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Sample records for adult human articular

  1. 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

  2. Human stem cells and articular cartilage regeneration.

    PubMed

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

    2012-11-05

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

  3. Basic calcium phosphate crystals activate human osteoarthritic synovial fibroblasts and induce matrix metalloproteinase-13 (collagenase-3) in adult porcine articular chondrocytes

    PubMed Central

    McCarthy, G; Westfall, P; Masuda, I; Christopherson, P; Cheung, H; Mitchell, P

    2001-01-01

    OBJECTIVE—To determine the ability of basic calcium phosphate (BCP) crystals to induce (a) mitogenesis, matrix metalloproteinase (MMP)-1, and MMP-13 in human osteoarthritic synovial fibroblasts (HOAS) and (b) MMP-13 in cultured porcine articular chondrocytes.
METHODS—Mitogenesis of HOAS was measured by [3H]thymidine incorporation assay and counts of cells in monolayer culture. MMP messenger RNA (mRNA) accumulation was determined either by northern blot analysis or reverse transcriptase-polymerase chain reaction (RT-PCR) of RNA from chondrocytes or HOAS treated with BCP crystals. MMP-13 secretion was identified by immunoprecipitation and MMP-1 secretion by western blot of conditioned media.
RESULTS—BCP crystals caused a 4.5-fold increase in [3H]thymidine incorporation by HOAS within 20 hours compared with untreated control cultures (p⩽0.05). BCP crystals induced MMP-13 mRNA accumulation and MMP-13 protein secretion by articular chondrocytes. In contrast, in HOAS, MMP-13 mRNA induced by BCP crystals was detectable only by RT-PCR, and MMP-13 protein was undetectable. BCP crystals induced MMP-1 mRNA accumulation and MMP-1 protein secretion by HOAS. MMP-1 expression was further augmented when HOAS were co-incubated with either BCP and tumour necrosis factor α (TNFα; threefold) or BCP and interleukin 1α (IL1α; twofold).
CONCLUSION—These data confirm the ability of BCP crystals to activate HOAS, leading to the induction of mitogenesis and MMP-1 production. MMP-13 production in response to BCP crystals is substantially more detectable in porcine articular chondrocytes than in HOAS. These data support the active role of BCP crystals in osteoarthritis and suggest that BCP crystals act synergistically with IL1α and TNFα to promote MMP production and subsequent joint degeneration.

 PMID:11247873

  4. 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

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

    PubMed Central

    Im, Hee-Jeong; Sharrocks, Andrew D; Lin, Xia; Yan, Dongyao; Kim, Jaesung; van Wijnen, Andre J; Hipskind, Robert A

    2009-01-01

    Degradation of the extracellular matrix (ECM) by matrix metalloproteinases (MMPs) and release of basic fibroblast growth factor (bFGF) are principal aspects of the pathology of osteoarthritis (OA). ECM disruption leads to bFGF release, which activates the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway and its downstream target the Ets-like transcription factor Elk-1. Previously we demonstrated that the bFGF-ERK-Elk-1 signaling axis is responsible for the potent induction of MMP-13 in human primary articular chondrocytes. Here we report that, in addition to phosphorylation of Elk-1, dynamic posttranslational modification of Elk-1 by small ubiquitin-related modifier (SUMO) serves as an important mechanism through which MMP-13 gene expression is regulated. We show that bFGF activates Elk-1 mainly through the ERK pathway and that increased phosphorylation of Elk-1 is accompanied by decreased conjugation of SUMO to Elk-1. Reporter gene assays reveal that phosphorylation renders Elk-1 competent for induction of MMP-13 gene transcription, while sumoylation has the opposite effect. Furthermore, we demonstrate that the SUMO-conjugase Ubc9 acts as a key mediator for Elk-1 sumoylation. Taken together, our results suggest that sumoylation antagonizes the phosphorylation-dependent transactivation capacity of Elk-1. This attenuates transcription of its downstream target gene MMP-13 to maintain the integrity of cartilage ECM homeostasis.

  6. Chondrocyte distribution in the articular cartilage of human femoral condyles.

    PubMed Central

    Gilmore, R S; Palfrey, A J

    1988-01-01

    The distribution of chondrocytes throughout the total thickness of articular cartilage from the femoral condyles of infants, children and adults has been studied using serial sections cut parallel as well as perpendicular to the articular surface. The thickness of the articular cartilage was estimated in fixed sections. In one of the adult specimens, the thickness of the articular cartilage was estimated firstly by direct measurement of the cut surfaces of a series of blocks cut from both condyles and then from the number of parallel sections of the cartilage prepared from those blocks. Cell density was highest in the superficial zone of all specimens examined, declining to lower values in the deep zone of the cartilage. Within this pattern the infant specimens had the highest values for cell density and the adults the lowest, with values for children in an intermediate range. There was no significant variation in cell density across the condyles of the selected adult specimen. The absolute values for cartilage thickness depended on the method used, but in general total thickness was found to approximately double from late gestation to maturity. In the selected adult specimen, the cartilage was thickest just anterior and posterior to the main weight-bearing area of the condyles. PMID:3198480

  7. 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.

  8. Human patellar articular proportions: recent and Pleistocene patterns

    PubMed Central

    TRINKAUS, ERIK

    2000-01-01

    The degrees of mediolateral asymmetry of the patellar articular facet, as well as the median and lateral articular angles of the facet, were compared across samples of recent humans and of Pleistocene archaic and modern fossil humans. All samples exhibit considerable variability in these patellar proportions. The articular angles are similar across the different samples, but there is a trend towards decreasing lateral angles with decreasing robusticity. The archaic humans exhibit significantly more symmetry of the medial and lateral facets than do any of the recent human samples. However, given the variability in medial versus lateral patellofemoral contact forces documented for extant humans and the roles of the distal oblique portions of vastus medialis and vastus lateralis in patellar stabilisation, it is unclear to what extent this variation in patellar articular proportions may affect knee kinesiology. The contrasts may be related to different levels of patellar stability and/or musculoskeletal hypertrophy, but they appear unlikely to have affected primary knee function. PMID:10853969

  9. Epidemiology and outcome of articular complications in adult onset Still's disease.

    PubMed

    Mahfoudhi, Madiha; Shimi, Rafik; Turki, Sami; Kheder, Adel

    2015-01-01

    The adult onset Still's disease is a rare inflammatory pathology of unknown pathogeny. The clinical features are variable. The diagnosis is difficult since exclusion of infectious, systemic and tumoral pathologies should be done. The articular complications are frequent and can be revelatory of this pathology. The articular prognosis depends on the diagnosis delay and the treatment efficiency. Our study aims to analyze different aspects of articular manifestations complicating adult onset Still disease to define epidemiological, clinical and evolving characteristics of these complications. It was a cross-sectional study concerning 18 cases of adult onset Still disease diagnosed from 1990 to 2014 in the internal medicine A department of Charles Nicolle Hospital in Tunis, meeting Yamaguchi criteria. We identified clinical, radiological, evolving and therapeutic profile of the articular manifestations occurred in these patients. There were 11 women and 7 men. The average age was 27 years. The arthralgias were reported in all cases; while, the arthritis interested thirteen patients. A hand deformation was found in four patients. A wrist ankylosis was noted in one case and a flexion elbow in one patient. The Standard articular radiographs were normal in ten cases. The treatment associated essentially non-steroidal anti-inflammatory and/or corticosteroids and/or methotrexate. Concerning the evolving profile, the monocyclic form was present in 25% of the cases, the intermittent form in 40% and the chronic articular form in 35% of our patients. The adult onset Still's disease is rare and heterogeneous. The articular disturbances are frequent and have various outcomes.

  10. 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.

  11. 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

  12. Degradome expression profiling in human articular cartilage

    PubMed Central

    Swingler, Tracey E; Waters, Jasmine G; Davidson, Rosemary K; Pennington, Caroline J; Puente, Xose S; Darrah, Clare; Cooper, Adele; Donell, Simon T; Guile, Geoffrey R; Wang, Wenjia; Clark, Ian M

    2009-01-01

    Introduction The molecular mechanisms underlying cartilage destruction in osteoarthritis are poorly understood. Proteolysis is a key feature in the turnover and degradation of cartilage extracellular matrix where the focus of research has been on the metzincin family of metalloproteinases. However, there is strong evidence to indicate important roles for other catalytic classes of proteases, with both extracellular and intracellular activities. The aim of this study was to profile the expression of the majority of protease genes in all catalytic classes in normal human cartilage and that from patients with osteoarthritis (OA) using a quantitative method. Methods Human cartilage was obtained from femoral heads at joint replacement for either osteoarthritis or following fracture to the neck of femur (NOF). Total RNA was purified, and expression of genes assayed using Taqman® low-density array quantitative RT-PCR. Results A total of 538 protease genes were profiled, of which 431 were expressed in cartilage. A total of 179 genes were differentially expressed in OA versus NOF cartilage: eight aspartic proteases, 44 cysteine proteases, 76 metalloproteases, 46 serine proteases and five threonine proteases. Wilcoxon ranking as well as the LogitBoost-NR machine learning approach were used to assign significance to each gene, with the most highly ranked genes broadly similar using each method. Conclusions This study is the most complete quantitative analysis of protease gene expression in cartilage to date. The data help give direction to future research on the specific function(s) of individual proteases or protease families in cartilage and may help to refine anti-proteolytic strategies in OA. PMID:19549314

  13. Articular to diaphyseal proportions of human and great ape metatarsals.

    PubMed

    Marchi, Damiano

    2010-10-01

    This study proposes a new way to use metatarsals to identify locomotor behavior of fossil hominins. Metatarsal head articular dimensions and diaphyseal strength in a sample of chimpanzees, gorillas, orangutans, and humans (n = 76) are used to explore the relationships of these parameters with different locomotor modes. Results show that ratios between metatarsal head articular proportions and diaphyseal strength of the hallucal and fifth metatarsal discriminate among extant great apes and humans based on their different locomotor modes. In particular, the hallucal and fifth metatarsal characteristics of humans are functionally related to the different ranges of motion and load patterns during stance phase in the forefoot of humans in bipedal locomotion. This method may be applicable to isolated fossil hominin metatarsals to provide new information relevant to debates regarding the evolution of human bipedal locomotion. The second to fourth metatarsals are not useful in distinguishing among hominoids. Further studies should concentrate on measuring other important qualitative and quantitative differences in the shape of the metatarsal head of hominoids that are not reflected in simple geometric reconstructions of the articulation, and gathering more forefoot kinematic data on great apes to better understand differences in range of motion and loading patterns of the metatarsals.

  14. Epidemiology and outcome of articular complications in adult onset still's disease

    PubMed Central

    Mahfoudhi, Madiha; Shimi, Rafik; Turki, Sami; Kheder, Adel

    2015-01-01

    The adult onset Still's disease is a rare inflammatory pathology of unknown pathogeny. The clinical features are variable. The diagnosis is difficult since exclusion of infectious, systemic and tumoral pathologies should be done. The articular complications are frequent and can be revelatory of this pathology. The articular prognosis depends on the diagnosis delay and the treatment efficiency. Our study aims to analyze different aspects of articular manifestations complicating adult onset Still disease to define epidemiological, clinical and evolving characteristics of these complications. It was a cross-sectional study concerning 18 cases of adult onset Still disease diagnosed from 1990 to 2014 in the internal medicine A department of Charles Nicolle Hospital in Tunis, meeting Yamaguchi criteria. We identified clinical, radiological, evolving and therapeutic profile of the articular manifestations occurred in these patients. There were 11 women and 7 men. The average age was 27 years. The arthralgias were reported in all cases; while, the arthritis interested thirteen patients. A hand deformation was found in four patients. A wrist ankylosis was noted in one case and a flexion elbow in one patient. The Standard articular radiographs were normal in ten cases. The treatment associated essentially non-steroidal anti-inflammatory and/or corticosteroids and/or methotrexate. Concerning the evolving profile, the monocyclic form was present in 25% of the cases, the intermittent form in 40% and the chronic articular form in 35% of our patients. The adult onset Still's disease is rare and heterogeneous. The articular disturbances are frequent and have various outcomes. PMID:26834930

  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.

  16. 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

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

    PubMed

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

    2016-04-01

    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 Ca(2+) 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

  19. 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

  20. 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

  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. 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

  4. The immunohistochemical localization of notch receptors and ligands in human articular cartilage, chondroprogenitor culture and ultrastructural characteristics of these progenitor cells.

    PubMed

    Ustunel, Ismail; Ozenci, Alpay Merter; Sahin, Zeliha; Ozbey, Ozlem; Acar, Nuray; Tanriover, Gamze; Celik-Ozenci, Ciler; Demir, Ramazan

    2008-01-01

    The presence of progenitor/stem cells in human articular cartilage remains controversial. Therefore, we attempted to isolate and culture progenitor/stem cells and to investigate their phenotypic characteristics. Biopsies were obtained (with consent) from patients undergoing arthroscopic surgery. Full depth explants were fixed and cryosectioned or enzymatically digested and the resulting cells cultured and plated on fibronectin-coated dishes. Chondrocytes were cultured until colonies of >32 cells were present. Colonies were trypsinized and expanded in monolayer for pellet culture. Immunolocalization of Notch and its ligands were detected in vivo and in vitro using immunocytochemistry. In vitro studies investigated differences in immunolocalization of Notch and its associated ligands in colony-forming cells and small clusters of non-colony-forming cells. The ultrastructure of the chondroprogenitors was examined by scanning and transmission electron microscopy. Results revealed that the immunolocalization of Notch-1 and its ligand Delta were concentrated in regions closest to the articular surface. Notch-1 was also densely localized in the deeper zone of articular cartilage. Notch-2 immunolabeling was densely localized in all zones of articular cartilage. Jagged-1 was concentrated in the deeper regions of articular cartilage. Notch-1, Delta and Jagged-1 were more abundant in colony-forming cells than non-colony-forming chondrocytes in vitro. Notch-3, Notch-4 and Jagged-2 were absent from all regions of the articular cartilage tissues and cultured cartilage cells in vitro. Ultrastructurally, chondrocytes cultured in monolayer dedifferentiated to fibroblast-like cells with cell surface processes of varying lengths, pellet cultured cells varied in morphology, as flattened and rounded. In conclusion, we propose that adult human articular cartilage may contain cells having progenitor cell features. PMID:18272209

  5. 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

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

    PubMed

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

    2015-12-07

    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.

  7. 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

  8. The role of BKCa channels on hyperpolarization mediated by hyperosmolarity in human articular chondrocytes.

    PubMed

    Sánchez, Julio C; López-Zapata, Diego F

    2011-03-01

    Chondrocytes, the only cell in cartilage, are subjected to hyperosmotic challenges continuously since extracellular osmolarity in articular cartilage increases in response to mechanical loads during joint movement. Hyperosmolarity can affect membrane transport, and it is possible that load modulates matrix synthesis through alterations in intracellular composition. In the present study, the effects of hyperosmotic challenges were evaluated using the whole-cell patch clamp technique, whole cell mode on freshly isolated human and bovine articular chondrocytes. In human chondrocytes, hypertonicity induced the activation of outward Ca(2+)-sensitive K(+) currents, which were inhibited by iberiotoxin and TEA-Cl. The current induced by hypertonic switching (osmolarity from 300 to 400 mOsm/l) caused cell hyperpolarization (from -39 mV to -70 mV) with a reversal potential of -96 ± 7 mV. These results suggest a role for Ca(2+)-activated K(+) channels in human articular chondrocytes, leading to hyperpolarization as a consequence of K(+) efflux through these channels. These channels could have a role in the articular chondrocyte's response to a hyperosmotic challenge and matrix metabolism regulation by load.

  9. 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

  10. 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.

  11. 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

  12. Hyperosmolarity protects chondrocytes from mechanical injury in human articular cartilage: an experimental report.

    PubMed

    Amin, A K; Huntley, J S; Patton, J T; Brenkel, I J; Simpson, A H R W; Hall, A C

    2011-02-01

    The aim of this study was to determine whether exposure of human articular cartilage to hyperosmotic saline (0.9%, 600 mOsm) reduces in situ chondrocyte death following a standardised mechanical injury produced by a scalpel cut compared with the same assault and exposure to normal saline (0.9%, 285 mOsm). Human cartilage explants were exposed to normal (control) and hyperosmotic 0.9% saline solutions for five minutes before the mechanical injury to allow in situ chondrocytes to respond to the altered osmotic environment, and incubated for a further 2.5 hours in the same solutions following the mechanical injury. Using confocal laser scanning microscopy, we identified a sixfold (p = 0.04) decrease in chondrocyte death following mechanical injury in the superficial zone of human articular cartilage exposed to hyperosmotic saline compared with normal saline. These data suggest that increasing the osmolarity of joint irrigation solutions used during open and arthroscopic articular surgery may reduce chondrocyte death from surgical injury and could promote integrative cartilage repair.

  13. 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

  14. Iron oxide labelling of human mesenchymal stem cells in collagen hydrogels for articular cartilage repair.

    PubMed

    Heymer, Andrea; Haddad, Daniel; Weber, Meike; Gbureck, Uwe; Jakob, Peter M; Eulert, Jochen; Nöth, Ulrich

    2008-04-01

    For the development of new therapeutical cell-based strategies for articular cartilage repair, a reliable cell monitoring technique is required to track the cells in vivo non-invasively and repeatedly. We present a systematic and detailed study on the performance and biological impact of a simple and efficient labelling protocol for human mesenchymal stem cells (hMSCs). Commercially available very small superparamagnetic iron oxide particles (VSOPs) were used as magnetic resonance (MR) contrast agent. Iron uptake via endocytosis was confirmed histologically with prussian blue staining and quantified by mass spectrometry. Compared with unlabelled cells, VSOP-labelling did neither influence the viability nor the proliferation potential of hMSCs. Furthermore, iron incorporation did not affect hMSCs in undergoing adipogenic, osteogenic or chondrogenic differentiation, as demonstrated histologically and by gene expression analyses. The efficiency of the labelling protocol was assessed with high-resolution MR imaging at 11.7T. VSOP-labelled hMSCs were visualised in a collagen type I hydrogel, which is in clinical use for matrix-based articular cartilage repair. The presence of VSOP-labelled hMSCs was indicated by distinct hypointense spots in the MR images, as a result of iron specific loss of signal intensity. In summary, this labelling technique has great potential to visualise hMSCs and track their migration after transplantation for articular cartilage repair with MR imaging.

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

    PubMed Central

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

    2015-01-01

    Hypertrophic differentiation of chondrocytes is a main barrier in application of mesenchymal stem cells (MSCs) for cartilage repair. In addition, hypertrophy occurs occasionally in osteoarthritis (OA). Here we provide a comprehensive review on recent literature describing signal pathways in the hypertrophy of MSCs-derived in vitro differentiated chondrocytes and chondrocytes, with an emphasis on the crosstalk between these pathways. Insight into the exact regulation of hypertrophy by the signaling network is necessary for the efficient application of MSCs for articular cartilage repair and for developing novel strategies for curing OA. We focus on articles describing the role of the main signaling pathways in regulating chondrocyte hypertrophy-like changes. Most studies report hypertrophic differentiation in chondrogenesis of MSCs, in both human OA and experimental OA. Chondrocyte hypertrophy is not under the strict control of a single pathway but appears to be regulated by an intricately regulated network of multiple signaling pathways, such as WNT, Bone morphogenetic protein (BMP)/Transforming growth factor-β (TGFβ), Parathyroid hormone-related peptide (PTHrP), Indian hedgehog (IHH), Fibroblast growth factor (FGF), Insulin like growth factor (IGF) and Hypoxia-inducible factor (HIF). This comprehensive review describes how this intricate signaling network influences tissue-engineering applications of MSCs in articular cartilage (AC) repair, and improves understanding of the disease stages and cellular responses within an OA articular joint. PMID:26287176

  16. 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

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

    PubMed

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

    2009-06-01

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

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

    PubMed

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

    2003-05-01

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

  19. 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.

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

    PubMed

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

    2012-05-01

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

  1. Opiates do not violate the viability and proliferative activity of human articular chondrocytes.

    PubMed

    Chechik, Ofir; Arbel, Ron; Salai, Moshe; Gigi, Roy; Beilin, Mark; Flaishon, Ron; Sever, Ronen; Khashan, Morsi; Ben-Tov, Tomer; Gal-Levy, Ronit; Yayon, Avner; Blumenstein, Sara

    2014-09-01

    Articular cartilage injuries present a challenge for the clinician. Autologous chondrocyte implantation embedded in scaffolds are used to treat cartilage defects with favorable outcomes. Autologous serum is often used as a medium for chondrocyte cell culture during the proliferation phase of the process of such products. A previous report showed that opiate analgesics (fentanyl, alfentanil and diamorphine) in the sera have a significant inhibitory effect on chondrocyte proliferation. In order to determine if opiates in serum inhibit chondrocyte proliferation, twenty two patients who underwent knee arthroscopy and were anesthetized with either fentanyl or remifentanil were studied. Blood was drawn before and during opiate administration and up to 2 h after its discontinuation. The sera were used as medium for in vitro proliferation of both cryopreserved and freshly isolated chondrocytes, and the number and viability of cells were measured. There was no difference in the yield or cell viability between the serum samples of patients anesthetized with fentanyl when either fresh or cryopreserved human articular chondrocytes (hACs) were used. Some non-significant reduction in the yield of cells was observed in the serum samples of patients anesthetized with remifentanil when fresh hAC were used. We conclude that Fentanyl in human autologous serum does not inhibit in vitro hAC proliferation. Remifentanil may show minimal inhibitory effect on in vitro fresh hAC proliferation.

  2. Effects of osmotic challenges on membrane potential in human articular chondrocytes from healthy and osteoarthritic cartilage.

    PubMed

    Sánchez, Julio C; López-Zapata, Diego F

    2010-01-01

    Changes in external osmolarity arise from variations in mechanical loads on joints and may affect the homeostasis of chondrocytes, which are the only cell type responsible for matrix turnover. Accordingly, variations in membrane potential may affect cartilage production. The present study assessed the effects of variations in external osmolarity on membrane potential and the possible mechanisms responsible for this response. Membrane potential was measured by the patch clamp whole-cell technique using human articular chondrocytes freshly isolated from healthy and osteoarthritic cartilage. The membrane potential was -39±4 mV in articular human chondrocytes from healthy cartilage and -26±4 mV in those from osteoarthritic cartilage. Increasing the osmolarity produced a reversible hyperpolarization mediated by K+ efflux through BKCa channels in both groups of chondrocytes, but the response in osteoarthritic cells was significantly reduced; no other K+ pathways were involved in this effect. Alternatively, decreasing the osmolarity elicited depolarization in healthy chondrocytes but did not produce any response in chondrocytes from osteoarthritic cartilage. The depolarization was dependent on Na+ influx through Gd3+-sensitive stretch-activated cation channels and was independent of external Ca2+. The differential responses observed in chondrocytes from osteoarthritic cartilage suggest that disregulation on the responses to external osmolarity may be involved in the process that leads to the alterations in the cartilage structure observed in osteoarthritis.

  3. The mechanical and material properties of elderly human articular cartilage subject to impact and slow loading.

    PubMed

    Burgin, L V; Edelsten, L; Aspden, R M

    2014-02-01

    The mechanical properties of articular cartilage vary enormously with loading rate, and how these properties derive from the composition and structure of the tissue is still unclear. This study investigates the mechanical properties of human articular cartilage at rapid rates of loading, compares these with measurements at slow rates of loading and explores how they relate to the gross composition of the tissue. Full-depth femoral head cartilage biopsies were subjected to a slow, unconfined compression test followed by an impact at an energy of 78.5mJ and velocity 1.25ms(-1). The modulus was calculated from the slope of the loading curve and the coefficient of restitution from the areas under the loading and unloading curves. Tissue composition was measured as water, collagen and glycosaminoglycan contents. The maximum dynamic modulus ranged from 25 to 150MPa. These values compared with 1-3MPa measured during quasi-static loading. The coefficient of restitution was 0.502 (0.066) (mean (standard deviation)) and showed no site variation. Water loss was not detectable. Composition was not strongly associated with modulus; water and collagen contents together predicted about 25% of the variance in modulus.

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

    PubMed

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

    2001-06-01

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

  5. Expression and cellular localization of human hyaluronidase-2 in articular chondrocytes and cultured cell lines

    PubMed Central

    Chow, G.; Knudson, C. B.; Knudson, W.

    2011-01-01

    Summary Objective There is debate whether hyaluronan (HA) can be enzymatically degraded within the extracellular matrix of cartilage and other tissues or whether its catabolism occurs strictly within the lysosomal compartment of chondrocytes and other cell types. Previous studies have suggested that one of the lysosomal hyaluronidases (hyaluronidase-2) can be expressed as a functionally-active glycosyl phosphatidylinositol-linked protein at the surface of mammalian cells. If this form of hyaluronidase expression occurs in chondrocytes, this could represent a possible mechanism for extracellular HA cleavage. Thus, which hyaluronidases are expressed and where was the objective of this study. Methods mRNA for hyaluronidases was quantified by reverse transcription-polymerase chain reaction (RT-PCR) and enzymatic activity by HA zymograms. Recombinant forms of hyaluronidase-2 were generated and expressed in model cell lines. A peptide-specific polyclonal antiserum was prepared to localize endogenous human hyaluronidase-2 in human articular chondrocytes. Results Hyaluronidase-2 is the principal mRNA transcript expressed by primary human articular chondrocytes as well as various model cell lines. Recombinant hyaluronidase-2, containing N-terminal or C-terminal epitope tags, was strictly localized intracellularly and not released by treatment with a phosphatidylinositol-specific phospholipase. Endogenous hyaluronidase-2 expressed by human chondrocytes as well as HeLa cells could only be detected following detergent permeabilization of the plasma membranes. Conclusions These data suggest that on chondrocytes and other cell types examined, hyaluronidase-2 is not present or functional at the external plasma membrane. Thus, local turnover of HA is dependent on receptor-mediated endocytosis and delivery to low pH intracellular organelles for its complete degradation. PMID:16600643

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

    PubMed

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

    2014-09-01

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

  7. 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.

  8. Effect of nitric oxide on mitochondrial respiratory activity of human articular chondrocytes

    PubMed Central

    Maneiro, E; Lopez-Armada, M; de Andres, M C; Carames, B; Martin, M; Bonilla, A; del Hoyo, P; Galdo, F; Arenas, J; Blanco, F

    2005-01-01

    Objective: To investigate the effect of nitric oxide (NO) on mitochondrial activity and its relation with the apoptosis of human articular chondrocytes. Materials and methods: Mitochondrial function was evaluated by analysing respiratory chain enzyme complexes, citrate synthase (CS) activities, and mitochondrial membrane potential (Δψm). The activities of the mitochondrial respiratory chain (MRC) complexes (complex I: NADH CoQ1 reductase, complex II: succinate dehydrogenase, complex III: ubiquinol cytochrome c reductase, complex IV: cytochrome c oxidase) and CS were measured in human articular chondrocytes isolated from normal cartilage. The Δψm was measured by 5,5',6,6'-tetracholoro-1,1',3,3'-tetraethylbenzimidazole carbocyanide iodide (JC-1) using flow cytometry. Apoptosis was analysed by flow cytometry. The mRNA expression of caspases was analysed by ribonuclease protection analysis and the detection of protein synthesis by western blotting. Sodium nitroprusside (SNP) was used as an NO compound donor. Results: SNP at concentrations higher than 0.5 mmol/l for 24 hours induced cellular changes characteristic of apoptosis. SNP elicited mRNA expression of caspase-3 and caspase-7 and down regulated bcl-2 synthesis in a dose and time dependent manner. Furthermore, 0.5 mM SNP induced depolarisation of the mitochondrial membrane at 5, 12, and 24 hours. Analysis of the MRC showed that at 5 hours, 0.5 mM SNP reduced the activity of complex IV by 33%. The individual inhibition of mitochondrial complex IV with azide modified the Δψm and induced apoptosis. Conclusions: This study suggests that the effect of NO on chondrocyte survival is mediated by its effect on complex IV of the MRC. PMID:15708893

  9. Stimulation of the Superficial Zone Protein and Lubrication in the Articular Cartilage by Human Platelet-Rich Plasma

    PubMed Central

    Sakata, Ryosuke; McNary, Sean M.; Miyatake, Kazumasa; Lee, Cassandra A.; Van den Bogaerde, James M.; Marder, Richard A.; Reddi, A. Hari

    2016-01-01

    Background Platelet-rich plasma (PRP) contains high concentrations of autologous growth factors that originate from platelets. Intra-articular injections of PRP have the potential to ameliorate the symptoms of osteoarthritis in the knee. Superficial zone protein (SZP) is a boundary lubricant in articular cartilage and plays an important role in reducing friction and wear and therefore is critical in cartilage homeostasis. Purpose To determine if PRP influences the production of SZP from human joint-derived cells and to evaluate the lubricating properties of PRP on normal bovine articular cartilage. Study Design Controlled laboratory study. Methods Cells were isolated from articular cartilage, synovium, and the anterior cruciate ligament (ACL) from 12 patients undergoing ACL reconstruction. The concentrations of SZP in PRP and culture media were measured by enzyme-linked immunosorbent assay. Cellular proliferation was quantified by determination of cell numbers. The lubrication properties of PRP from healthy volunteers on bovine articular cartilage were investigated using a pin-on-disk tribometer. Results In general, PRP stimulated proliferation in cells derived from articular cartilage, synovium, and ACL. It also significantly enhanced SZP secretion from synovium- and cartilage-derived cells. An unexpected finding was the presence of SZP in PRP (2.89 ± 1.23 µg/mL before activation and 3.02 ± 1.32 µg/mL after activation). In addition, under boundary mode conditions consisting of high loads and low sliding speeds, nonactivated and thrombin-activated PRP decreased the friction coefficient (μ = 0.012 and μ = 0.015, respectively) compared with saline (μ = 0.047, P < 0.004) and high molecular weight hyaluronan (μ = 0.080, P < 0.006). The friction coefficient of the cartilage with PRP was on par with that of synovial fluid. Conclusion PRP significantly stimulates cell proliferation and SZP secretion by articular cartilage and synovium of the human knee joint

  10. ROCK inhibition enhances aggrecan deposition and suppresses matrix metalloproteinase-3 production in human articular chondrocytes.

