can be distinguished from some types of differentiation.

  18. In vitro generation of mechanically functional cartilage grafts based on adult human stem cells and 3D-woven poly(ε-caprolactone) scaffolds

    PubMed Central

    Valonen, P.K.; Moutos, F.T.; Kusanagi, A.; Moretti, M.; Diekman, B.O.; Welter, J.F.; Caplan, A.I.; Guilak, F.

    2009-01-01

    Three-dimensionally woven poly(ε-caprolactone)(PCL) scaffolds were combined with adult human mesenchymal stem cells (hMSC) to engineer mechanically functional cartilage constructs in vitro. The specific objectives were to: (i) produce PCL scaffolds with cartilage-like mechanical properties, (ii) demonstrate that hMSCs formed cartilage after 21-days of culture on PCL scaffolds, and (iii) study effects of scaffold structure (loosely vs. tightly woven), culture vessel (static dish vs. oscillating bioreactor), and medium composition (chondrogenic additives with or without serum). Aggregate moduli of 21-day constructs approached normal articular cartilage for tightly woven PCL cultured in bioreactors, were lower for tightly woven PCL cultured statically, and lowest for loosely woven PCL cultured statically (p<0.05). Construct DNA, total collagen, and glyocosaminoglycans (GAG) increased in a manner dependent on time, culture vessel, and medium composition. Chondrogenesis was verified histologically by rounded cells within a hyaline-like matrix that immunostained for collagen type II but not type I. Bioreactors yielded constructs with higher collagen content (p<0.05) and more homogenous matrix than static controls. Chondrogenic additives yielded constructs with higher GAG (p<0.05) and earlier expression of collagen II mRNA if serum was not present in medium. These results show feasibility of functional cartilage tissue engineering from hMSC and 3D woven PCL scaffolds. PMID:20034665

  19. Inhibition of β-Catenin Signaling in Articular Chondrocytes Results in Articular Cartilage Destruction

    PubMed Central

    Zhu, Mei; Chen, Mo; Zuscik, Michael; Wu, Qiuqian; Wang, Yong-Jun; Rosier, Randy N.; O’Keefe, Regis J.; Chen, Di

    2009-01-01

    Objective Osteoarthritis is a degenerative joint disease whose molecular mechanism is currently unknown. Wnt/β-catenin signaling has been demonstrated to play a critical role in the development and function of articular chondrocytes. To determine the role of β-catenin signaling in articular chondrocyte function, we generated Col2a1-ICAT–transgenic mice to inhibit β-catenin signaling in chondrocytes. Methods The expression of the ICAT transgene was determined by immunostaining and Western blot analysis. Histologic analyses were performed to determine changes in articular cartilage structure and morphology. Cell apoptosis was determined by TUNEL staining and the immunostaining of cleaved caspase 3 and poly(ADP-ribose) polymerase (PARP) proteins. Expression of Bcl-2, Bcl-xL, and Bax proteins and caspase 9 and caspase 3/7 activities were examined in primary sternal chondrocytes isolated from 3-day-old neonatal Col2a1-ICAT–transgenic mice and their wild-type littermates and in primary chicken and porcine articular chondrocytes. Results Expression of the ICAT transgene was detected in articular chondrocytes of the transgenic mice. Associated with this, age-dependent articular cartilage destruction was observed in Col2a1-ICAT– transgenic mice. A significant increase in cell apoptosis in articular chondrocytes was identified by TUNEL staining and the immunostaining of cleaved caspase 3 and PARP proteins in these transgenic mice. Consistent with this, Bcl-2 and Bcl-xL expression were decreased and caspase 9 and caspase 3/7 activity were increased, suggesting that increased cell apoptosis may contribute significantly to the articular cartilage destruction observed in Col2a1-ICAT–transgenic mice. Conclusion Inhibition of β-catenin signaling in articular chondrocytes causes increased cell apoptosis and articular cartilage destruction in Col2a1-ICAT–transgenic mice. PMID:18576323

  20. Articular chondrocyte metabolism and osteoarthritis

    SciTech Connect

    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.

  1. Intra-articular therapy in osteoarthritis

    PubMed Central

    Uthman, I; Raynauld, J; Haraoui, B

    2003-01-01

    The medical literature was reviewed from 1968–2002 using Medline and the key words "intra-articular" and "osteoarthritis" to determine the various intra-articular therapies used in the treatment of osteoarthritis. Corticosteroids and hyaluronic acid are the most frequently used intra-articular therapies in osteoarthritis. Other intra-articular substances such as orgotein, radiation synovectomy, dextrose prolotherapy, silicone, saline lavage, saline injection without lavage, analgesic agents, non-steroidal anti-inflammatory drugs, glucosamine, somatostatin, sodium pentosan polysulfate, chloroquine, mucopolysaccharide polysulfuric acid ester, lactic acid solution, and thiotepa cytostatica have been investigated as potentially therapeutic in the treatment of arthritic joints. Despite the lack of strong, convincing, and reproducible evidence that any of the intra-articular therapies significantly alters the progression of osteoarthritis, corticosteroids and hyaluronic acid are widely used in patients who have failed other therapeutic modalities for lack of efficacy or toxicity. As a practical approach for a knee with effusion, steroid injections should be considered while the presence of symptomatic "dry" knees may favour the hyaluronic acid approach. The virtual absence of serious side effects, coupled with the perceived benefits, make these approaches attractive. PMID:12954956

  2. Corporate Human Resources Adult Training and Employment Program Description.

    ERIC Educational Resources Information Center

    Aetna Life and Casualty, Hartford, CT.

    In response to increasing difficulty in finding qualified candidates for entry-level positions, the Aetna company has developed an Adult Training and Employment program. This program (1) trains, hires, and retains nontraditional candidates from the area's public and private agencies; (2) focuses on issues that affect this population's ability to…

  3. The Human Function Compunction: Teleological Explanation in Adults

    ERIC Educational Resources Information Center

    Kelemen, Deborah; Rosset, Evelyn

    2009-01-01

    Research has found that children possess a broad bias in favor of teleological--or purpose-based--explanations of natural phenomena. The current two experiments explored whether adults implicitly possess a similar bias. In Study 1, undergraduates judged a series of statements as "good" (i.e., correct) or "bad" (i.e., incorrect) explanations for…

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

    ERIC Educational Resources Information Center

    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…

  5. Adult Literacy Programs in Uganda. Africa Region Human Development Series.

    ERIC Educational Resources Information Center

    Okech, Anthony; Carr-Hill, Roy A.; Katahoire, Anne R.; Kakooza, Teresa; Ndidde, Alice N.; Oxenham, John

    This report evaluates the outcomes and cost effectiveness of adult literacy programs in Ugandan villages and compares government programs with those provided by nongovernmental organizations (NGOs). Part 1 describes evaluation objectives, government and NGO literacy programs and the rural socioeconomic context, and evaluation design. About 100…

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

    ERIC Educational Resources Information Center

    Choy, Sarojni; Haukka, Sandra

    2007-01-01

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

  7. Changes in permeability of rabbit articular cartilage caused by joint contracture as revealed by the peroxidase method.

    PubMed

    Nakamura, K; Ohta, N; Kawaji, W; Takata, K; Hirano, H

    1984-11-01

    Changes in permeability of adult rabbit articular cartilage caused by joint contracture were studied by light and transmission electron microscopy, employing horseradish peroxidase (HRP) as an indicator. The knee joint was plaster-immobilized for 0, 2, 4, 6, or 8 weeks in the flexion position. One ml of 4% HRP was administered in the articular cavity of the knee joint and allowed to diffuse and permeate into the articular cartilage. Distribution of the permeated HRP was visualized in the cartilage taken from the lateral condyle of the femur, utilizing the DAB-H2O2 reaction. In the normal and the non-immobilized joints, the permeated HRP reached to the matrix and chondrocytes situated in the deep layer of the articular cartilage. HRP was heavily deposited in the intercellular matrices, particularly around the chondrocytes, and was actively endocytosed by these cells. In the plaster-immobilized joints, especially after 4 weeks or longer of immobilization, the administered HRP had not permeated well and was restricted to the surface (lamina splendens) and the superficial layer of the cartilage. These results show that administered HRP diffuses into the deep layer of the articular cartilage and is actively endocytosed by chondrocytes and that the permeability of articular cartilage is remarkably reduced by joint contracture. PMID:6532371

  8. Searching for the vomeronasal organ of adult humans: preliminary findings on location, structure, and size.

    PubMed

    Smith, T D; Siegel, M I; Burrows, A M; Mooney, M P; Burdi, A R; Fabrizio, P A; Clemente, F R

    1998-06-15

    The adult human vomeronasal organ (VNO) has been the focus of numerous recent investigations, yet its developmental continuity from the human fetal VNO is poorly understood. The present study compared new data on the adult human "VNO" with previous findings on the fetal human VNO. Nasal septa were removed from twelve adult human cadavers and each specimen was histologically sectioned. Coronal sections were stained with hematoxylin-eosin and periodic acid-Schiff-hematoxylin. The sections were examined by light microscopy for the presence of VNOs and the anterior paraseptal cartilages (PC). VNOs were quantified using a computer reconstruction technique to obtain VNO length, volume, and vomeronasal epithelium (VNE) volume. Histologically, VNOs and PCs were identified in eleven specimens. VNOs had ciliated, pseudostratified columnar epithelium with goblet cells. Variations (e.g., multiple communications to the nasal cavity) were observed in several specimens. Quantification was possible for 16 right or left VNOs. Right or left VNOs ranged from 3.5 to 11.8 mm in length, from 1.8 to 33.8 x 10(-4)cc in volume, and from 2.7 to 18.1 x 10(-4)cc in VNE volume. Results indicated that the adult human VNO was similar in VNE morphology, lumen shape, and spatial relationships when compared to human fetal VNOs. By comparison with previous fetal VNO measures, mean VNO length, volume, and VNE volume were larger in adult humans. These results support previous suggestions that postnatal VNO growth occurs. Findings on location and spatial relationships of the adult VNO were similar to those seen in human fetuses, but critical questions remain regarding the ontogeny of the vomeronasal nerves and VNE. PMID:9712196

  9. Radiation synovectomy stimulates glycosaminoglycan synthesis by normal articular cartilage

    SciTech Connect

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

    1989-07-01

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

  10. Teaching Adults with Learning Disabilities. Professional Practices in Adult Education and Human Resource Development Series.

    ERIC Educational Resources Information Center

    Jordan, Dale R.

    This book is designed to show teachers how to reach out to adults and adolescents with learning disabilities and employ specific strategies for helping them to compensate for the disabilities and acquire literacy skills. The ways in which specific differences in brain structure inhibit the mastery of reading, spelling, handwriting, phonics, and…

  11. Arts and Humanities in Adult and Continuing Education. Trends and Issues Alerts.

    ERIC Educational Resources Information Center

    Kerka, Sandra

    Trends and issues related to arts and humanities in adult and continuing education can be categorized in three ways: ways of knowing, informal sites of learning, and cultural pluralism. The arts and humanities are vehicles for critical reflection, and they present paths to the individual construction of knowledge that are intuitive, relational,…

  12. Actions of Two Bi-Articular Muscles of the Lower Extremity: A Review

    PubMed Central

    Landin, Dennis; Thompson, Melissa; Reid, Meghan

    2016-01-01

    The extremities of the human body contain several bi-articular muscles. The actions produced by muscles at the joints they cross are greatly influenced by joint moment arms and muscle length. These factors are dynamic and subject to change as joint angles are altered. Therefore, to more completely understand the actions of such muscles, the angles of both joints must be manipulated. This report reviews investigations, which have explored the actions of two bi-articular muscles of the lower extremities (gastrocnemius and rectus femoris) as the joints they cross are moved into various combinations of angles. The findings have both clinical and physical performance ramifications. PMID:27298656

  13. Actions of Two Bi-Articular Muscles of the Lower Extremity: A Review.

    PubMed

    Landin, Dennis; Thompson, Melissa; Reid, Meghan

    2016-07-01

    The extremities of the human body contain several bi-articular muscles. The actions produced by muscles at the joints they cross are greatly influenced by joint moment arms and muscle length. These factors are dynamic and subject to change as joint angles are altered. Therefore, to more completely understand the actions of such muscles, the angles of both joints must be manipulated. This report reviews investigations, which have explored the actions of two bi-articular muscles of the lower extremities (gastrocnemius and rectus femoris) as the joints they cross are moved into various combinations of angles. The findings have both clinical and physical performance ramifications. PMID:27298656

  14. The human function compunction: teleological explanation in adults.

    PubMed

    Kelemen, Deborah; Rosset, Evelyn

    2009-04-01

    Research has found that children possess a broad bias in favor of teleological--or purpose-based--explanations of natural phenomena. The current two experiments explored whether adults implicitly possess a similar bias. In Study 1, undergraduates judged a series of statements as "good" (i.e., correct) or "bad" (i.e., incorrect) explanations for why different phenomena occur. Judgments occurred in one of three conditions: fast speeded, moderately speeded, or unspeeded. Participants in speeded conditions judged significantly more scientifically unwarranted teleological explanations as correct (e.g., "the sun radiates heat because warmth nurtures life"), but were not more error-prone on control items (e.g., unwarranted physical explanations such as "hills form because floodwater freezes"). Study 2 extended these findings by examining the relationship between different aspects of adults' "promiscuous teleology" and other variables such as scientific knowledge, religious beliefs, and inhibitory control. Implications of these findings for scientific literacy are discussed. PMID:19200537

  15. Postnatal and adult neurogenesis in the development of human disease.

    PubMed

    Danzer, Steve C

    2008-10-01

    The mammalian brain contains a population of neurons that are continuously generated from late embryogenesis through adulthood-after the generation of almost all other neuronal types. This brain region-the hippocampal dentate gyrus-is in a sense, therefore, persistently immature. Postnatal and adult neurogenesis is likely an essential feature of the dentate, which is critical for learning and memory. Protracted neurogenesis after birth would allow the new cells to develop in conjunction with external events-but it may come with a price: while neurogenesis in utero occurs in a protected environment, children and adults are exposed to any number of hazards, such as toxins and infectious agents. Mature neurons might be resistant to such exposures, but new neurons may be vulnerable. Consistent with this prediction, in adult rodents seizures disrupt the integration of newly generated granule cells, whereas mature granule cells are comparatively unaffected. Significantly, abnormally interconnected cells may contribute to epileptogenesis and/or associated cognitive and memory deficits. Finally, studies increasingly indicate that new granule cells are extremely sensitive to a host of endogenous and exogenous factors, raising the possibility that disrupted granule cell integration may be a common feature of many neurological diseases. PMID:18997123

  16. The Adult Learning Disabled Employee: The Organization's Hidden Human Resource.

    ERIC Educational Resources Information Center

    Macomber, Janet A.

    This paper describes an experiment with background material designed to promote problem (learning disabled) employees as human resources rather than rejects. The material is presented in the form of the transcript of a fictional advisory committee meeting attended by the human resources manager, assistant corporate counsel, training director, line…

  17. The expression of c-kit protein in human adult and fetal tissues.

    PubMed

    Horie, K; Fujita, J; Takakura, K; Kanzaki, H; Suginami, H; Iwai, M; Nakayama, H; Mori, T

    1993-11-01

    The c-kit proto-oncogene encodes a tyrosine kinase receptor and is allelic with the dominant white-spotting (W) locus of the mouse. In this study we investigated the expression of human c-kit protein in various adult and fetal human tissues immunohistochemically using anti-human c-kit monoclonal antibody. To discriminate c-kit+ cells from mast cells expressing c-kit, mast cells were identified by staining with Toluidine blue. In oogonia, spermatogonia and skin melanocytes of the fetus and in oocytes of adult ovary, c-kit expression was detected. In adult uterus, c-kit+ cells were widely distributed in the basal layer of the endometrium, myometrium and cervix, the number and distribution being almost identical to those of mast cells. In fetal uterus, c-kit+ non-mast cells clustered beneath the epithelium and a few mast cells were observed in the myometrium and subserosal layer. In both adult and fetus, c-kit+ non-mast cells were detected within smooth muscle layers of the intestine, colon and oesophagus, while mast cells were observed in the mucosal and submucosal layers of these organs. In contrast to mice, no expression of c-kit protein was detected in the human placenta and decidua. Thus, the distribution of c-kit+ cells in various tissues is similar but not identical between adult and fetus and between human and mouse. PMID:7507133

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

    NASA Astrophysics Data System (ADS)

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

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

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

    PubMed Central

    Alibardi, Lorenzo

    2015-01-01

    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. PMID:26340619

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

    PubMed Central

    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

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

    PubMed

    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

  2. [Dietary phytoestrogen and its potential benefits in adult human health].

    PubMed

    Garrido, Argelia; de la Maza, María Pía; Valladares, Luis

    2003-11-01

    Human diet contains a series of bioactive vegetal compounds that can improve human health. Among these, there has been a special interest for phytoestrogens. This article reviews the evidence about the potential benefits of phytoestrogens for human health. Forty eight manuscripts were selected for their study design and relevance to human health. The cell growth inhibitory effects of phytoestrogens and their implication in breast cancer are reviewed. Also the effects of these compounds on serum lipid levels and the effectiveness of a phytoestrogen derivate, ipriflavone, on the prevention of osteoporosis are analyzed. Although these compounds have a great potential for improving health, there is still not enough evidence to recommend the routine use of phytoestrogens. PMID:14743696

  3. Intra-articular risks of suprapatellar nailing.

    PubMed

    Beltran, Michael J; Collinge, Cory A; Patzkowski, Jeanne C; Masini, Brendan D; Blease, Robert E; Hsu, Joseph R

    2012-12-01

    To determine the risks to local anatomy near the starting point for tibial nailing during suprapatellar nailing, 15 fresh-frozen hemipelvis specimens were nailed using a suprapatellar technique. After nail passage, the menisci and articular surfaces, anterior cruciate ligament (ACL) insertion, intermeniscal ligament, and fat pad were assessed for injury. The distance from the entry portal to the menisci, articular surfaces, and ACL insertion was determined. Medial meniscus injury occurred in 1 (6.7%) specimen and medial articular injury in 2 (13%). Nails passed through the fat pad in all specimens; intermeniscal ligament injury occurred in 3 (20%) specimens. The ACL insertion and lateral structures were not injured in any specimen. The distance from the entry portal margin to the lateral and medial menisci was 6.46±2.47 mm and 4.74±3.17 mm, respectively. The distances to the lateral and medial articular margins measured 10.33±3.62 mm and 6.54±3.57 mm, respectively. The distance to the ACL insertion averaged 5.80±3.94 mm. Suprapatellar nailing is associated with a risk of injury to anterior knee structures comparable to other nailing techniques. Additional clinical studies are warranted to further define the role of this technique in the management of tibial fractures. PMID:23550286

  4. A century of trends in adult human height.

    PubMed

    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, 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. PMID:27458798

  5. A century of trends in adult human height

    PubMed Central

    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, 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. DOI: http://dx.doi.org/10.7554/eLife.13410.001 PMID:27458798

  6. Resident aerobic microbiota of the adult human nasal cavity.

    PubMed

    Rasmussen, T T; Kirkeby, L P; Poulsen, K; Reinholdt, J; Kilian, M

    2000-10-01

    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 microbiota was dominated by species of the genera Corynebacterium, Aureobacterium, Rhodococcus, and Staphylococcus, including S. epidermis, S. capitis, S. hominis, S. haemolyticus, S. lugdunensis and S. warneri. These studies show that the microbiota of the nasal cavity of adults is strikingly different from that of the pharynx, and that the nasal cavity is a primary habitat for several species of diphtheroids recognized as opportunistic pathogens. Under special circumstances, single species, including IgA1 protease-producing bacteria, may become predominant in a restricted area of the nasal mucosa. PMID:11200821

  7. Body Weight Independently Affects Articular Cartilage Catabolism

    PubMed Central

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

    2015-01-01

    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 points Walking 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

  8. Immunohistochemical demonstration of fibronectin in the most superficial layer of normal rabbit articular cartilage.

    PubMed Central

    Nishida, K; Inoue, H; Murakami, T

    1995-01-01

    OBJECTIVE--To locate fibronectin ultrastructurally in the most superficial layer of normal articular cartilage of rabbits, in order to clarify its role in joint physiology. METHODS--Articular cartilage was obtained from the femoral condyle of seven normal adult rabbits and prepared by a method that included tannic acid fixation. Polyclonal antibodies against rabbit fibronectin were used in an immunohistochemical electron microscopic study, without any enzymic digestion but with a pre-embedding method for the transmission electron microscopy. RESULTS--The cartilage surface was successfully preserved by tannic acid fixation. The most superficial layer in electron photomicrographs was approximately 200-300 nm thick, cell free, and appeared to have two parallel components: the more superficial lamina and the deeper lamina. Gold labelled fibronectin lined this layer in immunohistochemical electron photomicrographs. CONCLUSIONS--Fibronectin covering the surface of the articular cartilage may have a role in joint lubrication and protection of the cartilage by binding with the collagenous matrix and hyaluronic acid in synovial fluid. Chondroitin sulphates may act as a charge barrier in close relationship with the collagen fibrils in the deeper lamina. Significant alteration in these functions may be one of the first causal steps leading to destruction of the articular cartilage. Images PMID:8546534

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

    PubMed

    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 < 0.01) and 1.1-fold (p < 0.01), respectively, and the corresponding increases in the case of 50 µM HSP were 1.9-fold (p < 0.001) and 1.3-fold (p < 0.001). Therefore, HSP could be considered a valuable photoprotective substance if its capacity to increase melanin production in human melanocyte cultures could be reproduced on human skin. PMID:25765751

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

    PubMed

    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

    2015-07-01

    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

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

    PubMed Central

    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

  12. Multiple cellular and molecular mechanisms are involved in human Aβ clearance by transplanted adult astrocytes.

    PubMed

    Pihlaja, Rea; Koistinaho, Jari; Kauppinen, Riitta; Sandholm, Jouko; Tanila, Heikki; Koistinaho, Milla

    2011-11-01

    Astrocytes and microglia are able to degrade potentially neurotoxic β-amyloid (Aβ) deposits typical for Alzheimer's disease (AD) pathology. Contrary to microglia, astrocytes degrade human Aβ from tissue sections in vitro without any additional stimulation, but it has remained unclear whether transplanted astrocytes are able to clear deposited human Aβ in vivo. We transplanted adult mouse astrocytes into the hippocampi of transgenic mice mimicking AD and observed their fate, effects on microglial responses, and Aβ clearance. After 2-months follow-up time, we discovered a significant reduction in Aβ burden compared with AD mice infused with PBS only. The remaining Aβ deposits were fragmented and most of the Aβ immunoreactivity was seen within the transplanted astrocytes. Concomitant to Aβ reduction, both CD68 and CD45 immunoreactivities were significantly upregulated but phagocytic microglia were often surrounding and engulfing Aβ burdened, TUNEL-positive astrocytes rather than co-localizing with Aβ alone. Astrocytes are known to degrade Aβ also by secreting proteases involved in Aβ catabolism. To study the contribution of neprilysin (NEP), angiotensin-converting enzyme-1 (ACE-1), and endothelin-converting enzyme-2 (ECE-2) in human Aβ clearance, we utilized an ex vivo assay to demonstrate that adult astrocytes respond to human Aβ by upregulating NEP expression. Further, incubation of adult astrocytes with known inhibitors of NEP, ACE-1, or ECE-2 significantly inhibited the removal of human Aβ from the tissue suggesting an important role for these proteases in Aβ clearance by adult astrocytes ex vivo. PMID:21826742

  13. Prospective heterotopic ossification progenitors in adult human skeletal muscle.

    PubMed

    Downey, Jennifer; Lauzier, Dominique; Kloen, Peter; Klarskov, Klaus; Richter, Martin; Hamdy, Reggie; Faucheux, Nathalie; Scimè, Anthony; Balg, Frédéric; Grenier, Guillaume

    2015-02-01

    Skeletal muscle has strong regenerative capabilities. However, failed regeneration can lead to complications where aberrant tissue forms as is the case with heterotopic ossification (HO), in which chondrocytes, osteoblasts and white and brown adipocytes can arise following severe trauma. In humans, the various HO cell types likely originate from multipotent mesenchymal stromal cells (MSCs) in skeletal muscle, which have not been identified in humans until now. In the present study, adherent cells from freshly digested skeletal muscle tissue were expanded in defined culture medium and were FACS-enriched for the CD73(+)CD105(+)CD90(-) population, which displayed robust multilineage potential. Clonal differentiation assays confirmed that all three lineages originated from a single multipotent progenitor. In addition to differentiating into typical HO lineages, human muscle resident MSCs (hmrMSCs) also differentiated into brown adipocytes expressing uncoupling protein 1 (UCP1). Characterizing this novel multipotent hmrMSC population with a brown adipocyte differentiation capacity has enhanced our understanding of the contribution of non-myogenic progenitor cells to regeneration and aberrant tissue formation in human skeletal muscle. PMID:25445454

  14. Testosterone affects language areas of the adult human brain

    PubMed Central

    Hahn, Andreas; Kranz, Georg S.; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F.

    2016-01-01

    Abstract Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high‐dose hormone application in adult female‐to‐male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel‐based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting‐state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone‐dependent neuroplastic adaptations in adulthood within language‐specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738–1748, 2016. © 2016 Wiley Periodicals, Inc. PMID:26876303

  15. Testosterone affects language areas of the adult human brain.

    PubMed

    Hahn, Andreas; Kranz, Georg S; Sladky, Ronald; Kaufmann, Ulrike; Ganger, Sebastian; Hummer, Allan; Seiger, Rene; Spies, Marie; Vanicek, Thomas; Winkler, Dietmar; Kasper, Siegfried; Windischberger, Christian; Swaab, Dick F; Lanzenberger, Rupert

    2016-05-01

    Although the sex steroid hormone testosterone is integrally involved in the development of language processing, ethical considerations mostly limit investigations to single hormone administrations. To circumvent this issue we assessed the influence of continuous high-dose hormone application in adult female-to-male transsexuals. Subjects underwent magnetic resonance imaging before and after 4 weeks of testosterone treatment, with each scan including structural, diffusion weighted and functional imaging. Voxel-based morphometry analysis showed decreased gray matter volume with increasing levels of bioavailable testosterone exclusively in Broca's and Wernicke's areas. Particularly, this may link known sex differences in language performance to the influence of testosterone on relevant brain regions. Using probabilistic tractography, we further observed that longitudinal changes in testosterone negatively predicted changes in mean diffusivity of the corresponding structural connection passing through the extreme capsule. Considering a related increase in myelin staining in rodents, this potentially reflects a strengthening of the fiber tract particularly involved in language comprehension. Finally, functional images at resting-state were evaluated, showing increased functional connectivity between the two brain regions with increasing testosterone levels. These findings suggest testosterone-dependent neuroplastic adaptations in adulthood within language-specific brain regions and connections. Importantly, deteriorations in gray matter volume seem to be compensated by enhancement of corresponding structural and functional connectivity. Hum Brain Mapp 37:1738-1748, 2016. © 2016 Wiley Periodicals, Inc. PMID:26876303

  16. Bacteriology of severe periodontitis in young adult humans.

    PubMed Central

    Moore, W E; Holdeman, L V; Smibert, R M; Hash, D E; Burmeister, J A; Ranney, R R

    1982-01-01

    A total of 78 bacteriological samples were taken from the supragingival tooth surface after superficial cleaning with toothpicks or from the periodontal sulci of 42 affected sites in 21 adolescents or young adults with severe generalized periodontitis. Of 190 bacterial species, subspecies, or serotypes detected among 2,723 isolates, 11 species exceeded 1% of the subgingival flora and were most closely associated with the diseased sulci. Eleven others were also sufficiently frequent to be suspect agents of tissue destruction. Many of these species are known pathogens of other body sites. In addition, 10 species of Treponema were isolated. One of these and the "large treponeme" were also more closely associated with severe periodontitis than they were with healthy sites or gingivitis. There were highly significant differences between the composition of the flora of the affected sulci and the flora of (i) the adjacent supragingival tooth surface, (ii) the gingival crevice of periodontally healthy people, and (iii) sites with a gingival index score of 0 or 2 in experimental gingivitis studies. The floras of different individuals were also significantly different. There was no statistically detectable effect of sampling per se upon the composition of the flora of subsequent samples from the same sites. The composition of the supragingival flora of the patients with severe generalized periodontitis that had serum antibody to Actinobacillus actinomycetemcomitans was significantly different from the supragingival flora of patients without this serum antibody. However, there was no statistically significant difference in the composition of their subgingival floras. PMID:7152665

  17. Damage Control Mechanisms in Articular Cartilage

    PubMed Central

    Martin, James A; Scherb, MB; Lembke, Lois A; Buckwalter, Joseph

    2000-01-01

    Articular chondrocytes maintain cartilage throughout life by replacing lost or damaged matrix with freshly synthesized material. Synthesis activity is regulated, rapidly increasing to well above basal levels in response to cartilage injury. Such responses suggest that synthesis activity is linked to the rate of matrix loss by endogenous "damage control" mechanisms. As a major stimulator of matrix synthesis in cartilage, insulin-like growth factor I (IGF-I) is likely to play a role in such mechanisms. Although IGF-I is nearly ubiquitous, its bioavailability in cartilage is controlled by IGF-I binding proteins (IGFBPs) secreted by chondrocytes. IGFBPs are part of a complex system, termed the IGF-I axis, that tightly regulates IGF-I activities. For the most part, IGFBPs block IGF-I activity by sequestering IGF-I from its cell surface receptor. We recently found that the expression of one binding protein, IGFBP-3, increases with chondrocyte age, paralleling an age-related decline in synthesis activity. In addition, IGFBP-3 is overexpressed in osteoarthritic cartilage, leading to metabolic disturbances that contribute to cartilage degeneration. These observations indicate that IGFBP-3 plays a crucial role in regulating matrix synthesis in cartilage, and suggest that cartilage damage control mechanisms may fail due to age-related changes in IGFBP-3 expression or distribution. Our investigation of this hypothesis began with immunolocalization studies to determine the tissue distribution of IGFBP-3 in human cartilage. We found that IGFBP-3 accumulated around chondrocytes in the pericellular/territorial matrix, where it co-localized with fibronectin, but not with the other matrix proteins tenascin-C and type VI collagen. This result suggested that the IGFBP-3 distribution is determined by binding to fibronectin. Binding studies using purified proteins demonstrated that IGFBP-3 does in fact bind to fibronectin, but not to tenascin-C or type VI collagen. Finally, we

  18. Profile of the Adult Education and Human Resource Development Professoriate: Characteristics and Professional Fulfillment.

    ERIC Educational Resources Information Center

    Peterson, Shari L.; Provo, Joanne

    1998-01-01

    A survey of 113 members of the Commission of Professors of Adult Education and 50 of the Academy of Human Resource Development found few differences except in age, rank, and salary. The two faculties are compatible and could be integrated. Overall job satisfaction is high. Professors tended to come from other fields and to remain. (SK)

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

    ERIC Educational Resources Information Center

    Hurley, Kevin

    2015-01-01

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

  20. An Instrument Development Model for Online Surveys in Human Resource Development and Adult Education

    ERIC Educational Resources Information Center

    Strachota, Elaine M.; Conceicao, Simone C. O.; Schmidt, Steven W.

    2006-01-01

    This article describes the use of a schematic model for developing and distributing online surveys. Two empirical studies that developed and implemented online surveys to collect data to measure satisfaction in various aspects of human resource development and adult education exemplify the use of the model to conduct online survey research. The…

  1. An Assessemnt of Graduate Adult Education and Human Resource Development Programs: A U.S. Perspective

    ERIC Educational Resources Information Center

    Akdere, Mesut; Conceicao, Simone C. O.

    2009-01-01

    Due to recent changes in the workplace, the workforce and higher education have driven academic programs of adult education (AE) and human resource development (HRD) in the U.S. to become more integrated as part of the mission of institutions of higher education. In this exploratory study, existing graduate programs in AE and HRD in the U.S. were…

  2. Adult attachment style is associated with cerebral μ-opioid receptor availability in humans.

    PubMed

    Nummenmaa, Lauri; Manninen, Sandra; Tuominen, Lauri; Hirvonen, Jussi; Kalliokoski, Kari K; Nuutila, Pirjo; Jääskeläinen, Iiro P; Hari, Riitta; Dunbar, Robin I M; Sams, Mikko

    2015-09-01

    Human attachment behavior mediates establishment and maintenance of social relationships. Adult attachment characteristically varies on anxiety and avoidance dimensions, reflecting the tendencies to worry about the partner breaking the social bond (anxiety) and feeling uncomfortable about depending on others (avoidance). In primates and other mammals, the endogenous μ-opioid system is linked to long-term social bonding, but evidence of its role in human adult attachment remains more limited. We used in vivo positron emission tomography to reveal how variability in μ-opioid receptor (MOR) availability is associated with adult attachment in humans. We scanned 49 healthy subjects using a MOR-specific ligand [(11) C]carfentanil and measured their attachment avoidance and anxiety with the Experiences in Close Relationships-Revised scale. The avoidance dimension of attachment correlated negatively with MOR availability in the thalamus and anterior cingulate cortex, as well as the frontal cortex, amygdala, and insula. No associations were observed between MOR availability and the anxiety dimension of attachment. Our results suggest that the endogenous opioid system may underlie interindividual differences in avoidant attachment style in human adults, and that differences in MOR availability are associated with the individuals' social relationships and psychosocial well-being. PMID:26046928

  3. Severe Infections with Human Adenovirus 7d in 2 Adults in Family, Illinois, USA, 2014

    PubMed Central

    Ison, Michael G.

    2016-01-01

    Human adenovirus 7d, a genomic variant with no reported circulation in the United States, was isolated from 2 adults with severe respiratory infections in Illinois. Molecular typing identified a close relationship with strains of the same genome type isolated from cases of respiratory disease in several provinces of China since 2009. PMID:26982199

  4. Evaluation of Serum Creatinine Changes With Integrase Inhibitor Use in Human Immunodeficiency Virus-1 Infected Adults

    PubMed Central

    Lindeman, Tara A.; Duggan, Joan M.; Sahloff, Eric G.

    2016-01-01

    This retrospective chart review evaluated changes in serum creatinine and creatinine clearance (CrCl) after initiation of an integrase inhibitor (INSTI)-based regimen as initial treatment in human immunodeficiency virus-infected adults. Serum creatinine and CrCl changes were similar to those seen in clinical trials for INSTIs. No renal-related serious adverse events or discontinuations occurred. PMID:27092314

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

    ERIC Educational Resources Information Center

    Hatcher, Tim; Bowles, Tuere

    2006-01-01

    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).…

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

    ERIC Educational Resources Information Center

    Hatcher, Tim; Bowles, Tuere

    2006-01-01

    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…

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

    ERIC Educational Resources Information Center

    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…

  8. PREDICTIONS OF OZONE ABSORPTION IN HUMAN LUNGS FROM NEWBORN TO ADULT

    EPA Science Inventory

    Dosimetry models for gases mainly have been used to predict absorption in adult humans and laboratory animals. he lack of lower respiratory tract (LRT) lung models for children has discouraged the application of theoretical gaseous dosimetry to this important subpopulation. o fil...

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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…

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

    ERIC Educational Resources Information Center

    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).…

  13. Human-derived neural progenitors functionally replace astrocytes in adult mice

    PubMed Central

    Chen, Hong; Qian, Kun; Chen, Wei; Hu, Baoyang; Blackbourn, Lisle W.; Du, Zhongwei; Ma, Lixiang; Liu, Huisheng; Knobel, Karla M.; Ayala, Melvin; Zhang, Su-Chun

    2015-01-01

    Astrocytes are integral components of the homeostatic neural network as well as active participants in pathogenesis of and recovery from nearly all neurological conditions. Evolutionarily, compared with lower vertebrates and nonhuman primates, humans have an increased astrocyte-to-neuron ratio; however, a lack of effective models has hindered the study of the complex roles of human astrocytes in intact adult animals. Here, we demonstrated that after transplantation into the cervical spinal cords of adult mice with severe combined immunodeficiency (SCID), human pluripotent stem cell–derived (PSC-derived) neural progenitors migrate a long distance and differentiate to astrocytes that nearly replace their mouse counterparts over a 9-month period. The human PSC-derived astrocytes formed networks through their processes, encircled endogenous neurons, and extended end feet that wrapped around blood vessels without altering locomotion behaviors, suggesting structural, and potentially functional, integration into the adult mouse spinal cord. Furthermore, in SCID mice transplanted with neural progenitors derived from induced PSCs from patients with ALS, astrocytes were generated and distributed to a similar degree as that seen in mice transplanted with healthy progenitors; however, these mice exhibited motor deficit, highlighting functional integration of the human-derived astrocytes. Together, these results indicate that this chimeric animal model has potential for further investigating the roles of human astrocytes in disease pathogenesis and repair. PMID:25642771

  14. Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome in Older Adults.

    PubMed

    Scott, Jake; Goetz, Matthew Bidwell

    2016-08-01

    Improved survival with combination antiretroviral therapy has led to a dramatic increase in the number of human immunodeficiency virus (HIV)-infected individuals 50 years of age or older such that by 2020 more than 50% of HIV-infected persons in the United States will be above this age. Recent studies confirm that antiretroviral therapy should be offered to all HIV-infected patients regardless of age, symptoms, CD4+ cell count, or HIV viral load. However, when compared with HIV-uninfected populations, even with suppression of measurable HIV replication, older individuals are at greater risk for cardiovascular disease, malignancies, liver disease, and other comorbidities. PMID:27394024

  15. Adult human adipose tissue contains several types of multipotent cells.

    PubMed

    Tallone, Tiziano; Realini, Claudio; Böhmler, Andreas; Kornfeld, Christopher; Vassalli, Giuseppe; Moccetti, Tiziano; Bardelli, Silvana; Soldati, Gianni

    2011-04-01

    Multipotent mesenchymal stromal cells (MSCs) are a type of adult stem cells that can be easily isolated from various tissues and expanded in vitro. Many reports on their pluripotency and possible clinical applications have raised hopes and interest in MSCs. In an attempt to unify the terminology and the criteria to label a cell as MSC, in 2006 the International Society for Cellular Therapy (ISCT) proposed a standard set of rules to define the identity of these cells. However, MSCs are still extracted from different tissues, by diverse isolation protocols, are cultured and expanded in different media and conditions. All these variables may have profound effects on the selection of cell types and the composition of heterogeneous subpopulations, on the selective expansion of specific cell populations with totally different potentials and ergo, on the long-term fate of the cells upon in vitro culture. Therefore, specific molecular and cellular markers that identify MSCs subsets as well as standardization of expansion protocols for these cells are urgently needed. Here, we briefly discuss new useful markers and recent data supporting the rapidly emerging concept that many different types of progenitor cells are found in close association with blood vessels. This knowledge may promote the necessary technical improvements required to reduce variability and promote higher efficacy and safety when isolating and expanding these cells for therapeutic use. In the light of the discussed data, particularly the identification of new markers, and advances in the understanding of fundamental MSC biology, we also suggest a revision of the 2006 ISCT criteria. PMID:21327755

  16. Canonical Genetic Signatures of the Adult Human Brain

    PubMed Central

    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

  17. Canonical genetic signatures of the adult human brain.

    PubMed

    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, Jörg; 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

    2015-12-01

    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 called differential stability to assess reproducibility of gene expression patterning across 132 structures in six individual brains, revealing mesoscale genetic organization. The genes with the highest differential stability are highly biologically relevant, with enrichment for brain-related annotations, disease associations, drug targets and literature citations. Using genes with high differential stability, 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 marked 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

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

    ERIC Educational Resources Information Center

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

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 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...

  20. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults initiated after April 7, 2006. 26.1705 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults initiated...

  1. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 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...

  2. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2010 CFR

    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...

  3. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults initiated after April 7, 2006. 26.1705 Section 26... Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults initiated...

  4. 40 CFR 26.1705 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 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...

  5. 40 CFR 26.1704 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 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...

  6. 40 CFR 26.1704 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults...

    Code of Federal Regulations, 2010 CFR

    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...

  7. Articular synovial chondromatosis of the finger.

    PubMed

    Sano, Kazufumi; Hashimoto, Tomohisa; Kimura, Kazumasa; Ozeki, Satoru

    2014-10-01

    A 40-year-old woman presented with a six-month history of synovial chondromatosis of the metacarpophalangeal joint of the right ring finger, which was resected through both dorsal and volar incisions. To our knowledge there have been only 17 reported cases of articular synovial chondromatosis of the digital joint so far. We present a case affecting the metacarpophalangeal joint with a review of scattered information found in other 17 reports. PMID:23596991

  8. Surface of articular cartilage: immunohistological studies.

    PubMed

    Duance, V C

    1983-10-01

    Using several physical techniques the surface of articular cartilage has been reported to be structurally different from the deeper layers. In this paper using immunohistochemical methods, the surface has been shown to contain a characteristically different collagen, Type I in contrast to Type II which is the major collagen of cartilage. These results support previous proposals for a surface layer, or lamina splendens, the presence of which would be of considerable importance in understanding the degradation of cartilage in arthritides. PMID:6678620

  9. Larval food quantity affects the capacity of adult mosquitoes to transmit human malaria.

    PubMed

    Shapiro, Lillian L M; Murdock, Courtney C; Jacobs, Gregory R; Thomas, Rachel J; Thomas, Matthew B

    2016-07-13

    Adult traits of holometabolous insects are shaped by conditions experienced during larval development, which might impact interactions between adult insect hosts and parasites. However, the ecology of larval insects that vector disease remains poorly understood. Here, we used Anopheles stephensi mosquitoes and the human malaria parasite Plasmodium falciparum, to investigate whether larval conditions affect the capacity of adult mosquitoes to transmit malaria. We reared larvae in two groups; one group received a standard laboratory rearing diet, whereas the other received a reduced diet. Emerging adult females were then provided an infectious blood meal. We assessed mosquito longevity, parasite development rate and prevalence of infectious mosquitoes over time. Reduced larval food led to increased adult mortality and caused a delay in parasite development and a slowing in the rate at which parasites invaded the mosquito salivary glands, extending the time it took for mosquitoes to become infectious. Together, these effects increased transmission potential of mosquitoes in the high food regime by 260-330%. Such effects have not, to our knowledge, been shown previously for human malaria and highlight the importance of improving knowledge of larval ecology to better understand vector-borne disease transmission dynamics. PMID:27412284

  10. Larval food quantity affects the capacity of adult mosquitoes to transmit human malaria

    PubMed Central

    Shapiro, Lillian L. M.; Murdock, Courtney C.; Jacobs, Gregory R.; Thomas, Rachel J.; Thomas, Matthew B.

    2016-01-01

    Adult traits of holometabolous insects are shaped by conditions experienced during larval development, which might impact interactions between adult insect hosts and parasites. However, the ecology of larval insects that vector disease remains poorly understood. Here, we used Anopheles stephensi mosquitoes and the human malaria parasite Plasmodium falciparum, to investigate whether larval conditions affect the capacity of adult mosquitoes to transmit malaria. We reared larvae in two groups; one group received a standard laboratory rearing diet, whereas the other received a reduced diet. Emerging adult females were then provided an infectious blood meal. We assessed mosquito longevity, parasite development rate and prevalence of infectious mosquitoes over time. Reduced larval food led to increased adult mortality and caused a delay in parasite development and a slowing in the rate at which parasites invaded the mosquito salivary glands, extending the time it took for mosquitoes to become infectious. Together, these effects increased transmission potential of mosquitoes in the high food regime by 260–330%. Such effects have not, to our knowledge, been shown previously for human malaria and highlight the importance of improving knowledge of larval ecology to better understand vector-borne disease transmission dynamics. PMID:27412284

  11. Predictions of ozone absorption in human lungs from newborn to adult

    SciTech Connect

    Overton, J.H.; Graham, R.C.

    1989-01-01

    Dosimetry models for gases mainly have been used to predict absorption in adult humans and laboratory animals. The lack of lower respiratory tract (LRT) lung models for children has discouraged the application of theoretical gaseous dosimetry to this important sub-population. To fill this gap the authors have used several sources of data on age dependent LRT volumes, age dependent airway dimensions, a model of an adult tracheobronchial region, and a model of the adult acinus to construct theoretical LRT lung models for humans from birth to adult. An ozone (O{sub 3}) dosimetry model was then used to estimate the regional and local uptake of O{sub 3} in the (theoretical) LRTs of children and adults. For sedentary breathing, the LRT distribution of absorbed O{sub 3}, the percent uptake (76 to 85%), and the centriacinar O{sub 3} tissue dose are not very sensitive to age. For maximal work during exercise, predicted uptakes range from 83 to 91%, and the regional percent uptakes are more dependent on age than during quiet breathing. In general, total O{sub 3} absorption per minute increases with age. Regardless of age and state of breathing, the largest tissue dose of O{sub 3} is predicted to occur in the centriacinar region, where many animal studies show the maximal morphological damage due to O{sub 3}.

  12. A humanized version of Foxp2 does not affect ultrasonic vocalization in adult mice.

    PubMed

    Hammerschmidt, K; Schreiweis, C; Minge, C; Pääbo, S; Fischer, J; Enard, W

    2015-11-01

    The transcription factor FOXP2 has been linked to severe speech and language impairments in humans. An analysis of the evolution of the FOXP2 gene has identified two amino acid substitutions that became fixed after the split of the human and chimpanzee lineages. Studying the functional consequences of these two substitutions in the endogenous Foxp2 gene of mice showed alterations in dopamine levels, striatal synaptic plasticity, neuronal morphology and cortico-striatal-dependent learning. In addition, ultrasonic vocalizations (USVs) of pups had a significantly lower average pitch than control littermates. To which degree adult USVs would be affected in mice carrying the 'humanized' Foxp2 variant remained unclear. In this study, we analyzed USVs of 68 adult male mice uttered during repeated courtship encounters with different females. Mice carrying the Foxp2(hum/hum) allele did not differ significantly in the number of call elements, their element structure or in their element composition from control littermates. We conclude that neither the structure nor the usage of USVs in adult mice is affected by the two amino acid substitutions that occurred in FOXP2 during human evolution. The reported effect for pup vocalization thus appears to be transient. These results are in line with accumulating evidence that mouse USVs are hardly influenced by vocal learning. Hence, the function and evolution of genes that are necessary, but not sufficient for vocal learning in humans, must be either studied at a different phenotypic level in mice or in other organisms. PMID:26250064

  13. Localization of PPAR isotypes in the adult mouse and human brain

    PubMed Central

    Warden, Anna; Truitt, Jay; Merriman, Morgan; Ponomareva, Olga; Jameson, Kelly; Ferguson, Laura B.; Mayfield, R. Dayne; Harris, R. Adron

    2016-01-01

    Peroxisome proliferator-activated receptors (PPARs) are nuclear hormone receptors that act as ligand-activated transcription factors. PPAR agonists have well-documented anti-inflammatory and neuroprotective roles in the central nervous system. Recent evidence suggests that PPAR agonists are attractive therapeutic agents for treating neurodegenerative diseases as well as addiction. However, the distribution of PPAR mRNA and protein in brain regions associated with these conditions (i.e. prefrontal cortex, nucleus accumbens, amygdala, ventral tegmental area) is not well defined. Moreover, the cell type specificity of PPARs in mouse and human brain tissue has yet to be investigated. We utilized quantitative PCR and double immunofluorescence microscopy to determine that both PPAR mRNA and protein are expressed ubiquitously throughout the adult mouse brain. We found that PPARs have unique cell type specificities that are consistent between species. PPARα was the only isotype to colocalize with all cell types in both adult mouse and adult human brain tissue. Overall, we observed a strong neuronal signature, which raises the possibility that PPAR agonists may be targeting neurons rather than glia to produce neuroprotection. Our results fill critical gaps in PPAR distribution and define novel cell type specificity profiles in the adult mouse and human brain. PMID:27283430

  14. Predictions of ozone absorption in human lungs from newborn to adult

    SciTech Connect

    Overton, J.H.; Graham, R.C. )

    1989-01-01

    Although children are an important human population, dosimetry models for gases have been used to predict absorption mainly in laboratory animals and adult humans. To correct this omission, we have used several sources of data on age-dependent lower respiratory tract (LRT) volumes, age-dependent airway dimensions, a model of the adult tracheobronchial region, and a model of the adult acinus to construct theoretical LRT lung models for humans from birth to adulthood. An ozone (O3) dosimetry model was then used to estimate the regional and local uptake of O3 in the (theoretical) LRT of children and adults. For sedentary or quiet breathing, the LRT distribution of absorbed O3, the percent uptake (84 to 88%) and the centriacinar O3 tissue dose are not very sensitive to age. For maximal work during exercise, predicted LRT uptakes range from 87 to 93%, and the regional percent uptakes are more dependent on age than during quiet breathing. In general, the total quantity of O3 absorbed per minute increases with age. Regardless of age and state of breathing, the largest tissue dose of O3 is predicted to occur in the centriacinar region, where many animal studies show the maximal morphological damage from O3.

  15. The response of the anterior striatum during adult human vocal learning

    PubMed Central

    Leech, Robert; Iverson, Paul; Wise, Richard J. S.

    2014-01-01

    Research on mammals predicts that the anterior striatum is a central component of human motor learning. However, because vocalizations in most mammals are innate, much of the neurobiology of human vocal learning has been inferred from studies on songbirds. Essential for song learning is a pathway, the homolog of mammalian cortical-basal ganglia “loops,” which includes the avian striatum. The present functional magnetic resonance imaging (fMRI) study investigated adult human vocal learning, a skill that persists throughout life, albeit imperfectly given that late-acquired languages are spoken with an accent. Monolingual adult participants were scanned while repeating novel non-native words. After training on the pronunciation of half the words for 1 wk, participants underwent a second scan. During scanning there was no external feedback on performance. Activity declined sharply in left and right anterior striatum, both within and between scanning sessions, and this change was independent of training and performance. This indicates that adult speakers rapidly adapt to the novel articulatory movements, possibly by using motor sequences from their native speech to approximate those required for the novel speech sounds. Improved accuracy correlated only with activity in motor-sensory perisylvian cortex. We propose that future studies on vocal learning, using different behavioral and pharmacological manipulations, will provide insights into adult striatal plasticity and its potential for modification in both educational and clinical contexts. PMID:24805076

  16. Predictions of ozone absorption in human lungs from newborn to adult.

    PubMed

    Overton, J H; Graham, R C

    1989-01-01

    Although children are an important human population, dosimetry models for gases have been used to predict absorption mainly in laboratory animals and adult humans. To correct this omission, we have used several sources of data on age-dependent lower respiratory tract (LRT) volumes, age-dependent airway dimensions, a model of the adult tracheobronchial region, and a model of the adult acinus to construct theoretical LRT lung models for humans from birth to adulthood. An ozone (O3) dosimetry model was then used to estimate the regional and local uptake of O3 in the (theoretical) LRT of children and adults. For sedentary or quiet breathing, the LRT distribution of absorbed O3, the percent uptake (84 to 88%) and the centriacinar O3 tissue dose are not very sensitive to age. For maximal work during exercise, predicted LRT uptakes range from 87 to 93%, and the regional percent uptakes are more dependent on age than during quiet breathing. In general, the total quantity of O3 absorbed per minute increases with age. Regardless of age and state of breathing, the largest tissue dose of O3 is predicted to occur in the centriacinar region, where many animal studies show the maximal morphological damage from O3. PMID:2606688

  17. Repair of articular cartilage and meniscal tears by photoactive dyes: in-vivo study

    NASA Astrophysics Data System (ADS)

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

    1996-12-01

    We describe healing results of our 6 month study of a repair procedure which evokes the healing response in meniscal tears and partial thickness defects in articular cartilage by a non-thermal tissue sparing photochemical weld using 1,8-naphthalimide dyes. Welds of incisional flaps in adult sheep meniscus and femoral articular cartilage were made using the dye MBM Gold 012011012 at 12 mM in PBS, 457.9nm Argon ion laser radiation at 800 mW/cm2, 7.5 minutes with approximately 1 kg/cm2 externally applied pressure. Gross appearance of tissues in all welded knees appeared normal. Hematoxylin and eosin stained sections disclosed close bonding of welded areas and continuing healing response as cellular recruitment.

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

    PubMed Central

    Harte, Richard P.; Glynn, Liam G.; Broderick, Barry J.; Rodriguez-Molinero, Alejandro; Baker, Paul M. A.; McGuiness, Bernadette; O’Sullivan, Leonard; Diaz, Marta; Quinlan, Leo R.; ÓLaighin, Gearóid

    2014-01-01

    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. PMID:25563225

  19. Short-term monocular deprivation alters GABA in the adult human visual cortex.

    PubMed

    Lunghi, Claudia; Emir, Uzay E; Morrone, Maria Concetta; Bridge, Holly

    2015-06-01

    Neuroplasticity is a fundamental property of the nervous system that is maximal early in life, within the critical period [1-3]. Resting GABAergic inhibition is necessary to trigger ocular dominance plasticity and to modulate the onset and offset of the critical period [4, 5]. GABAergic inhibition also plays a crucial role in neuroplasticity of adult animals: the balance between excitation and inhibition in the primary visual cortex (V1), measured at rest, modulates the susceptibility of ocular dominance to deprivation [6-10]. In adult humans, short-term monocular deprivation strongly modifies ocular balance, unexpectedly boosting the deprived eye, reflecting homeostatic plasticity [11, 12]. There is no direct evidence, however, to support resting GABAergic inhibition in homeostatic plasticity induced by visual deprivation. Here, we tested the hypothesis that GABAergic inhibition, measured at rest, is reduced by deprivation, as demonstrated by animal studies. GABA concentration in V1 of adult humans was measured using ultra-high-field 7T magnetic resonance spectroscopy before and after short-term monocular deprivation. After monocular deprivation, resting GABA concentration decreased in V1 but was unaltered in a control parietal area. Importantly, across participants, the decrease in GABA strongly correlated with the deprived eye perceptual boost measured by binocular rivalry. Furthermore, after deprivation, GABA concentration measured during monocular stimulation correlated with the deprived eye dominance. We suggest that reduction in resting GABAergic inhibition triggers homeostatic plasticity in adult human V1 after a brief period of abnormal visual experience. These results are potentially useful for developing new therapeutic strategies that could exploit the intrinsic residual plasticity of the adult human visual cortex. PMID:26004760

  20. Neuroscience of human social interactions and adult attachment style

    PubMed Central

    Vrtička, Pascal; Vuilleumier, Patrik

    2012-01-01

    attachment insecurity and particularly anxiety. Emotion regulation strategies such as reappraisal or suppression of social emotions are also differentially modulated by attachment style. This research does not only help better understand the neural underpinnings of human social behavior, but also provides important insights on psychopathological conditions where attachment dysregulation is likely to play an important (causal) role. PMID:22822396

  1. Planning for Effective Faculty Development: Using Adult Learning Strategies. Professional Practices in Adult Education and Human Resource Development Series.

    ERIC Educational Resources Information Center

    Lawler, Patricia A.; King, Kathleen P.

    This book describes how to use adult learning strategies in planning faculty development. Chapter 1 addresses concerns about success, demonstrating how to use an adult learning model to help faculty developers succeed. Chapter 2 presents the Adult Learning Model for Faculty Development, which has four stages grounded in adult learning and program…

  2. Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat.

    PubMed

    Cypess, Aaron M; White, Andrew P; Vernochet, Cecile; Schulz, Tim J; Xue, Ruidan; Sass, Christina A; Huang, Tian Liang; Roberts-Toler, Carla; Weiner, Lauren S; Sze, Cathy; Chacko, Aron T; Deschamps, Laura N; Herder, Lindsay M; Truchan, Nathan; Glasgow, Allison L; Holman, Ashley R; Gavrila, Alina; Hasselgren, Per-Olof; Mori, Marcelo A; Molla, Michael; Tseng, Yu-Hua

    2013-05-01

    The imbalance between energy intake and expenditure is the underlying cause of the current obesity and diabetes pandemics. Central to these pathologies is the fat depot: white adipose tissue (WAT) stores excess calories, and brown adipose tissue (BAT) consumes fuel for thermogenesis using tissue-specific uncoupling protein 1 (UCP1). BAT was once thought to have a functional role in rodents and human infants only, but it has been recently shown that in response to mild cold exposure, adult human BAT consumes more glucose per gram than any other tissue. In addition to this nonshivering thermogenesis, human BAT may also combat weight gain by becoming more active in the setting of increased whole-body energy intake. This phenomenon of BAT-mediated diet-induced thermogenesis has been observed in rodents and suggests that activation of human BAT could be used as a safe treatment for obesity and metabolic dysregulation. In this study, we isolated anatomically defined neck fat from adult human volunteers and compared its gene expression, differentiation capacity and basal oxygen consumption to different mouse adipose depots. Although the properties of human neck fat vary substantially between individuals, some human samples share many similarities with classical, also called constitutive, rodent BAT. PMID:23603815

  3. Various Spectrum of MRI Findings in Articular and Para-articular Tuberculosis: Pictorial Assay.

    PubMed

    Panchal, Hiten; Chiripal, Priyanka

    2015-12-01

    Tuberculosis continues to be a health-related issue in India. Musculoskeletal tuberculosis is noted to occur dramatically as isolates, primarily accounting for large numbers of extra-pulmonary tuberculosis since early diagnosis is always a priority; with good prognosis, it is a curable disease. Delayed treatment is associated with severe morbidity. Musculoskeletal tuberculosis accounts for a large number of extra-pulmonary tuberculosis. In this article, we describe various articular and para-articular MRI spectrum findings that are seen in patients with tuberculosis. MRI is the perfect modality to study the extent of involvement and its related complications. PMID:26730089

  4. Activated platelet-rich plasma improves adipose-derived stem cell transplantation efficiency in injured articular cartilage

    PubMed Central

    2013-01-01

    Introduction Adipose-derived stem cells (ADSCs) have been isolated, expanded, and applied in the treatment of many diseases. ADSCs have also been used to treat injured articular cartilage. However, there is controversy regarding the treatment efficiency. We considered that ADSC transplantation with activated platelet-rich plasma (PRP) may improve injured articular cartilage compared with that of ADSC transplantation alone. In this study, we determined the role of PRP in ADSC transplantation to improve the treatment efficiency. Methods ADSCs were isolated and expanded from human adipose tissue. PRP was collected and activated from human peripheral blood. The effects of PRP were evaluated in vitro and in ADSC transplantation in vivo. In vitro, the effects of PRP on ADSC proliferation, differentiation into chondrogenic cells, and inhibition of angiogenic factors were investigated at three concentrations of PRP (10%, 15% and 20%). In vivo, ADSCs pretreated with or without PRP were transplanted into murine models of injured articular cartilage. Results PRP promoted ADSC proliferation and differentiation into chondrogenic cells that strongly expressed collagen II, Sox9 and aggrecan. Moreover, PRP inhibited expression of the angiogenic factor vascular endothelial growth factor. As a result, PRP-pretreated ADSCs improved healing of injured articular cartilage in murine models compared with that of untreated ADSCs. Conclusion Pretreatment of ADSCs with PRP is a simple method to efficiently apply ADSCs in cartilage regeneration. This study provides an important step toward the use of autologous ADSCs in the treatment of injured articular cartilage. PMID:23915433

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

    PubMed Central

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

    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, 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 CB1HIGH cell subpopulation described in rodents. Our results support the existence of ependymal CB1HIGH 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. PMID:26634814

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

    PubMed

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

    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, 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. PMID:26634814

  7. Immunological characteristics of human mesenchymal stem cells and multipotent adult progenitor cells.

    PubMed

    Jacobs, Sandra A; Roobrouck, Valerie D; Verfaillie, Catherine M; Van Gool, Stefaan W

    2013-01-01

    Somatic, also termed adult, stem cells are highly attractive biomedical cell candidates because of their extensive replication potential and functional multilineage differentiation capacity. They can be used for drug and toxicity screenings in preclinical studies, as in vitro model to study differentiation or for regenerative medicine to aid in the repair of tissues or replace tissues that are lost upon disease, injury or ageing. Multipotent adult progenitor cells (MAPCs) and mesenchymal stem cells (MSCs) are two types of adult stem cells derived from bone marrow that are currently being used clinically for tissue regeneration and for their immunomodulatory and trophic effects. This review will give an overview of the phenotypic and functional differences between human MAPCs and MSCs, with a strong emphasis on their immunological characteristics. Finally, we will discuss the clinical studies in which MSCs and MAPCs are already used. PMID:23295415

  8. Intra-Articular Tibiofemoral Injection of a Nonsteroidal Anti-Inflammatory Drug has no Detrimental Effects on Joint Mechanics in a Rat Model

    PubMed Central

    Riggin, Corinne N.; Tucker, Jennica J.; Soslowsky, Louis J.; Kuntz, Andrew F.

    2015-01-01

    Administration of intra-articular medications, including corticosteroids and analgesics, is common clinical practice for knee pathology and dysfunction. Non-steroidal anti-inflammatory drugs (NSAIDs) are another category of medication commonly prescribed for their analgesic and anti-inflammatory properties. Recent studies have demonstrated the efficacy of injectable NSAIDs in the treatment of intra-articular pathology and postoperative analgesia.1–3 However, little data exist regarding the safety of intra-articular injection, despite the increase in its application.4 Therefore, the objective of this study was to investigate the effects of intra-articular NSAID injection on articular cartilage, the anterior cruciate ligament (ACL), and joint function in the rat. Sixty-four Sprague-Dawley rats were divided into either saline (SAL) or ketorolac (NSAID) tibiofemoral single injection treatment groups. Animals were sacrificed at 2, 7, 28, and 84 days post-injection for histological and mechanical analyses. Additionally, a subset of animals underwent longitudinal ambulatory evaluation to determine joint functional properties. We hypothesized that intra-articular ketorolac injection would result in no detrimental mechanical, histological, or functional changes. No differences were reported between the NSAID and SAL groups in any of the parameters measured at any time point, demonstrating the potential safety of intra-articular NSAID administration. Therefore, NSAID injection could be further considered for clinical application in humans. PMID:24981310

  9. Immuno-localisation of anti-thyroid antibodies in adult human cerebral cortex.

    PubMed

    Moodley, Kogie; Botha, Julia; Raidoo, Deshandra Munsamy; Naidoo, Strinivasen

    2011-03-15

    Expression of thyroid-stimulating hormone receptor (TSH-R) has been demonstrated in adipocytes, lymphocytes, bone, kidney, heart, intestine and rat brain. Immuno-reactive TSH-R has been localised in rat brain and human embryonic cerebral cortex but not in adult human brain. We designed a pilot study to determine whether anti-thyroid auto-antibodies immuno-localise in normal adult human cerebral cortex. Forensic samples from the frontal, motor, sensory, occipital, cingulate and parieto-occipito-temporal association cortices were obtained from five individuals who had died of trauma. Although there were no head injuries, the prior psychiatric history of patients was unknown. The tissues were probed with commercial antibodies against both human TSH-R and human thyroglobulin (TG). Anti-TSH-R IgG immuno-localised to cell bodies and axons of large neurones in all 6 regions of all 5 brains. The intensity and percentage of neurones labelled were similar in all tissue sections. TSH-R immuno-label was also observed in vascular endothelial cells in the cingulate gyrus. Although also found in all 5 brains and all six cortical regions, TG localised exclusively in vascular smooth muscle cells and not on neurones. Although limited by the small sample size and number of brain areas examined, this is the first study describing the presence of antigenic targets for anti-TSH-R IgG on human cortical neurons, and anti-TG IgG in cerebral vasculature. PMID:21196016

  10. Increased reprogramming of human fetal hepatocytes compared with adult hepatocytes in feeder-free conditions.

    PubMed

    Hansel, Marc C; Gramignoli, Roberto; Blake, William; Davila, Julio; Skvorak, Kristen; Dorko, Kenneth; Tahan, Veysel; Lee, Brian R; Tafaleng, Edgar; Guzman-Lepe, Jorge; Soto-Gutierrez, Alejandro; Fox, Ira J; Strom, Stephen C

    2014-01-01

    Hepatocyte transplantation has been used to treat liver disease. The availability of cells for these procedures is quite limited. Human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) may be a useful source of hepatocytes for basic research and transplantation if efficient and effective differentiation protocols were developed and problems with tumorigenicity could be overcome. Recent evidence suggests that the cell of origin may affect hiPSC differentiation. Thus, hiPSCs generated from hepatocytes may differentiate back to hepatocytes more efficiently than hiPSCs from other cell types. We examined the efficiency of reprogramming adult and fetal human hepatocytes. The present studies report the generation of 40 hiPSC lines from primary human hepatocytes under feeder-free conditions. Of these, 37 hiPSC lines were generated from fetal hepatocytes, 2 hiPSC lines from normal hepatocytes, and 1 hiPSC line from hepatocytes of a patient with Crigler-Najjar syndrome, type 1. All lines were confirmed reprogrammed and expressed markers of pluripotency by gene expression, flow cytometry, immunocytochemistry, and teratoma formation. Fetal hepatocytes were reprogrammed at a frequency over 50-fold higher than adult hepatocytes. Adult hepatocytes were only reprogrammed with six factors, while fetal hepatocytes could be reprogrammed with three (OCT4, SOX2, NANOG) or four factors (OCT4, SOX2, NANOG, LIN28 or OCT4, SOX2, KLF4, C-MYC). The increased reprogramming efficiency of fetal cells was not due to increased transduction efficiency or vector toxicity. These studies confirm that hiPSCs can be generated from adult and fetal hepatocytes including those with genetic diseases. Fetal hepatocytes reprogram much more efficiently than adult hepatocytes, although both could serve as useful sources of hiPSC-derived hepatocytes for basic research or transplantation. PMID:23394081

  11. Nasopharyngeal carriage of Streptococcus pneumoniae in adults infected with human immunodeficiency virus in Jakarta, Indonesia.

    PubMed

    Harimurti, Kuntjoro; Saldi, Siti R F; Dewiasty, Esthika; Khoeri, Miftahuddin M; Yunihastuti, Evi; Putri, Tiara; Tafroji, Wisnu; Safari, Dodi

    2016-01-01

    This study investigated the distribution of serotype and antimicrobial susceptibility of Streptococcus pneumoniae carried by adults infected with human immunodeficiency virus (HIV) in Jakarta, Indonesia. Specimens of nasopharyngeal swab were collected from 200 HIV infected adults aged 21 to 63 years. Identification of S. pneumoniae was done by optochin susceptibility test and PCR for the presence of psaA and lytA genes. Serotyping was performed with sequential multiplex PCR and antibiotic susceptibility with the disk diffusion method. S. pneumoniae strains were carried by 10% adults with serotype 6A/B 20% was common serotype among cultured strains in 20 adults. Most of isolates were susceptible to chloramphenicol (80%) followed by clindamycin (75%), erythromycin (75%), penicillin (55%), and tetracycline (50%). This study found resistance to sulphamethoxazole/trimethoprim was most common with only 15% of strains being susceptible. High non-susceptibility to sulphamethoxazole/trimethoprim was observed in S. pneumoniae strains carried by HIV infected adults in Jakarta, Indonesia. PMID:26896285

  12. Mechanisms of disruption of the articular cartilage surface in inflammation. Neutrophil elastase increases availability of collagen type II epitopes for binding with antibody on the surface of articular cartilage.