    PubMed

    Furumatsu, Takayuki; Matsumoto-Ogawa, Emi; Tanaka, Takaaki; Lu, Zhichao; Ozaki, Toshifumi

    2014-04-01

    Homeostasis of articular cartilage is maintained by a balance between catabolism and anabolism. Matrix metalloproteinase-3 (MMP-3) catabolism of cartilaginous extracellular matrix (ECM), including aggrecan (AGN), is an important factor in osteoarthritis progression. We previously reported that inhibition of Rho-associated coiled-coil forming kinase (ROCK), an effector of Rho family GTPases, activates the chondrogenic transcription factor SRY-type high-mobility-group box (SOX) 9 and prevents dedifferentiation of monolayer-cultured chondrocytes. We hypothesized that ROCK inhibition prevents chondrocyte dedifferentiation by altering the transcriptional balance between MMP-3 and AGN. Normal human articular chondrocytes were cultured in the presence or absence of ROCK inhibitor (ROCKi, Y-27632). Expression of MMP-3 and AGN during monolayer cultivation was assessed by quantitative real-time PCR and western blot analysis. Chondrogenic redifferentiation potential of ROCKi-treated chondrocytes was evaluated by immunohistological analysis of pellet cultures. ROCKi treatment suppressed MMP-3 expression in monolayer- and pellet-cultured chondrocytes but increased AGN expression. Chromatin immunoprecipitation revealed that the association between transcription factors E26 transformation specific (ETS)-1 and SOX9 and their target genes MMP-3 and AGN, respectively, was affected by ROCKi treatment. ROCKi decreased the association between ETS-1 and its binding sites on the MMP-3 promoter, whereas ROCKi promoted the interaction between SOX9 and the AGN promoter. Our results suggest that ROCK inhibition may have an important role in modulating the balance between degradation and synthesis of cartilaginous ECM, a finding that may facilitate development of techniques to prepare differentiated chondrocytes for cartilage regeneration therapy.

  11. Bovine Lactoferricin-induced Anti-inflammation Is, in Part, via Up-regulation of Interleukin-11 by Secondary Activation of STAT3 in Human Articular Cartilage*

    PubMed Central

    Yan, Dongyao; Kc, Ranjan; Chen, Di; Xiao, Guozhi; Im, Hee-Jeong

    2013-01-01

    Bovine lactoferricin (LfcinB), a multifunctional peptide, was recently demonstrated to be anti-catabolic and anti-inflammatory in human articular cartilage. LfcinB blocks IL-1-mediated proteoglycan depletion, matrix-degrading enzyme expression, and pro-inflammatory mediator induction. LfcinB selectively activates ERK1/2, p38 (but not JNK), and Akt signaling. However, the relationship between these pathways and LfcinB target genes has never been explored. In this study, we uncovered the remarkable ability of LfcinB in the induction of an anti-inflammatory cytokine, IL-11. LfcinB binds to cell surface heparan sulfate to initiate ERK1/2 signaling and activate AP-1 complexes composed of c-Fos and JunD, which transactivate the IL-11 gene. The induced IL-11 functions as an anti-inflammatory and chondroprotective cytokine in articular chondrocytes. Our data show that IL-11 directly attenuates IL-1-mediated catabolic and inflammatory processes ex vivo and in vitro. Moreover, IL-11 activates STAT3 signaling pathway to critically up-regulate TIMP-1 expression, as a consecutive secondary cellular response after IL-11 induction by LfcinB-ERK-AP-1 axis in human adult articular chondrocytes. The pathological relevance of IL-11 signaling to osteoarthritis is evidenced by significant down-regulation of its cognate receptor expression in osteoarthritic chondrocytes. Together, our results suggest a two-step mechanism, whereby LfcinB induces TIMP-1 through an IL-11-dependent pathway involving transcription factor AP-1 and STAT3. PMID:24036113

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

    PubMed

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

    2011-06-01

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

  13. Articular involvement in human brucellosis: a retrospective analysis of 304 cases.

    PubMed

    Gotuzzo, E; Alarcón, G S; Bocanegra, T S; Carrillo, C; Guerra, J C; Rolando, I; Espinoza, L R

    1982-11-01

    Brucellosis is a zoonosis which in humans is caused by one of four species of the Brucella genus: B. melitensis, B. abortus, B. suis and B. canis. B. abortus is the species prevalent in North America and Europe and B. melitensis in most developing countries. Differences in disease manifestations may be accounted for either by differences in the species or by differences in the host. Articular involvement in brucellosis, although recognized since 1904, has been variably emphasized. Three hundred and four cases of human Brucellosis caused by B. melitensis, the prevalent species in Perú, were seen during a 12-yr period in one Lima hospital. Fever, malaise and hepatomegaly were the most frequent findings. Diagnosis was greatly improved when cultures were done in the biphasic Ruiz-Castañeda medium, rather than in trypticase soy broth. Serologic diagnosis is still important, and it should include standard tube testing, detection of IgG blocking antibodies and fractionation with 2-ME in chronic cases. The disease may take one of three courses: acute, (< 8 wk), chronic (> 8 wk) or undulant (periods of remissions and exacerbations). Four syndromes were recognized in a total of 33.8% of patients with Brucellosis. The most frequent pattern (in approximately 46.6% of patients with arthritis) was sacroiliitis, usually non-destructive and either uni- or bilateral. The second most frequent articular syndrome was peripheral arthritis (38.8%), manifested either as a single large lower extremity joint or as an asymmetric pauciarthritis. Rarely patients presented with a rheumatoid-like arthritis. Mixed arthritis (7.8%) was a combination of the first two. The above forms occurred in patients with an acute or undulant course. Spondylitis was the least common form of arthritis (6.8%), and differed significantly from the other forms of arthritis in the duration of symptoms (chronic course), age of patients (older individuals) and the paucity of fever and malaise. It also tended to be

  14. A review of the human and veterinary literature on local anaesthetics and their intra-articular use. Relevant information for lameness diagnosis in the dog.

    PubMed

    Van Vynckt, D; Polis, I; Verschooten, F; Van Ryssen, B

    2010-01-01

    Lameness in dogs is often a diagnostic challenge. In many cases it is difficult to determine the exact localisation of lameness because of the absence of palpable changes, or because of unreliable pain response due to high pain tolerance, stress or aggression of the dog. In horses and humans, intra-articular administration of local anaesthetics is commonly used for diagnostic purposes. In this review, information from human and veterinary studies on different local anaesthetic agents and their application for diagnostic intra-articular anaesthesia is given. Based on this information, a protocol for diagnostic intra-articular anaesthesia in the dog can be developed and evaluated in future studies. PMID:20585716

  15. 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

  16. 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

  17. 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.

  18. 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

  19. Actinomyces timonensis sp. nov., isolated from a human clinical osteo-articular sample.

    PubMed

    Renvoise, Aurélie; Raoult, Didier; Roux, Véronique

    2010-07-01

    Gram-positive, non-spore-forming rods were isolated from a human osteo-articular sample (strain 7400942(T)). Based on cellular morphology and the results of biochemical analysis, this strain was tentatively identified as a novel species of the genus Actinomyces. Phylogenetic analysis based on 16S rRNA gene sequence comparisons showed that the bacterium was closely related to the type strain of Actinomyces denticolens (96.9 % 16S rRNA gene sequence similarity). A comparison of biochemical traits showed that strain 7400942(T) was distinct from A. denticolens in a number of characteristics, i.e. in contrast with A. denticolens, strain 7400942(T) was negative for nitrate reduction and for beta-galactosidase, alpha-glucosidase and alanine arylamidase activities, it was positive for acid production from N-acetylglucosamine, melezitose and glycogen, and it was negative for acid production from turanose. Matrix-assisted laser-desorption/ionization time-of-flight MS protein analysis confirmed that strain 7400942(T) represents a novel species, as scores obtained for its spectra were significant (>2.2) only with strain 7400942(T). On the basis of phenotypic data and phylogenetic inference, it is proposed that this strain should be designated Actinomyces timonensis sp. nov.; the type strain is strain 7400942(T) (=CSUR P35(T)=CCUG 55928(T)).

  20. 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

  1. Periodic rewetting enhances the viability of chondrocytes in human articular cartilage exposed to air.

    PubMed

    Pun, S Y; Teng, M S; Kim, H T

    2006-11-01

    Desiccation of articular cartilage during surgery is often unavoidable and may result in the death of chondrocytes, with subsequent joint degeneration. This study was undertaken to determine the extent of chondrocyte death caused by exposure to air and to ascertain whether regular rewetting of cartilage could decrease cell death. Macroscopically normal human cartilage was exposed to air for 0, 30, 60 or 120 minutes. Selected samples were wetted in lactated Ringer's solution for ten seconds every ten or 20 minutes. The viability of chondrocytes was measured after three days by Live/Dead staining. Chondrocyte death correlated with the length of exposure to air and the depth of the cartilage. Drying for 120 minutes caused extensive cell death mainly in the superficial 500 microm of cartilage. Rewetting every ten or 20 minutes significantly decreased cell death. The superficial zone is most susceptible to desiccation. Loss of superficial chondrocytes likely decreases the production of essential lubricating glycoproteins and contributes to subsequent degeneration. Frequent wetting of cartilage during arthrotomy is therefore essential.

  2. The articular disc surface in different functional conditions of the human temporo-mandibular joint.

    PubMed

    Marchetti, C; Bernasconi, G; Reguzzoni, M; Farina, A

    1997-07-01

    The peripheral discal tissue and the surface covering layer have been studied in normal and in variously damaged human temporo-mandibular joint discs. In the normal disc the tissue consisted of dense bundles of fibers and rare fibrocytes. The surface of the disc was covered by a regular basophilic and electron-dense layer. These morphological characteristics persisted also in some pathological discs in which fibrous derangements had already occurred in the deep parts. In very deformed and damaged discs associated with serious functional anomalies, the superficial discal tissue consisted of rare fibers dispersed in a loose ground substance and of an increased number of cells. The superficial coating was formed by an irregular dense lamina and aggregates of various materials containing cellular debris, vesicles, filaments and amorphous components. These deposits are probably due to degeneration processes of discal tissue. This investigation suggests that the superficial discal tissue and the covering layer are together involved in maintaining the functional properties of the articular surfaces. Their structural modification in severe functional anomalies leads to failure in the maintenance of nonadherence conditions and to deterioration of the functional defect.

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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).

  8. 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

  9. Collar-type osteophyte of the femur in young adults: is it a harbinger of intra-articular osteoid osteoma?

    PubMed

    Sanal, Hatice Tuba; Bozkurt, Yalcin

    2013-09-01

    Variable clinical and radiological findings for intra-articular osteoid osteoma (OO) of the hip joint make its diagnosis difficult. Because radiographs commonly do not identify the nidus, MR imaging becomes the second line of study. However, because the appearance varies, findings on MR images can be confusing. We found "collar type osteophyte" of the femur i.e. an osteophyte rim around the femoral neck, to be a conspicuous finding of intra-articular OO. Here, this feature will be emphasized and intra-articular OOs will be discussed, with a review of the literature.

  10. 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…

  11. Two-pore domain K⁺ channels regulate membrane potential of isolated human articular chondrocytes.

    PubMed

    Clark, Robert B; Kondo, Colleen; Belke, Darrell D; Giles, Wayne R

    2011-11-01

    Potassium channels that regulate resting membrane potential (RMP) of human articular chondrocytes (HACs) of the tibial joint maintained in short-term (0-3 days) non-confluent cell culture were studied using patch-clamp techniques. Quantitative PCR showed that transcripts of genes for two-pore domain K(+) channels (KCNK1, KCNK5 and KCNK6), and 'BK' Ca(2+)-activated K(+) channels (KCNMA1) were abundantly expressed. Immunocytological methods detected α-subunits for BK and K(2p)5.1 (TASK-2) K(+) channels. Electrophysiological recordings identified three distinct K(+) currents in isolated HACs: (i) a voltage- and time-dependent 'delayed rectifier', blocked by 100 nM α-dendrotoxin, (ii) a large 'noisy' voltage-dependent current that was blocked by low concentrations of tetraethylammonium (TEA; 50% blocking dose = 0.15 mM) and iberiotoxin (52% block, 100 nM) and (iii) a voltage-independent 'background' K(+) current that was blocked by acidic pH (5.5-6), was increased by alkaline pH (8.5), and was not blocked by TEA, but was blocked by the local anaesthetic bupivacaine (0.25 mM). The RMP of isolated HACs was very slightly affected by 5 mM TEA, which was sufficient to block both voltage-dependent K(+) currents, suggesting that these currents probably contributed little to maintaining RMP under 'resting' conditions (i.e. low internal [Ca(2+)]). Increases in external K(+) concentration depolarized HACs by 30 mV in response to a 10-fold increase in [K(+)], indicating a significant but not exclusive role for K(+) current in determining RMP. Increases in external [K(+)] in voltage-clamped HACs revealed a voltage-independent K(+) current whose inward current magnitude increased with external [K(+)]. Block of this current by bupivacaine (0.25-1 mM) in 5 and 25 mM external [K(+)] resulted in a large (8-25 mV) depolarization of RMP. The biophysical and pharmacological properties of the background K(+) current, together with expression of mRNA and α-subunit protein for TASK-2

  12. Human articular chondrocyte adhesion and proliferation on synthetic biodegradable polymer films.

    PubMed

    Ishaug-Riley, S L; Okun, L E; Prado, G; Applegate, M A; Ratcliffe, A

    1999-12-01

    The effect of polymer chemistry on adhesion, proliferation, and morphology of human articular cartilage (HAC) chondrocytes was evaluated on synthetic degradable polymer films and tissue culture polystyrene (TCPS) as a control. Two-dimensional surfaces of poly(glycolide) (PGA), poly(L-lactide) (L-PLA), poly(D,L-lactide) (D,L-PLA), 85:15 poly(D,L-lactide-co-glycolide) (D,L-PLGA), poly(epsilon-caprolactone) (PCL), 90:10 (D,L-lactide-co-caprolactone) (D,L-PLCL), 9:91 D,L-PLCL, 40:60 L-PLCL, 67:33 poly(glycolide-co-trimethylene carbonate) (PGTMC), and poly(dioxanone) (PDO) were made by spin-casting into uniform thin films. Adhesion kinetics were studied using TCPS and PCL films and revealed that the rate of chondrocyte adhesion began to level off after 6 h. Degree of HAC chondrocyte adhesion was studied on all the substrates after 8 h, and ranged from 47 to 145% of the attachment found on TCPS. The greatest number of chondrocytes attached to PGA and 67:33 PGTMC polymer films, and attachment to PCL and L-PLA films was statistically lower than that found on PGA (p < 0.05). There was no correlation between amount of chondrocyte attachment to the substrates and the substrates' water contact angle. Chondrocytes proliferated equally well on all the substrates resulting in equivalent cell numbers on all the substrates at both day 4 and day 7 of the culture. However, these total cell numbers were reached as a result of a 88- and 42-fold expansion on PDO and PLA, respectively, which was significantly higher than the 11-fold expansion found on TCPS (p < 0.05). The greater fold expansion of the cells on PDO and L-PLA films may be attributed to the availability of space for cells to grow, since their numbers at the start of culture were fewer following the 8 h attachment period. This suggests that regardless of initial seeding density on these degradable polymer substrates (i.e., if some minimum number of cells are able to attach), they will eventually populate the surfaces of all

  13. 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

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

    PubMed

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

    2015-11-09

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

  15. 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

  16. 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

  17. Fibrin sealant promotes migration and proliferation of human articular chondrocytes: possible involvement of thrombin and protease-activated receptors.

    PubMed

    Kirilak, Yaowanuj; Pavlos, Nathan J; Willers, Craig R; Han, Renzhi; Feng, Haotian; Xu, Jiake; Asokananthan, Nithiananthan; Stewart, Geoffrey A; Henry, Peter; Wood, David; Zheng, Ming H

    2006-04-01

    Fibrin sealant (FS), a biological adhesive material, has been recently recommended as an adjunct in autologous chondrocyte implantation (ACI). While FS has been shown to possess osteoinductive potential, little is known about its effects on chondrogenic cells. In this study, we assessed the bioactivity of FS (Tisseel) on the migration and proliferation of human articular chondrocytes in vitro. Using a co-culture assay to mimic matrix-induced ACI (MACI), chondrocytes were found to migrate from collagen membranes towards FS within 12 h of culture, with significant migratory activity evident by 24 h. In addition, 5-bromo-2'-deoxyuridine (BrdU) incorporation experiments revealed that thrombin, the active component of the tissue glue, stimulated chondrocyte proliferation, with maximal efficacy observed at 48 h post-stimulation (1-10 U/ml). In an effort to elucidate the molecular mechanisms underlying these thrombin-induced effects, we examined the expression and activation of protease-activated receptors (PARs), established thrombin receptors. Using a combination of RT-PCR and immunohistochemistry, all four PARs were detected in human chondrocytes, with PAR-1 being the major isoform expressed. Moreover, thrombin and a PAR-1, but not other PAR-isotype-specific peptide agonists, were found to induce rapid intracellular Ca2+ responses in human chondrocytes in calcium mobilization assays. Together, these data demonstrate that FS supports both the migration and proliferation of human chondrocytes. We propose that these effects are mediated, at least in part, via thrombin-induced PAR-1 signalling in human chondrocytes. PMID:16525709

  18. Application of stem cells for articular cartilage regeneration.

    PubMed

    Hwang, Nathaniel S; Elisseeff, Jennifer

    2009-01-01

    Articular cartilage is a highly organized tissue lacking self-regeneration capacity upon lesion. Current surgical intervention by application of in vitro-expanded autologous chondrocytes transplantation procedure is associated with several disadvantages, including donor-site morbidity and inferior fibrocartilage formation at the defect site. However, recent advancements in tissue engineering have provided notable strategies for stem cell-based therapies and articular cartilage tissue engineering. In this review, we discuss the current strategies to engineer cartilage tissues from adult stem cells and human embryonic stem cell-derived cells. The characteristics of adult stem cells, the microenvironmental control of cell fate determination, and the limitation imposed by the intrinsic nature of stem cells are discussed. The strategy to commit the stem cells for functional cartilage tissues in vivo is also discussed.

  19. 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

  20. Influence of dynamic load on friction behavior of human articular cartilage, stainless steel and polyvinyl alcohol hydrogel as artificial cartilage.

    PubMed

    Li, Feng; Su, Yonglin; Wang, Jianping; Wu, Gang; Wang, Chengtao

    2010-01-01

    Many biomaterials are being developed to be used for cartilage substitution and hemiarthroplasty implants. The lubrication property is a key feature of the artificial cartilage. The frictional behavior of human articular cartilage, stainless steel and polyvinyl alcohol (PVA) hydrogel were investigated under cartilage-on-PVA hydrogel contact, cartilage-on-cartilage contact and cartilage-on-stainless steel contact using pin-on-plate method. Tests under static load, cyclic load and 1 min load change were used to evaluate friction variations in reciprocating motion. The results showed that the lubrication property of cartilage-on-PVA hydrogel contact and cartilage-on-stainless steel contact were restored in both 1 min load change and cyclic load tests. The friction coefficient of PVA hydrogel decreased from 0.178 to 0.076 in 60 min, which was almost one-third of the value under static load in continuous sliding tests. In each test, the friction coefficient of cartilage-on-cartilage contact maintained far lower value than other contacts. It is indicated that a key feature of artificial cartilage is the biphasic lubrication properties.

  1. 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

  2. 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

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

    PubMed

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

    2010-01-01

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

  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. 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

  6. ICP-MS multielemental determination of metals potentially released from dental implants and articular prostheses in human biological fluids.

    PubMed

    Sarmiento-González, Alejandro; Marchante-Gayón, Juan Manuel; Tejerina-Lobo, José María; Paz-Jiménez, José; Sanz-Medel, Alfredo

    2005-06-01

    A sector field high-resolution (HR)-ICP-MS and an octapole reaction system (ORS)-ICP-MS have been compared for the simultaneous determination of traces of metals (Ti, V, Cr, Co, Ni, and Mo) released from dental implants and articular prostheses in human biological fluids. Optimum sample treatments were evaluated to minimize matrix effects in urine and whole blood. Urine samples were diluted tenfold with ultrapure water, whereas whole blood samples were digested with high-purity nitric acid and hydrogen peroxide and finally diluted tenfold with ultrapure water. In both matrices, internal standardization (Ga and Y) was employed to avoid potential matrix interferences and ICP-MS signal drift. Spectral interferences arising from the plasma gases or the major components of urine and whole blood were identified by (HR)-ICP-MS at 3,000 resolving power. The capabilities of (HR)-ICP-MS and (ORS)-ICP-MS for the removal of such spectral interferences were evaluated and compared. Results indicate that polyatomic interferences, which hamper the determination of such metallic elements in these biological samples, could be overcome by using a resolving power of 3,000. Using (ORS)-ICP-MS, all those elements could be quantified except Ti and V (due to the polyatomic ions 31P16O and 35Cl16O, respectively). The accuracy of the proposed methodologies by (HR)- and (ORS)-ICP-MS was checked against two reference materials. Good agreement between the given values and the concentrations obtained for all the analytes under scrutiny was found except for Ti and V when analyzed by (ORS)-ICP-MS. PMID:15877222

  7. Articular-cartilage matrix gamma-carboxyglutamic acid-containing protein. Characterization and immunolocalization.

    PubMed Central

    Loeser, R; Carlson, C S; Tulli, H; Jerome, W G; Miller, L; Wallin, R

    1992-01-01

    Matrix gamma-carboxyglutamic acid (Gla)-containing protein (MGP) was found to be present in articular cartilage by Western-blot analysis of guanidinium chloride extracts of human and bovine cartilage and was further localized by immunohistochemical studies on human and monkey specimens. In newborn articular cartilage MGP was present diffusely throughout the matrix, whereas in growth-plate cartilage it was seen mainly in late hypertrophic and calcifying-zone chondrocytes. In adult articular cartilage MGP was present primarily in chondrocytes and the pericellular matrix. Immunoelectron microscopy studies revealed an association between MGP and vesicular structures with an appearance consistent with matrix vesicles. MGP may be an important regulator of cartilage calcification because of its localization in cartilage and the known affinity of Gla-containing proteins for Ca2+ and hydroxyapatite. Images Fig. 1. Fig. 2. Fig. 3. PMID:1540125

  8. Spatial variation in T1 of healthy human articular cartilage of the knee joint

    PubMed Central

    Wiener, E; Pfirrmann, C W A; Hodler, J

    2010-01-01

    The longitudiual relaxation time T1 of native cartilage is frequently assumed to be constant. To redress this, the spatial variation of T1 in unenhanced healthy human knee cartilage in different compartments and cartilage layers was investigated. Knees of 25 volunteers were examined on a 1.5 T MRI system. A three-dimensional gradient-echo sequence with a variable flip angle, in combination with parallel imaging, was used for rapid T1 mapping of the whole knee. Regions of interest (ROIs) were defined in five different cartilage segments (medial and lateral femoral cartilage, medial and lateral tibial cartilage and patellar cartilage). Pooled histograms and averaged profiles across the cartilage thickness were generated. The mean values were compared for global variance using the Kruskal–Wallis test and pairwise using the Mann–Whitney U-test. Mean T1 decreased from 900–1100 ms in superficial cartilage to 400–500 ms in deep cartilage. The averaged T1 value of the medial femoral cartilage was 702±68 ms, of the lateral femoral cartilage 630±75 ms, of the medial tibial cartilage 700±87 ms, of the lateral tibial cartilage 594±74 ms and of the patellar cartilage 666±78 ms. There were significant differences between the medial and lateral compartment (p<0.01). In each cartilage segment, T1 decreased considerably from superficial to deep cartilage. Only small variations of T1 between different cartilage segments were found but with a significant difference between the medial and lateral compartments. PMID:19723767

  9. 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.

  10. Growth factor transgenes interactively regulate articular chondrocytes.

    PubMed

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

    2013-04-01

    Adult articular chondrocytes lack an effective repair response to correct damage from injury or osteoarthritis. Polypeptide growth factors that stimulate articular chondrocyte proliferation and cartilage matrix synthesis may augment this response. Gene transfer is a promising approach to delivering such factors. Multiple growth factor genes regulate these cell functions, but multiple growth factor gene transfer remains unexplored. We tested the hypothesis that multiple growth factor gene transfer selectively modulates articular chondrocyte proliferation and matrix synthesis. We tested the hypothesis by delivering combinations of the transgenes encoding insulin-like growth factor I (IGF-I), fibroblast growth factor-2 (FGF-2), transforming growth factor beta1 (TGF-β1), bone morphogenetic protein-2 (BMP-2), and bone morphogenetic protien-7 (BMP-7) to articular chondrocytes and measured changes in the production of DNA, glycosaminoglycan, and collagen. The transgenes differentially regulated all these chondrocyte activities. In concert, the transgenes interacted to generate widely divergent responses from the cells. These interactions ranged from inhibitory to synergistic. The transgene pair encoding IGF-I and FGF-2 maximized cell proliferation. The three-transgene group encoding IGF-I, BMP-2, and BMP-7 maximized matrix production and also optimized the balance between cell proliferation and matrix production. These data demonstrate an approach to articular chondrocyte regulation that may be tailored to stimulate specific cell functions, and suggest that certain growth factor gene combinations have potential value for cell-based articular cartilage repair.

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

    PubMed

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

    2012-03-01

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

  12. Tensorial electrokinetics in articular cartilage.

    PubMed

    Reynaud, Boris; Quinn, Thomas M

    2006-09-15

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

  13. 2-D finite difference time domain model of ultrasound reflection from normal and osteoarthritic human articular cartilage surface.

    PubMed

    Kaleva, Erna; Liukkonen, Jukka; Toyras, Juha; Saarakkala, Simo; Kiviranta, Panu; Jurvelin, Jukka

    2010-04-01

    Quantitative high-frequency ultrasonic evaluation of articular cartilage has shown a potential for the diagnosis of osteoarthritis, where the roughness of the surface, collagen and proteoglycan contents, and the density and mechanical properties of cartilage change concurrently. Experimentally, these factors are difficult to investigate individually and thus a numerical model is needed. The present study is the first one to use finite difference time domain modeling of pulse-echo measurements of articular cartilage. Ultrasound reflection from the surface was investigated with varying surface roughness, material parameters (Young's modulus, density, longitudinal, and transversal velocities) and inclination of the samples. The 2-D simulation results were compared with the results from experimental measurements of the same samples in an identical geometry. Both the roughness and the material parameters contributed significantly to the ultrasound reflection. The angular dependence of the ultrasound reflection was strong for a smooth cartilage surface but disappeared for the samples with a rougher surface. These results support the findings of previous experimental studies and indicate that ultrasound detects changes in the cartilage that are characteristic of osteoarthritis. In the present study there are differences between the results of the simulations and the experimental measurements. However, the systematic patterns in the experimental behavior are correctly reproduced by the model. In the future, our goal is to develop more realistic acoustic models incorporating inhomogeneity and anisotropy of the cartilage. PMID:20378451

  14. 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.

  15. Tantalum oxide nanoparticles for the imaging of articular cartilage using X-ray computed tomography: visualization of ex vivo/in vivo murine tibia and ex vivo human index finger cartilage.

    PubMed

    Freedman, Jonathan D; Lusic, Hrvoje; Snyder, Brian D; Grinstaff, Mark W

    2014-08-01

    The synthesis and characterization of tantalum oxide (Ta2O5) nanoparticles (NPs) as new X-ray contrast media for microcomputed tomography (μCT) imaging of articular cartilage are reported. NPs, approximately 5-10 nm in size, and possessing distinct surface charges, were synthesized using phosphonate (neutral), ammonium (cationic), and carboxylate (anionic) ligands as end functional groups. Assessment of a cartilage defect in a human cadaver distal metacarpophalangeal (MCP) joint with the ammonium nanoparticles showed good visualization of damage and preferential uptake in areas surrounding the defect. Finally, an optimized nontoxic cationic NP contrast agent was evaluated in an in vivo murine model and the cartilage was imaged. These nanoparticles represent a new type of contrast agent for imaging articular cartilage, and the results demonstrate the importance of surface charge in the design of nanoparticulate agents for targeting the surface or interior zones of articular cartilage.

  16. Articular cartilage biochemistry

    SciTech Connect

    Kuettner, K.E.; Schleyerbach, R.; Hascall, V.C.

    1986-01-01

    This book contains six parts, each consisting of several papers. The part titles are: Cartilage Matrix Components; Biosynthesis and Characterization of Cartilage--Specific Matrix Components and Events; Cartilage Metabolism; In Vitro Studies of Articular Cartilage Metabolism; Normal and Pathologic Metabolism of Cartilage; and Destruction of the Articular Cartilage in Rheumatoid Diseases. Some of the paper topics are: magnetic resonance imaging; joint destruction; age-related changes; proteoglycan structure; and biosynthesis of cartilage proteoglycan.

  17. Histological study of the extratympanic portion of the discomallear ligament in adult humans: a functional hypothesis.

    PubMed

    Mérida-Velasco, J R; de la Cuadra-Blanco, C; Pozo Kreilinger, J J; Mérida-Velasco, J A

    2012-01-01

    This study was carried out on histological aspects of the extratympanic portion of the discomallear ligament (DL) in adult humans. The temporomandibular joint (TMJ) was dissected bilaterally in 20 cadavers; in 15 cases the articular disc (AD) and the retroarticular tissue were extirpated. The extratympanic portion of the DL had the shape of a base-down triangle, in relation to the AD, and an upper vertex, in relation to the petrotympanic fissure. In five cases, the base, measured bilaterally, had an average length of 6.4 mm, while the distance from the base to the upper vertex averaged 9.3 mm in length. The extratypanic portion of the DL is an intrinsic ligament of the TMJ, composed of collagen fibres and abundant elastic fibres. We propose that this ligament could act as a tensor of the synovial membrane in movements of the TMJ.

  18. Histological study of the extratympanic portion of the discomallear ligament in adult humans: a functional hypothesis

    PubMed Central

    Mérida-Velasco, J R; de la Cuadra-Blanco, C; Pozo Kreilinger, J J; Mérida-Velasco, J A

    2012-01-01

    This study was carried out on histological aspects of the extratympanic portion of the discomallear ligament (DL) in adult humans. The temporomandibular joint (TMJ) was dissected bilaterally in 20 cadavers; in 15 cases the articular disc (AD) and the retroarticular tissue were extirpated. The extratympanic portion of the DL had the shape of a base-down triangle, in relation to the AD, and an upper vertex, in relation to the petrotympanic fissure. In five cases, the base, measured bilaterally, had an average length of 6.4 mm, while the distance from the base to the upper vertex averaged 9.3 mm in length. The extratypanic portion of the DL is an intrinsic ligament of the TMJ, composed of collagen fibres and abundant elastic fibres. We propose that this ligament could act as a tensor of the synovial membrane in movements of the TMJ. PMID:22050648

  19. Angiogenic properties of adult human thymus fat.

    PubMed

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

    2009-11-01

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

  20. 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

  1. Thiamin requirement of the adult human.

    PubMed

    Sauberlich, H E; Herman, Y F; Stevens, C O; Herman, R H

    1979-11-01

    Young adult male subjects maintained on a metabolic ward were fed diets providing controlled intakes of thiamin and either 2800 or 3600 kcal. The higher level of calories was attained by an increased intake of carbohydrates. Constant weights were maintained by the subjects by adjusting daily activity and exercise schedules. Thiamin requirements were evaluated in terms of erythrocyte transketolase activity and urinary excretion of the vitamin. The results of the study revealed that a relationship exists between thiamin requirement and caloric intake and expenditure. Thus, when the calories being utilized were derived primarily from carbohydrate sources, the minimum adult male requirement for thiamin appeared to be 0.30 mg of thiamin per 1000 kcal. Urinary excretion of thiamin and erythrocyte transketolase activity appear to be reasonably reliable reflections of thiamin intakes and thiamin nutritional status. The use of these measurements in nutrition surveys appears justified. The microbiological assay (Lactobacillus viridescens) for measuring thiamin levels in urine samples appears to be a somewhat more sensitive but valid procedure as an alternate for the thiochrome method. Judged from the results of this study, the recommended intake for the adult human of 0.40 mg of thiamin per 1000 kcal by FAO/WHO and the recommended allowance of 0.5 mg per 1000 kcal by the Food and Nutrition Board of the NAS-NRC appear reasonable and amply allow for biological variations and other factors that may influence the requirement for this vitamin.