    PubMed Central

    Jasin, H E; Taurog, J D

    1991-01-01

    We recently observed that specific antibodies to type II collagen do not bind in appreciable amounts to the intact surface of articular cartilage, whereas antibodies to the minor collagen types V, VI, and IX do. These results suggest that the outermost cartilage surface layer prevented interaction of the antibodies with the major collagen type in articular cartilage. The present studies were designed to investigate the pathogenic mechanisms involved in the disruption of the cartilage surface layer in inflammatory arthritis. Articular cartilage obtained from rabbits undergoing acute antigen-induced arthritis of 72 h duration showed a significant increase in binding of anti-type II antibody to cartilage surfaces compared with normal control cartilage (P less than 0.01). Augmentation of anti-type II binding was also observed upon in vitro incubation of bovine articular slices or intact rabbit patellar cartilage for 1 h with human polymorphonuclear neutrophils (PMN), PMN lysates, or purified human PMN elastase. This increase was not inhibited by sodium azide, nor was it enhanced by incubation of cartilage with the strong oxidant hypochlorous acid. Chondrocyte-mediated matrix proteoglycan degradation in cartilage explants cultured in the presence of cytokines failed to increase antibody binding appreciably. The augmentation in antibody binding seen with PMN lysates was inhibited by the nonspecific serine-esterase inhibitor PMSF, but not by the divalent metal chelator EDTA. The elastase-specific inhibitor AAPVCMK also inhibited most of the PMN-induced increase in antibody binding, whereas the cathepsin G-specific inhibitor GLPCMK was much less effective. Incubation of intact cartilage with purified human PMN elastase indicated that this serine esterase could account for the increase in anti-type II collagen antibody binding to intact cartilage surfaces. These studies suggest that in an inflammatory response, PMN-derived elastase degrades the outer layer of articular

  13. The determination of apoptosis rates on articular cartilages of ovariectomized rats with and without alendronate treatment.

    PubMed

    Acar, Nuray; Balkarli, Huseyin; Soyuncu, Yetkin; Ozbey, Ozlem; Celik-Ozenci, Ciler; Korkusuz, Petek; Ustunel, Ismail

    2016-06-01

    Osteoporosis (OP) is a major health problem characterized by compromised bone strength. Osteoarthritis (OA) is a joint disease that progresses slowly and is characterized by breakdown of the cartilage matrix. Alendronate (ALN), a nitrogen-containing bisphosphonate (BIS), inhibits bone loss and increases bone mineralization, and has been used clinically for the treatment of OP. It is still controversial whether BIS is effective in inhibiting the progression of OA. Chondrocyte apoptosis has been described in both human and experimentally induced OA models. In our study we aimed to detect whether ALN could protect articular cartilage from degeneration and reduce apoptosis rates in experimentally OA induced rats. For this rats were ovariectomized (ovex), nine weeks after operation rats were injected 30 µg/kg/week ALN subcutaneously for six weeks. After six weeks articular cartilages were obtained. We did Safranin O staining and Mankin and Pritzker scorings to evaluate degeneration and investigated the expressions of p53, cleaved caspase 3, Poly ADP-ribose (PAR), Poly ADP-ribose polymerase 1 (PARP 1), and applied TUNEL technique to determine apoptotis rates. We found a significant decrease in glycosaminoglycan (GAG) amount and increased apoptosis which indicates damage on articular cartilages of ovex rats. GAG amount was higher and apoptosis rate was lower on articular cartilages of ALN treated ovex rats compared to the ovex group. In contrary to studies showing that early ALN treatment has a protective effect, our study shows late ALN treatment has a chondroprotective effect on articular cartilage since we treated rats nine weeks after ovariectomy. PMID:26631351

  14. An Articular Cartilage Repair Model in Common C57Bl/6 Mice

    PubMed Central

    Matsuoka, Masatake; Sasazawa, Fumio; Momma, Daisuke; Baba, Rikiya; Hontani, Kazutoshi; Iwasaki, Norimasa

    2015-01-01

    To analyze the genetic and biomolecular mechanisms underlying cartilage repair, an optimized mouse model of osteochondral repair is required. Although several models of articular cartilage injury in mice have recently been established, the articular surface in adult C57Bl/6 mice heals poorly. Since C57Bl/6 mice are the most popular strain of genetically manipulated mice, an articular cartilage repair model using C57Bl/6 mice would be helpful for analysis of the mechanisms of cartilage repair. The purpose of this study was to establish a cartilage repair model in C57Bl/6 mice using immature animals. To achieve this goal, full-thickness injuries were generated in 3-week-old (young), 4-week-old (juvenile), and 8-week-old (adult) C57Bl/6 mice. To investigate the reproducibility and consistency of full-thickness injuries, mice were sacrificed immediately after operation, and cartilage thickness at the patellar groove, depth of the cartilage injury, cross-sectional width, and cross-sectional area were compared among the three age groups. The depth of cartilage injury/cartilage thickness ratio (%depth) and the coefficient of variation (CV) for each parameter were also calculated. At 8 weeks postoperatively, articular cartilage repair was assessed using a histological scoring system. With respect to the reproducibility and consistency of full-thickness injuries, cartilage thickness, depth of cartilage injury, and cross-sectional area were significantly larger in young and juvenile mice than in adult mice, whereas cross-sectional width and %depth were almost equal among the three age groups. CVs of %depths were less than 10% in all groups. With respect to articular cartilage repair, young and juvenile mice showed superior results. In conclusion, we established a novel cartilage repair model in C57Bl/6 mice. This model will be valuable in achieving mechanistic insights into the healing process of the joint surface, as it will facilitate the use of genetically modified mice

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

    PubMed

    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. PMID:27096360

  16. Isolation, characterization, and differentiation of progenitor cells from human adult adrenal medulla.

    PubMed

    Santana, Magda M; Chung, Kuei-Fang; Vukicevic, Vladimir; Rosmaninho-Salgado, Joana; Kanczkowski, Waldemar; Cortez, Vera; Hackmann, Klaus; Bastos, Carlos A; Mota, Alfredo; Schrock, Evelin; Bornstein, Stefan R; Cavadas, Cláudia; Ehrhart-Bornstein, Monika

    2012-11-01

    Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persists, and recently, we established a method to isolate and differentiate these progenitor cells from adult bovine adrenals. However, no studies have elucidated the existence of adrenal progenitor cells within the human adrenal medulla. Here we describe the isolation, characterization, and differentiation of chromaffin progenitor cells obtained from adult human adrenals. Human chromaffin progenitor cells were cultured in low-attachment conditions for 10-12 days as free-floating spheres in the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor. These primary human chromosphere cultures were characterized by the expression of several progenitor markers, including nestin, CD133, Notch1, nerve growth factor receptor, Snai2, Sox9, Sox10, Phox2b, and Ascl1 on the molecular level and of Sox9 on the immunohistochemical level. In opposition, phenylethanolamine N-methyltransferase (PNMT), a marker for differentiated chromaffin cells, significantly decreased after 12 days in culture. Moreover, when plated on poly-l-lysine/laminin-coated slides in the presence of FGF-2, human chromaffin progenitor cells were able to differentiate into two distinct neuron-like cell types, tyrosine hydroxylase (TH)(+)/β-3-tubulin(+) cells and TH(-)/β-3-tubulin(+) cells, and into chromaffin cells (TH(+)/PNMT(+)). This study demonstrates the presence of progenitor cells in the human adrenal medulla and reveals their potential use in regenerative medicine, especially in the treatment of neuroendocrine and neurodegenerative diseases. PMID:23197690

  17. Isolation, Characterization, and Differentiation of Progenitor Cells from Human Adult Adrenal Medulla

    PubMed Central

    Santana, Magda M.; Chung, Kuei-Fang; Vukicevic, Vladimir; Rosmaninho-Salgado, Joana; Kanczkowski, Waldemar; Cortez, Vera; Hackmann, Karl; Bastos, Carlos A.; Mota, Alfredo; Schrock, Evelin; Bornstein, Stefan R.; Cavadas, Cláudia

    2012-01-01

    Chromaffin cells, sympathetic neurons of the dorsal ganglia, and the intermediate small intensely fluorescent cells derive from a common neural crest progenitor cell. Contrary to the closely related sympathetic nervous system, within the adult adrenal medulla a subpopulation of undifferentiated progenitor cells persists, and recently, we established a method to isolate and differentiate these progenitor cells from adult bovine adrenals. However, no studies have elucidated the existence of adrenal progenitor cells within the human adrenal medulla. Here we describe the isolation, characterization, and differentiation of chromaffin progenitor cells obtained from adult human adrenals. Human chromaffin progenitor cells were cultured in low-attachment conditions for 10–12 days as free-floating spheres in the presence of fibroblast growth factor-2 (FGF-2) and epidermal growth factor. These primary human chromosphere cultures were characterized by the expression of several progenitor markers, including nestin, CD133, Notch1, nerve growth factor receptor, Snai2, Sox9, Sox10, Phox2b, and Ascl1 on the molecular level and of Sox9 on the immunohistochemical level. In opposition, phenylethanolamine N-methyltransferase (PNMT), a marker for differentiated chromaffin cells, significantly decreased after 12 days in culture. Moreover, when plated on poly-l-lysine/laminin-coated slides in the presence of FGF-2, human chromaffin progenitor cells were able to differentiate into two distinct neuron-like cell types, tyrosine hydroxylase (TH)+/β-3-tubulin+ cells and TH−/β-3-tubulin+ cells, and into chromaffin cells (TH+/PNMT+). This study demonstrates the presence of progenitor cells in the human adrenal medulla and reveals their potential use in regenerative medicine, especially in the treatment of neuroendocrine and neurodegenerative diseases. PMID:23197690

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

    PubMed Central

    Simon, Maciej; Peters, Stephanie; Baum, Wolfgang; Schett, Georg; Ruether, Wolfgang; Niemeier, Andreas; Schinke, Thorsten; Amling, Michael

    2015-01-01

    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 presence in the

  19. FGF2-induced effects on transcriptome associated with regeneration competence in adult human fibroblasts

    PubMed Central

    2013-01-01

    Background Adult human fibroblasts grown in low oxygen and with FGF2 supplementation have the capacity to tip the healing outcome of skeletal muscle injury – by favoring regeneration response in vivo over scar formation. Here, we compare the transcriptomes of control adult human dermal fibroblasts and induced regeneration-competent (iRC) fibroblasts to identify transcriptional changes that may be related to their regeneration competence. Results We identified a unique gene-expression profile that characterizes FGF2-induced iRC fibroblast phenotype. Significantly differentially expressed genes due to FGF2 treatment were identified and analyzed to determine overrepresented Gene Ontology terms. Genes belonging to extracellular matrix components, adhesion molecules, matrix remodelling, cytoskeleton, and cytokines were determined to be affected by FGF2 treatment. Conclusions Transcriptome analysis comparing control adult human fibroblasts with FGF2-treated fibroblasts identified functional groups of genes that reflect transcriptional changes potentially contributing to their regeneration competence. This comparative transcriptome analysis should contribute new insights into genes that characterize cells with greater regenerative potential. PMID:24066673

  20. Fas and Fas ligand expression in fetal and adult human testis with normal or deranged spermatogenesis.

    PubMed

    Francavilla, S; D'Abrizio, P; Rucci, N; Silvano, G; Properzi, G; Straface, E; Cordeschi, G; Necozione, S; Gnessi, L; Arizzi, M; Ulisse, S

    2000-08-01

    In mice, the Fas/Fas ligand (FasL) system has been shown to be involved in germ cell apoptosis. In the present study we evaluated the expression of Fas and Fas ligand (FasL) in fetal and adult human testis. Semiquantitative RT-PCR demonstrated the expression of Fas and FasL messenger ribonucleic acids in adult testis, but not in fetal testis (20-22 weeks gestation). In situ RT-PCR and immunohistochemistry experiments on adult human testis demonstrated the expression of FasL messenger ribonucleic acid and protein in Sertoli and Leydig cells, whereas the expression of Fas was confined to the Leydig cells and sporadic degenerating spermatocytes. The number of Fas-positive germ cells per 100 Sertoli cell nuclei was increased in 10 biopsies with postmeiotic germ cell arrest compared to 10 normal testis biopsies (mean, 3.82 +/- 0.45 vs. 2.02 +/- 0.29; P = 0.0001), but not in 10 biopsies with meiotic germ cell arrest (mean, 1.56 +/- 1.07). Fas and FasL proteins were not expressed in cases of idiopathic hypogonadotropic hypogonadism. Together, these findings may suggest that Fas/FasL expression in the human testis is developmentally regulated and under gonadotropin control. The increased germ cell expression of Fas in patients with postmeiotic germ cell arrest suggests that the Fas/FasL system may be involved in the quality control mechanism of the produced gametes. PMID:10946867

  1. Distinguishing ankle and knee articular cartilage.

    PubMed

    Cole, Ada A; Margulis, Arkady; Kuettner, Klaus E

    2003-06-01

    Degenerative changes in the tall and femoral distal cartilages of more than 2,000 tissue donors were graded based on the appearance of articular cartilage and osteophytes. In the ankle and the knee the degenerative changes increased with age; however, the rate of degeneration in the ankle was slower than in the knee. The degenerative changes in the ankle were more severe in men than in women, were predominantly bilateral, and seemed to be correlated with weight. The slower rate of change in the ankle may be caused, in part, by the biochemical and biomechanical tissue properties that distinguish ankle cartilage from that of the knee. PMID:12911243

  2. Poroviscoelastic finite element model including continuous fiber distribution for the simulation of nanoindentation tests on articular cartilage.

    PubMed

    Taffetani, M; Griebel, M; Gastaldi, D; Klisch, S M; Vena, P

    2014-04-01

    Articular cartilage is a soft hydrated tissue that facilitates proper load transfer in diarthroidal joints. The mechanical properties of articular cartilage derive from its structural and hierarchical organization that, at the micrometric length scale, encompasses three main components: a network of insoluble collagen fibrils, negatively charged macromolecules and a porous extracellular matrix. In this work, a constituent-based constitutive model for the simulation of nanoindentation tests on articular cartilage is presented: it accounts for the multi-constituent, non-linear, porous, and viscous aspects of articular cartilage mechanics. In order to reproduce the articular cartilage response under different loading conditions, the model considers a continuous distribution of collagen fibril orientation, swelling, and depth-dependent mechanical properties. The model's parameters are obtained by fitting published experimental data for the time-dependent response in a stress relaxation unconfined compression test on adult bovine articular cartilage. Then, model validation is obtained by simulating three independent experimental tests: (i) the time-dependent response in a stress relaxation confined compression test, (ii) the drained response of a flat punch indentation test and (iii) the depth-dependence of effective Poisson's ratio in a unconfined compression test. Finally, the validated constitutive model has been used to simulate multiload spherical nanoindentation creep tests. Upon accounting for strain-dependent tissue permeability and intrinsic viscoelastic properties of the collagen network, the model accurately fits the drained and undrained curves and time-dependent creep response. The results show that depth-dependent tissue properties and glycosaminoglycan-induced tissue swelling should be accounted for when simulating indentation experiments. PMID:24389384

  3. Attitudes of Korean adults towards human dignity: A Q methodology approach

    PubMed Central

    Kae Hwa, JO; Gyeong-Ju, AN; DOORENBOS, Ardith Z.

    2013-01-01

    Aim The aim of this study was to identify the perceived attitudes of Korean adults towards human dignity in order to determine the relationship of human dignity to its social and cultural background. Methods The Q methodology research technique was used to explore perceived attitude typology on the basis of the respondents’ ranking order for different statements. A convenience sampling method was used to select 40 Korean adults who were interested in human dignity to create statements. From the questionnaires, in-depth interviews, and a literature review, a total of 158 statements was obtained. The final 34 Q samples were selected from a review by two nursing professors and a Q methodology expert. Moreover, 38 respondents participated as P samples by sorting 34 Q statements on a nine-point normal distribution scale. The data were analyzed by using the QUANL software package. Results The following four types of attitudes about human dignity were identified in Korea: a happiness-oriented–self-pursuit type, relationship-oriented–self-recognition type, reflection-oriented–self-unification type, and discrimination-oriented–self-maintenance type. Conclusions The results indicate that approaches to developing human dignity education need to take this typology into account and the characteristics of the participants who fall into each category. These results provide general guidelines to understand Korean values for professional practice in various healthcare settings. PMID:22583944

  4. Quantitative MRI Evaluation of Articular Cartilage Using T2 Mapping Following Hip Arthroscopy for Femoroacetabular Impingement

    PubMed Central

    Mayer, Stephanie W.; Wagner, Naomi; Fields, Kara G.; Wentzel, Catherine; Burge, Alissa; Potter, Hollis G.; Lyman, Stephen; Kelly, Bryan T.

    2016-01-01

    Objectives: Cam-type femoroacetabular impingement (FAI) causes a shearing and delamination injury to the acetabular articular cartilage due to a mismatch between the size of the femoral head and the acetabulum. This mechanism is thought to lead to early osteoarthritis in this population. Cam decompression has been advocated to eliminate impingement, with the ultimate goal of halting the progression of articular cartilage delamination. Although outcomes following this procedure in the young adult population have been favorable at short and medium term follow up, it is not known whether the articular cartilage itself is protected from further injury by changing the biomechanics of the joint with decompression of the cam morphology. The purpose of this study is to compare the pre- and post-operative integrity of the acetabular articular cartilage using T2 mapping to determine if hip arthroscopy is protective of the articular cartilage at short- to medium term follow up. Methods: Males between 18 and 35 years of age who had pre-operative T2 mapping MRIs, underwent hip arthroscopy for cam or mixed-type FAI with an alpha angle greater than 50°, and had at least 2 year follow-up were identified. Post-operative MRIs were performed and T2 relaxation times in the transition zone and weight bearing articular cartilage in the anterosuperior acetabulum at deep and superficial chondral layers were recorded at nine points on three sagittal sequences on pre and post-operative MRIs. A paired t-test was used to compare T2 relaxation values between pre-operative and post-operative scans. Results: Eleven hips were evaluated. Mean age was 26.3 years (range 21 - 35). Mean follow up time to post-operative T2 mapping MRI was 2.6 years (range 2.4 - 2.7). The change in T2 relaxation time was not significantly different between pre- and post-operative MRI scans for any of the nine regions in the deep zone of the acetabular cartilage (p=0.065 - 0.969) or the superficial zone of the

  5. MRI rotating frame relaxation measurements for articular cartilage assessment

    PubMed Central

    Ellermann, Jutta; Ling, Wen; Nissi, Mikko J.; Arendt, Elizabeth; Carlson, Cathy S.; Garwood, Michael; Michaeli, Shalom; Mangia, Silvia

    2015-01-01

    In the present work we introduced two MRI rotating frame relaxation methods, namely adiabatic T1ρ and Relaxation Along a Fictitious Field (RAFF), along with an inversion-prepared Magnetization Transfer (MT) protocol for assessment of articular cartilage. Given the inherent sensitivity of rotating frame relaxation methods to slow molecular motions that are relevant in cartilage, we hypothesized that adiabatic T1ρ and RAFF would have higher sensitivity to articular cartilage degradation as compared to laboratory frame T2 and MT. To test this hypothesis, a proteoglycan depletion model was used. Relaxation time measurements were performed at 0 and 48 hours in ten bovine patellar specimens, 5 of which were treated with trypsin and 5 untreated controls were stored under identical conditions in isotonic saline for 48 hours. Relaxation times measured at 48 hours were longer than those measured at 0 hours in both groups. The changes in T2 and MT relaxation times after 48 hours were approximately 3 times larger in the trypsin treated specimens as compared to the untreated group, whereas increases of adiabatic T1ρ and RAFF were 4 to 5 fold larger. Overall, these findings demonstrate a higher sensitivity of adiabatic T1ρ and RAFF to the trypsin-induced changes in bovine patellar cartilage as compared to the commonly used T2 and MT. Since adiabatic T1ρ and RAFF are advantageous for human applications as compared to standard continuous-wave T1ρ methods, adiabatic T1ρ and RAFF are promising tools for assessing cartilage degradation in clinical settings. PMID:23993794

  6. Treatment of articular fractures with continuous passive motion.

    PubMed

    Onderko, Laura Lynn; Rehman, Saqib

    2013-07-01

    This article presents a review of the basic science and current research on the use of continuous passive motion therapy after surgery for an intra-articular fracture. This information is useful for surgeons in the postoperative management of intra-articular fractures in determining the best course of treatment to reduce complications and facilitate quicker recovery. PMID:23827837

  7. Isolation and culture of adult epithelial stem cells from human skin.

    PubMed

    Guo, Zhiru; Draheim, Kyle; Lyle, Stephen

    2011-01-01

    The homeostasis of all self-renewing tissues is dependent on adult stem cells. As undifferentiated stem cells undergo asymmetric divisions, they generate daughter cells that retain the stem cell phenotype and transit-amplifying cells (TA cells) that migrate from the stem cell niche, undergo rapid proliferation and terminally differentiate to repopulate the tissue. Epithelial stem cells have been identified in the epidermis, hair follicle, and intestine as cells with a high in vitro proliferative potential and as slow-cycling label-retaining cells in vivo (1-3). Adult, tissue-specific stem cells are responsible for the regeneration of the tissues in which they reside during normal physiologic turnover as well as during times of stress (4-5). Moreover, stem cells are generally considered to be multi-potent, possessing the capacity to give rise to multiple cell types within the tissue (6). For example, rodent hair follicle stem cells can generate epidermis, sebaceous glands, and hair follicles (7-9). We have shown that stem cells from the human hair follicle bulge region exhibit multi-potentiality (10). Stem cells have become a valuable tool in biomedical research, due to their utility as an in vitro system for studying developmental biology, differentiation, tumorigenesis and for their possible therapeutic utility. It is likely that adult epithelial stem cells will be useful in the treatment of diseases such as ectodermal dysplasias, monilethrix, Netherton syndrome, Menkes disease, hereditary epidermolysis bullosa and alopecias (11-13). Additionally, other skin problems such as burn wounds, chronic wounds and ulcers will benefit from stem cell related therapies (14,15). Given the potential for reprogramming of adult cells into a pluripotent state (iPS cells)(16,17), the readily accessible and expandable adult stem cells in human skin may provide a valuable source of cells for induction and downstream therapy for a wide range of disease including diabetes and

  8. Moxidectin causes adult worm mortality of human lymphatic filarial parasite Brugia malayi in rodent models.

    PubMed

    Verma, Meenakshi; Pathak, Manisha; Shahab, Mohd; Singh, Kavita; Mitra, Kalyan; Misra-Bhattacharya, Shailja

    2014-12-01

    Moxidectin is a macrocyclic lactone belonging to milbemycin family closely related to ivermectin and is currently progressing towards Phase III clinical trial against human infection with the filaria Onchocerca volvulus (Leuckart, 1894). There is a single report on the microfilaricidal and embryostatic activity of moxidectin in case of the human lymphatic filarial parasite Brugia malayi (Brug, 1927) in Mastomys coucha (Smith) but without any adulticidal action. In the present study, the in vitro and in vivo antifilarial efficacy of moxidectin was evaluated on, B. malayi. In vitro moxidectin showed 100% reduction in adult female worm motility at 0.6 μM concentration within 7 days with 68% inhibition in the reduction of MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide dye) (which is used to detect viability of worms). A 50% inhibitory concentration (IC50) of moxidectin for adult female parasite was 0.242 μM, for male worm 0.186 μM and for microfilaria IC50 was 0.813 μM. In adult B. malayi-transplanted primary screening model (Meriones unguiculatus Milne-Edwards), moxidectin at a single optimal dose of 20 mg/kg by oral and subcutaneous route was found effective on both adult parasites and microfilariae. In secondary screening (M coucha, subcutaneously inoculated with infective larvae), moxidectin at the same dose by subcutaneous route brought about death of 49% of adult worms besides causing sterilisation in 54% of the recovered live female worms. The treated animals exhibited a continuous and sustained reduction in peripheral blood microfilaraemia throughout the observation period of 90 days. The mechanism of action of moxidectin is suggested to be similar to avermectins. The in silico studies were also designed to explore the interaction of moxidectin with glutamate-gated chloride channels of B. malayi. The docking results revealed a close interaction of moxidectin with various GluCl ligand sites of B. malayi. PMID:25651699

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

    PubMed

    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. PMID:23744051

  10. Rabbit Neonates and Human Adults Perceive a Blending 6-Component Odor Mixture in a Comparable Manner

    PubMed Central

    Sinding, Charlotte; Thomas-Danguin, Thierry; Chambault, Adeline; Béno, Noelle; Dosne, Thibaut; Chabanet, Claire; Schaal, Benoist; Coureaud, Gérard

    2013-01-01

    Young and adult mammals are constantly exposed to chemically complex stimuli. The olfactory system allows for a dual processing of relevant information from the environment either as single odorants in mixtures (elemental perception) or as mixtures of odorants as a whole (configural perception). However, it seems that human adults have certain limits in elemental perception of odor mixtures, as suggested by their inability to identify each odorant in mixtures of more than 4 components. Here, we explored some of these limits by evaluating the perception of three 6-odorant mixtures in human adults and newborn rabbits. Using free-sorting tasks in humans, we investigated the configural or elemental perception of these mixtures, or of 5-component sub-mixtures, or of the 6-odorant mixtures with modified odorants' proportion. In rabbit pups, the perception of the same mixtures was evaluated by measuring the orocephalic sucking response to the mixtures or their components after conditioning to one of these stimuli. The results revealed that one mixture, previously shown to carry the specific odor of red cordial in humans, was indeed configurally processed in humans and in rabbits while the two other 6-component mixtures were not. Moreover, in both species, such configural perception was specific not only to the 6 odorants included in the mixture but also to their respective proportion. Interestingly, rabbit neonates also responded to each odorant after conditioning to the red cordial mixture, which demonstrates their ability to perceive elements in addition to configuration in this complex mixture. Taken together, the results provide new insights related to the processing of relatively complex odor mixtures in mammals and the inter-species conservation of certain perceptual mechanisms; the results also revealed some differences in the expression of these capacities between species putatively linked to developmental and ecological constraints. PMID:23341948

  11. The effects of hydrostatic pressure on matrix synthesis in articular cartilage

    SciTech Connect

    Hall, A.C.; Urban, J.P.; Gehl, K.A. )

    1991-01-01

    The direct effects of hydrostatic pressure on matrix synthesis in articular cartilage can be studied independently of the other factors that change during loading. We have found that the influence of hydrostatic pressure on incorporation rates of {sup 35}SO{sub 4} and ({sup 3}H)proline into adult bovine articular cartilage slices in vitro depends on the pressure level and on the time at pressure. Pressures in the physiological range (5-15 MPa) applied for 20 s or for 5 min could stimulate tracer incorporation (30-130%) during the following 2 h, but higher pressures (20-50 MPa) had no effect on incorporation rates. The degree of stimulation in cartilage obtained from different animals was found to vary; in some animals none was seen. Stimulation also varied with position along the joint. Physiological pressures (5-10 MPa) applied continuously for the 2-h incubation period also stimulated incorporation rates, but pressures greater than 20 MPa always produced a decrease that was related to the applied pressure and that was reversible. These results suggests that the hydrostatic pressure that occurs during loading is a signal that can stimulate matrix synthesis rates in articular cartilage.

  12. Epidemiologic, clinical, and virologic characteristics of human rhinovirus infection among otherwise healthy children and adults

    PubMed Central

    Chen, Wei-Ju; Arnold, John C.; Fairchok, Mary P.; Danaher, Patrick J.; McDonough, Erin A.; Blair, Patrick J.; Garcia, Josefina; Halsey, Eric S.; Schofield, Christina; Ottolini, Martin; Mor, Deepika; Ridoré, Michelande; Burgess, Timothy H.; Millar, Eugene V.

    2015-01-01

    Background Human rhinovirus (HRV) is a major cause of influenza-like illness (ILI) in adults and children. Differences in disease severity by HRV species have been described among hospitalized patients with underlying illness. Less is known about the clinical and virologic characteristics of HRV infection among otherwise healthy populations, particularly adults. Objectives To characterize molecular epidemiology of HRV and association between HRV species and clinical presentation and viral shedding. Study design Observational, prospective, facility-based study of ILI was conducted from February 2010 to April 2012. Collection of nasopharyngeal specimens, patient symptoms, and clinical information occurred on days 0, 3, 7, and 28. Patients recorded symptom severity daily for the first 7 days of illness in a symptom diary. HRV was identified by RT-PCR and genotyped for species determination. Cases who were co-infected with other viral respiratory pathogens were excluded from the analysis. We evaluated the associations between HRV species, clinical severity, and patterns of viral shedding. Results Eighty-four HRV cases were identified and their isolates genotyped. Of these, 62 (74%) were >18y. Fifty-four were HRV-A, 11 HRV-B, and 19 HRV-C. HRV-C infection was more common among children than adults (59% vs. 10%, P<0.001). Among adults, HRV-A was associated with higher severity of upper respiratory symptoms compared to HRV-B (P=0.02), but no such association was found in children. In addition, adults shed HRV-A significantly longer than HRV-C (Ptrend=0.01). Conclusions Among otherwise healthy adults with HRV infection, we observed species-specific differences in respiratory symptom severity and duration of viral shedding. PMID:25728083

  13. A Comparison between the Purpose and Goals of Human Resource Development and Adult Education: Whose Interests Are Being Served?

    ERIC Educational Resources Information Center

    Batchelder, John Stuart; Byxbe, Ferris

    2002-01-01

    The purposes and goals of adult education and human resource development (HRD) differ and even clash. They find common ground in the personal development function but differ in the control and motivation for learning. Adult education seeks to enable learner self-determination; HRD's focus is enabling organizational control through employee…

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

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults. 26.1704 Section 26.1704 Protection of Environment... research with non-pregnant, non-nursing adults. (a) This section applies to research subject to...

  15. 40 CFR 26.1704 - Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Prohibition of reliance on unethical human research with non-pregnant, non-nursing adults. 26.1704 Section 26.1704 Protection of Environment... research with non-pregnant, non-nursing adults. (a) This section applies to research subject to...

  16. Kinetics and genomic profiling of adult human and mouse β-cell maturation.

    PubMed

    Szabat, Marta; Pourghaderi, Poya; Soukhatcheva, Galina; Verchere, C Bruce; Warnock, Garth L; Piret, James M; Johnson, James D

    2011-01-01

    Diabetes is a multifactorial metabolic disorder defined by the loss of functional pancreatic insulin-producing β-cells. The functional maturation and dedifferentiation of adult β-cells is central to diabetes pathogenesis and to β-cell replacement therapy for the treatment of diabetes. Despite its importance, the dynamics and mechanisms of adult β-cell maturation remain poorly understood. Using a novel Pdx1/Ins1 dual fluorescent reporter lentiviral vector, we previously found that individual adult human and mouse β-cells exist in at least two differentiation states distinguishable by the activation of the rat Ins1 promoter and performed the first real-time imaging of the maturation of individual cultured β-cells. Our previous study focused on transformed (MIN6) β-cells as a model to investigatethe kinetics of β-cell maturation. In the present study, we investigated the kinetics of the maturation process in primary human and mouse β-cells and performed gene expression profiling. Gene expression profiling of FACS purified immature Pdx1 (+) /Ins1 (low) cells and mature Pdx1 (high) /Ins1 (high ) cells from cultures of human islets, mouse islets and MIN6 cells revealed that Pdx1 (+) /Ins1 (low) cells are enriched for multiple genes associated with β-cell development/progenitor cells, proliferation, apoptosis, as well as genes coding for other islet cell hormones such as glucagon. We also demonstrated that the heterogeneity in β-cell maturation states previously observed in vitro, can also be found in vivo. Collectively, these experiments contribute to the understanding of maturation, dedifferentiation and plasticity of adult pancreatic β-cells. The results have significant implications for islet regeneration and for in vitro generation of functional β-cells to treat diabetes. PMID:21633187

  17. The mental representation of the human gait in young and older adults

    PubMed Central

    Stöckel, Tino; Jacksteit, Robert; Behrens, Martin; Skripitz, Ralf; Bader, Rainer; Mau-Moeller, Anett

    2015-01-01

    The link between mental representation (MREP) structures and motor performance has been evidenced for a great variety of movement skills, but not for the human gait. Therefore the present study sought to investigate the cognitive memory structures underlying the human gait in young and older adults. In a first experiment, gait parameters at comfortable gait speed (OptoGait) were compared with gait-specific MREPs (structural dimensional analysis of MREP; SDA-M) in 36 young adults. Participants were divided into a slow- and fast-walking group. The proven relationship between gait speed and executive functions such as working memory led to the hypothesis that gait pattern and MREP differ between slow- and fast-walking adults. In a second experiment, gait performance and MREPs were compared between 24 young (27.9 years) and 24 elderly (60.1 years) participants. As age-related declines in gait performance occur from the seventh decade of life onward, we hypothesized that gait parameters would not be affected until the age of 60 years accompanied by unchanged MREP. Data of experiment one revealed that gait parameters and MREPs differed significantly between slow and fast walkers. Notably, eleven previously incurred musculoskeletal injuries were documented for the slow walkers but only two injuries and one disorder for fast walkers. Experiment two revealed no age-related differences in gait parameters or MREPs between healthy young and older adults. In conclusion, the differences in gait parameters associated with lower comfortable gait speeds are reflected by differences in MREPs, whereby SDA-M data indicate that the single limb support phase may serve as a critical functional period. These differences probably resulted from previously incurred musculoskeletal injuries. Our data further indicate that the human gait and its MREP are stable until the age of 60. SDA-M may be considered as a valuable clinical tool for diagnosis of gait abnormalities and monitoring of

  18. Location and phenotype of human adult keratinocyte stem cells of the skin.

    PubMed

    Webb, Angela; Li, Amy; Kaur, Pritinder

    2004-10-01

    The location and identity of interfollicular epidermal stem cells of adult human skin remain undefined. Based on our previous work in both adult murine and neonatal human foreskin, we demonstrate that cell surface levels of the alpha6 integrin and the transferrin receptor (CD71) are valid markers for resolving a putative stem cell, transit amplifying and differentiating compartment in adult human skin by flow cytometry. Specifically, epidermal cells expressing high levels of alpha6 integrin and low levels of the transferrin receptor CD71 (phenotype alpha6 (bri)CD71(dim)) exhibit several stem cell characteristics, comprising a minor population (2%-5%) of the K14(bri) fraction, enriched for quiescent and small blast-like cells with high clonogenic capacity, lacking the differentiation marker K10. Conversely, the majority of K14(bri) K10(neg) epidermal cells express high levels of CD71 (phenotype alpha6 (bri)CD71(bri)), and represent the actively cycling fraction of keratinocytes displaying greater cell size due to an increase in cytoplasmic area, consistent with their being transient amplifying cells. The alpha6 (bri)CD71(bri) population exhibited intermediate clonogenic capacity. A third population of K14(dim) but K10 positive epidermal cells could be identified by their low levels of alpha6 integrin expression (i.e. alpha6 (dim) cells), representing the differentiation compartment; predictably, this subpopulation exhibited poor clonogenic efficiency. Flow cytometric analysis for the hair follicle bulge region (stem cell) marker K15 revealed preferential expression of this keratin in alpha6 (bri) cells (i.e., both stem and transient amplifying fractions), but not the alpha6 (dim) population. Given that K15 positive cells could only be detected in the deep rete ridges of adult skin in situ, we conclude that stem and transient amplifying cells reside in this location, while differentiating (K15 negative) cells are found in the shallow rete ridges. PMID:15606498

  19. Brief Communication: Shape analysis of the MT 1 proximal articular surface in fossil hominins and shod and unshod Homo.

    PubMed

    Proctor, Daniel J

    2010-12-01

    As a follow-up study to Proctor et al. (Am J Phys Anthropol 135 (2008) 216-224), this study quantifies the first metatarsal proximal articular surface using three-dimensional morphometrics to test for differences in articular surface shape between habitually shod and habitually unshod humans. In addition, differences in shape between Homo, Pan, Gorilla, and Hylobates are compared to the fossil hominin specimens A. L. 333-54, Stw 562, Stw 573 ("Little Foot"), OH 8, SKX 5017, and SK 1813. No difference in surface shape was found between habitually shod and habitually unshod humans. There is a clear quantitative division in articular surface shape between humans and apes that is more pronounced than a previous study by Proctor et al. (Am J Phys Anthropol 135 (2008) 216-224), due to additional landmarks present in this study. The specimen OH 8 is indistinguishable from modern Homo. The fossils A. L. 333-54, Stw 562, and Stw 573 are intermediate in shape between humans and apes. The specimens SKX 5017 and SK 1813 have a more apelike articular surface. When combined with other characteristics, this trait suggests that Paranthropus used a degree of abduction during locomotion that was much less than that in extant apes, but greater than that in Australopithecus, allowing for some small degree of grasping ability. PMID:20925078

  20. Toward patient-specific articular contact mechanics

    PubMed Central

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

    2015-01-01

    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. PMID:25698236

  1. [Articular chondrocalcinosis after 80 years of age].

    PubMed

    Memin, Y; Monville, C; Ryckewaert, A

    1978-02-01

    In 108 women over 80 (mean age 88,4 years, extremes 80 and 99 years) hospitalized in a geriatric service for various reasons, radiograms were made of both knees in the frontal aspect on standard film to detect calcinosis of the meniscus and chondrocalcinosis of the joint. In 25 women (23.1%) the radiographs revealed calcinosis of the meniscus with or without chondrocalcinosis. In these 25 cases a lateral X-ray was also made of the two knees, frontal X-rays were made of the pelvis, thumbs and shoulders. In 22 cases (88%) these revealed calcification of the fibrocartilages or articular cartilages in joints other than the knee. Seven of the 25 women had at least one attack of articular inflammation (especially of the knee) resembling a pseudo-gout crisis. The frequency of chronic arthropathies resembling arthroses was high in the 25 patients with chondrocalcinosis: 8 (32%) had an internal or external femoro-tibial arthrosis, as against 11 of the 83 patients (13%) of the same age without chondrocalcinosis, a significant difference. Eleven of the 25 women had signs of femororotular arthrosis on the lateral X-rays of the knees, 5 had coxarthrosis (with in 3 cases a radiological image of fibrocartilaginous or coxofemoral cartilaginous calcification). One women had chronic radiocarpal arthropathy evocative or chondrocalcinosis. Ten had a scaphotrapezoidal arthrosis, 5 arthrosis of the shoulder, 3 with radiological aspect of glenohumeral chondrocalcinosis. PMID:644241

  2. Imaging of articular cartilage: current concepts

    PubMed Central

    RONGA, MARIO; ANGERETTI, GLORIA; FERRARO, SERGIO; DE FALCO, GIOVANNI; GENOVESE, EUGENIO A.; CHERUBINO, PAOLO

    2014-01-01

    Magnetic resonance imaging (MRI) is the gold standard method for non-invasive assessment of joint cartilage, providing information on the structure, morphology and molecular composition of this tissue. There are certain minimum requirements for a MRI study of cartilage tissue: machines with a high magnetic field (> 1.5 Tesla); the use of surface coils; and the use of T2-weighted, proton density-weighted fast-spin echo (T2 FSE-DP) and 3D fat-suppressed T1-weighted gradient echo (3D-FS T1W GRE) sequences. For better contrast between the different joint structures, MR arthography is a method that can highlight minimal fibrillation or fractures of the articular surface and allow evaluation of the integrity of the native cartilage-repair tissue interface. To assess the biochemical composition of cartilage and cartilage repair tissue, various techniques have been proposed for studying proteoglycans [dGEMRIC, T1rho mapping, sodium (23Na) imaging MRI, etc.], collagen, and water distribution [T2 mapping, “magnetisation transfer contrast”, diffusion-weighted imaging (DWI), and so on]. Several MRI classifications have been proposed for evaluating the processes of joint degeneration (WORMS, BLOKS, ICRS) and post-surgical maturation of repair tissue (MOCART, 3D MOCART). In the future, isotropic 3D sequences set to improve image quality and facilitate the diagnosis of disorders of articular structures adjacent to cartilage. PMID:25606557

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

    PubMed Central

    Llamazares, Marco; Smith?, Robert J

    2008-01-01

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

  4. Uptake of dietary milk miRNAs by adult humans: a validation study

    PubMed Central

    Auerbach, Amanda; Vyas, Gopi; Li, Anne; Halushka, Marc; Witwer, Kenneth

    2016-01-01

    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. PMID:27158459

  5. Quantitative analysis of miRNA expression in seven human foetal and adult organs.

    PubMed

    Tang, Yanping; Liu, Dong; Zhang, Lijie; Ingvarsson, Sigurdur; Chen, Huiping

    2011-01-01

    miRNAs have been found to repress gene expression at posttranscriptional level in cells. Studies have shown that expression of miRNAs is tissue-specific and developmental-stage-specific. The mechanism behind this could be explained by miRNA pathways. In this study, totally 54 miRNAs were analysed in 7 matched human foetal and adult organs (brain, colon, heart, kidney, liver, lung and spleen) using real-time PCR. Quantitative analysis showed that a big proportion of the 54 miRNAs have higher general expression in the organs of the foetal period than the adult period, with the exception of the heart. The miRNA gene promoter methylation level in the adult stages was higher than in the foetal stages. Moreover, there is a high general expression level of several miRNAs in both stages of brain, kidney, liver, lung and spleen, but not seen in colon and heart. Our results indicate that the miRNAs may play a bigger role in the foetal stage than the adult stage of brain, colon, kidney, liver, lung and spleen. The majority of the miRNAs analysed may play an important role in the growth and development of brain, kidney, liver, lung and spleen. However, a minority of the miRNAs may be functional in colon and heart. PMID:22194897

  6. Identification of novel molecular markers through transcriptomic analysis in human fetal and adult corneal endothelial cells.

    PubMed

    Chen, Yinyin; Huang, Kevin; Nakatsu, Martin N; Xue, Zhigang; Deng, Sophie X; Fan, Guoping

    2013-04-01

    The corneal endothelium is composed of a monolayer of corneal endothelial cells (CECs), which is essential for maintaining corneal transparency. To better characterize CECs in different developmental stages, we profiled mRNA transcriptomes in human fetal and adult corneal endothelium with the goal to identify novel molecular markers in these cells. By comparing CECs with 12 other tissue types, we identified 245 and 284 signature genes that are highly expressed in fetal and adult CECs, respectively. Functionally, these genes are enriched in pathways characteristic of CECs, including inorganic anion transmembrane transporter, extracellular matrix structural constituent and cyclin-dependent protein kinase inhibitor activity. Importantly, several of these genes are disease target genes in hereditary corneal dystrophies, consistent with their functional significance in CEC physiology. We also identified stage-specific markers associated with CEC development, such as specific members in the transforming growth factor beta and Wnt signaling pathways only expressed in fetal, but not in adult CECs. Lastly, by the immunohistochemistry of ocular tissues, we demonstrated the unique protein localization for Wnt5a, S100A4, S100A6 and IER3, the four novel markers for fetal and adult CECs. The identification of a new panel of stage-specific markers for CECs would be very useful for characterizing CECs derived from stem cells or ex vivo expansion for cell replacement therapy. PMID:23257286

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

    NASA Astrophysics Data System (ADS)

    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.

  8. 14C-labeled substrate catabolism by human diploid fibroblasts derived from infants and adults

    SciTech Connect

    Rhead, W.J.; Moon, A.; Roettger, V.; Henkle, K.

    1985-10-01

    Untransformed diploid skin fibroblasts from eight normal adults, aged 24 to 74 years, catabolized several 14C-labeled substrates less effectively than cells from ten normal male infants. 14C-labeled substrate metabolism was quantitated either by measuring the evolution of 14CO2 from the 14C-labeled compounds or the incorporation of 14C into cellular protein via transamination of tricarboxylic acid cycle intermediates derived from the 14C-labeled substrates. With these methods, adult cells catabolized (1-14C)butyrate, (1-14C)octanoate, and 1-(2-14C)leucine at rates 44 to 64% of those found in infant cells. The oxidation of (1,4-14C)succinate and (U-14C)malate was identical in both infant and adult cells, while (2,3-14C)succinate catabolism was mildly decreased in adult cells (65-80% of control). These observations parallel those made in rat tissues and confirm that the same phenomenon occurs in cultured human fibroblasts.

  9. Chondroprotective Effect of Kartogenin on CD44-Mediated Functions in Articular Cartilage and Chondrocytes

    PubMed Central

    Ono, Yohei; Ishizuka, Shinya; Knudson, Cheryl B.

    2014-01-01

    Objective: A recent report identified the small molecule kartogenin as a chondrogenic and chondroprotective agent. Since changes in hyaluronan metabolism occur during cartilage degeneration in osteoarthritis, we began studies to determine whether there was a connection between extracellular hyaluronan, CD44–hyaluronan interactions and the effects of kartogenin on articular chondrocytes. Methods: Chondrocytes cultured in monolayers, bioengineered neocartilages, or cartilage explants were treated with kartogenin with or without stimulation by IL-1β. Accumulation of matrix was visualized by a particle exclusion assay or by safranin O staining and release of sulfated glycosaminoglycans was determined. Production of aggrecanases and aggrecan G1-ITEGE neoepitope, fragmentation of CD44 and the SMAD1/5/8 signaling pathway were evaluated by western blotting. Results: Kartogenin treatment enhanced chondrocyte pericellular matrix assembly and retention in the presence of IL-1β. The chondroprotective effects of kartogenin on IL-1β-induced release of sulfated glycosaminoglycans from articular cartilage explants, reduction in safranin O staining of neocartilage discs as well as a reduction in aggrecan G1-ITEGE neoepitope in chondrocyte and explant cartilage cultures were observed. Kartogenin partially blocked the IL-1β-induced increased expression of ADAMTS-5. Additionally, kartogenin-treated articular chondrocytes exhibited a decrease in CD44 proteolytic fragmentation. However, kartogenin treatment did not enhance proteoglycan in control, non-IL-1β-treated cultures. Similarly, kartogenin enhanced the SMAD1 phosphorylation but only following pretreatment with IL-1β. Conclusion: These studies provide novel information on the chondroprotective function of kartogenin in adult articular cartilage. The effects of kartogenin are significant after activation of chondrocytic chondrolysis, which may occur following disruption of homeostasis maintained by hyaluronan–CD44

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

    PubMed

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

    2014-01-01

    Recent studies have shown that cognitive and social interventions are crucial to the overall health of older adults including their psychological, cognitive, and physical well-being. However, due to the rapidly growing elderly population of the world, the resources and people to provide these interventions is lacking. Our work focuses on the use of social robotic technologies to provide person-centered cognitive interventions. In this article, we investigate the acceptance and attitudes of older adults toward the human-like expressive socially assistive robot Brian 2.1 in order to determine if the robot's human-like assistive and social characteristics would promote the use of the robot as a cognitive and social interaction tool to aid with activities of daily living. The results of a robot acceptance questionnaire administered during a robot demonstration session with a group of 46 elderly adults showed that the majority of the individuals had positive attitudes toward the socially assistive robot and its intended applications. PMID:26131794

  11. Calpain proteolysis of alpha II-spectrin in the normal adult human brain.

    PubMed

    Huh, G Y; Glantz, S B; Je, S; Morrow, J S; Kim, J H

    2001-12-01

    The proteolysis of alphaII-spectrin by calpain may be physiologically involved with synaptic remodeling, long-term potentiation, and memory formation. Calpain activation may also mediate neuronal apoptosis, responses to hypoxic insult, and excitotoxic injury. Surprisingly little is known of the activity of these calpain-mediated processes in the adult human brain. Using an antibody that specifically recognizes calpain-cleaved alphaII-spectrin, we have mapped the topographic distribution of the major alphaII-spectrin break-down product (alphaII-bdp1) in six adult brains examined post-mortem. All brains were from patients without evident neurological disease. Focally positive alphaII-bdp1 was consistently detected in the neuropil of the cortical gray matter, in occasional pyramidal neurons, and in rare reactive astrocytes in the cerebral cortex and hippocampus. Cerebellar Purkinje cells were more frequently, and more intensely, immunopositive. In all fields, staining was most intense in the soma and dendrites of neurons. There was no correlation of the frequency of positive cells with the postmortem interval or clinical condition. While these findings do not rigorously exclude contributions from postmortem calpain activation, they do suggest that a low-level of calpain processing of alphaII-spectrin is likely to be a constitutive process in the adult human brain. PMID:11720774

  12. Identification of Distinct Layers Within the Stratified Squamous Epithelium of the Adult Human True Vocal Fold

    PubMed Central

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

    2016-01-01

    Objectives/Hypothesis A precise molecular schema for classifying the different cell types of the normal human vocal fold epithelium is lacking. We hypothesize that the true vocal fold epithelium has a cellular architecture and organization similar to that of other stratified squamous epithelia including the skin, cornea, oral mucosa, and esophagus. In analogy to disorders of the skin and gastrointestinal tract, a molecular definition of the normal cell types within the human vocal fold epithelium and a description of their geometric relationships should serve as a foundation for characterizing cellular changes associated with metaplasia, dysplasia, and cancer. Study Design Qualitative study with adult human larynges. Methods Histologic sections of normal human laryngeal tissue were analyzed for morphology (hematoxylin and eosin) and immunohistochemical protein expression profile, including cytokeratins (CK13 and CK14), cornified envelope proteins (involucrin), basal cells (NGFR/p75), and proliferation markers (Ki67). Results We demonstrated that three distinct cell strata with unique marker profiles are present within the stratified squamous epithelium of the true vocal fold. We used these definitions to establish that cell proliferation is restricted to certain cell types and layers within the epithelium. These distinct cell types are reproducible across five normal adult larynges. Conclusion We have established that three layers of cells are present within the normal adult stratified squamous epithelium of the true vocal fold. Furthermore, replicating cell populations are largely restricted to the parabasal strata within the epithelium. This delineation of distinct cell populations will facilitate future studies of vocal fold regeneration and cancer. Level of Evidence N/A. PMID:25988619

  13. Photoacoustic tomography through a whole adult human skull with a photon recycler

    NASA Astrophysics Data System (ADS)

    Nie, Liming; Cai, Xin; Maslov, Konstantin; Garcia-Uribe, Alejandro; Anastasio, Mark A.; Wang, Lihong V.

    2012-11-01

    Photoacoustic tomography (PAT) of the human brain is challenging due to the fact that the skull strongly absorbs and scatters light, and attenuates and distorts ultrasound as well. For the first time, we demonstrated the feasibility of PAT through a whole adult human skull. A photon recycler (PR) was built to increase light transmittance through the skull. Both a graphite target and a canine brain were imaged through the skull. Use of the PR was found to improve the photoacoustic signal-to-noise ratio by a factor of 2.4. In addition, subtraction of photoacoustic signals that arise from light absorption within the skull significantly improved the contrast of the target. Our results indicate that PAT can potentially be applied to in vivo human brain imaging.

  14. Stem cells for tissue engineering of articular cartilage.

    PubMed

    Gao, J; Yao, J Q; Caplan, A I

    2007-07-01

    Articular cartilage injuries are one of the most common disorders in the musculo-skeletal system. Injured cartilage tissue cannot spontaneously heal and, if not treated, can lead to osteoarthritis of the affected joints. Although a variety of procedures are being employed to repair cartilage damage, methods that result in consistent durable repair tissue are not yet available. Tissue engineering is a recently developed science that merges the fields of cell biology, engineering, material science, and surgery to regenerate new functional tissue. Three critical components in tissue engineering of cartilage are as follows: first, sufficient cell numbers within the defect, such as chondrocytes or multipotent stem cells capable of differentiating into chondrocytes; second, access to growth and differentiation factors that modulate these cells to differentiate through the chondrogenic lineage; third, a cell carrier or matrix that fills the defect, delivers the appropriate cells, and supports cell proliferation and differentiation. Stem cells that exist in the embyro or in adult somatic tissues are able to renew themselves through cell division without changing their phenotype and are able to differentiate into multiple lineages including the chondrogenic lineage under certain physiological or experimental conditions. Here the application of stem cells as a cell source for cartilage tissue engineering is reviewed. PMID:17822146

  15. Health and population effects of rare gene knockouts in adult humans with related parents.

    PubMed

    Narasimhan, Vagheesh M; Hunt, Karen A; Mason, Dan; Baker, Christopher L; Karczewski, Konrad J; Barnes, Michael R; Barnett, Anthony H; Bates, Chris; Bellary, Srikanth; Bockett, Nicholas A; Giorda, Kristina; Griffiths, Christopher J; Hemingway, Harry; Jia, Zhilong; Kelly, M Ann; Khawaja, Hajrah A; Lek, Monkol; McCarthy, Shane; McEachan, Rosie; O'Donnell-Luria, Anne; Paigen, Kenneth; Parisinos, Constantinos A; Sheridan, Eamonn; Southgate, Laura; Tee, Louise; Thomas, Mark; Xue, Yali; Schnall-Levin, Michael; Petkov, Petko M; Tyler-Smith, Chris; Maher, Eamonn R; Trembath, Richard C; MacArthur, Daniel G; Wright, John; Durbin, Richard; van Heel, David A

    2016-04-22

    Examining complete gene knockouts within a viable organism can inform on gene function. We sequenced the exomes of 3222 British adults of Pakistani heritage with high parental relatedness, discovering 1111 rare-variant homozygous genotypes with predicted loss of function (knockouts) in 781 genes. We observed 13.7% fewer homozygous knockout genotypes than we expected, implying an average load of 1.6 recessive-lethal-equivalent loss-of-function (LOF) variants per adult. When genetic data were linked to the individuals' lifelong health records, we observed no significant relationship between gene knockouts and clinical consultation or prescription rate. In this data set, we identified a healthy PRDM9-knockout mother and performed phased genome sequencing on her, her child, and control individuals. Our results show that meiotic recombination sites are localized away from PRDM9-dependent hotspots. Thus, natural LOF variants inform on essential genetic loci and demonstrate PRDM9 redundancy in humans. PMID:26940866

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

    NASA Astrophysics Data System (ADS)

    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.

  17. Health and population effects of rare gene knockouts in adult humans with related parents

    PubMed Central

    Narasimhan, Vagheesh M.; Hunt, Karen A.; Mason, Dan; Baker, Christopher L.; Karczewski, Konrad J.; Barnes, Michael R.; Barnett, Anthony H.; Bates, Chris; Bellary, Srikanth; Bockett, Nicholas A.; Giorda, Kristina; Griffiths, Christopher J.; Hemingway, Harry; Jia, Zhilong; Kelly, M. Ann; Khawaja, Hajrah A.; Lek, Monkol; McCarthy, Shane; McEachan, Rosie; O’Donnell-Luria, Anne; Paigen, Kenneth; Parisinos, Constantinos A.; Sheridan, Eamonn; Southgate, Laura; Tee, Louise; Thomas, Mark; Xue, Yali; Schnall-Levin, Michael; Petkov, Petko M.; Tyler-Smith, Chris; Maher, Eamonn R.; Trembath, Richard C.; MacArthur, Daniel G.; Wright, John; Durbin, Richard; van Heel, David A.

    2016-01-01

    Examining complete gene knockouts within a viable organism can inform on gene function. We sequenced the exomes of 3,222 British Pakistani-heritage adults with high parental relatedness, discovering 1,111 rare-variant homozygous genotypes with predicted loss of gene function (knockouts) in 781 genes. We observed 13.7% fewer than expected homozygous knockout genotypes, implying an average load of 1.6 recessive-lethal-equivalent LOF variants per adult. Linking genetic data to lifelong health records, knockouts were not associated with clinical consultation or prescription rate. In this dataset we identified a healthy PRDM9 knockout mother, and performed phased genome sequencing on her, her child and controls, which showed meiotic recombination sites localised away from PRDM9-dependent hotspots. Thus, natural LOF variants inform upon essential genetic loci, and demonstrate PRDM9 redundancy in humans. PMID:26940866

  18. Cyclophilin D-Sensitive Mitochondrial Permeability Transition in Adult Human Brain and Liver Mitochondria

    PubMed Central

    Morota, Saori; Chen, Li; Matsuyama, Nagahisa; Suzuki, Yoshiaki; Nakajima, Satoshi; Tanoue, Tadashi; Omi, Akibumi; Shibasaki, Futoshi; Shimazu, Motohide; Ikeda, Yukio; Uchino, Hiroyuki; Elmér, Eskil

    2011-01-01

    Abstract The mitochondrial permeability transition (mPT) is considered to be a major cause of cell death under a variety of pathophysiological conditions of the central nervous system (CNS) and other organs. Pharmacological inhibition or genetic knockout of the matrix protein cyclophilin D (CypD) prevents mPT and cell degeneration in several models of brain injury. If these findings in animal models are translatable to human disease, pharmacological inhibition of mPT offers a promising therapeutic target. The objective of this study was to validate the presence of a CypD-sensitive mPT in adult human brain and liver mitochondria. In order to perform functional characterization of human mitochondria, fresh tissue samples were obtained during hemorrhage or tumor surgery and mitochondria were rapidly isolated. Mitochondrial calcium retention capacity, a quantitative assay for mPT, was significantly increased by the CypD inhibitor cyclosporin A in both human brain and liver mitochondria, whereas thiol-reactive compounds and oxidants sensitized mitochondria to calcium-induced mPT. Brain mitochondria underwent swelling upon calcium overload, which was reversible upon calcium removal. To further explore mPT of human mitochondria, liver mitochondria were demonstrated to exhibit several classical features of the mPT phenomenon, such as calcium-induced loss of membrane potential and respiratory coupling, as well as release of the pro-apoptotic protein cytochrome c. We concluded that adult viable human brain and liver mitochondria possess an active CypD-sensitive mPT. Our findings support the rationale of CypD and mPT inhibition as pharmacological targets in acute and chronic neurodegeneration. PMID:21121808

  19. Inventory of Research on Adult Human Resource Development in Canada. Inventaire de la Recherche sur le Developpement des Ressources Humaines Adultes au Canada.

    ERIC Educational Resources Information Center

    Page, Garnet T.; Caldwell, George

    This bilingual directory of research (1963-68) in the development of adult human resources in Canada indicates types of projects undertaken, principal objectives, institutions involved, amounts and sources of funding. It also shows which areas of research have been well covered, those with little or no coverage, and those which might be given a…

  20. Naïve adult stem cells isolation from primary human fibroblast cultures.

    PubMed

    Wenzel, Vera; Roedl, Daniela; Ring, Johannes; Djabali, Karima

    2013-01-01

    Over the last decade, several adult stem cell populations have been identified in human skin (1-4). The isolation of multipotent adult dermal precursors was first reported by Miller F. D laboratory (5, 6). These early studies described a multipotent precursor cell population from adult mammalian dermis (5). These cells--termed SKPs, for skin-derived precursors-- were isolated and expanded from rodent and human skin and differentiated into both neural and mesodermal progeny, including cell types never found in skin, such as neurons (5). Immunocytochemical studies on cultured SKPs revealed that cells expressed vimentin and nestin, an intermediate filament protein expressed in neural and skeletal muscle precursors, in addition to fibronectin and multipotent stem cell markers (6). Until now, the adult stem cells population SKPs have been isolated from freshly collected mammalian skin biopsies. Recently, we have established and reported that a population of skin derived precursor cells could remain present in primary fibroblast cultures established from skin biopsies (7). The assumption that a few somatic stem cells might reside in primary fibroblast cultures at early population doublings was based upon the following observations: (1) SKPs and primary fibroblast cultures are derived from the dermis, and therefore a small number of SKP cells could remain present in primary dermal fibroblast cultures and (2) primary fibroblast cultures grown from frozen aliquots that have been subjected to unfavorable temperature during storage or transfer contained a small number of cells that remained viable (7). These rare cells were able to expand and could be passaged several times. This observation suggested that a small number of cells with high proliferation potency and resistance to stress were present in human fibroblast cultures (7). We took advantage of these findings to establish a protocol for rapid isolation of adult stem cells from primary fibroblast cultures that are

  1. Derivation of Neural Stem Cells from Human Adult Peripheral CD34+ Cells for an Autologous Model of Neuroinflammation

    PubMed Central

    Wang, Tongguang; Choi, Elliot; Monaco, Maria Chiara G.; Campanac, Emilie; Medynets, Marie; Do, Thao; Rao, Prashant; Johnson, Kory R.; Elkahloun, Abdel G.; Von Geldern, Gloria; Johnson, Tory; Subramaniam, Sriram; Hoffman, Dax; Major, Eugene; Nath, Avindra

    2013-01-01

    Proinflammatory factors from activated T cells inhibit neurogenesis in adult animal brain and cultured human fetal neural stem cells (NSC). However, the role of inhibition of neurogenesis in human neuroinflammatory diseases is still uncertain because of the difficulty in obtaining adult NSC from patients. Recent developments in cell reprogramming suggest that NSC may be derived directly from adult fibroblasts. We generated NSC from adult human peripheral CD34+ cells by transfecting the cells with Sendai virus constructs containing Sox2, Oct3/4, c-Myc and Klf4. The derived NSC could be differentiated to glial cells and action potential firing neurons. Co-culturing NSC with activated autologous T cells or treatment with recombinant granzyme B caused inhibition of neurogenesis as indicated by decreased NSC proliferation and neuronal differentiation. Thus, we have established a unique autologous in vitro model to study the pathophysiology of neuroinflammatory diseases that has potential for usage in personalized medicine. PMID:24303066

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

    PubMed

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

    2015-02-12

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

  3. Development of a Physiologically Based Model to Describe the Pharmacokinetics of Methylphenidate in Juvenile and Adult Humans and Nonhuman Primates

    PubMed Central

    Yang, Xiaoxia; Morris, Suzanne M.; Gearhart, Jeffery M.; Ruark, Christopher D.; Paule, Merle G.; Slikker, William; Mattison, Donald R.; Vitiello, Benedetto; Twaddle, Nathan C.; Doerge, Daniel R.; Young, John F.; Fisher, Jeffrey W.

    2014-01-01

    The widespread usage of methylphenidate (MPH) in the pediatric population has received considerable attention due to its potential effect on child development. For the first time a physiologically based pharmacokinetic (PBPK) model has been developed in juvenile and adult humans and nonhuman primates to quantitatively evaluate species- and age-dependent enantiomer specific pharmacokinetics of MPH and its primary metabolite ritalinic acid. The PBPK model was first calibrated in adult humans using in vitro enzyme kinetic data of MPH enantiomers, together with plasma and urine pharmacokinetic data with MPH in adult humans. Metabolism of MPH in the small intestine was assumed to account for the low oral bioavailability of MPH. Due to lack of information, model development for children and juvenile and adult nonhuman primates primarily relied on intra- and interspecies extrapolation using allometric scaling. The juvenile monkeys appear to metabolize MPH more rapidly than adult monkeys and humans, both adults and children. Model prediction performance is comparable between juvenile monkeys and children, with average root mean squared error values of 4.1 and 2.1, providing scientific basis for interspecies extrapolation of toxicity findings. Model estimated human equivalent doses in children that achieve similar internal dose metrics to those associated with pubertal delays in juvenile monkeys were found to be close to the therapeutic doses of MPH used in pediatric patients. This computational analysis suggests that continued pharmacovigilance assessment is prudent for the safe use of MPH. PMID:25184666

  4. Development of a physiologically based model to describe the pharmacokinetics of methylphenidate in juvenile and adult humans and nonhuman primates.

    PubMed

    Yang, Xiaoxia; Morris, Suzanne M; Gearhart, Jeffery M; Ruark, Christopher D; Paule, Merle G; Slikker, William; Mattison, Donald R; Vitiello, Benedetto; Twaddle, Nathan C; Doerge, Daniel R; Young, John F; Fisher, Jeffrey W

    2014-01-01

    The widespread usage of methylphenidate (MPH) in the pediatric population has received considerable attention due to its potential effect on child development. For the first time a physiologically based pharmacokinetic (PBPK) model has been developed in juvenile and adult humans and nonhuman primates to quantitatively evaluate species- and age-dependent enantiomer specific pharmacokinetics of MPH and its primary metabolite ritalinic acid. The PBPK model was first calibrated in adult humans using in vitro enzyme kinetic data of MPH enantiomers, together with plasma and urine pharmacokinetic data with MPH in adult humans. Metabolism of MPH in the small intestine was assumed to account for the low oral bioavailability of MPH. Due to lack of information, model development for children and juvenile and adult nonhuman primates primarily relied on intra- and interspecies extrapolation using allometric scaling. The juvenile monkeys appear to metabolize MPH more rapidly than adult monkeys and humans, both adults and children. Model prediction performance is comparable between juvenile monkeys and children, with average root mean squared error values of 4.1 and 2.1, providing scientific basis for interspecies extrapolation of toxicity findings. Model estimated human equivalent doses in children that achieve similar internal dose metrics to those associated with pubertal delays in juvenile monkeys were found to be close to the therapeutic doses of MPH used in pediatric patients. This computational analysis suggests that continued pharmacovigilance assessment is prudent for the safe use of MPH. PMID:25184666

  5. Understanding and Managing Learning Disabilities in Adults. Professional Practices in Adult Education and Human Resource Development Series.

    ERIC Educational Resources Information Center

    Jordan, Dale R.

    This book reviews learning disabilities (LD) in adults and makes suggestions for helping adults cope with these disabilities. Each chapter covers a type of learning disability or related syndrome or explains characteristics of the brain. Chapter 1 explains several types of specific learning disabilities that make classroom performance difficult…

  6. Isolation of Novel Multipotent Neural Crest-Derived Stem Cells from Adult Human Inferior Turbinate

    PubMed Central

    Hauser, Stefan; Widera, Darius; Qunneis, Firas; Müller, Janine; Zander, Christin; Greiner, Johannes; Strauss, Christina; Lüningschrör, Patrick; Heimann, Peter; Schwarze, Hartmut; Ebmeyer, Jörg; Sudhoff, Holger; Araúzo-Bravo, Marcos J.; Greber, Boris; Zaehres, Holm; Schöler, Hans; Kaltschmidt, Christian

    2012-01-01

    Adult human neural crest-derived stem cells (NCSCs) are of extraordinary high plasticity and promising candidates for the use in regenerative medicine. Here we describe for the first time a novel neural crest-derived stem cell population within the respiratory epithelium of human adult inferior turbinate. In contrast to superior and middle turbinates, high amounts of source material could be isolated from human inferior turbinates. Using minimally-invasive surgery methods isolation is efficient even in older patients. Within their endogenous niche, inferior turbinate stem cells (ITSCs) expressed high levels of nestin, p75NTR, and S100. Immunoelectron microscopy using anti-p75 antibodies displayed that ITSCs are of glial origin and closely related to nonmyelinating Schwann cells. Cultivated ITSCs were positive for nestin and S100 and the neural crest markers Slug and SOX10. Whole genome microarray analysis showed pronounced differences to human ES cells in respect to pluripotency markers OCT4, SOX2, LIN28, and NANOG, whereas expression of WDR5, KLF4, and c-MYC was nearly similar. ITSCs were able to differentiate into cells with neuro-ectodermal and mesodermal phenotype. Additionally ITSCs are able to survive and perform neural crest typical chain migration in vivo when transplanted into chicken embryos. However ITSCs do not form teratomas in severe combined immunodeficient mice. Finally, we developed a separation strategy based on magnetic cell sorting of p75NTR positive ITSCs that formed larger neurospheres and proliferated faster than p75NTR negative ITSCs. Taken together our study describes a novel, readily accessible source of multipotent human NCSCs for potential cell-replacement therapy. PMID:22128806

  7. Gastrointestinal absorption of plutonium, uranium and neptunium in fed and fasted adult baboons: Application to humans

    SciTech Connect

    Bhattacharyya, M.H.; Larsen, R.P.; Oldham, R.D.; Moretti, E.S. ); Cohen, N.; Ralston, L.G.; Ayres, L. )

    1992-03-01

    Gastrointestinal (GI) absorption values of plutonium, uranium, and neptunium were determined in fed and fasted adult baboons. A dual isotope method of determining GI absorption, which does not require animal sacrifice, was validated and shown to compare well with the sacrifice method (summation of oral isotope in urine with that in tissues at sacrifice). For all three elements, mean GI absorption values were significantly high (5- to 50-fold) in 24-hour (h)-fasted animals than in fed animals, and GI absorption values for baboons agreed well with those for humans.