  2. [Intra-articular injections].

    PubMed

    Chapelle, Ch

    2015-09-01

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

  3. Morphologic characteristics of processes of nucleus pulposus cells in adult human intervertebral disc

    NASA Astrophysics Data System (ADS)

    Liu, Xiaoyun; Wu, Xinghuo; Hui, Liu; Xu, Weihua; Liu, Xianze; Yang, Shuhua

    2008-12-01

    To explore morphologic characterizatics of cellular processes from adult human nucleus pulposus cells, the nucleus pulposus of adult human intervertebral disc were obtained from 8 patients (Thompson's grade I~II) and then the tissues specimens were carried out by frozen section and electron microscopic section as well as cell isolation and cultured, processes of nucleus pulposus cells were examined using light microscopy, laser scanning confocal microscopy and transmission electron microscopy. When examined at both the confocal and electron microscope level, all the cells possessed the processes and adjacent nucleus pulposus cells processes possessed a gap junction. But elongated and round cells can be examined when NP cells were monolayer cultured. The rate of elongated cells to round cells is 2.3 to 1. The elongated cells protrude along with the long axis of cell body without second processes. Dendritic processes of round cells protrude to all directions from the cell body with multiple-level processes. Processes are one of the morphologic characteristics of intervertebral disc cells which are different from articular cartilage chondrocytes. The research on processes functions will be helpful to understand pathomechanism of intervertebral disc degradation and open a new approach for cytobiology treatment of the intervertebral disc diseases.

  4. 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,…

  5. 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.

  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. 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

  8. 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…

  9. Could adult hippocampal neurogenesis be relevant for human behavior?

    PubMed Central

    Snyder, Jason S.; Cameron, Heather A.

    2011-01-01

    Although the function of adult neurogenesis is still unclear, tools for directly studying the behavioral role of new hippocampal neurons now exist in rodents. Since similar studies are impossible to do in humans, it is important to assess whether the role of new neurons in rodents is likely to be similar to that in humans. One feature of adult neurogenesis that varies tremendously across species is the number of neurons that are generated, so a key question is whether there are enough neurons generated in humans to impact function. In this review we examine neuroanatomy and circuit function in the hippocampus to ask how many granule neurons are needed to impact hippocampal function and then discuss what is known about numbers of new neurons produced in adult rats and humans. We conclude that relatively small numbers of neurons could affect hippocampal circuits and that the magnitude of adult neurogenesis in adult rats and humans is probably larger than generally believed. PMID:21736900

  10. Phytoestrogen Metabolism by Adult Human Gut Microbiota.

    PubMed

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

    2016-08-09

    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.

  11. 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

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

    PubMed

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

    2013-02-01

    Friction measurements of articular cartilage are important to determine the relative tribologic contributions made by synovial fluid or cartilage, and to assess the efficacy of therapies for preventing the development of post-traumatic osteoarthritis. Stanton's equation is the most frequently used formula for estimating the whole joint friction coefficient (μ) of an articular pendulum, and assumes pendulum energy loss through a mass-independent mechanism. This study examines if articular pendulum energy loss is indeed mass independent, and compares Stanton's model to an alternative model, which incorporates viscous damping, for calculating μ. Ten loads (25-100% body weight) were applied in a random order to an articular pendulum using the knees of adult male Hartley guinea pigs (n=4) as the fulcrum. Motion of the decaying pendulum was recorded and μ was estimated using two models: Stanton's equation, and an exponential decay function incorporating a viscous damping coefficient. μ estimates decreased as mass increased for both models. Exponential decay model fit error values were 82% less than the Stanton model. These results indicate that μ decreases with increasing mass, and that an exponential decay model provides a better fit for articular pendulum data at all mass values. In conclusion, inter-study comparisons of articular pendulum μ values should not be made without recognizing the loads used, as μ values are mass dependent. PMID:23122223

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

    PubMed

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

    2013-02-01

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

  14. 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

  15. Gustofacial and olfactofacial responses in human adults.

    PubMed

    Weiland, Romy; Ellgring, Heiner; Macht, Michael

    2010-11-01

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

  16. 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…

  17. 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

  18. 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

  19. Neural stem cells in the adult human brain

    PubMed Central

    Gonzalez-Perez, Oscar

    2012-01-01

    For decades, it was believed that the adult brain was a quiescent organ unable to produce new neurons. At the beginning of the1960's, this dogma was challenged by a small group of neuroscientists. To date, it is well-known that new neurons are generated in the adult brain throughout life. Adult neurogenesis is primary confined to the subventricular zone (SVZ) of the forebrain and the subgranular zone of the dentate gyrus within the hippocampus. In both the human and the rodent brain, the primary progenitor of adult SVZ is a subpopulation of astrocytes that have stem-cell-like features. The human SVZ possesses a peculiar cell composition and displays important organizational differences when compared to the SVZ of other mammals. Some evidence suggests that the human SVZ may be not only an endogenous source of neural precursor cells for brain repair, but also a source of brain tumors. In this review, we described the cytoarchitecture and cellular composition of the SVZ in the adult human brain. We also discussed some clinical implications of SVZ, such as: stem-cell-based therapies against neurodegenerative diseases and its potential as a source of malignant cells. Understanding the biology of human SVZ and its neural progenitors is one of the crucial steps to develop novel therapies against neurological diseases in humans. PMID:23181200

  20. 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…

  1. Extra-articular Snapping Hip

    PubMed Central

    2010-01-01

    Context: Snapping hip, or coxa saltans, is a vague term used to describe palpable or auditory snapping with hip movements. As increasing attention is paid to intra-articular hip pathologies such as acetabular labral tears, it is important to be able to identify and understand the extra-articular causes of snapping hip. Evidence Acquisition: The search terms snapping hip and coxa sultans were used in PubMed to locate suitable studies of any publication date (ending date, November 2008). Results: Extra-articular snapping may be caused laterally by the iliotibial band or anteriorly by the iliopsoas tendon. Snapping of the iliopsoas tendon usually requires contraction of the hip flexors and may be difficult to differentiate from intra-articular causes of snapping. Dynamic ultrasound can help detect abrupt tendon translation during movement, noninvasively supporting the diagnosis of extra-articular snapping hip. The majority of cases of snapping hip resolve with conservative treatment, which includes avoidance of aggravating activities, stretching, and anti-inflammatory medication. In recalcitrant cases, surgery to lengthen the iliotibial band or the iliopsoas tendon has produced symptom relief but may result in prolonged weakness. Conclusions: In treating active patients with snapping soft tissues around the hip, clinicians should recognize that the majority of cases resolve without surgical intervention, while being mindful of the potential for concomitant intra-articular and internal snapping hips. PMID:23015936

  2. Teaching Human Rights: Grades 7 through Adult.

    ERIC Educational Resources Information Center

    Shiman, David A.

    This curriculum resource on human rights is rooted in the United Nations Universal Declaration of Human Rights and seeks to help students understand the issues involved. Using the rights categories suggested by the Universal Declaration, this book offers new ways of teaching about familiar themes. The book contains activities to encourage students…

  3. A suppressive effect of prostaglandin E2 on the expression of SERPINE1/plasminogen activator inhibitor-1 in human articular chondrocytes: An in vitro pilot study

    PubMed Central

    Masuko, Kayo; Murata, Minako; Suematsu, Naoya; Okamoto, Kazuki; Yudoh, Kazuo; Shimizu, Hiroyuki; Beppu, Moroe; Nakamura, Hiroshi; Kato, Tomohiro

    2009-01-01

    Prostaglandin E2 (PGE2) is expressed in articular joints with inflammatory arthropathy and may exert catabolic effects leading to cartilage degradation. As we observed in a preliminary experiment that PGE2 suppressed the expression of SERPINE1/plasminogen activator inhibitor (PAI)-1 mRNA in chondrocytes, we focused on the effect of PGE2 on PAI-1 in a panel of cultured chondrocytes obtained from osteoarthritic patients. Specifically, articular cartilage specimens were obtained from patients with osteoarthritis who underwent joint surgery. Isolated chondrocytes were cultured in vitro as a monolayer and stimulated with PGE2. Stimulated cells and culture supernatants were analyzed using Western blotting and enzyme-linked immunosorbent assay. The results confirmed that the in vitro PGE2 stimulation suppressed the expression of PAI-1 in the tested chondrocyte samples. The inhibitory effect was partly abrogated by an antagonist of EP4 receptor of PGE2, but not by an EP2 antagonist. Although PGE2 induced activations of mitogen-activated protein kinases (MAPK), blocking of the MAPK did not abrogate the suppressive effect of PGE2, implying a distinct signaling pathway. In summary, prostaglandin is suggested to modulate the plasminogen system in chondrocytes. Further elucidation of the interaction might open a new avenue to understand the degradative process of cartilage.

  4. New neurons in the adult striatum: from rodents to humans

    PubMed Central

    Inta, Dragos; Cameron, Heather A.; Gass, Peter

    2015-01-01

    Most neurons are generated during development and are not replaced during adulthood, even if they are lost to injury or disease. It is firmly established, however, that new neurons are generated in the dentate gyrus of the hippocampus of virtually all adult mammals, including humans [1]. Many questions still remain, however, regarding adult neurogenesis in other brain regions and particularly in humans, where standard birthdating methods are not generally feasible. Exciting recent evidence indicates that calretinin-expressing interneurons are added to the adult human striatum at a substantial rate [2]. The role of new neurons is unknown, but studies in rodents will be able to further elucidate their identity and origin and then begin to understand their regulation and function. PMID:26298770

  5. Resident mesenchymal progenitors of articular cartilage

    PubMed Central

    Candela, Maria Elena; Yasuhara, Rika; Iwamoto, Masahiro; Enomoto-Iwamoto, Motomi

    2015-01-01

    Articular cartilage has poor capacity of self-renewal and repair. Insufficient number and activity of resident mesenchymal (connective tissue) progenitors is likely one of the underlying reasons. Chondroprogenitors reside not only in the superficial zone of articular cartilage but also in other zones of articular cartilage and in the neighboring tissues, including perichondrium (groove of Ranvier), synovium and fat pad. These cells may respond to injury and contribute to articular cartilage healing. In addition, marrow stromal cells can migrate through subchondral bone when articular cartilage is damaged. We should develop drugs and methods that correctly stimulate resident progenitors for improvement of repair and inhibition of degenerative changes in articular cartilage. PMID:25179676

  6. Resident mesenchymal progenitors of articular cartilage.

    PubMed

    Candela, Maria Elena; Yasuhara, Rika; Iwamoto, Masahiro; Enomoto-Iwamoto, Motomi

    2014-10-01

    Articular cartilage has poor capacity of self-renewal and repair. Insufficient number and activity of resident mesenchymal (connective tissue) progenitors is likely one of the underlying reasons. Chondroprogenitors reside not only in the superficial zone of articular cartilage but also in other zones of articular cartilage and in the neighboring tissues, including perichondrium (groove of Ranvier), synovium and fat pad. These cells may respond to injury and contribute to articular cartilage healing. In addition, marrow stromal cells can migrate through subchondral bone when articular cartilage is damaged. We should develop drugs and methods that correctly stimulate resident progenitors for improvement of repair and inhibition of degenerative changes in articular cartilage. PMID:25179676

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. Novel surface markers directed against adult human gallbladder.

    PubMed

    Galivo, Feorillo H; Dorrell, Craig; Grompe, Maria T; Zhong, YongPing; Streeter, Philip R; Grompe, Markus

    2015-07-01

    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.

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

    PubMed Central

    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

  14. Articular Cartilage Injury in Athletes

    PubMed Central

    McAdams, Timothy R.; Mithoefer, Kai; Scopp, Jason M.; Mandelbaum, Bert R.

    2010-01-01

    Articular cartilage lesions in the athletic population are observed with increasing frequency and, due to limited intrinsic healing capacity, can lead to progressive pain and functional limitation over time. If left untreated, isolated cartilage lesions can lead to progressive chondropenia or global cartilage loss over time. A chondropenia curve is described to help predict the outcome of cartilage injury based on different lesion and patient characteristics. Nutriceuticals and chondroprotective agents are being investigated as tools to slow the development of chondropenia. Several operative techniques have been described for articular cartilage repair or replacement and, more recently, cartilage regeneration. Rehabilitation guidelines are being developed to meet the needs of these new techniques. Next-generation techniques are currently evaluated to optimize articular cartilage repair biology and to provide a repair cartilage tissue that can withstand the high mechanical loads experienced by the athlete with consistent long-term durability. PMID:26069548

  15. [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

  16. 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

  17. 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.

  18. 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

  19. Predictors of food preferences in adult humans.

    PubMed

    Logue, A W; Smith, M E

    1986-06-01

    Predictors of preferences for a wide variety of foods were examined in 303 male and female human subjects ranging from 14-68 years of age. The subjects completed questionnaires which requested information on the subject's sex, age, thinness, sensation seeking and ethnic background, as well as on the subjects' food preferences. Largely consistent with previous studies, female subjects reported higher preferences for low-calorie foods, candy and wine, and lower preferences for meat, beer, spicy foods and milk. Younger subjects reported higher preferences for sweet foods and lower preferences for foods such as chili pepper that are considered acquired tastes. Thinner subjects tended to rate both sweet foods and meat lower than did other subjects. Preferences for spicy foods or foods likely to cause illness were positively correlated with sensation seeking while preferences for sweet or bland foods or foods unlikely to cause illness were negatively correlated with sensation seeking. Subjects for whom the primary cuisine on which they were raised was Oriental cuisine preferred alcoholic beverages and non-Oriental foods less than did other subjects. A factor analysis of the food preferences yielded ten factors including those for meat and potatoes, alcohol, spices and junk food. Data on predictors of food preferences can assist research on the determinants of food preferences, however much of the variance in food preferences remains to be explained.

  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. Utility of Intra-articular Hip Injections for Femoroacetabular Impingement

    PubMed Central

    Khan, Wahab; Khan, Moin; Alradwan, Hussain; Williams, Ryan; Simunovic, Nicole; Ayeni, Olufemi R.

    2015-01-01

    Background: Femoroacetabular impingement (FAI) is a condition that is becoming increasingly recognized as a common etiology of hip pain in athletes, adolescents, and adults. However, history and clinical examination are often inconclusive in reaching a diagnosis, while imaging often detects asymptomatic abnormalities. Treatment has traditionally been limited to surgery, with the role of conservative management remaining unclear. Purpose: To evaluate the utility of the intra-articular hip injection in the diagnosis and management of FAI. Study Design: Systematic review; Level of evidence, 4. Methods: MEDLINE, EMBASE, and PubMed databases were screened in duplicate for studies published between January 1946 and January 2014. Search terms included femoroacetabular impingement, hip impingement, and intra-articular injection. Quality assessment using the Methodological Index for Non-Randomized Studies (MINORS) scale was completed for all included studies. Data evaluated included study design, study objectives, number of hips, injected product, duration of pain relief, and outcomes measured. Results: Our search yielded 8 studies involving 281 hips. Studies were categorized into diagnostic (4 studies), therapeutic (3 studies), and prognostic (1 study) applications. Patients with FAI and its degenerative sequelae obtained greater relief from diagnostic intra-articular hip injection than those without (P < .05). The diagnostic intra-articular injection performed under ultrasound guidance was better tolerated than injections performed under fluoroscopic guidance (pain rating, 5.6 vs 3.0; P < .1). Intra-articular injection of hyaluronic acid was the most effective at providing pain relief (in 23 patients), with significant improvements of functional outcome measures (Harris Hip Score, visual analog scale) present at 12 months. Pooled results with corticosteroid injection resulted in improvement in only 15% (9/60) of patients at 6 weeks. A negative response to intra-articular

  2. 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

  3. 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

  4. 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

  5. [Generation of new nerve cells in the adult human brain].

    PubMed

    Poulsen, Frantz Rom; Meyer, Morten; Rasmussen, Jens Zimmer

    2003-03-31

    Generation of new nerve cells (neurogenesis) is normally considered to be limited to the fetal and early postnatal period. Thus, damaged nerve cells are not expected to be replaced by generation of new cells. The brain is, however, more plastic than previously assumed. This also includes neurogenesis in the adult human brain. In particular two brain regions show continuous division of neural stem and progenitor cells generating neurons and glial cells, namely the subgranular zone of the dentate gyrus and the subventricular zones of the lateral ventricles. From the latter region newly generated neuroblasts (immature nerve cells) migrate toward the olfactory bulb where they differentiate into neurons. In the dentate gyrus the newly generated neurons become functionally integrated in the granule cell layer, where they are believed to be of importance to learning and memory. It is at present not known whether neurogenesis in the adult human brain can be manipulated for specific repair after brain damage.

  6. 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

  7. Epidermal growth factor receptor in adult human dorsal root ganglia.

    PubMed

    Huerta, J J; Diaz-Trelles, R; Naves, F J; Llamosas, M M; Del Valle, M E; Vega, J A

    1996-09-01

    Transforming growth factor-alpha (TGFalpha) enhances neuronal survival and neurite outgrowth in cultured dorsal root ganglia (DRG) sensory neurons. It binds a membrane protein, denominated epidermal growth factor receptor (EGFr). EGFr has been localized in developing and adult human DRG. However, it remains to be elucidated whether all DRG neurons express EGFr or whether differences exist among neuronal subtypes. This study was undertaken to investigate these topics in adult human DRG using immunoblotting, and combined immunohistochemistry and image analysis techniques. A mouse monoclonal antibody (clone F4) mapping within the intracytoplasmic domain of EGFr was used. Immunoblotting revealed two main proteins with estimated molecular masses of approximately/equal to 65 kDa and 170 kDa, and thus consistent with the full-length EGFr. Additional protein bands were also encountered. Light immunohistochemistry revealed specific immunoreactivity (IR) for EGFr-like proteins in most (86%) primary sensory neurons, the intensity of immunostaining being stronger in the small- and intermediate-sized ones. Furthermore, EGFr-like IR was also observed in the satellite glial cells of the ganglia as well as in the intraganglionic and dorsal root Schwann cells. Taken together, our findings demonstrate that EGFr, and other related proteins containing the epitope labeled with the antibody F4, are responsible for the EGFr IR reported in DRG. Furthermore, we demonstrated heterogeneity in the expression of EGFr-like IR in adult human primary sensory neurons, which suggests different responsiveness to their ligands.

  8. Importance of material properties and porosity of bone on mechanical response of articular cartilage in human knee joint--a two-dimensional finite element study.

    PubMed

    Venäläinen, Mikko S; Mononen, Mika E; Jurvelin, Jukka S; Töyräs, Juha; Virén, Tuomas; Korhonen, Rami K

    2014-12-01

    Mechanical behavior of bone is determined by the structure and intrinsic, local material properties of the tissue. However, previously presented knee joint models for evaluation of stresses and strains in joints generally consider bones as rigid bodies or linearly elastic solid materials. The aim of this study was to estimate how different structural and mechanical properties of bone affect the mechanical response of articular cartilage within a knee joint. Based on a cadaver knee joint, a two-dimensional (2D) finite element (FE) model of a knee joint including bone, cartilage, and meniscus geometries was constructed. Six different computational models with varying properties for cortical, trabecular, and subchondral bone were created, while the biphasic fibril-reinforced properties of cartilage and menisci were kept unaltered. The simplest model included rigid bones, while the most complex model included specific mechanical properties for different bone structures and anatomically accurate trabecular structure. Models with different porosities of trabecular bone were also constructed. All models were exposed to axial loading of 1.9 times body weight within 0.2 s (mimicking typical maximum knee joint forces during gait) while free varus-valgus rotation was allowed and all other rotations and translations were fixed. As compared to results obtained with the rigid bone model, stresses, strains, and pore pressures observed in cartilage decreased depending on the implemented properties of trabecular bone. Greatest changes in these parameters (up to -51% in maximum principal stresses) were observed when the lowest modulus for trabecular bone (measured at the structural level) was used. By increasing the trabecular bone porosity, stresses and strains were reduced substantially in the lateral tibial cartilage, while they remained relatively constant in the medial tibial plateau. The present results highlight the importance of long bones, in particular, their mechanical

  9. Effect of jaw opening on the stress pattern in a normal human articular disc: finite element analysis based on MRI images

    PubMed Central

    2014-01-01

    Introduction Excessive compressive and shear stresses are likely related to condylar resorption and disc perforation. Few studies have reported the disc displacement and deformation during jaw opening. The aim of this study was to analyze stress distribution in a normal articular disc during the jaw opening movement. Methods Bilateral MRI images were obtained from the temporomandibular joint of a healthy subject for the jaw opening displacement from 6 to 24 mm with 1 mm increments. The disc contour for the jaw opening at 6 mm was defined as the reference state, and was used to establish a two dimensional finite element model of the disc. The contours of the disc at other degrees of jaw opening were used as the displacement loading. Hyperelastic material models were applied to the anterior, intermediate and posterior parts of the disc. Stress and strain trajectories were calculated to characterize the stress/strain patterns in the disc. Results Both the maximum and minimum principal stresses were negative in the intermediate zone, therefore, the intermediate zone withstood mainly compressive stress. On the contrary, the maximum and minimum principal stresses were most positive in the anterior and posterior zones, which meant that the anterior and posterior bands suffered higher tensile stresses. The different patterns of stress trajectories between the intermediate zone and the anterior and posterior bands might be attributed to the effect of fiber orientation. The compression of the intermediate zone and stretching of the anterior and posterior bands caused high shear deformation in the transition region, especially at the disc surfaces. Conclusions The stress and strain remained at a reasonable level during jaw opening, indicating that the disc experiences no injury during functional opening movements in a healthy temporomandibular joint. PMID:24943463

  10. In vivo cartilage formation from growth factor modulated articular chondrocytes.

    PubMed

    Bradham, D M; Horton, W E

    1998-07-01

    Recent procedures for autologous repair of cartilage defects may be difficult in elderly patients because of the loss of stem cells and chondrocytes that occurs with age and the slow in vitro proliferation of chondrocytes from aged cartilage. In this study secondary chondroprogenitor cells were obtained by modulating the phenotype of articular chondrocytes with growth factors and stimulating the proliferation of these cells in culture. Chondrocytes isolated from the articular cartilage of mature New Zealand White rabbits were exposed to a combination of transforming growth factor beta and basic fibroblast growth factor treatment. These cells ceased the production of Collagen II (a marker for the chondrocyte phenotype) and underwent a 136-fold increase in cell number. Next, the cells were placed in high density culture and reexpressed the chondrocyte phenotype in vitro and formed hyaline cartilage in an in vivo assay. Primary chondrocytes obtained from articular cartilage of elderly humans could be manipulated in a similar fashion in vitro. These human secondary chondroprogenitor cells formed only cartilage tissue when assayed in vivo and in tissue bioreactors. This approach may be essential for autologous repair of degenerated articular cartilage in elderly patients with osteoarthritis.

  11. Chondrogenesis, chondrocyte differentiation, and articular cartilage metabolism in health and osteoarthritis.

    PubMed

    Goldring, Mary B

    2012-08-01

    Chondrogenesis occurs as a result of mesenchymal cell condensation and chondroprogenitor cell differentiation. Following chondrogenesis, the chondrocytes remain as resting cells to form the articular cartilage or undergo proliferation, terminal differentiation to chondrocyte hypertrophy, and apoptosis in a process termed endochondral ossification, whereby the hypertrophic cartilage is replaced by bone. Human adult articular cartilage is a complex tissue of matrix proteins that varies from superficial to deep layers and from loaded to unloaded zones. A major challenge to efforts to repair cartilage by stem cell-based and other tissue-engineering strategies is the inability of the resident chondrocytes to lay down a new matrix with the same properties as it had when it was formed during development. Thus, understanding and comparing the mechanisms of cartilage remodeling during development, osteoarthritis (OA), and aging may lead to more effective strategies for preventing cartilage damage and promoting repair. The pivotal proteinase that marks OA progression is matrix metalloproteinase 13 (MMP-13), the major type II collagen-degrading collagenase, which is regulated by both stress and inflammatory signals. We and other investigators have found that there are common mediators of these processes in human OA cartilage. We also observe temporal and spatial expression of these mediators in early through late stages of OA in mouse models and are analyzing the consequences of knockout or transgenic overexpression of critical genes. Since the chondrocytes in adult human cartilage are normally quiescent and maintain the matrix in a low turnover state, understanding how they undergo phenotypic modulation and promote matrix destruction and abnormal repair in OA may to lead to identification of critical targets for therapy to block cartilage damage and promote effective cartilage repair. PMID:22859926

  12. 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

  13. 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

  14. 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

  15. [Multipotency of adult stem cells derived from human amnion].

    PubMed

    Shi, Mingxia; Li, Weijia; Li, Bingzong; Li, Jing; Zhao, Chunhua

    2009-05-01

    Adult stem cells are drawing more and more attention due to the potential application in degenerative medicine without posing any moral problem. There is growing evidence showing that the human amnion contains various types of adult stem cell. Since amniotic tissue is readily available, it has the potential to be an important source of regenerative medicine material. In this study we tried to find multipotent adult stem cells in human amnion. We isolated stem cells from amniotic mesenchymal cells by limiting dilution assay. Similar to bone marrow derived mesenchymal stem cells, these cells displayed a fibroblast like appearance. They were positive for CD105, CD29, CD44, negative for haematopoietic (GlyA, CD31, CD34, CD45) and epithelial cell (pan-CK) markers. These stem cells had the potential to differentiate not only into osteogenic, adipogenic and endothelial lineages, but also hepatocyte-like cells and neural cells at the single-cell level depending on the culture conditions. They had the capacity for self-renewal and multilineage differentiation even after being expanded for more than 30 population doublings in vitro. So they may be an ideal stem cell source for inherited or degenerative diseases treatment.

  16. 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

  17. 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.

  18. Neurons in the White Matter of the Adult Human Neocortex

    PubMed Central

    Suárez-Solá, M. Luisa; González-Delgado, Francisco J.; Pueyo-Morlans, Mercedes; Medina-Bolívar, O. Carolina; Hernández-Acosta, N. Carolina; González-Gómez, Miriam; Meyer, Gundela

    2009-01-01

    The white matter (WM) of the adult human neocortex contains the so-called “interstitial neurons”. They are most numerous in the superficial WM underlying the cortical gyri, and decrease in density toward the deep WM. They are morphologically heterogeneous. A subgroup of interstitial neurons display pyramidal-cell like morphologies, characterized by a polarized dendritic tree with a dominant apical dendrite, and covered with a variable number of dendritic spines. In addition, a large contingent of interstitial neurons can be classified as interneurons based on their neurochemical profile as well as on morphological criteria. WM- interneurons have multipolar or bipolar shapes and express GABA and a variety of other neuronal markers, such as calbindin and calretinin, the extracellular matrix protein reelin, or neuropeptide Y, somatostatin, and nitric oxide synthase. The heterogeneity of interstitial neurons may be relevant for the pathogenesis of Alzheimer disease and schizophrenia. Interstitial neurons are most prominent in human brain, and only rudimentary in the brain of non-primate mammals. These evolutionary differences have precluded adequate experimental work on this cell population, which is usually considered as a relict of the subplate, a transient compartment proper of development and without a known function in the adult brain. The primate-specific prominence of the subplate in late fetal stages points to an important role in the establishment of interstitial neurons. Neurons in the adult WM may be actively involved in coordinating inter-areal connectivity and regulation of blood flow. Further studies in primates will be needed to elucidate the developmental history, adult components and activities of this large neuronal system. PMID:19543540

  19. Lubrication of Articular Cartilage.

    PubMed

    Jahn, Sabrina; Seror, Jasmine; Klein, Jacob

    2016-07-11

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

  20. 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

  1. 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

  2. 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.

  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. 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

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

    PubMed

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

    2014-01-01

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

  6. Gustatory reaction time to various sweeteners in human adults.

    PubMed

    Yamamoto, T; Kato, T; Matsuo, R; Kawamura, Y; Yoshida, M

    1985-09-01

    Reaction times to recognize the sweet taste of 12 sweeteners at various concentrations were measured in 48 human adults. The reaction time (T) decreased with increasing concentration (C) of each sweetener applied to the anterior dorsal tongue. The relationships between T and C, and T and logC were well described by a rectangular hyperbola formula for each of the 12 sweeteners. Reaction times to discriminate sweet taste quality between pairs of sweeteners were measured, then a similarity index was calculated. Factor analysis based on correlation coefficients between pairs of sweeteners which were obtained by the similarity indices has indicated classification of the sweeteners. Sucrose, fructose, glucose, maltose, sorbitol and aspartame tend to group together. Na-cyclamate and Na-saccharin form another group. DL-alanine, stevioside and neohesperidin dihydrochalcone are rather independent and do not belong to any group.

  7. 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

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

    PubMed

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

    2014-04-01

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

  9. Footprint-Free Human Induced Pluripotent Stem Cells From Articular Cartilage With Redifferentiation Capacity: A First Step Toward a Clinical-Grade Cell Source

    PubMed Central

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

    2014-01-01

    Human induced pluripotent stem cells (iPSCs) are potential cell sources for regenerative medicine; however, clinical applications of iPSCs are restricted because of undesired genomic modifications associated with most reprogramming protocols. We show, for the first time, that chondrocytes from autologous chondrocyte implantation (ACI) donors can be efficiently reprogrammed into iPSCs using a nonintegrating method based on mRNA delivery, resulting in footprint-free iPSCs (no genome-sequence modifications), devoid of viral factors or remaining reprogramming molecules. The search for universal allogeneic cell sources for the ACI regenerative treatment has been difficult because making chondrocytes with high matrix-forming capacity from pluripotent human embryonic stem cells has proven challenging and human mesenchymal stem cells have a predisposition to form hypertrophic cartilage and bone. We show that chondrocyte-derived iPSCs can be redifferentiated in vitro into cartilage matrix-producing cells better than fibroblast-derived iPSCs and on par with the donor chondrocytes, suggesting the existence of a differentiation bias toward the somatic cell origin and making chondrocyte-derived iPSCs a promising candidate universal cell source for ACI. Whole-genome single nucleotide polymorphism array and karyotyping were used to verify the genomic integrity and stability of the established iPSC lines. Our results suggest that RNA-based technology eliminates the risk of genomic integrations or aberrations, an important step toward a clinical-grade cell source for regenerative medicine such as treatment of cartilage defects and osteoarthritis. PMID:24604283

  10. 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

  11. A biokinetic model for systemic technetium in adult humans

    DOE PAGES

    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

  12. Comprehensive cellular‐resolution atlas of the adult human brain

    PubMed Central

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

    2016-01-01

    ABSTRACT Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole‐brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high‐resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion‐weighted imaging (DWI), and 1,356 large‐format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto‐ and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127–3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:27418273

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

    PubMed

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

    2016-11-01

    Detailed anatomical understanding of the human brain is essential for unraveling its functional architecture, yet current reference atlases have major limitations such as lack of whole-brain coverage, relatively low image resolution, and sparse structural annotation. We present the first digital human brain atlas to incorporate neuroimaging, high-resolution histology, and chemoarchitecture across a complete adult female brain, consisting of magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and 1,356 large-format cellular resolution (1 µm/pixel) Nissl and immunohistochemistry anatomical plates. The atlas is comprehensively annotated for 862 structures, including 117 white matter tracts and several novel cyto- and chemoarchitecturally defined structures, and these annotations were transferred onto the matching MRI dataset. Neocortical delineations were done for sulci, gyri, and modified Brodmann areas to link macroscopic anatomical and microscopic cytoarchitectural parcellations. Correlated neuroimaging and histological structural delineation allowed fine feature identification in MRI data and subsequent structural identification in MRI data from other brains. This interactive online digital atlas is integrated with existing Allen Institute for Brain Science gene expression atlases and is publicly accessible as a resource for the neuroscience community. J. Comp. Neurol. 524:3127-3481, 2016. © 2016 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc. PMID:27418273

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

    PubMed

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

    2016-11-01

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

  15. 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.

  16. Cellular and Molecular Mechanisms of Synovial Joint and Articular Cartilage Formation

    PubMed Central

    Pacifici, Maurizio; Koyama, Eiki; Shibukawa, Yoshihiro; Wu, Changshan; Tamamura, Yoshihiro; Enomoto-Iwamoto, Motomi; Iwamoto, Masahiro

    2009-01-01

    Synovial joints and articular cartilage play crucial roles in skeletal function, but relatively little is actually known about their embryonic development. Here we first focused on the interzone, a thin mesenchymal cell layer forming at future joint sites that is widely thought to be critical for joint and articular cartilage development. To determine interzone cell origin and fate, we microinjected the vital fluorescent dye DiI at several peri-joint sites in chick limbs and monitored behavior and fate of labeled cells over time. Peri-joint mesenchymal cells located immediately adjacent to incipient joints migrated, became part of the interzone, and were eventually found in epiphyseal articular layer and joint capsule. Interzone cells isolated and reared in vitro expressed typical phenotypic markers, including GDF-5, Wnt-14 and CD-44, and differentiated into chondrocytes over time. To determine the molecular mechanisms of articular chondrocyte formation, we carried out additional studies on the ets transcription factor family member ERG and its alternatively-spliced variant C-1-1 that we previously found to be expressed in developing avian articular chondrocytes. We cloned the human counterpart of avian C-1-1 (ERGp55Δ81) and conditionally expressed it in transgenic mice under cartilage-specific Col2 gene promoter-enhancer control. The entire transgenic mouse limb chondrocyte population exhibited an immature articular-like phenotype and a virtual lack of growth plate formation and chondrocyte maturation compared to wild type littermate. Together, our studies reveal that peri-joint mesenchymal cells take part in interzone and articular layer formation, interzone cells can differentiate into chondrocytes, and acquisition of a permanent articular chondrocyte phenotype is aided and perhaps dictated by ets transcription factor ERG. PMID:16831907

  17. Expression of novel extracellular sulfatases Sulf-1 and Sulf-2 in normal and osteoarthritic articular cartilage

    PubMed Central

    Otsuki, Shuhei; Taniguchi, Noboru; Grogan, Shawn P; D'Lima, Darryl; Kinoshita, Mitsuo; Lotz, Martin

    2008-01-01

    Introduction Changes in sulfation of cartilage glycosaminoglycans as mediated by sulfatases can regulate growth factor signaling. The aim of this study was to analyze expression patterns of recently identified extracellular sulfatases Sulf-1 and Sulf-2 in articular cartilage and chondrocytes. Methods Sulf-1 and Sulf-2 expressions in human articular cartilage from normal donors and patients with osteoarthritis (OA) and in normal and aged mouse joints were analyzed by real-time polymerase chain reaction, immunohistochemistry, and Western blotting. Results In normal articular cartilage, Sulf-1 and Sulf-2 mRNAs and proteins were expressed predominantly in the superficial zone. OA cartilage showed significantly higher Sulf-1 and Sulf-2 mRNA expression as compared with normal human articular cartilage. Sulf protein expression in OA cartilage was prominent in the cell clusters. Western blotting revealed a profound increase in Sulf protein levels in human OA cartilage. In normal mouse joints, Sulf expression was similar to human cartilage, and with increasing age, there was a marked upregulation of Sulf. Conclusion The results show low levels of Sulf expression, restricted to the superficial zone in normal articular cartilage. Sulf mRNA and protein levels are increased in aging and OA cartilage. This increased Sulf expression may change the sulfation patterns of heparan sulfate proteoglycans and growth factor activities and thus contribute to abnormal chondrocyte activation and cartilage degradation in OA. PMID:18507859

  18. 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

  19. 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

  20. 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.

  1. [Present status and perspective of articular cartilage regeneration].

    PubMed

    Wakitani, Shigeyuki

    2007-05-01

    Because the capacity of articular cartilage for repair is limited, defects are a major clinical problem, and there is at present no satisfactory clinical technique to regenerate cartilage defects. Current clinical practice involves the bone stimulation technique, which breaks subchondral bone to facilitate cartilage repair from bone marrow derived cells and cytokines. This consists of multiple perforations, abrasions, and micro-fractures. However, with this procedure, cartilage defects are repaired with fibrocartilage, which is known to be biochemically and biomechanically different from normal hyaline cartilage and degeneration occurs in the reparative tissue. Autologous chondrocyte implantation (ACI) for repair of human articular cartilage was reported in 1994, and approved by the USA Food and Drug Association in 1997. This procedure has been performed for more than 20000 people all over the world, but its effectiveness is still controversial. Mosaic plasty was explored in the 1990s. Using this procedure, we can repair defects with hyaline cartilage, but the donor site morbidity is unsolved. To explore a new method for cartilage repair, we transplanted autologous culture-expanded bone marrow mesenchymal cells into articular cartilage defects. Clinical symptoms were improred but the repair cartilage was not hyaline cartilage. Further improvement is required. Many investigations have been made in the search for better means of repair, including gene transduction and the addition of growth factors during cell culture. In addition to bone marrow mesenchymal cells, synovial cells, adipocytes, muscle cells, etc. have been evaluated.

  2. 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…

  3. 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

  4. 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

  5. A biokinetic model for systemic technetium in adult humans.

    PubMed

    Leggett, R; Giussani, A

    2015-06-01

    This paper reviews biokinetic data for technetium and proposes a biokinetic model for systemic technetium in adult humans. The development of parameter values focuses on data for pertechnetate TcO(-)(4) the most commonly encountered form of technetium and the form expected to be present in body fluids. The model is intended as a default model for occupational or environmental intake of technetium, i.e. applicable in the absence of form- or site-specific information. Tissues depicted explicitly in the model include thyroid, salivary glands, stomach wall, right colon wall, liver, kidneys, and bone. Compared with the ICRP's current biokinetic model for occupational or environmental intake of technetium (ICRP 1993, 1994), the proposed model provides a more detailed and biologically realistic description of the systemic behaviour of technetium and is based on a broader set of experimental and medical data. For acute input of (99m)Tc (T(1/2) = 6.02 h) to blood, the ratios of cumulative (time-integrated) activity predicted by the current ICRP model to that predicted by the proposed model range from 0.4-7 for systemic regions addressed explicitly in both models. For acute input of (99)Tc (T(1/2) = 2.1 × 10(5) year) to blood, the corresponding ratios range from 0.2-30.

  6. 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

  7. Bone-forming capacity of adult human nasal chondrocytes

    PubMed Central

    Pippenger, Benjamin E; Ventura, Manuela; Pelttari, Karoliina; Feliciano, Sandra; Jaquiery, Claude; Scherberich, Arnaud; Walboomers, X Frank; Barbero, Andrea; Martin, Ivan

    2015-01-01

    Nasal chondrocytes (NC) derive from the same multipotent embryological segment that gives rise to the majority of the maxillofacial bone and have been reported to differentiate into osteoblast-like cells in vitro. In this study, we assessed the capacity of adult human NC, appropriately primed towards hypertrophic or osteoblastic differentiation, to form bone tissue in vivo. Hypertrophic induction of NC-based micromass pellets formed mineralized cartilaginous tissues rich in type X collagen, but upon implantation into subcutaneous pockets of nude mice remained avascular and reverted to stable hyaline-cartilage. In the same ectopic environment, NC embedded into ceramic scaffolds and primed with osteogenic medium only sporadically formed intramembranous bone tissue. A clonal study could not demonstrate that the low bone formation efficiency was related to a possibly small proportion of cells competent to become fully functional osteoblasts. We next tested whether the cues present in an orthotopic environment could induce a more efficient direct osteoblastic transformation of NC. Using a nude rat calvarial defect model, we demonstrated that (i) NC directly participated in frank bone formation and (ii) the efficiency of survival and bone formation by NC was significantly higher than that of reference osteogenic cells, namely bone marrow-derived mesenchymal stromal cells. This study provides a proof-of-principle that NC have the plasticity to convert into bone cells and thereby represent an easily available cell source to be further investigated for craniofacial bone regeneration. PMID:25689393

  8. Articular Cartilage Changes in Maturing Athletes

    PubMed Central

    Luria, Ayala; Chu, Constance R.

    2014-01-01

    Context: Articular cartilage has a unique functional architecture capable of providing a lifetime of pain-free joint motion. This tissue, however, undergoes substantial age-related physiologic, mechanical, biochemical, and functional changes that reduce its ability to overcome the effects of mechanical stress and injury. Many factors affect joint function in the maturing athlete—from chondrocyte survival and metabolism to structural composition and genetic/epigenetic factors governing cartilage and synovium. An evaluation of age-related changes for joint homeostasis and risk for osteoarthritis is important to the development of new strategies to rejuvenate aging joints. Objective: This review summarizes the current literature on the biochemical, cellular, and physiologic changes occurring in aging articular cartilage. Data Sources: PubMed (1969-2013) and published books in sports health, cartilage biology, and aging. Study Selection: Keywords included aging, athlete, articular cartilage, epigenetics, and functional performance with age. Study Design: Systematic review. Level of Evidence: Level 3. Data Extraction: To be included, research questions addressed the effect of age-related changes on performance, articular cartilage biology, molecular mechanism, and morphology. Results: The mature athlete faces challenges in maintaining cartilage health and joint function due to age-related changes to articular cartilage biology, morphology, and physiology. These changes include chondrocyte loss and a decline in metabolic response, alterations to matrix and synovial tissue composition, and dysregulation of reparative responses. Conclusion: Although physical decline has been regarded as a normal part of aging, many individuals maintain overall fitness and enjoy targeted improvement to their athletic capacity throughout life. Healthy articular cartilage and joints are needed to maintain athletic performance and general activities. Genetic and potentially reversible

  9. Adult Education and the Human Environment: Transactions of a Celebration.

    ERIC Educational Resources Information Center

    Jones-Quartey, K. A. B., Ed.; And Others

    The document comprises a collection of speeches and seminar reports arising from the 25th anniversary celebration of the Institute of Adult Education at the University of Ghana. The theme of the celebration, introduced in the first chapter, was Adult Education and Man's Environment--the Next Quarter-Century. The second chapter comprises the…

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

    PubMed

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

    2014-01-01

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

  11. Transcriptional Profiling of Adult Neural Stem-Like Cells from the Human Brain

    PubMed Central

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

    2014-01-01

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

  12. 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.

  13. 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

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

    PubMed

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

    2007-06-01

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

  15. 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

  16. 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.

  17. 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…

  18. 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…

  19. 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

  20. 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

  1. Intra-articular fractures of the hand.

    PubMed

    Oak, Nikhil; Lawton, Jeffrey N

    2013-11-01

    Fractures of the hand are common injuries and in particular, fractures involving the articular surfaces can present difficulties to the orthopedic surgeon in practice. Although the treatment of these fractures needs to be individualized based on fracture pattern and location, the goals for these fractures are to restore the alignment, stability, and congruity and to allow for early motion to prevent stiffness and traumatic arthritis. This article classifies the various types of intra-articular hand fractures as well as the workup and management of these injuries. PMID:24209952

  2. 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

  3. 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.

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

    PubMed

    Stupina, T A

    2016-08-01

    We developed and adapted a technology for preparation of articular cartilage specimens for scanning electron microscopy. The method includes prefixation processing, fixation, washing, and dehydration of articular cartilage specimens with subsequent treatment in camphene and air-drying. The technological result consists in prevention of deformation of the articular cartilage structures. The method is simpler and cheaper than the known technologies. PMID:27591865

  5. Investigation of genes important in neurodevelopment disorders in adult human brain.

    PubMed

    Maussion, Gilles; Diallo, Alpha B; Gigek, Carolina O; Chen, Elizabeth S; Crapper, Liam; Théroux, Jean-Francois; Chen, Gary G; Vasuta, Cristina; Ernst, Carl

    2015-10-01

    Several neurodevelopmental disorders (NDDs) are caused by mutations in genes expressed in fetal brain, but little is known about these same genes in adult human brain. Here, we test the hypothesis that genes associated with NDDs continue to have a role in adult human brain to explore the idea that NDD symptoms may be partially a result of their adult function rather than just their neurodevelopmental function. To demonstrate adult brain function, we performed expression analyses and ChIPseq in human neural stem cell(NSC) lines at different developmental stages and adult human brain, targeting two genes associated with NDDs, SATB2 and EHMT1, and the WNT signaling gene TCF7L2, which has not been associated with NDDs. Analysis of DNA interaction sites in neural stem cells reveals high (40-50 %) overlap between proliferating and differentiating cells for each gene in temporal space. Studies in adult brain demonstrate that consensus sites are similar to NSCs but occur at different genomic locations. We also performed expression analyses using BrainSpan data for NDD-associated genes SATB2, EHMT1, FMR1, MECP2, MBD5, CTNND2, RAI1, CHD8, GRIN2A, GRIN2B, TCF4, SCN2A, and DYRK1A and find high expression of these genes in adult brain, at least comparable to developing human brain, confirming that genes associated with NDDs likely have a role in adult tissue. Adult function of genes associated with NDDs might be important in clinical disease presentation and may be suitable targets for therapeutic intervention. PMID:26194112

  6. Investigation of genes important in neurodevelopment disorders in adult human brain.

    PubMed

    Maussion, Gilles; Diallo, Alpha B; Gigek, Carolina O; Chen, Elizabeth S; Crapper, Liam; Théroux, Jean-Francois; Chen, Gary G; Vasuta, Cristina; Ernst, Carl

    2015-10-01

    Several neurodevelopmental disorders (NDDs) are caused by mutations in genes expressed in fetal brain, but little is known about these same genes in adult human brain. Here, we test the hypothesis that genes associated with NDDs continue to have a role in adult human brain to explore the idea that NDD symptoms may be partially a result of their adult function rather than just their neurodevelopmental function. To demonstrate adult brain function, we performed expression analyses and ChIPseq in human neural stem cell(NSC) lines at different developmental stages and adult human brain, targeting two genes associated with NDDs, SATB2 and EHMT1, and the WNT signaling gene TCF7L2, which has not been associated with NDDs. Analysis of DNA interaction sites in neural stem cells reveals high (40-50 %) overlap between proliferating and differentiating cells for each gene in temporal space. Studies in adult brain demonstrate that consensus sites are similar to NSCs but occur at different genomic locations. We also performed expression analyses using BrainSpan data for NDD-associated genes SATB2, EHMT1, FMR1, MECP2, MBD5, CTNND2, RAI1, CHD8, GRIN2A, GRIN2B, TCF4, SCN2A, and DYRK1A and find high expression of these genes in adult brain, at least comparable to developing human brain, confirming that genes associated with NDDs likely have a role in adult tissue. Adult function of genes associated with NDDs might be important in clinical disease presentation and may be suitable targets for therapeutic intervention.

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

    PubMed

    Alibardi, Lorenzo

    2015-09-01

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

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

    PubMed

    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

  9. 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

  10. 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…

  11. 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…

  12. 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

  13. 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

  14. 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…

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

    ERIC Educational Resources Information Center

    Palmer, Teresa M.

    1992-01-01

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

  16. 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.

  17. 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.

  18. 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

  19. 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

  20. [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.

  1. Cold Preservation of Human Adult Hepatocytes for Liver Cell Therapy.

    PubMed

    Duret, Cedric; Moreno, Daniel; Balasiddaiah, Anangi; Roux, Solene; Briolotti, Phillipe; Raulet, Edith; Herrero, Astrid; Ramet, Helene; Biron-Andreani, Christine; Gerbal-Chaloin, Sabine; Ramos, Jeanne; Navarro, Francis; Hardwigsen, Jean; Maurel, Patrick; Aldabe, Rafael; Daujat-Chavanieu, Martine

    2015-01-01

    Hepatocyte transplantation is a promising alternative therapy for the treatment of hepatic failure, hepatocellular deficiency, and genetic metabolic disorders. Hypothermic preservation of isolated human hepatocytes is potentially a simple and convenient strategy to provide on-demand hepatocytes in sufficient quantity and of the quality required for biotherapy. In this study, first we assessed how cold storage in three clinically safe preservative solutions (UW, HTS-FRS, and IGL-1) affects the viability and in vitro functionality of human hepatocytes. Then we evaluated whether such cold-preserved human hepatocytes could engraft and repopulate damaged livers in a mouse model of liver failure. Human hepatocytes showed comparable viabilities after cold preservation in the three solutions. The ability of fresh and cold-stored hepatocytes to attach to a collagen substratum and to synthesize and secrete albumin, coagulation factor VII, and urea in the medium after 3 days in culture was also equally preserved. Cold-stored hepatocytes were then transplanted in the spleen of immunodeficient mice previously infected with adenoviruses containing a thymidine kinase construct and treated with a single dose of ganciclovir to induce liver injury. Engraftment and liver repopulation were monitored over time by measuring the blood level of human albumin and by assessing the expression of specific human hepatic mRNAs and proteins in the recipient livers by RT-PCR and immunohistochemistry, respectively. Our findings show that cold-stored human hepatocytes in IGL-1 and HTS-FRS preservative solutions can survive, engraft, and proliferate in a damaged mouse liver. These results demonstrate the usefulness of human hepatocyte hypothermic preservation for cell transplantation. PMID:25622096

  2. A century of trends in adult human height.

    PubMed

    2016-07-26

    Being taller is associated with enhanced longevity, and higher education and earnings. We reanalysed 1472 population-based studies, with measurement of height on more than 18.6 million participants to estimate mean height for people born between 1896 and 1996 in 200 countries. The largest gain in adult height over the past century has occurred in South Korean women and Iranian men, who became 20.2 cm (95% credible interval 17.5-22.7) and 16.5 cm (13.3-19.7) taller, respectively. In contrast, there was little change in adult height in some sub-Saharan African countries and in South Asia over the century of analysis. The tallest people over these 100 years are men born in the Netherlands in the last quarter of 20th century, whose average heights surpassed 182.5 cm, and the shortest were women born in Guatemala in 1896 (140.3 cm; 135.8-144.8). The height differential between the tallest and shortest populations was 19-20 cm a century ago, and has remained the same for women and increased for men a century later despite substantial changes in the ranking of countries.

  3. 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

  4. 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

  5. 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

  6. 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.

  7. 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

  8. The quality of healing: articular cartilage.

    PubMed

    Gomoll, Andreas H; Minas, Tom

    2014-05-01

    Articular cartilage lacks an intrinsic capacity for self-repair, and once damaged, it never heals. This creates an opportunity for surgical intervention, whether to stimulate a healing response that results in the formation of a lower-quality fibrocartilaginous scar or formal cartilage repair in the form of cartilage transplants. This article will review the nature of cartilage injury and discuss indications and techniques for repair.

  9. Inducing articular cartilage phenotype in costochondral cells

    PubMed Central

    2013-01-01

    Introduction Costochondral cells may be isolated with minimal donor site morbidity and are unaffected by pathologies of the diarthrodial joints. Identification of optimal exogenous stimuli will allow abundant and robust hyaline articular cartilage to be formed from this cell source. Methods In a three factor, two level full factorial design, the effects of hydrostatic pressure (HP), transforming growth factor β1 (TGF-β1), and chondroitinase ABC (C-ABC), and all resulting combinations, were assessed in third passage expanded, redifferentiated costochondral cells. After 4 wks, the new cartilage was assessed for matrix content, superficial zone protein (SZP), and mechanical properties. Results Hyaline articular cartilage was generated, demonstrating the presence of type II collagen and SZP, and the absence of type I collagen. TGF-β1 upregulated collagen synthesis by 175% and glycosaminoglycan synthesis by 75%, resulting in a nearly 200% increase in tensile and compressive moduli. C-ABC significantly increased collagen content, and fibril density and diameter, leading to a 125% increase in tensile modulus. Hydrostatic pressure increased fibril diameter by 30% and tensile modulus by 45%. Combining TGF-β1 with C-ABC synergistically increased collagen content by 300% and tensile strength by 320%, over control. No significant differences were observed between C-ABC/TGF-β1 dual treatment and HP/C-ABC/TGF-β1. Conclusions Employing biochemical, biophysical, and mechanical stimuli generated robust hyaline articular cartilage with a tensile modulus of 2 MPa and a compressive instantaneous modulus of 650 kPa. Using expanded, redifferentiated costochondral cells in the self-assembling process allows for recapitulation of robust mechanical properties, and induced SZP expression, key characteristics of functional articular cartilage. PMID:24330640

  10. 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

  11. Polarized IR microscopic imaging of articular cartilage.

    PubMed

    Ramakrishnan, Nagarajan; Xia, Yang; Bidthanapally, Aruna

    2007-08-01

    The objective of this spectroscopic imaging study is to understand the anisotropic behavior of articular cartilage under polarized infrared radiation at 6.25 microm pixel resolution. Paraffin embedded canine humeral cartilage-bone blocks were used to obtain 6 microm thick tissue sections. Two wire grid polarizers were used to manipulate the polarization states of IR radiation by setting them for various polarizer/analyzer angles. The characteristics of the major chemical components (amide I, amide II, amide III and sugar) of articular cartilage were investigated using (a) a polarizer and (b) a combination of a polarizer and an analyzer. These results were compared to those obtained using only an analyzer. The infrared anisotropy (variation in infrared absorption as a function of polarization angles) of amide I, amide II and amide III bands correlates with the orientation of collagen fibrils along the tissue depth in different histological zones. An 'anisotropic flipping' region of amide profiles indicates the possibility of using Fourier transform infrared imaging (FTIRI) to determine the histological zones in cartilage. Cross-polarization experiment indicates the resolution of overlapping peaks of collagen triple helix and/or proteoglycan in articular cartilage.

  12. Articular Cartilage Injury and Potential Remedies.

    PubMed

    Chubinskaya, Susanna; Haudenschild, Dominik; Gasser, Seth; Stannard, James; Krettek, Christian; Borrelli, Joseph

    2015-12-01

    Osteoarthritis affects millions of people worldwide, is associated with joint stiffness and pain, and often causes significant disability and loss of productivity. Osteoarthritis is believed to occur as a result of ordinary "wear and tear" on joints during the course of normal activities of daily living. Posttraumatic osteoarthritis is a particular subset of osteoarthritis that occurs after a joint injury. Developing clinically relevant animal models will allow investigators to delineate the causes of posttraumatic osteoarthritis and develop means to slow or prevent its development after joint injury. Chondroprotectant compounds, which attack the degenerative pathways at a variety of steps, are being developed in an effort to prevent posttraumatic osteoarthritis and offer great promise. Often times, cartilage degradation after joint injury occurs despite our best efforts. When this happens, there are several evolving techniques that offer at least short-term relief from the effects of posttraumatic osteoarthritis. Occasionally, these traumatic lesions are so large that dramatic steps must be taken in an attempt to restore articular congruity and joint stability. Fresh osteochondral allografts have been used in these settings and offer the possibility of joint preservation. For patients presenting with neglected displaced intra-articular fractures that have healed, intra-articular osteotomy techniques are being developed in an effort to restore joint congruity and function. This article reviews the results of a newly developed animal model of posttraumatic osteoarthritis, several promising chondroprotectant compounds, and also cartilage techniques that are used when degenerative cartilage lesions develop after joint injury. PMID:26584267

  13. Polarized IR microscopic imaging of articular cartilage

    NASA Astrophysics Data System (ADS)

    Ramakrishnan, Nagarajan; Xia, Yang; Bidthanapally, Aruna

    2007-08-01

    The objective of this spectroscopic imaging study is to understand the anisotropic behavior of articular cartilage under polarized infrared radiation at 6.25 µm pixel resolution. Paraffin embedded canine humeral cartilage-bone blocks were used to obtain 6 µm thick tissue sections. Two wire grid polarizers were used to manipulate the polarization states of IR radiation by setting them for various polarizer/analyzer angles. The characteristics of the major chemical components (amide I, amide II, amide III and sugar) of articular cartilage were investigated using (a) a polarizer and (b) a combination of a polarizer and an analyzer. These results were compared to those obtained using only an analyzer. The infrared anisotropy (variation in infrared absorption as a function of polarization angles) of amide I, amide II and amide III bands correlates with the orientation of collagen fibrils along the tissue depth in different histological zones. An 'anisotropic flipping' region of amide profiles indicates the possibility of using Fourier transform infrared imaging (FTIRI) to determine the histological zones in cartilage. Cross-polarization experiment indicates the resolution of overlapping peaks of collagen triple helix and/or proteoglycan in articular cartilage.

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

    PubMed

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

    1990-01-01

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

  16. 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.

  17. 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.

  18. Human germ cell differentiation from fetal- and adult-derived induced pluripotent stem cells

    PubMed Central

    Panula, Sarita; Medrano, Jose V.; Kee, Kehkooi; Bergström, Rosita; Nguyen, Ha Nam; Byers, Blake; Wilson, Kitchener D.; Wu, Joseph C.; Simon, Carlos; Hovatta, Outi; Reijo Pera, Renee A.

    2011-01-01

    Historically, our understanding of molecular genetic aspects of human germ cell development has been limited, at least in part due to inaccessibility of early stages of human development to experimentation. However, the derivation of pluripotent stem cells may provide the necessary human genetic system to study germ cell development. In this study, we compared the potential of human induced pluripotent stem cells (iPSCs), derived from adult and fetal somatic cells to form primordial and meiotic germ cells, relative to human embryonic stem cells. We found that ∼5% of human iPSCs differentiated to primordial germ cells (PGCs) following induction with bone morphogenetic proteins. Furthermore, we observed that PGCs expressed green fluorescent protein from a germ cell-specific reporter and were enriched for the expression of endogenous germ cell-specific proteins and mRNAs. In response to the overexpression of intrinsic regulators, we also observed that iPSCs formed meiotic cells with extensive synaptonemal complexes and post-meiotic haploid cells with a similar pattern of ACROSIN staining as observed in human spermatids. These results indicate that human iPSCs derived from reprogramming of adult somatic cells can form germline cells. This system may provide a useful model for molecular genetic studies of human germline formation and pathology and a novel platform for clinical studies and potential therapeutical applications. PMID:21131292

  19. 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

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

    ERIC Educational Resources Information Center

    Matthieu, Monica; Ivanoff, Andre

    2006-01-01

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

  1. 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

  2. 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…

  3. 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…

  4. 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…

  5. 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

  6. NIRS Measurement of Venous Oxygen Saturation in the Adult Human Head

    NASA Astrophysics Data System (ADS)

    Brown, Derek W.; Haensse, Daniel; Bauschatz, Andrea; Wolf, Martin

    Provided that both the breathing frequency remains constant and that the temporal resolution of the instrument is sufficiently high, NIRS spiroximetry enables measurement of cerebral SvO2 in healthy human adults. Furthermore, simultaneous measurements of StO2, SaO2, and SvO2 enable calculation of both OEF and the compartmental distribution of cerebral blood volume.

  7. 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…

  8. 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

  9. 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).…

  10. 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…

  11. 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…

  12. 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…

  13. 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).…

  14. 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  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, 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...

  1. 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...

  2. 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…

  3. Extra-articular deformity is always correctable intra-articularly: to the contrary.

    PubMed

    Hungerford, David S

    2009-09-01

    The operative word in this debate is "always." In my opinion, there are some cases better served by extra-articular correction. The question then becomes which ones, and how does the surgeon determine? There are 4 considerations: the magnitude of the deformity, the relationship of the deformity to the knee, the side of the deformity (varus or valgus), and whether the femur or the tibia is affected by the deformity. A larger deformity is more important, but just as important is its relationship to the knee. Large deformities distant to the knee have little impact on the knee. Varus deformities require lateral intra-articular overresection, which produces lateral instability. Valgus deformities require medial overresection, which produces medial instability. Lateral instability is stabilized by the dynamic lateral stabilizers (popliteus, lateral head of the gastrocnemius, biceps femoris, and iliotibial tract) and is better tolerated than medial instability. The best way to determine the consequence of the malalignment in question is to template the knee by drawing the mechanical axis from the femoral head or ankle to the center of the knee, and then the resection level that will be required. This will demonstrate the amount of overresection required to correct the extra-articular deformity, and in some cases will indicate the advantage of an extra-articular correction.

  4. 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}.

  5. 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

  6. The mechanical properties of human ribs in young adult.

    PubMed

    Pezowicz, Celina; Głowacki, Maciej

    2012-01-01

    A good understanding of thoracic biomechanics is important for complete examination and control of chest behaviour under conditions of physiological and pathological work, and under the impact of external forces leading to traumatic loading of the chest. The purpose of the study was to analyse the mechanical properties of human ribs obtained from individuals under the age of 25 with scoliosis deformation and to correlate them with geometric properties of ribs. Thirty three fragments of ribs (9th to 12th) were tested in three-point bending. Rib fragments were collected intraoperatively from female patients treated for scoliosis in the thoracic, thoracolumbar, and lumbar spine. The results were used to determine the maximum failure force, stiffness, and Young's modulus. A significant relationship was found between the age and elastic modulus of the ribs. The analysis was carried out for two age groups, i.e., between the ages of 10 and 15 and between the ages of 16 and 22, and statistically significant differences were obtained for Young's modulus (p = 0.0001) amounting to, respectively, 2.79 ± 1.34 GPa for the first group and 7.44 ± 2.85 GPa for the second group. The results show a significant impact of age on the mechanical properties of ribs.

  7. 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.

  8. 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

  9. [Intra-articular infiltrations in rheumatology: update].

    PubMed

    Chevalier-Ruggeri, Paola; Zufferey, Pascal

    2016-01-13

    Intra-articular treatments are very useful in the daily practice of rheumatology, although their survival in the joint cavity is short and their mode of action still widely misunderstood. Corticosteroids were first used in fifty's, and are still the most widely used, despite potential local and systemic side effects. In recentyears, other molecules have been developed, especially in the treatment of osteoarthritis, but their effectiveness is controversial. Therapeutic trials were conducted with biological treatments in inflammatory arthritis, without success so far In the area of biotechnology, molecules to increase the survival of drugs into the joint are in preparation.