  8. 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.

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    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 177Lu-labeled hydroxyapatite (177Lu-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 177Lu-HA particles administered intra-articularly. Monitoring of activity distribution was performed by static imaging of knee joint and whole-body gamma imaging. The patients were evaluated clinically before RSV and at 6 months after the treatment by considering the pain improvement from baseline values in terms of a 100-point visual analog scale (VAS), the improvement of knee flexibility and the pain remission during the night. RSV response was classified as poor (VAS < 25), fair (VAS ≥ 25-50), good (VAS ≥ 50-75) and excellent (VAS ≥ 75), with excellent and good results considered to be success, while fair and poor as failure and also by range of motion. Three phase bone scan (BS) was repeated after 6 months and changes in the second phase of BS3 were assessed visually, using a four-degree scale and in the third phase, semiquantitatively with J/B ratio to see the response. Biochemical analysis of C-reactive protein (CRP) and fibrinogen was repeated after 48 h, 4 and 24 weeks. In all 10 patients, no leakage of administered activity to nontarget organs was visible in the whole-body scan. Static scans of the joint at 1 month revealed complete retention of 177Lu-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

  10. Innate Immunity in Human Embryonic Stem Cells: Comparison with Adult Human Endothelial Cells

    PubMed Central

    Badiger, Rekha; Paul-Clark, Mark; Moreno, Laura; Lendvai, Zsuzsanna; Wright, Jamie S.; Ali, Nadire N.; Harding, Sian E.; Mitchell, Jane A.

    2010-01-01

    Treatment of human disease with human embryonic stem cell (hESC)-derived cells is now close to reality, but little is known of their responses to physiological and pathological insult. The ability of cells to respond via activation of Toll like receptors (TLR) is critical in innate immune sensing in most tissues, but also extends to more general danger sensing, e.g. of oxidative stress, in cardiomyocytes. We used biomarker release and gene-array analysis to compare responses in hESC before and after differentiation, and to those in primary human endothelial cells. The presence of cardiomyocytes and endothelial cells was confirmed in differentiated cultures by immunostaining, FACS-sorting and, for cardiomyocytes, beating activity. Undifferentiated hESC did not respond with CXCL8 release to Gram positive or Gram negative bacteria, or a range of PAMPs (pathogen associated molecular patterns) for TLRs 1-9 (apart from flagellin, an activator of TLR5). Surprisingly, lack of TLR-dependent responses was maintained over 4 months of differentiation of hESC, in cultures which included cardiomyocytes and endothelial cells. In contrast, primary cultures of human aortic endothelial cells (HAEC) demonstrated responses to a broad range of PAMPs. Expression of downstream TLR signalling pathways was demonstrated in hESC, and IL-1β, TNFα and INFγ, which bypass the TLRs, stimulated CXCL8 release. NFκB pathway expression was also present in hESC and NFκB was able to translocate to the nucleus. Low expression levels of TLRs were detected in hESC, especially TLRs 1 and 4, explaining the lack of response of hESC to the main TLR signals. TLR5 levels were similar between differentiated hESC and HAEC, and siRNA knockdown of TLR5 abolished the response to flagellin. These findings have potential implications for survival and function of grafted hESC-derived cells. PMID:20463927

  11. Human herpesvirus 6-related fulminant myocarditis and hepatitis in an immunocompetent adult with fatal outcome.

    PubMed

    Chang, Yilan L; Parker, Mark E; Nuovo, Gerard; Miller, Joel B

    2009-05-01

    A 59-year-old previously healthy man had flulike symptoms of fever and diarrhea for a week, which worsened despite treatment with antibiotics. After admission, his medical condition rapidly deteriorated with renal failure, heart failure, and a marked increase of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase. The patient died of a cardiac arrhythmia 3 days after the admission. The autopsy showed diffuse myocarditis with a granulocytic and monocytic infiltrate, necrotizing arteritis of the coronary arteries, and fulminant hepatitis, with microvesicular steatosis and necrosis. Cell-free serum showed high copies of human herpesvirus 6 B variant DNA by polymerase chain reaction. Human herpesvirus 6 B was identified in the heart, liver, lung, and spleen by immunohistochemistry. No parvovirus B19 was evident in the heart by immunohistochemistry. Human herpesvirus 6 is increasingly found in association with myocarditis in immunocompromised patients; however, histopathologic features and the clinical severity of this disease have not yet been clearly defined. Only 4 to 5 cases of human herpesvirus 6 fulminant myocarditis have been reported, all in young children or immunosuppressed patients. To the best of our knowledge, this is the first case in the English literature of human herpesvirus 6 fulminant myocarditis and hepatitis in an immunocompetent adult with a fatal outcome. In addition, several pathologic features of our case have not been previously reported. PMID:19144379

  12. Human herpesvirus 7: antigenic properties and prevalence in children and adults.

    PubMed Central

    Wyatt, L S; Rodriguez, W J; Balachandran, N; Frenkel, N

    1991-01-01

    The recent isolation of human herpesvirus 7 (HHV-7) from activated CD4+ T lymphocytes of a healthy individual raises questions regarding the prevalence of this virus in humans and its immunological relationship to previously characterized human herpesviruses. We report that HHV-7 is a ubiquitous virus which is immunologically distinct from the highly prevalent T-lymphotropic HHV-6. Thus, (i) only two of six monoclonal antibodies to HHV-6 cross-reacted with HHV-7-infected cells, (ii) Western immunoblot analyses of viral proteins revealed different patterns for HHV-6- and HHV-7-infected cells, (iii) tests of sequential serum samples from children revealed seroconversion to HHV-6 without concomitant seroconversion to HHV-7, and (iv) in some instances HHV-7 infection occurred in the presence of high titers of HHV-6 antibodies, suggesting the lack of apparent protection of children seropositive for HHV-6 against subsequent infection with HHV-7. On the basis of the analyses of sera from children and adults it can be concluded that HHV-7 is a prevalent human herpesvirus which, like other human herpesviruses, infects during childhood. The age of infection appears to be somewhat later than the very early age documented for HHV-6. Images PMID:1656093

  13. Proteome Mapping of Adult Zebrafish Marrow Neutrophils Reveals Partial Cross Species Conservation to Human Peripheral Neutrophils

    PubMed Central

    Singh, Sachin Kumar; Sethi, Sachin; Aravamudhan, Sriram; Krüger, Marcus; Grabher, Clemens

    2013-01-01

    Neutrophil granulocytes are pivotal cells within the first line of host defense of the innate immune system. In this study, we have used a gel-based LC-MS/MS approach to explore the proteome of primary marrow neutrophils from adult zebrafish. The identified proteins originated from all major cellular compartments. Gene ontology analysis revealed significant association of proteins with different immune-related network and pathway maps. 75% of proteins identified in neutrophils were identified in neutrophils only when compared to neutrophil-free brain tissue. Moreover, cross-species comparison with human peripheral blood neutrophils showed partial conservation of immune-related proteins between human and zebrafish. This study provides the first zebrafish neutrophil proteome and may serve as a valuable resource for an understanding of neutrophil biology and innate immunity. PMID:24019943

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

    PubMed

    Schlenker, R A

    1988-04-01

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

  15. Cryoscanning electron microscopic study of the surface amorphous layer of articular cartilage.

    PubMed Central

    Kobayashi, S; Yonekubo, S; Kurogouchi, Y

    1995-01-01

    In order to elucidate the structure near the articular surface, frozen unfixed hydrated articular cartilage with subchondral bone from the pig knee was examined using a cryoscanning electron microscope (cryo-SEM). This method is considered to reduce the introduction of artefacts due to fixation and drying. An amorphous layer, without a collagen-fibril network or chondrocytes, covered most of the surface of the cartilage. This layer was termed the surface amorphous layer. It showed various appearances, which were classified into 4 groups. The average thickness of the layer did not differ among the 8 anatomical regions from which the specimens were taken. The thickness of the layer was found to correlate with the type of appearance of the layer. The 4 appearances associated with thicknesses in descending order are: 'streaked', 'foliate', 'spotted', and 'vestigial'. The surface layer observed in the cryo-SEM was thicker than that observed by a conventional SEM. This difference may be attributable to dehydration of the specimen used in specimen preparation for the latter technique. The layer was also observed in articular cartilage taken from human and rabbit knees. The layer was found to be unstable and to have very variable features. Its thickness and appearance may be influenced by various factors such as dehydration, fluid absorption or mechanical stress. Images Fig. 1 Fig. 3 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 Fig. 10 Fig. 11 Fig. 12 Fig. 13 Fig. 14 Fig. 15 Fig. 16 Fig. 17 Fig. 18 Fig. 19 PMID:7592006

  16. Learning new color names produces rapid increase in gray matter in the intact adult human cortex

    PubMed Central

    Kwok, Veronica; Niu, Zhendong; Kay, Paul; Zhou, Ke; Mo, Lei; Jin, Zhen; So, Kwok-Fai; Tan, Li Hai

    2011-01-01

    The human brain has been shown to exhibit changes in the volume and density of gray matter as a result of training over periods of several weeks or longer. We show that these changes can be induced much faster by using a training method that is claimed to simulate the rapid learning of word meanings by children. Using whole-brain magnetic resonance imaging (MRI) we show that learning newly defined and named subcategories of the universal categories green and blue in a period of 2 h increases the volume of gray matter in V2/3 of the left visual cortex, a region known to mediate color vision. This pattern of findings demonstrates that the anatomical structure of the adult human brain can change very quickly, specifically during the acquisition of new, named categories. Also, prior behavioral and neuroimaging research has shown that differences between languages in the boundaries of named color categories influence the categorical perception of color, as assessed by judgments of relative similarity, by response time in alternative forced-choice tasks, and by visual search. Moreover, further behavioral studies (visual search) and brain imaging studies have suggested strongly that the categorical effect of language on color processing is left-lateralized, i.e., mediated by activity in the left cerebral hemisphere in adults (hence “lateralized Whorfian” effects). The present results appear to provide a structural basis in the brain for the behavioral and neurophysiologically observed indices of these Whorfian effects on color processing. PMID:21464316

  17. Adult human arterial smooth muscle cells in primary culture. Modulation from contractile to synthetic phenotype.

    PubMed

    Thyberg, J; Nilsson, J; Palmberg, L; Sjölund, M

    1985-01-01

    Smooth muscle cells were isolated enzymatically from adult human arteries, grown in primary culture in medium containing 10% whole blood serum, and studied by transmission electron microscopy and [3H]thymidine autoradiography. In the intact arterial wall and directly after isolation, each smooth muscle cell had a nucleus with a wide peripheral zone of condensed chromatin and a cytoplasm dominated by myofilament bundles with associated dense bodies. After 1-2 days of culture, the cells had attached to the substrate and started to spread out. At the same time, a characteristic fine-structural modification took place. It included nuclear enlargement, dispersion of the chromatin and formation of large nucleoli. Moreover, myofilament bundles disappeared and an extensive rough endoplasmic reticulum and a large Golgi complex were organized in the cytoplasm. This morphological transformation of the cells was completed in 3-4 days. It was accompanied by initiation of DNA replication and mitosis. The observations demonstrate that adult human arterial smooth muscle cells, when cultivated in vitro, pass through a phenotypic modulation of the same type as arterial smooth muscle cells from experimental animals. This modulation gives the cells morphological and functional properties resembling those of the modified smooth muscle cells found in fibroproliferative lesions of atherosclerosis. Further studies of the regulation of smooth muscle phenotype and growth may provide important clues for a better understanding of the pathogenesis of atherosclerosis. PMID:3967287

  18. The Human Adult Skeletal Muscle Transcriptional Profile Reconstructed by a Novel Computational Approach

    PubMed Central

    Bortoluzzi, Stefania; d'Alessi, Fabio; Romualdi, Chiara; Danieli, Gian Antonio

    2000-01-01

    By applying a novel software tool, information on 4080 UniGene clusters was retrieved from three adult human skeletal muscle cDNA libraries, which were selected for being neither normalized nor subtracted. Reconstruction of a transcriptional profile of the corresponding tissue was attempted by a computational approach, classifying each transcript according to its level of expression. About 25% of the transcripts accounted for about 80% of the detected transcriptional activity, whereas most genes showed a low level of expression. This in silico transcriptional profile was then compared with data obtained by a SAGE study. A fairly good agreement between the two methods was observed. About 400 genes, highly expressed in skeletal muscle or putatively skeletal muscle-specific, may represent the minimal set of genes needed to determine the tissue specificity. These genes could be used as a convenient reference to monitor major changes in the transcriptional profile of adult human skeletal muscle in response to different physiological or pathological conditions, thus providing a framework for designing DNA microarrays and initiating biological studies. PMID:10720575

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

    PubMed

    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. PMID:24172073

  20. Long-Term Culture of Genome-Stable Bipotent Stem Cells from Adult Human Liver

    PubMed Central

    Huch, Meritxell; Gehart, Helmuth; van Boxtel, Ruben; Hamer, Karien; Blokzijl, Francis; Verstegen, Monique M.A.; Ellis, Ewa; van Wenum, Martien; Fuchs, Sabine A.; de Ligt, Joep; van de Wetering, Marc; Sasaki, Nobuo; Boers, Susanne J.; Kemperman, Hans; de Jonge, Jeroen; Ijzermans, Jan N.M.; Nieuwenhuis, Edward E.S.; Hoekstra, Ruurdtje; Strom, Stephen; Vries, Robert R.G.; van der Laan, Luc J.W.; Cuppen, Edwin; Clevers, Hans

    2015-01-01

    Summary Despite the enormous replication potential of the human liver, there are currently no culture systems available that sustain hepatocyte replication and/or function in vitro. We have shown previously that single mouse Lgr5+ liver stem cells can be expanded as epithelial organoids in vitro and can be differentiated into functional hepatocytes in vitro and in vivo. We now describe conditions allowing long-term expansion of adult bile duct-derived bipotent progenitor cells from human liver. The expanded cells are highly stable at the chromosome and structural level, while single base changes occur at very low rates. The cells can readily be converted into functional hepatocytes in vitro and upon transplantation in vivo. Organoids from α1-antitrypsin deficiency and Alagille syndrome patients mirror the in vivo pathology. Clonal long-term expansion of primary adult liver stem cells opens up experimental avenues for disease modeling, toxicology studies, regenerative medicine, and gene therapy. PMID:25533785

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

    PubMed

    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. PMID:25783792

  2. Human amniotic epithelial cells are reprogrammed more efficiently by induced pluripotency than adult fibroblasts.

    PubMed

    Easley, Charles A; Miki, Toshio; Castro, Carlos A; Ozolek, John A; Minervini, Crescenzio F; Ben-Yehudah, Ahmi; Schatten, Gerald P

    2012-06-01

    Cellular reprogramming from adult somatic cells into an embryonic cell-like state, termed induced pluripotency, has been achieved in several cell types. However, the ability to reprogram human amniotic epithelial cells (hAECs), an abundant cell source derived from discarded placental tissue, has only recently been investigated. Here we show that not only are hAECs easily reprogrammed into induced pluripotent stem cells (AE-iPSCs), but hAECs reprogram faster and more efficiently than adult and neonatal somatic dermal fibroblasts. Furthermore, AE-iPSCs express higher levels of NANOG and OCT4 compared to human foreskin fibroblast iPSCs (HFF1-iPSCs) and express decreased levels of genes associated with differentiation, including NEUROD1 and SOX17, markers of neuronal differentiation. To elucidate the mechanism behind the higher reprogramming efficiency of hAECs, we analyzed global DNA methylation, global histone acetylation, and the mitochondrial DNA A3243G point mutation. Whereas hAECs show no differences in global histone acetylation or mitochondrial point mutation accumulation compared to adult and neonatal dermal fibroblasts, hAECs demonstrate a decreased global DNA methylation compared to dermal fibroblasts. Likewise, quantitative gene expression analyses show that hAECs endogenously express OCT4, SOX2, KLF4, and c-MYC, all four factors used in cellular reprogramming. Thus, hAECs represent an ideal cell type for testing novel approaches for generating clinically viable iPSCs and offer significant advantages over postnatal cells that more likely may be contaminated by environmental exposures and infectious agents. PMID:22686477

  3. BCRP protein levels do not differ regionally in adult human livers, but decline in the elderly.

    PubMed

    Riches, Zoe; Abanda, Ngu; Collier, Abby C

    2015-12-01

    The aim of this study was to characterize the ontogeny and variability of the BCRP (ABCG2) transporter in healthy human liver. Levels of BCRP mRNA and protein were determined with q-RT-PCR and western blot in a cohort of 87 human livers aged from 7 days to 87 years. A study of the regional expression of BCRP within adult livers was also performed in a nested cohort of 14 individuals with multiple samples per person collected from pre-selected sites. Levels of BCRP mRNA were not significantly different at any age, but protein levels for BCRP were lower in the elderly compared with adults (p < 0.001) and children (p < 0.05). The intra-liver levels of BCRP protein ranged approximately 6.5-fold and inter-liver BCRP protein varied 8.5-fold in the cohort. No differences in BCRP mRNA or protein were observed with sex or ethnicity, although higher levels of BCRP mRNA were observed in livers from overweight individuals (Body Mass Index ≥ 25-29.9) as compared to underweight or ideal weight individuals. There were no differences in the levels of BCRP mRNA or protein in different regions of the large lobe (n = 3 regions), small lobe (n = 3 regions), directly adjacent to the portal vein or directly adjacent to the common bile duct. This indicates that BCRP researchers can source tissue from all parts of the adult liver without artificial bias in their results. Lower BCRP protein expression in the elderly may be associated with compromised xeno- and endobiotic transport. PMID:26462791

  4. Body size and human energy requirements: Reduced mass-specific total energy expenditure in tall adults.

    PubMed

    Heymsfield, Steven B; Pietrobelli, Angelo

    2010-01-01

    Mammalian resting energy expenditure (REE) increases as approximately weight(0.75) while mass-specific REE scales as approximately weight(-0.25). Energy needs for replacing resting losses are thus less relative to weight (W) in large compared with small mammals, a classic observation with biological implications. Human weight scales as approximately height(2) and tall adults thus have a greater weight than their short counterparts. However, it remains unknown if mass-specific energy requirements are less in tall adults; allometric models linking total energy expenditure (TEE) and weight with height (H) are lacking. We tested the hypothesis that mass-specific energy requirements scale inversely to height in adults by evaluating TEE (doubly labeled water) data collected by the National Academy of Sciences. Activity energy expenditure (AEE) was calculated from TEE, REE (indirect calorimetry), and estimated diet-induced energy expenditure. Main analyses focused on nonmorbidly obese subjects < or =50 yrs of age with non-negative AEE values (n = 404), although results were directionally similar for all samples. Allometric models, including age as a covariate, revealed significantly (P < 0.05) greater REE, AEE, and TEE as a function of height (range H(1.5-1.7)) in both men and women. TEE/W scaled negatively to height ( approximately H(-0.7), P < 0.01) with predicted mass-specific TEE (kcal/kg/d) at +/-2 SD for US height lower in tall compared with short men (40.3 vs. 46.5) and women (37.7 vs. 42.7). REE/W also scaled negatively to height in men (P < 0.001) and women (P < 0.01). Results were generally robust across several different analytic strategies. These observations reveal previously unforeseen associations between human stature and energy requirements that have implications for modeling efforts and provide new links to mammalian biology as a whole. PMID:19856424

  5. Technique for ultrasound-guided intraarticular cervical articular process injection in the dog.

    PubMed

    Levy, Matthew; Gaschen, Lorrie; Rademacher, Nathalie; Bragulla, Hermann

    2014-01-01

    Ultrasound-guided intraarticular injection of cervical articular process joints is a well-established procedure in both humans and horses for neck pain resulting from osteoarthritis, but the technique has not been described in dogs. Aims of this study were to describe the ultrasonographic anatomy and landmarks for cervical articular process joint injections in the dog, develop a technique for articular process joint injections using these landmarks, and determine the accuracy of injections and factors that may influence it. Eleven canine cadavers were used and bilateral joint spaces from C2-3 to C7-T1 were injected under ultrasound guidance with a blue radiopaque solution. A computed tomographic scan was acquired following each injection, and an injection score was assigned and compared with other patient-specific factors. Of the 132 injections performed, 110 (83.3%) were intraarticular, 20 (15.1%) were periarticular within 5 mm, and 2 (1.5%) were periarticular beyond 5 mm from the joint. There was no significant difference in mean scores between dogs. Only C2-3 had a significantly lower mean score than any other joint. There was no significant correlation between injection score and any other factors measured. The transverse processes of the cervical vertebrae served as excellent ultrasonographic landmarks for identifying the cervical articular process joints in dogs regardless of the size of the dog or location along the vertebrae. Accuracy of ultrasound-guided intraarticular process joint injection was 83% in dogs and similar to published techniques in horses. Further studies are needed to examine the safety and efficacy of this procedure in live animals. PMID:24506833

  6. Tissue Engineering of Articular Cartilage with Biomimetic Zones

    PubMed Central

    Klein, Travis J.; Malda, Jos; Sah, Robert L.

    2009-01-01

    Articular cartilage damage is a persistent and increasing problem with the aging population, and treatments to achieve biological repair or restoration remain a challenge. Cartilage tissue engineering approaches have been investigated for over 20 years, but have yet to achieve the consistency and effectiveness for widespread clinical use. One of the potential reasons for this is that the engineered tissues do not have or establish the normal zonal organization of cells and extracellular matrix that appears critical for normal tissue function. A number of approaches are being taken currently to engineer tissue that more closely mimics the organization of native articular cartilage. This review focuses on the zonal organization of native articular cartilage, strategies being used to develop such organization, the reorganization that occurs after culture or implantation, and future prospects for the tissue engineering of articular cartilage with biomimetic zones. PMID:19203206

  7. Simultaneous magnetic resonance imaging and consolidation measurement of articular cartilage.

    PubMed

    Wellard, Robert Mark; Ravasio, Jean-Philippe; Guesne, Samuel; Bell, Christopher; Oloyede, Adekunle; Tevelen, Greg; Pope, James M; Momot, Konstantin I

    2014-01-01

    Magnetic resonance imaging (MRI) offers the opportunity to study biological tissues and processes in a non-disruptive manner. The technique shows promise for the study of the load-bearing performance (consolidation) of articular cartilage and changes in articular cartilage accompanying osteoarthritis. Consolidation of articular cartilage involves the recording of two transient characteristics: the change over time of strain and the hydrostatic excess pore pressure (HEPP). MRI study of cartilage consolidation under mechanical load is limited by difficulties in measuring the HEPP in the presence of the strong magnetic fields associated with the MRI technique. Here we describe the use of MRI to image and characterize bovine articular cartilage deforming under load in an MRI compatible consolidometer while monitoring pressure with a Fabry-Perot interferometer-based fiber-optic pressure transducer. PMID:24803188

  8. Simultaneous Magnetic Resonance Imaging and Consolidation Measurement of Articular Cartilage

    PubMed Central

    Wellard, Robert Mark; Ravasio, Jean-Philippe; Guesne, Samuel; Bell, Christopher; Oloyede, Adekunle; Tevelen, Greg; Pope, James M.; Momot, Konstantin I.

    2014-01-01

    Magnetic resonance imaging (MRI) offers the opportunity to study biological tissues and processes in a non-disruptive manner. The technique shows promise for the study of the load-bearing performance (consolidation) of articular cartilage and changes in articular cartilage accompanying osteoarthritis. Consolidation of articular cartilage involves the recording of two transient characteristics: the change over time of strain and the hydrostatic excess pore pressure (HEPP). MRI study of cartilage consolidation under mechanical load is limited by difficulties in measuring the HEPP in the presence of the strong magnetic fields associated with the MRI technique. Here we describe the use of MRI to image and characterize bovine articular cartilage deforming under load in an MRI compatible consolidometer while monitoring pressure with a Fabry-Perot interferometer-based fiber-optic pressure transducer. PMID:24803188

  9. A literature review of lasers and articular cartilage.

    PubMed

    Vangsness, C T; Ghaderi, B

    1993-05-01

    Articles from the English literature concerning lasers and articular cartilage were reviewed. Different experimental methods and laser systems were analyzed. Many studies lacked scientific validity. Future investigations with sound biologic foundations are recommended. PMID:8327386

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

    PubMed Central

    Yamada, Jun; Abula, Kahaer; Inoue, Makiko; Sekiya, Ichiro; Muneta, Takeshi

    2014-01-01

    Activins are proinflammatory cytokines which belong to the TGFβ superfamily. Follistatin is an extracellular decoy receptor for activins. Since both activins and follistatin are expressed in articular cartilage, we hypothesized that activin-follistatin signaling participates in the process of joint inflammation and cartilage degeneration. To test this hypothesis, we examined the effects of follistatin in a carrageenan-induced mouse arthritis model. Synovitis induced by intra-articular injection of carrageenan was significantly alleviated by preinjection with follistatin. Macrophage infiltration into the synovial membrane was significantly reduced in the presence of follistatin. In addition, follistatin inhibited proteoglycan erosion induced by carrageenan in articular cartilage. These data indicate that activin-follistatin signaling is involved in joint inflammation and cartilage homeostasis. Our data suggest that follistatin can be a new therapeutic target for inflammation-induced articular cartilage degeneration. PMID:25574420

  11. Fractures of the articular processes of the cervical spine

    SciTech Connect

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

    1982-08-01

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

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

    NASA Astrophysics Data System (ADS)

    Carrete, Martina; Tella, José L.

    2013-12-01

    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.

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

    PubMed

    Carrete, Martina; Tella, José L

    2013-01-01

    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. PMID:24343659

  14. Extra-Articular Ganglion Cysts around the Knee Joint

    PubMed Central

    Park, Sang-Eun; Panchal, Karnav; Kim, Young-Yul; Ji, Jong-Hun; Park, Sung-Ryeoll; Park, Min-Kyu

    2015-01-01

    Purpose The purpose of this study was to report clinical results of open excision of extra-articular ganglion cysts around the knee joint combined with arthroscopic management of intra-articular pathologies if present. Materials and Methods Of the total 107 cases of cystic lesions around the knee, 23 cases of extra-articular ganglion cysts were reviewed between January 2006 and July 2011. There were 13 males and 10 females with a mean age of 48 years (range, 30 to 73 years). The mean follow-up duration was 40 months (range, 30 to 60 months). Preoperative magnetic resonance imaging (MRI) scan was done in all cases. Open surgical excision of the cyst was performed after arthroscopic management of intra-articular pathologies in all but 1 case. At the last follow-up, Lysholm and International Knee Documentation Committee (IKDC) scores were evaluated and MRI was conducted to detect recurrence. Results The mean Lysholm and IKDC scores showed significant improvement (p=0.005 and 0.013, respectively).The location of the cysts was anterior in 9, lateral in 7, medial in 6, and posterosuperior in 1. Intra-articular pathologies were found in 16/23 cases (69.6%). In 10/23 cases (43%), the cyst was connected to the knee joint. Three months postoperative MRI did not show any recurrence of ganglion cysts except for 1 case. Conclusions In the treatment of extra-articular ganglion cysts, MRI can be useful for detecting intra-articular lesions and connecting orifices, and arthroscopic management of intra-articular pathologies with open excision of the cyst should be considered as a viable treatment option. PMID:26672721

  15. Effect of pulsed electromagnetic fields on proteoglycan biosynthesis of articular cartilage is age dependent

    PubMed Central

    Bobacz, K; Graninger, W B; Amoyo, L; Smolen, J S

    2006-01-01

    Objective To investigate the effects of a pulsed electromagnetic field (EMF) on articular cartilage matrix biosynthesis with regard to age and cartilage damage using a matrix depleted cartilage explant model. Methods Cartilage explants were obtained from metacarpophalangeal joints of calves and adult cows. After depletion of the extracellular matrix by trypsin digestion, samples were maintained in serum‐free basal medium with and without the addition of interleukin 1β (IL1β). Half the samples were subjected to an EMF for 24 minutes daily; the other half were left untreated. Undigested and untreated explants served as negative controls. After 7 days, biosynthesis of matrix macromolecules was assessed by [35S]sulphate incorporation and values were normalised to hydroxyproline content. Results The EMF increased matrix macromolecule synthesis in undigested, untreated explants (p<0.009). In matrix depleted samples the EMF had no stimulatory effect on proteoglycan biosynthesis. IL1β significantly decreased the de novo synthesis of matrix macromolecules (p<0.00004) in young and adult samples, but an EMF partly counteracted this inhibitory effect in cartilage samples from young, but not old animals. Conclusion EMF promoted matrix macromolecule biosynthesis in intact tissue explants but had no stimulatory effect on damaged articular cartilage. The supressive effects of IL1β were partially counteracted by EMF exposure, exclusively in cartilage derived from young animals. An EMF has age dependent chondroprotective but not structure modifying properties when cartilage integrity is compromised. PMID:16769781

  16. Examining the relationship between childhood animal cruelty motives and recurrent adult violent crimes toward humans.