  10. 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.

  11. 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

  12. 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

  13. 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

  14. 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

  15. Short-Term Monocular Deprivation Alters GABA in the Adult Human Visual Cortex

    PubMed Central

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

    2016-01-01

    Summary 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

  16. 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

  17. 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

  18. 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

    2015-12-04

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

  19. 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

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

    PubMed Central

    Zhang, Xiaoli; Liu, Ruihua; Su, Zhongxue; Zhang, Yuecun; Zhang, Wenfang; Liu, Xinyu; Wang, Fuwu; Guo, Yuji; Li, Chuangang; Hao, Jing

    2015-01-01

    The expression pattern of Sohlh1 (spermatogenesis and oogenesis specific basic helix-loop-helix 1) and Sohlh2 in mice has been reported in previous studies. Sohlh1 and Sohlh2 are specifically expressed in spermatogonia, prespermatogonia in male mice and oocytes of primordial and primary follicles in female mice. In this report, we studied the expression pattern of Sohlh1 and Sohlh2 in human adult tissues. Immunohistochemical staining of Sohlh1 and Sohlh2 was performed in 5 samples of normal ovaries and testes, respectively. The results revealed that Sohlh genes are not only expressed in oocytes and spermatogonia, but also in granular cells, theca cells, Sertoli cells and Leydig cells, and in smooth muscles of blood vessel walls. To further investigate the expression of Sohlh genes in other adult human tissues, we collected representative normal adult tissues developed from three embryonic germ layers. Compared with the expression in mice, Sohlhs exhibited a much more extensive expression pattern in human tissues. Sohlhs were detected in testis, ovary and epithelia developed from embryonic endoderm, ectoderm and tissues developed from embryonic mesoderm. Sohlh signals were found in spermatogonia, Sertoli cells and also Leydig cells in testis, while in ovary, the expression was mainly in oocytes of primordial and primary follicles, granular cells and theca cells of secondary follicles. Compared with Sohlh2, the expression of Sohlh1 was stronger and more extensive. Our study explored the expression of Sohlh genes in human tissues and might provide insights for functional studies of Sohlh genes. PMID:26375665

  1. 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

  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. Lucigenin-dependent chemiluminescence in articular chondrocytes.

    PubMed

    Rathakrishnan, C; Tiku, M L

    1993-08-01

    We were recently able to measure intracellular levels of hydrogen peroxide within normal articular chondrocytes using the trapped indicator 2',7'-dichlorofluorescein diacetate. Further studies have shown that stimulated chondrocytes produce luminol-dependent chemiluminescence, suggesting that these cells produce hydrogen peroxide and singlet oxygen. In the present study, we have investigated the lucigenin-dependent chemiluminescence response in normal articular chondrocytes. Chondrocytes either in suspension or adhered to cover slips showed lucigenin-dependent chemiluminescence. There was a dose-dependent increase in chemiluminescence response when chondrocytes were incubated with soluble stimuli like phorbol-myristate-acetate, concanavalin A, and f-met-leu-phe. Catalase and the metabolic inhibitor, sodium azide, which inhibits the enzyme myeloperoxidase, had no inhibitory effect on lucigenin-dependent chemiluminescence production. Only the antioxidant, superoxide dismutase, prevented lucigenin-dependent chemiluminescence, indicating that this assay measures the production of superoxide anions by chondrocytes. We confirmed that chondrocytes release superoxide radicals using the biochemical assay of ferricytochrome c reduction. Since cartilage tissue is semi-transparent, we were able to measure chemiluminescence response in live cartilage tissue, showing that chondrocytes which are embedded within the matrix can also generate superoxide anion radicals. Reactive oxygen intermediates have been shown to play a significant role in the degradation of matrix in arthritis. Our previous and present studies suggest that oxygen radicals produced by chondrocytes may be an important mechanism by which chondrocytes induce cartilage matrix degradation.

  4. Toward patient-specific articular contact mechanics.

    PubMed

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

    2015-03-18

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

  5. 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

  6. Origin of germ cells and formation of new primary follicles in adult human ovaries

    PubMed Central

    Bukovsky, Antonin; Caudle, Michael R; Svetlikova, Marta; Upadhyaya, Nirmala B

    2004-01-01

    Recent reports indicate that functional mouse oocytes and sperm can be derived in vitro from somatic cell lines. We hypothesize that in adult human ovaries, mesenchymal cells in the tunica albuginea (TA) are bipotent progenitors with a commitment for both primitive granulosa and germ cells. We investigated ovaries of twelve adult women (mean age 32.8 ± 4.1 SD, range 27–38 years) by single, double, and triple color immunohistochemistry. We show that cytokeratin (CK)+ mesenchymal cells in ovarian TA differentiate into surface epithelium (SE) cells by a mesenchymal-epithelial transition. Segments of SE directly associated with ovarian cortex are overgrown by TA, forming solid epithelial cords, which fragment into small (20 micron) epithelial nests descending into the lower ovarian cortex, before assembling with zona pellucida (ZP)+ oocytes. Germ cells can originate from SE cells which cover the TA. Small (10 micron) germ-like cells showing PS1 meiotically expressed oocyte carbohydrate protein are derived from SE cells via asymmetric division. They show nuclear MAPK immunoexpression, subsequently divide symmetrically, and enter adjacent cortical vessels. During vascular transport, the putative germ cells increase to oocyte size, and are picked-up by epithelial nests associated with the vessels. During follicle formation, extensions of granulosa cells enter the oocyte cytoplasm, forming a single paranuclear CK+ Balbiani body supplying all the mitochondria of the oocyte. In the ovarian medulla, occasional vessels show an accumulation of ZP+ oocytes (25–30 microns) or their remnants, suggesting that some oocytes degenerate. In contrast to males, adult human female gonads do not preserve germline type stem cells. This study expands our previous observations on the formation of germ cells in adult human ovaries. Differentiation of primitive granulosa and germ cells from the bipotent mesenchymal cell precursors of TA in adult human ovaries represents a most

  7. 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

  8. Self-control in adult humans: variation in positive reinforcer amount and delay.

    PubMed Central

    Logue, A W; Peña-Correal, T E; Rodriguez, M L; Kabela, E

    1986-01-01

    In five experiments, choice responding of female human adults was examined, as a function of variations in reinforcer amount and reinforcer delay. Experiment 1 used a discrete-trials procedure, and Experiments 2, 3, 4, and 5 used a concurrent variable-interval variable-interval schedule. Reinforcer amount and reinforcer delay were varied both separately and together. In contrast to results previously reported with pigeons, the subjects in the present experiments usually chose the larger reinforcers even when those reinforcers were delayed. Together, the results from all the experiments suggest that the subjects followed a maximization strategy in choosing reinforcers. Such behavior makes it easy to observe self-control and difficult to observe impulsiveness in traditional laboratory experiments that use adult human subjects. PMID:3760749

  9. Monocular advantage for face perception implicates subcortical mechanisms in adult humans.

    PubMed

    Gabay, Shai; Nestor, Adrian; Dundas, Eva; Behrmann, Marlene

    2014-05-01

    The ability to recognize faces accurately and rapidly is an evolutionarily adaptive process. Most studies examining the neural correlates of face perception in adult humans have focused on a distributed cortical network of face-selective regions. There is, however, robust evidence from phylogenetic and ontogenetic studies that implicates subcortical structures, and recently, some investigations in adult humans indicate subcortical correlates of face perception as well. The questions addressed here are whether low-level subcortical mechanisms for face perception (in the absence of changes in expression) are conserved in human adults, and if so, what is the nature of these subcortical representations. In a series of four experiments, we presented pairs of images to the same or different eyes. Participants' performance demonstrated that subcortical mechanisms, indexed by monocular portions of the visual system, play a functional role in face perception. These mechanisms are sensitive to face-like configurations and afford a coarse representation of a face, comprised of primarily low spatial frequency information, which suffices for matching faces but not for more complex aspects of face perception such as sex differentiation. Importantly, these subcortical mechanisms are not implicated in the perception of other visual stimuli, such as cars or letter strings. These findings suggest a conservation of phylogenetically and ontogenetically lower-order systems in adult human face perception. The involvement of subcortical structures in face recognition provokes a reconsideration of current theories of face perception, which are reliant on cortical level processing, inasmuch as it bolsters the cross-species continuity of the biological system for face recognition.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. Characterization of a macroporous polyvinyl alcohol scaffold for the repair of focal articular cartilage defects.

    PubMed

    Ng, Kenneth W; Torzilli, Peter A; Warren, Russell F; Maher, Suzanne A

    2014-02-01

    Focal cartilage defects reduce the ability of articular cartilage to resist mechanical loading and provide lubrication during joint motion. The limitations in current surgical treatments have motivated the use of biocompatible scaffolds as a future treatment option. Here we describe a second generation macroporous, polyvinyl alcohol (PVA) scaffold with independently tunable morphological and mechanical properties. The compressive moduli of the PVA scaffold increased with increasing polymer concentration and applied compressive strain, with values in the range for human articular cartilage (HA  > 1000 kPa, EY  > 500 kPa). Scaffolds also possessed strain-dependent permeability and Poisson's ratio. The interconnected macroporous network was found to facilitate chondrocyte seeding and proliferation through the scaffold over one week in culture. Overall, these promising characteristics demonstrate the potential of this macroporous scaffold for future studies in focal cartilage defect repair.

  15. Designing Instruction for Adult Learners. Second Edition. Professional Practices in Adult Education and Human Resource Development Series.

    ERIC Educational Resources Information Center

    Dean, Gary J.

    This book focuses on applying instructional design to development of classroom learning for adults. Chapter 1 presents an overview of the model and addresses concerns about use of instructional design in adult education. Chapter 2 deals with assessing and developing skills as an adult educator; a literature review on behavior, beliefs, knowledge,…

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

    PubMed

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

    1990-03-01

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

  17. Articular and abarticular manifestations in type 2 diabetes mellitus

    PubMed Central

    Abourazzak, Fatima Ezzahra; Akasbi, Nessrine; Houssaini, Ghita Sqalli; Bazouti, Sabah; Bensbaa, Salma; Hachimi, Hicham; Ajdi, Farida; Harzy, Taoufik

    2014-01-01

    Objective Diabetes mellitus (DM), a worldwide high-prevalence disease, is associated with a large variety of rheumatic manifestations. It affects the connective tissues in many ways and causes alterations in the periarticular and the musculoskeletal systems. In most cases, these manifestations are associated with functional disability and pain, affecting the quality of life of the diabetic patient. The aim of our study is to review the different articular and abarticular manifestations in diabetic patients and the associated factors of these rheumatic manifestations. Material and Methods A cross-sectional study that includes all patients suffering from type 2 DM who present with articular or abarticular manifestations. Results We included 116 diabetic patients presenting with articular or abarticular manifestations. Our study showed four important findings. First, a large variety of articular and abarticular manifestations were present in patients with type 2 DM. Second, osteoarthritis (OA) of the knee was the most frequent articular manifestations. It was seen in 49% of our patients. Third, the most common manifestations in diabetic Moroccan patients were carpal tunnel syndrome (CTS), adhesive capsulitis of the shoulder, and diabetic cheiroarthropathy (29%, 23%, and 16%, respectively). Fourth, there was a significant association between vascular complications and the development of articular and abarticular manifestations. Conclusion This study shows that the articular and abarticular manifestations in diabetic Moroccan patients are dominated by CTS, adhesive capsulitis of the shoulder, and diabetic cheiroarthropathy, with a significant association between vascular complications and the development of some of these manifestations. PMID:27708897

  18. 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

  19. 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.

  20. Palmitate has proapoptotic and proinflammatory effects on articular cartilage and synergizes with interleukin-1

    PubMed Central

    Alvarez-Garcia, Oscar; Rogers, Nicole H; Smith, Roy G; Lotz, Martin K

    2014-01-01

    Objectives Obesity is a major risk factor for the development of osteoarthritis (OA) that is associated with a state of low-grade inflammation, and increased circulating adipokines and free fatty acids (FFA). The aim of this study was to analyze effects of saturated (palmitate) and monounsaturated (oleate) free fatty acids (FFA) on articular chondrocytes and cartilage. Methods Human articular chondrocytes and fibroblast-like synoviocytes obtained from young healthy donors, and OA chondrocytes from patients undergoing total knee replacement were treated with palmitate or oleate alone or with interleukin 1-β (IL-1β). Cell viability, caspase activation, and gene expression of proinflammatory factors, extracellular matrix proteins, and extracellular proteases were studied. In addition, chondrocyte viability, interleukin-6 (IL-6) production and matrix damage were assessed in bovine and human articular cartilage explants cultured with FFA with or without IL-1β. Results Palmitate, but not oleate, induced caspase activation and cell death in IL-1β-stimulated normal chondrocytes, and upregulated il6 and cox2 expression in chondrocytes and fibroblast-like synoviocytes through toll-like receptor-4 signaling. In cartilage explants, palmitate induced chondrocyte death, IL-6 release and extracellular matrix degradation. Palmitate synergized with IL-1β in stimulating proapoptotic and proinflammatory cellular responses. Pharmacological inhibition of caspases or TLR-4 signaling reduced palmitate and IL-1β-induced cartilage damage. Conclusions Palmitate acts as a pro-inflammatory and catabolic factor that, in synergy with IL-1β, induces chondrocyte apoptosis and articular cartilage breakdown. Collectively, our data suggest that elevated levels of saturated FFA often found in obesity may contribute to OA pathogenesis. PMID:24591481

  1. Osteoarthritis and articular chondrocalcinosis in the elderly.

    PubMed Central

    Wilkins, E; Dieppe, P; Maddison, P; Evison, G

    1983-01-01

    One hundred consecutive admissions to an acute geriatric unit were examined for clinical and radiographic evidence of osteoarthritis (OA) and articular chondrocalcinosis (ACC). Thirty-four patients had ACC. This was age related, the prevalence rising from 15% in patients aged 65-74 years to 44% in patients over 84 years. The commonly involved joints were the knee (25%), public symphysis (15%), and wrist (9%). No other aetiological factors predisposing to ACC were found. Of the 25 patients with ACC in the knee 7 had no symptoms or signs and no radiographic evidence of OA at that site. However, the combination of ACC and radiographic OA was characterised by an increase in clinical joint disease. Features of inflammation (joint swelling and joint line tenderness) involving the knee, wrist, and elbow were particularly common in ACC. It is concluded that ACC is common in the elderly and is associated with an increased incidence of joint disease. PMID:6859960

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

    PubMed Central

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

    2010-01-01

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

  3. Drosophila as a model for the identification of genes causing adult human heart disease

    PubMed Central

    Wolf, Matthew J.; Amrein, Hubert; Izatt, Joseph A.; Choma, Michael A.; Reedy, Mary C.; Rockman, Howard A.

    2006-01-01

    Drosophila melanogaster genetics provides the advantage of molecularly defined P-element insertions and deletions that span the entire genome. Although Drosophila has been extensively used as a model system to study heart development, it has not been used to dissect the genetics of adult human heart disease because of an inability to phenotype the adult fly heart in vivo. Here we report the development of a strategy to measure cardiac function in awake adult Drosophila that opens the field of Drosophila genetics to the study of human dilated cardiomyopathies. Through the application of optical coherence tomography, we accurately distinguish between normal and abnormal cardiac function based on measurements of internal cardiac chamber dimensions in vivo. Normal Drosophila have a fractional shortening of 87 ± 4%, whereas cardiomyopathic flies that contain a mutation in troponin I or tropomyosin show severe impairment of systolic function. To determine whether the fly can be used as a model system to recapitulate human dilated cardiomyopathy, we generated transgenic Drosophila with inducible cardiac expression of a mutant of human δ-sarcoglycan (δsgS151A), which has previously been associated with familial dilated cardiomyopathy. Compared to transgenic flies overexpressing wild-type δsg, or the standard laboratory strain w1118, Drosophila expressing δsgS151A developed marked impairment of systolic function and significantly enlarged cardiac chambers. These data illustrate the utility of Drosophila as a model system to study dilated cardiomyopathy and the applicability of the vast genetic resources available in Drosophila to systematically study the genetic mechanisms responsible for human cardiac disease. PMID:16432241

  4. 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

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

    PubMed

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

    2007-09-01

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

  6. 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

  7. The Ecology of Human Performance Framework: A Model for Identifying and Designing Appropriate Accommodations for Adult Learners.

    ERIC Educational Resources Information Center

    Dunn, Winnie; Gilbert, Mary Pat; Parker, Kathy

    This paper proposes a model framework, The Ecology of Human Performance (EHP) framework, for organizing adult basic education to utilize the skills of occupational therapists. The paper also includes two responses to the proposed framework by Janet S. Stotts and Cheryl Keenan. Reasons for the inclusion of occupational therapy in adult education…

  8. 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...

  9. 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...

  10. Maternal and child undernutrition: consequences for adult health and human capital.

    PubMed

    Victora, Cesar G; Adair, Linda; Fall, Caroline; Hallal, Pedro C; Martorell, Reynaldo; Richter, Linda; Sachdev, Harshpal Singh

    2008-01-26

    In this paper we review the associations between maternal and child undernutrition with human capital and risk of adult diseases in low-income and middle-income countries. We analysed data from five long-standing prospective cohort studies from Brazil, Guatemala, India, the Philippines, and South Africa and noted that indices of maternal and child undernutrition (maternal height, birthweight, intrauterine growth restriction, and weight, height, and body-mass index at 2 years according to the new WHO growth standards) were related to adult outcomes (height, schooling, income or assets, offspring birthweight, body-mass index, glucose concentrations, blood pressure). We undertook systematic reviews of studies from low-income and middle-income countries for these outcomes and for indicators related to blood lipids, cardiovascular disease, lung and immune function, cancers, osteoporosis, and mental illness. Undernutrition was strongly associated, both in the review of published work and in new analyses, with shorter adult height, less schooling, reduced economic productivity, and--for women--lower offspring birthweight. Associations with adult disease indicators were not so clear-cut. Increased size at birth and in childhood were positively associated with adult body-mass index and to a lesser extent with blood pressure values, but not with blood glucose concentrations. In our new analyses and in published work, lower birthweight and undernutrition in childhood were risk factors for high glucose concentrations, blood pressure, and harmful lipid profiles once adult body-mass index and height were adjusted for, suggesting that rapid postnatal weight gain--especially after infancy--is linked to these conditions. The review of published works indicates that there is insufficient information about long-term changes in immune function, blood lipids, or osteoporosis indicators. Birthweight is positively associated with lung function and with the incidence of some cancers, and

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

    PubMed

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

    2015-03-01

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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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.

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

    PubMed Central

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

    2014-01-01

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

  18. Adoptive transfer of macrophages from adult mice reduces mortality in mice infected with human enterovirus 71.

    PubMed

    Liu, Jiangning; Li, Xiaoying; Fan, Xiaoxu; Ma, Chunmei; Qin, Chuan; Zhang, Lianfeng

    2013-02-01

    Human enterovirus 71 (EV71) causes hand, foot and mouth disease in children under 6 years of age, and the neurological complications of this virus can lead to death. Until now, no vaccines or drugs have been available for the clinical control of this epidemic. Macrophages can engulf pathogens and mediate a series of host immune responses that play a role in the defence against infectious diseases. Using immunohistochemistry, we observed the localizations of virus in muscle tissues of EV71-infected mice. The macrophages isolated from the adult mice could kill the virus gradually in vitro, as shown using quantitative real-time PCR (qRT-PCR) and virus titration. Co-localisation of lysosomes and virus within macrophages suggested that the lysosomes were possibly responsible for the phagocytosis of EV71. Activation of the macrophages in the peritoneal cavity of mice four days pre-infection reduced the mortality of mice upon lethal EV71 infection. The adoptive transfer of macrophages from adult mice inhibited virus replication in the muscle tissues of infected mice, and this was followed by a relief of symptoms and a significant reduction of mortality, which suggested that the adoptive transfer of macrophages from adult humans represents a potential strategy to treat EV71-infected patients.

  19. 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.

  20. 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.

  1. 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

  2. Adult stem cells: simply a tool for regenerative medicine or an additional piece in the puzzle of human aging?

    PubMed

    Tollervey, James R; Lunyak, Victoria V

    2011-12-15

    Adult stem cells have taken center stage in current research related to regenerative medicine and pharmacogenomic studies seeking new therapeutic interventions. As we learn more about these cells, it is becoming apparent that the next big leap in our understanding of adult stem cell biology and adult stem cell aging will depend on the integration of approaches from various disciplines. Major advances and technological breakthroughs at the crossroad of fields such as biomaterials, genomics, epigenomics, and proteomics will enable the design of better tools to model human diseases, and warrant safe usage of adult stem cells in the clinic.

  3. Ultrasound Backscattering Is Anisotropic in Bovine Articular Cartilage.

    PubMed

    Inkinen, Satu I; Liukkonen, Jukka; Tiitu, Virpi; Virén, Tuomas; Jurvelin, Jukka S; Töyräs, Juha

    2015-07-01

    Collagen, proteoglycans and chondrocytes can contribute to ultrasound scattering in articular cartilage. However, anisotropy of ultrasound scattering in cartilage is not fully characterized. We investigate this using a clinical intravascular ultrasound device with ultrasound frequencies of 9 and 40 MHz. Osteochondral samples were obtained from intact bovine patellas, and cartilage was imaged in two perpendicular directions: through articular and lateral surfaces. At both frequencies, ultrasound backscattering was higher (p < 0.05) when measured through the lateral surface of cartilage. In addition, the composition and structure of articular cartilage were investigated with multiple reference methods involving light microscopy, digital densitometry, polarized light microscopy and Fourier infrared imaging. Reference methods indicated that acoustic anisotropy of ultrasound scattering arises mainly from non-uniform distribution of chondrocytes and anisotropic orientation of collagen fibers. To conclude, ultrasound backscattering in articular cartilage was found to be anisotropic and dependent on the frequency in use. PMID:25933711

  4. Ultrasound Backscattering Is Anisotropic in Bovine Articular Cartilage.

    PubMed

    Inkinen, Satu I; Liukkonen, Jukka; Tiitu, Virpi; Virén, Tuomas; Jurvelin, Jukka S; Töyräs, Juha

    2015-07-01

    Collagen, proteoglycans and chondrocytes can contribute to ultrasound scattering in articular cartilage. However, anisotropy of ultrasound scattering in cartilage is not fully characterized. We investigate this using a clinical intravascular ultrasound device with ultrasound frequencies of 9 and 40 MHz. Osteochondral samples were obtained from intact bovine patellas, and cartilage was imaged in two perpendicular directions: through articular and lateral surfaces. At both frequencies, ultrasound backscattering was higher (p < 0.05) when measured through the lateral surface of cartilage. In addition, the composition and structure of articular cartilage were investigated with multiple reference methods involving light microscopy, digital densitometry, polarized light microscopy and Fourier infrared imaging. Reference methods indicated that acoustic anisotropy of ultrasound scattering arises mainly from non-uniform distribution of chondrocytes and anisotropic orientation of collagen fibers. To conclude, ultrasound backscattering in articular cartilage was found to be anisotropic and dependent on the frequency in use.

  5. 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.

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

    PubMed

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

    1983-10-01

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

  7. 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

  8. 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

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

    PubMed

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

    2015-06-01

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

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

    PubMed

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

    1999-04-01

    The three-dimensional arrangement of dental cusps and incisal edges in human dentitions has been reported to fit the surface of a sphere (the curve of Monson), with a radius of about 4 inches in adults. The objective of the current study was to compare the three-dimensional curvature of the mandibular dental arch in healthy permanent dentitions of young adults and adolescents. The mandibular casts of 50 adults (aged 19 to 22 years) and 20 adolescents (aged 12 to 14 years) with highly selected sound dentitions that were free from temporomandibular joint problems were obtained. The three coordinates of cusp tips excluding the third molars were digitized with a three-dimensional digitizer, and used to derive a spherical model of the curvature of the occlusal surfaces. From the best interpolating sphere, the radii of the left and right curves of Spee (quasi-sagittal plane) and of molar curve of Wilson (frontal plane) were computed. Mandibular arch size (interdental distances) was also calculated. The occlusal curvature of the mandibular arch was not significantly influenced by sex, although a significant effect of age was found (Student t, P <.005). The radii of the overall sphere, right and left curves of Spee, and curve of Wilson in the molar area were about 101 mm in adults, and about 80 mm in adolescents. Arch size was not influenced by either sex or age. The different curvatures of the occlusal plane in adolescents and adults may be explained by a progressive rotation of the major axis of the teeth moving the occlusal plane toward a more buccal position. These dental movements should be performed in a frontal plane on an anteroposterior axis located next to the dental crown.

  11. Characterization of diverse forms of myosin heavy chain expressed in adult human skeletal muscle.

    PubMed Central

    Saez, L; Leinwand, L A

    1986-01-01

    In an attempt to define myosin heavy chain (MHC) gene organization and expression in adult human skeletal muscle, we have isolated and characterized genomic sequences corresponding to different human sarcomeric MHC genes (1). In this report, we present the complete DNA sequence of two different adult human skeletal muscle MHC cDNA clones, one of which encodes the entire light meromyosin (LMM) segment of MHC and represents the longest described MHC cDNA sequence. Additionally, both clones provide new sequence data from a 228 amino acid segment of the MHC tail for which no protein or DNA sequence has been previously available. One clone encodes a "fast" form of skeletal muscle MHC while the other clone most closely resembles a MHC form described in rat cardiac ventricles. We show that the 3' untranslated region of skeletal MHC cDNAs are homologous from widely separated species as are cardiac MHC cDNAs. However, there is no homology between the 3' untranslated region of cardiac and skeletal muscle MHCs. Isotype-specific preservation of MHC 3' untranslated sequences during evolution suggests a functional role for these regions. Images PMID:2421254

  12. The surface of articular cartilage contains a progenitor cell population.

    PubMed

    Dowthwaite, Gary P; Bishop, Joanna C; Redman, Samantha N; Khan, Ilyas M; Rooney, Paul; Evans, Darrell J R; Haughton, Laura; Bayram, Zubeyde; Boyer, Sam; Thomson, Brian; Wolfe, Michael S; Archer, Charles W

    2004-02-29

    It is becoming increasingly apparent that articular cartilage growth is achieved by apposition from the articular surface. For such a mechanism to occur, a population of stem/progenitor cells must reside within the articular cartilage to provide transit amplifying progeny for growth. Here, we report on the isolation of an articular cartilage progenitor cell from the surface zone of articular cartilage using differential adhesion to fibronectin. This population of cells exhibits high affinity for fibronectin, possesses a high colony-forming efficiency and expresses the cell fate selector gene Notch 1. Inhibition of Notch signalling abolishes colony forming ability whilst activated Notch rescues this inhibition. The progenitor population also exhibits phenotypic plasticity in its differentiation pathway in an embryonic chick tracking system, such that chondroprogenitors can engraft into a variety of connective tissue types including bone, tendon and perimysium. The identification of a chondrocyte subpopulation with progenitor-like characteristics will allow for advances in our understanding of both cartilage growth and maintenance as well as provide novel solutions to articular cartilage repair. PMID:14762107

  13. Morphological characteristics of posterolateral articular fragments in tibial plateau fractures.

    PubMed

    Xiang, Gao; Zhi-Jun, Pan; Qiang, Zheng; Hang, Li

    2013-10-01

    Treatment of posterolateral tibial plateau fractures is controversial, and information regarding this specific fracture pattern is lacking. The purpose of this study was to elucidate the frequency and morphological features of posterolateral articular fragments in tibial plateau fractures. A retrospective radiographic and chart review was performed on a consecutive series of patients who sustained tibial plateau fractures between May 2008 and August 2012. The articular surface area, maximum posterior cortical height, sagittal fracture angle, and amount of displacement were measured on computed tomography scans using the Picture and Archiving Communication System. Thirty-six (15%) of 242 injuries demonstrated a posterolateral fracture fragment comprising a mean 14.3% of the articular surface of the total tibial plateau (range, 8% to 32%). Mean major articular fragment angle was 23° (range, 62° to -43°), mean maximum posterior cortical height was 29 mm (range, 18 to 42 mm), and mean sagittal fracture angle was 77° (range, 58° to 97°). The posterolateral plateau articular fracture fragment has morphological characteristics of a conically shaped fragment with a relatively small articular surface area and sagittal fracture angle. Recognizing these morphological features will help the clinician formulate an effective surgical plan.

  14. 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

  15. 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…

  16. 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

  17. 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.

  18. Arthroscopic transtendinous repair of articular-sided pasta (partial articular supraspinatus tendon avulsion) injury

    PubMed Central

    Wang, Yi; Lu, Liangyu; Lu, Zhe; Xiao, Lei; Kang, Yifan; Wang, Zimin

    2015-01-01

    Objective: To evaluate clinical efficacy of arthroscopic transtendinous repair of partial articular-sided PASTA (partial articular supraspinatus tendon avulsion) injury. Methods: From February 2011 to July 2014, 12 cases of PASTA, aged 29 to 72 years with an average of 52.9 ± 13.3 years, were treated arthoscopically. To repair PASTA, articular-sided rotator cuff tear was explored, injury site was punctured and labeled with PDS absorbable monofilament suture (Ethicon, Somerville, NJ, USA) suture, subacromial bursa was cleaned up with acromioplasty, and integrity of bursa-side rotator cuff was assessed. Then with arthroscope in glenohumeral joint, footprint of the bursa-side supraspinatus tendon was preserved, rivets were introduced into the joint through supraspinatus tendon, joint-side partial tear was sutured, and anatomical reconstruction of the rotator cuff footprint was established. The patients were followed up post-operatively for 12-36 months, average 22 ± 7.3 months. The clinical outcomes were emulated with ASES (American Shoulder and Elbow Surgeons) Shoulder Score system and UCLA (University of California at Los Angeles) Shoulder rating scale. Results: The post-operative ASES score was 89.7 ± 5.6, higher than the pre-operative one 49.8 ± 9.8 (t = 12.25, P <0.0001). While UCLA scale increased from the pre-operative 17.3, ± 3.3 to the post-operative 30.4 ± 3.2 points (t = 9.87, P <0.0001), with a satisfaction rate of 11/12 (91.7%). Conclusion: Trans-tendon repair is ideal for PASTA with advantage of maximal preservation of the normal rotator cuff tissue, anatomical reconstruction of the rotator cuff footprint and stable fixation of tendon-bone interface. PMID:25784979

  19. Pannocytes: distinctive cells found in rheumatoid arthritis articular cartilage erosions.

    PubMed Central

    Zvaifler, N. J.; Tsai, V.; Alsalameh, S.; von Kempis, J.; Firestein, G. S.; Lotz, M.

    1997-01-01

    A distinctive cell was identified from sites of rheumatoid arthritis cartilage injury. Similar cells are not found in lesions of osteoarthritis cartilage. We have designated them as pannocytes (PCs). Their rhomboid morphology differs from the bipolar shape of fibroblast-like synoviocytes or the spherical configuration of primary human articular chondrocytes. Chondrocytes are short-lived, whereas the original PC line grew for 25 passages before becoming senescent. Features in common with cultured primary chondrocytes include maximal proliferation in response to transforming growth factor-beta a catabolic response to interleukin-1 beta, collagenase production, and mRNA for the induced lymphocyte antigen and inducible nitric oxide synthase. Despite the presence of the inducible nitric oxide synthase message, PCs do not produce NO either constitutively or when cytokine stimulated. Each of the mesenchymal cells, fibroblast-like synoviocytes, primary chondrocytes, and PCs have the gene for type I collagen, but the type II collagen gene is detected only in primary chondrocytes. PCs can be distinguished from fibroblast-like synoviocytes and primary chondrocytes by their morphology, bright VCAM-1 staining, and growth response to cytokines and growth factors. Their prolonged life span in vitro suggests that PCs might represent an earlier stage of mesenchymal cell differentiation, and they could have a heretofore unrecognized role in rheumatoid arthritis joint destruction. Images Figure 1 Figure 2 Figure 7 Figure 8 Figure 10 PMID:9060847

  20. Articular cartilage repair with autologous bone marrow mesenchymal cells.

    PubMed

    Matsumoto, Tomiya; Okabe, Takahiro; Ikawa, Tesshu; Iida, Takahiro; Yasuda, Hiroyuki; Nakamura, Hiroaki; Wakitani, Shigeyuki

    2010-11-01

    Articular cartilage defects that do not repair spontaneously induce osteoarthritic changes in joints over a long period of observation. In this study, we examined the usefulness of transplanting culture-expanded bone marrow mesenchymal cells into osteochondral defects of joints with cartilage defects. First, we performed experiments on rabbits and up on obtaining good results proceeded to perform the experiments on humans. Macroscopic and histological repair with this method was good, and good clinical results were obtained although there was no significant difference with the control group. Recent reports have indicated that this procedure is comparable to autologous chondrocyte implantation, and concluded that it was a good procedure because it required one step less than that required by surgery, reduced costs for patients, and minimized donor site morbidity. Although some reports have previously shown that progenitor cells formed a tumor when implanted into immune-deficient mice after long term in vitro culture, the safety of the cell transplantation was confirmed by our clinical experience. Thus, this procedure is useful, effective, and safe, but the repaired tissues were not always hyaline cartilage. To obtain better repair with this procedure, treatment approaches using some growth factors during in vitro culture or gene transfection are being explored.

  1. Telomerase Activity in Articular Chondrocytes Is Lost after Puberty

    PubMed Central

    Wilson, Brooke; Novakofski, Kira D.; Donocoff, Rachel Sacher; Liang, Yan-Xiang Amber

    2014-01-01

    Objective: Telomere length and telomerase activity are important indicators of cellular senescence and replicative ability. Loss of telomerase is associated with ageing and the development of osteoarthritis. Implantation of telomerase-positive cells, chondrocytes, or stem cells expressing a normal chondrocyte phenotype is desired for cartilage repair procedures. The objective of this study was to identify at what age chondrocytes and at what passage bone marrow–derived mesenchymal stem cells (MSCs) become senescent based on telomerase activity. The effect of osteogenic protein–1 (OP-1) or interleukin-1α (IL-1α) treatment on telomerase activity in chondrocytes was also measured to determine the response to anabolic or catabolic stimuli. Methods: Articular cartilage was collected from horses (n = 12) aged 1 month to 18 years. Chondrocytes from prepubescent horses (<15 months) were treated with OP-1 or IL-1α. Bone marrow aspirate from adult horses was collected and cultured for up to 10 days to isolate MSCs. Telomerase activity was measured using the TeloTAGGG Telomerase PCR ELISA kit. Results: Chondrocytes from prepubescent horses were positive for telomerase activity. Treatment with IL-1α resulted in a decrease in chondrocyte telomerase activity; however, treatment with OP-1 did not change telomerase activity. One MSC culture sample was positive for telomerase activity on day 2; all samples were negative for telomerase activity on day 10. Conclusions: These results suggest that chondrocytes from prepubescent donors are potentially more suitable for cartilage repair procedures and that telomerase activity is diminished by anabolic and catabolic cytokine stimulation. If MSCs are utilized in cartilage repair, minimal passaging should be performed prior to implantation. PMID:26069700

  2. Pediatric and adolescent intra-articular fractures of the calcaneus.

    PubMed

    Dudda, Marcel; Kruppa, Christiane; Geßmann, Jan; Seybold, Dominik; Schildhauer, Thomas A

    2013-06-01

    Calcaneal fractures in childhood are very rare, whereas particularly intra-articular displaced fractures are not typical in skeletally immature children. Various techniques of osteosynthesis have been described. This study aimed to determine clinical and radiological outcome after surgical treatment of intraarticular calcaneal fractures. Fourteen intraarticular fractures of the calcaneus were included in this retrospective study. Eleven children (2 girls and 9 boys) aged 6-16 years (average age 11.5 years) underwent surgical treatment. One child sustained a Type II open fracture of both calcanei. All injuries occurred after a high-energy trauma; 3 patients had multiple additional fractures. The clinical and radiological postoperative follow up was an average 44 months. In 4 cases, a reduction through a minimally invasive approach and fixation with K-wires or screws could be achieved. Eleven fractures were treated with open reduction and internal fixation with plate osteosynthesis, K-wires or screws. In one case with open fractures of both heel bones, an additional external fixator was applied. The surgical treatment approach adopted enabled the pre-operative Böhler's angle (average 16°) to be improved to an average 30°. In all cases, except for the patient with open fractures, a good functional result and outcome could be achieved. In calcaneal fractures in childhood, anatomical reduction is the determining factor, as in fractures in adults, whereas the surgical technique seems to have no influence on clinical outcome in children. The wound healing problems that have often been described were not observed in this age group.

  3. Pediatric and Adolescent Intra-Articular Fractures of the Calcaneus

    PubMed Central

    Dudda, Marcel; Kruppa, Christiane; Geßmann, Jan; Seybold, Dominik; Schildhauer, Thomas A.

    2013-01-01

    Calcaneal fractures in childhood are very rare, whereas particularly intra-articular displaced fractures are not typical in skeletally immature children. Various techniques of osteosynthesis have been described. This study aimed to determine clinical and radiological outcome after surgical treatment of intraarticular calcaneal fractures. Fourteen intraarticular fractures of the calcaneus were included in this retrospective study. Eleven children (2 girls and 9 boys) aged 6-16 years (average age 11.5 years) underwent surgical treatment. One child sustained a Type II open fracture of both calcanei. All injuries occurred after a high-energy trauma; 3 patients had multiple additional fractures. The clinical and radiological postoperative follow up was an average 44 months. In 4 cases, a reduction through a minimally invasive approach and fixation with K-wires or screws could be achieved. Eleven fractures were treated with open reduction and internal fixation with plate osteosynthesis, K-wires or screws. In one case with open fractures of both heel bones, an additional external fixator was applied. The surgical treatment approach adopted enabled the pre-operative Böhler’s angle (average 16°) to be improved to an average 30°. In all cases, except for the patient with open fractures, a good functional result and outcome could be achieved. In calcaneal fractures in childhood, anatomical reduction is the determining factor, as in fractures in adults, whereas the surgical technique seems to have no influence on clinical outcome in children. The wound healing problems that have often been described were not observed in this age group. PMID:23888207

  4. Long-term culture of genome-stable bipotent stem cells from adult human liver.

    PubMed

    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

    2015-01-15

    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

  5. 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

  6. Adult Human Nasal Mesenchymal-Like Stem Cells Restore Cochlear Spiral Ganglion Neurons After Experimental Lesion

    PubMed Central

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

    2014-01-01

    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

  7. 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

  8. 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

  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. 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.

  11. 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

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

    PubMed

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

    2014-06-01

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

  13. 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

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

    PubMed Central

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

    2015-01-01

    In this study we used differentiated adult human upcyte® cells for the in vitro generation of liver organoids. Upcyte® cells are genetically engineered cell strains derived from primary human cells by lenti-viral transduction of genes or gene combinations inducing transient proliferation capacity (upcyte® process). Proliferating upcyte® cells undergo a finite number of cell divisions, i.e., 20 to 40 population doublings, but upon withdrawal of proliferation stimulating factors, they regain most of the cell specific characteristics of primary cells. When a defined mixture of differentiated human upcyte® cells (hepatocytes, liver sinusoidal endothelial cells (LSECs) and mesenchymal stem cells (MSCs)) was cultured in vitro on a thick layer of Matrigel™, they self-organized to form liver organoid-like structures within 24 hours. When further cultured for 10 days in a bioreactor, these liver organoids show typical functional characteristics of liver parenchyma including activity of cytochromes P450, CYP3A4, CYP2B6 and CYP2C9 as well as mRNA expression of several marker genes and other enzymes. In summary, we hereby describe that 3D functional hepatic structures composed of primary human cell strains can be generated in vitro. They can be cultured for a prolonged period of time and are potentially useful ex vivo models to study liver functions. PMID:26488607

  15. 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.

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

    PubMed

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

    2015-01-01

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

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

    PubMed Central

    Maucksch, C; Firmin, E; Butler-Munro, C; Montgomery, JM; Dottori, M; Connor, B

    2012-01-01

    Recent studies have reported direct reprogramming of human fibroblasts to mature neurons by the introduction of defined neural genes. This technology has potential use in the areas of neurological disease modeling and drug development. However, use of induced neurons for large-scale drug screening and cell-based replacement strategies is limited due to their inability to expand once reprogrammed. We propose it would be more desirable to induce expandable neural precursor cells directly from human fibroblasts. To date several pluripotent and neural transcription factors have been shown to be capable of converting mouse fibroblasts to neural stem/precursor-like cells when delivered by viral vectors. Here we extend these findings and demonstrate that transient ectopic insertion of the transcription factors SOX2 and PAX6 to adult human fibroblasts through use of non-viral plasmid transfection or protein transduction allows the generation of induced neural precursor (iNP) colonies expressing a range of neural stem and pro-neural genes. Upon differentiation, iNP cells give rise to neurons exhibiting typical neuronal morphologies and expressing multiple neuronal markers including tyrosine hydroxylase and GAD65/67. Importantly, iNP-derived neurons demonstrate electrophysiological properties of functionally mature neurons with the capacity to generate action potentials. In addition, iNP cells are capable of differentiating into glial fibrillary acidic protein (GFAP)-expressing astrocytes. This study represents a novel virusfree approach for direct reprogramming of human fibroblasts to a neural precursor fate. PMID:24693194

  18. The Model Human Processor and the older adult: parameter estimation and validation within a mobile phone task.

    PubMed

    Jastrzembski, Tiffany S; Charness, Neil

    2007-12-01

    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; M-sub(age) = 20) and older (N = 20; M-sub(age) = 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.

  19. 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

  20. Modeling the biomechanics of articular eminence function in anthropoid primates.

    PubMed

    Terhune, Claire E

    2011-11-01

    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.

  1. Activity, inhibition, and induction of cytochrome P450 2J2 in adult human primary cardiomyocytes.

    PubMed

    Evangelista, Eric A; Kaspera, Rüdiger; Mokadam, Nahush A; Jones, J P; Totah, Rheem A

    2013-12-01

    Cytochrome P450 2J2 plays a significant role in the epoxidation of arachidonic acid to signaling molecules important in cardiovascular events. CYP2J2 also contributes to drug metabolism and is responsible for the intestinal clearance of ebastine. However, the interaction between arachidonic acid metabolism and drug metabolism in cardiac tissue, the main expression site of CYP2J2, has not been examined. Here we investigate an adult-derived human primary cardiac cell line as a suitable model to study metabolic drug interactions (inhibition and induction) of CYP2J2 in cardiac tissue. The primary human cardiomyocyte cell line demonstrated similar mRNA-expression profiles of P450 enzymes to adult human ventricular tissue. CYP2J2 was the dominant isozyme with minor contributions from CYP2D6 and CYP2E1. Both terfenadine and astemizole oxidation were observed in this cell line, whereas midazolam was not metabolized suggesting lack of CYP3A activity. Compared with recombinant CYP2J2, terfenadine was hydroxylated in cardiomyocytes at a similar K(m) value of 1.5 μM. The V(max) of terfenadine hydroxylation in recombinant enzyme was found to be 29.4 pmol/pmol P450 per minute and in the cells 6.0 pmol/pmol P450 per minute. CYP2J2 activity in the cell line was inhibited by danazol, astemizole, and ketoconazole in submicromolar range, but also by xenobiotics known to cause cardiac adverse effects. Of the 14 compounds tested for CYP2J2 induction, only rosiglitazone increased mRNA expression, by 1.8-fold. This cell model can be a useful in vitro model to investigate the role of CYP2J2-mediated drug metabolism, arachidonic acid metabolism, and their association to drug induced cardiotoxicity. PMID:24021950

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

    PubMed

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

    2014-02-01

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

  3. Extra-articular Mimickers of Lateral Meniscal Tears

    PubMed Central

    Barker, Joseph U.; Strauss, Eric J.; Lodha, Sameer; Bach, Bernard R.

    2011-01-01

    Context: Lateral meniscus tears are a common entity seen in sports medicine. Although lateral-side knee pain is often the result of a meniscus injury, several extra-articular pathologies share signs and symptoms with a meniscus tear. It is critical for the clinician to be able to identify and understand extra-articular pathologies that can present similar to a lateral meniscus tear. Evidence Acquisition: Data were collected through a thorough review of the literature conducted through a MEDLINE search for all relevant articles between 1980 and February 2010. Study Type: Clinical review. Results: Common extra-articular pathologies that can mimic lateral meniscal tears include iliotibial band syndrome, proximal tibiofibular joint instability, snapping biceps femoris or popliteus tendons, and peroneal nerve compression syndrome or neuritis. The patient history, physical examination features, and radiographic findings can be used to separate these entities from the more common intra-articular knee pathologies. Conclusions: In treating patients who present with lateral-sided knee pain, clinicians should be able to recognize and treat extra-articular pathologies that can present in a similar fashion as lateral meniscus tears. PMID:23015995

  4. 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

  5. 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

  6. 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.

  7. 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

  8. 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

  9. 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

  10. Chondrocyte-intrinsic Smad3 represses Runx2-inducible MMP-13 expression to maintain articular cartilage and prevent osteoarthritis

    PubMed Central

    Chen, Carol G.; Thuillier, Daniel; Chin, Emily N.; Alliston, Tamara

    2012-01-01

    Objective To identify mechanisms by which Smad3 maintains articular cartilage and prevents osteoarthritis. Methods A combination of in vivo and in vitro approaches was used to test the hypothesis that Smad3 represses Runx2-inducible gene expression to prevent articular cartilage degeneration. Col2-Cre;Smad3fl/fl mice allowed study of the chondrocyte-intrinsic role of Smad3, independently of its role in the perichondrium or other tissues. Primary Smad3fl/fl articular chondrocytes and ATDC5 chondroprogenitors were employed to evaluate Smad3 and Runx2 regulation of matrix metalloproteinase-13 (MMP-13) mRNA and protein expression. Results Chondrocyte-specific reduction of Smad3 causes progressive articular cartilage degeneration due to imbalanced cartilage matrix synthesis and degradation. In addition to reduced collagen II mRNA expression, Col2-Cre;Smad3fl/fl articular cartilage is severely deficient in collagen II and aggrecan protein, due to excessive MMP-13-mediated proteolysis of these key cartilage matrix constituents. Normally, TGF-β signals through Smad3 to confer a rapid and dynamic repression of Runx2-inducible MMP-13 expression. However, in the absence of Smad3, TGF-β signals through p38 and Runx2 to induce MMP-13 expression. Conclusion This work elucidates a mechanism by which Smad3 mutations in humans and mice cause cartilage degeneration and osteoarthritis. Specifically, Smad3 maintains the balance between cartilage matrix synthesis and degradation by inducing collagen II expression and repressing Runx2-inducible MMP-13 expression. Selective activation of TGF-β signaling through Smad3, rather than p38, may help to restore the balance between matrix synthesis and proteolysis that is lost in osteoarthritis. PMID:22674505

  11. 24R,25-Dihydroxyvitamin D3 Protects against Articular Cartilage Damage following Anterior Cruciate Ligament Transection in Male Rats

    PubMed Central

    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

  12. 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

  13. Behaviour of Solitary Adult Scandinavian Brown Bears (Ursus arctos) when Approached by Humans on Foot

    PubMed Central

    Moen, Gro Kvelprud; Støen, Ole-Gunnar; Sahlén, Veronica; Swenson, Jon E.

    2012-01-01

    Successful management has brought the Scandinavian brown bear (Ursus arctos L.) back from the brink of extinction, but as the population grows and expands the probability of bear-human encounters increases. More people express concerns about spending time in the forest, because of the possibility of encountering bears, and acceptance for the bear is decreasing. In this context, reliable information about the bear's normal behaviour during bear-human encounters is important. Here we describe the behaviour of brown bears when encountering humans on foot. During 2006–2009, we approached 30 adult (21 females, 9 males) GPS-collared bears 169 times during midday, using 1-minute positioning before, during and after the approach. Observer movements were registered with a handheld GPS. The approaches started 869±348 m from the bears, with the wind towards the bear when passing it at approximately 50 m. The bears were detected in 15% of the approaches, and none of the bears displayed any aggressive behaviour. Most bears (80%) left the initial site during the approach, going away from the observers, whereas some remained at the initial site after being approached (20%). Young bears left more often than older bears, possibly due to differences in experience, but the difference between ages decreased during the berry season compared to the pre-berry season. The flight initiation distance was longer for active bears (115±94 m) than passive bears (69±47 m), and was further affected by horizontal vegetation cover and the bear's age. Our findings show that bears try to avoid confrontations with humans on foot, and support the conclusions of earlier studies that the Scandinavian brown bear is normally not aggressive during encounters with humans. PMID:22363710

  14. Human Adult Dental Pulp Stem Cells Enhance Poststroke Functional Recovery Through Non-Neural Replacement Mechanisms

    PubMed Central

    Leong, Wai Khay; Henshall, Tanya L.; Arthur, Agnes; Kremer, Karlea L.; Lewis, Martin D.; Helps, Stephen C.; Field, John; Hamilton-Bruce, Monica A.; Warming, Scott; Manavis, Jim; Vink, Robert; Gronthos, Stan

    2012-01-01

    Human adult dental pulp stem cells (DPSCs), derived from third molar teeth, are multipotent and have the capacity to differentiate into neurons under inductive conditions both in vitro and following transplantation into the avian embryo. In this study, we demonstrate that the intracerebral transplantation of human DPSCs 24 hours following focal cerebral ischemia in a rodent model resulted in significant improvement in forelimb sensorimotor function at 4 weeks post-treatment. At this time, 2.3 ± 0.7% of engrafted cells had survived in the poststroke brain and demonstrated targeted migration toward the stroke lesion. In the peri-infarct striatum, transplanted DPSCs differentiated into astrocytes in preference to neurons. Our data suggest that the dominant mechanism of action underlying DPSC treatment that resulted in enhanced functional recovery is unlikely to be due to neural replacement. Functional improvement is more likely to be mediated through DPSC-dependent paracrine effects. This study provides preclinical evidence for the future use of human DPSCs in cell therapy to improve outcome in stroke patients. PMID:23197777

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. Comparison of Human Neonatal and Adult Blood Leukocyte Subset Composition Phenotypes.

    PubMed

    Prabhu, Savit B; Rathore, Deepak K; Nair, Deepa; Chaudhary, Anita; Raza, Saimah; Kanodia, Parna; Sopory, Shailaja; George, Anna; Rath, Satyajit; Bal, Vineeta; Tripathi, Reva; Ramji, Siddharth; Batra, Aruna; Aggarwal, Kailash C; Chellani, Harish K; Arya, Sugandha; Agarwal, Nidhi; Mehta, Umesh; Natchu, Uma Chandra Mouli; Wadhwa, Nitya; Bhatnagar, Shinjini

    2016-01-01

    The human peripheral leukocyte subset composition depends on genotype variation and pre-natal and post-natal environmental influence diversity. We quantified this composition in adults and neonates, and compared the median values and dispersal ranges of various subsets in them. We confirmed higher frequencies of monocytes and regulatory T cells (Tregs), similar frequencies of neutrophils, and lower frequencies of CD8 T cells, NKT cells, B1 B cells and gamma-delta T cells in neonatal umbilical cord blood. Unlike previous reports, we found higher frequencies of eosinophils and B cells, higher CD4:CD8 ratios, lower frequencies of T cells and iNKT cells, and similar frequencies of CD4 T cells and NK cells in neonates. We characterized monocyte subsets and dendritic cell (DC) subsets in far greater detail than previously reported, using recently described surface markers and gating strategies and observed that neonates had lower frequencies of patrolling monocytes and lower myeloid dendritic cell (mDC):plasmacytoid DC (pDC) ratios. Our data contribute to South Asian reference values for these parameters. We found that dispersal ranges differ between different leukocyte subsets, suggesting differential determination of variation. Further, some subsets were more dispersed in adults than in neonates suggesting influences of postnatal sources of variation, while some show the opposite pattern suggesting influences of developmental process variation. Together, these data and analyses provide interesting biological possibilities for future exploration. PMID:27610624

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

    PubMed

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

    2014-06-26

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

  2. 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

  3. Collection of Clonorchis sinensis adult worms from infected humans after praziquantel treatment

    PubMed Central

    Shen, Chenghua; Kim, Jae-hwan; Lee, Jeong-Keun; Bae, Young Mee; Oh, Jin-Kyoung; Lim, Min Kyung; Shin, Hai-Rim; Hong, Sung-Tae

    2007-01-01

    A cohort was established for evaluation of cancer risk factors in Sancheong-gun, Gyeongsangnam-do, Korea. As one of the cohort studies, stools of 947 residents (403 males and 544 females, age range: 29-86 years) were screened for Clonorchis sinensis eggs using both Kato-Katz method and formalin-ether sedimentation technique. The overall egg positive rate of C. sinensis was 37.7% and individual EPG (eggs per gram of feces) counts ranged from 24 to 28,800. Eight egg positive residents voluntarily joined a process of collection of the passed worms after praziquantel treatment. A total of 158 worms were recovered from 5 of the 8 treated persons, ranged from 3 to 108 in each individual. The worms were 15-20 mm × 2-3 mm in size, and showed brown-pigmented, red, or white body colors. This is the first collection record of C. sinensis adult worms from humans through anthelmintic treatment and purgation. The adult worms of C. sinensis may be paralyzed by praziquantel and then discharged passively through bile flow in the bile duct and by peristaltic movement of the bowel. PMID:17570980

  4. 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

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

    PubMed

    Neves, R H; Pereira, M J; de Oliveira, R M; Gomes, D C; Machado-Silva, J R

    1998-01-01

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

  6. Comparison of Human Neonatal and Adult Blood Leukocyte Subset Composition Phenotypes

    PubMed Central

    Rathore, Deepak K.; Nair, Deepa; Chaudhary, Anita; Raza, Saimah; Kanodia, Parna; Sopory, Shailaja; George, Anna; Rath, Satyajit; Bal, Vineeta; Tripathi, Reva; Ramji, Siddharth; Batra, Aruna; Aggarwal, Kailash C.; Chellani, Harish K.; Arya, Sugandha; Agarwal, Nidhi; Mehta, Umesh; Natchu, Uma Chandra Mouli; Wadhwa, Nitya; Bhatnagar, Shinjini

    2016-01-01

    The human peripheral leukocyte subset composition depends on genotype variation and pre-natal and post-natal environmental influence diversity. We quantified this composition in adults and neonates, and compared the median values and dispersal ranges of various subsets in them. We confirmed higher frequencies of monocytes and regulatory T cells (Tregs), similar frequencies of neutrophils, and lower frequencies of CD8 T cells, NKT cells, B1 B cells and gamma-delta T cells in neonatal umbilical cord blood. Unlike previous reports, we found higher frequencies of eosinophils and B cells, higher CD4:CD8 ratios, lower frequencies of T cells and iNKT cells, and similar frequencies of CD4 T cells and NK cells in neonates. We characterized monocyte subsets and dendritic cell (DC) subsets in far greater detail than previously reported, using recently described surface markers and gating strategies and observed that neonates had lower frequencies of patrolling monocytes and lower myeloid dendritic cell (mDC):plasmacytoid DC (pDC) ratios. Our data contribute to South Asian reference values for these parameters. We found that dispersal ranges differ between different leukocyte subsets, suggesting differential determination of variation. Further, some subsets were more dispersed in adults than in neonates suggesting influences of postnatal sources of variation, while some show the opposite pattern suggesting influences of developmental process variation. Together, these data and analyses provide interesting biological possibilities for future exploration. PMID:27610624

  7. 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

  8. Collagen fibre arrangement in the tibial plateau articular cartilage of man and other mammalian species

    PubMed Central

    KÄÄB, M. J.; AP GWYNN, I.; NÖTZLI, H. P.

    1998-01-01

    Experimental animal models are frequently used to study articular cartilage, but the relevance to man remains problematic. In this study animal models were compared by examination of the collagen fibre arrangement in the medial tibial plateau of human, cow, pig, dog, sheep, rabbit and rat specimens. 24 cartilage samples from each species were prepared and maximum cartilage thickness in the central tibial plateau measured. Samples were fixed, dehydrated, freeze-fractured and imaged by scanning electron microscopy (SEM). At low magnification, 2 different arrangements of collagen fibres were observed: leaf-like (human, pig, dog) and columnar (cow, sheep, rabbit, rat). The porcine collagen structure was the most similar to that of man. This arrangement was consistent from the radial to the upper zones. Under higher magnification at the surface of the leaves, the collagen was more randomly oriented, whereas the columns consisted of parallel collagen fibrils. The maximum thickness of cartilage did not correlate with the type of collagen arrangement but was correlated with the body weight of the species (r=0.785). When using animal models for investigating human articular cartilage function or pathology, the differences in arrangement of collagen fibres in tibial plateau cartilage between laboratory animals should be considered especially if morphological evaluation is planned. PMID:9758134

  9. 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.

  10. The Evidence for Increased L1 Activity in the Site of Human Adult Brain Neurogenesis

    PubMed Central

    Kurnosov, Alexey A.; Ustyugova, Svetlana V.; Nazarov, Vadim I.; Minervina, Anastasia A.; Komkov, Alexander Yu.; Shugay, Mikhail; Pogorelyy, Mikhail V.; Khodosevich, Konstantin V.; Mamedov, Ilgar Z.; Lebedev, Yuri B.

    2015-01-01

    Retroelement activity is a common source of polymorphisms in human genome. The mechanism whereby retroelements contribute to the intraindividual genetic heterogeneity by inserting into the DNA of somatic cells is gaining increasing attention. Brain tissues are suspected to accumulate genetic heterogeneity as a result of the retroelements somatic activity. This study aims to expand our understanding of the role retroelements play in generating somatic mosaicism of neural tissues. Whole-genome Alu and L1 profiling of genomic DNA extracted from the cerebellum, frontal cortex, subventricular zone, dentate gyrus, and the myocardium revealed hundreds of somatic insertions in each of the analyzed tissues. Interestingly, the highest concentration of such insertions was detected in the dentate gyrus—the hotspot of adult neurogenesis. Insertions of retroelements and their activity could produce genetically diverse neuronal subsets, which can be involved in hippocampal-dependent learning and memory. PMID:25689626

  11. Fourier analysis of human soft tissue facial shape: sex differences in normal adults.

    PubMed Central

    Ferrario, V F; Sforza, C; Schmitz, J H; Miani, A; Taroni, G

    1995-01-01

    Sexual dimorphism in human facial form involves both size and shape variations of the soft tissue structures. These variations are conventionally appreciated using linear and angular measurements, as well as ratios, taken from photographs or radiographs. Unfortunately this metric approach provides adequate quantitative information about size only, eluding the problems of shape definition. Mathematical methods such as the Fourier series allow a correct quantitative analysis of shape and of its changes. A method for the reconstruction of outlines starting from selected landmarks and for their Fourier analysis has been developed, and applied to analyse sex differences in shape of the soft tissue facial contour in a group of healthy young adults. When standardised for size, no sex differences were found between both cosine and sine coefficients of the Fourier series expansion. This shape similarity was largely overwhelmed by the very evident size differences and it could be measured only using the proper mathematical methods. PMID:8586558

  12. Growth of immature articular cartilage in vitro: correlated variation in tensile biomechanical and collagen network properties.

    PubMed

    Williamson, Amanda K; Masuda, Koichi; Thonar, Eugene J-M A; Sah, Robert L

    2003-08-01

    Articular cartilage biochemical composition and mechanical properties evolve during in utero and in vivo growth, with marked differences between fetus, newborn, and young adult. The objectives of this study were to test whether in vitro growth of bovine fetal and newborn calf articular cartilage explants resulted in changes in biochemical and tensile properties during up to 6 weeks of free-swelling culture in serum-supplemented medium. During this culture period, both fetal and calf cartilage grew markedly in size, increasing in dry and wet mass by 150-270%. This was due in part to increases in sulfated glycosaminoglycan (+248%), collagen (+96%), and pyridinoline cross-link (+133%). This was accompanied by an increase in water content so that the concentration of matrix components decreased, despite the overall net increase in mass. The ratio of pyridinoline cross-link to collagen remained low and characteristic of immature tissue. The equilibrium and dynamic tensile moduli and strength of both fetal and calf cartilage decreased during the culture period. The biochemical and biomechanical properties of the cartilage explants were correlated, such that the low values of modulus and strength were associated with low concentrations of collagen and pyridinoline. Thus, the tested culture conditions supported growth and maintenance cartilage in an immature state, but did not induce biomechanical or collagen network maturation.

  13. 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.