    PubMed

    Overton, Joshua C; Hensley, Christopher; Tallichet, Suzanne E

    2012-03-01

    Few researchers have studied the predictive ability of childhood animal cruelty motives as they are associated with later recurrent violence toward humans. Based on a sample of 180 inmates at one medium- and one maximum-security prison in a Southern state, the present study examines the relationship among several retrospectively identified motives (fun, out of anger, hate for the animal, and imitation) for childhood animal cruelty and the later commission of violent crimes (murder, rape, assault, and robbery) against humans. Almost two thirds of the inmates reported engaging in childhood animal cruelty for fun, whereas almost one fourth reported being motivated either out of anger or imitation. Only one fifth of the respondents reported they had committed acts of animal cruelty because they hated the animal. Regression analyses revealed that recurrent animal cruelty was the only statistically significant variable in the model. Respondents who had committed recurrent childhood animal cruelty were more likely to have had committed recurrent adult violence toward humans. None of the motives for committing childhood animal cruelty had any effect on later violence against humans. PMID:22007109

  17. Isolation and Characterization of Human Adult Epithelial Stem Cells from the Periodontal Ligament.

    PubMed

    Athanassiou-Papaefthymiou, M; Papagerakis, P; Papagerakis, S

    2015-11-01

    We report a novel method for the isolation of adult human epithelial stem cells (hEpiSCs) from the epithelial component of the periodontal ligament-the human epithelial cell rests of Malassez (hERM). hEpiSC-rich integrin-α6(+ve) hERM cells derived by fluorometry can be clonally expanded, can grow organoids, and express the markers of pluripotency (OCT4, NANOG, SOX2), polycomb protein RING1B, and the hEpiSC supermarker LGR5. They maintain the growth profile of their originating hERM in vitro. Subcutaneous cotransplantation with mesenchymal stem cells from the dental pulp on poly-l-lactic acid scaffolds in nude mice gave rise to perfect heterotopic ossicles in vivo with ultrastructure of dentin, enamel, cementum, and bone. These remarkable fully mineralized ossicles underscore the importance of epithelial-mesenchymal crosstalk in tissue regeneration using human progenitor stem cells, which may have already committed to lineage despite maintaining hallmarks of pluripotency. In addition, we report the clonal expansion and isolation of human LGR5(+ve) cells from the hERM in xeno-free culture conditions. The genetic profile of LGR5(+ve) cells includes both markers of pluripotency and genes important for secretory epithelial and dental epithelial cell differentiation, giving us a first insight into periodontal ligament-derived hEpiSCs. PMID:26392003

  18. Inhibition of ZEB1 expression induces redifferentiation of adult human β cells expanded in vitro

    PubMed Central

    Sintov, Elad; Nathan, Gili; Knoller, Sarah; Pasmanik-Chor, Metsada; Russ, Holger A.; Efrat, Shimon

    2015-01-01

    In-vitro expansion of functional adult human β-cells is an attractive approach for generating insulin-producing cells for transplantation. However, human islet cell expansion in culture results in loss of β-cell phenotype and epithelial-mesenchymal transition (EMT). This process activates expression of ZEB1 and ZEB2, two members of the zinc-finger homeobox family of E-cadherin repressors, which play key roles in EMT. Downregulation of ZEB1 using shRNA in expanded β-cell-derived (BCD) cells induced mesenchymal-epithelial transition (MET), β-cell gene expression, and proliferation attenuation. In addition, inhibition of ZEB1 expression potentiated redifferentiation induced by a combination of soluble factors, as judged by an improved response to glucose stimulation and a 3-fold increase in the fraction of C-peptide-positive cells to 60% of BCD cells. Furthermore, ZEB1 shRNA led to increased insulin secretion in cells transplanted in vivo. Our findings suggest that the effects of ZEB1 inhibition are mediated by attenuation of the miR-200c target genes SOX6 and SOX2. These findings, which were reproducible in cells derived from multiple human donors, emphasize the key role of ZEB1 in EMT in cultured BCD cells and support the value of ZEB1 inhibition for BCD cell redifferentiation and generation of functional human β-like cells for cell therapy of diabetes. PMID:26264186

  19. The Model Human Processor and the Older Adult: Parameter Estimation and Validation Within a Mobile Phone Task

    PubMed Central

    Jastrzembski, Tiffany S.; Charness, Neil

    2009-01-01

    The authors estimate weighted mean values for nine information processing parameters for older adults using the Card, Moran, and Newell (1983) Model Human Processor model. The authors validate a subset of these parameters by modeling two mobile phone tasks using two different phones and comparing model predictions to a sample of younger (N = 20; Mage = 20) and older (N = 20; Mage = 69) adults. Older adult models fit keystroke-level performance at the aggregate grain of analysis extremely well (R = 0.99) and produced equivalent fits to previously validated younger adult models. Critical path analyses highlighted points of poor design as a function of cognitive workload, hardware/software design, and user characteristics. The findings demonstrate that estimated older adult information processing parameters are valid for modeling purposes, can help designers understand age-related performance using existing interfaces, and may support the development of age-sensitive technologies. PMID:18194048

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

    PubMed

    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. PMID:26860863

  1. Health Human Capital in Sub-Saharan Africa: Conflicting Evidence from Infant Mortality Rates and Adult Heights

    PubMed Central

    Akachi, Yoko; Canning, David

    2011-01-01

    We investigate trends in cohort infant mortality rates and adult heights in 39 developing countries since 1960. In most regions of the world improved nutrition, and reduced childhood exposure to disease, have lead to improvements in both infant mortality and adult stature. In Sub-Saharan Africa, however, despite declining infant mortality rates, adult heights have not increased. We argue that in Sub-Saharan Africa the decline in infant mortality may have been due to interventions that prevent infant deaths rather than improved nutrition and childhood morbidity. Despite declining infant mortality, Sub-Saharan Africa may not be experiencing increases in health human capital. PMID:20634153

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

    NASA Astrophysics Data System (ADS)

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

    2005-05-01

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

  3. Spatial Mapping of the Biomechanical Properties of the Pericellular Matrix of Articular Cartilage Measured In Situ via Atomic Force Microscopy

    PubMed Central

    Darling, Eric M.; Wilusz, Rebecca E.; Bolognesi, Michael P.; Zauscher, Stefan; Guilak, Farshid

    2010-01-01

    Abstract In articular cartilage, chondrocytes are surrounded by a narrow region called the pericellular matrix (PCM), which is biochemically, structurally, and mechanically distinct from the bulk extracellular matrix (ECM). Although multiple techniques have been used to measure the mechanical properties of the PCM using isolated chondrons (the PCM with enclosed cells), few studies have measured the biomechanical properties of the PCM in situ. The objective of this study was to quantify the in situ mechanical properties of the PCM and ECM of human, porcine, and murine articular cartilage using atomic force microscopy (AFM). Microscale elastic moduli were quantitatively measured for a region of interest using stiffness mapping, or force-volume mapping, via AFM. This technique was first validated by means of elastomeric models (polyacrylamide or polydimethylsiloxane) of a soft inclusion surrounded by a stiff medium. The elastic properties of the PCM were evaluated for regions surrounding cell voids in the middle/deep zone of sectioned articular cartilage samples. ECM elastic properties were evaluated in regions visually devoid of PCM. Stiffness mapping successfully depicted the spatial arrangement of moduli in both model and cartilage surfaces. The modulus of the PCM was significantly lower than that of the ECM in human, porcine, and murine articular cartilage, with a ratio of PCM to ECM properties of ∼0.35 for all species. These findings are consistent with previous studies of mechanically isolated chondrons, and suggest that stiffness mapping via AFM can provide a means of determining microscale inhomogeneities in the mechanical properties of articular cartilage in situ. PMID:20550897

  4. Articular cartilage: from formation to tissue engineering.

    PubMed

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

    2016-05-26

    Hyaline cartilage is the nonlinear, inhomogeneous, anisotropic, poro-viscoelastic connective tissue that serves as friction-reducing and load-bearing cushion in synovial joints and is vital for mammalian skeletal movements. Due to its avascular nature, low cell density, low proliferative activity and the tendency of chondrocytes to de-differentiate, cartilage cannot regenerate after injury, wear and tear, or degeneration through common diseases such as osteoarthritis. Therefore severe damage usually requires surgical intervention. Current clinical strategies to generate new tissue include debridement, microfracture, autologous chondrocyte transplantation, and mosaicplasty. While articular cartilage was predicted to be one of the first tissues to be successfully engineered, it proved to be challenging to reproduce the complex architecture and biomechanical properties of the native tissue. Despite significant research efforts, only a limited number of studies have evolved up to the clinical trial stage. This review article summarizes the current state of cartilage tissue engineering in the context of relevant biological aspects, such as the formation and growth of hyaline cartilage, its composition, structure and biomechanical properties. Special attention is given to materials development, scaffold designs, fabrication methods, and template-cell interactions, which are of great importance to the structure and functionality of the engineered tissue. PMID:26923076

  5. Extensive Neuronal Differentiation of Human Neural Stem Cell Grafts in Adult Rat Spinal Cord

    PubMed Central

    Yan, Jun; Xu, Leyan; Welsh, Annie M; Hatfield, Glen; Hazel, Thomas; Johe, Karl; Koliatsos, Vassilis E

    2007-01-01

    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 challenges remain

  6. Feasibility study of a novel intraosseous device in adult human cadavers

    PubMed Central

    Singh, Sandeep; Aggarwal, Praveen; Lodha, Rakesh; Agarwal, Ramesh; Gupta, Arun Kr.; Dhingra, Renu; Karve, Jayant Sitaram; Jaggu, Srinivas Kiran; Bhargava, Balram

    2016-01-01

    Background & objectives: Intraosseous (IO) access is an alternative to difficult intravenous (iv) access during emergency clinical situations. Existing IO solutions are expensive, require power supply and trained manpower; limiting their use in resource constrained settings. To address these limitations, a novel IO device has been developed. The objectives of this study were to evaluate functionality and safety of this device in adult human cadavers. Methods: The ability of the IO device to penetrate the proximal and/or distal tibia was evaluated in three adult cadavers. Subjective parameters of loss of resistance, stable needle hold, easy needle withdrawal and any damage to the device were evaluated during the study. The insertion time was the objective parameter measured. Four sets of radiographs per insertion confirmed the position of the needle and identified complications. Results: A single physician performed 12 IO access procedures using the same device. Penetration of proximal and/or distal tibia was achieved in all instances. It was successful in the first attempt in eight (66.7%) and during second attempt in the remaining. The mean time to insertion was 4.1 ± 3.1 sec. Appropriate insertion of needle in the intra-medullary space of bone was confirmed with radiological examination in 10 (83.3%) insertions. In two occasions after penetrating the cortical layer of bone, the device overshot the intra-medullary space, as detected by radiological examination. Device got bent during insertion in one instance. There was no evidence of needle breakage or bone fracture. The needle could be withdrawn effortlessly in all instances. Interpretation & conclusions: The novel IO device could successfully penetrate the adult cadaver bones in most cases. Further studies are needed to confirm these results on a large sample. PMID:27241639

  7. Isolation of high-purity myenteric plexus from adult human and mouse gastrointestinal tract

    PubMed Central

    Grundmann, David; Klotz, Markus; Rabe, Holger; Glanemann, Matthias; Schäfer, Karl-Herbert

    2015-01-01

    The enteric nervous system (ENS) orchestrates a broad range of important gastrointestinal functions such as intestinal motility and gastric secretion. The ENS can be affected by environmental factors, diet and disease. Changes due to these alterations are often hard to evaluate in detail when whole gut samples are used. Analyses based on pure ENS tissue can more effectively reflect the ongoing changes during pathological processes. Here, we present an optimized approach for the isolation of pure myenteric plexus (MP) from adult mouse and human. To do so, muscle tissue was individually digested with a purified collagenase. After incubation and a gentle mechanical disruption step, MP networks could be collected with anatomical integrity. These tissues could be stored and used either for immediate genomic, proteomic or in vitro approaches, and enteric neurospheres could be generated and differentiated. In a pilot experiment, the influence of bacterial lipopolysaccharide on human MP was analyzed using 2-dimensional gel electrophoresis. The method also allows investigation of factors that are secreted by myenteric tissue in vitro. The isolation of pure MP in large amounts allows new analytical approaches that can provide a new perspective in evaluating changes of the ENS in experimental models, human disease and aging. PMID:25791532

  8. Parietal Bone Thickness and Vascular Diameters in Adult Modern Humans: A Survey on Cranial Remains.

    PubMed

    Eisová, Stanislava; Rangel de Lázaro, Gizéh; Píšová, Hana; Pereira-Pedro, Sofia; Bruner, Emiliano

    2016-07-01

    Cranial bone thickness varies among modern humans, and many factors influencing this variability remain unclear. Growth hormones and physical activity are thought to influence the vault thickness. Considering that both systemic factors and energy supply influence the vascular system, and taking into account the structural and biomechanical interaction between endocranial vessels and vault bones, in this study we evaluate the correlation between vascular and bone diameters. In particular, we tested the relationship between the thickness of the parietal bone (which is characterized, in modern humans, by a complex vascular network) and the lumen size of the middle meningeal and diploic vessels, in adult modern humans. Our results show no patent correlation between the thickness of parietal bone and the size of the main vascular channels. Values and distributions of the branching patterns, as well as anatomical relationships between vessels and bones, are also described in order to provide information concerning the arrangement of the endocranial vascular morphology. This information is relevant in both evolutionary and medical contexts. Anat Rec, 299:888-896, 2016. © 2016 Wiley Periodicals, Inc. PMID:27072555

  9. Adipogenic potential in human mesenchymal stem cells strictly depends on adult or foetal tissue harvest.

    PubMed

    Ragni, Enrico; Viganò, Mariele; Parazzi, Valentina; Montemurro, Tiziana; Montelatici, Elisa; Lavazza, Cristiana; Budelli, Silvia; Vecchini, Alba; Rebulla, Paolo; Giordano, Rosaria; Lazzari, Lorenza

    2013-11-01

    Cell-based therapies promise important developments for regenerative medicine purposes. Adipose tissue and the adipogenic process has become central to an increasing number of translational efforts in addition to plastic and reconstructive surgical applications. In recent experimental clinical trials, human mesenchymal stem cells (MSC) have been proven to be well tolerated because of their low immunoreactivity. MSC are multipotent cells found among mature cells in different tissues and organs with the potentiality to differentiate in many cell types, including osteocytes, chondrocytes and adipocytes, thus being a suitable cell source for tissue engineering strategies. We compared the adipogenic potential of MSC originated from two adult sources as fat pads and bone marrow, and from four foetal sources as umbilical cord blood, Wharton's jelly, amniotic fluid and preterm umbilical cord perivascular cells. Surprisingly, adult MSC displayed higher differentiation capacities confirmed by gene expression analysis on a selected panel of adipogenesis-related genes. Further, an in-depth molecular analysis highlighted the early and vigorous activation of the PPARγ transcription factor-cascade in adipose-derived MSC that resulted to be both delayed and reduced in foetal MSC accounting for their lack of adipogenic potential. Thus, MSC show a different degree of phenotypic plasticity depending on the source tissue, that should be taken into consideration for the selection of the most appropriate MSC type for specific tissue regeneration purposes. PMID:23942228

  10. Sex differences in spatial navigation and perception in human adolescents and emerging adults

    PubMed Central

    Sneider, Jennifer Tropp; Hamilton, Derek A.; Cohen-Gilbert, Julia E.; Crowley, David J.; Rosso, Isabelle M.; Silveri, Marisa M.

    2014-01-01

    Males typically outperform females on spatial tasks, beginning early in life and continuing into adulthood. This study aimed to characterize age and sex differences in human spatial ability using a virtual Water Maze Task (vWMT), which is based on the classic Morris water maze spatial navigation task used in rodents. Performance on the vWMT and on a task assessing visuospatial perception, Mental Rotations Test (MRT), was examined in 33 adolescents and 39 emerging adults. For the vWMT, significant effects of age and sex were observed for path length in the target region (narrower spatial sampling), and heading error, with emerging adults performing better than adolescents, and an overall male advantage. For the MRT, males scored higher than females, but only in emerging adulthood. Overall, sex differences in visuospatial perception (MRT) emerge differently from those observed on a classic navigation task, with age and sex-specific superior vWMT performance likely related to the use of more efficient strategies. Importantly, these results extend the developmental timeline of spatial ability characterization to include adolescent males and females performing a virtual version of the classic vWMT. PMID:25464337

  11. Human-figure drawing and memory functioning across the adult life span.

    PubMed

    Ericsson, K; Winblad, B; Nilsson, L -G.

    2001-03-01

    The main objective was to evaluate changes in the ability to draw the human figure (HFD) across adult life span and to relate these changes to those known to exist in memory function. Healthy adults (1000) from each of 10 five-year cohorts between 35 and 80 years were recruited randomly from a population in northern Sweden. Each participant was administered a health examination including cognitive testing and a drawing test, and an extensive examination of memory functions. For the drawing variables HFDarch and HFDtot, there is a steady decrease in episodic memory with poor drawers performing at a lower level. For semantic memory up to 65 years of age, there is no difference in performance, but thereafter a decrease. Good drawers show a better memory performance than poor drawers. For priming data for both HFDarch and HFDtot, there seems to be an interaction between age and drawing, such that poor drawers perform at a lower level for the two oldest groups but not for the youngest group. The HFDess is a valuable instrument and can support clinical evaluation as a screening for cognitive decline. The reduction of essential body details was strongly related to dementia progression, and thus as good a predictor of cognitive decline as episodic memory performance. The reduced capacity to perform a complex HFD declines with age and is most pronounced in the oldest age groups. PMID:11313105

  12. Prevalence of human norovirus and Clostridium difficile coinfections in adult hospitalized patients

    PubMed Central

    Stokely, Janelle N; Niendorf, Sandra; Taube, Stefan; Hoehne, Marina; Young, Vincent B; Rogers, Mary AM; Wobus, Christiane E

    2016-01-01

    Objective Human norovirus (HuNoV) and Clostridium difficile are common causes of infectious gastroenteritis in adults in the US. However, limited information is available regarding HuNoV and C. difficile coinfections. Our study was designed to evaluate the prevalence of HuNoV and C. difficile coinfections among adult patients in a hospital setting and disease symptomatology. Study design and setting For a cross-sectional analysis, 384 fecal samples were tested for the presence of C. difficile toxins from patients (n=290), whom the provider suspected of C. difficile infections. Subsequent testing was then performed for HuNoV genogroups I and II. Multinomial logistic regression was performed to determine symptoms more frequently associated with coinfections. Results The final cohort consisted of the following outcome groups: C. difficile (n=196), C. difficile + HuNoV coinfection (n=40), HuNoV only (n=12), and neither (n=136). Coinfected patients were more likely to develop nausea, gas, and abdominal pain and were more likely to seek treatment in the winter season compared with individuals not infected or infected with either pathogen alone. Conclusion Our study revealed that patients with coinfection are more likely to experience certain gastrointestinal symptoms, in particular abdominal pain, suggesting an increased severity of disease symptomatology in coinfected patients. PMID:27418856

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

    PubMed Central

    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

  14. Schizophrenia susceptibility alleles are enriched for alleles that affect gene expression in adult human brain

    PubMed Central

    Richards, Alexander L; Jones, Lesley; Moskvina, Valentina; Kirov, George; Gejman, Pablo V; Levinson, Douglas F; Sanders, Alan R; Purcell, Shaun; Visscher, Peter M; Craddock, Nick; Owen, Michael J; Holmans, Peter; O’Donovan, Michael C

    2016-01-01

    It is widely thought that alleles that influence susceptibility to common diseases, including schizophrenia, will frequently do so through effects on gene expression. Since only a small proportion of the genetic variance for schizophrenia has been attributed to specific loci, this remains an unproven hypothesis. The International Schizophrenia Consortium (ISC) recently reported a substantial polygenic contribution to that disorder, and that schizophrenia risk alleles are enriched among SNPs selected for marginal evidence for association (p<0.5) from genome wide association studies (GWAS). It follows that if schizophrenia susceptibility alleles are enriched for those that affect gene expression, those marginally associated SNPs which are also eQTLs should carry more true association signals compared with SNPs which are not. To test this, we identified marginally associated (p<0.5) SNPs from two of the largest available schizophrenia GWAS datasets. We assigned eQTL status to those SNPs based upon an eQTL dataset derived from adult human brain. Using the polygenic score method of analysis reported by the ISC, we observed and replicated the observation that higher probability cis-eQTLs predicted schizophrenia better than those with a lower probability for being a cis-eQTL. Our data support the hypothesis that alleles conferring risk of schizophrenia are enriched among those that affect gene expression. Moreover, our data show that notwithstanding the likely developmental origin of schizophrenia, studies of adult brain tissue can in principle allow relevant susceptibility eQTLs to be identified. PMID:21339752

  15. Experimental Infection of Adults With Recombinant Wild-Type Human Metapneumovirus

    PubMed Central

    Talaat, Kawsar R.; Karron, Ruth A.; Thumar, Bhagvanji; McMahon, Bridget A.; Schmidt, Alexander C.; Collins, Peter L.; Buchholz, Ursula J.

    2013-01-01

    Background. Human metapneumovirus (HMPV) causes lower respiratory tract infections in young children. rHMPV-SHs is a recombinant HMPV (rHMPV) based on a biologically derived wild-type HMPV strain. We characterized its infectivity and immunogenicity in healthy adults to determine whether it would be suitable for use as the parent virus for the development of live attenuated rHMPV vaccines. Methods. Twenty-one healthy adults were inoculated intranasally with 106 plaque-forming units of rHMPV-SHs. Respiratory symptoms and shedding of challenge virus were assessed. Neutralizing antibody responses, serum immunoglobulin G and A, and nasal wash specimen immunoglobulin A antibody responses to the HMPV F protein were also measured. Induction of nasal cytokines was assessed with electrochemiluminescence assays. Results. Nine subjects (43%) were infected with challenge virus as determined by virus detection and/or ≥4-fold rise in serum antibody titers. Peak viral shedding occurred on days 7–9 after infection. Four weeks after inoculation, 35% of subjects had any antibody response. Six of 9 infected subjects had respiratory symptoms, and 3 had headache after inoculation. Cytokine patterns differed considerably between subjects with similar illness severity and viral shedding. Conclusions. The rHMPV-SHs virus is infectious and is a suitable parent virus for development of live-attenuated HMPV vaccine candidates. Clinical Trials Registration. NCT01109329. PMID:23908489

  16. Micropatterning control of tubular commitment in human adult renal stem cells.

    PubMed

    Sciancalepore, Anna G; Portone, Alberto; Moffa, Maria; Persano, Luana; De Luca, Maria; Paiano, Aurora; Sallustio, Fabio; Schena, Francesco P; Bucci, Cecilia; Pisignano, Dario

    2016-07-01

    The treatment of renal injury by autologous, patient-specific adult stem cells is still an unmet need. Unsolved issues remain the spatial integration of stem cells into damaged areas of the organ, the commitment in the required cell type and the development of improved bioengineered devices. In this respect, biomaterials and architectures have to be specialized to control stem cell differentiation. Here, we perform an extensive study on micropatterned extracellular matrix proteins, which constitute a simple and non-invasive approach to drive the differentiation of adult renal progenitor/stem cells (ARPCs) from human donors. ARPCs are interfaced with fibronectin (FN) micropatterns, in the absence of exogenous chemicals or cellular reprogramming. We obtain the differentiation towards tubular cells of ARPCs cultured in basal medium conditions, the tubular commitment thus being specifically induced by micropatterned substrates. We characterize the stability of the tubular differentiation as well as the induction of a polarized phenotype in micropatterned ARPCs. Thus, the developed cues, driving the functional commitment of ARPCs, offer a route to recreate the microenvironment of the stem cell niche in vitro, that may serve, in perspective, for the development of ARPC-based bioengineered devices. PMID:27105437

  17. Localization of cyclooxygenase-1 and -2 in adult and fetal human kidney: implication for renal function.

    PubMed

    Kömhoff, M; Grone, H J; Klein, T; Seyberth, H W; Nüsing, R M

    1997-04-01

    To gain insight into the roles of cyclooxygenase (COX)-1 and -2 in human kidney, we analyzed their expressions and localization in adult and fetal normal kidney. Immunohistology showed expression of COX-1 in collecting duct cells, interstitial cells, endothelial cells, and smooth muscle cells of pre- and postglomerular vessels. Expression of COX-2 immunoreactive protein could be localized to endothelial and smooth muscle cells of arteries and veins and intraglomerularly in podocytes. In contrast to the rat, COX isoforms were not detected in the macula densa. These data were confirmed by in situ mRNA analysis using digoxigenin-labeled riboprobes. In fetal kidney, COX-1 was primarily expressed in podocytes and collecting duct cells. Expression levels of COX-1 in both cell types increased markedly from subcapsular to juxtamedullary cortex. Glomerular staining of COX-2 was detectable in podocytes only at the endstage of renal development. In summary, the localization of COX-2 suggests that this enzyme may be primarily involved in the regulation of renal perfusion and glomerular hemodynamics. The expression of COX-1 in podocytes of the fetal kidney and its absence in adult glomeruli suggests that this isoform might be involved in glomerulogenesis. PMID:9140046

  18. Pharmacological Induction of Human Fetal Globin Gene in Hydroxyurea-Resistant Primary Adult Erythroid Cells.

    PubMed

    Chou, Yu-Chi; Chen, Ruei-Lin; Lai, Zheng-Sheng; Song, Jen-Shin; Chao, Yu-Sheng; Shen, Che-Kun James

    2015-07-01

    Pharmacological induction of the fetal γ globin gene and the consequent formation of HbF (α2/γ2) in adult erythroid cells are one feasible therapeutic strategy for sickle cell disease (SCD) and severe β-thalassemias. Hydroxyurea (HU) is the current drug of choice for SCD, but serious side effects limit its clinical use. Moreover, 30 to 50% of patients are irresponsive to HU treatment. We have used high-throughput screening to identify benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one and its derivatives (compounds I to VI) as potent γ globin inducers. Of the compounds, I to V exert superior γ globin induction and have better therapeutic potential than HU, likely because of their activation of the p38 mitogen-activated protein kinase (MAPK) signaling pathway and modulation of expression levels and/or chromosome binding of γ globin gene regulators, including BCL11A, and chromatin structure over the γ globin promoter. Unlike sodium butyrate (NaB), the global levels of acetylated histones H3 and H4 are not changed by compound II treatment. Remarkably, compound II induces the γ globin gene in HU-resistant primary human adult erythroid cells, the p38 signaling pathway of which appears to be irresponsive to HU and NaB as well as compound II. This study provides a new framework for the development of new and superior compounds for treating SCD and severe β-thalassemias. PMID:25986606

  19. Sex differences in spatial navigation and perception in human adolescents and emerging adults.

    PubMed

    Sneider, Jennifer T; Hamilton, Derek A; Cohen-Gilbert, Julia E; Crowley, David J; Rosso, Isabelle M; Silveri, Marisa M

    2015-02-01

    Males typically outperform females on spatial tasks, beginning early in life and continuing into adulthood. This study aimed to characterize age and sex differences in human spatial ability using a virtual Water Maze Task (vWMT), which is based on the classic Morris water maze spatial navigation task used in rodents. Performance on the vWMT and on a task assessing visuospatial perception, Mental Rotations Test (MRT), was examined in 33 adolescents and 39 emerging adults. For the vWMT, significant effects of age and sex were observed for path length in the target region (narrower spatial sampling), and heading error, with emerging adults performing better than adolescents, and an overall male advantage. For the MRT, males scored higher than females, but only in emerging adulthood. Overall, sex differences in visuospatial perception (MRT) emerge differently from those observed on a classic navigation task, with age and sex-specific superior vWMT performance likely related to the use of more efficient strategies. Importantly, these results extend the developmental timeline of spatial ability characterization to include adolescent males and females performing a virtual version of the classic vWMT. PMID:25464337

  20. Large-scale remapping of visual cortex is absent in adult humans with macular degeneration.

    PubMed

    Baseler, Heidi A; Gouws, André; Haak, Koen V; Racey, Christopher; Crossland, Michael D; Tufail, Adnan; Rubin, Gary S; Cornelissen, Frans W; Morland, Antony B

    2011-05-01

    The occipital lobe contains retinotopic representations of the visual field. The representation of the central retina in early visual areas (V1-3) is found at the occipital pole. When the central retina is lesioned in both eyes by macular degeneration, this region of visual cortex at the occipital pole is accordingly deprived of input. However, even when such lesions occur in adulthood, some visually driven activity in and around the occipital pole can be observed. It has been suggested that this activity is a result of remapping of this area so that it now responds to inputs from intact, peripheral retina. We evaluated whether or not remapping of visual cortex underlies this activity. Our functional magnetic resonance imaging results provide no evidence of remapping, questioning the contemporary view that early visual areas of the adult human brain have the capacity to reorganize extensively. PMID:21441924

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

    PubMed

    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. PMID:25070322

  2. Augmenting NMDA receptor signaling boosts experience-dependent neuroplasticity in the adult human brain

    PubMed Central

    Forsyth, Jennifer K.; Bachman, Peter; Mathalon, Daniel H.; Roach, Brian J.; Asarnow, Robert F.

    2015-01-01

    Experience-dependent plasticity is a fundamental property of the brain. It is critical for everyday function, is impaired in a range of neurological and psychiatric disorders, and frequently depends on long-term potentiation (LTP). Preclinical studies suggest that augmenting N-methyl-d-aspartate receptor (NMDAR) signaling may promote experience-dependent plasticity; however, a lack of noninvasive methods has limited our ability to test this idea in humans until recently. We examined the effects of enhancing NMDAR signaling using d-cycloserine (DCS) on a recently developed LTP EEG paradigm that uses high-frequency visual stimulation (HFvS) to induce neural potentiation in visual cortex neurons, as well as on three cognitive tasks: a weather prediction task (WPT), an information integration task (IIT), and a n-back task. The WPT and IIT are learning tasks that require practice with feedback to reach optimal performance. The n-back assesses working memory. Healthy adults were randomized to receive DCS (100 mg; n = 32) or placebo (n = 33); groups were similar in IQ and demographic characteristics. Participants who received DCS showed enhanced potentiation of neural responses following repetitive HFvS, as well as enhanced performance on the WPT and IIT. Groups did not differ on the n-back. Augmenting NMDAR signaling using DCS therefore enhanced activity-dependent plasticity in human adults, as demonstrated by lasting enhancement of neural potentiation following repetitive HFvS and accelerated acquisition of two learning tasks. Results highlight the utility of considering cellular mechanisms underlying distinct cognitive functions when investigating potential cognitive enhancers. PMID:26621715

  3. A Morphologic and Morphometric Study of Foramen Vesalius in Dry Adult Human Skulls of Gujarat Region

    PubMed Central

    Singh, Praveen R.; Rajguru, Jaba

    2015-01-01

    Introduction: The foramen Vesalius is located within bony plate between the foramen ovale and the foramen rotundum in the floor of middle cranial fossa. This foramen allows passage of emissary veins which communicate cavernous sinus and pterygoid plexus of veins. AIM: To study the morphological and morphometric variations of foramen Vesalius in dry adult human skulls. Materials and Methods: One hundred and fifty dry adult human skulls were studied for variations in size, shape, presence/absence and any duplication/multiplication of the foramen Vesalius. After collecting data, appropriate statistical analysis was done. Results: The mean maximum dimension of foramen Vesalius was 0.98±0.67 mm on right side and 1.12±0.73 mm on left side. Foramen Vesalius was present in 90 (60%) skulls out of 150 observed. The incidence was 41(27.33%) on right side and 49 (32.67%) on left side. Foramen Vesalius was present unilaterally in 32 (35.56%) and bilaterally in 29 (32.23%) out of 90 skulls. Duplication of this foramen was observed in two skulls (one right side and one on left side). Foramen Vesalius was round in 72%, oval in 24% and irregular in 4% of total foramina present. Conclusion: Foramen Vesalius was present in 60% of total skulls studied. The foramen showed variations in incidence and shapes, while there was no statistically significant difference in the maximum dimension between foramen Vesalius on right and left side. There could be some developmental reasons to explain these variations. The findings of this study could be important to anatomists and also equally essential for clinicians who approach middle cranial cavity for various procedures. PMID:25859437

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

    PubMed

    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. PMID:26247808

  5. Augmenting NMDA receptor signaling boosts experience-dependent neuroplasticity in the adult human brain.

    PubMed

    Forsyth, Jennifer K; Bachman, Peter; Mathalon, Daniel H; Roach, Brian J; Asarnow, Robert F

    2015-12-15

    Experience-dependent plasticity is a fundamental property of the brain. It is critical for everyday function, is impaired in a range of neurological and psychiatric disorders, and frequently depends on long-term potentiation (LTP). Preclinical studies suggest that augmenting N-methyl-d-aspartate receptor (NMDAR) signaling may promote experience-dependent plasticity; however, a lack of noninvasive methods has limited our ability to test this idea in humans until recently. We examined the effects of enhancing NMDAR signaling using d-cycloserine (DCS) on a recently developed LTP EEG paradigm that uses high-frequency visual stimulation (HFvS) to induce neural potentiation in visual cortex neurons, as well as on three cognitive tasks: a weather prediction task (WPT), an information integration task (IIT), and a n-back task. The WPT and IIT are learning tasks that require practice with feedback to reach optimal performance. The n-back assesses working memory. Healthy adults were randomized to receive DCS (100 mg; n = 32) or placebo (n = 33); groups were similar in IQ and demographic characteristics. Participants who received DCS showed enhanced potentiation of neural responses following repetitive HFvS, as well as enhanced performance on the WPT and IIT. Groups did not differ on the n-back. Augmenting NMDAR signaling using DCS therefore enhanced activity-dependent plasticity in human adults, as demonstrated by lasting enhancement of neural potentiation following repetitive HFvS and accelerated acquisition of two learning tasks. Results highlight the utility of considering cellular mechanisms underlying distinct cognitive functions when investigating potential cognitive enhancers. PMID:26621715

  6. Alpha actin isoforms expression in human and rat adult cardiac conduction system.

    PubMed

    Orlandi, Augusto; Hao, Hiroyuki; Ferlosio, Amedeo; Clément, Sophie; Hirota, Seiichi; Spagnoli, Luigi Giusto; Gabbiani, Giulio; Chaponnier, Christine

    2009-04-01

    In the adult heart, cardiac muscle comprises the working myocardium and the conduction system (CS). The latter includes the sinoatrial node (SAN), the internodal tract or bundle (IB), the atrioventricular node (AVN), the atrioventricular bundle (AVB), the bundle branches (BB) and the peripheral Purkinje fibers (PF). Most of the information concerning the phenotypic features of CS tissue derives from the characterization of avian and rodent developing hearts; data concerning the expression of actin isoforms in adult CS cardiomyocytes are scarce. Using specific antibodies, we investigated the distribution of alpha-skeletal (alpha-SKA), alpha-cardiac (alpha-CA), alpha-smooth muscle (alpha-SMA) actin isoforms and other muscle-typical proteins in the CS of human and rat hearts at different ages. SAN and IB cardiomyocytes were characterized by the presence of alpha-SMA, alpha-CA, calponin and caldesmon, whereas alpha-SKA and vimentin were absent. Double immunofluorescence demonstrated the co-localisation of alpha-SMA and alpha-CA in I-bands of SAN cardiomyocytes. AVN, AVB, BB and PF cardiomyocytes were alpha-SMA, calponin, caldesmon and vimentin negative, and alpha-CA and alpha-SKA positive. No substantial differences in actin isoform distribution were observed in human and rat hearts, except for the presence of isolated subendocardial alpha-SMA positive cardiomyocytes co-expressing alpha-CA in the ventricular septum of the rat. Aging did not influence CS cardiomyocyte actin isoform expression profile. These findings support the concept that cardiomyocytes of SAN retain the phenotype of a developing myogenic cell throughout the entire life span. PMID:19281784

  7. Technological Overview of iPS Induction from Human Adult Somatic Cells

    PubMed Central

    Bayart, Emilie; Cohen-Haguenauer, Odile

    2013-01-01

    The unlimited proliferation capacity of embryonic stem cells (ESCs) combined with their pluripotent differentiation potential in various lineages raised great interest in both the scientific community and the public at large with hope for future prospects of regenerative medicine. However, since ESCs are derived from human embryos, their use is associated with significant ethical issues preventing broad studies and therapeutic applications. To get around this bottleneck, Takahashi and Yamanaka have recently achieved the conversion of adult somatic cells into ES-like cells via the forced expression of four transcription factors: Oct3/4, Sox2, Klf4 and c-Myc. This first demonstration attracted public attention and opened a new field of stem cells research with both cognitive – such as disease modeling - and therapeutic prospects. This pioneer work just received the 2012 Nobel Prize in Physiology or Medicine. Many methods have been reported since 2006, for the generation of induced pluripotent stem (iPS) cells. Most strategies currently under use are based on gene delivery via gamma-retroviral or lentiviral vectors; some experiments have also been successful using plasmids or transposons-based systems and few with adenovirus. However, most experiments involve integration in the host cell genome with an identified risk for insertional mutagenesis and oncogenic transformation. To circumvent such risks which are deemed incompatible with therapeutic prospects, significant progress has been made with transgene-free reprogramming methods based on e.g.: sendaï virus or direct mRNA or protein delivery to achieve conversion of adult cells into iPS. In this review we aim to cover current knowledge relating to both delivery systems and combinations of inducing factors including chemicals which are used to generate human iPS cells. Finally, genetic instability resulting from the reprogramming process is also being considered as a safety bottleneck for future clinical

  8. Technological overview of iPS induction from human adult somatic cells.

    PubMed

    Bayart, Emilie; Cohen-Haguenauer, Odile

    2013-04-01

    The unlimited proliferation capacity of embryonic stem cells (ESCs) combined with their pluripotent differentiation potential in various lineages raised great interest in both the scientific community and the public at large with hope for future prospects of regenerative medicine. However, since ESCs are derived from human embryos, their use is associated with significant ethical issues preventing broad studies and therapeutic applications. To get around this bottleneck, Takahashi and Yamanaka have recently achieved the conversion of adult somatic cells into ES-like cells via the forced expression of four transcription factors: Oct3/4, Sox2, Klf4 and c-Myc. This first demonstration attracted public attention and opened a new field of stem cells research with both cognitive - such as disease modeling - and therapeutic prospects. This pioneer work just received the 2012 Nobel Prize in Physiology or Medicine. Many methods have been reported since 2006, for the generation of induced pluripotent stem (iPS) cells. Most strategies currently under use are based on gene delivery via gamma-retroviral or lentiviral vectors; some experiments have also been successful using plasmids or transposons- based systems and few with adenovirus. However, most experiments involve integration in the host cell genome with an identified risk for insertional mutagenesis and oncogenic transformation. To circumvent such risks which are deemed incompatible with therapeutic prospects, significant progress has been made with transgene-free reprogramming methods based on e.g.: sendai virus or direct mRNA or protein delivery to achieve conversion of adult cells into iPS. In this review we aim to cover current knowledge relating to both delivery systems and combinations of inducing factors including chemicals which are used to generate human iPS cells. Finally, genetic instability resulting from the reprogramming process is also being considered as a safety bottleneck for future clinical translation

  9. A possible barrier function of the articular surface.

    PubMed

    Takada, N; Wada, I; Sugimura, I; Sakuma, E; Maruyama, H; Matsui, N

    1999-12-01

    Since MacConaill first reported the existence of a thin additional layer of the articular cartilage and named it the lamina splendens, there have been various opinions as to the role of this layer in the lubrication of the articular surface. We studied the superficial portion of the articular cartilage in the 20 day-old and 30 day-old rats using light and transmission electron microscopy. Furthermore, we studied the articular cartilage of the rat whose "cover layer" had been removed mechanically. Also, intraarticular latex beads injection, intraarticular dye injection using lithium carmine and supravital staining experiments were performed. On day 20, dye injected intraarticularly was clearly observed by light microscopy in chondrocytes situated in the deeper layers. The dye injected in the 30 day-old rats, however, was not seen in the chondrocytes but was found only in the superficial layer. Dye was found in the chondrocytes when supravital staining was performed in the articular cartilage of 30 day-old rats after mechanical removal of the cover layer. By transmission electron microscopy, a superficial layer consisted of fine filamentous structures was observed on the articular surface of the 30 day-old rats. The cover layer was destroyed by intraarticular injected latex beads in 30 day-old rats. These findings strongly support the idea that the cover layer acts as a barrier against substances which invade from the surface of the articular cartilage. The development period of the cover layer coincides with the initiation of weight bearing, and joint cartilage debris and pressure changes might further promote maturation. PMID:10659579

  10. Alloproliferation of purified CD4+ T cells to adult human heart endothelial cells, and study of second-signal requirements.