  14. 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

  15. 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

  16. 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

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

    PubMed

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

    2011-01-01

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

  18. 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

  19. Aging-related loss of the chromatin protein HMGB2 in articular cartilage is linked to reduced cellularity and osteoarthritis

    PubMed Central

    Taniguchi, Noboru; Caramés, Beatriz; Ronfani, Lorenza; Ulmer, Ulrich; Komiya, Setsuro; Bianchi, Marco E.; Lotz, Martin

    2009-01-01

    Osteoarthritis (OA) is the most common joint disease and typically begins with an aging-related disruption of the articular cartilage surface. Mechanisms leading to the aging-related cartilage surface degeneration remain to be determined. Here, we demonstrate that nonhistone chromatin protein high-mobility group box (HMGB) protein 2 is uniquely expressed in the superficial zone (SZ) of human articular cartilage. In human and murine cartilage, there is an aging-related loss of HMGB2 expression, ultimately leading to its complete absence. Mice genetically deficient in HMGB2 (Hmgb2−/−) show earlier onset of and more severe OA. This is associated with a profound reduction in cartilage cellularity attributable to increased cell death. These cellular changes precede glycosaminoglycan depletion and progressive cartilage erosions. Chondrocytes from Hmgb2−/− mice are more susceptible to apoptosis induction in vitro. In conclusion, HMGB2 is a transcriptional regulator specifically expressed in the SZ of human articular cartilage and supports chondrocyte survival. Aging is associated with a loss of HMGB2 expression and reduced cellularity, and this contributes to the development of OA. PMID:19139395

  20. Microarray Analysis of Cell Cycle Gene Expression in Adult Human Corneal Endothelial Cells

    PubMed Central

    Ha Thi, Binh Minh; Campolmi, Nelly; He, Zhiguo; Pipparelli, Aurélien; Manissolle, Chloé; Thuret, Jean-Yves; Piselli, Simone; Forest, Fabien; Peoc'h, Michel; Garraud, Olivier; Gain, Philippe; Thuret, Gilles

    2014-01-01

    Corneal endothelial cells (ECs) form a monolayer that controls the hydration of the cornea and thus its transparency. Their almost nil proliferative status in humans is responsible, in several frequent diseases, for cell pool attrition that leads to irreversible corneal clouding. To screen for candidate genes involved in cell cycle arrest, we studied human ECs subjected to various environments thought to induce different proliferative profiles compared to ECs in vivo. Donor corneas (a few hours after death), organ-cultured (OC) corneas, in vitro confluent and non-confluent primary cultures, and an immortalized EC line were compared to healthy ECs retrieved in the first minutes of corneal grafts. Transcriptional profiles were compared using a cDNA array of 112 key genes of the cell cycle and analysed using Gene Ontology classification; cluster analysis and gene map presentation of the cell cycle regulation pathway were performed by GenMAPP. Results were validated using qRT-PCR on 11 selected genes. We found several transcripts of proteins implicated in cell cycle arrest and not previously reported in human ECs. Early G1-phase arrest effectors and multiple DNA damage-induced cell cycle arrest-associated transcripts were found in vivo and over-represented in OC and in vitro ECs. Though highly proliferative, immortalized ECs also exhibited overexpression of transcripts implicated in cell cycle arrest. These new effectors likely explain the stress-induced premature senescence that characterizes human adult ECs. They are potential targets for triggering and controlling EC proliferation with a view to increasing the cell pool of stored corneas or facilitating mass EC culture for bioengineered endothelial grafts. PMID:24747418

  1. Norovirus-Specific Memory T Cell Responses in Adult Human Donors

    PubMed Central

    Malm, Maria; Tamminen, Kirsi; Vesikari, Timo; Blazevic, Vesna

    2016-01-01

    Norovirus (NoV) is a leading cause of acute gastroenteritis in people of all ages worldwide. NoV-specific serum antibodies which block the binding of NoV virus-like particles (VLPs) to the cell receptors have been thoroughly investigated. In contrast, only a few publications are available on the NoV capsid VP1 protein-specific T cell responses in humans naturally infected with the virus. Freshly isolated peripheral blood mononuclear cells of eight healthy adult human donors previously exposed to NoV were stimulated with purified VLPs derived from NoV GII.4-1999, GII.4-2012 (Sydney), and GI.3, and IFN-γ production was measured by an ELISPOT assay. In addition, 76 overlapping synthetic peptides spanning the entire 539-amino acid sequence of GII.4 VP1 were pooled into two-dimensional matrices and used to identify putative T cell epitopes. Seven of the eight subjects produced IFN-γ in response to the peptides and five subjects produced IFN-γ in response to the VLPs of the same origin. In general, stronger T cell responses were induced with the peptides in each donor compared to the VLPs. A CD8+ T cell epitope in the shell domain of the VP1 (134SPSQVTMFPHIIVDVRQL151) was identified in two subjects, both having human leukocyte antigen (HLA)-A∗02:01 allele. To our knowledge, this is the first report using synthetic peptides to study NoV-specific T cell responses in human subjects and identify T cell epitopes. PMID:27752254

  2. 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

  3. 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; Gieger, Christian; Golay, Alain; Gottesman, Omri; Gudnason, Vilmundur; Gyllensten, Ulf; Haas, David W; Hall, Alistair S; Harris, Tamara B; Hattersley, Andrew T; Heath, Andrew C; Hengstenberg, Christian; Hicks, Andrew A; Hindorff, Lucia A; Hingorani, Aroon D; Hofman, Albert; Hovingh, G Kees; Humphries, Steve E; Hunt, Steven C; Hypponen, Elina; Jacobs, Kevin B; Jarvelin, Marjo-Riitta; Jousilahti, Pekka; Jula, Antti M; Kaprio, Jaakko; Kastelein, John J P; Kayser, Manfred; Kee, Frank; Keinanen-Kiukaanniemi, Sirkka M; Kiemeney, Lambertus A; Kooner, Jaspal S; Kooperberg, Charles; Koskinen, Seppo; Kovacs, Peter; Kraja, Aldi T; Kumari, Meena; Kuusisto, Johanna; Lakka, Timo A; Langenberg, Claudia; Le Marchand, Loic; Lehtimäki, Terho; Lupoli, Sara; Madden, Pamela A F; Männistö, Satu; Manunta, Paolo; Marette, André; Matise, Tara C; McKnight, Barbara; Meitinger, Thomas; Moll, Frans L; Montgomery, Grant W; Morris, Andrew D; Morris, Andrew P; Murray, Jeffrey C; Nelis, Mari; Ohlsson, Claes; Oldehinkel, Albertine J; Ong, Ken K; Ouwehand, Willem H; Pasterkamp, Gerard; Peters, Annette; Pramstaller, Peter P; Price, Jackie F; Qi, Lu; Raitakari, Olli T; Rankinen, Tuomo; Rao, D C; Rice, Treva K; Ritchie, Marylyn; Rudan, Igor; Salomaa, Veikko; Samani, Nilesh J; Saramies, Jouko; Sarzynski, Mark A; Schwarz, Peter E H; Sebert, Sylvain; Sever, Peter; Shuldiner, Alan R; Sinisalo, Juha; Steinthorsdottir, Valgerdur; Stolk, Ronald P; Tardif, Jean-Claude; Tönjes, Anke; Tremblay, Angelo; Tremoli, Elena; Virtamo, Jarmo; Vohl, Marie-Claude; Amouyel, Philippe; Asselbergs, Folkert W; Assimes, Themistocles L; Bochud, Murielle; Boehm, Bernhard O; Boerwinkle, Eric; Bottinger, Erwin P; Bouchard, Claude; Cauchi, Stéphane; Chambers, John C; Chanock, Stephen J; Cooper, Richard S; de Bakker, Paul I W; Dedoussis, George; Ferrucci, Luigi; Franks, Paul W; Froguel, Philippe; Groop, Leif C; Haiman, Christopher A; Hamsten, Anders; Hayes, M Geoffrey; Hui, Jennie; Hunter, David J; Hveem, Kristian; Jukema, J Wouter; Kaplan, Robert C; Kivimaki, Mika; Kuh, Diana; Laakso, Markku; Liu, Yongmei; Martin, Nicholas G; März, Winfried; Melbye, Mads; Moebus, Susanne; Munroe, Patricia B; Njølstad, Inger; Oostra, Ben A; Palmer, Colin N A; Pedersen, Nancy L; Perola, Markus; Pérusse, Louis; Peters, Ulrike; Powell, Joseph E; Power, Chris; Quertermous, Thomas; Rauramaa, Rainer; Reinmaa, Eva; Ridker, Paul M; Rivadeneira, Fernando; Rotter, Jerome I; Saaristo, Timo E; Saleheen, Danish; Schlessinger, David; Slagboom, P Eline; Snieder, Harold; Spector, Tim D; Strauch, Konstantin; Stumvoll, Michael; Tuomilehto, Jaakko; Uusitupa, Matti; van der Harst, Pim; Völzke, Henry; Walker, Mark; Wareham, Nicholas J; Watkins, Hugh; Wichmann, H-Erich; Wilson, James F; Zanen, Pieter; Deloukas, Panos; Heid, Iris M; Lindgren, Cecilia M; Mohlke, Karen L; Speliotes, Elizabeth K; Thorsteinsdottir, Unnur; Barroso, Inês; Fox, Caroline S; North, Kari E; Strachan, David P; Beckmann, Jacques S; Berndt, Sonja I; Boehnke, Michael; Borecki, Ingrid B; McCarthy, Mark I; Metspalu, Andres; Stefansson, Kari; Uitterlinden, André G; van Duijn, Cornelia M; Franke, Lude; Willer, Cristen J; Price, Alkes L; Lettre, Guillaume; Loos, Ruth J F; Weedon, Michael N; Ingelsson, Erik; O'Connell, Jeffrey R; Abecasis, Goncalo R; Chasman, Daniel I; Goddard, Michael E; Visscher, Peter M; Hirschhorn, Joel N; Frayling, Timothy M

    2014-11-01

    Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

  4. Lack of tissue renewal in human adult Achilles tendon is revealed by nuclear bomb 14C

    PubMed Central

    Heinemeier, Katja Maria; Schjerling, Peter; Heinemeier, Jan; Magnusson, Stig Peter; Kjaer, Michael

    2013-01-01

    Tendons are often injured and heal poorly. Whether this is caused by a slow tissue turnover is unknown, since existing data provide diverging estimates of tendon protein half-life that range from 2 mo to 200 yr. With the purpose of determining life-long turnover of human tendon tissue, we used the 14C bomb-pulse method. This method takes advantage of the dramatic increase in atmospheric levels of 14C, produced by nuclear bomb tests in 1955–1963, which is reflected in all living organisms. Levels of 14C were measured in 28 forensic samples of Achilles tendon core and 4 skeletal muscle samples (donor birth years 1945–1983) with accelerator mass spectrometry (AMS) and compared to known atmospheric levels to estimate tissue turnover. We found that Achilles tendon tissue retained levels of 14C corresponding to atmospheric levels several decades before tissue sampling, demonstrating a very limited tissue turnover. The tendon concentrations of 14C approximately reflected the atmospheric levels present during the first 17 yr of life, indicating that the tendon core is formed during height growth and is essentially not renewed thereafter. In contrast, 14C levels in muscle indicated continuous turnover. Our observation provides a fundamental premise for understanding tendon function and pathology, and likely explains the poor regenerative capacity of tendon tissue.—Heinemeier, K. M., Schjerling, P., Heinemeier, J., Magnusson, S. P., Kjaer, M. Lack of tissue renewal in human adult Achilles tendon is revealed by nuclear bomb 14C. PMID:23401563

  5. 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.

  6. 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

  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. Endotoxin and tumor necrosis factor induce interleukin-1 gene expression in adult human vascular endothelial cells.

    PubMed

    Libby, P; Ordovas, J M; Auger, K R; Robbins, A H; Birinyi, L K; Dinarello, C A

    1986-08-01

    Interleukin 1 (IL-1) can induce potentially pathogenic functions of vascular endothelial cells. This mediator was formerly thought to be produced primarily by activated macrophages. We report here that bacterial endotoxin and recombinant human tumor necrosis factor cause accumulation of IL-1 beta mRNA in adult human vascular endothelial cells. IL-1 alpha mRNA was also detected when endothelial cells were exposed to endotoxin under "superinduction" conditions in the presence of cycloheximide. Metabolic labeling of these cells during endotoxin stimulation demonstrated increased synthesis and secretion of immunoprecipitable IL-1 protein that comigrated electrophoretically with the predominant monocyte species. In parallel with increased IL-1 mRNA and protein, endothelial cells exposed to endotoxin also release biologically active IL-1 that was neutralized by anti-IL-1-antibody. Because bloodborne agents must traverse the endothelium before entering tissues, endothelial IL-1 production induced by microbial products or other injurious stimuli could initiate local responses to invasion. Endothelial cells are both a source of and target for IL-1; accordingly, this novel autocrine mechanism might play an early role in the pathogenesis of vasculitis, allograft rejection, and arteriosclerosis.

  9. 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; Gejman, Pablo V; Gieger, Christian; Golay, Alain; Gottesman, Omri; Gudnason, Vilmundur; Gyllensten, Ulf; Haas, David W; Hall, Alistair S; Harris, Tamara B; Hattersley, Andrew T; Heath, Andrew C; Hengstenberg, Christian; Hicks, Andrew A; Hindorff, Lucia A; Hingorani, Aroon D; Hofman, Albert; Hovingh, G Kees; Humphries, Steve E; Hunt, Steven C; Hypponen, Elina; Jacobs, Kevin B; Jarvelin, Marjo-Riitta; Jousilahti, Pekka; Jula, Antti M; Kaprio, Jaakko; Kastelein, John JP; Kayser, Manfred; Kee, Frank; Keinanen-Kiukaanniemi, Sirkka M; Kiemeney, Lambertus A; Kooner, Jaspal S; Kooperberg, Charles; Koskinen, Seppo; Kovacs, Peter; Kraja, Aldi T; Kumari, Meena; Kuusisto, Johanna; Lakka, Timo A; Langenberg, Claudia; Le Marchand, Loic; Lehtimäki, Terho; Lupoli, Sara; Madden, Pamela AF; Männistö, Satu; Manunta, Paolo; Marette, André; Matise, Tara C; McKnight, Barbara; Meitinger, Thomas; Moll, Frans L; Montgomery, Grant W; Morris, Andrew D; Morris, Andrew P; Murray, Jeffrey C; Nelis, Mari; Ohlsson, Claes; Oldehinkel, Albertine J; Ong, Ken K; Ouwehand, Willem H; Pasterkamp, Gerard; Peters, Annette; Pramstaller, Peter P; Price, Jackie F; Qi, Lu; Raitakari, Olli T; Rankinen, Tuomo; Rao, DC; Rice, Treva K; Ritchie, Marylyn; Rudan, Igor; Salomaa, Veikko; Samani, Nilesh J; Saramies, Jouko; Sarzynski, Mark A; Schwarz, Peter EH; Sebert, Sylvain; Sever, Peter; Shuldiner, Alan R; Sinisalo, Juha; Steinthorsdottir, Valgerdur; Stolk, Ronald P; Tardif, Jean-Claude; Tönjes, Anke; Tremblay, Angelo; Tremoli, Elena; Virtamo, Jarmo; Vohl, Marie-Claude; Amouyel, Philippe; Asselbergs, Folkert W; Assimes, Themistocles L; Bochud, Murielle; Boehm, Bernhard O; Boerwinkle, Eric; Bottinger, Erwin P; Bouchard, Claude; Cauchi, Stéphane; Chambers, John C; Chanock, Stephen J; Cooper, Richard S; de Bakker, Paul IW; Dedoussis, George; Ferrucci, Luigi; Franks, Paul W; Froguel, Philippe; Groop, Leif C; Haiman, Christopher A; Hamsten, Anders; Hayes, M Geoffrey; Hui, Jennie; Hunter, David J.; Hveem, Kristian; Jukema, J Wouter; Kaplan, Robert C; Kivimaki, Mika; Kuh, Diana; Laakso, Markku; Liu, Yongmei; Martin, Nicholas G; März, Winfried; Melbye, Mads; Moebus, Susanne; Munroe, Patricia B; Njølstad, Inger; Oostra, Ben A; Palmer, Colin NA; Pedersen, Nancy L; Perola, Markus; Pérusse, Louis; Peters, Ulrike; Powell, Joseph E; Power, Chris; Quertermous, Thomas; Rauramaa, Rainer; Reinmaa, Eva; Ridker, Paul M; Rivadeneira, Fernando; Rotter, Jerome I; Saaristo, Timo E; Saleheen, Danish; Schlessinger, David; Slagboom, P Eline; Snieder, Harold; Spector, Tim D; Strauch, Konstantin; Stumvoll, Michael; Tuomilehto, Jaakko; Uusitupa, Matti; van der Harst, Pim; Völzke, Henry; Walker, Mark; Wareham, Nicholas J; Watkins, Hugh; Wichmann, H-Erich; Wilson, James F; Zanen, Pieter; Deloukas, Panos; Heid, Iris M; Lindgren, Cecilia M; Mohlke, Karen L; Speliotes, Elizabeth K; Thorsteinsdottir, Unnur; Barroso, Inês; Fox, Caroline S; North, Kari E; Strachan, David P; Beckmann, Jacques S.; Berndt, Sonja I; Boehnke, Michael; Borecki, Ingrid B; McCarthy, Mark I; Metspalu, Andres; Stefansson, Kari; Uitterlinden, André G; van Duijn, Cornelia M; Franke, Lude; Willer, Cristen J; Price, Alkes L.; Lettre, Guillaume; Loos, Ruth JF; Weedon, Michael N; Ingelsson, Erik; O’Connell, Jeffrey R; Abecasis, Goncalo R; Chasman, Daniel I; Goddard, Michael E

    2014-01-01

    Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explain one-fifth of heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ~2,000, ~3,700 and ~9,500 SNPs explained ~21%, ~24% and ~29% of phenotypic variance. Furthermore, all common variants together captured the majority (60%) of heritability. The 697 variants clustered in 423 loci enriched for genes, pathways, and tissue-types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/beta-catenin, and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants. PMID:25282103

  10. Retinotopic mapping of adult human visual cortex with high-density diffuse optical tomography

    PubMed Central

    Zeff, Benjamin W.; White, Brian R.; Dehghani, Hamid; Schlaggar, Bradley L.; Culver, Joseph P.

    2007-01-01

    Functional neuroimaging is a vital element of neuroscience and cognitive research and, increasingly, is an important clinical tool. Diffuse optical imaging is an emerging, noninvasive technique with unique portability and hemodynamic contrast capabilities for mapping brain function in young subjects and subjects in enriched or clinical environments. We have developed a high-performance, high-density diffuse optical tomography (DOT) system that overcomes previous limitations and enables superior image quality. We show herein the utility of the DOT system by presenting functional hemodynamic maps of the adult human visual cortex. The functional brain images have a high contrast-to-noise ratio, allowing visualization of individual activations and highly repeatable mapping within and across subjects. With the improved spatial resolution and localization, we were able to image functional responses of 1.7 cm in extent and shifts of <1 cm. Cortical maps of angle and eccentricity in the visual field are consistent with retinotopic studies using functional MRI and positron-emission tomography. These results demonstrate that high-density DOT is a practical and powerful tool for mapping function in the human cortex. PMID:17616584

  11. 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.

  12. 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

  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. 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

    2015-11-19

    An understanding of all aspects of fluoride metabolism is critical to identify its biological effects and avoid fluoride toxicity in humans. Fluoride metabolism and subsequently its body retention may be affected by physiological responses to acute exercise. This pilot study investigated the effect of exercise on plasma fluoride concentration, urinary fluoride excretion and fluoride renal clearance following no exercise and three exercise intensity conditions in nine healthy adults after taking a 1-mg Fluoride tablet. After no, light, moderate and vigorous exercise, respectively, the mean (SD) baseline-adjusted i) plasma fluoride concentration was 9.6(6.3), 11.4(6.3), 15.6(7.7) and 14.9(10.0) ng/ml; ii) rate of urinary fluoride excretion over 0-8 h was 46(15), 44(22), 34(17) and 36(17) μg/h; and iii) rate of fluoride renal clearance was 26.5(9.0), 27.2(30.4), 13.1(20.4) and 18.3(34.9) ml/min. The observed trend of a rise in plasma fluoride concentration and decline in rate of fluoride renal clearance with increasing exercise intensity needs to be investigated in a larger trial. This study, which provides the first data on the effect of exercise with different intensities on fluoride metabolism in humans, informs sample size planning for any subsequent definitive trial, by providing a robust estimate of the variability of the effect.

  15. 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

  16. Dedifferentiation of Adult Human Myoblasts Induced by Ciliary Neurotrophic Factor In Vitro

    PubMed Central

    Chen, Xiaoping; Mao, Zebin; Liu, Shuhong; Liu, Hong; Wang, Xuan; Wu, Haitao; Wu, Yan; Zhao, Tong; Fan, Wenhong; Li, Yong; Yew, David T.; Kindler, Pawel M.; Li, Linsong; He, Qihua; Qian, Lingjia; Wang, Xiaomin; Fan, Ming

    2005-01-01

    Ciliary neurotrophic factor (CNTF) is primarily known for its important cellular effects within the nervous system. However, recent studies indicate that its receptor can be highly expressed in denervated skeletal muscle. Here, we investigated the direct effect of CNTF on skeletal myoblasts of adult human. Surprisingly, we found that CNTF induced the myogenic lineage-committed myoblasts at a clonal level to dedifferentiate into multipotent progenitor cells—they not only could proliferate for over 20 passages with the expression absence of myogenic specific factors Myf5 and MyoD, but they were also capable of differentiating into new phenotypes, mainly neurons, glial cells, smooth muscle cells, and adipocytes. These “progenitor cells” retained their myogenic memory and were capable of redifferentiating into myotubes. Furthermore, CNTF could activate the p44/p42 MAPK and down-regulate the expression of myogenic regulatory factors (MRFs). Finally, PD98059, a specific inhibitor of p44/p42 MAPK pathway, was able to abolish the effects of CNTF on both myoblast fate and MRF expression. Our results demonstrate the myogenic lineage-committed human myoblasts can dedifferentiate at a clonal level and CNTF is a novel regulator of skeletal myoblast dedifferentiation via p44/p42 MAPK pathway. PMID:15843428

  17. Effect of exercise on fluoride metabolism in adult humans: a pilot study

    PubMed Central

    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

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

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

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

  19. 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; Gieger, Christian; Golay, Alain; Gottesman, Omri; Gudnason, Vilmundur; Gyllensten, Ulf; Haas, David W; Hall, Alistair S; Harris, Tamara B; Hattersley, Andrew T; Heath, Andrew C; Hengstenberg, Christian; Hicks, Andrew A; Hindorff, Lucia A; Hingorani, Aroon D; Hofman, Albert; Hovingh, G Kees; Humphries, Steve E; Hunt, Steven C; Hypponen, Elina; Jacobs, Kevin B; Jarvelin, Marjo-Riitta; Jousilahti, Pekka; Jula, Antti M; Kaprio, Jaakko; Kastelein, John J P; Kayser, Manfred; Kee, Frank; Keinanen-Kiukaanniemi, Sirkka M; Kiemeney, Lambertus A; Kooner, Jaspal S; Kooperberg, Charles; Koskinen, Seppo; Kovacs, Peter; Kraja, Aldi T; Kumari, Meena; Kuusisto, Johanna; Lakka, Timo A; Langenberg, Claudia; Le Marchand, Loic; Lehtimäki, Terho; Lupoli, Sara; Madden, Pamela A F; Männistö, Satu; Manunta, Paolo; Marette, André; Matise, Tara C; McKnight, Barbara; Meitinger, Thomas; Moll, Frans L; Montgomery, Grant W; Morris, Andrew D; Morris, Andrew P; Murray, Jeffrey C; Nelis, Mari; Ohlsson, Claes; Oldehinkel, Albertine J; Ong, Ken K; Ouwehand, Willem H; Pasterkamp, Gerard; Peters, Annette; Pramstaller, Peter P; Price, Jackie F; Qi, Lu; Raitakari, Olli T; Rankinen, Tuomo; Rao, D C; Rice, Treva K; Ritchie, Marylyn; Rudan, Igor; Salomaa, Veikko; Samani, Nilesh J; Saramies, Jouko; Sarzynski, Mark A; Schwarz, Peter E H; Sebert, Sylvain; Sever, Peter; Shuldiner, Alan R; Sinisalo, Juha; Steinthorsdottir, Valgerdur; Stolk, Ronald P; Tardif, Jean-Claude; Tönjes, Anke; Tremblay, Angelo; Tremoli, Elena; Virtamo, Jarmo; Vohl, Marie-Claude; Amouyel, Philippe; Asselbergs, Folkert W; Assimes, Themistocles L; Bochud, Murielle; Boehm, Bernhard O; Boerwinkle, Eric; Bottinger, Erwin P; Bouchard, Claude; Cauchi, Stéphane; Chambers, John C; Chanock, Stephen J; Cooper, Richard S; de Bakker, Paul I W; Dedoussis, George; Ferrucci, Luigi; Franks, Paul W; Froguel, Philippe; Groop, Leif C; Haiman, Christopher A; Hamsten, Anders; Hayes, M Geoffrey; Hui, Jennie; Hunter, David J; Hveem, Kristian; Jukema, J Wouter; Kaplan, Robert C; Kivimaki, Mika; Kuh, Diana; Laakso, Markku; Liu, Yongmei; Martin, Nicholas G; März, Winfried; Melbye, Mads; Moebus, Susanne; Munroe, Patricia B; Njølstad, Inger; Oostra, Ben A; Palmer, Colin N A; Pedersen, Nancy L; Perola, Markus; Pérusse, Louis; Peters, Ulrike; Powell, Joseph E; Power, Chris; Quertermous, Thomas; Rauramaa, Rainer; Reinmaa, Eva; Ridker, Paul M; Rivadeneira, Fernando; Rotter, Jerome I; Saaristo, Timo E; Saleheen, Danish; Schlessinger, David; Slagboom, P Eline; Snieder, Harold; Spector, Tim D; Strauch, Konstantin; Stumvoll, Michael; Tuomilehto, Jaakko; Uusitupa, Matti; van der Harst, Pim; Völzke, Henry; Walker, Mark; Wareham, Nicholas J; Watkins, Hugh; Wichmann, H-Erich; Wilson, James F; Zanen, Pieter; Deloukas, Panos; Heid, Iris M; Lindgren, Cecilia M; Mohlke, Karen L; Speliotes, Elizabeth K; Thorsteinsdottir, Unnur; Barroso, Inês; Fox, Caroline S; North, Kari E; Strachan, David P; Beckmann, Jacques S; Berndt, Sonja I; Boehnke, Michael; Borecki, Ingrid B; McCarthy, Mark I; Metspalu, Andres; Stefansson, Kari; Uitterlinden, André G; van Duijn, Cornelia M; Franke, Lude; Willer, Cristen J; Price, Alkes L; Lettre, Guillaume; Loos, Ruth J F; Weedon, Michael N; Ingelsson, Erik; O'Connell, Jeffrey R; Abecasis, Goncalo R; Chasman, Daniel I; Goddard, Michael E; Visscher, Peter M; Hirschhorn, Joel N; Frayling, Timothy M

    2014-11-01

    Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants. PMID:25282103

  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. 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

  2. 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;…

  3. Evidence against T-cell development in the adult human intestinal mucosa based upon lack of terminal deoxynucleotidyltransferase expression.

    PubMed Central

    Taplin, M E; Frantz, M E; Canning, C; Ritz, J; Blumberg, R S; Balk, S P

    1996-01-01

    Several lines of evidence indicate that a subset of murine intestinal intraepithelial lymphocytes (iIEL), particularly those which express the CD8 alpha alpha homodimer, mature extrathymically. This study confirms that a small fraction of adult human iIEL also express the CD8 alpha alpha homodimer and demonstrates that most of these cells in the small intestine are T cells using the alpha beta T-cell receptor (TCR). Whether these cells or other subsets of adult human iIEL mature extrathymically in the intestine was assessed by measuring the expression of terminal deoxynucleotidyltransferase (TdT), an enzyme expressed exclusively by immature lymphocytes. Very low levels of TdT message could be detected by polymerase chain reaction (PCR) amplification in some iIEL samples. The level of TdT expression was assayed by competitive PCR amplification and compared with thymocytes and peripheral blood lymphocytes. These measurements indicated that the number of immature T cells expressing TdT in the intestinal epithelium was less than one cell per 10(7) lymphocytes. This demonstrates that there are few if any TdT expressing immature T cells in the adult human intestinal mucosa and indicates, therefore, that T-cell development in the intestinal mucosa does not contribute significantly to the T-cell repertoire of the adult human intestine. Images Figure 1 Figure 2 Figure 3 PMID:8778025

  4. 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...

  5. Cryoscanning electron microscopy of loaded articular cartilage with special reference to the surface amorphous layer.

    PubMed

    Kobayashi, S; Yonekubo, S; Kurogouchi, Y

    1996-04-01

    The surface layer (i.e. the surface lamina) of articular cartilage, which is devoid of a collagen fibril network or cells, was investigated in the pig and human. It overlies the collagenous main part of the articular cartilage which contains chondrocytes and is thought to be important biomechanically. In order to examine morphological changes in this layer when under load, knee articular cartilage of the pig, along with the underlying subchondral bone, was compressed with a cylindrical indenter. The specimen was frozen by immersion in liquid nitrogen to maintain the loaded condition and was then freeze-fractured at the indented region. The fracture face was examined with a cryoscanning electron microscope. The surface layer was compressed beneath the indenter regardless of loading pressure or period and was expanded around the indenter to form a triangular bulge in cross section. The height of the bulge was related to the applied pressure and not to the loading period. Recovery of the cartilage from indentation was also examined. Immediately after removal of the indenter, the bulge of the surface layer moved back into the previously indented region. The region was covered by a thick surface layer after 2 s. The response of the surface layer to and recovery from indentation was largely instantaneous and elastic. Under heavy load conditions, the main part of the cartilage under the indenter was observed to have a striped pattern which was made up of bands of densely packed collagen fibrils with fibrillar networks remaining between them. These morphological findings agree well with previously reported biomechanical hypotheses and can be explained by the flow of interstitial fluid provoked by stress application. PMID:8621329

  6. Cell-Based Articular Cartilage Repair: The Link between Development and Regeneration

    PubMed Central

    Caldwell, Kenneth L.; Wang, Jinxi

    2014-01-01

    Context Clinical efforts to repair damaged articular cartilage (AC) currently face major obstacles due to limited intrinsic repair capacity of the tissue and unsuccessful biological interventions. This highlights a need for better therapeutic strategies. Evidence Acquisition Relevant articles were identified through a search of the PubMed database from January 1956 to August 2014 using the following keywords: articular cartilage repair, stem cell, cartilage tissue-engineering, synovium, and NFAT. Evidence Synthesis In both animals and humans, AC defects that penetrate into the subchondral bone marrow are mainly filled with fibrocartilaginous tissue through the differentiation of bone marrow mesenchymal stem cells (MSCs), followed by degeneration of repaired cartilage and osteoarthritis. Cell therapy and tissue engineering techniques using culture-expanded chondrocytes, bone marrow MSCs, or pluripotent stem cells with chondroinductive growth factors may generate cartilaginous tissue in AC defects but do not form hyaline cartilage-based articular surface because repair cells often lose chondrogenic activity or result in chondrocyte hypertrophy. The new evidence that AC and synovium develop from the same pool of precursors with similar gene profiles and that synovium-derived chondrocytes have stable chondrogenic activity has promoted use of synovium as a new cell source for AC repair. The recent finding that NFAT1 and NFAT2 transcription factors inhibit chondrocyte hypertrophy and maintain metabolic balance in AC is a significant advance in the field of AC repair. Conclusions The use of synovial MSCs and discovery of upstream transcriptional regulators that help maintain the AC phenotype have opened new avenues to improve the outcome of AC regeneration. PMID:25450846

  7. Intra-Articular Transplantation of Atsttrin-Transduced Mesenchymal Stem Cells Ameliorate Osteoarthritis Development

    PubMed Central

    Xia, Qingqing; Zhu, Shouan; Wu, Yan; Wang, Jiaqiu; Cai, Youzhi; Chen, Pengfei; Li, Jie; Heng, Boon Chin

    2015-01-01

    Osteoarthritis (OA) remains an intractable clinical challenge. Few drugs are available for reversing this degenerative disease, although some promising candidates have performed well in preclinical studies. Tumor necrosis factor α (TNFα) has been identified as a crucial effector modulating OA pathogenesis. This study aimed to investigate the therapeutic effects of Atsttrin, a novel TNFα blocker, on OA treatment. We developed genetically modified mesenchymal stem cells (MSCs) that expressed recombinant Atsttrin (named as MSC-Atsttrin). Expression levels of ADAMTS-5, MMP13, and iNOS of human chondrocytes were analyzed when cocultured with MSC-GFP/Atsttrin. OA animal models were induced by anterior cruciate ligament transection, and MSC-GFP/Atsttrin were injected into the articular cavity 1 week postsurgery. The results showed that MSC-Atsttrin significantly suppressed TNFα-driven up-regulation of matrix proteases and inflammatory factors. Intra-articular injection of MSC-Atsttrin prevented the progression of degenerative changes in the surgically induced OA mouse model. Additionally, levels of detrimental matrix hydrolases were significantly diminished. Compared with nontreated OA samples at 8 weeks postsurgery, the percentages of MMP13- and ADAMTS-5-positive cells were significantly reduced from 91.33% ± 9.87% to 24.33% ± 5.7% (p < .001) and from 91.33% ± 7.1% to 16.67% ± 3.1% (p < .001), respectively. Our results thus indicated that suppression of TNFα activity is an effective strategy for OA treatment and that intra-articular injection of MSCs-Atsttrin could be a promising therapeutic modality. PMID:25824140

  8. Induction of Stem Cell Gene Expression in Adult Human Fibroblasts without Transgenes

    PubMed Central

    Ambady, Sakthikumar; Holmes, William F.; Vilner, Lucy; Kole, Denis; Kashpur, Olga; Huntress, Victoria; Vojtic, Ina; Whitton, Holly; Dominko, Tanja

    2009-01-01

    Abstract Reprogramming of differentiated somatic cells into induced pluripotent stem (iPS) cells has potential for derivation of patient-specific cells for therapy as well as for development of models with which to study disease progression. Derivation of iPS cells from human somatic cells has been achieved by viral transduction of human fibroblasts with early developmental genes. Because forced expression of these genes by viral transduction results in transgene integration with unknown and unpredictable potential mutagenic effects, identification of cell culture conditions that can induce endogenous expression of these genes is desirable. Here we show that primary adult human fibroblasts have basal expression of mRNA for OCT4, SOX2, and NANOG. However, translation of these messages into detectable proteins and their subcellular localization depends on cell culture conditions. Manipulation of oxygen concentration and FGF2 supplementation can modulate expression of some pluripotency related genes at the transcriptional, translational, and cellular localization level. Changing cell culture condition parameters led to expression of REX1, potentiation of expression of LIN28, translation of OCT4, SOX2, and NANOG, and translocation of these transcription factors to the cell nucleus. We also show that culture conditions affect the in vitro lifespan of dermal fibroblasts, nearly doubling the number of population doublings before the cells reach replicative senescence. Our results suggest that it is possible to induce and manipulate endogenous expression of stem cell genes in somatic cells without genetic manipulation, but this short-term induction may not be sufficient for acquisition of true pluripotency. Further investigation of the factors involved in inducing this response could lead to discovery of defined culture conditions capable of altering cell fate in vitro. This would alleviate the need for forced expression by transgenesis, thus eliminating the risk of

  9. 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

  10. 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

  11. Pseudomonas arthritis treated with parenteral and intra-articular ceftazidime.

    PubMed Central

    Walton, K; Hilton, R C; Sen, R A

    1985-01-01

    A 73-year-old diabetic presented with septic arthritis of the knee; Pseudomonas aeruginosa was isolated. She was successfully treated with a combination of parenteral and intra-articular ceftazidime, after failure to eradicate the organism with adequate serum levels of gentamicin and full doses of azlocillin. PMID:3896166

  12. ELASTICITY OF ARTICULAR CARTILAGE: EFFECT OF IONS AND VISCOUS SOLUTIONS.

    PubMed

    SOKOLOFF, L

    1963-09-13

    The deformability of articular cartilage is increased by cations, more so by polyvalent than monovalent ones. Trivalent cations also depress elastic recovery. Failure of viscous solutions to alter the elastic behavior suggests ultra-filtration by cartilage as a possible mechanism in synovial lubrication.

  13. Current Concepts of Articular Cartilage Restoration Techniques in the Knee

    PubMed Central

    Camp, Christopher L.; Stuart, Michael J.; Krych, Aaron J.

    2014-01-01

    Context: Articular cartilage injuries are common in patients presenting to surgeons with primary complaints of knee pain or mechanical symptoms. Treatment options include comprehensive nonoperative management, palliative surgery, joint preservation operations, and arthroplasty. Evidence Acquisition: A MEDLINE search on articular cartilage restoration techniques of the knee was conducted to identify outcome studies published from 1993 to 2013. Special emphasis was given to Level 1 and 2 published studies. Study Design: Clinical review. Level of Evidence: Level 3. Results: Current surgical options with documented outcomes in treating chondral injuries in the knee include the following: microfracture, osteochondral autograft transfer, osteochondral allograft transplant, and autologous chondrocyte transplantation. Generally, results are favorable regarding patient satisfaction and return to sport when proper treatment algorithms and surgical techniques are followed, with 52% to 96% of patients demonstrating good to excellent clinical outcomes and 66% to 91% returning to sport at preinjury levels. Conclusion: Clinical, functional, and radiographic outcomes may be improved in the majority of patients with articular cartilage restoration surgery; however, some patients may not fully return to their preinjury activity levels postoperatively. In active and athletic patient populations, biological techniques that restore the articular surface may be options that provide symptom relief and return patients to their prior levels of function. PMID:24790697

  14. Corrective Osteotomy for Intra-Articular Distal Humerus Malunion

    PubMed Central

    Kinaci, Ahmet; Buijze, Geert A.; Leeuwen, Diederik H.van; Jupiter, Jesse B.; Marti, Rene K.; Kloen, Peter

    2016-01-01

    Background: An intra-articular distal humerus malunion can be disabling. To improve function, reduce pain and/or prevent further secondary osteoarthritis an intra-articular corrective osteotomy can be considered. Herein we present the indications, practical guidelines for pre- operative planning and surgical technique. Subsequently, we provide long-term results in a small series. Methods: We included six consecutive patients operated for intra-articular distal humerus malunion. Mean follow-up was 88 months. At lastest follow up elbow function was assessed according to standardized questionnaires and classification systems. Results: All six patients healed their osteotomies. Three patients had a postoperative complication which were treated succesfully. Range of motion improved significantly and all patients were satisfied with the outcome. The elbow performance scores were good to excellent in all. Correlation analyses showed that age and level of osteoarthritis are very strong predictors for the long-term elbow function and quality of life. Conclusion: An intra-articular corrective osteotomy for a malunited distal humerus fracture is a worthwhile procedure. Based on our results it should particularly be considered in young patients with minimal osteoarthritis and moderate to severe functional disability and/or pain. PMID:27200396

  15. Evaluation of apparent fracture toughness of articular cartilage and hydrogels

    PubMed Central

    Xiao, Yinghua; Rennerfeldt, Deena A.; Friis, Elizabeth A.; Gehrke, Stevin H.; Detamore, Michael S.

    2014-01-01

    Recently, biomaterials-based tissue-engineering strategies, including the use of hydrogels, have offered great promise for repairing articular cartilage. Mechanical failure testing in outcome analyses is of crucial clinical importance to the success of engineered constructs. Interpenetrating networks (IPNs) are gaining more attention, due to their superior mechanical integrity. This study provided a combination testing method of apparent fracture toughness, which was applied to both articular cartilage and hydrogels. The apparent fracture toughnesses of two groups, hydrogels and articular cartilage, were evaluated based on the modified single-edge notch test and ASTM standards on the single-edge notch test and compact tension test. The results demonstrated that the toughness for articular cartilage (348 ± 43 MPa/mm½) was much higher than that for hydrogels. With a toughness value of 10.8 ± 1.4 MPa/mm½, IPNs of agarose and poly(ethylene glycol) diacrylate (PEG-DA) looked promising. The IPNs were 1.4 times tougher than PEG-DA alone, although still over an order of magnitude less tough than cartilage. A new method was developed to evaluate hydrogels and cartilage in a manner that enabled a more relevant direct comparison for fracture testing of hydrogels for cartilage tissue engineering. Moreover, a target toughness value for cartilage of using this direct comparison method has been identified (348 ± 43 MPa/mm½), and the toughness discrepancy to be overcome between hydrogels and cartilage has been quantified. PMID:24700577

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

    PubMed

    Mohammadi, Hadi; Mequanint, Kibret; Herzog, Walter

    2013-04-01

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

  17. Biphasic surface amorphous layer lubrication of articular cartilage.

    PubMed

    Graindorge, Simon; Ferrandez, Wendy; Jin, Zhongmin; Ingham, Eileen; Grant, Colin; Twigg, Peter; Fisher, John

    2005-12-01

    The biphasic nature of articular cartilage has been acknowledged for some time and is known to play an important role in many of the biomechanical functions performed by this unique tissue. From the lubrication point of view however, a simple biphasic model is unable to account for the extremely low friction coefficients that have been recorded experimentally, particularly during start-up. In addition, research over the last decade has indicated the presence of a surface amorphous layer on top of articular cartilage. Here, we present results from a finite element model of articular cartilage that includes a thin, soft, biphasic surface amorphous layer (BSAL). The results of this study show that a thin BSAL, with lower elastic modulus, dramatically altered the load sharing between the solid and liquid phases of articular cartilage, particularly in the near-surface regions of the underlying bulk cartilage and within the surface amorphous layer itself where the fluid load support exceeded 85%. By transferring the load from the solid phase to the fluid phase, the biphasic surface layer improves lubrication and reduces friction, whilst also protecting the underlying cartilage surface by 'shielding' the solid phase from elevated stresses. The increase in lubrication effectiveness is shown to be greatest during short duration loading scenarios, such as shock loads.

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

    PubMed

    Lee, R B; Urban, J P

    1997-01-01

    Uptake of external glucose and production of lactate were measured in freshly-excised bovine articular cartilage under O2 concentrations ranging from 21% (air) to zero (N2-bubbled). Anoxia (O2 concentration < 1% in the gas phase) severely inhibited both glucose uptake and lactate production. The decrease in lactate formation correlated closely with the decrease in glucose uptake, in a mole ratio of 2:1. This reduction in the rate of glycolysis in anoxic conditions is seen as evidence of a negative Pasteur effect in bovine articular cartilage. Anoxia also suppressed glycolysis in articular cartilage from horse, pig and sheep. Inhibitors acting on the glycolytic pathway (2-deoxy-D-glucose, iodoacetamide or fluoride) strongly decreased aerobic lactate production and ATP concentration, consistent with the belief that articular cartilage obtains its principal supply of ATP from substrate-level phosphorylation in glycolysis. Azide or cyanide lowered the ATP concentration in aerobic cartilage to approximately the same extent as did anoxia but, because glycolysis (lactate production) was also inhibited by these treatments, the importance of any mitochondrial ATP production could not be assessed. A negative Pasteur effect would make chondrocytes particularly liable to suffer a shortage of energy under anoxic conditions. Incorporation of [35S]sulphate into proteoglycan was severely curtailed by treatments, such as anoxia, which decreased the intracellular concentration of ATP.

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

    PubMed Central

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

    2016-01-01

    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

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

    PubMed

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

    2006-01-01

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

  1. The organization of collagen in cryofractured rabbit articular cartilage: a scanning electron microscopic study.

    PubMed

    Clark, J M

    1985-01-01

    Adult rabbit articular cartilage was prepared for scanning electron microscopy using, in order, glutaraldehyde fixation, enzymatic removal of proteoglycan, dehydration in ethanol, cryofracture in liquid nitrogen, and critical-point drying. Enzymes were effective in fixed material. Fixation, cryofracture, alignment of fracture surfaces with "split lines," and retention of subchondral bone were found to be necessary steps for the preservation of collagen detail. The fibrous framework was found to be similar to that proposed by Benninghoff and favored by more recent phase-contrast microscopic studies. Vertical fibers extending from subchondral bone and a network of tangentially oriented superficial fibrils converge in the transitional zone. No random layer is seen. Pericellular capsules interdigitate with the vertical fibers. When cartilage is prepared in a manner that minimizes tissue damage, scanning electron microscopy provides useful, unique information. PMID:3981292

  2. Empowering Adult Learners. NIF Literacy Program Helps ABE Accomplish Human Development Mission.

    ERIC Educational Resources Information Center

    Hurley, Mary E.

    1991-01-01

    The National Issues Forum's Literacy Program uses study circles and group discussion to promote empowerment and enhance adult literacy through civic education. The program has helped the Westonka (Minnesota) Adult Basic Education project accomplish its mission and has expanded the staff's view of adult learning. (SK)

  3. The Role of Tissue Engineering in Articular Cartilage Repair and Regeneration

    PubMed Central

    Zhang, Lijie; Hu, Jerry; Athanasiou, Kyriacos A.

    2011-01-01

    Articular cartilage repair and regeneration continue to be largely intractable due to the poor regenerative properties of this tissue. The field of articular cartilage tissue engineering, which aims to repair, regenerate, and/or improve injured or diseased articular cartilage functionality, has evoked intense interest and holds great potential for improving articular cartilage therapy. This review provides an overall description of the current state and progress in articular cartilage repair and regeneration. Traditional therapies and related problems are introduced. More importantly, a variety of promising cell sources, biocompatible tissue engineered scaffolds, scaffoldless techniques, growth factors, and mechanical stimuli used in current articular cartilage tissue engineering are reviewed. Finally, the technical and regulatory challenges of articular cartilage tissue engineering and possible future directions are discussed. PMID:20201770

  4. 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

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

    PubMed Central

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

    2010-01-01

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

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

    PubMed

    Kristensen, Helene Bjoerg; Andersen, Thomas Levin; Marcussen, Niels; Rolighed, Lars; Delaisse, Jean-Marie

    2013-03-01

    Vascularization is a prerequisite for osteogenesis in a number of situations, including bone development, fracture healing, and cortical bone remodeling. It is unknown whether a similar link exists between cancellous bone remodeling and vascularization. Here, we show an association between remodeling sites, capillaries, proliferative cells, and putative osteoblast progenitors. Iliac crest biopsies from normal human individuals were subjected to histomorphometry and immunohistochemistry to identify the respective positions of bone remodeling sites, CD34-positive capillaries, smooth muscle actin (SMA)-positive putative osteoblast progenitors, including pericytes, Ki67-positive proliferative cells, and bone remodeling compartment (BRC) canopies. The BRC canopy is a recently described structure separating remodeling sites from the bone marrow, consisting of CD56-positive osteoblasts at an early differentiation stage. We found that bone remodeling sites were associated with a significantly increased presence of capillaries, putative osteoblast progenitors, and proliferative cells in a region within 50 µm of the bone or the canopy surface. The increases were the highest above eroded surfaces and at the level of the light-microscopically assessed contact of these three entities with the bone or canopy surfaces. Between 51 and 100 µm, their densities leveled to that found above quiescent surfaces. Electron microscopy asserted the close proximity between BRC canopies and capillaries lined by pericytes. Furthermore, the BRC canopy cells were found to express SMA. These ordered distributions support the existence of an osteogenic-vascular interface in adult human cancellous bone. The organization of this interface fits the current knowledge on the mode of action of vasculature on osteogenesis, and points to the BRC canopy as a central player in this mechanism. We propose a model where initiation of bone remodeling coincides with the induction of proximity of the

  10. 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.

  11. Sexual dimorphism of facial appearance in ageing human adults: A cross-sectional study.

    PubMed

    Mydlová, Miriama; Dupej, Ján; Koudelová, Jana; Velemínská, Jana

    2015-12-01

    In the forensic sciences, knowledge of facial ageing is very important in searching for both dead and living individuals. Ageing estimations typically model the biological profile, which can be compared to missing persons. The main goals of this current study were to construct ageing trajectories for adult human faces of both sexes and evaluate sexual dimorphism in relation to static allometry. Our study was based on the analysis of three-dimensional facial surface models of 194 individuals 20-80 years of age. The evaluation consisted of a dense correspondence analysis of facial scans and multivariate statistics. It was shown that both age and sex have a significant influence on facial form and shape. Male features included a longer face, with more protruded foreheads, eyebrow ridges and nose, including the region under the upper lip and mandible region, but more retruded cheeks compared to females. Ageing in both sexes shared common traits, such as more pronounced roundness of the face (rectangular in males), decreased facial convexity, increased visibility of skin folds and wrinkles connected with the loss of skin elasticity, and soft tissue stretching, especially in the orbital area and lower face; however, male faces exhibited more intense ageing changes. The above-mentioned sexual dimorphic traits tended to diminish in the elderly age category, though overall sexual dimorphism was heightened with age. The static allometric relationships between size and form or shape were similar in both sexes, except that the larger faces of elderly males displayed more intensive ageing changes.

  12. Adult human keratinocyte cultures express 40, 52, 58 and 67 KD keratins

    SciTech Connect

    Bhatnagar, R.S.; Chandrakasan, G.; Hussain, M.Z.; Enriquez, B.; Ryder, M.I.

    1986-03-01

    Keratins are complex fibrous proteins characteristic of epithelial cells. Although several different classes of keratins are known to occur in the epidermis, the expression of all keratins has not been observed in vitro. The authors have developed a procedure that allows us to culture and passage up to ten times, adult human kerationcytes, in the absence of mesenchymal substrates. EM examination of stratifying cultures showed the presence of numerous tonofilaments, desmosomes and keratohyaline granules. The expression of different classes of keratins was examined by immunofluorescence, radiolabeling, SDS-PAGE and Western blot, using mouse monoclonal antibodies. Analysis of water-insoluble proteins showed the presence of keratins of M.W. 40 kd, 50-52 kd, 56-57 kd and 65-67 kd. The expression of 40kd keratin is known to be associated with basal cells. In their culture system basal cells secrete a well-defined basement membrane on which they rest. These cells may be responsible for the 40kd keratin. The expression of 65-67kd keratins has not previously been observed in vitro. These keratins are considered to be markers for terminal differentiation of epidermal cells. These proteins are presumed to be synthesized in their cultures by sloughing layers of rough, granular cells.

  13. 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

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

    PubMed

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

    2016-02-01

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

  15. 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

  16. Pneumocystis Pneumonia in Human Immunodeficiency Virus–infected Adults and Adolescents: Current Concepts and Future Directions

    PubMed Central

    Tasaka, Sadatomo

    2015-01-01

    Pneumocystis jirovecii pneumonia (PCP) is one of the most common opportunistic infections in human immunodeficiency virus–infected adults. Colonization of Pneumocystis is highly prevalent among the general population and could be associated with the transmission and development of PCP in immunocompromised individuals. Although the microscopic demonstration of the organisms in respiratory specimens is still the golden standard of its diagnosis, polymerase chain reaction has been shown to have a high sensitivity, detecting Pneumocystis DNA in induced sputum or oropharyngeal wash. Serum β-D-glucan is useful as an adjunctive tool for the diagnosis of PCP. High-resolution computed tomography, which typically shows diffuse ground-glass opacities, is informative for the evaluation of immunocompromised patients with suspected PCP and normal chest radiography. Trimethoprim–sulfamethoxazole (TMP-SMX) is the first-line agent for the treatment of mild to severe PCP, although it is often complicated with various side effects. Since TMP-SMX is widely used for the prophylaxis, the putative drug resistance is an emerging concern. PMID:26327786

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

    PubMed

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

    2016-02-01

    Current obesity prevention strategies recommend increasing daily physical activity, assuming that increased activity will lead to corresponding increases in total energy expenditure and prevent or reverse energy imbalance and weight gain [1-3]. Such Additive total energy expenditure models are supported by exercise intervention and accelerometry studies reporting positive correlations between physical activity and total energy expenditure [4] but are challenged by ecological studies in humans and other species showing that more active populations do not have higher total energy expenditure [5-8]. Here we tested a Constrained total energy expenditure model, in which total energy expenditure increases with physical activity at low activity levels but plateaus at higher activity levels as the body adapts to maintain total energy expenditure within a narrow range. We compared total energy expenditure, measured using doubly labeled water, against physical activity, measured using accelerometry, for a large (n = 332) sample of adults living in five populations [9]. After adjusting for body size and composition, total energy expenditure was positively correlated with physical activity, but the relationship was markedly stronger over the lower range of physical activity. For subjects in the upper range of physical activity, total energy expenditure plateaued, supporting a Constrained total energy expenditure model. Body fat percentage and activity intensity appear to modulate the metabolic response to physical activity. Models of energy balance employed in public health [1-3] should be revised to better reflect the constrained nature of total energy expenditure and the complex effects of physical activity on metabolic physiology. PMID:26832439

  18. Sexual dimorphism of facial appearance in ageing human adults: A cross-sectional study.

    PubMed

    Mydlová, Miriama; Dupej, Ján; Koudelová, Jana; Velemínská, Jana

    2015-12-01

    In the forensic sciences, knowledge of facial ageing is very important in searching for both dead and living individuals. Ageing estimations typically model the biological profile, which can be compared to missing persons. The main goals of this current study were to construct ageing trajectories for adult human faces of both sexes and evaluate sexual dimorphism in relation to static allometry. Our study was based on the analysis of three-dimensional facial surface models of 194 individuals 20-80 years of age. The evaluation consisted of a dense correspondence analysis of facial scans and multivariate statistics. It was shown that both age and sex have a significant influence on facial form and shape. Male features included a longer face, with more protruded foreheads, eyebrow ridges and nose, including the region under the upper lip and mandible region, but more retruded cheeks compared to females. Ageing in both sexes shared common traits, such as more pronounced roundness of the face (rectangular in males), decreased facial convexity, increased visibility of skin folds and wrinkles connected with the loss of skin elasticity, and soft tissue stretching, especially in the orbital area and lower face; however, male faces exhibited more intense ageing changes. The above-mentioned sexual dimorphic traits tended to diminish in the elderly age category, though overall sexual dimorphism was heightened with age. The static allometric relationships between size and form or shape were similar in both sexes, except that the larger faces of elderly males displayed more intensive ageing changes. PMID:26548377

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

    PubMed

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

    2016-01-01

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

  20. Prostate-regenerating capacity of cultured human adult prostate epithelial cells.

    PubMed

    Yao, M; Taylor, R A; Richards, M G; Sved, P; Wong, J; Eisinger, D; Xie, C; Salomon, R; Risbridger, G P; Dong, Q

    2010-01-01

    Experimentation with the progenitor/stem cells in adult prostate epithelium can be inconvenient due to a tight time line from tissue acquisition to cell isolation and to downstream experiments. To circumvent this inconvenience, we developed a simple technical procedure for culturing epithelial cells derived from human prostate tissue. In this study, benign prostate tissue was enzymatically digested and fractionated into epithelium and stroma, which were then cultured in the medium designed for prostate epithelial and stromal cells, respectively. The cultured cells were analyzed by immunocytochemical staining and flow cytometry. Prostate tissue-regenerating capacity of cultured cells in vitro was determined by co-culturing epithelial and stromal cells in dihydrotestosterone-containing RPMI. Cell lineages in formed acini-like structures were determined by immunohistochemistry. The culture of epithelial cells mainly consisted of basal cells. A minor population was negative for known lineage markers and positive for CD133. The culture also contained cells with high activity of aldehyde dehydrogenase. After co-culturing with stromal cells, the epithelial cells were able to form acini-like structures containing multiple cell lineages. Thus, the established culture of prostate epithelial cells provides an alternative source for studying progenitor/stem cells of prostate epithelium.

  1. Pneumocystis Pneumonia in Human Immunodeficiency Virus-infected Adults and Adolescents: Current Concepts and Future Directions.

    PubMed

    Tasaka, Sadatomo

    2015-01-01

    Pneumocystis jirovecii pneumonia (PCP) is one of the most common opportunistic infections in human immunodeficiency virus-infected adults. Colonization of Pneumocystis is highly prevalent among the general population and could be associated with the transmission and development of PCP in immunocompromised individuals. Although the microscopic demonstration of the organisms in respiratory specimens is still the golden standard of its diagnosis, polymerase chain reaction has been shown to have a high sensitivity, detecting Pneumocystis DNA in induced sputum or oropharyngeal wash. Serum β-D-glucan is useful as an adjunctive tool for the diagnosis of PCP. High-resolution computed tomography, which typically shows diffuse ground-glass opacities, is informative for the evaluation of immunocompromised patients with suspected PCP and normal chest radiography. Trimethoprim-sulfamethoxazole (TMP-SMX) is the first-line agent for the treatment of mild to severe PCP, although it is often complicated with various side effects. Since TMP-SMX is widely used for the prophylaxis, the putative drug resistance is an emerging concern.

  2. Ultrastructure of the condylar articular surface in severe mandibular pain-dysfunction syndrome.

    PubMed

    Toller, P A

    1977-12-01

    Specimens from articular surfaces of normal human mandibular condyles are compared with very small biopsies from articular surfaces of condyles taken at conservative operations in severe pain-dysfunction syndrome (P.D.S.). Immediate fixation was followed by examination using transmission electron-micrography. Normal surfaces exhibit a nearly structureless layer about 2 micron thick, which corresponds with the lamina splendens described in other diarthrodial joints. This layer surmounts a dense main structure of wavy interlacing bundles of collagen interspersed with fibrocytes. Occasional straight elastic fibres were found. Surfaces of all condyles from P.D.S. patients showed loss of lamina splendens, alteration of collagen fibre size, and tendency to dissociation of both collagen and its surrounding ground substance. Depper levels showed aggregations of bizarre structures which the author terms "vermiform bodies", and which appear to be collections of abnormal amounts and types of elastic tissue. It is suggested that the appearances are those of stress elastosis. Such profound ultrastructural changes may affect the joint sliding properties, and also its mechanical integrity under stress. Examination at this degree of magnification suggests a direct relationship between long-standing pain-dysfunction syndrome and the onset of degenerative disease. PMID:415013

  3. A biphasic viscohyperelastic fibril-reinforced model for articular cartilage: formulation and comparison with experimental data.

    PubMed

    García, José Jaime; Cortés, Daniel Humberto

    2007-01-01

    Experiments in articular cartilage have shown highly nonlinear stress-strain curves under finite deformations, nonlinear tension-compression response as well as intrinsic viscous effects of the proteoglycan matrix and the collagen fibers. A biphasic viscohyperelastic fibril-reinforced model is proposed here, which is able to describe the intrinsic viscoelasticity of the fibrillar and nonfibrillar components of the solid phase, the nonlinear tension-compression response and the nonlinear stress-strain curves under tension and compression. A viscohyperelastic constitutive equation was used for the matrix and the fibers encompassing, respectively, a hyperelastic function used previously for the matrix and a hyperelastic law used before to represent biological connective tissues. This model, implemented in an updated Lagrangian finite element code, displayed good ability to follow experimental stress-strain equilibrium curves under tension and compression for human humeral cartilage. In addition, curve fitting of experimental reaction force and lateral displacement unconfined compression curves showed that the inclusion of viscous effects in the matrix allows the description of experimental data with material properties for the fibers consistent with experimental tensile tests, suggesting that intrinsic viscous effects in the matrix of articular cartilage plays an important role in the mechanical response of the tissue.

  4. A biphasic viscohyperelastic fibril-reinforced model for articular cartilage: formulation and comparison with experimental data.

    PubMed

    García, José Jaime; Cortés, Daniel Humberto

    2007-01-01

    Experiments in articular cartilage have shown highly nonlinear stress-strain curves under finite deformations, nonlinear tension-compression response as well as intrinsic viscous effects of the proteoglycan matrix and the collagen fibers. A biphasic viscohyperelastic fibril-reinforced model is proposed here, which is able to describe the intrinsic viscoelasticity of the fibrillar and nonfibrillar components of the solid phase, the nonlinear tension-compression response and the nonlinear stress-strain curves under tension and compression. A viscohyperelastic constitutive equation was used for the matrix and the fibers encompassing, respectively, a hyperelastic function used previously for the matrix and a hyperelastic law used before to represent biological connective tissues. This model, implemented in an updated Lagrangian finite element code, displayed good ability to follow experimental stress-strain equilibrium curves under tension and compression for human humeral cartilage. In addition, curve fitting of experimental reaction force and lateral displacement unconfined compression curves showed that the inclusion of viscous effects in the matrix allows the description of experimental data with material properties for the fibers consistent with experimental tensile tests, suggesting that intrinsic viscous effects in the matrix of articular cartilage plays an important role in the mechanical response of the tissue. PMID:17014853

  5. Reference values for echocardiographic parameters and indexes of left ventricular function in healthy, young adult sheep used in translational research: comparison with standardized values in humans

    PubMed Central

    Locatelli, Paola; Olea, Fernanda D; Lorenzi, Andrea De; Salmo, Fabián; Janavel, Gustavo L Vera; Hnatiuk, Anna P; Guevara, Eduardo; Crottogini, Alberto J

    2011-01-01

    Ovine models of ischemic heart disease and cardiac failure are increasingly used in translational research. However, reliable extrapolation of the results to the clinical setting requires knowing if ovine normal left ventricular (LV) function is comparable to that of humans. We thus assessed for echocardiographic LV dimensions and indexes in a large normal adult sheep population and compared them with standardized values in normal human adults. Bidimensional and tissue Doppler echocardiograms were performed in 69 young adult Corriedale sheep under light sedation. LV dimensions and indexes of systolic and diastolic function were measured. Absolute and body surface areanormalized values were compared to those for normal adult humans and their statistical distribution was assessed. Normalized dimensions (except for end diastolic diameter) as well as ejection fraction and fractional shortening fell within the ranges established by the American Society of Echocardiography and European Association of Echocardiography for normal adult humans. Normalized end diastolic diameter exceeded the upper normal limit but got close to it when correcting for the higher heart mass/body surface area ratio of sheep with respect to humans. Diastolic parameters also fell within normal human ranges except for a slightly lower mitral deceleration time. All values exhibited a Gaussian distribution. We conclude that echocardiographic parameters of systolic and diastolic LV performance in young adult sheep can be reliably extrapolated to the adult human, thus supporting the use of ovine models of human heart disease in translational research. PMID:22140597

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

    PubMed

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

    2016-09-14

    In this study, acesulfame (ACE), saccharin (SAC) and cyclamate (CYC) were found in all paired urine and blood samples collected from healthy adults, with mean values of 4070, 918 and 628 ng mL(-1), respectively, in urine and 9.03, 20.4 and 0.72 ng mL(-1), respectively, in blood. SAC (mean: 84.4 ng g(-1)) and CYC (4.29 ng g(-1)) were detectable in all liver samples collected from liver cancer patients, while ACE was less frequently detected. Aspartame (ASP) was not found in any analyzed human sample, which can be explained by the fact that this