    PubMed Central

    McDouall, R M; Page, C S; Hafizi, S; Yacoub, M H; Rose, M L

    1996-01-01

    Human endothelial cells have been shown to be capable of causing direct allostimulation of T cells. However, the majority of immunological studies of human endothelial cells have been performed on cells of fetal origin. Here we use endothelial cells isolated from the adult human heart, both large vessel (coronary artery, pulmonary artery and aorta) and also microvascular. We have examined the ability of all these endothelial cells to cause direct allostimulation of T cells, and show that purified CD4+ T cells can proliferate in response to adult human heart endothelial cells, the response being dependent on pretreatment of the endothelial cells with interferon-gamma (IFN-gamma) and inhibited by anti-HLA-DR monoclonal antibody. The proliferative responses of CD8+ T cells to adult but not fetal endothelial cells was inconsistent and weak. Proliferative responses were not blocked by CTLA4-Ig, which inhibits T-cell responses to "classical' antigen-presenting cells (APC), but > 50% inhibition was achieved with monoclonal antibody to lymphocyte function-associated antigen-3 (LFA-3). These results show that adult human cardiovascular endothelial cells are capable of causing allostimulation of resting CD4+ T cells, using a different second signal to classical APC. In view of these findings endothelial cells should be considered as APC following solid organ transplantation. PMID:8943718

  11. Vulnerability of the superficial zone of immature articular cartilage to compressive injury

    PubMed Central

    Rolauffs, Bernd; Muehleman, Carol; Li, Jun; Kurz, Bodo; Kuettner, Klaus E.; Frank, Eliot; Grodzinsky, Alan J.

    2010-01-01

    Objective The zonal composition and functioning of adult articular cartilage causes depth-dependent responses to compressive injury. In immature cartilage, shear and compressive modulus, collagen and glycosaminoglycan (GAG) content also vary with depth. However, there is little understanding of depth-dependent damage caused by injury. Since injury to immature knee joints most often causes articular cartilage lesions, our objectives were to characterize the zonal dependence of biomechanical, biochemical and matrix-associated changes cause by injury. Methods Superficial and deeper zones disks from bovine calves were biomechanically characterized, injured (50% compression, 100%/sec) and re-characterized. Tissue compaction upon injury, GAG-density, GAG loss and biosynthesis were measured. Collagen-fiber-orientation and matrix damage was assessed using histology, Diffraction-Enhanced-X-Ray-Imaging, and texture analysis. Results Injured superficial disks showed surface disruption, compaction by 20.3±4.3%, and immediate biomechanical impairment: dynamic stiffness decreased to 7.1±3.3% of its initial value and equilibrium modulus was below detection. Tissue areas apparently intact by histology showed clear textural alterations. Injured deeper zones disks showed collagen crimping but remained undamaged and biomechanically intact. Superficial zone disks did not lose GAG immediately after injury but lost 17.8±1.4% by 48h; deeper zones disks lost only 2.8±0.3% GAG. Biomechanical impairment was primarily associated with structural damage. Conclusion The soft superficial zone of immature cartilage is vulnerable to compressive injury causing superficial matrix disruption, extensive compaction, and textural alteration, and resulting in immediate loss of biomechanical function. In conjunction with delayed superficial GAG loss, these changes may predispose the articular surface to further softening, damage, and increased risk of developing secondary OA. PMID:20556809

  12. Intra-articular Enzyme Replacement Therapy with rhIDUA is Safe, Well-Tolerated, and Reduces Articular GAG Storage in the Canine Model of Mucopolysaccharidosis Type I

    PubMed Central

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

    2014-01-01

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

  13. Modeling the biomechanics of articular eminence function in anthropoid primates

    PubMed Central

    Terhune, Claire E

    2011-01-01

    One of the most prominent features of the cranial component of the temporomandibular joint (TMJ) is the articular eminence (AE). This bar of bone is the primary surface upon which the condyle translates and rotates during movements of the mandible, and is therefore the primary point at which forces are transmitted from the mandible to the cranium during loading of the masticatory apparatus. The shape of the AE is highly variable across primates, and the raised eminence of humans has often been considered a defining feature of the human TMJ, yet few data exist to address whether this variation is functionally significant. This study used a broad interspecific sample of anthropoid primates to elaborate upon and test the predictions of a previously proposed model of AE function. This model suggests that AE inclination acts to resist non-normal forces at the TMJ, thereby maximizing bite forces (BFs). AE inclination was predicted to covary with two specific features of the masticatory apparatus: height of the TMJ above the occlusal plane; and inclination of the masticatory muscles. A correlate of this model is that taxa utilizing more resistant food objects should also exhibit relatively more inclined AEs. Results of the correlation analyses found that AE inclination is strongly correlated with height of the TMJ above the occlusal plane, but less so with inclination of the masticatory muscles. Furthermore, pairwise comparisons of closely related taxa with documented dietary differences found that the AE is consistently more inclined in taxa that utilize more resistant food items. These data preliminarily suggest that variation in AE morphology across anthropoid primates is functionally related to maximizing BFs, and add to the growing dataset of masticatory morphologies linked to feeding behavior. PMID:21923720

  14. Novel Observations From Next-Generation RNA Sequencing of Highly Purified Human Adult and Fetal Islet Cell Subsets.

    PubMed

    Blodgett, David M; Nowosielska, Anetta; Afik, Shaked; Pechhold, Susanne; Cura, Anthony J; Kennedy, Norman J; Kim, Soyoung; Kucukural, Alper; Davis, Roger J; Kent, Sally C; Greiner, Dale L; Garber, Manuel G; Harlan, David M; diIorio, Philip

    2015-09-01

    Understanding distinct gene expression patterns of normal adult and developing fetal human pancreatic α- and β-cells is crucial for developing stem cell therapies, islet regeneration strategies, and therapies designed to increase β-cell function in patients with diabetes (type 1 or 2). Toward that end, we have developed methods to highly purify α-, β-, and δ-cells from human fetal and adult pancreata by intracellular staining for the cell-specific hormone content, sorting the subpopulations by flow cytometry, and, using next-generation RNA sequencing, we report the detailed transcriptomes of fetal and adult α- and β-cells. We observed that human islet composition was not influenced by age, sex, or BMI, and transcripts for inflammatory gene products were noted in fetal β-cells. In addition, within highly purified adult glucagon-expressing α-cells, we observed surprisingly high insulin mRNA expression, but not insulin protein expression. This transcriptome analysis from highly purified islet α- and β-cell subsets from fetal and adult pancreata offers clear implications for strategies that seek to increase insulin expression in type 1 and type 2 diabetes. PMID:25931473

  15. A three-dimensional analysis of the geometry and curvature of the proximal tibial articular surface of hominoids

    NASA Astrophysics Data System (ADS)

    Landis, Emily K.; Karnick, Pushpak

    2006-02-01

    This study uses new three-dimensional imaging techniques to compare the articular curvature of the proximal tibial articular surface of hominoids. It has been hypothesized that the curvature of the anteroposterior contour of the lateral condyle in particular can be used to differentiate humans and apes and reflect locomotor function. This study draws from a large comparative sample of extant hominoids to obtain quantitative curvature data. Three-dimensional models of the proximal tibiae of 26 human, 15 chimpanzee, 15 gorilla, 17 orangutan, 16 gibbon and four Australopithecus fossil casts (AL 129-1b, AL 288-1aq, AL 333x-26, KNM-KP 29285A) were acquired with a Cyberware Model 15 laser digitizer. Curvature analysis was accomplished using a software program developed at Arizona State University's Partnership for Research In Stereo Modeling (PRISM) lab, which enables the user to extract curvature profiles and compute the difference between analogous curves from different specimens. Results indicate that the curvature of chimpanzee, gorilla and orangutan tibiae is significantly different from the curvature of human tibiae, thus supporting the hypothesized dichotomy between humans and great apes. The non-significant difference between gibbons and all other taxa indicates that gibbons have an intermediate pattern of articular curvature. All four Australopithecus tibia were aligned with the great apes.

  16. The Functions of BMP3 in Rabbit Articular Cartilage Repair.

    PubMed

    Zhang, Zhe; Yang, Wenyu; Cao, Yiting; Shi, Yanping; Lei, Chen; Du, Bo; Li, Xuemin; Zhang, Qiqing

    2015-01-01

    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. PMID:26528966

  17. Targeting TGFβ Signaling in Subchondral Bone and Articular Cartilage Homeostasis

    PubMed Central

    Zhen, Gehau; Cao, Xu

    2014-01-01

    Osteoarthritis (OA) is the most common degenerative joint disease, and there is no disease-modifying therapy for OA currently available. Targeting of articular cartilage alone may not be sufficient to halt this disease progression. Articular cartilage and subchondral bone act as a functional unit. Increasing evidence indicates that transforming growth factor β (TGFβ) plays a crucial role in maintaining homeostasis of both articular cartilage and subchondral bone. Activation of extracellular matrix latent TGFβ at the appropriate time and location is the prerequisite for its function. Aberrant activation of TGFβ in the subchondral bone in response to abnormal mechanical loading environment induces formation of osteroid islets at onset of osteoarthritis. As a result, alteration of subchondral bone structure changes the stress distribution on the articular cartilage and leads to its degeneration. Thus, inhibition of TGFβ activity in the subchondral bone may provide a new avenue of treatment for OA. In this review, we will respectively discuss the role of TGFβ in homeostasis of articular cartilage and subchondral bone as a novel target for OA therapy. PMID:24745631

  18. Remobilization does not fully restore immobilization induced articular cartilage atrophy.

    PubMed

    Haapala, J; Arokoski, J P; Hyttinen, M M; Lammi, M; Tammi, M; Kovanen, V; Helminen, H J; Kiviranta, I

    1999-05-01

    The recovery of articular cartilage from immobilization induced atrophy was studied. The right hind limbs of 29-week-old beagle dogs were immobilized for 11 weeks and then remobilized for 50 weeks. Cartilage from the immobilized knee was compared with tissue from age matched control animals. After the immobilization period, uncalcified articular cartilage glycosaminoglycan concentration was reduced by 20% to 23%, the reduction being largest (44%) in the superficial zone. The collagen fibril network showed no significant changes, but the amount of collagen crosslinks was reduced (13.5%) during immobilization. After remobilization, glycosaminoglycan concentration was restored at most sites, except for in the upper parts of uncalcified cartilage in the medial femoral and tibial condyles (9% to 17% less glycosaminoglycans than in controls). The incorporation of 35SO4 was not changed, and remobilization also did not alter the birefringence of collagen fibrils. Remobilization restored the proportion of collagen crosslinks to the control level. The changes induced by joint unloading were reversible at most sites investigated, but full restoration of articular cartilage glycosaminoglycan concentration was not obtained in all sites, even after remobilization for 50 weeks. This suggests that lengthy immobilization of a joint can cause long lasting articular cartilage proteoglycan alterations at the same time as collagen organization remains largely unchanged. Because proteoglycans exert strong influence on the biomechanical properties of cartilage, lengthy immobilization may jeopardize the well being of articular cartilage. PMID:10335301

  19. The Functions of BMP3 in Rabbit Articular Cartilage Repair

    PubMed Central

    Zhang, Zhe; Yang, Wenyu; Cao, Yiting; Shi, Yanping; Lei, Chen; Du, Bo; Li, Xuemin; Zhang, Qiqing

    2015-01-01

    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. PMID:26528966

  20. Leptin plays a catabolic role on articular cartilage.

    PubMed

    Bao, Jia-peng; Chen, Wei-ping; Feng, Jie; Hu, Peng-fei; Shi, Zhong-li; Wu, Li-dong

    2010-10-01

    Leptin has been shown to play a crucial role in the regulation of body weight. There is also evidence that this adipokine plays a key role in the process of osteoarthritis. However, the precise role of leptin on articular cartilage metabolism is not clear. We investigate the role of leptin on articular cartilage in vivo in this study. Recombinant rat leptin (100 μg) was injected into the knee joints of rats, 48 h later, messenger RNA (mRNA) expression and protein levels of basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), matrix metalloproteinases 2 and 9 (MMP-2, MMP-9), cathepsin D, and collagen II from articular cartilage were analyzed by real-time quantitative polymerase chain reaction (PCR) and western blot. Two important aggrecanases ADAMTS-4 and -5 (a disintegrin and metalloproteinase with thrombospondin motifs 4 and 5) were also analyzed by real-time quantitative PCR. Besides, articular cartilage was also assessed for proteoglycan/GAG content by Safranin O staining. Leptin significantly increased both gene and protein levels of MMP-2, MMP-9, cathepsin D, and collagen II, while decreased bFGF markedly in cartilage. Moreover, the gene expression of ADAMTS-4 and -5 were markedly increased, and histologically assessed depletion of proteoglycan in articular cartilage was observed after treatment with leptin. These results strongly suggest that leptin plays a catabolic role on cartilage metabolism and may be a disadvantage factor involve in the pathological process of OA. PMID:19876764

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

    PubMed

    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. PMID:14521517

  2. 24R,25-Dihydroxyvitamin D3 Protects against Articular Cartilage Damage following Anterior Cruciate Ligament Transection in Male Rats.

    PubMed

    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

  3. Preventing surgical complications: A survey on surgeons' perception of intra-articular malleolar screw misplacement in a cadaveric study

    PubMed Central

    2011-01-01

    Background Intra-articular hardware penetration can occur during osteosynthesis of ankle fractures, jeopardizing patients' outcomes. The intraoperative recognition of misplaced screws may be difficult due to the challenge of adequate interpretation of specific radiographic views. The present study was designed to investigate the diagnostic accuracy of standardized radiographic ankle views to determine the accuracy of diagnosis for intra-articular hardware placement of medial malleolar screws in a cadaveric model. Methods Nine preserved human cadaveric lower extremity specimens were used. Under direct visualization, two 4.0 mm cancellous screws were inserted into the medial malleolus. Each specimen was analyzed radiographically using antero-posterior (AP) and mortise views. The X-rays were randomly uploaded on a CD-ROM and included in a survey submitted to ten selected orthopaedic surgeons. The "Standards for Reporting of Diagnostic Accuracy" (STARD) questionnaire was used to determine the surgeons' perception of accuracy of screw placement in the medial malleolus. The selection of items was based on evidence whenever possible, therefore the "inconclusive" category was added. Inter and intraobserver variations were analyzed by kappa statistics to measure the amount of agreement. Results There was a poor level of agreement (kappa 0.4) both in the AP and in the mortise view among all the examiners. Associating the two x-rays, the agreement remained poor (kappa 0.4). In the cases in which there was a diagnosis of articular penetration, there was a poor agreement related to which of the screws was intra-articular. The number of "inconclusive" responses was low and constant, without a statistically significant difference between the subspecialists Conclusion The routine intraoperative radiographic imaging of the ankle is difficult to interpret and unreliable for detection of intra-articular hardware penetration. We therefore recommend to reposition medial malleolar

  4. Variant Human T-cell Lymphotropic Virus Type 1c and Adult T-cell Leukemia, Australia

    PubMed Central

    Cassar, Olivier; Bardy, Peter; Kearney, Daniel; Gessain, Antoine

    2013-01-01

    Human T-cell lymphotropic virus type 1 is endemic to central Australia among Indigenous Australians. However, virologic and clinical aspects of infection remain poorly understood. No attempt has been made to control transmission to indigenous children. We report 3 fatal cases of adult T-cell leukemia/lymphoma caused by human T-cell lymphotropic virus type 1 Australo-Melanesian subtype c. PMID:24047544

  5. Morphometry of cytoplasmic components of mammalian articular chondrocytes and corneal keratocytes: species and zonal variations of mitochondria in relation to nutrition.

    PubMed Central

    Stockwell, R A

    1991-01-01

    A morphometric analysis was made of nuclei and cytoplasmic structures in electron micrographs of chondrocytes in the non-calcified layer of articular cartilage of the femoral condyles in adult mouse and dog and of the human incus. Mitochondrial volume density (% cytoplasm) was lower in dog than in mouse cells or cells of the incus. It was also lower in the cells of deep zone cartilage than in superficial cells. Analysis of keratocytes of the corneal stroma in mouse and sheep gave similar findings to that in cartilage. Mitochondrial volume density was higher in mouse than in sheep keratocytes and, in sheep, higher in subepithelial (anterior) cells than in cells of the intermediate and subendothelial strata. Values in human stromal cells were similar to those in the sheep. Endoplasmic reticulum volume density was higher in mouse than in sheep keratocytes. Lipid and filaments were more abundant in dog than in mouse chondrocytes but keratocytes contained little or none. Mitochondrial volume densities correlate with diffusion distances (tissue thickness) from the sources of nutrition, for example, for oxygen, in the two tissues. The relationship to certain aspects of chondroitin sulphate and keratansulphate synthesis and topographical distribution in cartilage and cornea is discussed. Images Fig. 1 Fig. 2 PMID:2050570

  6. ECM microenvironment unlocks brown adipogenic potential of adult human bone marrow-derived MSCs.

    PubMed

    Lee, Michelle H; Goralczyk, Anna G; Kriszt, Rókus; Ang, Xiu Min; Badowski, Cedric; Li, Ying; Summers, Scott A; Toh, Sue-Anne; Yassin, M Shabeer; Shabbir, Asim; Sheppard, Allan; Raghunath, Michael

    2016-01-01

    Key to realizing the diagnostic and therapeutic potential of human brown/brite adipocytes is the identification of a renewable, easily accessible and safe tissue source of progenitor cells, and an efficacious in vitro differentiation protocol. We show that macromolecular crowding (MMC) facilitates brown adipocyte differentiation in adult human bone marrow mesenchymal stem cells (bmMSCs), as evidenced by substantially upregulating uncoupling protein 1 (UCP1) and uncoupled respiration. Moreover, MMC also induced 'browning' in bmMSC-derived white adipocytes. Mechanistically, MMC creates a 3D extracellular matrix architecture enshrouding maturing adipocytes in a collagen IV cocoon that is engaged by paxillin-positive focal adhesions also at the apical side of cells, without contact to the stiff support structure. This leads to an enhanced matrix-cell signaling, reflected by increased phosphorylation of ATF2, a key transcription factor in UCP1 regulation. Thus, tuning the dimensionality of the microenvironment in vitro can unlock a strong brown potential dormant in bone marrow. PMID:26883894

  7. A mystery unraveled: nontumorigenic pluripotent stem cells in human adult tissues

    PubMed Central

    Simerman, Ariel A; Perone, Marcelo J; Gimeno, María L; Dumesic, Daniel A; Chazenbalk, Gregorio D

    2014-01-01

    Introduction: Embryonic stem cells and induced pluripotent stem cells have emerged as the gold standard of pluripotent stem cells and the class of stem cell with the highest potential for contribution to regenerative and therapeutic application; however, their translational use is often impeded by teratoma formation, commonly associated with pluripotency. We discuss a population of nontumorigenic pluripotent stem cells, termed Multilineage Differentiating Stress Enduring (Muse) cells, which offer an innovative and exciting avenue of exploration for the potential treatment of various human diseases. Areas covered: This review discusses the origin of Muse cells, describes in detail their various unique characteristics, and considers future avenues of their application and investigation with respect to what is currently known of adult pluripotent stem cells in scientific literature. We begin by defining cell potency, then discuss both mesenchymal and various reported populations of pluripotent stem cells, and finally delve into Muse cells and the characteristics that set them apart from their contemporaries. Expert opinion: Muse cells derived from adipose tissue (Muse-AT) are efficiently, routinely and painlessly isolated from human lipoaspirate material, exhibit tripoblastic differentiation both spontaneously and under media-specific induction, and do not form teratomas. We describe qualities specific to Muse-AT cells and their potential impact on the field of regenerative medicine and cell therapy. PMID:24745973

  8. Electrophysiological Profiles of Induced Neurons Converted Directly from Adult Human Fibroblasts Indicate Incomplete Neuronal Conversion

    PubMed Central

    Koppensteiner, Peter; Boehm, Stefan

    2014-01-01

    Abstract The direct conversion of human fibroblasts to neuronal cells, termed human induced neuronal (hiN) cells, has great potential for future clinical advances. However, previous studies have not provided an in-depth analysis of electrophysiological properties of adult fibroblast-derived hiN cultures. We have examined the electrophysiological profile of hiN cells by measuring passive and active membrane properties, as well as spontaneous and evoked neurotransmission. We found that hiN cells exhibited passive membrane properties equivalent to perinatal rodent neurons. In addition, 30% of hiN cells were incapable of action potential (AP) generation and did not exhibit rectifying membrane currents, and none of the cells displayed firing patterns of typical glutamatergic pyramidal neurons. Finally, hiN cells exhibited neither spontaneous nor evoked neurotransmission. Our results suggest that current methods used to produce hiN cells provide preparations in which cells do not achieve the cellular properties of fully mature neurons, rendering these cells inadequate to investigate pathophysiological mechanisms. PMID:25437871

  9. Defining the role of common variation in the genomic and biological architecture of adult human height.

    PubMed

    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

    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. PMID:25282103

  10. Effect of exercise on fluoride metabolism in adult humans: a pilot study.

    PubMed

    V Zohoori, Fatemeh; Innerd, Alison; Azevedo, Liane B; Whitford, Gary M; Maguire, Anne

    2015-01-01

    An understanding of all aspects of fluoride metabolism is critical to identify its biological effects and avoid fluoride toxicity in humans. Fluoride metabolism and subsequently its body retention may be affected by physiological responses to acute exercise. This pilot study investigated the effect of exercise on plasma fluoride concentration, urinary fluoride excretion and fluoride renal clearance following no exercise and three exercise intensity conditions in nine healthy adults after taking a 1-mg Fluoride tablet. After no, light, moderate and vigorous exercise, respectively, the mean (SD) baseline-adjusted i) plasma fluoride concentration was 9.6(6.3), 11.4(6.3), 15.6(7.7) and 14.9(10.0) ng/ml; ii) rate of urinary fluoride excretion over 0-8 h was 46(15), 44(22), 34(17) and 36(17) μg/h; and iii) rate of fluoride renal clearance was 26.5(9.0), 27.2(30.4), 13.1(20.4) and 18.3(34.9) ml/min. The observed trend of a rise in plasma fluoride concentration and decline in rate of fluoride renal clearance with increasing exercise intensity needs to be investigated in a larger trial. This study, which provides the first data on the effect of exercise with different intensities on fluoride metabolism in humans, informs sample size planning for any subsequent definitive trial, by providing a robust estimate of the variability of the effect. PMID:26581340

  11. Expression of gangliosides on glial and neuronal cells in normal and pathological adult human brain.

    PubMed

    Marconi, Silvia; De Toni, Luca; Lovato, Laura; Tedeschi, Elisa; Gaetti, Luigi; Acler, Michele; Bonetti, Bruno

    2005-12-30

    Few studies have assessed the glycolipid phenotype of glial cells in the human central nervous system (CNS) in situ. We investigated by immunohistochemistry the expression and cellular distribution of a panel of gangliosides (GM1, GM2, acetyl-GM3, GD1a, GD1b, GD2, GD3, GT1b, GQ1b and the A2B5 antibody) in adult, human normal and pathological brain, namely multiple sclerosis (MS) and other neurological diseases (OND). In normal conditions, we found diffuse expression in the white matter of most gangliosides tested, with the exception of acetyl-GM3, GT1b and GQ1b. By double immunofluorescence with phenotypic markers, GM1 and GD1b were preferentially expressed on GFAP+ astrocytes, GD1a on NG2+ oligodendrocyte precursors, A2B5 immunostained both populations, while GD2 was selectively present on mature oligodendrocytes. In the gray matter, only GM1, GD2 and A2B5 were present on neuronal cells. Interestingly, those gangliosides present on astrocytes in normal conditions were preferentially expressed on NG2+ cells in chronic MS lesions and in OND. Selective expression of GT1b upon astrocytes and NG2+ cells was instead observed in MS lesions, but not in OND. The definition of the glycolipid phenotype of CNS glial cells may be useful to identify distinct biological glial subsets and provide insights on the potential autoantigenic role of gangliosides in CNS autoimmune diseases. PMID:16313974

  12. Defining the role of common variation in the genomic and biological architecture of adult human height

    PubMed Central

    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

    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

  13. ECM microenvironment unlocks brown adipogenic potential of adult human bone marrow-derived MSCs

    PubMed Central

    Lee, Michelle H.; Goralczyk, Anna G.; Kriszt, Rókus; Ang, Xiu Min; Badowski, Cedric; Li, Ying; Summers, Scott A.; Toh, Sue-Anne; Yassin, M. Shabeer; Shabbir, Asim; Sheppard, Allan; Raghunath, Michael

    2016-01-01

    Key to realizing the diagnostic and therapeutic potential of human brown/brite adipocytes is the identification of a renewable, easily accessible and safe tissue source of progenitor cells, and an efficacious in vitro differentiation protocol. We show that macromolecular crowding (MMC) facilitates brown adipocyte differentiation in adult human bone marrow mesenchymal stem cells (bmMSCs), as evidenced by substantially upregulating uncoupling protein 1 (UCP1) and uncoupled respiration. Moreover, MMC also induced ‘browning’ in bmMSC-derived white adipocytes. Mechanistically, MMC creates a 3D extracellular matrix architecture enshrouding maturing adipocytes in a collagen IV cocoon that is engaged by paxillin-positive focal adhesions also at the apical side of cells, without contact to the stiff support structure. This leads to an enhanced matrix-cell signaling, reflected by increased phosphorylation of ATF2, a key transcription factor in UCP1 regulation. Thus, tuning the dimensionality of the microenvironment in vitro can unlock a strong brown potential dormant in bone marrow. PMID:26883894

  14. Delayed intramuscular human neurotrophin-3 improves recovery in adult and elderly rats after stroke

    PubMed Central

    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.

    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. PMID:26614754

  15. Delayed intramuscular human neurotrophin-3 improves recovery in adult and elderly rats after stroke.

    PubMed

    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. PMID:26614754

  16. Differential expression of TYRP1 in adult human retinal pigment epithelium and uveal melanoma cells

    PubMed Central

    QIU, CHUN; LI, PENG; BI, JIANJUN; WU, QING; LU, LINNA; QIAN, GUANXIANG; JIA, RENBING; JIA, RONG

    2016-01-01

    Uveal melanoma (UM) is the most frequently occurring primary intraocular malignancy in adults. Tyrosinase (TYR) is a copper-containing enzyme and a type I membrane protein that is involved in the generation of melanin, the main pigment in vertebrates. TYR-related protein 1 (TYRP1) is regarded to have a crucial role in the immunotherapy of melanoma. As biomarkers, the TYR-related proteins, TYRP1 and TYRP2, exhibit specific expression in melanocytes, while also contributing to melanin synthesis within melanosomes. In the present study, the differential expression of TYRP1 was investigated at the mRNA, protein and morphological levels in four human UM cell lines (SP6.5, OM431, OCM1 and OCM290) and the human retinal pigment epithelium (RPE) cell line, using polymerase chain reaction, western blotting, immunocytochemistry and immunofluorescence staining. It was found that SP6.5 cells expressed the highest level of TYRP1, in comparison to SP6.5 OCM1 and OM431 cells, which produced less TYRP1, and OCM290 cells, which produced almost no TYRP1. No TYRP1 protein expression was identified in the RPE cell line. These findings indicate the potential use of TYRP1 in the development of therapy for UM. PMID:27073483

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

    NASA Astrophysics Data System (ADS)

    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.

  18. Carbon turnover in the water-soluble protein of the adult human lens

    PubMed Central

    Stewart, Daniel N.; Lango, Jozsef; Nambiar, Krishnan P.; Falso, Miranda J. S.; FitzGerald, Paul G.; Rocke, David M.; Hammock, Bruce D.

    2013-01-01

    Purpose Human eye lenses contain cells that persist from embryonic development. These unique, highly specialized fiber cells located at the core (nucleus) of the lens undergo pseudo-apoptosis to become devoid of cell nuclei and most organelles. Ostensibly lacking in protein transcriptional capabilities, it is currently believed that these nuclear fiber cells owe their extreme longevity to the perseverance of highly stable and densely packed crystallin proteins. Maintaining the structural and functional integrity of lenticular proteins is necessary to sustain cellular transparency and proper vision, yet the means by which the lens actually copes with a lifetime of oxidative stress, seemingly without any capacity for protein turnover and repair, is not completely understood. Although many years of research have been predicated upon the assumption that there is no protein turnover or renewal in nuclear fiber cells, we investigated whether or not different protein fractions possess protein of different ages by using the 14C bomb pulse. Methods Adult human lenses were concentrically dissected by gently removing the cell layers in water or shaving to the nucleus with a curved micrometer-controlled blade. The cells were lysed, and the proteins were separated into water-soluble and water-insoluble fractions. The small molecules were removed using 3 kDa spin filters. The 14C/C was measured in paired protein fractions by accelerator mass spectrometry, and an average age for the material within the sample was assigned using the 14C bomb pulse. Results The water-insoluble fractions possessed 14C/C ratios consistent with the age of the cells. In all cases, the water-soluble fractions contained carbon that was younger than the paired water-insoluble fraction. Conclusions As the first direct evidence of carbon turnover in protein from adult human nuclear fiber cells, this discovery supports the emerging view of the lens nucleus as a dynamic system capable of maintaining

  19. Helicobacter pylori Eradication Causes Perturbation of the Human Gut Microbiome in Young Adults

    PubMed Central

    Yap, Theresa Wan-Chen; Gan, Han-Ming; Lee, Yin-Peng; Leow, Alex Hwong-Ruey; Azmi, Ahmad Najib; Francois, Fritz; Perez-Perez, Guillermo I.; Loke, Mun-Fai; Goh, Khean-Lee; Vadivelu, Jamuna

    2016-01-01

    Background Accumulating evidence shows that Helicobacter pylori protects against some metabolic and immunological diseases in which the development of these diseases coincide with temporal or permanent dysbiosis. The aim of this study was to assess the effect of H. pylori eradication on the human gut microbiome. Methods As part of the currently on-going ESSAY (Eradication Study in Stable Adults/Youths) study, we collected stool samples from 17 H. pylori-positive young adult (18–30 years-old) volunteers. The same cohort was followed up 6, 12 and 18 months-post H. pylori eradication. The impact of H. pylori on the human gut microbiome pre- and post-eradication was investigated using high throughput 16S rRNA gene (V3-V4 region) sequencing using the Illumina Miseq followed by data analysis using Qiime pipeline. Results We compared the composition and diversity of bacterial communities in the fecal microbiome of the H. pylori-positive volunteers, before and after H. pylori eradication therapy. The 16S rRNA gene was sequenced at an average of 150,000–170,000 reads/sample. The microbial diversity were similar pre- and post-H. pylori eradication with no significant differences in richness and evenness of bacterial species. Despite that the general profile of the gut microbiome was similar pre- and post-eradication, some changes in the bacterial communities at the phylum and genus levels were notable, particularly the decrease in relative abundance of Bacterioidetes and corresponding increase in Firmicutes after H. pylori eradication. The significant increase of short-chain fatty acids (SCFA)-producing bacteria genera could also be associated with increased risk of metabolic disorders. Conclusions Our preliminary stool metagenomics study shows that eradication of H. pylori caused perturbation of the gut microbiome and may indirectly affect the health of human. Clinicians should be aware of the effect of broad spectrum antibiotics used in H. pylori eradication regimen

  20. Administering Successful Programs for Adults. Promoting Excellence in Adult, Community, and Continuing Education. Professional Practices in Adult Education and Human Resource Development Series.

    ERIC Educational Resources Information Center

    Galbraith, Michael W.; And Others

    This book provides a practical orientation as well as a conceptual framework for understanding the administrative process by examining the primary elements, functions, and processes involved with effective administration of adult, community, and continuing education agencies and organizations. The book is organized in nine chapters. Chapter 1…

  1. The Model Human Processor and the Older Adult: Parameter Estimation and Validation within a Mobile Phone Task

    ERIC Educational Resources Information Center

    Jastrzembski, Tiffany S.; Charness, Neil

    2007-01-01

    The authors estimate weighted mean values for nine information processing parameters for older adults using the Card, Moran, and Newell (1983) Model Human Processor model. The authors validate a subset of these parameters by modeling two mobile phone tasks using two different phones and comparing model predictions to a sample of younger (N = 20;…

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  3. An ultrasound biomicroscopic and water jet ultrasound indentation method for detecting the degenerative changes of articular cartilage in a rabbit model of progressive osteoarthritis.

    PubMed

    Wang, Yuexiang; Huang, Yan-Ping; Liu, Aijun; Wan, Wenbo; Zheng, Yong-Ping

    2014-06-01

    It is important to assess the early degeneration of articular cartilage associated with osteoarthritis (OA) for early intervention and treatment planning. Previously, we have developed a high frequency ultrasound and water jet indentation method for the morphologic, acoustic and mechanical assessment of articular cartilage, using the enzymatic digestion as a model of osteoarthritic degeneration. No naturally degenerated articular cartilage has been tested with the developed method. In this study, we aimed to determine the usefulness of the developed method for detecting the natural degeneration of articular cartilage in a standard surgical model of OA in rabbits. Forty adult New Zealand white female rabbits were used in this study, which included 30 experimental rabbits undergoing the right anterior cruciate ligament transection surgery and 10 control rabbits. At the 3rd, 6th, and 9th week post-surgery, 10 experimental rabbits were sacrificed, respectively, for assessment of the knee cartilage quality. The cartilage at the medial and lateral femoral condyles and tibial plateaus (four points) was measured by the high frequency ultrasound biomicroscopy, the water jet ultrasound indentation and a contact mechanical indentation test before a histopathologic analysis for grading of degeneration severity. Measured parameters were compared among different groups classified either by post-surgery time or by histopathologic grade. The results showed a general trend of increase for ultrasound roughness index and a general trend of decrease for integrated reflection coefficient, stiffness coefficient from water-jet indentation and Young's modulus (E) from the mechanical indentation with the increase of post-surgery time. Comparisons among groups with different histopathologic grades showed similar trend with the increase of degeneration severity. The water jet ultrasound indentation method was demonstrated to be an effective method to measure the mechanical properties of the

  4. BAY11 enhances OCT4 synthetic mRNA expression in adult human skin cells

    PubMed Central

    2013-01-01

    Introduction The OCT4 transcription factor is involved in many cellular processes, including development, reprogramming, maintaining pluripotency and differentiation. Synthetic OCT4 mRNA was recently used (in conjunction with other reprogramming factors) to generate human induced pluripotent stem cells. Here, we discovered that BAY 11-7082 (BAY11), at least partially through an NF-κB-inhibition based mechanism, could significantly increase the expression of OCT4 following transfection of synthetic mRNA (synRNA) into adult human skin cells. Methods We tested various chemical and molecular small molecules on their ability to suppress the innate immune response seen upon synthetic mRNA transfection. Three molecules - B18R, BX795, and BAY11 - were used in immunocytochemical and proliferation-based assays. We also utilized global transcriptional meta-analysis coupled with quantitative PCR to identify relative gene expression downstream of OCT4. Results We found that human skin cells cultured in the presence of BAY11 resulted in reproducible increased expression of OCT4 that did not inhibit normal cell proliferation. The increased levels of OCT4 resulted in significantly increased expression of genes downstream of OCT4, including the previously identified SPP1, DUSP4 and GADD45G, suggesting the expressed OCT4 was functional. We also discovered a novel OCT4 putative downstream target gene SLC16A9 which demonstrated significantly increased expression following elevation of OCT4 levels. Conclusions For the first time we have shown that small molecule-based stabilization of synthetic mRNA expression can be achieved with use of BAY11. This small molecule-based inhibition of innate immune responses and subsequent robust expression of transfected synthetic mRNAs may have multiple applications for future cell-based research and therapeutics. PMID:23388106

  5. Variation of bone layer thicknesses and trabecular volume fraction in the adult male human calvarium.

    PubMed

    Boruah, Sourabh; Paskoff, Glenn R; Shender, Barry S; Subit, Damien L; Salzar, Robert S; Crandall, Jeff R

    2015-08-01

    The human calvarium is a sandwich structure with two dense layers of cortical bone separated by porous cancellous bone. The variation of the three dimensional geometry, including the layer thicknesses and the volume fraction of the cancellous layer across the population, is unavailable in the current literature. This information is of particular importance to mathematical models of the human head used to simulate mechanical response. Although the target geometry for these models is the median geometry of the population, the best attempt so far has been the scaling of a unique geometry based on a few median anthropometric measurements of the head. However, this method does not represent the median geometry. This paper reports the average three dimensional geometry of the calvarium from X-ray computed tomography (CT) imaging and layer thickness and trabecular volume fraction from micro CT (μCT) imaging of ten adult male post-mortem human surrogates (PMHS). Skull bone samples have been obtained and μCT imaging was done at a resolution of 30 μm. Monte Carlo simulation was done to estimate the variance in these measurements due to the uncertainty in image segmentation. The layer thickness data has been averaged over areas of 5mm(2). The outer cortical layer was found to be significantly (p < 0.01; Student's t test) thicker than the inner layer (median of thickness ratio 1.68). Although there was significant location to location difference in all the layer thicknesses and volume fraction measurements, there was no trend. Average distribution and the variance of these metrics on the calvarium have been shown. The findings have been reported as colormaps on a 2D projection of the cranial vault. PMID:25920690

  6. New perspectives for articular cartilage repair treatment through tissue engineering: A contemporary review

    PubMed Central

    Musumeci, Giuseppe; Castrogiovanni, Paola; Leonardi, Rosalia; Trovato, Francesca Maria; Szychlinska, Marta Anna; Di Giunta, Angelo; Loreto, Carla; Castorina, Sergio

    2014-01-01

    In this paper review we describe benefits and disadvantages of the established methods of cartilage regeneration that seem to have a better long-term effectiveness. We illustrated the anatomical aspect of the knee joint cartilage, the current state of cartilage tissue engineering, through mesenchymal stem cells and biomaterials, and in conclusion we provide a short overview on the rehabilitation after articular cartilage repair procedures. Adult articular cartilage has low capacity to repair itself, and thus even minor injuries may lead to progressive damage and osteoarthritic joint degeneration, resulting in significant pain and disability. Numerous efforts have been made to develop tissue-engineered grafts or patches to repair focal chondral and osteochondral defects, and to date several researchers aim to implement clinical application of cell-based therapies for cartilage repair. A literature review was conducted on PubMed, Scopus and Google Scholar using appropriate keywords, examining the current literature on the well-known tissue engineering methods for the treatment of knee osteoarthritis. PMID:24829869

  7. Baseline Articular Contact Stress Levels Predict Incident Symptomatic Knee Osteoarthritis Development in the MOST Cohort

    PubMed Central

    Segal, Neil A.; Anderson, Donald D.; Iyer, Krishna S.; Baker, Jennifer; Torner, James C.; Lynch, John A.; Felson, David T.; Lewis, Cora E.; Brown, Thomas D.

    2010-01-01

    We studied whether contact stress estimates from knee magnetic resonance images (MRI) predict the development of incident symptomatic tibiofemoral osteoarthritis (OA) 15 months later in an at-risk cohort. This nested case-control study was conducted within a cohort of 3026 adults, age 50 to 79 years. Thirty cases with incident symptomatic tibiofemoral OA by their 15-month follow-up visit were randomly selected and matched with 30 control subjects. Symptomatic tibiofemoral OA was defined as daily knee pain/stiffness and Kellgren-Lawrence Grade ≥2 on weight bearing, fixed-flexion radiographs. Tibiofemoral geometry was segmented on baseline knee MRI, and contact stresses were estimated using discrete element analysis. Linear mixed models for repeated measures were used to examine the association between articular contact stress and case/control status. No significant inter-group differences were found for age, sex, BMI, weight, height, or limb alignment. However, the maximum articular contact stress was 0.54 ± 0.77 MPa (mean ± SD) higher in incident OA cases compared to that in control knees (p=0.0007). The interaction between case-control status and contact stress was significant above 3.2 MPa (p<0.0001). The presence of differences in estimated contact stress 15 months prior to incidence suggests a biomechanical mechanism for symptomatic tibiofemoral OA and supports the ability to identify risk by subject-specific biomechanical modeling. PMID:19533741

  8. Sclerostin Immunoreactivity Increases in Cortical Bone Osteocytes and Decreases in Articular Cartilage Chondrocytes in Aging Mice.

    PubMed

    Thompson, Michelle L; Jimenez-Andrade, Juan Miguel; Mantyh, Patrick W

    2016-03-01

    Sclerostin is a 24-kDa secreted glycoprotein that has been identified as a negative modulator of new bone formation and may play a major role in age-related decline in skeletal function. Although serum levels of sclerostin markedly increase with age, relatively little is known about whether cells in the skeleton change their expression of sclerostin with aging. Using immunohistochemistry and confocal microscopy, we explored sclerostin immunoreactivity (sclerostin-IR) in the femurs of 4-, 9-, and 24-month-old adult C3H/HeJ male mice. In the femur, the only two cell types that expressed detectable levels of sclerostin-IR were bone osteocytes and articular cartilage chondrocytes. At three different sites along the diaphysis of the femur, only a subset of osteocytes expressed sclerostin-IR and the percentage of osteocytes that expressed sclerostin-IR increased from approximately 36% to 48% in 4- vs. 24-month-old mice. In marked contrast, in the same femurs, there were ~40% fewer hypertrophic chondrocytes of articular cartilage that expressed sclerostin-IR when comparing 24- vs. 4-month-old mice. Understanding the mechanism(s) that drive these divergent changes in sclerostin-IR may provide insight into understanding and treating the age-related decline of the skeleton. PMID:26701970

  9. Intra-articular Placement of an Intraosseous Catheter.

    PubMed

    Grabel, Zachary; DePasse, J Mason; Lareau, Craig R; Born, Christopher T; Daniels, Alan H

    2015-02-01

    Gaining vascular access is essential in the resuscitation of critically ill patients. Intraosseous (IO) placement is a fundamentally important alternative to intravenous (IV) access in conditions where IV access delays resuscitation or is not possible. This case report presents a previously unreported example of prehospital misplacement of an IO catheter into the intra-articular space of the knee joint. This report serves to inform civilian and military first responders, as well as emergency medicine physicians, of intra-articular IO line placement as a potential complication of IO vascular access. Infusion of large amounts of fluid into the joint space could damage the joint and be catastrophic to a patient who needs immediate IV fluids or medications. In addition, intra-articular IO placement could result in septic arthritis of the knee. PMID:25483729

  10. Radiography of rabbit articular cartilage with diffraction-enhanced imaging.

    PubMed

    Muehleman, Carol; Chapman, L Dean; Kuettner, Klaus E; Rieff, Joel; Mollenhauer, Juergen A; Massuda, Koichi; Zhong, Zhong

    2003-05-01

    Articular cartilage of synovial joints is not visible with conventional X-ray imaging. Hence, the gradual degeneration and destruction of articular cartilage, which is characteristic of degenerative joint diseases, is only detected at a late stage when the cartilage is lost and the joint space that it once occupied narrows. The development of an X-ray imaging technique that could detect both the degenerative cartilage and bone features of joint diseases is of special interest. Here we show, for the first time, that a high-contrast imaging technique, diffraction-enhanced X-ray imaging (DEI), allows the visualization of articular cartilage of both disarticulated and articulated rabbit knee joints. Furthermore, a single cartilage lesion can be visualized within an intact joint. The results suggest that DEI has the potential to be of use in the study of cartilage degeneration. PMID:12704696

  11. Three-dimensional collagen architecture in bovine articular cartilage.

    PubMed

    Jeffery, A K; Blunn, G W; Archer, C W; Bentley, G

    1991-09-01

    The three-dimensional architecture of bovine articular cartilage collagen and its relationship to split lines has been studied with scanning electron microscopy. In the middle and superficial zones, collagen was organised in a layered or leaf-like manner. The orientation was vertical in the intermediate zone, curving to become horizontal and parallel to the articular surface in the superficial zone. Each leaf consisted of a fine network of collagen fibrils. Adjacent leaves merged or were closely linked by bridging fibrils and were arranged according to the split-line pattern. The surface layer (lamina splendens) was morphologically distinct. Although ordered, the overall collagen structure was different in each plane (anisotropic) a property described in previous morphological and biophysical studies. As all components of the articular cartilage matrix interact closely, the three-dimensional organisation of collagen is important when considering cartilage function and the processes of cartilage growth, injury and repair. PMID:1894669

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

    PubMed

    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. PMID:26948153

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

    PubMed

    Becker, Martin; Guadalupe, Tulio; Franke, Barbara; Hibar, Derrek P; Renteria, Miguel E; Stein, Jason L; Thompson, Paul M; Francks, Clyde; Vernes, Sonja C; Fisher, Simon E

    2016-05-01

    Genome-wide association screens aim to identify common genetic variants contributing to the phenotypic variability of complex traits, such as human height or brain morphology. The identified genetic variants are mostly within noncoding genomic regions and the biology of the genotype-phenotype association typically remains unclear. In this article, we propose a complementary targeted strategy to reveal the genetic underpinnings of variability in subcortical brain volumes, by specifically selecting genomic loci that are experimentally validated forebrain enhancers, active in early embryonic development. We hypothesized that genetic variation within these enhancers may affect the development and ultimately the structure of subcortical brain regions in adults. We tested whether variants in forebrain enhancer regions showed an overall enrichment of association with volumetric variation in subcortical structures of >13,000 healthy adults. We observed significant enrichment of genomic loci that affect the volume of the hippocampus within forebrain enhancers (empirical P = 0.0015), a finding which robustly passed the adjusted threshold for testing of multiple brain phenotypes (cutoff of P < 0.0083 at an alpha of 0.05). In analyses of individual single nucleotide polymorphisms (SNPs), we identified an association upstream of the ID2 gene with rs7588305 and variation in hippocampal volume. This SNP-based association survived multiple-testing correction for the number of SNPs analyzed but not for the number of subcortical structures. Targeting known regulatory regions offers a way to understand the underlying biology that connects genotypes to phenotypes, particularly in the context of neuroimaging genetics. This biology-driven approach generates testable hypotheses regarding the functional biology of identified associations. Hum Brain Mapp 37:1788-1800, 2016. © 2016 Wiley Periodicals, Inc. PMID:26890892

  14. Human fetal and adult chondrocytes. Effect of insulinlike growth factors I and II, insulin, and growth hormone on clonal growth.

    PubMed Central

    Vetter, U; Zapf, J; Heit, W; Helbing, G; Heinze, E; Froesch, E R; Teller, W M

    1986-01-01

    Clonal proliferation of freshly isolated human fetal chondrocytes and adult chondrocytes in response to human insulinlike growth factors I and II (IGF I, IGF II), human biosynthetic insulin, and human growth hormone (GH) was assessed. IGF I (25 ng/ml) stimulated clonal growth of fetal chondrocytes (54 +/- 12 colonies/1,000 inserted cells, mean +/- 1 SD), but IGF II (25 ng/ml) was significantly more effective (106 +/- 12 colonies/1,000 inserted cells, P less than 0.05, unstimulated control: 14 +/- 4 colonies/1,000 inserted cells). In contrast, IGF I (25 ng/ml) was more effective in adult chondrocytes (42 +/- 6 colonies/1,000 inserted cells) than IGF II (25 ng/ml) (21 +/- 6 colonies/1,000 inserted cells; P less than 0.05, unstimulated control: 6 +/- 3 colonies/1,000 inserted cells). GH and human biosynthetic insulin did not affect clonal growth of fetal or adult chondrocytes. The clonal growth pattern of IGF-stimulated fetal and adult chondrocytes was not significantly changed when chondrocytes were first grown in monolayer culture, harvested, and then inserted in the clonal culture system. However, the adult chondrocytes showed a time-dependent decrease of stimulation of clonal growth by IGF I and II. This was not true for fetal chondrocytes. The results are compatible with the concept that IGF II is a more potent stimulant of clonal growth of chondrocytes during fetal life, whereas IGF I is more effective in stimulating clonal growth of chondrocytes during postnatal life. Images PMID:3519682

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

    PubMed Central

    Tong, Fei; Yao, Dongqi; Walline, Joseph; Xu, Jun; Yu, Xuezhong

    2016-01-01

    Background 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. Methods 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. Results 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. Conclusions 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

  16. A Critical Evaluation of Adult Learning Theories and Implication for Human Resource Development

    ERIC Educational Resources Information Center

    Yang, Baiyin

    2004-01-01

    Based on a newly developed holistic theory of knowledge and learning, this paper critically evaluates several contemporary theories of adult learning. Most of existing adult learning theories tend to narrowly define knowledge and learning and fail to offer adequate explanation for adult learning. Implications for HRD theory, research, and practice…

  17. Use magnetic resonance imaging to assess articular cartilage

    PubMed Central

    Wang, Yuanyuan; Wluka, Anita E.; Jones, Graeme; Ding, Changhai

    2012-01-01

    Magnetic resonance imaging (MRI) enables a noninvasive, three-dimensional assessment of the entire joint, simultaneously allowing the direct visualization of articular cartilage. Thus, MRI has become the imaging modality of choice in both clinical and research settings of musculoskeletal diseases, particular for osteoarthritis (OA). Although radiography, the current gold standard for the assessment of OA, has had recent significant technical advances, radiographic methods have significant limitations when used to measure disease progression. MRI allows accurate and reliable assessment of articular cartilage which is sensitive to change, providing the opportunity to better examine and understand preclinical and very subtle early abnormalities in articular cartilage, prior to the onset of radiographic disease. MRI enables quantitative (cartilage volume and thickness) and semiquantitative assessment of articular cartilage morphology, and quantitative assessment of cartilage matrix composition. Cartilage volume and defects have demonstrated adequate validity, accuracy, reliability and sensitivity to change. They are correlated to radiographic changes and clinical outcomes such as pain and joint replacement. Measures of cartilage matrix composition show promise as they seem to relate to cartilage morphology and symptoms. MRI-derived cartilage measurements provide a useful tool for exploring the effect of modifiable factors on articular cartilage prior to clinical disease and identifying the potential preventive strategies. MRI represents a useful approach to monitoring the natural history of OA and evaluating the effect of therapeutic agents. MRI assessment of articular cartilage has tremendous potential for large-scale epidemiological studies of OA progression, and for clinical trials of treatment response to disease-modifying OA drugs. PMID:22870497

  18. Colo-articular fistula following a Girdlestone resection arthroplasty

    PubMed Central

    El-Daly, Ibraheim; Natarajan, Brenavan; Rajakulendran, Karthig; Symons, Sean

    2014-01-01

    Colo-articular fistulas are rare complications that are usually associated with inflammatory, infective or malignant bowel disease. We report the case of a 44-year-old male who was found to have a colo-articular fistula intra-operatively during the washout of a septic hip joint. The patient had no pre-existing bowel disease, but was an intravenous drug user, who had previously undergone a Girdlestone procedure for osteomyelitis of the proximal femur. The patient was managed through a multi-disciplinary team approach with subsequent debridement and formation of a transverse loop colostomy to control the faeculent fistulous discharge. PMID:24876512

  19. Corrective Osteotomies for Malunited Extra-Articular Calcaneal Fractures.

    PubMed

    Ketz, John; Clare, Michael; Sanders, Roy

    2016-03-01

    The most effective way to treat calcaneal malunions is avoidance. With any articular fracture, progressive arthrosis and dysfunction are common. By restoring the anatomy initially through reduction, late reconstructive options become less complicated. Numerous studies have shown that restoration of the anatomic alignment either through percutaneous or open techniques is effective. In patients with no or minimal articular degeneration, extrarticular joint-sparing procedures can be performed. This represents a small select group who may benefit from simple osteotomy procedures with associated soft tissue reconstruction, if needed. PMID:26915784

  20. Effects of surgically induced instability on rat knee articular cartilage.

    PubMed Central

    Williams, J M; Felten, D L; Peterson, R G; O'Connor, B L

    1982-01-01

    Degenerative lesions in the articular cartilage were present following transection of the anterior cruciate ligament in the rat. These lesions included surface disruptions, a reduction in matrix proteoglycans, and cellular changes and therefore were similar to lesions seen in dogs following transection of the anterior cruciate ligament as well as lesions seen in other mechanical derangement models. Lesions were more frequently encountered in animals that had been exercised on a treadmill. This suggests that the rat knee joint may be a useful small animal model in studying the effect of mechanical derangement on articular tissues. Images Figs. 1-2 Figs. 3-4 Figs. 5-6 PMID:7076535

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

    PubMed Central

    Mustafa, Mohamed S.; Mahmoud, Omayma M.; El Raouf, Hoda H. A.; Atef, Hosam M.

    2012-01-01

    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 important guide

  2. Proximal metatarsal articular surface shape and the evolution of a rigid lateral foot in hominins.

    PubMed

    Proctor, Daniel J

    2013-12-01

    This study quantifies the proximal articular surface shape of metatarsal (MT) 4 and MT 5 using three-dimensional morphometrics. Humans and apes are compared to test whether they have significantly different shapes that are skeletal correlates to comparative lateral foot function. In addition, shod and unshod humans are compared to test for significant differences in surface shape. The MT 4 fossils OH 8, Stw 628, and AL 333-160, and the MT 5 fossils AL 333-13, AL 333-78, OH 8, and Stw 114/115 are compared with humans and apes to assess whether they bear greater similarities to humans, which would imply a relatively stable lateral foot, or to apes, which would imply a flexible foot with a midfoot break. Apes have a convex curved MT 4 surface, and humans have a flat surface. The MT 4 fossils show greater similarity to unshod humans, suggesting a stable lateral foot. Unshod humans have a relatively flatter MT 4 surface compared with shod humans. There is much overlap in MT 5 shape between humans and apes, with more similarity between humans and Gorilla. The fossil MT 5 surfaces are generally flat, most similar to humans and Gorilla. Because of the high degree of shape overlap between humans and apes, one must use caution in interpreting lateral foot function from the proximal MT 5 surface alone. PMID:24149023

  3. Ex vivo Expansion of Human Adult Pancreatic Cells with Properties of Distributed Stem Cells by Suppression of Asymmetric Cell Kinetics

    PubMed Central

    Paré, JF; Sherley, JL

    2013-01-01

    Transplantation therapy for type I diabetes (T1D) might be improved if pancreatic stem cells were readily available for investigation. Unlike macroscopic islets, pancreatic tissue stem cells could more easily access the retroperitoneal pancreatic environment and thereby might achieve more effective pancreatic regeneration. Unfortunately, whether the adult pancreas actually contains renewing stem cells continues as a controversial issue in diabetes research. We evaluated a new method developed in our lab for expanding renewing distributed stem cells (DSCs) from adult tissues as a means to provide more evidence for adult pancreatic stem cells, and potentially advance their availability for future clinical investigation. The new method was designed to switch DSCs from asymmetric self-renewal to symmetric self-renewal, which promotes their exponential expansion in culture with reduced production of differentiated cells. Called suppression of asymmetric cell kinetics (SACK), the method uses natural purine metabolites to accomplish the self-renewal pattern shift. The SACK purine metabolites xanthine, xanthosine, and hypoxanthine were evaluated for promoting expansion of DSCs from the pancreas of adult human postmortem donors. Xanthine and xanthosine were effective for deriving both pooled and clonal populations of cells with properties indicative of human pancreatic DSCs. The expanded human cell strains had signature SACK agent-suppressible asymmetric cell kinetics, produced Ngn3+ bipotent precursors for α-cells and β-cells, and were non-tumorigenic in immunodeficient mice. Our findings support the existence of pancreatic DSCs in the adult human pancreas and indicate a potential path to increasing their availability for future clinical evaluation. PMID:25197614

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

    PubMed Central

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

    2012-01-01

    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

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

    PubMed

    Na, Yong Hum; 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 Carlo

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

    NASA Astrophysics Data System (ADS)

    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

  7. Preliminary report on the correlations among pineal concretions, prostatic calculi and age in human adult males.

    PubMed

    Mori, Ryoichi; Kodaka, Tetsuo; Sano, Tsuneyoshi

    2003-09-01

    By using quantitative image analysis of soft X-ray photographs on the bulk of extracted pineal glands and prostates, we made a preliminary investigation into the correlations among pineal concretions (% by mass), prostatic calculi (% by mass) and age (years) in 40 human adult males, ranging in age from 31 to 95 years (mean (+/-SD) 69.9 +/- 15.2 years), who died and underwent the routine dissection course. The mass concentrations of pineal concretions and prostatic calculi were 17.68 +/- 13.56% (range 0-51.34%) and 0.93 +/- 1.31% (range 0-5.82%), respectively. There was no correlation between the mass concentration of pineal concretions and aging (r = 0.03; P < 1.0). There was no correlation between mass concentration of prostatic calculi and aging (r = 0.28; P < 0.5). No pineal concretions and no prostatic calculi were observed in seven and 10 cases, respectively; in addition, in one case, neither-concretions nor calculi were seen. From such data and from the previously reported suggestion on the counteracting functions between the pineal gland and prostate, a negative correlation between the mass concentrations of pineal concretions and prostatic calculi was expected. This was certainly obtained, but the correlation was low (r = -0.39; P < 0.05). Such a low correlation and no correlations between the concentrations of pineal concretions and aging or between prostatic calculi and aging may have been caused by the examination of relatively older humans. Therefore, further investigations using a number of pair samples collected from males including younger age generations will be necessary. PMID:14527133

  8. Functional Consequences of Neurite Orientation Dispersion and Density in Humans across the Adult Lifespan

    PubMed Central

    Nazeri, Arash; Chakravarty, M. Mallar; Rotenberg, David J.; Rajji, Tarek K.; Rathi, Yogesh; Michailovich, Oleg V.

    2015-01-01

    As humans age, a characteristic pattern of widespread neocortical dendritic disruption coupled with compensatory effects in hippocampus and other subcortical structures is shown in postmortem investigations. It is now possible to address age-related effects on gray matter (GM) neuritic organization and density in humans using multishell diffusion-weighted MRI and the neurite-orientation dispersion and density imaging (NODDI) model. In 45 healthy individuals across the adult lifespan (21–84 years), we used a multishell diffusion imaging and the NODDI model to assess the intraneurite volume fraction and neurite orientation-dispersion index (ODI) in GM tissues. We also determined the functional correlates of variations in GM microstructure by obtaining resting-state fMRI and behavioral data. We found a significant age-related deficit in neocortical ODI (most prominently in frontoparietal regions), whereas increased ODI was observed in hippocampus and cerebellum with advancing age. Neocortical ODI outperformed cortical thickness and white matter fractional anisotropy for the prediction of chronological age in the same individuals. Higher GM ODI sampled from resting-state networks with known age-related susceptibility (default mode and visual association networks) was associated with increased functional connectivity of these networks, whereas the task-positive networks tended to show no association or even decreased connectivity. Frontal pole ODI mediated the negative relationship of age with executive function, whereas hippocampal ODI mediated the positive relationship of age with executive function. Our in vivo findings align very closely with the postmortem data and provide evidence for vulnerability and compensatory neural mechanisms of aging in GM microstructure that have functional and cognitive impact in vivo. PMID:25632148

  9. Low Power Laser Irradiation Stimulates the Proliferation of Adult Human Retinal Pigment Epithelial Cells in Culture

    PubMed Central

    Song, Qing; Uygun, Basak; Banerjee, Ipsita; Nahmias, Yaakov; Zhang, Quan; Berthiaume, François; Latina, Mark; Yarmush, Martin L.

    2015-01-01

    We investigated the effects of low power laser irradiation on the proliferation of retinal pigment epithelial (RPE) cells. Adult human RPE cells were artificially pigmented by preincubation with sepia melanin, and exposed to a single sublethal laser pulse (590 nm, 1 µs, <200 mJ/cm2). DNA synthesis, cell number, and growth factor activity in irradiated RPE cells were subsequently monitored. The effect of sublethal laser irradiation on the “wound” healing response of an RPE monolayer in an in vitro scratch assay was also investigated. Single pulsed laser irradiation increased DNA synthesis in pigmented RPE cells measured 6 h post-treatment. In the scratch assay, laser irradiation increased the rates of cell proliferation and wound closure. Conditioned medium, collected 48 h following laser treatment, increased cell proliferation of unirradiated cells. Irradiation increased RPE cell secretion of platelet-derived growth factor (PDGF)-B chain, and increased mRNA levels of several growth factors and their receptors, including PDGF, transforming growth factor-β1, basic fibroblast growth factor, epidermal growth factor, insulin-like growth factor, as well as heat shock proteins. This demonstrates, for the first time, that low power single pulsed laser irradiation stimulates the proliferation of RPE cells, and upregulates growth factors that are mitogenic for RPE cells. PMID:26740823

  10. A nonsense mutation of human XRCC4 is associated with adult-onset progressive encephalocardiomyopathy

    PubMed Central

    Bee, Leonardo; Nasca, Alessia; Zanolini, Alice; Cendron, Filippo; d'Adamo, Pio; Costa, Rodolfo; Lamperti, Costanza; Celotti, Lucia; Ghezzi, Daniele; Zeviani, Massimo

    2015-01-01

    We studied two monozygotic twins, born to first cousins, affected by a multisystem disease. At birth, they both presented with bilateral cryptorchidism and malformations. Since early adulthood, they developed a slowly progressive neurological syndrome, with cerebellar and pyramidal signs, cognitive impairment, and depression. Dilating cardiomyopathy is also present in both. By whole-exome sequencing, we found a homozygous nucleotide change in XRCC4 (c.673C>T), predicted to introduce a premature stop codon (p.R225*). XRCC4 transcript levels were profoundly reduced, and the protein was undetectable in patients' skin fibroblasts. XRCC4 plays an important role in non-homologous end joining of DNA double-strand breaks (DSB), a system that is involved in repairing DNA damage from, for example, ionizing radiations. Gamma-irradiated mutant cells demonstrated reduction, but not abolition, of DSB repair. In contrast with embryonic lethality of the Xrcc4 KO mouse, nonsense mutations in human XRCC4 have recently been associated with primordial dwarfism and, in our cases, with adult-onset neurological impairment, suggesting an important role for DNA repair in the brain. Surprisingly, neither immunodeficiency nor predisposition to malignancy was reported in these patients. PMID:25872942

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

    PubMed Central

    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. PMID:27403430

  12. Dynamic Gene Expression in the Human Cerebral Cortex Distinguishes Children from Adults

    PubMed Central

    Sterner, Kirstin N.; Weckle, Amy; Chugani, Harry T.; Tarca, Adi L.; Sherwood, Chet C.; Hof, Patrick R.; Kuzawa, Christopher W.; Boddy, Amy M.; Abbas, Asad; Raaum, Ryan L.; Grégoire, Lucie; Lipovich, Leonard; Grossman, Lawrence I.; Uddin, Monica; Wildman, Derek E.

    2012-01-01

    In comparison with other primate species, humans have an extended juvenile period during which the brain is more plastic. In the current study we sought to examine gene expression in the cerebral cortex during development in the context of this adaptive plasticity. We introduce an approach designed to discriminate genes with variable as opposed to uniform patterns of gene expression and found that greater inter-individual variance is observed among children than among adults. For the 337 transcripts that show this pattern, we found a significant overrepresentation of genes annotated to the immune system process (pFDR≅0). Moreover, genes known to be important in neuronal function, such as brain-derived neurotrophic factor (BDNF), are included among the genes more variably expressed in childhood. We propose that the developmental period of heightened childhood neuronal plasticity is characterized by more dynamic patterns of gene expression in the cerebral cortex compared to adulthood when the brain is less plastic. That an overabundance of these genes are annotated to the immune system suggests that the functions of these genes can be thought of not only in the context of antigen processing and presentation, but also in the context of nervous system development. PMID:22666384

  13. Adult human mesenchymal stem cells enhance breast tumorigenesis and promote hormone independence

    PubMed Central

    Rhodes, Lyndsay V.; Muir, Shannon E.; Elliott, Steven; Guillot, Lori M.; Antoon, James W.; Penfornis, Patrice; Tilghman, Syreeta L.; Salvo, Virgilio A.; Fonseca, Juan P.; Lacey, Michelle R.; Beckman, Barbara S.; McLachlan, John A.; Rowan, Brian G.; Pochampally, Radhika

    2016-01-01

    Adult human mesenchymal stem cells (hMSCs) have been shown to home to sites of breast cancer and integrate into the tumor stroma. We demonstrate here the effect of hMSCs on primary breast tumor growth and the progression of these tumors to hormone independence. Co-injection of bone marrow-derived hMSCs enhances primary tumor growth of the estrogen receptor-positive, hormone-dependent breast carcinoma cell line MCF-7 in the presence or absence of estrogen in SCID/beige mice. We also show hormone-independent growth of MCF-7 cells when co-injected with hMSCs. These effects were found in conjunction with increased immunohistochemical staining of the progesterone receptor in the MCF-7/hMSC tumors as compared to MCF-7 control tumors. This in